Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials.

BACKGROUND: There is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF). METHODS: The REDUCE LAP-HF I (n = 44) and II (n = 621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n = 313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up. RESULTS: At 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P = .006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P = .005; and greater improvement in KCCQ overall summary score [+17.9 ± 20.0 vs. +7.6 ± 20.4], P < .001), while nonresponders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2%-6.1%, P = .032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, P = .041). CONCLUSIONS: With up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up. GOV REGISTRATION: NCT02600234, NCT03088033.

Atrial Mechanics, Atrial Cardiomyopathy and Impact of Atrial Interventions.

Our comprehension of atrial mechanics, atrial cardiomyopathy and their clinical implications across various cardiovascular conditions has advanced significantly. Atrial interventions can have differing effects on atrial mechanics. With the rapid increase in the use of atrial interventions, it is crucial for investigators and clinicians to acknowledge the potential adverse effects of these interventions on atrial mechanics that might not be clinically significant at the time of interventions. Recognizing the preclinical stage of atrial maladaptation might enable early interventions before the development of irreversible atrial remodeling and clinical manifestation. We review normal atrial function and mechanics, and atrial cardiomyopathy in select cardiovascular conditions. We also summarize and discuss the current evidence of the impact of various atrial interventions on atrial function and mechanics.

Endovascular Ablation of the Right Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: Rationale, Design and Lead-in Phase Results of the REBALANCE-HF Trial.

OBJECTIVE: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants. METHODS: REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up. RESULTS: The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing. CONCLUSION: REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. TRIAL REGISTRATION: NCT04592445.

Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial.

BACKGROUND: Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients. METHODS: In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged ≥40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033. FINDINGS: Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1·0 [95% CI 0·8-1·2]; p=0·85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (pinteraction=0·002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (pinteraction=0·012 [≥29·7 mL/m2, worse outcomes]), and sex (pinteraction=0·02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0·11). INTERPRETATION: Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. FUNDING: Corvia Medical.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II.

BACKGROUND: The REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, "responders" (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified. OBJECTIVES: This study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt. METHODS: The study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status. RESULTS: In 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]). CONCLUSIONS: At 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033).

Endovascular Ablation of the Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: The REBALANCE-HF Randomized Clinical Trial.

Importance: Greater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF). Objective: To explore the feasibility and safety of endovascular right-sided splanchnic nerve ablation for volume management (SAVM). Design, Setting, and Participants: This was a phase 2, double-blind, 1:1, sham-controlled, multicenter, randomized clinical trial conducted at 14 centers in the US and 1 center in the Republic of Georgia. Patients with HFpEF, left ventricular ejection fraction of 40% or greater, and invasively measured peak exercise pulmonary capillary wedge pressure (PCWP) of 25 mm Hg or greater were included. Study data were analyzed from May 2023 to June 2024. Intervention: SAVM vs sham control procedure. Main Outcomes and Measures: The primary efficacy end point was a reduction in legs-up and exercise PCWP at 1 month. The primary safety end point was serious device- or procedure-related adverse events at 1 month. Secondary efficacy end points included HF hospitalizations, changes in exercise function and health status through 12 months, and baseline to 1-month change in resting, legs-up, and 20-W exercise PCWP. Results: A total of 90 patients (median [range] age, 71 [47-90] years; 58 female [64.4%]) were randomized at 15 centers (44 SAVM vs 46 sham). There were no differences in adverse events between groups. The primary efficacy end point did not differ between SAVM or sham (mean between-group difference in PCWP, -0.03 mm Hg; 95% CI, -2.5 to 2.5 mm Hg; P = .95). There were also no differences in the secondary efficacy end points. There was no difference in the primary safety end point between the treatment (6.8% [3 of 44]) and sham (2.2% [1 of 46]) groups (difference, 4.6%; 95% CI, -6.1% to 15.4%; P = .36). There was no difference in the incidence of orthostatic hypotension between the treatment (11.4% [5 of 44]) and sham (6.5% [3 of 46]) groups (difference, 4.9%; 95% CI, -9.2% to 18.8%; P = .48). Conclusions and Relevance: Results show that SAVM was safe and technically feasible, but it did not reduce exercise PCWP at 1 month or improve clinical outcomes at 12 months in a broad population of patients with HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04592445.

Diagnosis and Management of Blunt Cardiac Injury: What You Need to Know.

