Algorithm can help optimize device therapy for patients with HFrEF
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Key takeaways:
- Device-based therapy may be necessary for certain patients with NYHA class II/III heart failure with reduced ejection fraction.
- An algorithm has been developed to help with device selection for these patients.
HF is associated with a fourfold increased risk for death and a sixfold to ninefold increased risk for sudden cardiac death, and its direct and indirect costs are estimated to reach $69.8 billion annually in the United States by 2030.
Current HF treatment goals are to slow disease progression to improve symptoms and outcomes, including reducing HF-related hospitalization, improving survival and reducing/avoiding need for left ventricular assist device or transplant. Equally important is improving symptoms and health status (quality of life) and improving functional capacity.
As a chronic, progressive condition requiring lifelong management, patients with HF seek effective treatments — medications, procedures and devices — to relieve their HF symptoms and improve their quality of life. Despite advancements in guideline-directed medical therapy (GDMT), HF symptom burden remains high, and outcomes remain poor with high residual morbidity and mortality.
Some of these patients, particularly those with NYHA class II/III HF, may be candidates for a variety of device-based interventions, including cardiac resynchronization therapy, cardiac contractility modulation (CCM) and baroreflex activation therapy (BAT).
A key challenge in optimizing therapy for patients with class II/III HF is the lack of standardized approaches for initiation and up-titration of GDMT, as well as a formal approach for determining the most appropriate device-based intervention. Clinicians in the Heart Failure Clinical Program at SSM Health in St. Louis have developed a patient stratification algorithm for standardizing care and optimizing outcomes for these patients. This algorithm has been deployed at this care center for 1 year, with promising results that are shared below.
Standardizing GDMT
First-line treatment for patients with HF is to optimize GDMT, which remains foundational and has been shown to improve clinical outcomes including reducing HF hospitalization and improving survival. But there is a lack of standardized approach for initiation and optimization of GDMT.
Our Heart Failure Clinical Program has standardized our approach to GDMT optimization, which both streamlines clinical decision-making and ensures consistency of care for all patients in the program. Patients are seen within 1 week of their initial HF diagnosis and then biweekly for 90 days. GDMT is up-titrated over the first 4 to 6 weeks of care, and patients are evaluated for HF symptoms at 90 days. Optimizing GDMT may at times be challenging because about 40% of patients are not fully adherent to their GDMT regimen for a variety of reasons that include medication costs, side effects and lack of efficacy.
The standard approach in our HF disease management clinic is early initiation of the four pillars of GDMT — beta-blockers, angiotensin receptor/neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs) and SGLT2 inhibitors — with a focus on rapid sequencing by initiating all four classes of GDMT before hospital discharge followed by aggressive up-titration to the target dose (or maximally tolerated dose) of each of the pillars. Patients are seen within 5 to 7 days after hospital discharge for decompensated HF (or after outpatient identification), then biweekly for 90 days. During each of these visits, we either add or up-titrate one of the classes of GDMT to get to the target dose or the maximally tolerated dose. This process used to take 3 months, but our more intensive approach allows us to reach the target dose or maximally tolerated dose within 4 weeks, on average.
Optimizing GDMT is an essential first-line treatment that can reduce disease-related morbidity and mortality for patients with HF, but it is important to acknowledge that this approach has only modest effects with respect to improving exercise capacity and patient QOL. Additionally, about one-third of patients will continue to experience HF symptoms after GDMT and may be candidates for device-based interventions.
The evolving landscape of device-based interventions
For patients with HF with reduced ejection fraction, defined as 35% or less, regardless if related to ischemic or nonischemic dilated cardiomyopathy, and associated HF with NYHA functional class II or III status, it is recommend to use implanted cardiac device therapy for primary prevention of sudden cardiac death.
Patients who remain symptomatic despite GDMT optimizations, especially those with NYHA class II/III HF, may benefit from an additional device-based intervention to improve symptoms, QOL and exercise tolerance. Device therapy including CRT has greater effects on improving symptoms compared with GDMT (20% compared with 2% to 5% change in exercise capacity), but CRT is only indicated in approximately 16% to 30% of patients with NYHA class II/III HFrEF.
Recently the FDA has approved two new device-based therapies for patients with symptomatic HF patients, namely CCM (Optimizer Smart Mini system, Impulse Dynamics) and BAT (Barostim, CVRx). CRT, CCM and BAT therapies are currently used in our program based on the algorithm described below. Patients with LVEF 25% to 45% may be eligible for CCM, whereas patients with LVEF less than 35% may be eligible for BAT.
CRT and CCM are devices that are implanted in the heart to improve cardiac function. CRT is a modality of cardiac pacing that provides simultaneous or nearly simultaneous electrical activation of the LV and right ventricle via stimulation of the LV and RV (biventricular pacing) or LV alone to correct cardiac dyssynchrony and resynchronize the heart. CRT can increase cardiac efficiency and blood flow, which may relieve some HF symptoms, such as shortness of breath. CCM is designed to deliver a biphasic, high-voltage signal to the right ventricular septum that improves cardiac contractility without increasing oxygen consumption. This results in improved cardiac efficiency, which can improve exercise tolerance and measures of QOL.
