Jul 24, 2020 This Week in Cardiology Podcast

John M. Mandrola, MD


July 24, 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 July 24, 2020, John Mandrola, MD comments on the following news and features stories.

COVID This Week

The short story: America remains in a hot mess. Yesterday we hit 4 million cases. As expected, hospitalizations are increasing and early data looks like deaths are tracking up. US deaths a week ago were 141,000 and this week they are 147,000, so the rate of rise is 1.04x, which is steady but belies the focal nature of the pandemic. Florida, Arizona, California, and Texas all show clear signals of increasing rates of deaths.

COVID Vaccines

Numerous studies on multiple vaccines are out.

Moderna mRNA1273. Phase 1 dose escalation study in 45 adults: the vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. 

Pfizer/BioNTech vaccine. This is a follow-up study on previous phase 1 study of this mRNA encoding the receptor binding domain (RBD) of the spike protein. No severe adverse effects though most report fever, fatigue, and headache.

This study had encouraging results: 1) neutralizing antibody response from the vaccine can handle a wide range of mutations in the Spike protein and its receptor-binding domain. 2) There was a robust CD8+ T-cell response (29/36 patients), which did not necessarily correlate with the antibody titers raised by the vaccine. This differs a bit from Moderna’s mRNA response, which induced mostly CD4 cells.

Oxford/AstraZeneca vaccine. This is a chimpanzee adenovirus-vectored vaccine expressing the coronavirus spike protein. In healthy adults; phase 1 and 2 studies: low side effects and both humoral and T-cell responses that support large-scale evaluation of this vaccine in an ongoing phase 3 program.

CanSino Vaccine. Chinese investigators did a phase 2 RCT of another adenovirus type 5-vectored (AD5) vaccine. They looked at two doses in about 500 patients. Both doses induced neutralizing antibodies and T-cell responses. Minimal side effects noted. The main limitation seemed to be that people who had existing levels of antibodies to the AD5 vector had diminished immune responses. The authors tells us that in the Chinese population, about 50% of the population is in that category, in India it’s 80%, and in the US around 30%. Of note, this is a one-shot vaccine.

The Pfizer CEO gave an interview to Time magazine and said they are spending $2 billion on the vaccine program and there are plans to have 100 million doses by year’s end. They aim to charge governments a nominal fee for this so it can be given free to citizens. I’ve been tough on pharma, but here we need them to come through for us.

Brief Note on T-cells

A paper in Nature looked at memory T-cells in 36 recovered COVID-19 patients. The study demonstrated the presence of CD4 and CD8 T-cells recognizing multiple regions of the nucleocapsid phosphorprotein (NP). They then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak and it displayed robust cross-reactivity to SARS-CoV-2 NP.

Surprisingly, they frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19, or contact with SARS/COVID-19 patients (n=37). Pause there for a second. That is wild. The T cells are recognizing particular protein regions that have low homology to those found in the “common cold” coronaviruses, but do have very high homology to various animal coronaviruses.

ICD Effects Over the Long-term

Professor Jeanne Poole from the University of Washington, along with other investigators of the landmark SCD-HeFT trial have published an intriguing, highly relevant but imperfect post-hoc analysis of their landmark trial. The Journal of the American College of Cardiology published the long-term follow-up paper and Eric Stecker from Oregon co-authored a worthy editorial.

Recall that SCD-HeFT, published in 2005, was one of the landmark trials that established implantable cardioverter defibrillator (ICD) benefit in patients with heart failure. It was a three-arm RCT of ICD, amiodarone, and placebo. Half of the patients were ischemics and half non-ischemics.

There were two interesting pre-specified subgroup findings: One was that while class 2 patients enjoyed a huge 46% reduction of death from the ICD, those with class 3 got no benefit. In fact, the point estimate of the hazard ratio was 1.16. The second key subgroup finding was that while both non-ischemic and ischemic patients had similar hazard ratio for ICD benefit (about a 25%) reduction, the smaller number of events in the non-ischemic arm did not meet statistical significance. These two findings were ignored and ICD implantation went on in earnest in patients with heart failure who met ejection fraction criteria.

Today, one of the most pressing questions in all of everyday electrophysiology practice is what to do with patients with heart failure who have an ICD and present with battery depletion. Dr. Poole’s analysis of the long-term results of SCD-HeFT inform that decision as well as shedding light on the original findings from the main trial and also the equally landmark DANISH (no ICD benefit in non-ischemic cardiomyopathy [NICM]).

They had mortality outcomes for 1855 alive at the end of the main trial in 2010-2011.These data were combined with the 666 deaths from the main trial in an effort to compare long-term outcomes overall and for the two subgroups.

The median follow-up was 11 years. Overall ICD benefit held up though the hazard ratio had dropped to 0.87 or 13% reduction with the CI ranging from a 24% benefit to only a 2% benefit. The subgroup findings were upheld and strengthened in long-term follow-up. For ischemic heart failure, the hazard ratio was a highly significant 0.81 or 19% benefit but for the non-ischemic, the hazard ratio was a nonsignificant 0.97. For heart failure class, the hazard ratio was a highly significant 24% reduction for those in class 2 and a nonsignificant 1.06 for those in class 3.

In a 2008 landmark paper, one that I think is pinnacle of critical appraisal, Rod Tung, Peter Zimetbaum, and the late Mark Josephson exactly predicted these results and the DANISH results. ICD benefit has a classic notch: You have to be healthy enough so that arrhythmic risk is your main threat, but not so sick that advanced heart failure or other non-cardiac causes of death dominate.

Tung, Zimetbaum, and Josephson also warned us about the diminished benefit in patients with NICM. And this long-term analysis confirms the many signals from days of old that patients with NICM stand to benefit less from an ICD.

The two most important caveats of this paper, which the authors state clearly, are loss to follow-up and that many patients crossed over to an ICD after the main trial. But still the NICM vs ischemic cardiomyopathy comparison is upheld as was the class 2 vs class 3.


This week the US Food and Drug Administration approved the WATCHMAN Flex device for left atrial appendage (LAA) occlusion. You expect this with devices. Over time, there are iterative improvements. Multiple colleagues tell me this iteration is an advance.

Approval was based on a 12-month industry sponsored single arm study of 400 pts. The study met its safety endpoint with a low-incidence of complications of 0.5%, and a 100% rate of LAA closure at 12 months with leaks less than 5mm. About 96% of patients were able to discontinue oral anticoagulation following their 45-day follow up.

The caveats are that 1) This is an unpublished report, 2) no control arm, 3) no outcomes. My view of the data from PREVAIL and PROTECT, and the pathophysiology of stroke in patients with AF, and the safety profile of direct oral anticoagulants relative to aspirin and warfarin means that we need outcomes data with the new devices.

I challenge you to go over to the virtual Heart Rhythm Society website and peruse the WATCHMAN studies. There are a number of concerning studies. I am not saying these imperfect abstracts prove the procedure does not work, it’s just that the existing RCT data is dubious and the patients being included now were excluded from these trials.

Two Features Worth a Note

The first is a podcast interview that Eric Topol and Abraham Verghese did with Dr. Fauci. The second is a surprise column from my colleague Melissa Walton-Shirley in which she defends the controversial Sandeep Jauhar’s op-ed in the New York Times. Dr. Jauhar encountered some vitriol online when he dared suggest that perhaps Americans don’t require the volume of care that their doctors are used to providing.


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