ABSTRACT: Blunt cardiac injury (BCI) encompasses a wide spectrum, from occult and inconsequential contusion to rapidly fatal cardiac rupture. A small percentage of patients present with abnormal electrocardiogram (ECG) or shock, but most are initially asymptomatic. The potential for sudden dysrhythmia or cardiac pump failure mandates consideration of the presence of BCI, including appropriate monitoring and management. In this review we will present what you need to know to diagnose and manage BCI.

A Review of Current and Evolving Imaging Techniques in Cardiac Amyloidosis.

Purpose of review: Establishing an early, efficient diagnosis for cardiac amyloid (CA) is critical to avoiding adverse outcomes. We review current imaging tools that can aid early diagnosis, offer prognostic information, and possibly track treatment response in CA. Recent findings: There are several current conventional imaging modalities that aid in the diagnosis of CA including electrocardiography, echocardiography, bone scintigraphy, cardiac computed tomography (CT), and cardiac magnetic resonance (CMR) imaging. Advanced imaging techniques including left atrial and right ventricular strain, and CMR T1 and T2 mapping as well as ECV quantification may provide alternative non-invasive means for diagnosis, more granular prognostication, and the ability to track treatment response. Summary: Leveraging a multimodal imaging toolbox is integral to the early diagnosis of CA; however, it is important to understand the unique role and limitations posed by each modality. Ongoing studies are needed to help identify imaging markers that will lead to an enhanced ability to diagnose, subtype and manage this condition.

Wild type cardiac amyloidosis: is it time to order a nuclear technetium pyrophosphate SPECT imaging study?

Transthyretin (ATTR) amyloidosis is a debilitating systemic disease often associated with symptomatic cardiac involvement. Diagnosis has dramatically changed with the advent of Technetium-99 m pyrophosphate (Tc-PYP) single-photon emission computed tomography (SPECT). With the ability to diagnose ATTR amyloidosis noninvasively and offer newer therapies, it is increasingly important to identify which patients should be referred for this testing. Relative apical sparing of longitudinal strain on echocardiogram can be potentially used to screen such patients. We sought to describe electrocardiogram (ECG) and echocardiogram (TTE) findings, including relative apical sparing of longitudinal strain, in ATTR amyloidosis patients diagnosed non-invasively with 99mTc-PYP imaging. This was a single-center, retrospective study with 64 patients who underwent 99mTc-PYP imaging between June 2016 and February 2019. Relative apical longitudinal strain was calculated from left ventricular longitudinal strain (LV LS) values. No ECG parameters were meaningfully associated with of 99 m Tc-PYP positive patients. LV mass index (p = 0.001), IVSd (p < 0.001), and LVPWd (< 0.001) demonstrated a highly significant difference between positive and negative 99mTc-PYP groups. 99mTc-PYP positive patients had a higher relative apical sparing of LV LS (p < 0.001), and notably, no 99mTc-PYP negative patient had a ratio > 1.0. The finding of relative apical sparing of longitudinal strain can reliably guide clinicians in triaging which patients to consider ordering 99mTc-PYP imaging for the noninvasive diagnosis of wild type cardiac amyloidosis. A patient with clinically suggestive features and an LV LS relative apical sparing ratio > 0.8 can be considered for 99mTc-PYP imaging to evaluate for ATTR cardiac amyloidosis.

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. OBJECTIVES: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). METHODS: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). RESULTS: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. CONCLUSIONS: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).

Endovascular ablation of the right greater splanchnic nerve in heart failure with preserved ejection fraction: early results of the REBALANCE-HF trial roll-in cohort.

AIMS: In heart failure (HF) with preserved ejection fraction (HFpEF), excessive redistribution of blood volume into the central circulation leads to elevations of intracardiac pressures with exercise limitations. Splanchnic ablation for volume management (SAVM) has been proposed as a therapeutic intervention. Here we present preliminary safety and efficacy data from the initial roll-in cohort of the REBALANCE-HF trial. METHODS AND RESULTS: The open-label (roll-in) arm of REBALANCE-HF will enrol up to 30 patients, followed by the randomized, sham-controlled portion of the trial (up to 80 additional patients). Patients with HF, left ventricular ejection fraction (LVEF) ≥50%, and invasive peak exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg underwent SAVM. Baseline and follow-up assessments included resting and exercise PCWP, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-min walk test, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Efficacy and safety were assessed at 1 and 3 months. Here we report on the first 18 patients with HFpEF that have been enrolled into the roll-in, open-label arm of the study across nine centres; 14 (78%) female; 16 (89%) in NYHA class III; and median (interquartile range) age 75.2 (68.4-81) years, LVEF 61.0 (56.0-63.2)%, and average (standard deviation) 20 W exercise PCWP 36.4 (±8.6) mmHg. All 18 patients were successfully treated. Three non-serious moderate device/procedure-related adverse events were reported. At 1-month, the mean PCWP at 20 W exercise decreased from 36.4 (±8.6) to 28.9 (±7.8) mmHg (p < 0.01), NYHA class improved by at least one class in 33% of patients (p = 0.02) and KCCQ score improved by 22.1 points (95% confidence interval 9.4-34.2) (p < 0.01). CONCLUSION: The preliminary open-label results from the multicentre REBALANCE-HF roll-in cohort support the safety and efficacy of SAVM in HFpEF. The findings require confirmation in the ongoing randomized, sham-controlled portion of the trial.

Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N-terminal pro B-type natriuretic peptide levels.

BACKGROUND: Widespread use of angiotensin receptor blocker and neprilysin inhibitor (ARNI) remains low, and many patients are unable to tolerate the medication due to hypotension at the currently recommended starting dose. HYPOTHESIS: The aim of this study is to assess if lower than standard doses of ARNI, sacubitril/valsartan (S/V), significantly reduces NT-proBNP and leads to any change in diuretic dose, serum potassium, or creatinine. METHODS: In a retrospective study of 278 patients who were started on a low dose S/V at a single medical center, 45 patients were selected for the study cohort. Patients were subcategorized to Group 1 (n = 10): very low dose S/V (half a tab of 24/26 mg BID), Group 2 (n = 10): very low dose titrated to low dose S/V, and Group 3 (n = 25): low dose S/V (24/26 mg BID). NT-proBNP, diuretic dose, serum potassium, and creatinine were compared before and after initiation of S/V. RESULTS: Among all groups, there was a significant reduction in NT-proBNP level (Group 1: p < .01, Group 2: p < .01, and Group 3: p < .001). In addition, there was a significant reduction in diuretic dose across all groups combined (furosemide 53 mg/day vs. 73 mg/day; p = .03), with 17.8% (8/45) patients being able to discontinue their diuretic completely. There was no significant change in potassium or creatinine. CONCLUSIONS: Lower than standard dose of S/V significantly reduces NT-proBNP and diuretic requirement without change in potassium or creatinine, which provides hope that patients who cannot tolerate standard doses of S/V due to hypotension may be able to receive the benefits of S/V therapy.

Remote Monitoring in Heart Failure: the Current State.

OPINION STATEMENT: The treatment of congestive heart failure is an expensive undertaking with much of this cost occurring as a result of hospitalization. It is not surprising that many remote monitoring strategies have been developed to help patients maintain clinical stability by avoiding congestion. Most of these have failed. It seems very unlikely that these failures were the result of any one underlying false assumption but rather from the fact that heart failure is a progressive, deadly disease and that human behavior is hard to modify. One lesson that does stand out from the myriad of methods to detect congestion is that surrogates of congestion, such as weight and impedance, are not reliable or actionable enough to influence outcomes. Too many factors influence these surrogates to successfully and confidently use them to affect HF hospitalization. Surrogates are often attractive because they can be inexpensively measured and followed. They are, however, indirect estimations of congestion, and due to the lack specificity, the time and expense expended affecting the surrogate do not provide enough benefit to warrant its use. We know that high filling pressures cause transudation of fluid into tissues and that pulmonary edema and peripheral edema drive patients to seek medical assistance. Direct measurement of these filling pressures appears to be the sole remote monitoring modality that shows a benefit in altering the course of the disease in these patients. Congestive heart failure is such a serious problem and the consequences of hospitalization so onerous in terms of patient well-being and costs to society that actual hemodynamic monitoring, despite its costs, is beneficial in carefully selected high-risk patients. Those patients who benefit are ones with a prior hospitalization and ongoing New York Heart Association (NYHA) class III symptoms. Patients with NYHA class I and II symptoms do not require hemodynamic monitoring because they largely have normal hemodynamics. Those with NYHA class IV symptoms do not benefit because their hemodynamics are so deranged that they cannot be substantially altered except by mechanical circulatory support or heart transplantation. Finally, hemodynamic monitoring offers substantial hope to those patients with normal ejection fraction (EF) heart failure, a large group for whom medical therapy has largely been a failure. These patients have not benefited from the neurohormonal revolution that improved the lives of their brothers and sisters with reduced ejection fractions. Hemodynamic stabilization improves the condition of both but more so of the normal EF cohort. This is an important observation that will help us design future trials for the 50% of heart failure patients with normal systolic function.