In April, the cardiology community converged face-to-face in Orlando for The American College of Cardiology’s (ACC22) Annual Scientific Session after a two-year hiatus that forced the conference to go virtual due to the ongoing COVID-19 pandemic. An estimated 7,700 in-person and 4,400 virtual cardiovascular professionals from around the globe came together to connect with peers and top experts in the field, and discuss practice-changing science and innovations in cardiovascular medicine.
The past two years have placed a significant amount of stress on the cardiovascular workforce, particularly given the well-established cardiovascular complications of COVID-19. Over the past few years, ACC has conducted a series of surveys and needs assessments, and has made a strong investment in the well-being of its members by providing resources and programming to support healthier work/life balance, and also help manage clinician burnout.
During ACC22, I was able to connect with Pamela Morris, M.D., who is the ACC22 Chair and Professor of Medicine, Cardiology; Director, Seinsheimer Cardiovascular Health Program; and Co-director, Women’s Heart Care at the Medical University of South Carolina, to discuss both the current state of the cardiology industry and the conference.
“The pandemic has affected the cardiology workforce. ACC22, however, really clearly demonstrated that cardiovascular clinicians and scientists have remarkable resilience in the face of these challenges, and that we still maintain that unwavering commitment to our patients,” stressed Morris. “I think the return to in person education, and that scientific exchange that we had at ACC, to me, was actually very much needed to maintain the connectivity that has always been such an important part of the culture of cardiology. It was very inspirational. At the meeting, we could say that the quality of the science of late-breaking clinical trials and abstracts were as sound as ever before. The pandemic really has not slowed the pace of discovery.”
Combined, this was a hearty reassurance that the cardiovascular community is thriving, and building for the future. According to Morris, the biggest issues that became glaringly clear throughout the pandemic were telehealth, trust in the scientific community, prioritizing financial well-being and avoiding burnout.
“Prior to the pandemic, we were dragging our feet a little bit about jumping into the telehealth role,” she stated. “I think the pandemic really made that glaringly clear, sort of making significant advancements in that respect. The pandemic also took an incredible toll on trust in the scientific community because of the unnecessary and unwarranted politicization of the virus and the mitigation strategies.”
Key ACC22 Highlights
One of the key highlights of the ACC annual Scientific Sessions is always the science, and this year was no exception. Noteworthy was the wide variety of clinical trials being presented.
VALOR-HCM Trial. Of these was the VALOR-HCM Trial. According to results from the VALOR-HCM trial presented April 2 during ACC22, use of mavacamten to treat patients with obstructive hypertrophic cardiomyopathy (HCM) who were referred as candidates for invasive septal reduction therapy (SRT) significantly reduced the need for the surgical intervention at 16 weeks.
“This is really the first pharmacotherapy that offers a viable medical option for patients with this under diagnosed and somewhat under treated disease, so I was really excited about this trial,” shared Morris.
The randomized, double-blind, placebo-controlled study evaluated the use of mavacamten in 112 adults with symptomatic obstructive HCM who were referred to an HCM expert at 19 HCM centers. All patients had documented HCM with maximum septal wall thickness ≥15 mm or ≥13 mm; family history of HCM; severe symptoms despite maximally tolerated medical therapy; dynamic left ventricular outflow tract (LVOT) gradient at rest or with provocation ≥50 mmHg; and documented left ventricular ejection fraction ≥60%, according to the data that was presented.
For the trial, researchers randomly assigned each patient to receive mavacamten or a placebo for 16 weeks. The primary endpoint was a composite of patient decision to proceed with SRT or continue to meet 2011 ACC/AHA guideline eligibility for SRT after 16 weeks.
At 16 weeks, only 18% of patients on mavacamten were still eligible for SRT, compared with 77% of those on placebo, according to the trial results. The researchers also observed significant improvements across all secondary endpoints, including reduction in resting LVOT gradient; ≥1 class improvement in NYHA Class; improvement in KCCQ-clinical summary score; reduction in N-terminal pro-B-type natriuretic peptide; and reduction in troponin I. It was reported that no patients experienced serious adverse cardiac events.
