ACC 2022: Expert Analysis of New Data in HFpEF

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The diagnosis and treatment of HFpEF has evolved in recent years, including new recommendations from the American Heart Association/American College of Cardiology (ACC)/Heart Failure Society of America heart failure guidelines. New data presented at the 2022 ACC Annual Scientific Sessions highlight a novel approach to an underused diagnostic technique and demonstrate the utility of both pharmacologic and procedural interventions for patients with HFpEF. Here’s my take.

HFpEF Diagnosis
Passive Leg Raise During Right Heart Catheterization
Diagnosing HFpEF is often challenging. The resting hemodynamics or the resting echocardiogram (ECHO) do not always catch it. A patient may have mild diastolic dysfunction or modest left ventricular hypertrophy and complain of significant exercise dyspnea, but the resting studies are reassuring. In these cases, exercise right heart catheterization (RHC) is useful. In my lab, we have a bicycle at the end of the table that patients can pedal while lying down. It is amazingly instructive for a healthcare professional. Within 2 minutes, the pressures elevate, and it is clear that the patient has HFpEF.

However, not all patients are able to perform exercise during RHC. To this end, van de Bovenkamp and colleagues investigated the value of the passive leg raise during RHC to diagnose HFpEF. Among 109 patients—including 39 without HFpEF, 33 with occult HFpEF, and 37 with manifest HFpEF—they found that RHC with passive leg raise had 100% specificity and 100% sensitivity for diagnosing occult HFpEF. These findings were validated in an external cohort of 74 patients.

This study is a useful addition to the body of evidence around diagnosing HFpEF and reinforces the utility of RHC, which is underused outside of academic medical centers. Although many healthcare professionals are now integrating dobutamine ECHO and exercise ECHO, which are less invasive diagnostic methods that sometimes can unmask HFpEF, we should be doing more RHCs. Given that we finally have specific medications shown to improve quality of life and outcomes in HFpEF, making the diagnosis is more important than ever. These findings may not radically change practice in the clinic; however, they reinforce physiology that we have known about for decades but is not leveraged enough diagnostically.

HFpEF Treatment
PARAGON-HF: Sacubitril/Valsartan and Renal Function in Diabetic Patients With HFpEF
When managing patients with heart failure, we are often contending with multiple comorbid conditions that make it challenging to find medications that are both safe and effective. In the case of HFpEF, we are seeing a shift around which medications are useful based on recent data demonstrating that certain pharmacotherapies are more useful than others. That raises the question of how these medications affect other conditions, such as diabetes, that we must comanage.

At ACC 2022, Peikert and colleagues presented a post hoc analysis of the phase III PARAGON-HF study asking how angiotensin receptor–neprilysin inhibition (ARNI) with sacubitril and valsartan affected renal function in persons with HFpEF with and without diabetes. Previous data from PARAGON-HF suggested that patients with heart failure with left ventricular ejection fraction between 45% and 57% benefit from sacubitril/valsartan vs valsartan alone. In the current analysis, we saw how these agents affected renal function, which is critical for understanding when managing patients with concomitant diabetes.

They found that sacubitril/valsartan was superior to valsartan in attenuating the decline of renal function in all patients; there was no difference in the extent of the attenuation between patients with diabetes vs without diabetes. This finding was reassuring and suggested there should be no barrier to implementing sacubitril/valsartan in patients with HFpEF and diabetes.

If I were a practicing healthcare professional in the community who was torn between the diabetes guidelines, the renal guidelines, and the new updated heart failure guidelines that discuss the role of ARNI in HFpEF, this subanalysis of PARAGON-HF would help identify an ARNI treatment regimen that can improve outcomes in more than one disease state. I think that is a big win.

Implant-Free Interatrial Shunt for HFpEF
Finally, we saw results from a small, first-in-human clinical trial of an implant-free therapeutic interatrial shunt in patients with HFpEF. Instead of implanting a device, Udelson and colleagues used radiofrequency energy to essentially punch a hole in the interatrial septum. They enrolled 15 patients aged 40 and older, New York Heart Association class II-IV, with left ventricular ejection fraction greater than 40%, diastolic dysfunction, and elevated peak wedge pressure during pulmonary artery catheterization with supine ergometry (aka, pedaling a bicycle while lying on the table).

In this very small study, they demonstrated good safety and some benefit. The procedure, which uses the Alleviant System, was successfully completed in all 15 patients; there were no device-related or procedure-related adverse events. At 30 days, peak exercise wedge pressure was significantly decreased compared with baseline. At 6 months, there were significant improvements in the 6-minute walk test, NT-proBNP levels, and the Kansas City Cardiomyopathy Questionnaire score.

Some outstanding questions include: Will the hole stay open over time or gradually close? Will this continue over an extended period to be an effective therapy to decongest patients by creating a left-to-right shunt to unload the left side of the heart? Will there ultimately be consequences for the right side of the heart with this ongoing shunt?

One theory is that patients with persistent interatrial septal defects will develop pulmonary hypertension over decades. Other complications could include the risk of increasing right-sided pressures leading to paradoxical embolisms. The dogma is typically that we should close holes, not open them.

I think one reason the investigators enrolled patients aged 40 and older was to minimize the chance of adverse events over time. This is not a procedure that you would want to do in a young person. Moreover, if a young person needs this intervention, there is probably something else going on.

In summary, this is an intriguing proof of concept study. It will be interesting to see further evaluation of this technology. Without an implanted device, the risk of infection is lower, and there is no risk of a device shifting or coming loose. But on the other hand, is there a chance that the interatrial shunt will close over time? We will have to await more data.

Your Thoughts?
How will new data in HFpEF diagnosis and treatment influence your practice? Answer the polling question and join the discussion by posting a comment.

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