Sep 18, 2020 This Week in Cardiology Podcast

John M. Mandrola, MD


September 18, 2020

Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast.

In This Week’s Podcast

For the week ending September 18, 2020, John Mandrola, MD comments on the following news and features stories.


Deaths per day in the United States are staying around a 1000 per day. The Oxford vaccine trial is back on. American society is struggling.

I've seen a number of patients who want procedures done soon because they lost their job and insurance is running out. More and more I see patients who are having arrhythmia flare-ups and believe it is due to the stress. I ask, "From the pandemic?" Sort of, but mostly from the civil and political unrest. If you are retired, or out of work, and have time, you may have more time to watch the news or be on social media.

This is a quote from March from a Stanford scientist:

"One of the bottom lines is that we don't know how long social distancing measures and lockdowns can be maintained without major consequences to the economy, society, and mental health. Unpredictable evolutions may ensue, including financial crisis, unrest, civil strife, war, and a meltdown of the social fabric."

I don't how much, but I suspect lots of human health stems from the social fabric; human beings are social and without cohesion we are surely less healthy.

Cardiac Magnetic Resonance (CMR) Imaging and COVID-19

One of the first things you learn in cardiology is that a common cause of cardiomyopathy is viral myocarditis. It's rare and stochastic and it often improves. This week I was a signatory (along with ≈ 50 other medical professionals) on a letter to professional societies of cardiology on the matter of CMR after COVID-19.

Professor Venk Murthy, from University of Michigan began the initiative after a handful of studies using CMR raised public fears over the increased risk to the heart in patients following infection with coronavirus. Our main concern with the studies was not the reports themselves, but the massive misinterpretation of their clinical significance.

Three quick points:

  • Abnormalities on CMR such as late gadolinium enhancement have been found to be predictive in disease states like ischemic heart disease. Whether these same abnormalities have predictive power in viral infection is unknown.

  • Abnormalities on CMR have been observed in healthy long-term endurance athletes, which raises the hugest issue with some of these reports—the lack of control arm. When you find aberrations on a scan of a post-COVID patient, you need to have a control arm to see if these same aberrations are there as well.

  • The abnormalities being diagnosed as possible myocarditis have been characterized in patients with clinical symptoms and signs of myocarditis—abnormal ECG, chest pain, arrhythmias, elevated troponins.

People are seeking CMR testing despite the absence of symptoms or signs. I have heard about this from affected individuals and I have had groups discuss the idea of setting up post-COVID testing programs. This is premature.

To be sure, none of the signatories, me included, are against studying the potential cardiac implications of COVID-19 infection. These efforts should go forward. But to take the data that we have and apply it clinically would be potentially disastrous.

ISCHEMIA Trial Revisited

This week, the ISCHEMIA investigators were back in the news with a substudy that—sit down for this—found a positive p-value for the invasive arm in a tiny subgroup. Recall that the ISCHEMIA trial published earlier this year is one of medicine's most important trials. More than 5000 patients with serious coronary artery disease (CAD) and documented ischemia were randomly assigned to an early invasive strategy (PCI) or a conservative strategy of optimal medical therapy (OMT) and catheterization only for failure of medical therapy.

The priors before ISCHEMIA were crystal clear: every study in patients with stable CAD had found no reductions in poor outcomes by adding PCI to OMT. ISCHEMIA found the same. Notable was that over two-thirds in the conservative arm never had cath or PCI. Also notable was a lack of heterogeneity of treatment effect based on CAD severity, baseline ischemia level, or even the presence of left anterior descending disease. For instance, patients with three-vessel disease had higher event rates than patients with one-vessel disease, but " there was no advantage to the invasive approach," according to co-PI Judith Hochman.

For the substudy, ISCHEMIA investigators asked a reasonable question: do patients with a history of heart failure (HF) or left ventricular dysfunction (LVD) do better with an invasive strategy? Remember, you had to have an ejection fraction (EF) ≥ 35% to be in the trial. Nearly 8% of patients enrolled in ISCHEMIA had either a history of HF or an EF 35%-45%.

