Apr 1, 2022 This Week in Cardiology Podcast

John M. Mandrola, MD


April 01, 2022

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 on Apple Podcasts, Spotify, or your preferred podcast provider. This podcast is intended for healthcare professionals only.

In This Week’s Podcast

For the week ending April 1, 2022, John Mandrola, MD comments on the following news and features stories.

Listener Feedback on Coronary CT Imaging

A practicing non-invasive general cardiologist from the United States wrote to me, saying he is a loyal listener and self-described medical conservative. But he had serious criticism of my “generally negative approach to cardiac computed tomography (CT).”

“Every time a positive cardiac CT trial comes out you tend to focus on the negative aspects of it and forget to include the positive outcomes.”

He listed a number of ways that CT angiography (CTA) helps him. Among them:

  • CTA is a good test for reassurance—akin to an electrophysiologist (EP) ordering a cardiac monitor for benign palpitations. When it’s normal, anxious people with atypical chest pain can become less anxious.

Then he listed the advantages of CTA over stress testing:

  • CTA can identify left main disease.

  • CTA can put the brakes on revascularization. “I have had multiple patients with identified obstructive plaque on the cardiac CT and they have minimal angina or atypical chest pains that we pursue medical therapy with antianginal therapy as well as optimal medical therapy for reducing the risk.”

  • CTA can induce positive lifestyle changes in patients with low-intermediate risk lesions.

  • Other countries are using it as first line.

My Comments. First, I love notes like this. It was strong but respectful criticism. And that a busy clinician took time to write a detailed response to the podcast really moved me. Criticism is absolutely necessary. I remind everyone of Christopher Hitchens famous quote in Letters to a Young Contrarian: “Oddly enough, time spent in argument is time hardly ever wasted.”

On the first point – use of tests for reassurance. I worry a lot about this. To my young listeners, you should almost never order a test hoping it will be negative.

Of course, as a pragmatic practicing doc, it is true that I occasionally order monitors to reassure people. But I would argue a cardiac monitor ordered by an EP who knows the patient has less risk of starting a downstream cascade than an imaging test of the heart.

My colleague tells of CTA putting the brakes on revascularization. I’ve had a different experience, and the data speak otherwise. I’ve seen CTAs lead quickly to angiography and revascularization — if not immediately, then later. For example, I’ve seen patients develop symptoms once they learn of having unstented blockages.

What’s more, imaging tests find spots. Incidentalomas. It happened to me. I had an abdominal CT scan for another reason and come to find out the cardiac slices showed a small node in my epicardial fat. This caused (and still causes) angst. Why do I have epicardial fat? I am a cyclist. And despite numerous radiologists reassuring me that it is likely benign, I am worried. I’d be healthier had I not known about this spot. As for CTA being superior to stress testing, I don’t agree. And here I can cite a meta-analysis and systematic review I co-authored with the Penn State group led by Andrew Foy. This meta-analysis of 13 trials comparing CTA vs stress testing found no difference in death or cardiac hospitalization. CTA did lead to a 0.4% absolute risk reduction in myocardial infarction (MI) but this was sensitive to inclusion of the SCOT-HEART study, which we did not feel was to fair to include because it was not a direct comparison of CTA vs stress testing. SCOT-HEART compared CTA and stress testing to stress testing alone (we lost the peer-review battle). We also found that CTA led to more coronary diagnoses, invasive coronary angiography, and revascularization.

Finally, I don’t mean to defend low-value stress testing, of which there is too much. If CTA was used by thoughtful doctors like the one who wrote to me, we’d have less overdiagnosis and over-treatment. As my mentor Bill Miles taught me: Mandrola, you shouldn’t be against the test or treatment. Rather it is the unwise use of these tests and treatments that you should criticize.


This week the US Food and Drug Administration (FDA) approved a higher-2-mg-dose of the glucagon-like peptide GLP-1 agonist semaglutide for adults with type 2 diabetes. Semaglutide as an injection has been available in 0.5 and 1 mg doses.

Last summer, the Lancet Diabetes journal published the results of the SUSTAIN FORTE trial of 2 mg vs 1 mg semaglutide. The higher dose resulted in a greater reduction in HbA1c and in weight loss.

I realize that cardiologists haven’t (note past tense) been familiar with diabetes drugs, but increasingly I find myself thinking about diabetes regimens. Recently I had a patient with an implantable cardioverter defibrillator, heart failure with reduced ejection fraction, and diabetes who was on three diabetes meds but not on an SGLT2 inhibitor. I called the primary clinicians, and they agreed that yes, he should be on dapagliflozin or empagliflozin. Semaglutide has two connections to cardiovascular practice.

  • In the SUSTAIN-6 cardiovascular (CV) outcomes trial, published in the New England Journal of Medicine (NEJM) in 2016, semaglutide vs placebo resulted in a lower rate of CV disease, MI, and stroke in high-risk-patients with diabetes.

  • The semaglutide 2.4 mg dose has been shown to induce weight loss in patients with obesity. Last year, NEJM published the Step-1 Study showing significant and sustained weight loss with semaglutide. FDA subsequently approved this dose.

This melding of cardiology with diabetes reminds me of why I love cardiology, EP especially. First, you have to be a good clinician. Of course, many of us are attracted by the procedures. And procedures are nice, but procedures are far easier to learn than being a good clinician. Young people may think this sounds funny, but over years, procedures can actually get boring. EP is great because half the week you do procedures and the other half you do doctoring. I love the challenge of learning new ways to treat patients with conditions. I am no diabetic specialist, but I want to know enough to help my cardiac patients get the best approach to all the conditions that could affect heart health: guess what? That includes just about everything.

