BY ANISH KOKA

Filling in the holes of recent stories in the New York Times, and Propublica on the outpatient care of patients with peripheral arterial disease

Most have gotten used to egregiously bad coverage of current events that fills the pages of today’s New York Times, but even by their now very low standards a recent telling of a story about peripheral artery disease was very bad.

The scintillating allegation by Katie Thomas, Jessica Silver-Greenberg and Robert Gebeloff is that “medical device makers are bankrolling doctors to perform artery clearing procedures that can lead to amputations”.

The reporters go on to tell a story about patient Kelly Hanna, who presented to a physician, Dr. Jihad Mustapha, in a private clinic with a festering wound. After being diagnosed with a poor flow to her leg that was likely contributing to the wound, Dr. Mustapha performed multiple procedures on her leg to improve blood flow in an attempt to ward off a future amputation. The procedures were unsuccessful, and Ms. Hanna ultimately did need an amputation.

The Times also briefly touches on some other patients of Mustapha who had bad outcomes. The majority of these cases appear to be related to complications patients suffered during surgeries. Multiple surgeons reported having to have done multiple procedures on Mustapha’s patients who had had complications. In 2020, the state medical board investigated Dr. Mustapha and referred him to the Michigan attorney general. An expert hired by the state medical board reviewed 8 cases and concluded the practice was characterized by overtreatment and poor documentation. Mustapha reached a settlement with the Attorney general where he was fined $25,000 but did not acknowledge any wrongdoing.

Mustapha questioned the expertise of the medical board that was overseeing him, and noted that any significant wrongdoing would have resulted in a much more significant punishment.

I’m sympathetic to Dr. Mustapha after reading the New York times article for a number of reasons. The claims of wrongdoing appear to stem from:

1. Dr. Mustapha is a high volume operator that does lots of limb salvage procedures and has been paid a lot of money for this.
2. Vascular surgeons at nearby hospitals had complained because they were seeing “a lot” of his patients having complications.
3. An insurance company reported 45 patients over a course of 4 years needed amputations.
4. Device companies that manufacture the tools used by physicians to open up arteries provide loans to physicians to buy these tools.
5. There have been many more attempts to open arteries that have taken place in private clinics since reimbursement rules changed.

This is all extraordinarily thin evidence to suggest wrongdoing on a grand scale.

First of all, the case the New York Times chose to present involved a patient with a wound due to poor peripheral blood flow from critical narrowing of arteries. Presenting with a wound like this is a very poor prognostic sign, and indicative of Chronic Limb-threatening ischemic (CLTI): a condition that carries a 1-year amputation rate of 20%, meaning 1 in 5 patients presenting like Ms. Hanna end up with an amputation. Dr. Mustapha, who also happens to be widely regarded as a pioneer in the PAD field, self-reported a 30-day amputation rate of 1.3%. This provides the appropriate context for the 45 amputations in 4 years reported by an insurance company. A successful, high-volume operator working with difficult cases is bound to have numerically more complications. Without denominators, “more complications” means little.

It is possible that Dr. Mustapha’s rate of complications look good because the patients being taken to the lab are lower risk patients who shouldn’t be in the lab having procedures done. However, there is little evidence presented to suggest that this is the case outside of anecdotes from disgruntled former partners who note they were pressured to refer patients for vascular procedures.

It is similarly challenging to know what to make of the complaints from neighboring vascular surgeons about complications in Dr. Mustapha’s patients. The surgeons are generally unhappy with other specialties managing PAD patients without their involvement, and they also don’t know the the denominator to know if the complications occurring are at a higher rate than what would be expected.

Unfortunately, and especially in complex patients, wires may break while doing procedures, and the only treatment at that point is a vascular surgeon. Again, without knowing the denominator of total cases, it’s irresponsible to suggest there is something deeply wrong going on.

The New York Times also accepts as fact the assertion from surgeons that more endovascular procedures lead to more amputations. While this may be true in individual cases of unscrupulous physicians, the national story does not support this claim. Despite the significant increase in the complexity and illness of patients that have been presenting with peripheral arterial disease, the rate of amputations has actually gone down, despite the fact endovascular interventions have rapidly increased.

While it’s possible to attribute the lower amputation rate to other improvements in wound care, the likelihood of this being the fundamental driver of fewer amputations over time is very low. At the very least, the graphs make it highly unlikely that the main contention of the New York Times article – that higher rates of endovascular interventions leads to more amputations – is true.

It’s unfortunate the New York Times screwed this story up so much, because there are real issues to consider in this space. There is little question that the financial incentives to find and treat peripheral arterial disease leads to inscrupulous operators that harm patients. Propublica does a much better job in their deep-dive into the PAD story which focuses on vascular surgeon Jeffery Dormu.

Jeffery Dormu was a double board certified vascular surgeon who was paid $13 million dollars by Medicare alone between 2013 and 2017. In 2018, he even opened a state of the art lab nicknamed “the Watcher” and was paid $18 million from Medicare in the next 3 years.

These payments made him one of the highest paid vascular surgeons in the country. The numbers reflected a high volume of care delivered but there were concerning indications much of the care delivered was unnecessary. Unlike the New York Times story that featured a patient with a non-healing wound that put her at high risk of losing her limbs, some of the patients featured in the Propublica article had mild symptoms. Propublica does a pretty good job diving into each patient story, but the US medical malpractice system is challenging for laypersons. Highly paid expert witnesses on both sides make strong assertions, and lawsuits are frequently settled because it makes the most financial sense to do so, not because the case itself may merit it. So its worth a closer look at the patients discussed

The first patient Propublica discusses is Mr. Rosenberg, an auto mechanic who sought out care from Dormu for increasing leg pain.

12.27.2016. Mr. Rosenberg meets Dr. Dormu.

A lower extremity arterial ultrasound revealed elevated velocities in the right proximal superficial femoral artery.

1.19.2017. Dr. Dormu performed an aortogram of the bilateral lower extremity with bilateral iliac runoff, which revealed a 90% stenosis of the right superficial femoral artery and 100% occlusion of all three tibial vessels. Based on these results, Dormu performed a percutaneous transluminal balloon angioplasty and a mechanical atherectomy and stenting of the right superficial femoral artery and stenting of the right superficial femoral artery. Dr. Dormu also performed a mechanical atherectomy of all three tibial vessels.

3.23.2017. In response to increasing severity of his leg pain, Dr. Dormu performed another angiogram. These studies revealed an 80% stenosis of the left superficial femoral artery and 100% occlusion of all three tibial vessels. Dr. Dormu performed a percutaneous transluminal balloon angioplasty, a mechanical atherectomy, a stenting of the left superficial femoral artery, a mechanical atherectomy of all three tibial vessels.

3.31.2017. Mr. Rosenberg presents to the hospital complaining of left foot numbness and coolness when laying down. He is again sent to Dr. Dormu, who on the same day, performs another angiogram which revealed an in-stent restenosis of the superficial femoral artery stent and a 60% stenosis of the tibioperoneal trunk. Dormu replaced the stent due to “recoil”, and performed another mechanical atherectomy and a percutaneous transluminal balloon angioplasty of the left superficial femoral artery and a percutaneous transluminal balloon angioplasty of the tibioperoneal trunk.

4.1.2017. Mr. Rosenberg again presents with leg pain. Dr. Dormu performed another angiogram which revealed an in-stent occlusion/restenosis of the superficial femoral artery stent and restenosis of the tibioperoneal trunk. Based on the results, Dormu performed a percutaneous transluminal balloon angioplasty of the left superficial femoral artery and tibioperoneal trunk. Another superficial femoral artery stent was placed as well. Dormu also sends Rosenberg to the hospital after this procedure for evaluation for bypass as well as a thrombolytic.

4.2.2017. A thrombolysis is performed in the hospital via a catheter.

4.3.2017. Rosenberg develops a large hematoma and a cold foot. Dormu removes the catheter and recommends an amputation.

4.8.2017. Rosenberg is transferred to another hospital for a second opinion. A CT angiogram shows a left common femoral dissection. No blood flow is seen below the mid thigh. All stents were occluded. On the same day, Mr. Rosenberg undergoes an above the knee amputation.

Dr. Dormu’s expert witness, Dr. Garry Ruben, said the interventions were warranted, and blamed Rosenberg’s course to not consistently taking anti-platelet medication that may have kept the stents open, and his preexisting medical conditions.

Mr. Rosenberg’s expert witness, Dr. Christopher Abularrage, a vascular surgeon at Johns Hopkins, disagreed. He found several “breaches of the standard of care.” : failing to prescribe conservative therapy and lifestyle modifications first, and persisting with “unindicated, endovascular interventions in the face of persistently poor outcomes and diminishing returns”.

It’s possible that Mr. Rosenberg did have severe claudication causing him to have pain at rest, and that he was appropriately diagnosed. There is little question, however, that there appeared to be no attempt to attempt to conservatively manage Mr. Rosenberg’s symptoms. Only 23 days passed between the initial meeting with Dormu, and the subsequent intervention on his leg.

The Maryland State Medical Board initiated an investigation in 2020 after a patient complaint that noted Dr. Dormu recommended an angiogram for severe itching in the legs. A second opinion from another physician at another facility resulted in a normal ultrasound. The itching turned out to have been a bad reaction to an insect bite. This and other patient complaints triggered a review of 11 patient records by two independent peer reviewers who found that not only were conservative measures not employed prior to progressing to more invasive procedures, but patients with normal diagnostic studies were also subject to invasive procedures with “no clinical justification”.

The cases supported the claim that Dormu was performing procedures with serious complications in patients that did not need them. Patient 6 could walk a mile prior to having symptoms. After a procedure with Dr. Dormu, the patient endured worsening symptoms and an inability to walk after the initial left leg arteriogram performed by Dormu. Dormu then continued to perform left leg arteriograms on Patient 6 despite worsening perfusion and more severe symptoms in that leg.

Dormu also appeared to misdiagnose individuals, incorrectly diagnosing Patient 10 with peripheral arterial disease, and then performing procedures that ultimately worsened lower extremity perfusion. In October 2022, the state medical board found him in violation of state medical law, citing, in part, his overuse of procedure. He was fined $10,000, his license was suspended and he was placed on a two-year probation, during which he must be supervised.

It does not appear Dormu has practiced since.

The story for Dr. Dormu gets even stranger. A press release from May 24, 2023 advertises a TV show medical drama that purports to be a retelling of the life of Dr. Dormu that references a past as a drug kingpin in Washington DC.

This hard-hitting retelling of Dr. Jeffery Dormu’s dangerous past as a former District of Columbia drug kingpin intersperses storylines from the doctor’s past and present. The series navigates his life and illustrates how one margin of error could mean the difference between life or death on the streets as well as in the operating room. From narrowly escaping life as a Liberian child soldier, organizing one of the largest gangs in DC history, the Gangsta Chronicles and becoming a drug kingpin, to attending an ivy league school, Dormu went on to win a civil rights lawsuit against four corrupt police officers. During the span of his career, he has surgically saved tens of thousands of lives and built the only black owned cardiovascular hospital in the world, a multi-million dollar facility. Margin of Error is a unique rags to riches story that will take fans on a multi-sensory journey.