The chief finding of this paper was that in the subgroup that had HF and LVD, there was a benefit to the invasive arm in the primary endpoint and in the secondary endpoint of cardiovascular death + MI; the p value for interaction was almost significant at 0.55. The authors wrote, "This difference in outcomes was driven by a large effect of the invasive strategy on the subgroup of patients with heart failure and LVEF 35- 45%." This was a group of 28 patients, out of more than 5000.

My friends, these sorts of studies are really problematic. While it's an important area of investigation, as patients with LVD often go to cath, you cannot make inferences from such a small subgroup of patients. Especially when the overall finding of ISCHEMIA was non-significant.

In 1988, the ISIS-2 Trial enrolled 17,000 patients and proved the benefit of aspirin post-MI. The Lancet agreed to publish the data, but with a catch: The editors wanted to determine which patients had benefited the most. Older or younger subjects? Men or women?

One of the senior trialists, Dr. Peto, refused — such analyses would inevitably lead to artifactual conclusions — but the editors persisted, declining to advance the paper otherwise. Peto sent the paper back, but with a prank buried inside. The clinical subgroups were there, as requested, but he had inserted an additional group: "The patients were subdivided into 12 ... groups according to their medieval astrological birth signs." Geminis and Libras were found to have no benefit from aspirin, but the drug "produced halving of risk if you were born under Capricorn."

Thus, getting back to the super-tiny subgroup of patients with HF and LVD in ISCHEMIA, the best you could say is: Don't dare make anything of it.

Low-Risk Valvular AF

What do you do if a 55-year-old patient who has had mitral valve repair for mitral valve prolapse develops atrial fibrillation (AF)? This patient does not have any of the CHADSVASC risks but does have valvular heart disease (VHD). Should he or she be anticoagulated? What if it's a patient with a bioprosthetic atrial valve and zero or one risk factors? A recent study led by a Danish team, published in JACC, tries to sort out the risk of stroke and thus inform the decision to use oral anticoagulation (AC).

In 2017, an international group of experts put together a consensus statement on using AC in patients with VHD. In it, they separate valvular disease into Type 1 and 2.

Type 1 is moderate to severe rheumatic mitral stenosis and mechanical heart valves; these patients should receive warfarin or vitamin K antagonists.

Type 2 is everything else—mitral regurgitation, mitral valve repair, aortic stenosis, aortic insufficiency, tricuspid insufficiency, aortic valve, and transcatheter aortic valve implantation; these patients can receive warfarin or a direct oral anticoagulant (DOAC) depending on CHADSVASC.

The new paper looks at the patients who don't have a CHADSVASC risk factor. The authors used Danish registries to assess stroke risk in those with EHRA Type 2 VHD who were not anticoagulated.

At 1 year after AF diagnosis, patients with EHRA Type 2 VHD had a risk of thromboembolism between 1.2% and 1.5% according to age group (<65 or 65 to 74 years of age) and number of non-sex comorbidities of the CHADSVASC score (0 or 1 comorbidities), respectively. In patients with EHRA Type 2 VHD who were <65 years of age with 0 or 1 comorbidity, the risk was 1.5% and 1.5% at 1 year after the diagnosis of atrial fibrillation, respectively.

Now what? The general consensus holds that if your stroke risk is > 1% per year, AC is felt to be beneficial on net. This makes sense but there are caveats; even in the large Danish registries, these rates came from quite small numbers of events. The central figure describes 8 events out of 444 patients at risk. This puts the lower bound of the confidence interval at 0.7% which is below the risk threshold.

Another uncertainty that this paper cannot answer is that Type 2 VHD is a vast category. Is a 64-year-old who has AF and bioprosthetic valve at the same risk as a 44-year-old runner with mild aortic insufficiency?

Medical decisions are binary – yes or no on AC. But here, the benefit in stroke prevention will be low—because a 50% reduction in a very small stroke risk is very small. Bleeding risk is also low, but it's not zero. Ultimately, you decide and reassess next visit. You live with the uncertainty.


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