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Background Currently, there are knowledge gaps that prevent the proper design of an efficacy trial to determine optimal dietary sodium intake in high-risk patients with HFrEF. Objectives (1) Assess what % of patients recently hospitalized with HFrEF would be willing to participate in a 12-week feeding trial and eligible from a dietary sodium intake perspective. (2) Randomize 50 patients to meals with 1500 vs. 3000 mg sodium daily for 12 weeks to estimate on-study retention and compliance; trends in clinical events and NT-proBNP; quality of life and food satisfaction; and safety. Methods and Results Out of 196 patients (admitted 1/2015-12/2017) approached ≤2 weeks after hospitalization for a primary diagnosis of HF and LVEF ≤40%, who were on optimal medial therapy, functionally independent, and able to communicate, 83 (47.4%) consented to participate. Of these, only 27 (age, 62±11 years; 22 men; 20 White; LVEF 26±8%) had 24-h urine sodium ≥3000mg and agreed to receive meals with either 1500 mg (N=12) or 3000 mg (N=15) sodium daily. On-study retention at 12 weeks was 77.4% (82.5% vs. 73.3%; P=0.53); 6 patients (2 in 1500 mg, 4 in 3000 mg) withdrew before study completion. Quality of life and food satisfaction questionnaires indicated that both diets were well tolerated. Average compliance with meals was 52% (based on urinary sodium) with numerically lower compliance in the 1500-mg arm (42% vs. 60%; P=0.25). Both arms exhibited reduced 24-h urinary sodium while on study meals (Fig. 1), but NT-proBNP was not affected (Fig. 2). There were 24 hospitalizations and ED visits in 9 patients by 24 weeks; event rates were 41.7% (1500 mg) vs. 26.7% (3000 mg); P=0.50. One patient (1500 mg) developed persistently low blood pressure and 1 patient (3000 mg) creatinine increase >0.5 mg. Conclusions Despite providing prepared meals, an efficacy study to assess optimal dietary sodium in HF is associated with significant challenges. These include need for extensive screening, overcoming unwillingness to participate in a feeding study, retention, and compliance. However, both 1500-mg and 3000-mg diets reduced urinary sodium without any adverse safety signal and while maintaining quality of life.

In contrast to chronic heart failure (HF), the use of echocardiography in acute HF (AHF) is less well defined, both in clinical practice and in clinical trials. Current guidelines recommend the utility of echocardiography as an adjunct diagnostic tool in the clinical setting of new-onset or decompensated HF. However, despite its unique advantages as the only practical imaging modality in AHF, echocardiography poses unique challenges in this setting. Data from early-phase clinical studies and trials provide evidence that echocardiographic end points can be clinically meaningful surrogate end points as a means to track response to treatment in AHF; however, the optimal timing and selection of echocardiographic measures is under active investigation. In addition, despite a number of studies indicating that certain echocardiographic measures of cardiac function are predictive of post-discharge prognosis, the role of echocardiography as a tool for patient classification and risk determination in AHF is less well defined. Importantly, it is unclear whether echocardiography can be used to phenotype and select AHF patients for interventions. In this article, we (1) appraise the current evidence for use of echocardiographic measures in AHF, (2) identify knowledge gaps regarding optimal use of echocardiography in AHF, and (3) assess the evidence for echocardiography as a prognosis determination and risk stratification tool in AHF.

Advances in modern echocardiography for quantification of cardiac structure and function have not been translated in clinical trial or practice applications to date. Imaging endpoints are especially well-suited for early trials with investigational therapies for heart failure as most drugs and devices approved for heart failure have shown favorable effects on cardiac structure and function also. Echocardiography is versatile and can be performed in most clinical settings. The modest interobserver and test-retest reproducibility of specific structural and functional parameters with conventional echocardiography can be improved on by using contemporary modalities, including 3-dimensional (3D) echocardiography for assessment of volumes and ejection fraction and speckle tracking for detailed functional assessment of the ventricles with mechanics-based parameters (strain and strain rate). The appropriate imaging endpoints (global vs. regional, systolic vs. diastolic) should be tailored to the specific research question and the mode of action of the therapy under investigation. The newer echocardiographic modalities, namely 3D echocardiography and speckle tracking, are more demanding in terms of equipment and personnel and therefore are better suited for implementation in experienced research centers with central interpretation. However, these modalities provide the best opportunity currently available to demonstrate treatment effects on the myocardium with investigational therapies and provide mechanistic insights for future directions.