"These were very symptomatic, sick patients who were on maximally tolerated medical therapy and were faced with the decision of whether or not to have septal reduction therapy to relieve the obstruction. In taking this drug, they got a whole lot better across the board," said Milind Y. Desai, MD, MBA, FACC, the study's lead author, at ACC22. "This is really the first pharmacotherapy that offers a viable medical option for people with obstructive HCM short of needing a procedure."
Desai noted that additional data is needed to assess the durability of improvement in SRT eligibility over longer time periods. "We are hoping this study will also draw much-needed attention to HCM," he said. "This disease is woefully underrecognized. There are not enough HCM experts and not enough proven medical therapies, so there are many opportunities to do better."
Mavacamten was approved by the U.S. Food and Drug Administration (FDA) for use in obstructive HCM in late-April.
CHAP Trial. The CHAP Trial was a late-breaking trial presented at ACC22 on Chronic Hypertension and Pregnancy (CHAP). The trial showed that antihypertensive therapy improves pregnancy outcomes among pregnant women with mild chronic hypertension. The goal of the trial was to evaluate antihypertensive therapy compared with control among pregnant women with mild chronic hypertension.
“Previously, it was thought that when women were pregnant, you needed to allow a higher level of blood pressure to maintain perfusion of the fetus,” said Morris. “This trial found that there were no adverse effects on the fetus. There was no increased risk of small-for-gestational-age infants, or any effect on fetal growth. So that's very important and will be practice changing for the future.”
Based on the findings presented, treating mild chronic hypertension during pregnancy was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension. Researchers also observed no increase in the risk of infants born with "small-for-gestational-age birth weight."
The open-labeled, randomized, controlled trial enrolled 2,408 women with known mild chronic hypertension (<160/110 mm Hg) and who were less than 23 weeks into their pregnancy at 61 sites between 2015 and 2021. Women were similar across groups with over half (56%) already on medication for hypertension at enrollment; 48% were Black, 28% non-Hispanic White and 20% Hispanic, according to data presented.
A total of 1,208 pregnant women were assigned to receive treatment with a first-line antihypertensive medication with a blood pressure goal of less than 140/90 mm Hg, and another 1,200 received no treatment unless blood pressure became more severe (160/105 mm Hg or higher), according to the data. Centers were given general guidance on which medications to prescribe using the patient's previously prescribed dose or the lowest recommended dose and escalating the dose during clinic visits to achieve the blood pressure goal. Women in the treatment group who were already taking other blood pressure-lowering medication could remain on that drug if they wished and as long as it was safe in pregnancy.
The researchers found significantly lower rates of the primary outcome – a composite of preeclampsia with severe features, preterm birth less than 35 weeks, abruption and neonatal/fetal death – among pregnant women who received treatment (30.2%) compared with those who did not (37%). When looking at each outcome individually, antihypertensive treatment significantly lowered the risk for preeclampsia and birth before 35 weeks. The rates of placenta abruption and fetal or neonatal death were not significantly different between the groups. Researchers did not see a significant difference in the rate of babies who were small for gestational age – the study's safety endpoint – between the two groups, with 11.2% of babies in the treatment group and 10.4% of babies in the no treatment group falling below the 10th percentile.
“After many decades of uncertainty, results of this study support the need for clinical guidance to treat mild as well as severe chronic hypertension in pregnancy and to educate patients about the benefits of doing so," said Alan Tita, MD, PhD, the study's lead author, at ACC22. "To date, there have been disparate recommendations and hesitancy to treat women with milder forms of high blood pressure during pregnancy for fear of hurting the growing fetus but based on the data, doing so may be good for mom and baby."
PACMAN-AMI Trial. The PACMAN-AMI trial showed that, compared with placebo, administration of alirocumab 150 mg biweekly within 24 hours after PCI for AMI results in a greater reduction in plaque burden and plaque regression at 52 weeks in the nonculprit vessel, according to data presented at ACC22. All patients were on high-dose rosuvastatin. The goal of the trial was to demonstrate the efficacy of early administration of alirocumab on plaque characteristics among patients undergoing percutaneous coronary intervention (PCI) for an acute myocardial infarction (AMI).
