Neuromodulation of the failing heart: Lost in translation?

SummarySympathovagal imbalance contributes to progressive worsening of heart failure (HF) and is associated with untoward clinical outcomes. Based on compelling pre-clinical studies that supported the role of autonomic modulation in HF models, a series of clinical studies were initiated using spinal cord stimulation, vagus nerve stimulation, and baroreceptor activation therapy in patients with HF with a reduced ejection fraction. Whereas the phase II studies with baroreceptor activation therapy remain encouraging, the larger clinical studies with spinal cord stimulation and vagus nerve stimulation have yielded disappointing results. Here we will focus on the pre-clinical studies that supported the role of neuromodulation in the failing heart, as well provide a critical review of the recent clinical trials that have sought to modulate autonomic tone in HF patients. This review will conclude with an analysis of some of the difficulties in translating device-based modulation of the autonomic nervous system from pre-clinical models into successful clinical trials, as well as provide suggestions for how to move the field of neuromodulation forward

Valve-in-valve Transcatheter Aortic Valve Replacement for Failed Surgical Valves and Adjunctive Therapies

While redo surgical aortic valve replacement has traditionally been the gold standard for the treatment of failed surgical valves, valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) has arisen as a viable, less invasive option with the potential for improved short-term morbidity and mortality. Retrospective registry data regarding ViV TAVR outcomes have been encouraging, with excellent 1-year mortality, and sustained valve performance and quality of life improvement out to 3 years. Operators must be comfortable with CT analysis for procedural planning, and be able to identify and troubleshoot patients who are at risk for coronary obstruction and patient prosthesis mismatch. The authors provide a review of clinical outcomes associated with ViV TAVR, procedural planning recommendations, and strategies to overcome technical challenges that can occur during ViV TAVR

Use of mechanical circulatory support and survival for heart and heart-kidney transplant recipients in the new allocation system

Background The 2018 United Network for Organ Sharing organ allocation change aimed to distribute donor hearts to the sickest patients on the waitlist. Whether this change differentially affected outcomes in heart-only vs heart-kidney transplant recipients is unknown. Methods This study used the Scientific Registry of Transplant Recipients to compare outcomes, including survival, of heart-only and heart-kidney transplant recipients from 2015 to 2021, from the old vs new allocation system, including use of mechanical circulatory support (MCS), prior to transplant. Results During the study period, 16,696 patients underwent heart transplant alone (9,320 in the old and 7,376 in the new system) and 1,156 patients underwent heart-kidney transplant (529 in the old and 627 in the new system). For both heart and heart-kidney transplant populations, there was a 3- to 5-fold increase in the use of temporary MCS. Heart-only recipients had worse survival when temporary MCS was used in the old allocation system. Heart-only recipients with durable MCS had worse survival both in the old and the new allocation system. There was no difference in survival in heart-kidney recipients in the old vs new allocation system, regardless of MCS use. Conclusions The new heart allocation system was associated with increased use of temporary MCS in both heart and heart-kidney recipients. However, this change only differentially affected survival in heart-only recipients with improved survival if on temporary MCS, but worse survival if on durable MCS. Unlike prior studies, heart-kidney recipients did not have different outcomes after the heart allocation change, which may reflect outcomes in more current times

Supportive Care and Symptom Management for Patients With Immunoglobulin Light Chain (AL) Amyloidosis

Immunoglobulin light chain (AL) amyloidosis is a disorder of clonal plasma cells characterized by deposition of amyloid fibrils in a variety of tissues, leading to end-organ injury. Renal or cardiac involvement is most common, though any organ outside the central nervous system can develop amyloid deposition, and symptomatic presentations may consequently vary. The variability and subtlety of initial clinical presentations may contribute to delayed diagnoses, and organ involvement is often quite advanced and symptomatic by the time a diagnosis is established. Additionally, while organ function can improve with plasma-cell-directed therapy, such improvement lags behind hematologic response. Consequently, highly effective supportive care, including symptom management, is essential to improve quality of life and to maximize both tolerance of therapy and likelihood of survival. Considering the systemic nature of the disease, close collaboration between clinicians is essential for effective management

Optogenetic Stimulation of Vagal Efferent Activity Preserves Left Ventricular Function in Experimental Heart Failure.

Large clinical trials designed to test the efficacy of vagus nerve stimulation (VNS) in patients with heart failure did not demonstrate benefits with respect to the primary endpoints. The nonselective nature of VNS may account for the failure to translate promising results of preclinical and earlier clinical studies. This study showed that optogenetic stimulation of vagal pre-ganglionic neurons transduced to express light-sensitive channels preserved left ventricular function and exercise capacity in a rat model of myocardial infarction-induced heart failure. These data suggested that stimulation of vagal efferent activity is critically important to deliver the therapeutic benefit of VNS in heart failure

Special Considerations in the Care of Women With Advanced Heart Failure

Advanced heart failure (AHF) is associated with increased morbidity and mortality, and greater healthcare utilization. Recognition requires a thorough clinical assessment and appropriate risk stratification. There are persisting inequities in the allocation of AHF therapies. Women are less likely to be referred for evaluation of candidacy for heart transplantation or left ventricular assist device despite facing a higher risk of AHF-related mortality. Sex-specific risk factors influence progression to advanced disease and should be considered when evaluating women for advanced therapies. The purpose of this review is to discuss the role of sex hormones on the pathophysiology of AHF, describe the clinical presentation, diagnostic evaluation and definitive therapies of AHF in women with special attention to pregnancy, lactation, contraception and menopause. Future studies are needed to address areas of equipoise in the care of women with AHF

Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats

The sympathetic nervous system and renin-angiotensin system are both thought to contribute to the development and maintenance of hypertension in experimental models such as the spontaneously hypertensive rat (SHR). We demonstrated that periarterial nerve stimulation (NS) increased the perfusion pressure (PP) and neuropeptide Y (NPY) overflow from perfused mesenteric arterial beds of SHRs at 4–6, 10–12, and 18–20 wk of age, which correspond to prehypertensive, developing hypertensive, and maintained hypertensive stages, respectively, in the SHR. NS also increased PP and NPY overflow from mesenteric beds of Wistar-Kyoto (WKY) normotensive rats. NS-induced increases in PP and NPY were greater in vessels obtained from SHRs of all three ages compared with WKY rats. ANG II produced a greater increase in PP in preparations taken from SHRs than WKY rats. ANG II also resulted in a greater increase in basal NPY overflow from 10- to 12-wk-old and 18- to 20-wk-old SHRs than age-matched WKY rats. ANG II enhanced the NS-induced overflow of NPY from SHR preparations more than WKY controls at all ages studied. The enhancement of NS-induced NPY overflow by ANG II was blocked by the AT1 receptor antagonist EMD-66684 and the angiotensin type 2 receptor antagonist PD-123319. In contrast, ANG II greatly enhanced norepinephrine overflow in the presence of PD-123319. Both captopril and EMD-66684 decreased neurotransmitter overflow from SHR mesenteric beds; therefore, we conclude that an endogenous renin-angiotensin system is active in this preparation. It is concluded that the ANG II-induced enhancement of sympathetic nerve stimulation may contribute to the development and maintenance of hypertension in the SHR