The contrast between the New York Times story and the ProPublica story is striking. The New York Times chose to attack a well-respected pioneer of the field who does a lot of procedures that result in some patients having complications and needing amputations. The grievances about practicing below the standard of care come almost entirely from neighboring vascular surgeons with an axe to grind. A review from the State medical board and the Attorney general resulted in a fine with no admission of wrongdoing. His license was not suspended, and he continues to operate a busy practice today.

ProPublica showcased a vascular surgeon with a checkered past who clearly was unable to diagnose peripheral arterial disease appropriately and was doing a high volume of procedures on asymptomatic or minimally symptomatic patients. The investigation by the state medical board resulted in a suspension of his license, he does not appear to be actively practicing today, and the website for his vascular center is no longer available.

Both articles unfortunately leave readers with the impression that all endovascular interventions are suspect and are primarily driven by a need for profit rather than any desire to help patients.

Academic vascular surgeons who have been long banging the drum of overuse of endovascular procedures seized on these articles to call for greater regulation of vascular centers and the operators working at these facilities. Dr. Joseph Mills , President of the Society of Vascular Surgery encouraged vascular surgeons be involved in the decision making process for patients with peripheral arterial disease (PAD), and noted that very few patients with PAD actually should qualify for interventions.

But everyone involved with taking care of patients with PAD agree that critical peripheral arterial disease leading to amputation is a major problem that disproportionately impacts poor, black communities. Even the vascular surgery comment on the New York Times article ends with an entreaty to the media :

SVS urges media professionals to be diligent in presenting health care and medical information that is fully balanced, as coverage could lead to patient distrust and delays in necessary care with potentially adverse consequences.  

Unfortunately, the pull for the salacious storyline that sells regarding greedy doctors hurting patients in the name of the dollar is too strong for most in the media to resist. In choosing the easy path to clicks, ignored are the real issues :

1. Medical training programs (funded with taxpayer dollars) that appear to rubber stamp the unethical and the incompetent. The egregious practice patterns of Dr. Dormu should raise serious questions of the programs that trained him (Vascular surgery specialization at Deborah Heart and Lung). Should programs and program directors responsible for signing off on trainees as competent to perform procedures independently face sanction when graduates of their program fail to do so?
2. If training programs are turning out some combination of incompetent and unethical graduates, the onus falls on state medical boards responsible for protecting the public from bad operators. The system appears to work in the case of Drs. Dormu and Mustapha, but the timeline for corrective action is too long. The first complaint reported to the Maryland medical board was in October of 2020. The resulting investigation and sanction to suspend his medical license did not take place until late in 2022. Two years of a dangerous operator like Dormu practicing medicine is too long.
3. The peer review process as a means of regulation appears to be highly susceptible to internecine squabbles that make it difficult to delineate right from wrong. Vascular surgery has a strong stance that has a protectionist bent to it. It is clearly in their interest to cast other specialties operating in this space in a poor light. Academics, especially, are hostile to all work being done outsie their purview. The currency in health systems is volume of procdures performed. Private clinics located in areas with a high prevalence of PAD threatens hospital volume. This makes peer review provided by vascular surgeons as a means of regulation suspect.
4. Atherectomy is controversial in part because the evidence in the form of clinical trials for their use is poor. More trials may shed light on exactly how inappropriate atherectomy is and define the population best suited for it.
5. Reducing or changing reimbursement for procedures in the outpatient/non-hospital setting is a common solution proffered by a number of commenters. Unfortunately, many of these commenters are in the academic hospital space and have much to gain from this type of regulation, and ignores the possibility that there have indeed been countless limbs saved by expanding access to those most at risk to revascularization.

This is certainly a good discussion worth having that deserves attention. The New York Times doesn’t appear to be the best place to moderate that debate.

Anish Koka is a cardiologist. Follow him on twitter @anish_koka

To listen to more of the discussion, tune in at 1 pm EST July 23rd on TwitterSpaces (Go to twitter and click on the pinned tweet on my profile @anish_koka )

BY ANISH KOKA

The All-in podcast is a fairly popular show that features successful silicon valley investors commenting about everything worth commenting on from politics to health. The group has good chemistry and interesting insights that breaks the mold of the usual tribal politics that controls legacy media analysis of current events.

Last week, the podcast touched on a topic I spend a fair amount of time on: Cardiology.

Brad Gerstner, who is actually a guest host for this particular episode starts off by referencing something called Heartflow to evaluate the heart that has been recommended by one of the other hosts: Chamath Palihapitiya. Brad apparently asked his primary care physician about Heartflow and was instead directed to get a calcium scan.

Heartflow is a proprietary technology that purports to evaluate the presence of significant narrowing in the coronary arteries just by doing a heart CT scan. A calcium score is a low-dose CT scan used to identify the presence of calcium in coronary vessels.

The segment ends with a recommendation for everyone over the age of 40 to get some type of heart scan, so I thought it would be worth reviewing some of the main claims.

Question 1. Does Brad need a calcium scan?

Brad notes that his primary care physician told him he was young, fit, and had a low bad cholesterol (LDL) and needed a calcium scan rather than a heart flow scan. The answer to this question and the questions to follow depend on what outcome Brad is looking for. If the goal is to feel happier knowing if he has coronary calcium than the resounding answer is to get the calcium scan. But if the goal is to live longer and healthier, there is nothing to suggest a calcium scan will help. Most cardiologists believe that the lower the LDL, the better cardiovascular outcomes are. So if a calcium scan convinces Brad to NOT lower his LDL further either naturally or with medications, a calcium scan may be detrimental.

We have zero evidence to suggest patients who get calcium scans lower their risk of future mortality.

Question 2. Does Brad need a Heartflow scan?

Heartflow is a California based company that claims to be able to identify heart vessels leading to a lack of blood to the heart muscle that need coronary stents to fix. Ordinarily this determination is done with a combination of tests that include a stress test and an invasive heart catheterization that involves a catheter being snaked into the heart. Heartflow puports to do all of this with a single 20 minute CAT scan that only involves placement of a peripheral IV using artificial intelligence/machine learning. The evidence to support the use of Heartflow comes mostly from small studies that show no difference in outcomes relative to the standard of care in relatively low risk populations. I could probably use a theragun based AI aproach in 500 carefully selected patients and show no difference in clinical outcomes to the standard of care. This is because the absolute risk of bad clinical events is too low for the size of studies generally being performed. You would need larger numbers to show small differences in outcomes and the Heartflow trials don’t have large numbers – which is convenient when you need series B funding. The small trials do still provide some interesting data about how Heartflow peforms.

The image below from this “positive” Heartflow study shows that almost a quarter of patients who did not have a significant narrowing in their arteries were judged to have a significant narrowing based on Heartflow. And regardless of whether you have a 26-50% narrowing or a 51-70% narrowing, you have a 1 in 4 chance Heartflow will say there’s a problem (when there isn’t).

So if Brad wants a pretty picture with some numbers attached to make him feel good, he should definitely pony up a few thousand dollars for a Heartflow scan.

Question 3. Will Heartflow or Calcium scans save lives if deployed broadly in the population?

While it seems intuitively obvious that doing more tests to find heart disease will decrease the likelihood of dying from heart disease, the reality is anything but obvious. The history of diagnostic testing for coronary disease shows that we are better and better at identifying disease, but simply identifying coronary plaque isn’t the home run people think because of how ubiquitous the development of coronary plaque is in humans. By the age of 60 it is only the small minority of men and women who have no coronary calcium present (6% of older men, 11% of older women).

To make matters even more complicated, plaque in younger patients may be non-calcified and invisible to CT-calcium scans. A calcium score of 0 in a younger patient could provide a false sense of security. In the figure below, almost 60% of patients with “obstructive CAD” had a Calcium score of 0 !

Whether or not discovering and treating “obstructive CAD” as defined in the study is beneficial is another complex topic with much nuance.

And lastly, there’s a potential for harm driven by overdiagnosing coronary disease! Every cardiologist that has seen enough patients has a story of a patient with an elevated asymptomatic calcium score that ends up with a disastrous outcome from a cardiac catheterization. The field of interventional cardiology has a remarkable safety profile but the rate of severe complications related to the procedure alone is not zero.

Summary

Calcium scans and HeartFlow are interesting tools, but proponents are well out of their depth to think a universal screening approach using these tools will be beneficial.

The problem here is that these mostly middle aged men discussing the topic are appropriately concerned about the most likely cause of their early demise : heart disease. I’ve written a number of times about the scourge of heart disease in men. It can strike suddenly and without any warning, even in the apparently healthy. The absolute risk of men dying due to their heart giving out is ~ 1/600 in men aged 35-44, ~1/250 in men aged 45-54, ~1/100 in men aged 55-64.

This is enough death to strike fear into the hearts of the healthy, and provides ample opportunity to make billions selling men on the keys to cheating death.

If this topic piques your interest, and you want to dive even deeper, tune in tomorrow, July 16th at 1 pm EST to hear a discussion with cardiologists and other experts on Twitter!

Anish Koka is a cardiologist. Follow him @anish_koka on twitter.

Rough transcript of all-in-pod provided by YouTube:

1:31:50

about this pod is we cover everything from science to politics and and chamoth last year

1:31:56

um you know in his biohacking series told us all to get pre-nuvo scans which I did which is interesting and I think I

1:32:02

don’t know maybe 10 people have have sent you notes and said hey you helped me discover a tumor you know really

1:32:09

amazing well so this year and I did that um you know this year you’ve been talking a lot about heart flow so I said

1:32:15

to my general practitioner at my annual checkup hey I want to do this heart flow and she said oh you don’t need to do a

1:32:21

heart flow your ldls all your stuff looks real wait wait wait wait wait wait wait wait you have a female GP

1:32:27

uh she’s fantastic fantastic Stanford educated really terrific I don’t care

1:32:32

where she went who does the prostate test he does Hey listen it’s it you know

1:32:38

the perks that come check in the PSAs I mean no but seriously you have it really I do I do that’s a level of intimacy I

1:32:46

didn’t expect from you wow and so you know but what I found interesting is

1:32:51

when I suggested I get the heart flow she said oh you don’t need it Etc your ldls are low you’re very fit and she

1:32:59

said but on second you know maybe you could go get this calcium score test right

1:33:04

um I didn’t know anything about this but you know I did a little quick research and it turns out a big Jam of study in

1:33:10

2017 over 50 percent of men and women over the age of 40 Carrie plaque

1:33:16

plaque’s the number one killer it’s a source of heart uh disease and and heart attacks and as Chamas been talking about

1:33:23

there’s you know a a prophylactic called Statin which is basically like a supplement very little downside no

1:33:30

long-term downside effects but it immediately starts cutting down the amount of fatty cells and and and plaque

1:33:36

that’s carried in your blood so I thought it was interesting I went and I had chemath uh as you know the core the

1:33:42

coronary calcium scan it takes five minutes it costs between a hundred and four hundred dollars the fact that we

1:33:47

don’t have every person taking this over 40 is crazy and Frontline doctors should all be prescribed in it but it

1:33:53

particularly if there’s family history sorry but did you also do a contrast CT with heart flow yeah so I started with

1:33:59

the calcium score 150 bucks over at Stanford took five minutes and you know it told me uh you know which wasn’t

1:34:06

terribly surprising I was one of the 50 percent that did carry some level of calcium so it was called a non-zero