“I think clinical implications where the take home message from that trial will really be earlier initiation of combination therapy in higher risk patients and also going lower than previously achieved levels of LDL cholesterol,” stated Morris.
Compared with placebo, the addition of subcutaneous biweekly alirocumab to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks in patients with acute myocardial infarction (AMI), based on findings presented April 3 at ACC22. However, researchers noted that further studies are needed to understand whether alirocumab improves clinical outcomes in this patient population.
Researchers randomized 300 patients undergoing PCI for AMI to receive biweekly subcutaneous alirocumab (150 mg; n=148) or placebo (n=152), initiated less than 24 hours after urgent PCI of the culprit lesion, for a total of 52 weeks. All patients received high-intensity statin therapy (rosuvastatin, 20 mg). The primary efficacy endpoint was the change in IVUS-derived percent atheroma volume from baseline to week 52. Secondary endpoints included changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm, as well as optical coherence tomography-derived minimal fibrous cap thickness from baseline to week 52.
According to the researchers, the mean change in percent atheroma volume was -2.13% with alirocumab vs. -0.92% with placebo at 52 weeks. In addition, the mean change in maximum lipid core burden index within 4 mm was -79.42 in the alirocumab group compared with -37.60 in the placebo group, while the mean change in minimal fibrous cap thickness was 62.67 μm with alirocumab vs. 33.19 μm with placebo. Adverse events were reported in 70.7% of patients treated with alirocumab compared with 72.8% receiving placebo.
"Following early initiation of alirocumab on top of high-intensity statin therapy in a high-risk population with AMI, we observed a twofold regression of coronary atherosclerosis and stabilization of high-risk plaques when compared with treatment with statins alone," said Lorenz Räber, MD, PhD, the trial's principal investigator, at ACC22. "These findings provide insights to support more-frequent, early and targeted use of alirocumab on top of high-intensity statin therapy in patients who have had a heart attack and are at high risk for a second one."
Heart Failure Guidelines
A new joint guideline was published during ACC22 from the American College of Cardiology, the American Heart Association and the Heart Failure Society of America that increases the focus on preventing heart failure (HF) in people who are showing early signs of “pre-heart failure,” and updates treatment strategies for people with symptomatic heart failure to include SGLT-2 inhibitor (SGLT2i) medicines. The guideline also offers recommendations for managing cardiac amyloidosis, cardio-oncology complications, comorbidities in the setting of heart failure, as well as consideration for implantable devices and advanced therapies for people with stage D heart failure.
“One primary goal with the new guideline was to use recently published data to update our recommendations for the evaluation and management of heart failure,” said Paul A. Heidenreich, MD, MS, guideline writing committee chair, at ACC22. “One focus was prevention of heart failure through optimizing blood pressure control and adherence to a healthy lifestyle.”
The ACC/AHA stages of heart failure, from A – D, emphasize the development and progression of the disease, with advanced stages indicating more serious disease and reduced survival rate. The new guideline revised these stages to identify HF risk factors early, which is stage A, at risk for HF, and to provide treatment before structural changes or signs of decreased heart function occur, which is stage B, pre-HF. New York Heart Association classification (Class I – IV) is used when people reach symptomatic (stage C) or advanced (stage D) HF, to describe their functional capacity and determine treatment strategies.
With approximately 121.5 million people in the U.S. with high blood pressure, 100 million with obesity, and 28 million with diabetes, a large proportion of the U.S. population can be categorized as stage A and at risk for HF. For people in this category the guideline recommends blood pressure control according to the latest guidelines. A normal resting blood pressure should be below 120/80 mmHg. People with Type 2 diabetes and either established cardiovascular disease or at high cardiovascular risk are recommended to consider SGLT2i medicines, which are shown to improve survival in these populations. In general, the mainstays of cardiovascular disease prevention are recommended to reduce HF risk: healthy lifestyle habits such as physical activity, healthful dietary patterns, avoiding smoking and maintaining a healthy weight.
