May 7 2021 This Week in Cardiology – Medscape

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For the week ending May 7, 2021, John Mandrola, MD comments on the following news and features stories.

Rates of COVID infection continue to decrease in the United States, European Union, United Kingdom, and Canada. As a doctor I am an observer of human nature, and the most interesting aspect of the pandemic now is the tension on returning to normal after vaccination. I see this tension on social media, in the hospital and out there in the neighborhood. The Centers for Disease Control and Prevention (CDC) released new guidelines on wearing masks outdoors. Yet some communities kept mask mandates in place. Some fully vaccinated docs still wear N95 and eye shields around the hospital. Its been a very hard 16 months. It will take time. I keep going back to those mRNA Kaplan Meier curves and Israel real world evidence. We just arent accustomed to therapeutics this good. But Indiagosh, I hope we are surging vaccines to this country.

Lancet Diabetes & Endocrinology published an important observational study from UK researchers (first author Min Gao) in which they studied the association of body mass index (BMI) and bad COVID-19 outcomes in Public Health England's database.

While we all know that obesity is a risk factor for severe COVID-19, this paper found linear associations beginning at even slightly overweight BMIs, greater than 23; linear, meaning that the risk is higher at 24 than 23 and higher at 25 than 24. The paper is open access and Figure 1 depicts a gradually rising hazard ratio (HR) starting at a BMI of about 23-24. The association was not attributable to excess risks from diabetes and BMI was a greater risk for younger people than for older people, and for Black people compared with White people.

I realize this is totally anecdotal but its what weve seen at my institution. Its rare to see normal-weight young people in ICUs. I cant help but think theres something very curious about how this virus interacts with the cardiometabolic effects of being overweight. The implication is that overweight is a utterly modifiable risk factor.

Here we go again. Last month, the European Heart Journal and JACC published the newly updated Valve Academic Research Consortium 3 (VARC-3) definitions and endpoints proposed for transcatheter and surgical aortic valve replacement (TAVR/SAVR) research.

The 23 authors, 20 of whom have also been authors on TAVR trials, wrote that the aim of these new definitions was to add more granularity and a patient focus to a rapidly evolving field. Patrice Wendling has a superb news recap on this important change in definitions. In the third paragraph she quotes the first author Philipe Genereux who said: The main change in VARC-3 is really that we tried to define not only procedural outcome, both but also more the long-term outcomes mainly based on the patient so quality of life, bioprosthetic valve failure, how do we define a valve failure, and also the need for rehospitalization."

The long update document details each of the important outcomes in future research of these two techniques. This includes mortality, neuro events, hospitalization, bleeding, new conduction disturbances and arrhythmia, vascular complications, MI, and valve dysfunctionincluding the issue of valve thrombosis. Sounds mundane, right? These are legit outcomes. Well, the new document raised the ire of some cardiac surgeons who pointed out several important issuesthat I think are worthy of mention.

First issue: VARC-3 defines hospitalization (or re-hospitalization) as any admission to an inpatient unit or hospital ward for 24hours or more. Recall that all the TAVR and SAVR trials, except PARTNER 3, had as their primary efficacy endpoint stroke and death. Inexplicably, PARTNER 3 added rehospitalization and of course this turned out higher in the SAVR arm. Patients who have surgery will have more early post-op rehospitalizations. On social media, Victor Dayan from Uruguay rightly counters that this will bias trials against SAVR. I think it would be fine to use hospital admissions, but you need a blanking period of weeks to months.

Second issue: VARC-3 redefines the previously vague definition of valve thrombosis to be clinically significant valve thrombosis. That sounds reasonable, but Dayan points out that now a thrombus is not a thrombus unless it is associated with a clinical event or a severe hemodynamic deterioration, and this change would erase the worrisome finding in the two-year results of PARTNER 3 that found a 3.7-fold higher rate of valve thrombosis in the TAVR arm.