1:34:13

score and then what they suggest is because you have a non-zero score you get this

1:34:19

you know chamoth you told me go do the contrast CT which then will image what

1:34:25

this looks like actually in your artery so this past week in Boston I did the contrast CT again this took 10 minutes

1:34:32

non-invasive like you know it just they run you into it invasive because you have to put the dye so they put yes so

1:34:41

so a tiny bit I I suppose they shoot a little die into you but you know um uh it didn’t feel like anything

1:34:48

I was in and out of the of the place in 40 minutes and what it found is you know

1:34:54

fortunately that very little of this calcium had turned into what they call stenosis any narrowing of of the

1:35:01

arteries okay but then it gave you just a very clear picture that if you are one

1:35:07

of the 50 who carry plaque over the age of 40 you should be on a prophylactic

1:35:13

Statin so it’s chamat knows I signed up to 10 milligrams of crestar which I’m taking daily has had zero you know zero

1:35:20

adverse consequences and in two or three months they’ll test the amount of you know we’ll revisit this calcium score

1:35:28

um but when I talked to the head of Cardiology what was so interesting he said every one of his friends over the

1:35:34

age of 40 he has them do this calcium coronary scan it’s so cheap and if

1:35:39

they’re zero on their calcium reading that that’s the end of the line but if they have a non-zero reading then he’ll

1:35:45

do the the CT coronary scan which is again very cheap more expensive than the

1:35:51

calcium test but very cheap and when you think about the cost of the patients in this country right in our health care

1:35:58

System due to heart disease and when you think about the needless lives cut short I was shocked how easy all of this was

1:36:07

and how empowered I feel by the data and how fortunate I feel that I’m actually

1:36:12

taking a supplement I call it a supplement instead of statins because I think Statin has some spooky name it

1:36:17

sounds to me like a better supplement than any vitamins I can take and you know it’s reducing the ldls or these

1:36:24

fatties in your you know in your blood and I’ll keep you posted but I was very grateful and you know as you know I

1:36:29

posted it in our thread and I think all the besties you know we saw responses out of a bunch of folks in the thread

1:36:35

this week are going to go get their calcium uh you know coronary scan and I

1:36:41

I think it should be Common Sense on the front lines for people over 40 particularly if there’s any family

1:36:46

history go get this calcium test done this summer while you have a little extra time there you have it folks

1:36:53

100 to 400 could save your life calcium coronary scan Brad gerstner thanks so much for science Corner this week

BY ANISH KOKA

A national study from Korea published in the European Heart Journal sheds important new light on complications related to COVID vaccine related myocarditis. While US public health authorities have been convinced from the very beginning about how safe and effective the new vaccines are, researchers in other countries with far smaller budgets have been testing that theory.

It was Israeli researchers that first highlighted the novel mRNA vaccines as potentially causing myocarditis in the Spring of 2021, but it has proven difficult to quantify the risk of severe complications beyond scattered case reports of severe morbidity and mortality. In part, US researchers are hampered by vaccine reporting systems in the US that are passive surveillance systems relying on voluntary reporting of vaccine adverse events. This has the potential of under-reporting adverse events, which was exactly the conclusion of an earlier JAMA analysis on US VAERS vaccine myocarditis cases.

Diving deep into the methods and results of the study

The South Korean approach was to organize a national reporting system under the auspices of the Korean Disease Control and Prevention Agency (KDCA). The KDCA also established a reporting system with a legal obligation for special adverse events including myocarditis and pericarditis after COVID-19 vaccination. To evaluate all reported cases of suspected myocarditis or pericarditis after COVID-19 vaccination, the KDCA organized an “Expert Adjudication Committee on COVID-19 Vaccination Pericarditis/Myocarditis”. The committee comprised 7 experts in cardiology, 1 in infectious disease, 2 in epidemiology, epidemiologic investigators in 16 regional centers, and officials from the KDCA.

Among 44,276,704 subjects vaccinated from 26 February to 31 December 2021, 1533 cases of suspected myocarditis were reported to the KDCA. The committee adopted the myocarditis case definition and classification of the Brighton Collaboration (BC) (see figure below) for the diagnosis and degree of certainty of a Vaccine Related Myocarditis (VRM) diagnosis.

Acute myocarditis that developed within 42 days after COVID-19 vaccination was considered a COVID-19 VRM. To minimize the risk of an inaccurate diagnosis, the committee rejected the level 3 BC case definition of myocarditis and the level 2 BC case definition that did not have associated cardiac damage evident on a blood test or any case with a positive result for COVID-19 infection. In the few cases where cardiac markers were not performed or were not in an abnormal range, confirmatory testing with endocardial biopsy or cardiac MRI confirmed the diagnosis of VRM.

The adjudication committee also examined other potential causes of myocarditis, such as the presence of antibodies against various viruses and autoimmune markers in their review of the medical records.

A review of the South Korean vaccination record shows 86% of the population was vaccinated in the 10 months the study examined (Feb 2021 – Dec 2021). The vaccine most commonly used was the Pfizer BNT162b2 mrna vaccine (56%), followed by the AstraZeneca adenoviral vector vaccine ChadOx1 (25%), and the moderna mrna-1273 vaccine (15%).

Of the 1533 cases of potential vaccine myocarditis reported, the expert adjudication committee confirmed 480 Covid 19 VRM cases. The incidence of VRM was highest in 12-17 year old males with a rate of 5.29 /100,000 persons.

Severe COVID-19 VRM was identified in 95 cases (19.8%), 85 ICU admissions (17.7%), 36 Fulminant Myocarditis cases (7.5%), 21 ECMO therapies (4.4%) ( a modified heart lung bypass), 21 deaths (4.4%), and 1 heart transplantation (0.2%).

Autopsy studies were done for all sudden death cases after COVID-19 vaccination in Korea because of a national compensation program for vaccine injuries. This identified eight cases of sudden cardiac death as caused by VRM that were not known until the autopsy was performed. All sudden cardiac death developed within a week after mRNA vaccination and occurred in individuals under the age of 45.

What we learn from this study

The South Koreans would appear to have hit on how to minimize both under and over-reporting of vaccine adverse events by combining a legal obligation to report that makes underreporting less likely, and assembling an expert committee to review individual case reports to adjudicate cause appropriately. Extrapolating their results to other vaccinated populations still needs to be done carefully because vaccine adverse events may differ by race/ethnicity , as well as type of vaccine that was primarily deployed in a population. The Moderna mrna-1273 vaccine has 3x the dose as the Pfizer BNT162b2 mrna vaccine and has been widely reported to have higher rates of vaccine myocarditis. The South Korean population was mostly vaccinated with the Pfizer mRNA vaccine and the AstraZeneca adenoviral vector vaccine (rarely associated with VRM).

The highest risk group, as has been repeatedly shown elsewhere, was 12-17 year old boys with a rate of 5.2/100,000 boys. This rate, in the United States, would conservatively translate to ~650 boys (~160 girls) with vaccine related myocarditis if the entire population of 12-17 year olds was vaccinated. The US did have a lot more moderna vaccine available which means the rate of VRM would likely have been higher (37% of vaccines given in the US were moderna vaccines per the CDC) here than in South Korea.

These are all approximate numbers , of course, and a variety of factors could move these estimates up or down. We don’t have details of the ~1100 potential cases of VRM that were thrown out by the expert committee, vaccination rates vary widely in different populations, the type of vaccine available with differing rates of VRM, and certain adverse events may differ based on race/ethnicity.

But these rates are in line with a few other large datasets which lends credibility to the estimates. There are some results here that are surprising and concerning. It is little secret by this point that US public health authorities have been so committed to the vaccines being safe and effective to support their universal vaccination campaign that their first response to reports of vaccine myocarditis was to first deny, and once that ship sailed, to emphasize the ‘mildness’ of vaccine myocarditis.

The incomplete datasets available to date have largely characterized VRM as a self limited illness that requires a precautionary hospital stay for 24 hours that can be treated with Motrin. While there have been case reports published of severe VRM, Israeli and US data found no severe cases in their published series. The South Korean data, in stark contrast to the ‘mild and favorable prognosis’ narrative found 20% of VRM cases were severe.

– Severe VRM was identified in 95 cases (19.8% of total VRM)

– 85 intensive care unit admission (17.7%)

– 21 extracorporeal membrane oxygenation therapy (4.4%)

– 21 deaths (4.4%), and 1 heart transplantation (0.2%)

– 8 of 21 deaths were sudden cardiac death (SCD) attributable to VRM proved by an autopsy.

The sudden cardiac death data is also interesting because of how these deaths were found. South Korea requires autopsies on deaths that occur soon after vaccine administration as part of their vaccine compensation/liability program. Of the 21 deaths that were attributed to the vaccine, 8 were found to have myocarditis only at autopsy. No one suspected myocarditis in these cases until the autopsy was done. We have no similar mechanism in the US, which means we are not tracking these deaths. This may be convenient for public health authorities who don’t want to answer tough questions, but it doesn’t help citizens or doctors trying to figure out what’s best for individuals and it certainly isn’t helping anyone harmed by the vaccine who turns to the US national vaccine compensation program.

My understanding of the vaccine program in the US is that vaccines that are net positive for the population are approved by the regulatory agencies and then delivered to the populace with the assumption that those few that do end up injured for ‘the greater good’ are compensated from a national fund filled via taxes on the vaccines paid by the vaccine manufacturers. That tax is passed on to those paying for the vaccines, and in the case of the COVID vaccines, that means the generous US taxpayer is funding all of it. The compensation mechanism in part was what being “in this together” was supposed to mean.

But can anyone confidently speak to net benefit of an intervention without quantifying its risks? How many 12-17 year olds should have been enrolled in a trial before approving a drug for this segment of the population ? If you do go ahead and approve a therapy because of an emergency, shouldn’t there be a robust mechanism of adverse event surveillance to allow novel adverse events to be picked up so that the authorities could quickly adjust vaccine recommendations ?

The questions are rhetorical. We don’t actually have a plan for any of this, and if we did have any hope of formulating a plan, the sheer panic from COVID induced in the laptop class destroyed any hope a rational plan would come to be.

COVID risk estimates are always controversial but it was pretty clear early on that even at the worst points of the pandemic the risk of COVID to the young was very, very low. At least one meta-analysis suggested an Infection Fatality Rate (IFR) for ages 0-19 of 0.0003%. From the South Korean Data, the rate of VRM in about the same age range is ~0.004% (80/2M), and the rate of severe vaccine myocarditis is ~0.0008%. If one can safely assume that the IFR of COVID in young people is disproportionately driven by children with severe comorbidities, it is easy to build a case for the rate of vaccine related severe cardiac complications being worse than COVID for young, fit, healthy children even at the outset of the pandemic. To be clear, I don’t think anyone should put tremendous faith in the exact point estimates because these are such rare events but the overall point is that patients and parents may be interested in knowing that even if we could time travel with a vaccine to the early Spring of 2020, the risk of a severe complication from the vaccine in young healthy individuals approximates the risk of dying from COVID. Perhaps you decide vaccination is the right thing for you or your 13 year old after weighing the pros and cons.

Great.

But not having the conversation at all after the Spring of 2021, when the link between myocarditis and the vaccines became firmly established, was a failure on the part of public health officials.