Coronary Artery Calcium and Sudden Cardiac Death

The Journal of the American College of Cardiology (JACC) Imaging just published an observational study on the association of coronary artery calcium (CAC) with future risk of sudden cardiac death (SCD). It is also to be presented at the ACC meeting.

A group of authors, many of them on the record as being CAC proponents, studied more than 66,000 patients from the CAC Consortium — a cohort study from four high volume US centers. For this study, the patients are included if they had a CAC score and were free of known heart disease or symptoms. They were then followed and SCD was assessed by linking patients with Social Security Administration records and the National Death Index. Risk factors for heart disease were assessed at the time of the CAC scan. About 55% had a CAC score > 0.

Over 10 years they tallied 211 sudden deaths, an incidence of 0.3%. The investigators then divided the population into five categories: CAC 0, which was the reference; then CAC 1-99; 100-399; and 400-999; and >1000.

The main results were:

  • Compared with CAC 0, there was a stepwise higher risk in SCD for CAC 100-399; CAC 400-999; and CAC >1000.

  • These risks were adjusted for basic risk factors.

  • CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk < 7.5% (P=0.02) and 7.5%-20% (P=0.003), which were larger when compared with persons with a 10-year risk >20% (P=0.54).

The authors concluded that higher CAC burden strongly associates with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.

Comments. You all know that I am on record for not being a proponent of CAC. But this conclusion is really problematic. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.

The news headline reads: “Calcium Scores Predict Sudden-Death Risk in Preclinical CAD in Large Cohort Study.” I would not use causal constructions in this retrospective nonrandomized convenience sample of patients from four centers. You can’t make these conclusions from this study.

  • First, the absolute rate of SCD in a decade was only 0.3%. When events are that uncommon, it’s hard to say much about modifying risk factors, even if the data were stronger.

  • Second, 19 human beings with CAC 0 died suddenly; that is 10% of the total of 211.

  • Third, as the authors write: “multiple imputation was performed on 28% of individuals who were missing data on ASCVD risk factors.” So nearly one-third of the patients had missing data on risk factors that surely impact SCD risk.

  • Fourth, there are many factors that influence both CAC and SCD risk. So, there is a huge risk of confounding.

You can argue with me about CAC usage for statin decision-making in medium risk individuals. I think I have the winning side, but there is an argument. But if you cite this sort of data to say you can “predict” SCD or identify patients “most likely to benefit” from further downstream testing, I am going to fight you. Hard. Why does this rile me up so much? Because the main problem I have with CAC is that it leads to disease creation and serious increases in downstream testing, which likely benefits doctors and hospitals far more than patients. This sort of conclusion gives tacit approval for what happens nearly every day in my zip code: high CAC does not only lead to statins, but a hotline to the nuclear camera and often straight to the cath lab.

Exercise and COVID-19 Infection

The British Journal of Sports Medicine published an observational study from a South African research group studying the association between physical activity and COVID-19.

The topic piqued my interest because I love endurance exercise, and because it was so rare to see fit runners and cyclists get acute respiratory distress syndrome (ARDS) during the pandemic. I did an informal poll of hospitalists and ICU docs at our hospital, and none could remember any serious athletes who had severe disease. I am also in a community of 300 cyclists here and I know of no one admitted to an ICU for COVID-19. I am sure there have been a handful of athletes with severe disease, but it seems very rare.

The South African authors collected data from about 65,000 patients with a COVID-19 diagnosis, and then grouped them by activity level – low, moderate, high activity. They then did regression, also known as correlation.

High vs low activity results:

  • 34% lower risk for hospitalization;

  • 41% lower risk for ICU admission;

  • 45% lower risk of requiring ventilation;

  • 42% lower risk for death.

Superstar journalist Patrice Wendling has coverage on | Medscape Cardiology, and she also smartly cites similar data from both a US and South Korean cohort.

The paper has all the normal caveats of retrospective observational comparisons, including confounding — people who have high levels of exercise may be healthier in many other ways, and likely have a higher SE status.

But here’s my thinking. Tell me if I am wrong: there seemed to be something uncanny with SARS-CoV-2 in that many of the risk factors for cardiovascular disease were also strong risk factors for severe COVID-19. Obesity, diabetes, hypertension all seemed to be risk factors for COVID-19. Well, people who exercise a lot, don’t have a lot of these risk factors. So at least there is plausibility that the association between exercise and less severe COVID-19 could be partially causal.

The other reason I mention this study is that exercise is under prescribed. I bet I prescribe regular daily exercise five times in every clinic. I liken it to their heart pill. I say, “Do a little exercise every day that you eat.” Seriously, I do believe it is like a prevention pill. I don’t know how successful I am, but the framing of exercise as medicine seems right to me.

ACC Preview

This morning, I leave for the ACC meeting in Washington DC. I wrote an ACC preview column. Steve Stiles wrote a better one. They are both up on the | Medscape Cardiology webpage.

The biggest news of the meeting will have to be that it is happening in-person. Yes there will be virtual parts, but more than 12,000 people have registered as in-person. This is a big deal for the United States. It has been a very hard 2 years, and just walking the convention halls and going to dinner with colleagues will be a wonderful thing. I look forward to walking past the posters.

It’s hard to say what study will emerge as a big one. The lead study is on mavacamten for hypertrophic cardiomyopathy – will it reduce the need for septal reduction therapy? I’m seeing a lot of ads for the drug, so my bet is the data will be positive, but we shall see.

Another late-breaker tests the old notion of salt restriction for heart failure. I would not be surprised if another dogma in medicine fails the RCT. There is one arrhythmia-centric session of featured research, but keep in mind also that the European Heart Rhythm Association (EHRA) meeting starts Sunday in Copenhagen. And you can bet there will be tons of arrhythmia news coming from that meeting. What’s up with having two great meetings overlap? I hope that changes in the future.


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