While stage A (at risk) recommendations are also applicable for those in stage B, people who have pre-HF have an opportunity to incorporate additional medications to prevent symptomatic HF. For people with stage B HF with left ventricle ejection fraction (LVEF) ≤40%, ACE-inhibitors (angiotensin-converting-enzyme inhibitors, or ACEi) should be used to prevent HF symptoms from developing. Angiotensin receptor blockers (ARBs) may be prescribed for individuals with an intolerance or contraindication to ACEi. Both medications help relax the blood vessels and reduce blood pressure. Cholesterol-lowering statins are recommended for people with a history of heart attack or acute coronary syndrome.
People who have progressed to stage C with HF symptoms should receive care from multidisciplinary teams to facilitate guideline-directed medical therapy and self-care support for learning to manage symptoms. Self-care support includes understanding the importance of taking medicine as directed and maintaining healthy behaviors such as restricting sodium intake and staying physically active. They should also understand how to monitor themselves for signs of worsening HF and what to do about these symptoms. Screenings to identify potential medical or social barriers for effective self-care are recommended, as well as education and support reduce rehospitalization and improve survival. Individuals with stage C HF should be fully vaccinated against respiratory illnesses including COVID-19.
“In recent years, there has been an increase in rigorous science assessing how best to treat symptomatic heart failure. With this new guideline, the writing committee hopes to inform better treatment options for a broader number of our patients with heart failure,” Heidenreich said.
Left ventricular ejection fraction (LVEF) informs prognosis and response treatments for people with HF. The left ventricle of the heart is responsible for pumping blood out to the rest of the body. The percentage of blood that is pumped out of the left ventricle is measured as a percentage called ejection fraction. In general, LVEF of ≥50-55% is considered normal.
For individuals with stage C HF, the new guideline refines the current four classifications of HF based on LVEF with new terminology:
- HF with reduced ejection fraction (HFrEF) includes people with LVEF ≤40%.
- HF with improved ejection fraction (HFimpEF) includes individuals with previous LVEF ≤40% and a follow-up measurement of LVEF >40%.
- HF with mildly reduced ejection fraction (HFmrEF) includes people with LVEF 41-49% and evidence of increased LV filling pressures.
- HF with preserved ejection fraction (HFpEF) includes individuals with LVEF ≥50% and evidence of increased LV filling pressures.
“After careful evaluation of new evidence, guideline-directed medical therapy now includes four medication classes that include SGLT-2 inhibitors. Irrespective of diabetes status, the DAPA-HF and EMPEROR-HF trials have shown the benefit of treating patients with HFrEF with SGLT-2 inhibitors, showing a 30% reduction in heart failure rehospitalization. This is a major step forward in reducing mortality rates in this vulnerable population,” said Biykem Bozkurt, MD, PhD, guideline writing committee vice-chair, at ACC22.
This new heart failure guideline replaces the 2013 ACCF/AHA Guideline for the Management of Heart Failure and the 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. The guideline is targeted to all clinicians who are involved in the care of people with cardiovascular disease with or without heart failure.
“There were some interesting refinements or developments in this timeline. These were very patient centric recommendations to help the clinicians to better prevent, diagnose and treat heart failure and one of the things that I really appreciated about the guideline was its focus on prevention of heart failure in patients who are at risk of heart failure,” said Morris. “This is certainly a step forward in management and prevention. It also refined the current four classifications of heart failure into heart failure with reduced ejection fraction, heart failure with improved ejection fraction, heart failure with mildly reduced ejection fraction and then heart failure with preserved ejection fraction.”
The Future of Cardiac Care
The American College of Cardiology remains committed to its mission of transforming cardiovascular care for the future for clinicians and scientists, and importantly, for patients. “I think the key components of the strategy will include digital transformation, and that will include improvements in an expansion of telehealth opportunities for patients, certainly in this era of focus on improving health equity, which is a strong focus of the college,” stated Morris.
“Another important strategy for the future is diversification of the current cardiovascular workforce, and then building a more diverse pipeline of cardiovascular professionals for the future. We also see that there will need to be a global emphasis on global cardiovascular health,” she continued. “And we are really striving to continue to work together with our international chapters, our international cardiovascular community, and our international number experts.”
The ACC is committed to providing actionable knowledge and the practical tools that clinicians can use at the point of care every day in their clinics. This will help guide the future for clinicians. “I'd say that the future of cardiology is bright, and the community is truly thriving,” concluded Morris.