Even worse, vaccine mandates that are still in place (160 US Colleges continue to mandate a vaccine) tie participation in normal society to vaccination and effectively disallow individuals from deciding against vaccination.

The 2023 risk/benefit calculus casts a very long shadow on those who seek to compel their fellow citizens to vaccinate. The vast majority of the population has already received a vaccine or been infected with COVID, and most hospitals in the United States have not seen any significant influx of severe COVID in more than a year. While the Korean data finds a low absolute rate of vaccine myocarditis that ranges from an overall rate of 1/100,000 to a peak rate of 1/18,000 in 12-17 year old boys, it is inexplicable that there remains any appetite for vaccine mandates when 20% of these cases are severe, 4% require a modified heart lung machine, 4% die, 2% suddenly from an arrhythmia.

It’s pretty clear now that the descriptors used for the vaccine for much of the pandemic were hyperbolic and lacked nuance. The vaccines appeared to be very effective in the framework of the trials that were performed at one point and time during the pandemic. Public health, and doctors like me who became vaccine providers needed to be a lot more measured with our assurances about safety of the vaccine. It was hubris and hope that drove the vaccination campaign in the healthy young, and we should have been much more cautious in extrapolating the perceived benefits and risks seen in the early trials of the vaccine to low risk groups.

Moving forward, one would hope the credentialed class that somehow are in charge of nearly every aspect of our life will learn important lessons for the future.

I doubt it.

Anish Koka is a Cardiologist. Follow him on Twitter @anish_koka

I have to make the obligatory post-script here that I oversaw the administration of hundreds of mrna vaccines starting in March of 2021 in my cardiology clinic. The vaccine efficacy data for the original data was from thousands of patients and I certainly felt given the devastation wreaked on many of my patients in 2020 that the vaccines were the best chance of avoiding morbidity and mortality. The process to get the vaccines from the city department of health was a somewhat arduous 3 month process, and once the vaccines were on hand, there were daily reporting requirements that I dutifully performed for the many months we were administering vaccines. To accommodate the rush of patients, employees, volunteers, and conscripted children worked multiple weekends to administer the vaccines. So I’m especially disgusted by medical colleagues who label any concerns registered about vaccine adverse events as “anti-vaxx”. Registering concern over a vaccine adverse event does not make doctors or patients “anti-vaxx”. It makes them pro-vaxx!

BY ANISH KOKA

On March 25th, 1971, the Pakistani army launched Operation Searchlight, a military campaign to brutally suppress a Bengali nationalist movement.

The roots of the genocide lie in the parting gift British rulers gave to the Indian subcontinent at the time of independence in 1947. British controlled India was separated into Hindu majority India and Muslim majority Pakistan. But because there were two dense non-contiguous Muslim majority areas in British controlled India, the muslim majority country of Pakistan was divided into East and West Pakistan.

East and West Pakistan were linked by religion, but little else. East Pakistan was culturally Bengali, and had much more in common with Bengali Hindus than Muslims in West Pakistan. While Bengalis took pride in their culture and language, West Pakistani’s looked down on the Bengali’s because it was deemed to be too influenced by Hindu culture. While Bengali muslims may have identified themselves with Pakistan’s islamic project, by the 1970s many in East Pakistan had given priority to their Bengali ethnicity over their religious identity, desiring a society more in accordance with Western principles of secularism and democracy. A growing opposition in East Pakistan strongly objected to the Islamist paradigm being imposed the West Pakistani state.

But West Pakistan controlled the military, and formed much of the ruling elite after the partition in 1947. In a move designed to send a message to Bengali speaking East Pakistani’s , the founding father of Pakistan, Muhammad Jinna even made Urdu the national language of all of Pakistan, and branded those opposed as enemies of the State.

The predominantly Bengali East Pakistanis outnumbered West Pakistanis and chafed at control from Islamabad. It was little suprise then, that in the first general election, the Awami league, campaigning for more local control, under the leadership of Sheikh Mujibur Rahman won a majority of votes and demanded control of the government shift to East Pakistan.

The president of Pakistan at the time – General Yahya Khan and the leader of the dominant PPP party in the West Pakistan – resisted. They had no intentions of a transfer of power to Sheikh Rahman. Negotiations between the two sides broke down, and a disabling strike called by Rahman effectively shut down the East Pakistani economy.

Shortly after, West Pakistan launched Operation Searchlight. The goal ? To extinguish the nascent Bengali nationalist movement by killing or imprisoning its leadership, and even more importantly, destroy any possibility of a future nationalist movement. The Pakistani Armed Forces and supporting pro-Pakistani Islamist militias from Jamaat-e-Islami began an ethnic cleansing campaign that claimed the lives of 300,000 to 3 million people. The army also launched a systemic rape campaign of Bengali women, raping between 200,000 and 400,000 Bengali women.

One of the groups that were eyewitness to the atrocities was the American consulate stationed in Dacca, East Pakistan. Daily telegrams were sent to US President Richard Nixon, and National Security Advisor/Secretary of State Henry Kissinger about the brutality being carried out with American weapons supplied to Pakistan.

The systemic rape of Bangladeshi women was without precedent in the modern era. Australian doctor, Geoffrey Davis, was brought to Dacca by the International Planned Parenthood Federation (IPPF) and the United Nations.

His task?

Perform late term abortions, and facilitate large scale international adoption of the war babies born to Bangladeshi women. In an interview, Davis was asked why the Pakistani’s had to impregnate the women. “

“… so there would be a whole generation of children in East Pakistan that would be born with the blood from the West. That’s what they said.”

Arthur Blood was the American diplomat stations in Dacca and increasingly grew more horrified. His daily cables to DC became more urgent – but continued to be steadfastly ignored by Nixon and Kissinger.

Blood was particularly moved by the killing of a Hindu Bengali professor he had befriended on the very first night of the Pakistani operation.

Early in the crackdown, Dev was dragged out of his home, hauled to a field in front of the Hindu dormitory at the university and shot dead. There was no other reason that he was killed other than being a Hindu professor

Neighboring India was quickly deluged by millions of East Pakistani’s fleeing the Pakistani genocide, and quickly decided to prepare to launch a military operation. This would take time, and in the interim, India became active in support of the Bengali East Pakistan guerilla’s that called themselves the Mukti Bahini (Freedom fighters).

Tipped off to the looming Indian offensive, Pakistan launched a pre-emptive airstrike meant to neutralize the Indian airforce. This failed miserably, and thus started the formal war between India and Pakistan. The Indian strategy was primarily a defensive war on India’s Western border with Pakistan, and an all out Blitzkrieg on the East Pakistani front to liberate the Bengali’s.

The plan was masterminded by Major General Jacob-Farj-Rafael Jacob, the chief of staff of the Indian army’s eastern command who also happened to be a Sephardic Jew born in Calcutta.

Nixon and Kissinger, silent partners in the genocide to date, now sprung into action with a multi-pronged strategy to stop India.

1. Future POTUS George W Bush was sent to the United Nations to call for an immediate ceasefire (the only no votes came from the India friendly Soviet bloc) on the grounds India was violating the sovereignty of a neighboring nation.
2. Push Iran and Jordan to supply US arms to Pakistan with the understanding the US would replace the equipment during the next budgetary cycle
3. Push China to mass its troop on the Chinese border with India
4. Move a US carrier into the Bay of Bengal

Supplying arms to Pakistan without going through Congress was illegal because the Democrat controlled congress had been leaked the Blood telegrams and had cut off all further military aid to Pakistan. It didn’t matter to Nixon/Kissinger that what they were doing was illegal, or that involving China risked spreading the conflict.

China had a deep animosity to India, but reluctant to anger the Soviets demurred. The Soviets also moved their own aircraft carrier into the Bay of Bengal.

The Indian army destroyed the heavily outnumbered Pakistani army in rapid fashion, before any US machinations could bear fruit, and on December 16th, over 93,000 Pakistani troops surrendered, making it the largest surrender since World War 2.

In contrast to the atrocities meted out by the Pakistani army, India treated all Prisoners of War in strict accordance with the Geneva convention. It released more than 93,000 Pakistani’s in 5 months. The Pakistani’s were humiliated, and Bangladesh came into existence.

Anish Koka is a cardiologist. Follow him on twitter @anish_koka . Link to this story on twitter here.

Pakistan continues to dispute the events that transpired despite overwhelming evidence to the contrary. The US involvement is subject of a fantastic book by Gary Bass.

BY ANISH KOKA

If there was any doubt the academic research enterprise is completely broken, we have an absolute train wreck of a study in one of the many specialty journals of the Journal of the American Medical Association — JAMA Health.

I had no idea the journal even existed until today, but I now know to approach the words printed in this journal to the words printed in supermarket tabloids. You should too!

The paper that was brought to my attention is one that purports to examine the deleterious health effects of Long COVID. A sizable group of intellectuals who are still socially distancing and wearing n95s live in fear of a syndrome that persists long after a person recovers from COVID. There are any number of papers that argue a variety of putative mechanisms for how an acute COVID infection may result in long term health concerns. This particular piece of research that is amplified by the usual credentialed suspects on social media found “increased rates of adverse outcomes over a 1-year period for a PCC (post-COVID conditions) cohort surviving the acute phase of illness.”

In this case PCC (Post-COVID conditions), is the stand-in for Long COVID, and leading commentators use this paper to explicitly state that heart attacks, strokes and other major adverse outcomes doubled in people post-COVID at 1 year…

It is a crazy statement, and anyone regurgitating this has no business commenting on any scientific papers. Let me explain why.

In order to find out about the potential ravages of long COVID researchers need to be able to compare outcomes between those who were infected with COVID and now have long covid to those who were never infected with COVID. At this point finding a large enough group of people that never had covid is impossible, because everyone in the world will have been infected with COVID many, many times. It’s also really hard to define the nebulous long COVID because a study after study finds no clear objective markers of the disease.

The syndrome is defined by a nebulous collection of subjective symptoms COVID survivors feel. In cases like this, an ideal control group is people that think they had COVID, but never tested positive for COVID. This was achieved in this study in the midst of the pandemic which compared self-reported COVID19 infection with sars-cov2 serology results (published in the JAMA network too!) and found that persistent physical long-term symptoms were associated more with the belief of having experienced COVID-19 infection than with having had a positive Sars-COV2 lab test. (The notable exception was loss of smell).

The most recent study in JAMA-Health defines long COVID as patients who had at least 3 diagnoses coded in an electronic medical records claims database in patients who had a prior diagnosis of COVID or a prior COVID positive test. Individuals in the PCC cohort received 3 or more diagnoses for COVID-19 or COVID-19 symptoms across more than 1 visit during weeks 5 to 12 after their defined index date. Essentially everyone with COVID by default makes up the potential PCC sample. Of the 205,307 patients available for analysis with prior COVID, ~36,000 individuals were excluded for not having three or more COVID 19 symptoms at multiple visits 5-12 weeks after the COVID diagnosis. This left ~169,000 patients who continued to have at least three COVID symptoms that met criteria and were defined as having PCC or “longCOVID”.

The authors, and those amplifying this study seem to believe that ~70% of patients with COVID will go on to have chronic symptoms related to COVID. This is an absurd statement that has no basis in reality for anyone who lives in the real world. If it were true, everyone would be confined to their basement as opposed to packing Superbowl stadiums.