In contrast to CRT and CCM, BAT is extravascular and designed to stimulate baroreceptors within the carotid artery. The baroreceptors play a critical role in maintaining CV homeostasis by simultaneously regulating the sympathetic and parasympathetic branches of the autonomic nervous system. Afferent signals from carotid baroreceptors are constantly transmitted to the brain to interpret. The brain uses these signals to regulate the heart, kidney and vascular function via the autonomic nervous system. Patients with HF have decreased signaling from baroreceptors, which results in an increase in sympathetic and a decrease in parasympathetic tone. This imbalance in the autonomic nervous system leads to worsening HF symptoms. Continuous electrical stimulation of carotid baroreceptors increases signaling to the brain, resulting in a decrease in sympathetic tone and an increase in parasympathetic tone. This restores balance in the autonomic nervous system and has been shown to significantly improve patients’ exercise capacity and QOL.
BeAT-HF was a prospective, multicenter, randomized, two-arm, parallel-group, open-label with masked evaluation clinical trial in which 323 patients with NYHA class III or class II (with recent history of class III) HF and LVEF less than 35% who were not candidates for CRT were randomly assigned to BAT plus GDMT or GDMT alone. Long-term results of the trial favored BAT. This study was the first to demonstrate the long-term benefit of a device-based intervention in this patient population. Key findings from this study include:
- long-term symptom improvement for BAT plus GDMT compared with GDMT alone;
- 6-minute walk distance improved by 44 m at 12 months;
- QOL improved by 10 points in Minnesota Living with Heart Failure Questionnaire at 24 months;
- NYHA class improved 27% more in patients assigned BAT at 24 months;
- a 34% relative reduction in all-cause mortality (all-cause death, LVAD, heart transplant) in BAT compared with control (HR = 0.66; 95% CI, 0.44-1.007; and
- a 97% rate of freedom from system or procedure-related major adverse neurological or CV events in the Barostim arm.
An algorithm for determining device stratification
Currently, there are no formal guidelines to support clinical decision-making regarding device selection for patients with NYHA class II/III HF who are not candidates for CRT. Our clinical program has developed a stratification algorithm for these patients based on the patient’s EF (Figure).
After completing the GDMT optimization process outlined above, LVEF is assessed using an echocardiogram, multigated acquisition scan or cardiac MRI, and QRS duration is assessed with repeat ECG to determine the appropriate device therapy.
Based on this evaluation, patients are screened for an implantable cardiac device to prevent sudden cardiac death and/or novel device therapy to improve HF symptoms. Patients with a wide QRS complex and left bundle branch block typically receive a CRT defibrillator device. Patients with a narrow QRS who are not candidates for CRT receive either a CCM or BAT device, based on their EF. In our algorithm, patients with NYHA III (or NYHA class II with recent class III symptoms) and EF 35% or less are recommended for BAT, whereas those with NYHA III and EF 25% to 45% are candidates for CCM.
All patients who are deemed candidates for novel HF device therapy are discussed in our monthly Heart Team meeting before they undergo device implant. This team includes general cardiologists, electrophysiologists, cardiothoracic surgeons/vascular surgeons and HF specialists.
Throughout this process outlined above we objectively assess the patient’s functional capacity/exercise tolerance using the 6-minute walk test as well as their QOL using the 12-item version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at baseline and then at 90 days and 180 days post-device implant to assess improvement in patients’ symptoms on optimal GDMT and device therapy.
Lessons learned and next steps
One of the most important lessons I’ve learned in treating patients with class II/III HF is that a large proportion of them place greater emphasis on QOL rather than their longevity. Physicians often prioritize longevity, but it is incumbent on us to understand our patients’ health goals, make sure they have information to make decisions about the risks and benefits associated with those goals, and then respect the choices they make.
I’ve also seen that patients generally achieve the greatest improvements in their QOL and exercise capacity with the use of novel HF device therapy. Many of my patients using these novel HF devices can perform their activities of daily living, engage in hobbies, and do more activities with their families than they were able to do prior to device implant.
Today’s physicians and patients are fortunate to have treatment options that can help improve QOL. With continued research and innovation, I hope that we will have additional options that help patients live both better and longer.
References:
- Abraham WT, et al. JACC Heart Fail. 2018;doi:10.1016/j.jchf.2018.04.010.
- Benjamin EJ, et al. Circulation. 2019;doi:10.1161/CIR.0000000000000659.
- Clinical trials.gov. https://clinicaltrials.gov/study/NCT02627196. Updated Jan. 23, 2023. Accessed April 12, 2024.
- CVRx Inc. Barostim instructions for use. https://www.cvrx.com/healthcare-professionals/ifu/us. Updated Dec. 23, 2023. Accessed April 12, 2024.
- Lewis GD, et al. Circ Heart Fail. 2022;doi:10.1161/CIRCHEARTFAILURE.121.008970.
- Lloyd-Jones DM, et al. Circulation. 2002;doi:10.1161/01.cir.0000039105.49749.6f.
- McMurray JJ, et al. Eur Heart J. 1998(12);19 Suppl P:9-16.
- Ponikowski P, et al. ESC Heart Fail. 2014;doi:10.1002/ehf2.12005.
- Savarese G, et al. JACC Heart Fail. 2023;doi:10.1016/j.jchf.2022.08.009.
For more information:
Georges Chahoud, MD, FACC, FAHA, FHFSA, FASE, is regional director of the Heart Failure Clinical Program and director of cardiology at SSM Health St. Joseph Hospital–Lake St. Louis in Lake St. Louis, Missouri. He can be reached at georges.e.chahoud@ssmhealth.org.
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