Digest 46: A STEP forward for HFpEF?

October 22, 2023 | By Nora Taranto

Welcome Back to The Curbsiders Digest!
We cover STEP-HFpEF, alongside fresh takes on blood pressure cuff size, steroids for Tb meningitis, carbohydrate types and weight loss, and paternal postpartum depression  
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Issue 46

10/21/2023

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
Jen Desalvo MD; Hannah Smith MD

• Dads get sad, too! A new study has assessed the utility of screening for paternal postpartum depression in the year after birth, just published in BMC Pregnancy and Childbirth. Postpartum depression (PPD) is estimated to affect around 10% of fathers, with later onset after childbirth, yet there are no current recommendations for PPD screening among fathers. In 2021, The University of Illinois at Chicago Health System expanded maternal PPD screening to include fathers. With maternal permission, clinic staff contacted fathers either in person or by phone, at an average of 7 months postpartum, and screened for PPD with the Edinburgh Postnatal Depression Scale. A majority (24/29) agreed to complete screening, and nearly one-third screened positive for PPD, with several subsequently requesting mental health services and several establishing primary care. (HS) 
• Vegetable type matters – Food for thought?  In a study just published in BMJ, researchers examined the relationship between diet and weight gain using data collected in three large, prospective observational studies of healthcare workers.  Over 135,000 individuals reported details of their diet and weight changes every 2-4 years over 24-28 years of follow-up. Increases in dietary glycemic index and glycemic load, starch content and starchy vegetable consumption, added sugar, and refined grains were associated with greater weight gain. Meanwhile, increased intake of fiber, natural sugars, whole grains, fruit, and non-starchy vegetables were associated with less weight gain–with stronger associations for those who were overweight or obese. Giving advice about the starch and sugar content of different vegetables and grains–and that type of vegetable matters–may be useful in making dietary recommendations. (HS)
• It’s getting to be appropriate cuff(ing) sz(n). With the Cuff(SZ) trial recently published in JAMA, don’t forget to use an appropriately sized blood pressure (BP) cuff. This randomized crossover trial studied nearly 200 adults using triplicate BP measurements, with the initial three measurement sets using an appropriate (defined based on mid-arm circumference), too-small, or too-large BP cuff in random order, and the fourth set using an appropriately sized BP cuff. Using a regular BP cuff in those requiring a small BP cuff lead to a 3.6 mm Hg lower systolic BP (SBP) recording, and 4.8 / 19.5 mm Hg higher SBP measures among patients requiring a large or extra large BP cuff, respectively. (JD)  
• Steroids for Tb Meningitis? Not a Slam Dunk.  Though steroids are recommended in multiple treatment guidelines for the treatment of tuberculous meningitis in patients with HIV, a new randomized, double-blind, placebo-controlled trial just published in NEJM calls this approach into question. In the ACT HIV Trial, 520 HIV-positive adults with tuberculous meningitis were randomized to 6-8 weeks of adjunctive tapered dexamethasone or placebo, in addition to standard antiretroviral/anti-tuberculosis therapy. There was a slightly lower all-cause mortality rate among those treated with dexamethasone (44% vs 49% with placebo, P=0.22), but this difference was not statistically significant. There were similar rates of secondary end-points (neurologic events, immune reconstitution inflammatory syndrome, and new AIDS-defining events), as well as similar rates of adverse events, between the two groups. As this editorial points out, mortality rates with or without steroids remain high, demonstrating the ongoing need for novel approaches to treatment. (JD) 
• Clopidogrel over aspirin monotherapy maintenance after PCI, regardless of risk?! This post-hoc analysis of the HOST-EXAM trial published in JACC randomized >5400 patients who were event-free on DAPT (dual antiplatelet therapy) for 6-18 months following percutaneous coronary intervention (PCI) to be switched to either clopidogrel or aspirin monotherapy, stratifying them by clinical risk based on the TRS 2P and DAPT clinical risk scores (taking into account both ischemic and bleeding risks).  Patients treated with clopidogrel compared to aspirin monotherapy experienced lower rates of the primary composite endpoint of all-cause mortality, nonfatal myocardial infarction, stroke, readmission due to ACS, or major bleeding (HR: 0.73; 95% CI: 0.59-0.90), with similar trends when stratified by clinical risk scores, at 2 years following randomization. (JD) 

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

As another wave of COVID variants loom on the horizon, “A Case for Moral Healing” provides a shimmer of light for physicians searching for ways to combat moral injury in a peri-pandemic world. The author, Dr. Jimmy Ching-Man Leung, uses his love of the TV sitcom “MASH” to explore the meaning of moral injury and disengagement. He also emphasizes their impact within medicine, as “we are also beginning to realize that, independent of burnout, the mental health of health care workers is itself a health care crisis.” Although he endorses the need for top-down interventions to address this, Dr. Leung highlights several key approaches that empower physicians to discover moral healing within their personal and professional lives – compassion, humility, resilience, nourishment, and forgiveness. 