Of the massive list of diagnoses that would qualify a patient to have a chronic covid condition, the authors helpfully provide a distribution of the symptoms that made patients qualify.

Almost half of the patients still had an ICD10 diagnosis of hypoxemia, and a third had a diagnosis of cough coded 5-12 weeks after having had COVID. Researchers than compare this group of patients to a historical control that consists of patients matched for age, gender, socioeconomic status, and major comorbidities.

This allowed the researchers to come up with an expected rate of adverse events for a population that did not have COVID, and compare it to observed adverse events in the longCOVID group at 12 months.

The relative risk of every major adverse event is significantly increased in the post COVID group.

But what does this mean? Does COVID actually increase the risk of getting COPD , coronary disease, and an ischemic stroke by a factor of 2?

NO!

It means that patients who have a diagnosis of shortness of breath or hypoxemia coded in an electronic medical record are more likely to have a diagnosis of COPD placed in the electronic medical record in the 12 months after having had COVID. Vulnerable patients in a population who do not carry any official medical diagnoses are at risk of being hospitalized or falling ill when a novel respiratory virus appears. These same patients are then going to be more likely to have persistent symptoms regardless of whether the virus is a new strain of RSV, influenza, or the novel coronavirus. Patients who are admitted to the hospital with a covid pneumonia are also a lot more likely to be diagnosed with every single outcome that the study authors are looking for!

The COVID research explosion uncovers the dirty secret that much of academic medicine has turned into plumbing large datasets to fabricate clickbait conclusions to serve some ideological purpose. It’s hard to sort this out when the topic relates to a complicated medical topic in a prestigious journal. The default is to believe the conclusions published by credentialed people in big-name journals. But when the public that has had COVID multiple times over is told that 70% of patients who survived covid have long-covid symptoms and are now at twice the risk of every single major cardio/pulmonary/vascular recognized the statement for the lie it clearly is.

One can only hope the public wakes to the generally awful level of research being produced by a vast array of academics on topics well beyond COVID.

Anish Koka is a cardiologist in Philadelphia. Follow him on twitter @anish_koka

BY ANISH KOKA

The COVID19/vaccine myocarditis debate continues in large part because our public health institutions are grossly mischaracterizing the risks and benefits of vaccines to young people.

A snapshot of what the establishment says as it relates to the particular area of concern: college vaccine mandates:

Dr. Arthur Reingold, an epidemiology professor at UC-Berkeley, notes that UC also requires immunizations for measles and chickenpox, and people still are dying from COVID at rates that exceed those for influenza. As of Feb. 1, there were more than 400 COVID deaths a day across the U.S.

“The argument in favor of mandatory vaccination for COVID is no different than the argument for mandatory vaccination for flu, measles and meningitis,” Reingold said. “For a 20-year-old college student, how likely are they to die? The risk is very low. But it’s not zero. The vaccines are safe, so the argument of continuing to mandate vaccination fits very well with the argument for the other vaccines we continue to require.”

Safety is a relative term that needs to be constantly updated when you’re talking about administering a therapeutic to “not-yet-sick” individuals. We do not vaccinate against smallpox anymore because the absence of circulating smallpox (thanks to the smallpox vaccine campaign) makes the risks of the smallpoxt vaccine too great to be administered to the public.

We can argue endlessly about what exactly the risk of COVID19 was in the Spring of 2020, or 2021, but there should be little argument in 2023 that the risks of COVID pneumonia striking down a young healthy individual is now extremely low.

The other argument made by public health authorities is that myocarditis, the major adverse event linked to the mrna vaccines (Moderna worse than Pfizer), and Novovax actually happens more commonly with a COVID infection. I have made the case repeatedly since the Fall of 2020 that sars-cov2 (the virus that causes COVID), like the coronavirus family it comes from, has no specific proclivity for the heart, and that the published papers describing COVID19 myocarditis come from highly motivated cardiac imagers finding random bright spots on cardiac MRI devoid of clinical context and epidemiologists striking fools gold in research based on diagnostically sloppy electronic health record billing codes.

More evidence this past week that vaccine myocarditis is very much a real entity while COVID19 myocarditis is mostly a fabrication of academic researchers comes from Scandinavian countries.

A record request from a random Swedish twitter account reveals this impressive chart about myocarditis trends.

Notice that there is no spike in myocarditis diagnoses until the second half of 2021. Sweden, notably took a light approach to mitigation measures in 2020. They kept schools open, and they suffered large losses of life in care homes (as did every country) as evidence of a virus that was circulating widely through the population. And yet, there is no uptick in myocarditis cases in 2020.

This discrepancy isn’t a result of unawareness of COVID related heart issues as some have proposed because in 2020 the hysteria that surrounded COVID and the heart in 2020 was at a fever pitch. Viral videos from China of people suddenly collapsing, and the very bad German cardiac MRI paper I referenced earlier meant that everyone was looking for a tsunami of COVID heart disease. It just never materialized in the real world.

This data that was known to Swedish authorities in 2021, but not publicized to my knowledge, may have been why the Moderna vaccine with 3x the dose of mrna than Pfizer was banned for anyone < 30 years of age in the Fall of 2021 in Sweden.

The other dataset from last week comes from an epidemiological study that sought to understand the differences in prognosis between COVID19 myocarditis and vaccine myocarditis. The epidemiologists involved clearly were unaware about the issues related to the validity of the diagnosis of COVID19 myocarditis compared to vaccine myocarditis, and to top it off, were unable to specify simple things like what the severity or type of the numerically tiny primary outcome events (heart failure) they did find. As a study of prognosis of COVID vs. vaccine myocarditis, it’s a flimsy paper that is of zero clinical value. What is interesting about the study, despite the study authors admonishments not to look, is the number of vaccine associated myocarditis cases picked up during the study period¹.

There were almost 5 times as many vaccine myocarditis cases as there were “COVID19 myocarditis” cases in the time window in Scandinavia that was studied. The study authors caution against making a comparison about rates of vaccine vs. covid myocarditis using these numbers because no attempt to present any denominators for covid infections or people vaccinated is given, but given the multiple other rigorous datasets that have shown spikes in vaccine myocarditis cases after the vaccine and not COVID, it’s hard not to notice that over a common number of years studied, there are a lot more vaccine myocarditis cases being diagnosed.

And so we have a tale of two countries.

One that observed a spike in a novel serious adverse event primarily in young healthy males in the Fall of 2021, and chose to restrict the mrna vaccine that caused the most myocarditis to anyone < 30 years of age, and the other country that in February of 2023 still thinks heart problems after COVID 19 is five times more likely than vaccine myocarditis and recommends all COVID vaccines to everyone over 6 months of age.

If no one was paying attention to what the CDC said it wouldn’t really matter, but apparently epidemiologists and others with a weak handle on reality are still mandating vaccines for college kids.

It is well beyond time for these mandates to end, and well beyond time to strip the powers of the innumerate public health hypochondriacs that are running things. There’s at least a semblance of a debate to have about what powers competent public health authorities should have over society, but there can be little argument that inmates should not be running the asylum.

Anish Koka is a Cardiologist. Follow him on twitter @anish_koka

I have to make the obligatory post-script here that I oversaw the administration of hundreds of mrna vaccines starting in March of 2021 in my cardiology clinic. The vaccine efficacy data for the original data was from thousands of patients and I certainly felt given the devastation wreaked on many of my patients in 2020 that the vaccines were the best chance of avoiding morbidity and mortality. The process to get the vaccines from the city department of health was a somewhat arduous 3 month process, and once the vaccines were on hand, there were daily reporting requirements that I dutifully performed for the many months we were administering vaccines. To accommodate the rush of patients, employees, volunteers, and conscripted children worked multiple weekends to administer the vaccines. So I’m especially disgusted by medical colleagues who label any concerns registered about vaccine adverse events as “anti-vaxx”. Registering concern over a vaccine adverse event does not make doctors or patients “anti-vaxx”. It makes them pro-vaxx!

Footnote:

1. Recall that vaccine myocarditis cases are straightforward, usually previously healthy young men complaining of chest pain who have evidence of cardiac muscle cell necrosis and supporting cardiac imaging, while COVID myocarditis cases are almost always older, very ill hospitalized patients with pre-existing (sometimes undiagnosed) cardiac disease who have myocardial injury related to the stress of the primary diagnosis. The other COVID19 related myocarditis is not acute myocarditis, but an autoimmune condition that usually occurs months after recovery from COVID called MIS-C myocarditis. Important to note this entity has a lot of overlapping features with an autoimmune diagnosis called Kawasaki’s, and is now so rare that the CDC no longer tracks it.

BY ANISH KOKA

I recently saw a young man who came to see me because his place of future employment, a large health system was requiring him to complete the 1º series of his COVID-19 vaccination. He was concerned because he had chest pain after his first mRNA vaccine and was uncomfortable with the risks of a second mRNA dose. He attempted to get a Johnson and Johnson vaccine and was told by pharmacists he was not allowed to mix and match this particular vaccine as he had already received an mRNA dose. With no other option, he came to ask me whether I thought a vaccine exemption was reasonable in his case. He already had a family medicine physician sign an exemption that had been denied by his future employer’s vaccine exemption committee. The young man works on the “back end” of the health system remotely from home and he has no patient contact. The entire process has caused him to lose his health insurance from his former employer, and he was now paying out of pocket for an expensive COBRA health insurance plan. What follows is my letter to the vaccine exemption review committee regarding his case. (Published with permission, only the relevant names have been changed/redacted)

Dear Vaccine Exemption Review Committee,

I am writing this letter on behalf of John Smith DOB: xx/xx/xx in regard to a mandate from xxxx Health that Mr. Smith receive a second dose of an mRNA vaccine to complete his primary COVID-19 vaccine series.

Mr. Smith has asked me to render an opinion specifically related to his cardiac risk of receiving a second dose of an mRNA vaccine. I am a board-certified cardiologist in Philadelphia, Pennsylvania, and have been in active clinical practice for 13 years.

After reviewing the details of his case, I have grave concerns about compelling him to receive a second dose of an mRNA vaccine and would like to outline the reasons for my conclusion in this letter. I am going to specifically discuss his risk of an important, now well-recognized, adverse event: vaccine myocarditis.

What follows is some important background information about vaccine myocarditis that has been gleaned over the last 2 years before I discuss the particulars of Mr. Smith’s case.

It is relevant to note here that as a physician active clinically in both the inpatient and outpatient arenas, I am an eyewitness to the severe toll COVID-19 took on my patients in the Spring or 2020. I was impressed enough with the initial mRNA vaccine data to acquire the vaccine available from the Philadelphia Department of Health (Moderna) and ran multiple vaccine clinics in order to vaccinate my mostly high-risk patients.

What follows is data produced since the vaccine rollout that is relevant to Mr. Smith’s case.

The mRNA vaccines cause myocarditis

The risks of the novel mRNA vaccine were first clarified in April 2021 by Israeli researchers who first identified a causal link between the mRNA vaccines and myocarditis and also noted the higher incidence of myocarditis after the “second dose in young males.”

