Sep 25 2020 This Week in Cardiology – Medscape

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For the week ending September 25, 2020, John Mandrola, MD comments on the following news and features stories.

The American Academy of Pediatrics (AAP) released guidance on return to sport after COVID-19. It is a well-meaning document, but it is a mess, and it is potentially dangerous to youngers. There are specific lessons and general ones.

SARS-CoV-2 is a virus. The most common cause of myocarditis is viral infection. People with myocarditis appear sick; they have chest pain, arrhythmia, often there are ECG changes, and you can measure blood markers of inflammation like CRP or ESR. Troponin assays these days are so darn sensitive that even a minimal amount of heart irritation will cause the troponin enzyme to be elevated. If a person has active myocarditis from ANY virus, it is a bad idea to stress the heart by exercising.

Back in pre-COVID times, did cases of myocarditis from Coxsackie or RSV, or adenovirus, or influenza, or para-influenzas, or the hundreds of other pathogens that can inflame the heart go viral online? Were they covered in the Washington Post, the New York Times, or ESPN? No. Now, however, any case of heart inflammation is likely to amplified. But there is no compelling evidence (right now) that SARS-CoV-2 is any more likely than other viruses to cause myocarditis, especially in young people, who seem mostly spared.

The JAMA-Cardiology paper that stirred this issue with its 700k pageviews has now been corrected, and if you compare magnetic resonance imaging (MRI) abnormalities to risk factor-matched controls, there is no significant difference. Whats more, patients in that series who were thought to have inflammation seen on MRI had normal CRP and troponin levels.

The most recent research letter from the Ohio State University group, on 26 competitive athletes, was hyped initially, but once the paper was published, found that, There were no diagnostic ST/T wave changes on electrocardiogram, and ventricular volumes and function were within the normal range in all athletes by echo and CMR imaging. No athlete had elevated serum levels of troponin I. In sum, we havent had adequate time to study this virus, and the statement in the AAP document that reads, Because of the growing literature about the relationship between COVID-19 and myocarditis has no basis in science. My friend Venk Murthy, an academic cardiologist at University of Michigan and a cardiac imaging expert has a great thread on Twitter. The specific issues are the recommendations:

First, youngsters who have very severe infections (needing ECMO, ventilators, etc) should be treated as if they have myocarditis and sit out of exercise for 3-6 months. Why 3 months or 6 months? What if they are recovered clinically, have normal enzymes, and ECG at 6 weeks. Why do they need more testing? What is a kid to do for the remaining weeks to months?

Second, kids with moderate disease need to by asymptomatic for 14 days and obtain primary care provider clearance (including an ECG) before return to exercise. Dr. Murthy asks what is moderate disease? The writers hint that prolonged fever is one predictor. But what the heck is prolonged?

And then, perhaps the worst recommendation is that allchildren andadolescentswithexposureto SARS-CoV-2, regardless of symptoms, require a minimum14-dayresting periodandmustbe asymptomatic for more than 14 days before returning toexerciseand/or competition.

If you are an American who leaves your house, you are likely exposed to this virus. Whats more, as Dr. Murthy writes, there are all sorts of exposures, some high-risk based on duration or proximity, and some low-risk. But they are all exposures.

I dont want to downplay COVID-19. We should all do the smart things, but making a guideline like this is hazardous because it promotes fear, and fear shreds good decision-making. As Ivan Illich wrote, it creates a social iatrogenesis in which people fear lurking disease. Fear plus a risk averse culture, will expose young people to all manner of harms from cascades of testing. Illich called this clinical iatrogenesis.

Two of my favorite follows on Twitter, Dr. Raj Mehta and Dr. Richard Lehman, penned a brilliant editorial on uncertainty in guidelines in JAMA-Internal Medicine. This line is pure gold: Evidence-based medicine (EBM) guidelines should look like half-drawn maps, indicating the good roads but, equally importantly, showing where there are no good roads.

In COVID-19 there are a handful of good roadsdistancing and masks, for examplebut there are far more areas where there are no good roads.

This seems like a nutty question. Of course, they are. Every guideline everywhere says so. My electronic heath record says so. My chart auditors say so. My pay for performance measures say so.

