Jun 21, 2024 This Week in Cardiology Podcast

MRAs in HF with renal dysfunction, coronary autoregulation, the hubris of US doctors, NSTEMI in older patients, survival after STEMI, and new leaders at JACC are discussed by John Mandrola, MD.
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-TRANSCRIPT-
In This Week’s Podcast
For the week ending June 21, 2024, John Mandrola, MD, comments on the following news and features stories.
MRAs in HF With Renal Dysfunction
Prof Doron Zahger centered on my coverage of the combined analysis of RALES and EMPHASIS, first author Matsumato, in JACC.
This was a paper that looked at effect of mineralocorticoid receptor antagonists (MRA) in a subgroup of patients who had a drop in GFR to 30 ml/min/1.73 m2 . The authors found that these patients had higher risk of the primary outcome, compared with those who did not have a drop in GFR, but the effect of MRA persisted.
Zahger smartly points out that of the 295 patients in both arms (MRA and placebo) who had a decrease in GFR, one in 4 or 78 discontinued the MRA therapy.
He writes that
These discontinuations were probably mostly decided by the study team based on clinical judgment and hyperkalemia. We are not told whether such discontinuations were protocol mandated.
Therefore, a more accurate interpretation of the results would be that the benefit of MRAs is maintained among patients who experience a GFR decline PROVIDED their physicians did not decide to stop the medication....
A take home message that MRAs may be continued in the face of eGFR decline would be both inaccurate based on the data and potentially harmful.
I really appreciate this point. It emphasizes trial environment vs real world care.
I should have mentioned though that authors thought of this issue and did a sensitivity analysis depending on MRA discontinuation or not. The HR remained beneficial even in the small numbers of patients who discontinued the drug during the trial. Here the numbers are small and I reiterate my comment
We need to always be mindful that individuals are not populations. These net benefits were obtained in a trial setting-where you can be sure there was careful monitoring.
Coronary artery autoregulation with increasing stenosis
Today we talk about coronary autoregulation. That’s a bit of medical jargon but at the core of this issue is the matter of why people do so well despite severe CAD.
Angiograms often don’t match up with symptoms. Angiograms are often much worse than symptoms.
NEJM published this research letter of sorts. A single patient. 63 years old with refractory angina and an LAD sent. Imagine a study in NEJM with one patient. You know it must be an elegant study.
He then had a pressure and temperature wire placed in the distal LAD. After the stent was placed.
The investigators then placed an undersized balloon within the stent to test varying degrees of occlusion.
They then plotted the distal LAD pressure and absolute coronary flow. This like a fractional flow reserve (FFR). They did it at rest and then with saline infusion to simulate hyperemia.
Resting flow remained stable over the range of distal coronary-to-aorta pressure ratios. Let me say that again. As they inflated the balloon and caused varying degrees of epicardial stenosis, distal flow did not change.
Why? Because the coronary microcirculation vasodilates and compensates. Increasing epicardial resistance induces instantaneous microcirculatory vasodilation resulting in a compensatory decrease in microvascular resistance.
Then they did hyperemia. First point-the flow increased 4-fold. But as the balloon was inflated, creating more and more stenosis, flow decreased in a linear fashion.
Hyperemic flow approximated a linear relationship with the FFR reserve. Decreasing from 176 ml to 81 ml per minute.
These two findings show the autoregulatory capacity of the coronary microcirculation. I, maybe you too, don’t think about the microcirculation that much. Modern cardiology focuses on the epicardial stenoses. We can stent those.
Total coronary resistance therefore is the sum of epicardial resistance (stenosis on angiogram) and microvascular resistance.
I was struck by the fact that flow was absolutely maintained despite major stenoses. Because of the vasodilation of the microcirculation.
The three Belgian authors also showed that the vasodilation can max out, and then with increased demand, flow goes down.
I spoke with Venk Murthy, MD from the University of Michigan, about this study, and he emphasized that people with microvascular dysfunction, say from diabetes, obesity, HTN, or other conditions, may lose the dilatory properties of the micro-circulation, and if that happens, stenoses of 30%-40% may cause significant ischemia.
Transcript in its entirety can be found by clicking here: www.medscape.c...