The highest incidence of vaccine myocarditis is in young men after the second dose

A number of subsequent studies that have attempted to quantify the risk of myocarditis are of variable quality largely because a number of studies used pooled risk estimates across the entire population, ignoring the observation that vaccine myocarditis has its highest incidence in young males. Studies that examine the incidence of myocarditis by age, sex, dose and manufacturer provide the most granularity with regard to risk estimation. A systematic review of vaccine myocarditis papers clearly demonstrates the highest incidence of vaccine myocarditis in young males after dose 2, and also highlights the uselessness of papers that do not stratify incidence of myocarditis by age, sex and dose of vaccine.

Vaccine myocarditis is higher risk than COVID myocarditis in young men

A comprehensive study from England clearly demonstrated vaccine myocarditis to be more common than COVID19 myocarditis in age < 40 despite the fact this study greatly overestimates COVID19 myocarditis rates because it underestimates the total number of COVID19 infections.

Recent studies bring into question the diagnosis of COVID19 myocarditis

A recent cardiac imaging study suggest myocarditis is not the major mechanism of cardiac injury after a COVID-19 infection.

An accompanying editorial notes “Data from COVID-Heart provide reassuring evidence that myocarditis, once predicted to be an emerging public health crisis attributable to COVID-19, is relatively uncommon even among hospitalized patients and is less virulent than predicted during the early days of the pandemic. It is likely that elevated cardiac troponin concentrations during COVID-19 in many patients do not reflect significant new myocardial injury and fibrosis, but rather cardiac troponin release from vulnerable hearts with pre-existing scar in the setting of severe illness”

Data obtained by a record request from Sweden clearly demonstrate elevated rates of myocarditis in the time period after initiation of the COVID mass vaccination campaign, with no appreciable increase in the rate of myocarditis during widespread COVID in the year prior.

This spike in myocarditis diagnoses seen only after initiation of the vaccination campaign is corroborated by rigorous studies

6. requiring corroboration of a myocarditis diagnosis with the appropriate clinical context and cardiac imaging.

Recovery from a COVID infection confers strong, durable protection against future COVID infections

A systematic review and meta-analysis of prior infection with COVID suggests protection against re-infection “was very high and remained high even after 40 weeks.” The authors of this paper go on to suggest that “the immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19”.

Vaccine myocarditis can be serious and life threatening.

The vast majority of cases of vaccine myocarditis requires hospitalization for monitoring for deterioration. While the majority of patients are discharged home to recover, the current recommendation is for recovering patients to avoid strenuous activity for 6 months. A majority of patients that follow up for cardiac MRI imaging are seen to have scar in long term follow up. There are also case reports of severe morbidity and mortality from vaccine myocarditis resulting in critical illness or death.

Prior episodes of vaccine myocarditis have been linked to an increased risk of myocarditis with future vaccinations

Two case reports from Australia describe myocarditis after administration of the Novavax vaccine to two young individuals who had recovered from mRNA vaccine myocarditis. 

The two case reports from Australia aren’t even the first reports of Novovax myocarditis after mRNA vaccine myocarditis. In August, the CDC reported 29 cases of pericarditis, including five in persons with a history of pericarditis after mRNA COVID-19 vaccine; 

Importantly, the Novovax vaccine is a protein-based vaccine that was hoped to not be associated with myocarditis as was noted with the mRNA vaccines. Unfortunately, these report of myocarditis occurring after Novovax delivery in patients who had a prior case of mRNA vaccine myocarditis suggests a history of vaccine myocarditis should serve as a contraindication to any future COVID-19 vaccines.

Summary / Recommendations:

Mr. Smith is a 31 year old man with no medical history. He emphatically denies any history of cardiopulmonary disease. He received his first dose of a Pfizer mRNA COVID-19 vaccine in June 2021. He subsequently describes having sharp chest pain over the next few weeks. He did not seek any medical evaluation at the time as he did not link the chest pain with the first dose of the vaccine he received. The pain resolved a few weeks later. He has had COVID twice, first in September of 2020, and his second time in January of 2023.

His cardiac testing completed to date consist of an electrocardiogram and an echocardiogram performed Feb 16th, 2023 that were both normal.

I think it is certainly possible Mr. Smith may have had myocarditis after the first dose of his mRNA vaccine. As I discussed with Mr. Smith, a cardiac MRI would not change my opinion on the matter as a normal result this many months from his original presentation would not rule out acute myocarditis. If he did have a case of vaccine myocarditis after his first dose of an mRNA vaccine, I think he would be at risk for developing myocarditis with another COVID-19 vaccination. I will note here that Mr. Smith did try to fulfill the mandate to complete a primary series of a COVID-19 vaccination by attempting to get a Johnson and Johnson vaccine. He was turned away by the pharmacists who noted the Johnson and Johnson vaccine was not approved to be given after a first dose of an mRNA vaccine.

As I have detailed, while most cases of vaccine myocarditis have not been shown to result in severe morbidity or mortality, there are clearly case reports of severe vaccine myocarditis. Especially given Mr. Smith has had two separate COVID infections, with his most recent infection in January of 2023, it is very unlikely that the unclear benefits of a second dose of a COVID-19 vaccine are outweighed by the risk of vaccine myocarditis.

I understand the committee has concerns beyond individual protection with regards to vaccination as it was hoped that vaccinations against COVID19 would reduce the likelihood of transmission of the virus and thus provide protection to the community in addition to the individual. As you know, the initial randomized control trials were not designed to test for reduction in transmission, and the degree of reduction in transmission is a matter of debate now. Beyond the unknown efficacy of the vaccines related to transmission risk, there does appear to be growing consensus about the equivalence of a prior infection from COVID and vaccination. The meta-analysis on prior infection referenced above prompted the Chairman of Medicine from UCSF, Dr. Bob Wachter to write :

Since nearly all unvaxxed have been infected by now (many>once), study lowers the case for vax mandates, since those w/ prior infection likely have protection not materially worse than if they were vaxxed.

It should also be relevant that Mr. Smith is a non-clinical, remote worker who has no direct contact with patients or other healthcare staff.

For all of the above reasons, I would respectfully ask members of the vaccine exemption committee to reconsider and grant Mr. Smith an exemption from the company’s vaccine mandate.

Yours Sincerely,

Anish Koka MD

Cardiologist

Philadelphia, Pennsylvania

One of the hallmarks of the last two years has been the distance that frequently exists between published research and reality. I’m a cardiologist, and the first disconnect that became glaringly obvious very quickly was the impact COVID was having on the heart. As I walked through COVID rooms in the Spring of 2020 trying to hold my breath, I waited for a COVID cardiac tsunami. After all social media had been full of videos from Wuhan and Iran of people suddenly dropping in the streets. My hyperventilating colleagues made me hyperventilate. Could it be that Sars-COV2 had some predilection for heart damage?

Happily, I was destined for disappointment. There never was a cardiac tsunami from COVID.

There were, unhappily, lots of severely ill patients with lungs that were whited out who quickly developed multi-organ dysfunction while hospitalized. The lungs were where almost all the action was. Every other organ got hit hard because of the systemic illness that unfortunately often is a downstream result of a severe respiratory illness. Cardiac Cath labs waiting for some major influx of COVID heart damage not only didn’t see patients presenting with COVID heart attacks, but they idled as patients terrified of coming to the hospital stayed home rather than come to the hospital with chest pain. (Public health messaging about COVID appears to have kept people away from hospitals, and autopsy series of deaths during the pandemic found that reduced access to health care systems (for conditions such as myocardial infarction) was further likely to be identified as a contributory factor to death than undiagnosed COVID-19).

So imagine my surprise when I saw peer-reviewed research based on a cardiac MRI study come out in 2020 suggesting that 78% of patients who survived COVID may have significant heart damage. A more detailed read of the paper, of course, threw up massive problems. The article and authors were more suited as writers for Oprah and Dr. Phil than for a well-respected academic journal. But the damage was done, and the notion that COVID was attacking hearts spread via a social media influencer class that should have had the credentials and smarts to know better, but clearly didn’t.

This was all completely bonkers to witness in real-time. But it got worse.

The next blow to reality came from epidemiologists seeking to capitalize on journals’ hunger for COVID research. They were aided by sloppy electronic medical record databases that contained lots and lots of ICD10 diagnoses. The specific problem when it comes to diagnosing myocarditis by ICD10 codes only is that there is remarkably little work that goes into verifying the patient actually has myocarditis. When someone presents to the hospital with chest pain and clinicians go through the appropriate steps to diagnose myocarditis (exclude other diagnostic possibilities, supportive imaging/biopsy data), one can be fairly certain the diagnosis is indeed correct. But too often, a diagnosis of myocarditis is attached to severely ill patients who have evidence of myocardial injury as a result of the severe illness that brought them to the hospital. Importantly these diagnoses get attached to patients despite missing the traditional clinical context of myocarditis (chest pain) or imaging/biopsy evidence. The exact same pattern of heart damage would likely have been seen after an illness for the flu virus, or really any other diagnosis that resulted in a severe medical illness.

But the politics was all-pervasive. Vaccine myocarditis was recognized as a serious adverse event of concern in April of 2021, and a growing public outcry about the danger could only be quelled by data that showed COVID myocarditis was an even riskier proposition. And so the CDC gave marching orders to convince the population to be vaccinated trotted out their own bad EMR studies to show COVID myocarditis was a far greater risk than vaccine myocarditis.

The party told you to reject the evidence of your eyes and ears. It was their final, most essential command. – George Orwell, 1984

The evidence of your eyes and ears can only be rejected for so long apparently. A recent paper from the United Kingdom attempted to examine the mechanism of cardiac injury in COVID hospitalized patients by performing cardiac MRIs within 28 days of a discharge for a COVID hospitalization. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 patients without COVID-19 or elevated troponin levels matched by age and cardiovascular comorbidities (COVID−/comorbidity+). Cardiac MRI studies that go hunting for a particular diagnosis are always going to be plagued by overdiagnosis and this study is no exception. 1.7% of the community control group were diagnosed with recent myocarditis using MRI criteria – a rate that is well in excess of the 0.01-02% background rate of myocarditis. The vast majority of MRI abnormalities found in recently hospitalized COVID patients are related to pre-existing cardiac disease. The accompanying editorial concurred.

Data from COVID-Heart provide reassuring evidence that myocarditis, once predicted to be an emerging public health crisis attributable to COVID-19, is relatively uncommon even among hospitalized patients and is less virulent than predicted during the early days of the pandemic. It is likely that elevated cardiac troponin concentrations during COVID-19 in many patients do not reflect significant new myocardial injury and fibrosis, but rather cardiac troponin release from vulnerable hearts with pre-existing scar in the setting of severe illness

This whole saga should raise a lot of questions about the role of the medical community, and specifically the academic cardiology community in fanning the flames of the panic that directly lead to the massive societal disruption of the last 2 years.

Essentially a number of motivated researchers rushed bad studies to publication in major journals that suggested COVID had a special proclivity for heart damage. This was, in part, what was used to support vaccine mandates, school closures, and minimizing vaccine myocarditis!

After all, who cares about vaccine myocarditis in young boys and men, if the prevalence of covid myocarditis was higher? But it’s not. And it never was.

The epidemic of COVID myocarditis was a creation of really bad academic imaging researchers and epidemiologists who went on Electronic Medical Record diagnosis code data mining expeditions. The safeguards that exist specifically to safeguard the truth – the CDC, peer review, and academic culture not only failed to contain the spread of this myth but actively participated in the promulgation of misinformation!