– Jen DeSalvo MD

The Main Course

Alyssa Mancini MD

Semaglutide: A STEP in the Right Direction for Patients with HFpEF and Obesity

Heart failure with preserved ejection fraction (HFpEF) is defined as heart failure with a left ventricular ejection fraction > 50% at diagnosis, and affects around 3 million people in the US (and approximately 32 million worldwide), with an annual mortality rate of ~15% and limited therapeutic options. Obesity has been implicated in the development and progression of HFpEF, possibly via inflammatory and metabolic pathways associated with excess visceral adipose tissue. Furthermore, patients with HFpEF and obesity have greater symptom burden and worse functional capacity than those without obesity. 

Enter Semaglutide–a glucagon-like peptide 1 (GLP-1) receptor agonist that is currently approved for long-term weight management and that was shown to improve cardiometabolic risk factors in adults with overweight or obesity in STEP trial exploratory analyses. The STEP-HFpEF trial has now investigated whether semaglutide might cause both weight loss and symptom improvement in patients with HFpEF and obesity.

Breaking it Down

STEP-HFpEF was a randomized, double-blind, placebo-controlled trial conducted at 96 sites in 13 countries. The trial included adults with an EF >45%; BMI >30; NYHA functional class II-IV; a Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) of <90 (scores range from 0-100, with higher scores indicating fewer symptoms and physical limitations), and a 6-minute walk distance >100 meters.  Patients also had to have elevated filling pressures, elevated natriuretic peptide levels plus echo abnormalities, or hospitalization for heart failure in the prior year.  Participants were excluded if they had diabetes or significant body weight change shortly prior to enrollment. Ultimately, 529 participants (56% women, 96% White, median age 69, median BMI 37) were randomly assigned 1:1 to receive once weekly subcutaneous semaglutide 2.4 mg (started at 0.25 mg weekly with dose escalation every 4 weeks) or placebo for 52 weeks, followed by a 5-week follow-up period.

The mean change in KCCQ-CSS at week 52, one of the primary endpoints, was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference 7.8 points, 95% CI 4.8-10.9, P<0.001). The other primary endpoint, mean percentage change in body weight at week 52, was -13.3% for semaglutide and -2.6% for placebo (estimated difference -10.7%, 95% CI -11.9 to -9.4, P<0.001).  The mean change in 6-minute walk distance at week 52 was 21.5 meters with semaglutide and 1.2 meters with placebo (estimated difference 20.3 m, P<0.001). Serious adverse events occurred in 13.3% of those receiving semaglutide and 26.7% of those receiving placebo–primarily reflective of decreased cardiac events with semaglutide. 

The Takeaways

In patients with HFpEF and obesity, treatment with semaglutide 2.4 mg weekly led to larger reductions in symptoms and physical limitations, greater improvements in exercise capacity, and greater weight loss than treatment with placebo. Notable limitations of the study include low numbers of non-White participants, a relatively short follow-up period, low levels of baseline SGLT2 inhibitor use in the trial population (as this trial was ongoing as EMPEROR-Preserved was published), and a lack of power to evaluate clinical events such as hospitalizations for heart failure.  Of note, there is an ongoing trial investigating semaglutide 2.4 mg weekly vs. placebo in patients with HFpEF, obesity, and type 2 diabetes.  In the meantime, the data from STEP-HFpEF adds to our metabolism-targeted arsenal of drugs in HFpEF–if only from a symptom and weight perspective, for now–with hard outcome endpoints still to be established that will help us think through the role of GLP1- versus SGLT2-targeted agents in managing HFpEF. 

Read The STEP-HFpEF Trial Results HERE

Digestifs

Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: This week, we’ve got Episode #24 in the Curbsiders Addiction Medicine Series, “Treating OUD in the Fentanyl Era: ASAM Treatment Week with Dr. Melissa Weimer.” This episode is packed full of pearls about treatment initiation in patients who are exposed to high-potency synthetic opioids (HPSOs) like fentanyl, including the details of initiating high-dose buprenorphine, starting methadone, and even using ketamine to manage buprenorphine-precipitated opioid withdrawal. It’s a fascinating and useful one, folks. 

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The Curbsiders Digest

Issue 46

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures:

Alyssa Mancini, Jennifer DeSalvo, Hannah Smith and Nora Taranto report no disclosures. 

Kate Grant reports no disclosures.

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