Guideline-recommended Heart Failure Therapies Research Articles

Impact of Visit Volume on the Effectiveness of Electronic Tools to Improve Heart Failure Care

BackgroundElectronic health record (EHR) tools can improve prescribing of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), but their effectiveness may vary by physician workload. ObjectivesThis paper aims to assess whether physician workload modifies the effectiveness of EHR tools for HFrEF. MethodsThis was a prespecified subgroup analysis of the BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) cluster-randomized trial, which compared effectiveness of an alert vs message vs usual care on prescribing of mineralocorticoid antagonists (MRAs). The trial included adults with HFrEF seen in cardiology offices who were eligible for and not prescribed MRAs. Visit volume was defined at the cardiologist-level as number of visits per 6-month study period (high = upper tertile vs non-high = remaining). Analysis at the patient-level used likelihood ratio test for interaction with log-binomial models. ResultsAmong 2,211 patients seen by 174 cardiologists, 932 (42.2%) were seen by high-volume cardiologists (median: 1,853; Q1-Q3: 1,637-2,225 visits/6 mo; and median: 10; Q1-Q3: 9-12 visits/half-day). MRA was prescribed to 5.5% in the high-volume vs 14.8% in the non–high-volume groups in the usual care arm, 10.3% vs 19.6% in the message arm, and 31.2% vs 28.2% in the alert arm, respectively. Visit volume modified treatment effect (P for interaction = 0.02) such that the alert was more effective in the high-volume group (relative risk: 5.16; 95% CI: 2.57-10.4) than the non–high-volume group (relative risk: 1.93; 95% CI: 1.29-2.90). ConclusionsAn EHR-embedded alert increased prescribing by >5-fold among patients seen by high-volume cardiologists. Our findings support use of EHR alerts, especially in busy practice settings. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure [BETTER CARE-HF]; NCT05275920)

Are heart failure patients with mildly reduced ejection fraction treated according to current international guidelines?

Abstract Objective This study aims to investigate the guideline adherence and prognostic role of guideline recommended heart failure (HF) therapies in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). Background Limited data regarding the guideline adherence and prognostic impact of different pharmacotherapies in patients with HFmrEF is available. Methods A large retrospective study was used including all consecutive hospitalized patients with HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41 – 49%) from 2016 to 2022 according to current European guidelines. The prescription rates and the prognostic role of angiotensin-converting enzyme and receptor blockers (ACEi/ARB), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium glucose linked transporter 2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitor"(ARNi) was assessed. The primary endpoint was the first heart-failure related re-hospitalization at 3 years. Secondary endpoints comprised amongst others cardiovascular re-hospitalization. Kaplan-Meier, uni- and multivariable Cox regression analyses were applied for statistics. Results 775 consecutive patients with HFmrEF surviving index hospitalization were included. Of those, 73% were discharged on ACEi/ARB, followed by BB (26%), 14% MRA, whereas only minor part was treated with SGLT2i (3%). In HFmrEF patients, no prognostic impact of BB (10% vs. 7%; log rank p=0.218; HR=1.474; 95% CI 0.792-2.742; p=0.220), ACEi/ARB (9% vs. 10%; log rank p=0.444; HR=0.822; 95% CI 0.497-1.359; p=0.445), SGLT2i (8% vs. 9%; log rank p=0.821; HR=0.851; 95% CI 0.209-3.470; p=0.445), MRA (8% vs. 9%; log rank p=0.748; HR=0.892; 95% CI 0.443-1.794; p=0.748) regarding the risk of heart-failure related re-hospitalization at 3 years was observed. In line, these pharmacotherapies were not associated with the risk of cardiovascular re-hospitalization. Conclusions In patients hospitalized with HFmrEF between 2016 and 2022, only infrequent treatment with guideline recommended HF therapies was observed, whereas non of the current HF therapies was associated with the risk of heart-failure related rehospitalization.

