COMMENTARY

Feb 26, 2021 This Week in Cardiology Podcast

John M. Mandrola, MD

Disclosures

February 26, 2021

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 February 26, 2021, John Mandrola, MD comments on the following news and features stories.

COVID

FDA gave a nod to the JNJ vaccine – which is spectacular because it is one shot and does not require special refrigeration for shipment.

A group at Tufts university published a paper looking at the association of cardiometabolic conditions and COVID-19 hospitalizations.

This involved a complicated mathematical simulation in which they assessed the population attributable fraction for conditions like obesity, diabetes, heart failure.

The population attributable fraction is an epidemiologic measure used to assess the public health impact of exposures in populations. Basically, the number or proportion of hospitalizations for COVID-19 that would not occur if the risk factor were eliminated.

The main findings will not surprise you

  • Among >900,000 US COVID-19 hospitalizations, nearly two thirds were estimated to be attributable to 4 cardiometabolic conditions

  • Top risks were obesity (30.2%), hypertension (26.2%), and diabetes mellitus (20.5%)

Journalist Sue Hughes has excellent coverage of this paper published in JAHA. Senior author Dariush Mozaffarian, MD made an obvious statement:

"We are closing businesses and stopping people from seeing their loved ones, but we are not telling them to lose weight and do some exercise. We should be focusing public health messages on reducing diabetes and obesity as a means to reducing severe COVID disease,”

I follow COVID-19 closely and it’s not common to hear this message from public health leaders.

COVID and the Heart

The University College London team published a nice study of CMR scans in 148 patients who were sick enough with COVID-19 to have had troponin elevations.

The MRI scans were done at a median of 68 days after discharge.

I like this study, because it focuses on a homogenous patient population enriched with people who could have cardiac involvement.

That’s different than previous CMR post-covid studies. The control arm included 40 patients who had CMR done for clinical reasons before the pandemic. They were matched for age, gender, diabetes, and hypertension.

In addition, 40 healthy volunteer scans performed were also analyzed to derive normal ranges for native T1 and T2

Results:

  • Approx. 1 in 4 CMR scans had infarcts or ischemia patterns

  • Approx. 1 in 4 had a #myocarditis LIKE pattern of injury. The authors emphasized myocarditis-LIKE – b/c they we don’t

  • About a third of patients with myocarditis-like picture had findings compatible with active inflammation

  • Biventricular function was preserved in patients with myocarditis and no different to those without myocarditis

  • Some CMRs had a mix of infarct, ischemia and myocarditis-like findings

  • Troponin levels were not predictive of the diagnosis of myocarditis

  • There was no difference in mean native T1 in the remote myocardium between controls and COVID-19 patients but both groups had higher T1 than healthy volunteers

  • There was no difference in T2 in the remote myocardium between COVID-19 patients and controls

  • Approx. 50% had no major abnormality

The findings on CMR suggest that in at least some cases, the troponin elevations may have been due to Type 2 demand > supply MI.

While myocarditis was present in small numbers, it was not associated with regional wall motion abnormality or left ventricular dysfunction, and was limited to ≤3 segments in most– these CMR observations confer a favorable prognosis

This study differs from the Puntmann study that garnered 900k pageviews and nearly shut down US collegiate sports.

The UCL authors write that

“We believe our data challenge the hypothesis that chronic inflammation, diffuse fibrosis or long-term LV dysfunction is a dominant feature in those surviving COVID-19.”

The news story quotes Aloke V. Finn, MD, who noted that

"MRI can't diagnose myocarditis. It is a specific diagnosis that requires, ideally, histology, as the investigators acknowledged,"

Final Point: I noticed a number of commenters on the news story complained about the headline –As a writer this makes me mad as a hornet. Read the darn story.

Ms Beck’s coverage was superb. She reported the data, relayed the authors’ reassuring nature of their experiment, and got useful comments from an outside expert.