Well, the beta-blocker post-MI trials undergirding the evidence for this were done between 1975 and 1987. That was when we treated MI with bedrest and morphine. Adrenergic blockade was really important then. The average length of follow-up was 1-3 years and the average age of patients in these trials was 55-60 years.

A Danish observational study presented at the European Society of Cardiology and smartly covered by Bruce Jancin suggests such data may be obsolete in an era when blockages are vanquished by on-call cath lab teams. This was a study of post-MI patients stable for at least 3 months. Patients were from a Danish national registry; the study compared 5400 patients who did not get beta blockers with 24,000 who did get beta-blockers after MI. The study found no difference between groups in any cardiac events and no difference in absolute risk of all-cause death.

This is observational data you cant infer lack of effect but if there is an effect it, would probably be small. These data should not be used to say beta-blockers do not work post MI. They should stimulate us to do a proper randomized controlled trial (RCT) to evaluate this question; at minimum, a study looking at stopping beta-blockers after 3 or 6 months in non-heart failure post-MI patients. Fortunately, Prof Dan Atar from Oslo University is leading a 10,000 patient-strong RCT of beta-blockers vs no beta-blockers in post-MI patients.

You know the story: a patient is older, or frail, or has kidney function right above the cutoff for a low-dose direct-acting oral anticoagulant (DOAC). On paper they should receive the higher dose, but your gut says go with the lower dose. A paper published in the Journal of the American College of Cardiology, from the GARFIELD-AF registry (a prospective registry in 35 countries), looked at the effect on mortality, stroke, and bleeding based on DOAC dosing. This study involved new onset AF cases followed for up to 2 years

The GARFIELD-AF registry has nearly 35,000 patients and about 10,000 received a DOAC. About three-quarters of these 10,000 patients received the standard DOAC dose. About one-quarter were underdosed.

Underdosing was associated with higher risk of death (1.25), but the excess deaths were from heart failure and MI.

Underdosing did not associate with an increase in stroke.

Underdosing did associate with less bleeding.

This is an important study because it teaches important lessons about evidence-translation. Lets start with the authors second sentence in the discussion: Use of nonrecommended doses of DOACs had an impact on outcomes.

No. That is wrong. Use of nonrecommended doses of DOACs did have an association with outcomes. This is an observational study and there are surely reasons that doctors throughout these 35 countries decided to use lower dose DOACs.

Journalist Steve Stiles quoted the principal investigator, Dr. A John Camm, as saying that, Underdosing is not just a little problem. It's a very big problem."

Then this: "So I think there's some confusion and a lot of caution that physicians use with anticoagulants, and they often forget that the purpose of the anticoagulant is to prevent strokes and adverse outcomes such as mortality," Camm said. "But by reducing the dose, they expose their patients to these other major cardiovascular events." Camm then triples down on this confounded data: "It might also be argued that a physician who fails to treat a patient adequately in one arena may also be failing to treat the patient well in other aspects of their care."

My friend and colleague Dr. Gerald Naccarelli wrote the editorial and largely agreed with this sentiment, closing with, Underdosing of a DOAC may break that oath.

I respect Drs. Camm and Naccarelli immensely but I strongly disagree with their comments. If you are going to posit that underdosing of DOACs led to worse outcomes, it had better be in higher strokes, not heart failure and MI. In this study, underdosing was not associated with a higher stroke rate. The fact that underdosing associated with higher MI and heart failure tells you one thing: doctors decided to use lower doses in sicker patients. Sicker patients have more MI, heart failure,and death.

Similar findings were also noted in ORBIT-AF, another observational registry study; it also found that nonrecommended doses of DOAC associated with higher risk of death and cardiovascular hospitalization. Same deal sicker patients get lower doses. Look at the RCTs: in the original ENGAGE AF edoxaban trial, one-third of the patients were deliberately and blindly underdosed and the mortality was significantly lower than on warfarin (the p-value was 0.006). Then there was most recent ELDERCARE AF study in which very elderly Japanese patients with AF received once daily 15 mg dose of edoxaban and it was found superior to placebo in stroke prevention and did not result in an increase in bleeding.

I am all about correct dosing of any drug, but I push back on using confounded observational data like this to pile on against physician judgement.

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Sep 25 2020 This Week in Cardiology - Medscape