Predictors of Ejection Fraction Improvement in Northland Heart Failure Patients

Northland has a disproportionately high burden of cardiovascular disease, including heart failure (HF). Since 2019, there has been an increase in clinical focus on mid and far north HF patients, aiming to understand and improve HF care to this challenging and often comorbid patient group. Clinical data were prospectively collected, between October 2019 and March 2020, on 86 consecutive cardiology clinic patients with heart failure with reduced ejection fraction (HFrEF) in Kaitaia and Bay of Islands hospitals. Table 1 shows cohort demographics.Table 1Patient demographics.Number of patients86Mean age (yr)62% male85% Māori71% diabetic38 Open table in a new tab A total of 42% of patients had a >15% increase in ejection fraction (EF), as show in Figure 1. The strongest predictor of EF improvement was lack of ischaemic heart disease as a cause/contributor to HFrEF (Table 2). Figure 2 shows the uptake of Entresto (sacubitril/valsartan) and empagliflozin over time. The relationship with Entresto use largely reflects the fact that most patients NOT prescribed Entresto had an early significant improvement with other management.Table 2Predictors of EF improvement.EFDecline or no change≤15% increase>15% increasePatients (%)25 (29)25 (29)36 (42)Mean age (yr)616461% Māori727269% male888881Alcohol %402836Ischaemic %283217Non-adherence522Entresto %1008461Empagliflozin %202825Death310 Open table in a new tab Figure 2Use of newer guideline recommended HF therapy for the 86 patientsView Large Image Figure ViewerDownload Hi-res image Download (PPT) There has been a steady increase in used of guideline-recommended HF therapy in Northland rural hospital patients.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

Introduction: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. Risk factors contributing to this condition are: advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, hypertension and In patients with gestational hypertension (GH) and other risk factors close monitoring is mandatory during pregnancy as well as in the postpartum period. Case report: A 38 year- old patient previously treated for endometriosis, infertility and GH was transferred from the Clinic of Gynecology due to diagnosed congestive heart failure. Five days prior admission she gave birth to her first child. Prior delivery she was treated with tocolytic therapy. She received methyldopa due to GH, that was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension (PAH) secondary to left ventricular failure. During hospitalization the patient was with signs of volume overload, but with well response on parenteral diuretic therapy. She was additionally treated with guideline recommended heart failure therapy. The controlled echocardiography showed improvement of the left ventricular function with an EF of 42%. Conclusion: PPCM is a rare condition with high morbidity and mortality. An LVEF <30%, marked LV dilatation, LV end-diastolic diameter >6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta trigger resolution of symptoms and recovery to the nonpregnant state of various organism, the contrary happens with blood pressure. Its peaking time is three to six days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy are a risk factor for PPCM due to causing decreased baroreflex sensitivity Patients with risk factors should be closely monitored for eventual cardiac complications.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. The risk factors contributing to this condition are advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, and hypertension. In patients with gestational hypertension (GH) and other risk factors, close monitoring is mandatory during pregnancy as well as in the postpartum period. CASE REPORT: A 38-year-old patient previously treated for endometriosis, infertility, and GH was transferred from the clinic of gynecology due to diagnosed congestive heart failure. 5 days before admission, she gave birth to her first child. Before delivery, she was treated with tocolytic therapy. She received methyldopa due to GH which was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular (LV) systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension secondary to LV failure. During hospitalization, the patient was with signs of volume overload, but with a good response on parenteral diuretic therapy. She was additionally treated with guideline-recommended heart failure therapy. The controlled echocardiography showed improvement of LV function with an EF of 42%. CONCLUSION: PPCM is a rare condition with high morbidity and mortality. An LVEF <30%, marked LV dilatation, LV end-diastolic diameter >6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta triggers the resolution of symptoms and recovery to the nonpregnant state of various organisms, the contrary happens with blood pressure. Its peak time is 3–6 days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy is a risk factor for PPCM due to causing decreased baroreflex sensitivity. Patients with risk factors should be closely monitored for eventual cardiac complications.