Patients with heart failure (HF) are hospitalized over a million times annually in the United States. Hospitalization marks a fundamental change in the natural history of HF, leading to frequent subsequent rehospitalizations and a significantly higher mortality compared with nonhospitalized patients. Three-fourths of all HF hospitalizations are due to exacerbation of symptoms in patients with known HF. One-half of hospitalized HF patients experience readmission within 6 months. Preventing HF hospitalization and rehospitalization is important to improve patient outcomes and curb health care costs. To implement cost-effective strategies to contain the HF hospitalization epidemic, optimal schemes to identify high-risk individuals are needed. In this review, we describe the risk factors that have been associated with hospitalization risk in HF and the various multimarker risk prediction schemes developed to predict HF rehospitalization. We comment on areas that represent gaps in our knowledge or difficulties in interpretation of the current literature, representing opportunities for future research. We also discuss issues with using HF readmission rate as a quality indicator.

months). The same institutions and physician/care teams participated in both the RCT and long-term longitudinal follow-up, thus allowing for a more clear assessment of the technology learning curve. Results: New users of the technology were able to generate robust treatment effect sizes from the RCT period for hospitalizations and mortality. With continued experience and implementation of the PAP-HF management strategy, the same users were able to replicate their initial results and generate even larger treatment effect sizes during long-term longitudinal follow-up (Table & Figure 1). Conclusions: PAP-HF management by new users of the technology resulted in significant clinical benefit in a RCT and even larger treatment effect sizes with continued experience and implementation of the PAP-HF management strategy during long-term longitudinal follow-up. These results demonstrate the absence of a steep learning curve, the durability of the treatment effects, and its applicability in the ‘real-world’ clinical setting.

Introduction: Hypertensive heart disease (HHD) is characterized by altered myocardial structure and function, which is leading cause of heart failure and death. CD-NP is a newly developed dual guanylyl cyclase (GC)-A and GC-B agonist that is currently in clinical trials in post acute heart failure as a chronically delivered peptide. CD-NP has direct anti-hypertrophic and anti-fibrotic actions independent of blood pressure lowering. Hypothesis: We hypothesized that cardiac overexpression of CD-NP would result in a superior anti-remodeling effect than a single GC-A agonist, BNP.Methods: Here we defined the chronic effects of cardiac overexpression of CDNP we using adeno-associated vector serotype 9 (AAV9) in spontaneously hypertensive rats (SHR). We further compared the cardiac action of CD-NP to those of the single GC-A agonist, BNP. Results: The main findings of the study are illustrated on figure 1. A single intravenous injection of AAV9 induced sustained overexpression of CD-NP and BNP in the heart of SHR as verified by ELISA. The CNP ELISA assay also detected modest, but significantly elevated levels of circulating CD-NP in plasma. More importantly, compared to chronic overexpression of BNP, that has previously shown to induce significant reduction of cardiac weight, CD-NP had greater anti-hypertrophic actions 5 weeks post injection (p!0.05). Importantly, the anti-hypertrophic effects of CD-NP occurred with no changes in BP, suggesting a direct cardiac effect of this autacoid. Conclusion: Our studies demonstrate successful sustained cardiac CD-NP overexpression through a single systemic gene delivery approach. Of note, this novel peptide that combines the anti-hypertrophic and anti-fibrotic actions of both GC-A and GC-B activation, resulted in a significant reduction of cardiac mass, which was independent of BP lowering action and greater than that of the single CG-A agonist, BNP. These studies underscore that gene delivery of CD-NP can be useful in the treatment of HHD.