COMMENTARY

June 26, 2020 This Week in Cardiology Podcast

John M. Mandrola, MD

Disclosures

June 26, 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 June 26, 2020, John Mandrola, MD comments on the following news and features stories.

COVID Update

With 2.45 million cases in the United States, the rate of growth is 1.11x, about flat from last week. US deaths last week were at 120,000 and this week they are at about 124,000, for a rate of rise of 1.03x, which is steady.

The big story is increases in cases in the West and South. This week, California, Arizona, Florida, and Texas, especially Houston, have seen significantly higher rates of hospital admissions. Deaths from COVID are still trending down, but COVID is a long illness and deaths may start trending up in the coming weeks.

Some interesting details:

  1. The rise in cases does not seem to correlate with cities that had the largest protests. This is an unfolding story, but aligns well with the notion that indoors looks riskier than outdoors.

  2. While there is more testing going on, the rate of test positivity is increasing, which suggests more community spread.

  3. The median age of new cases is dropping in many areas. This also aligns with the increase in testing, greater community spread, less cautious youth, and more careful behavior of older people.

The good news is that masks are becoming part of the new normal. Kentucky’s been one of those mask resistant places and even here, I am seeing gradual acceptance.

Big News in Science

The RECOVERY trial is an RCT from University of Oxford researchers. On June 8, recruitment in the dexamethasone arm was halted by the data safety monitoring board because of efficacy. This week the authors put the primary findings on a preprint server. That is huge news for two reasons: one specific and one general.

The specific reason is that we learned about the subgroup effects. Recall that dexamethasone reduced mortality overall, but by much more in COVID patients on ventilatorss, less so on those taking oxygen, and trended towards harm in those with no ventilatory support.

We learned in the preprint that baseline characteristics of patients were not matched. Dr. Marcio Bittencourt, from Brazil, had a nice Twitter thread on this. In short, those on ventilators were younger, had COVID longer, and had less cardiopulmonary disease.

This baseline differences could explain both the dexamethasone trend toward harm in patients with newer onset disease and benefit in those with more advanced later stage disease. Think about COVID pathophysiology: people with early-onset disease have high viral loads. They need their immune systems. Blocking them with dexamethasone could be bad. Conversely, later in the stage of COVID19, the problem seems to be the excess immune response. Here, immune suppression with steroids could have great effect.

The general (and more important) reason to highlight the use of preprint servers is that it is a real positive for the communication of science. Data on a preprint allows public peer review, which in turn, allows clinicians to translate the evidence immediately.

IMHO, this should become the norm. If you have enough data to put out a press release, put the preliminary data online.

Tricuspid Valve Repair

One of the many features of the TheHeart.org | Medscape Cardiology that I like is their section that reposts journal articles. Recently, I found The Tricuspid Tragedy: From Cinderella to Celebrity . I didn’t look at it initially, but last week, I heard whispers in the cath lab about using percutaneous techniques to fix tricuspid valve regurgitation (TR), and the whispers sent me back to the paper, which was actually an editorial describing the undertreatment of TR in patients with mitral valve regirgitation and the association of TR with bad outcomes.

Boom—I had uncovered the beginnings of a new movement in cardiology: intervention on the tricuspid valve. The short summary is this:

Lots of observational studies consistently find TR associated with bad outcomes. This has led some to make causal leaps: the TR must be causing these bad outcomes, and hence, we should fix it.

The first problem is that TR is most often functional and due to other left sided diseases. Annular dilation and tethering of the leaflets lead to TR, more TR dilates the right ventricle, which leads to more TR and the cycle continues. The issue is that the cause of the TR is the other pathology. Observational studies can’t say whether TR causes the bad outcomes or is just a marker for other bad things, like heart failure, MR, aortic insufficiency, pulmonary hypertension, or even just old age. The second issue is that the studies underpinning intervention on TR are extremely weak. This starts with the surgical literature in which tricuspid valve repair with a rigid annular ring at the time of left-sided surgery has become codified in guidelines with no RCT-level evidence. Observational data show that concomitant tricuspid valve repair associates with less TR post-operatively. Studies looking at percutaneous approaches are even weaker. These are often single-arm studies with no control group. Endpoints include estimates of TR, which we all know is difficult to quantify and highly load dependent.

I am afraid that if TR intervention makes it past regulatory hurdles without proper trials. it’s possible that the main beneficiaries may be the doctors and hospitals rather than the patients.

AF Burden Post Ablation in CABANA

Dr. Jeane Poole from the University of Washington is one of the CABANA investigators and is lead author of a recent substudy of the landmark outcomes RCT comparing AF ablation to antiarrhythmic drug therapy (AAD). The Journal of the American College of Cardiology published the paper looking deeper at the effect on AF burden in the two groups, and Dr Poole presented it virtually as part of the European Society of Cardiology-Heart Failure meeting.

The main CABANA study included 2200 patients with symptomatic AF randomized to either a strategy of AF ablation or AAD. The main finding was that AF ablation did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. In 1240 of the 2200 patients who had a symptom-activated proprietary ECG event recording system, AF ablation reduced time to first recurrence of AF by about 47%.

The current substudy looked at this group who also had 96-hour Holter monitoring done biannually. From the abstract I cite two of the main findings: Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. And AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p < 0.001).

These findings led to the warm conclusions that AF ablation not only reduced the endpoint of time to first recurrence (not the best endpoint) but also AF burden (a better and more patient-centered endpoint). There is nothing false about these statements. Also true was Dr. Poole’s statement to journalist Steve Stiles: “I think it's really important that, even for the persistent and longstanding-persistent AF patients, you may be able to significantly improve the overall frequency and duration of AF."

But look at the figures in this paper is sobering. For example, Figure 2 shows that before ablation the average AF burden was 48% in both groups. This is a lot of AF. At five years, in the ablation arm, the average AF burden went from 48% to 15%. But in the drug arm—and remember AF drugs are terrible—the AF burden went from 48% to 21%. That’s only a 6% difference in AF burden—and this in the setting of carefully done RCT, one which included experienced AF centers.

To be fair, there were crossovers and some of the impressive reductions of AF burden in the drug arm may have been due to patients in the drug arm getting ablation.

Nonetheless, I find differences in the two arms very sobering for our field. These findings are highly consistent with the main paper findings, which used time-to-first-recurrence. In this endpoint, yes, AF ablation did better than drugs, but at five years, in the best centers in the world, in a selected population, less than half the patients in the ablation arm were free of AF.

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