Obesity

Two RCTs, one in NEJM and the other in JAMA, have found that the once-weekly injectable glucagon-like peptide 1 agonist semaglutide induces significant weight loss in patients with obesity.

Preclinical studies suggest that weight loss with this class may results from effects on GLP 1 receptors that mediate direct and indirect effects on the brain areas involved in regulation of appetite in the hypothalamus and hindbrain.

Semaglutide if FDA approved for glycemic control in T2D and MACE reduction in patients with T2D and heart disease.

The makers, Novo Nordisk, have undertaken a series of placebo-controlled trials, called Step 1-4, targeting obesity in non-diabetic patients.

NEJM published the Step I trial: It was a landslide victory. You hardly need stats.

Percent decrease was −14.9% in the semaglutide group as compared with −2.4% with placebo.

As you would expect, physical function and cardiometabolic indices such as BP, HBA1C, glucose, LDL and TG favored semaglutide

There was cost to these gains. More patients had serious adverse events (9.6 per 100 pt-years vs 6.4 per 100 pt-years) and those causing discontinuation of the drug were also greater in the semaglutide arm (7.2 vs 2.8 per 100 patient-years)

JAMA published the smaller Step 3 trial of this series.

The big difference in this trial was more aggressive lifestyle intervention in both groups. Patients in this trial received more counseling visits, meal replacements and met with a dietician.

The mean body weight change from baseline was –16.0% for semaglutide vs –5.7% for placebo (difference, −10.3 percentage points.

This is a big significant difference—though notice the better weight loss in the placebo group. In this study the mean loss was nearly 6% of body weight vs 2.4% in Step 1.

Same story with adverse events: GI side effects occurred in 83% of those on semaglutide vs 63% on placebo.

The authors noted that inclusion of intensive behavioral therapy plus an 8-week low-calorie diet ultimately may not contribute significant additional weight loss beyond that achieved by semaglutide and less-intensive lifestyle intervention. 

Discussion Points:

These are big effects. A 15% weight loss in a person weighing 300lbs is 45 lbs. That is both statistically and clinically significant.

Obesity is a major health problem. If sustained, this sort of weight loss will surely lead to better CV outcomes through reduction in blood pressure, lipids, inflammation, and better physical functioning.

The effect size is larger than seen in another GLP-1 agonist liraglutide—but it is hard to compare diff trials.

Journalist Marlene Busko excellent coverage of both studies; I learned that there is an ongoing study of liraglutide vs semaglutide.

Concerns and limitations:

The sponsor (Novo Nordisk) designed the trial and oversaw its conduct; authors participated in drafting the manuscript but were assisted by a sponsor-funded medical writer.

Three authors of the NEJM were industry employees.

This does not negate the findings. But it is something to make note of.

On Twitter, trial expert Sanjay Kaul wrote of this increasing trend.

Generally, a good idea for an independent statistician to replicate the results. The FDA will conduct a thorough evaluation of data collection, endpoint adjudication, and statistical analysis. They will have access to all raw data.

The trial was carried out for slightly more than a year. Obesity is a lifelong condition that requires lifelong attention. All weight loss interventions struggle over the long-term.

No doubt, this will be costly therapy and the adverse effects are real. Some patients will not tolerate it.

Finally is this good idea? Should we be chemically inducing people to eat less rather than changing societal norms towards eating better and eating less?

Well, that hasn’t been working. I’ve spent two-plus decades watching obesity sicken and kill people.

if this sort of weight loss through a weekly injection can be sustained, there are millions of people who could benefit.

Often, people struggling with obesity need that initial kick; something happens, and many are transformed. I’ve seen it happen and its wonderful.

Features

Before I sign off, let me recommend the latest column from Melissa Walton Shirley who comments on the terrible decision to fire a doctor who decided to vaccinate 10 strangers and acquaintances with soon-to-expire doses of the Moderna COVID-19 vaccine.

My tribute to Bernard Lown is also posted.

Comments

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