Anuradha Lala-Trindade, MD

I’m excited about a lot in heart failure. I’m always excited about heart failure. I’m excited about a couple of things, depending on the realm of heart failure we’re talking about. So, I’m excited about implementation strategies and leveraging data science and electronic health record-based technology to optimize guideline-directed medical therapy. We saw this with PROMPT-HF, and we’re seeing this more and more in terms of utilizing it and leveraging something that can be the bane of many physicians’ existence in terms of note writing to actually ensure optimal medical therapy, that’s 1.

Number 2, I’m also excited about this newer paradigm of thinking of allowing device-based therapies to complement pharmacologic therapies rather than being so polarizing to one or the other. I think we’re recognizing the importance of integrated approaches. Third, I am excited about really making a dent in access and allowing for more equitable care across different populations, across socioeconomic status, race, ethnicity, gender. And 5, I am also excited in the advanced heart failure space. I think we’ve made a lot of really exciting strides, but I’m also looking forward to seeing the newer emergence of smaller mechanical circulatory support pumps that may allow for an assessment of improvement of ejection fraction and potentially divert the need or delay the need for more definitive, durable therapies like LVAD [left ventricular assist device] and transplant.

My personal approach is to really emphasize language and relatability, to recognize that I’m a human just like the patient opposite me is, and to feel empathy towards what they’re experiencing and meet them at their level. I think the way we interact with patients is contingent upon feeling one with them on some level. That helps me formulate plans that are tailored to an individual.

Recognizing that heart failure is a systemic process; it’s not just about the heart, it never was and never will be, is very humbling because you, as a clinician, recognize the tremendous value and importance you have in really improving a patient’s health from head to toe. And so, I think once you have that humility, you recognize how much there is to be done and how much care coordination can be spearheaded by heart failure clinicians.

I think we are so blessed to have really clear-cut guidelines that have evolved tremendously with respect to GDMT [guideline-directed medical therapy], with respect to amyloid detection, with respect to consideration of device-based therapies. Once you have that framework that I just mentioned, then you can reach into the armamentarium and ensure that you’ve used all the tools we have, all the therapies we have, to improve the lives of our patients. And just recognize that it’s a privilege.

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Anuradha Lala-Trindade, MD, shares developments in the pipeline for heart failure therapy, as well as clinical pearls for health care providers managing patients with heart failure.

The Future of Heart Failure Therapy

Recently we’ve gained information as to the effects of sacubitril/valsartan on NT-proBNP [N-terminal prohormone of brain natriuretic peptide] amongst patients with acute heart failure. So, these were not patients who were included in the PARAGON-HF study who had chronic heart failure with preserved ejection fraction [HFpEF], nor quite frankly, was there an adequate representation of individuals of Black race in PARAGON-HF, as well. PARAGLIDE-HF really served to fill these gaps in that it looked at an acute heart failure population. It really sought to have diverse enrollment, which was really important.

What we saw from that study really extended what we learned from PARAGON-HF as well across a different setting, which is that ARNis [angiotensin receptor/neprilysin inhibitors] do reduce NT-proBNP, which we know is a very powerful surrogate for clinical outcomes. Of course, this trial wasn’t adequately powered for clinical outcomes. However, we see suggestions that there was an improvement in clinical outcomes, particularly in the renal outcomes in this population.

I would say for me, personally, my practice remains the same. I’m still reaching for an ARNi in those patients with an adequate blood pressure because we have to remember from PARAGLIDE-HF that we did see a higher incidence of symptomatic hypotension. So, in those patients with an adequate blood pressure, I’m still reaching for ARNi across the spectrum of ejection fraction and across different settings, where appropriate.

I think what was really nice about PARAGLIDE-HF was that it sought to fill gaps in knowledge and in evidence, and I really appreciate the way the trial was conducted. It sought to include diverse populations; 50% women, and high prevalence of Black patients, as we already mentioned. Patients included a high BMI, which were not previously included in PARAGON-HF. And also de novo heart failure with preserved ejection fraction or mildly reduced ejection fraction. And so it expands our knowledge and our evidence base for use of this particular agent across more generalizable populations.

I think it’s important to keep in mind blood pressure. I think it’s important to keep in mind that only 12% of patients in that study were on SGLT2 [sodium-glucose cotransporter-2] inhibitors, so I still think that there’s a greater body of evidence to support the use of SGLT2 inhibitors in HFpEF or across the ejection fraction spectrum. But certainly, ARNi should be considered in those patients with blood pressure room and who met the criteria of the trial, which was really a broad population. So, I think it just offers us additional evidence.

Anuradha Lala-Trindade, MD, discusses the PARAGLIDE-HF trials, highlighting the use of sacubitril/valsartan for the management of heart failure in certain populations.