The damage is far from contained. Epidemiologists from Scandinavia just released another comparison of vaccine myocarditis, covid myocarditis, and conventional myocarditis. There are all sorts of conclusions that are drawn based on the data, but the same disconnected-from-reality formula applies: use a database of diagnosis codes to arrive at relative rates of myocarditis, without trying to establish the veracity of the myocarditis diagnosis clinically by chart review. As a result, these are hopelessly confounded comparisons that are almost completely irrelevant. When questioned on the matter, first author Anders Hviid suggests ignoring the COVID-19 myocarditis data, and just focusing on the vaccine myocarditis data.

Recall that the vaccine myocarditis diagnoses are much less likely to suffer from diagnostic uncertainty because their primary presentation involves a formerly healthy individual presenting with chest pain and cardiac biomarker release indicating cardiac cell death shortly after vaccine administration. All of these patients are then ruled out for other causes of chest pain, and then almost invariably get cardiac imaging or a biopsy to support the diagnosis of myocarditis. Focusing only on the vaccine myocarditis outcomes as Dr. Hviid recommends is not pretty.

Of the 530 cases of diagnosed vaccine myocarditis, 22 had a diagnosis of heart failure within 90 days of follow-up, and 6 died. Frustratingly, without any additional clinical information, it is impossible to read any further into this data. Were the 6 deaths related to vaccine myocarditis? How bad was the heart failure reported? I have no idea.

One hopes the recent imaging studies will put an end to the fictional beast of COVID-19 myocarditis, but I’m doubtful.

Anish Koka is a Cardiologist. Follow him on twitter @anish_koka

I have to make the obligatory post-script here that I oversaw the administration of hundreds of mrna vaccines starting in March of 2021 in my cardiology clinic. The vaccine efficacy data for the original data was from thousands of patients and I certainly felt given the devastation wreaked on many of my patients in 2020 that the vaccines were the best chance of avoiding morbidity and mortality. The process to get the vaccines from the city department of health was a somewhat arduous 3 month process, and once the vaccines were on hand, there were daily reporting requirements that I dutifully performed for the many months we were administering vaccines. To accommodate the rush of patients, employees, volunteers, and conscripted children worked multiple weekends to administer the vaccines. So I’m especially disgusted by medical colleagues who label any concerns registered about vaccine adverse events as “anti-vaxx”. Registering concern over a vaccine adverse event does not make doctors or patients “anti-vaxx”. It makes them pro-vaxx!

BY ANISH KOKA

Myopericarditis is a now a well reported complication associated with Sars-Cov-2 (COVID-19) vaccinations. This has been particularly common with the messenger RNA (mRNA) vaccines (BNT162b2 and mrna-1273), with a particular predilection for young males.

Current guidance by the Australian government “technical advisory groups” as well as the Australian Cardiology Society suggest patients who have experienced myocarditis after an mRNA vaccine may consider a non-mRNA vaccine once “symptom free for at least 6 weeks”.

A just published report of 2 cases from Australia that document myopericarditis after use of the non-mRNA Novavax vaccine in patients that had recovered from mRNA vaccine myocarditis suggests this is a very bad idea.

The case reports

Case 1 involves a 26 year old man who developed pericarditis after the Pfizer vaccine. Pericarditis, an inflammation of the sac the heart lives in, developed about 7 days after the Pfizer vaccine. The diagnosis was made based on classic findings of inflammation on an electrocardiogram associated with acute chest pain. The symptoms lasted 3 months, and a total of 6 months after the first episode of pericarditis, he received a booster vaccination with the Novovax (NVX-CoV2373) vaccine. 2-3 days after this he developed the same sharp chest pain and shortness of breath with elevated inflammatory markers (CRP) as well as typical findings of pericarditis seen on ECG. To add insult to injury, he contracted COVID 2 months after the second episode of pericarditis, but had no recurrence of the symptoms of pericarditis.

Case 2 involves a 25 year old Australian female who presented with chest pain, shortness of breath and palpitations 2 days after her 2nd dose of Pfizer vaccination. Abnormal cardiac biomarkers suggested damage to the heart muscle confirming myocarditis. The distinction between pericarditis and myocarditis generally hinges on the presence of damage to the cardiac muscle that’s discovered based on blood tests for cardiac biomarkers that suggest ongoing damage/necrosis of heart cells. Case 1 was a case of pericarditis, not myocarditis, because there was no evidence of damage to cardiac cells (cardiac blood test Troponin biomarkers were not elevated).

Myocarditis is generally considered a more serious clinical condition because of the association of damage to the cardiac muscle that is, unfortunately, irreversible. Her course was, as a result, more complicated with persistent symptoms that required recurrent hospital presentations for 5 months. While two-thirds of patients in the pediatric US experience demonstrate a persistent scar on cardiac MRI at 6 month follow-up, a repeat MRI in this case was normal with complete resolution of previously seen abnormalities.

Remarkably, and I suspect in no small part due to the guidance of the Australian technical advisory committee, and the defacto blessing of the Australian cardiac society, she went on to be vaccinated with the Novovax vaccine. 5 days later she once again complained of chest pain, shortness of breath and palpitations. An evaluation revealed another episode of myocarditis. She has had multiple repeat hospital presentations and 2 months later continues to be symptomatic.

There is no clinical history or context provided to help us understand why these two young people needed another COVID19 vaccine booster. It is certainly possible both were considered very high risk for developing a serious COVID infection, but that information is not provided in the published case report. Recall, that the young man in case 1 still went on to contract COVID-19 even after his Novovax booster.

These cases, while unfortunate, do provide some very important insights about the potential mechanism of vaccine associated myocarditis.

Vaccine myocarditis : mechanistic insights

The molecular mimicry theory posits that antibodies the body is induced to produce to the viral S-protein also may recognize parts of the body as foreign and attack itself. But the molecular mimicry hypothesis should result in similar rates of vaccine myocarditis with mrna and non-mRNA vaccines, and this is clearly not the case. Rates of vaccine myocarditis are clearly lower with the more traditional AstraZeneca protein based vaccine.

Hypotheses to try to explain why the mRNA vaccines specifically seem to have more myocarditis focus on the novel nature of using mRNA as a vaccine delivery vehicle.

It is possible that the mRNA strand that is supposed to be locally taken up by muscle cells in the deltoid muscle in the arm, may not be as prone as a protein based system to staying local and instead may be taken up by far flung organs like the heart. Cardiac cells would then transcribe the mRNA message and “present” the S-protein on their cell surface. The inevitable antibody response would result in the body’s immune system attacking cardiac cells that incorporated the S-protein.

Other hypotheses focus on the delivery platform that makes the normally fragile mRNA stable enough to be used as a vaccine : a lipid “sheath” the mRNA is encased in that is referred to as a lipid nanoparticle (LNP). Lipid nanoparticles have a long history of being used as a drug delivery mechanism and the major issue pharmaceutical companies have struggled with using LNPs is immune activation.

As a result, the prior most commonly used drug delivered in a lipid nanoparticle, the cardiac anti-amyloid drug Onpattro, required pre-medication with a high dose of steroids before every 80 minute infusion to make it tolerable for patients.

The arrival of the Novavax vaccine added to the COVID vaccine armamentarium by taking the viral S-protein and enclosing it in a lipid sheath, which is distinct from the widely used Moderna/Pfizer product that encloses RNA in a lipid nanoparticle, and the Oxford-AstraZeneca and Janssen product that puts DNA in a viral vector.

If vaccine myocarditis was primarily a function of mRNA, the protein based Novovax vaccine would hopefully be able to deliver protection from COVID without the risk of myocarditis. Unfortunately, the occurrence of 2 almost identical presentations of myopericarditis with the Novovax and mRNA vaccine suggests otherwise.

The tragedy here is that this wasn’t a surprise. Myocarditis and/or pericarditis were reported by two participants after the Novavax COVID-19 Vaccine, Adjuvanted (0.01%) and no participants after placebo. Events of cardiomyopathy or cardiac failure were reported by eight participants after the Novavax COVID-19 Vaccine, Adjuvanted (0.03%) and one participant after placebo (<0.01%). Per the FDA Emergency Use Authorization, the available information on cardiomyopathy or cardiac failure was insufficient to determine a causal relationship with the vaccine.

Post-approval surveillance brought to light more cardiac activity of the Novovax vaccine. Among a total of 41,546 vaccine recipients aged ≥16 years, six cases of myocarditis or pericarditis were detected; five occurred within 20 days of vaccination. Among these five, four did not have likely alternative etiologies, suggesting a possible causal relationship with vaccine.

In global post-authorization surveillance, among 744,235 doses of Novavax COVID-19 vaccine administered in Australia, Canada, the European Union, New Zealand, and South Korea, 35 reports (representing 36 adverse events) were identified among 20 male and 15 female vaccine recipients with a median age of 34 years (range = 23–62 years).

The 2 case reports from Australia aren’t even the first reports of Novovax myocarditis after mRNA vaccine myocarditis. In July, the CDC reported 29 cases of pericarditis, including five in persons with a history of pericarditis after mRNA COVID-19 vaccine; four myocarditis cases; two myopericarditis cases; and one case of carditis, not otherwise specified. A postmarketing analysis from Australia also identified three cases of myocarditis and 12 cases of pericarditis reported during a period in which 160,000 Novavax COVID-19 vaccine doses were administered.

So even though the US CDC had noted cases of Novovax vaccine related myocarditis in August 2022 in patients with a prior history of mRNA pericarditis, the Australian guidelines fail to list a prior history of mRNA vaccine myocarditis as a contraindication to future COVID19 vaccinations.

If you dig a little bit you will eventually find that the current US CDC guidelines is actually more sane than the Australian guidelines and generally advises prior mRNA vaccine myocarditis cases not receive subsequent doses of any COVID-19 vaccine.

It is a bit confusing as you can see from the CDC summary that recommends COVID-19 vaccination for everyone 6 months of age and older because “the benefits… outweight the risk of myocarditis and pericarditis after receipt of mRNA COVID-19 vaccines”

The just published case-reports should be the nail in the coffin for anyone, anywhere trying to give a COVID-19 vaccine to someone with a prior episode of COVID-19 vaccine myocarditis.

Despite the fact vaccine myocarditis has been associated with the Novovax vaccine since the trials that lead to its approval in the US, vaccine advisory panels and medical societies seemingly stuck their heads firmly in the sand. Those in charge of vaccine policy were so averse to recommending against vaccine administration to anyone, that they couldn’t even explicitly warn those with a prior episode of COVID vaccine myocarditis against receiving future COVID vaccines.

The Novovax myocarditis cases that occurred after the US CDC summer analysis were clearly preventable adverse events. It is very hard to understand, even without this data, how physicians or medical societies sanctioned administration of a COVID vaccine to those who had already had COVID vaccine myocarditis.

Interestingly, the Novovax social media team has clearly picked up on the prevailing mRNA vaccine hesitancy to try to generate demand for their product at a time there is very little demand for any COVID vaccines.

The story is a nice distillation of what lies at the heart of the outsize influence random dudes on twitter have developed relative to White House COVID czars. If the real leaders of medicine can’t critically analyze the data to explicitly recommend against those with prior COVID vaccine myocarditis receiving future COVID vaccines, what else are they getting wrong?