Third issue: VARC-3 also changed the definition of periprocedural MI to the definition used in the controversial EXCEL trial of drug eluting stents vs surgery for left main disease. The old VARC-2 definition required clinical symptoms or signs and biomarkers. VARC-3 has now changed to the modified Society for Cardiovascular Angiography and Intervention (SCAI) definition, which uses biomarkers and is procedurally agnostic. That of course is a problem because surgery is always going to release more enzymes than a procedure.

Fourth is the meta-issue: Dayan and others point out that 20 of the 23 authors of VARC-3 are trial authors and they feel that scientists cant be the judge, jury, and attorney for the evaluation of science. Another point was that only 3 of the 23 committee members were surgeons. The American College of Physicians recommendsthat guideline committee members with moderate- or high-level conflicts of interest recuse themselves from authorship. One VARC-3 author has received more than $2 million in fees from industry in the past 4 to 5 years.

I am sympathetic to all these concerns. Hospitalization should not be a primary endpoint in these trials, subclinical thrombosis enough to limit leaflet mobility is an important issue, MI definitions that include clinical symptoms is a fair debate, and it hardly needs saying that intellectual and financial conflicts of interest are relevant.

Ive said this many times before on this podcast, guideline and consensus documents should include far more neutral judges and far fewer content experts. TAVR has been a huge advance, but we need to keep studying this procedureespecially as it is extended to lower risk younger patients.

This podcast is acutely aware of and concerned with disparities in healthcare outcomes and variation in care. Patrice Wendling has another nicely written report on a related TAVR study that was reported at the SCAI meeting.

Using Medicare claims data, University of Pennsylvania investigators identified 554 new TAVR programs, and found less use of TAVR in poorer communities. The topline finding was that 98% of new TAVR programs were established in metropolitan areas and about half were started in areas with pre-existing TAVR programs. This increases the number of programs but does not necessarily increase the geographic availability of the procedure.

Using demographic data, the authors concluded that the increased number of TAVR programs that we found during the study period did not necessarily translate to increased access to TAVR. Wealthy, more privileged patients had more access to TAVR by virtue of the hospitals that serve them.

This is a tricky topic. Yes, ideally, we should have absolutely equal care in all parts of the country. But we dont have a National Health Service system here. That poor areas of the United States dont have the same access is a tradeoff of our profit-driven system. Not having skilled TAVR operators in poor areas will deny poor patients with high surgical risk the ability to have a transformative procedure.

But lets also move past first order thinking and consider that simply putting out more TAVR programs with low-volume procedures isnt free of issues either. Ive seen some electrophysiology in rural areas and sometimes it isnt ideal. TAVR, like so many new procedures, requires big teams of multiple specialists who do lots of procedures. Volume is key. You can start a TAVR program in rural areas or poor areas, but if the team doesnt do enough procedures the patients arent any better served.

I remain drawn to the Canadian system in which few centers do tons of procedures. Even though this requires folks to travel longer distances, wouldnt it be better to do that than having a procedure done at a low-volume center?

At the European Heart Rhythm Association meeting, Dr Pier Lambiase presented 5-year data from the EFFORTLESS registry of the subcutaneous implantable cardioverter defibrillator (S-ICD). Steve Stiles has excellent news coverage of the abstract presentation.

Briefly, the S-ICD is a device placed in the left lateral chest approximately at the mid-axillary line. The one lead is tunneled just outside the chest wall to the sternum and then it takes a right northward turn and sits parallel to the sternum outside the chest. The idea of having an extra-thoracic device with no transvenous leads is that you can sense and defibrillate ventricular fibrillation (VF) without the downside of venous lead complicationslike infection, lead failure, tricuspid regurgitation, and venous obstruction. The downside of course is that having no lead in the heart means no pacing, no painless anti-tachycardia pacing of ventricular tachycardia (VT), and serious challenges to sensing the atrial and ventricular signals.