Clinical Trials of Sacubitril/Valsartan in Heart Failure

I think current unmet needs for patients with mildly reduced or preserved ejection fraction are as follows. Despite the advent of SGLT2 [sodium-glucose cotransporter-2] inhibitors, which are so efficacious in this population, I think we still have a lot to learn as to how to better characterize these patients and not lump them all together. I think we recognize the groups of patients who benefit from ARNi [angiotensin receptor/neprilysin inhibitor] in the chronic setting. In the acute setting, those patients certainly with mildly reduced ejection fraction do stand to benefit from this class of drugs in these various settings.

And then you have the mineralocorticoid receptor antagonists as well, despite the controversy after the TOPCAT trial, I think there’s a large cohort of patients who benefit from this drug across the spectrum of ejection fraction and particularly also inclusive of the mildly reduced and preserved ejection fraction.

So, I think we’ve come a long way. We still need to better understand exactly how to categorize these patients better so that we can personalize and tailor our therapies. And I think we’re still learning in terms of the device-based realms, as well. In terms of relieving elevated filling pressures that develop particularly with exercise, I think we’re learning the importance. I certainly make it a point to provoke or exercise these patients who may not have symptoms at rest or evidence of congestion at rest, but who really manifest limitations in functional capacity by virtue of elevated filling pressures with exercise.

An expert cardiologist comments on unmet needs in the management of heart failure, highlighting the need to categorize patients with heart failure in order to better treat them.

Unmet Needs in the Management of Heart Failure

In terms of how to respond or treat a patient with heart failure with reduced ejection fraction [HFrEF]. First, I take a really thorough family history. I take a history of from when they were a child through adolescence and young adulthood into adulthood, because I think it speaks a lot to how they were brought up, what their habits were in terms of exercise and diet and otherwise, whether they were hospitalized or chronically ill from an early age on or not. So that’s one; I dig deep going back.

No. 2 is, I also try to understand their current circumstances. What is the affordability for certain medications? How frequently are they able to come to the office? What is their understanding of heart failure? Have I done a good job as their clinician or their physician in relaying what heart failure actually entails and how this is a symbiotic relationship to ensure their long-term health? I really drive home the point that ejection fraction is just a number. It doesn’t relate directly, necessarily, to what the patient will be able to do. And I try to reassure them on that basis. And I spend a lot of time talking about language that is well received. That’s sort of my touchy-feely aspect of things.

Then, of course for HFrEF, I’m doing everything in my power to ensure that they are on all 4 pillars of guideline-directed medical therapy (GDMT). If, despite being on all 4 pillars, they have not been able to see an improvement in their ejection fraction, I am quick to proceed with implantable cardioverter defibrillators or cardiac resynchronization therapy. I’m also equally open to considering other pharmacotherapies, where relevant and appropriate. So, let’s say I have someone who’s persistently hypertensive, I will reach out for the appropriate additional therapies, such as hydralazine, nitrates, or vericiguat. Again, I’m seeking to address their comorbid conditions, like we talked about for diabetes, A-fib, etc, so I’m really trying to get those nailed down and employing a team of clinicians that can help take care of that individual.

And then I’m considering other device-based therapies. Is this someone who’s frequently hospitalized? Is this someone who would really derive benefit from PA [pulmonary artery] pressure sensor monitoring and remote management of their heart failure? Are there other reconstructive therapies that may be in clinical trial that might be a good fit for this individual? Is this someone who may benefit from cardiac contractility modulation? I would say my practice has evolved to being more open, such that once I’ve optimized a patient quickly, expeditiously to maximal doses of GDMT, I’m also simultaneously considering the impact and role of device-based therapies.

One cannot emphasize enough how important it is to start early, in terms of optimizing guideline-directed medical therapy and ensuring rapid up-titration, as tolerated. And I think the best study to show us that was conducted by Alexandre Mebazaa, MD, PhD and others in the STRONG-HF study, which really showed that it was safe and important to get patients on all 4 pillars of guideline-directed medical therapy early on in the hospitalization with rapid up-titration within weeks of discharge.

So, the TRED-HF study was a very interesting one, just over 50 patients, but it gave us so much information that was so valuable to our community. What we have recognized, and it used to be a black hole, and I will say that there’s still room for more data, but we have enough at least to understand this much. If you’ve previously had reduced ejection fraction that has now improved, you likely need to stay on all 4 pillars of guideline-directed medical therapy, as tolerated. And I say “likely” not to be flexible —it is the rule—but only to just recognize the need for individual tailoring sometimes, where applicable. So, I think TRED-HF showed us that in individuals where guideline-directed medical therapy was discontinued, there was a very high rate of recurrence of symptomatic heart failure and a subsequent reduction in ejection fraction once again. So, it is my rule of thumb, once you’re on GDMT for HFrEF, you stay on GDMT, regardless of where your ejection fraction is.

Anuradha Lala-Trindade, MD, shares approaches to personalizing quadruple therapy for people with heart failure, focusing on family history, device-based therapies, and optimizing therapy early.

Anuradha Lala-Trindade, MD

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