Our public health officials are just not very good. The scorn much of the public feels for the institutions and the credentialed class that purport to have the public’s best interest at heart is well earned. Hopefully Santa has stuffed their stockings with common sense for the New Year.

I’m not holding my breath.

Anish Koka is a cardiologist. Follow him on Twitter @anish_koka.

I have to make the obligatory post-script here that I oversaw the administration of hundreds of mrna vaccines starting in March of 2021 in my cardiology clinic. The vaccine efficacy data for the original data was from thousands of patients and I certainly felt given the devastation wreaked on many of my patients in 2020 that the vaccines were the best chance of avoiding morbidity and mortality. The process to get the vaccines from the city department of health was a somewhat arduous 3 month process, and once the vaccines were on hand, there were daily reporting requirements that I dutifully performed for the many months we were administering vaccines. To accommodate the rush of patients, employees, volunteers, and conscripted children worked multiple weekends to administer the vaccines. So I’m especially disgusted by medical colleagues who label any concerns registered about vaccine adverse events as “anti-vaxx”. Registering concern over a vaccine adverse event does not make doctors or patients “anti-vaxx”. It makes them pro-vaxx!

BY ANISH KOKA

Reanalysis of a trial used to approve a commonly used injectable cholesterol-lowering drug confirms the original analysis by accident.

The open-data movement seeks to liberate the massive amount of data generated in running clinical trials from the grasp of the academic medical-pharmaceutical industrial complex that mostly runs the most important trials responsible for bringing novel therapeutics to market.

There are only a few elite academic trialist groups capable of running large trials and there’s ample reason to be suspicious about the nexus that has developed between academia and the pharmaceutical companies that shower them with cash to hopefully get a positive study result and pay off the pharmaceutical research investment manifold. The FDA is the major regulator of the whole process, but the expertise required for regulation means that the FDA is frequently comprised of ex-pharma employees or ex-academics.

The voluminous data generated in trials is usually owned by the academic group doing the research and is frequently guarded heavily from outsiders who may seek to probe it. Many, of course, believe that the data should be made public for independent third-party review.

Discovering discrepancies in a major published trial from the pharma-academic complex would be a boost to those seeking to force trial data to be public, and that is exactly what a group of investigators attempted to do with a major cholesterol-lowering trial published in 2017.

But first, some background.

Cholesterol-lowering is big business.

The global market for the most commonly used class of drugs used to improve cholesterol levels is $14.3 billion dollars. Highly potent statins are now generic, accessible to most Americans for ~$4/month, and when tolerated, very effective at reducing a sticky molecule that floats around in the bloodstream called low-density lipoprotein (LDL).

LDL floats around in the bloodstream and is thought to incrementally accumulate on blood vessels in the body, ultimately increasing the risk of heart attacks and strokes. There is some controversy about whether LDL is the best metric to follow with regards to cardiovascular risk, but there are a wealth of randomized control trials of a variety of therapeutics that reduce LDL and also reduce the risk of heart attacks and strokes (the LDL hypothesis).

Statins inhibit the intracellular liver enzyme HMG-CoA reductase, which then results in up-regulation of LDL receptors on the surface of the liver cell. These receptors “catch” LDL particles that are floating by and incorporate them into the liver cell leading to less LDL in the bloodstream to cause vascular problems.

But while statins are believed to have been a big part of the reduction in cardiovascular morbidity seen in the last three decades, people still have heart attacks and strokes.

The obvious question when dealing with this residual cardiovascular risk is whether driving LDL concentrations down even further would significantly lower or even abolish heart attacks and strokes.

The effort to suppress LDL even further lead to the development of an entirely new class of lipid lowering agents that boosted the concentration of LDL receptors on the liver cell surface. Scientists noted an intracellular protein called PCSK9 combined with LDL and the LDL receptor lead to degradation of the entire complex in the cell’s incinerator otherwise known as the lysosome. A monoclonal antibody developed to bind the PCSK9 protein (a PCSK9 inhibitor) that prevented formation of the PCSK9-LDL receptor-LDL complex, prevented the LDL receptor from being degraded in the lysosome, and resulted in recycling of the LDL receptor to the cell surface. Use of a PCSK9 inhibitor in addition to a statin results in much higher concentration of LDL receptors on the cell surface than with a statin alone, which results in profound lowering of LDL well beyond what was seen with statins alone.

Proving benefit, and ensuring safety of this novel class of drugs with potential wide applicability requires large randomized clinical trials, and the FOURIER trial was just that vehicle. Trials of this size are complex and can’t be done by just anyone, which is why the famed TIMI group was tasked with the job. The TIMI (Thrombolysis in Myocardial Infarction) Study Group is a Division of Cardiovascular Medicine at the esteemed Brigham and Women’s Hospital and Harvard Medical School.

Those of us hoping that super low LDL levels would abolish cardiovascular disease were pretty disappointed with the results of the trial published in 2017. While the drug destroyed LDL levels in blood compared to the control arm, it didn’t come anywhere close to abolishing cardiovascular disease.

It did, however, reduce a composite cardiovascular endpoint by a statistically significant 1.5% which greatly impressed some clinical trialists.

But the primary endpoint here was a composite endpoint of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The positive results described were driven almost entirely by fewer heart attacks and fewer revascularization procedures in the evolocumab arm. Importantly, there was no difference in cardiovascular death or death from any cause.

As a brief aside: The PCSK9 inhibitor class of drugs were approved by the FDA because of trials like FOURIER, and the drug hit the US market with a list price of $14,000 / year. Insurance companies balked at those prices and put up road blocks to patient access by way of onerous prior authorization processes. The makers of the 2 PCSK9 inhibitors eventually buckled and slashed list prices of the drug by 60% in 2019 in an effort to expand use of the drug.

The FOURIER results piqued the curiosity of another group of investigators who were suspicious about certain irregularities they noticed. The Restoring Invisible and Abandoned Trials (RIAT) initiative is an international effort to tackle bias in research reporting whose goal is to provide more accurate information to patients and other healthcare decision makers. This group noticed the numerically higher (but statistically insignificant) number of cardiovascular deaths and all cause deaths in the evolocumab arm in the FOURIER trial. They also noted that most cardiovascular deaths (n=372/491; 75.8%) were classified as ‘other cardiovascular death’, not as myocardial infarctions or congestive heart failure, which typically predominate among cardiovascular deaths.

To the RIAT group, this was grounds for a re-analysis based on the Clinical Study Report (CSR) that provides more abundant and detailed evidence than had been published. The CSR is a technical document prepared by the manufacturer and submitted to regulators as part of the approval package for drug evaluation. It contains information about the trial’s protocol, amendments, inclusion and exclusion criteria, outcome definitions and measurement, efficacy and safety results and statistical analysis plan. The main FOURIER CSR is over 25,000 pages.

The RIAT analysis, published in the BMJ Open found that for 360/870 deaths (41.4%), the cause of death adjudicated by the FOURIER clinical events committee differed from that declared by the local clinical investigator. After readjudication, deaths of cardiac origin were numerically higher (though still statistically insignificant) in the evolocumab group than in the placebo group in the FOURIER trial, suggesting possible cardiac harm. Based on this, the RIAT authors advised “clinicians should be sceptical about prescribing evolocumab for patients with established atherosclerotic cardiovascular disease.”

The gravity of the charges made can’t be understated. The RIAT group essentially was calling out the prestigious TIMI investigators, alleging incompetence.. or worse. They were also calling into question the FDA oversight of the trial that was supposed to be doing the job of verifying the data submitted. It made for a neat story for those suspicious of the pharmaceutical-medical complex and the FDA regulators frequently supplied from academia and industry.

The TIMI group was not shy in their response.

Writing in a rapid response comment to the RIAT analysis, the TIMI group noted they had a lot more information that was available to the RIAT investigators to adjudicate adverse events.

The article by Erviti et al. is fundamentally flawed, using incomplete data to reach incorrect conclusions. In FOURIER, 2 event adjudication followed a rigorous, pre-specified, blinded process by the TIMI Clinical Events Committee (CEC). The occurrence of potential cardiovascular events of interest triggered collection of a full dossier containing all relevant and available source documents, including hospital notes, laboratory, ECG and imaging data, procedure reports, resuscitation or code summaries, death certificates, and autopsy reports. Each dossier was independently evaluated by 2 experienced, board-certified cardiologists (cardiovascular events) or neurologists (cerebrovascular events), blinded to treatment allocation.

The TIMI group also noted the FDA audited the adjudication process, and questioned the training the RIAT investigators had to adjudicate deaths.

The adjudication charter was approved by the FDA before the trial commenced. At the end of the trial the FDA audited the adjudication process and results and had no findings of concern.
In contrast, the authors’ work was post hoc and relied only on one document: the CSR narrative, which was generated predominantly based on limited information provided by the site upon learning of the event and not intended for the purpose of formal event adjudication. It is unclear what training and expertise, if any, those classifying events for this paper had.

Even more devastating was the TIMI group’s examination of two examples of mistaken death adjudication the RIAT group had forwarded in their BMJ Open analysis. It turns out the RIAT death adjudication process consisted primarily of re-affirming the local investigators initial cause of death. The TIMI group pointed out that the job of their clinical events committee was to investigate each death using local source documents and reclassify deaths when appropriate.

In the first case, the authors state the patient “clearly” had an MI, which was “neglected” by the FOURIER CEC. In reality, the source documents show this patient died in his sleep, and thus according to the FDA definitions, the FOURIER (TIMI) CEC properly adjudicated this as sudden cardiac death. In the second case, the authors state the patient died of an MI that was “misadjudicated” by the FOURIER CEC as a non-cardiovascular death. In reality, the source documents show this patient slipped in his kitchen, struck his head, was admitted to the ED with head trauma and died, which would not be considered a CV death.

It would appear to the objective observer that the RIAT group may have had good intentions, but had no idea what they were doing. The other curiosity here is the editorial freedom given the RIAT authors to publish a warning to physicians about prescribing these drugs based on a signal of harm that was essentially fabricated. Given how careful authors must be in their wording in manuscripts when presenting positive results of drug/device trials, it would appear there’s a fair degree of editorial bias that allows the publication of salacious claims about a pharmaceutical company and the group tapped to run their trials with much less evidence. At the very least, a discriminating editor would have vetted the allegations with the TIMI group before publishing a document that suggested clinicians be cautious of prescribing a drug because of a signal of harm.

But beyond this particular trial, and the controversy surrounding the poorly done reanalysis there are important questions regarding the responsibility trialists have for transparency of data. The reanalysis failed in this case because the RIAT authors did not have access to the same data the primary investigators had. It should be particularly galling that there is no easy mechanism for the public to access primary source documents even in taxpayer-funded trials. The current approach gives a virtual monopoly to a few large trialist groups like the TIMI group and makes the FDA the only oversight body. At a time when trust in the pharmacy-academic industrial complex and the public institutions is at an all time low, it’s understandable there’s a hunger for independent analysis and oversight.

This would require a significant infrastructure investment , and clearly badly done analyses performed by amateurs would only worsen the signal-to-noise ratio and confuse the public.

The Open Data movement stumbled badly here, but in doing so provides much food for thought.

Anish Koka is a cardiologist. Follow him on twitter @anish_koka