Remember the rule: Science tells us what we can do; Trials tell us what we should do, and registries tell us what we actually are doing. The industry-sponsored registry enrolled 984 participants from multiple centers in Europe and New Zealand. The main purpose was to document the complication rate, incidence of inappropriate therapy, and the extrapolated costs associated with the S-ICD system. The registry started in 2012 with early generation devices. The last report of the registry was in JACC in 2017.

Remember, this was not a mandated registry. This was an industry-sponsored registry in which patients were enrolled at the discretion of the investigators. Id expect it to be the best-case scenario. The results are sobering.

At 5 years, the overall complication rate was 18.4%--nearly one in five. There were 328 inappropriate episodes in 155 patients (about 16% of patients). The 5-year inappropriate shock (IS) rate was 16.9%. The majority was due to over-sensing. Only a small percent of IS were due to atrial fibrillation (AF). For reference, I went to some other studies and found an inappropriate shock rate of roughly 3% in the MADIT-RIT and PAIN-FREE SST studies.

Appropriate shocks occurred in about 16%, a substantial portion of whom had monomorphic VT that may have been terminated painlessly with antitachycardia pacing (ATP) from a transvenous device. One important caveat regarding inappropriate shocks was that this registry included S-ICDs implanted before the advent of what Boston Scientific calls the smart-pass filter, which reduces but does not eliminate t-wave oversensing.

Still though, I disagree with one of the Dr. Lambiases concluding comments. He said: In this diverse registry, complications primarily occurred in the first year, but remained low through 5 years. I dont consider a complication rate of nearly 1 in 5 to be low. And things havent gotten better for the S-ICD. We now have two Class 1 US Food and Drug Administration (FDA) recalls for this device, one for the only lead, the other for an older-generation generator.

You may know this, but JACC Clinical Electrophysiology has published a point-counterpoint argument from Dr Bogdan Enache and me vs Drs. Raul Weiss and Emile Daoud on pausing implantation of this device in lieu of the well-studied transvenous ICD. I encourage you to read the arguments on both sides of this debate.

The FDA has approved dapagliflozin to reduce the risk for kidney function decline, kidney failure, cardiovascular death, and heart failure hospitalizations in patients with chronic kidney disease (CKD). This is now the third indication for this drug. It was approved in 2014 for use in patients with type 2 diabetes, and in 2020 for patients with heart failure with reduced ejection fraction (HFrEF).

The approval in patients with CKD was based on the DAPA-CKD trial. DAPA-CKD enrolled about 4300 patients with CKD, average estimated glomerular filtration rate eGFR 43 mL/minute/1.73 m2, and randomly assigned them to dapagliflozin vs placebo. The primary outcome was a composite of a sustained decline in the eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. The trial was terminated early because of efficacy.

A primary endpoint event occurred in 9.2% in the dapa arm vs 14.5% in the placebo arm, yielding a hazard ratio of 0.61; with confidence interval ranging from 0.51 to 0.72. This absolute risk reduction (ARR) of 5.3% puts it in the highest tier of preventive therapeuticseven greater than the 4.7% ARR seen in PARADIGM HF of sacubitril/valsartan vs enalapril in HFrEF.

And this was not one of those stories where the composite endpoint was driven by soft outcomes. Dapagliflozin treatment also cut all-cause mortality by a statistically significant relative reduction of 31%. I consider this huge news because there are a bunch of patients in cardiac and arrhythmia clinics with CKD. Keep in mind that only 10% of patients in DAPA-CKD had heart failure.

Dr. Michelle ODonoghue has an excellent videoblog about the many challenges of being a new physician Mom. This is definitely worth a listen. Two of her key points are that we need to acknowledge that working moms dont want to be treated differently but they do need time to, for example, break away from rounds; and better communicate about resources available to doctor-Moms.

My daughter isnt a doctor, but she is in the healthcare field, and I see these challenges first-hand. This is a tension that male doctors cant fully appreciate. All the more reason to take a listen.

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May 7 2021 This Week in Cardiology - Medscape