Emerging Treatment Approaches to Improve Outcomes in Patients with Heart Failure

Heart failure (HF) is a major public health problem around the world. Although currently available therapies have improved outcomes, morbidity and mortality in patients with HF remain unacceptably high. Most guideline-recommended therapies for HF are indicated for patients with a reduced left ventricular ejection fraction (HFrEF). Until recently, treatment options that improved outcomes in patients with HF and preserved left ventricular ejection fraction or mildly reduced ejection fraction were limited. Over the past several years, however, several new drugs including angiotensin receptor neprilysin inhibitors (ARNIs), sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors), soluble guanylate cyclase stimulators, and a cardiac myotrope, omecamtiv mecarbil have all reported positive results in pivotal phase III clinical trials. Moreover, the results of these studies have provided evidence that both ARNIs and SGLT2 inhibitors can improve clinical outcomes in patients with HF across a broad spectrum of LVEF, not just in HFrEF. This article presents the rationale for the use of each of these 4 new classes of drugs, reviews the results from pivotal clinical trials showing their safety and efficacy, and provides a framework for how each drug has begun to be integrated into new HF management guidelines. Collectively, these new drugs provide hope for the millions of patients around the world who suffer from HF.

Abstract 8895: Design of Phase IV, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate for the Management of Hyperkalemia in Patients With Symptomatic Heart Failure With Reduced Ejection Fraction (REALIZE-K Trial)

Introduction: International guideline-recommended therapies for heart failure (HF) with reduced ejection fraction (HFrEF), including mineralocorticoid receptor antagonists (MRA), are underutilized, in part due to concerns of hyperkalemia (HK) especially among those at high risk. The REALIZE-K trial aims to evaluate the efficacy and safety of sodium zirconium cyclosilicate (SZC), a selective potassium (K + ) binder, to enable MRA use in patients with HFrEF at high risk for HK. Methods: REALIZE-K is a prospective, double-blind, placebo (PBO)-controlled randomized withdrawal trial enrolling symptomatic HFrEF (NYHA class II-IV and LVEF ≤40%) patients on guideline-directed medical therapy (but not full-dose MRA) with either HK (serum K + 5.1-5.9 mmol/L) or high risk for HK during MRA titration. All eligible patients enter a 1-month open-label run-in phase, during which patients with hyperkalemia receive SZC to correct HK; all patients undergo protocol-mandated titration of spironolactone (SPL) as tolerated to a target of 50 mg QD with supplemental SZC to maintain normokalemia (serum K + 3.5-5.0 mmol/L; Figure ). All patients tolerating ≥25 mg QD of SPL will be randomly assigned to continued SPL+SZC or SPL+PBO during an 8-month double-blind withdrawal phase. Serial K + monitoring will guide protocol-directed dosing of SZC/PBO and SPL during the randomized period. The primary study endpoint is the occurrence at 8 months of normokalemia on SPL ≥25 mg QD without the need for rescue therapy for severe HK in the SZC vs PBO group. Secondary endpoints include individual components of the primary endpoint and health status assessed by Kansas City Cardiomyopathy Questionnaire Total Symptom Score. Exploratory endpoints include time to first occurrence of the composite of CV death or worsening HF, and change in mean urine albumin-creatinine ratio. Conclusions: REALIZE-K will evaluate the efficacy and safety of SZC, enabling MRA therapy for HFrEF patients at high risk for HK.

Evaluation of Quality of Care for US Veterans With Recent-Onset Heart Failure With Reduced Ejection Fraction

Multiple guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF) are available and promoted by performance measures. However, contemporary data on the use of these therapies are limited. To evaluate trends in guideline-directed medical therapy, implantable cardioverter-defibrillator (ICD) use, and risk-adjusted mortality among patients with recent-onset HFrEF. This cohort study analyzed claims and electronic health record data of patients with recent-onset HFrEF diagnosed at US Department of Veterans Affairs (VA) health care system facilities from July 1, 2013, through June 30, 2019. Veterans who had a history of heart transplant or used a ventricular assist device were among the patients who were excluded. Guideline-directed medical therapy (any β-blocker, guideline-recommended β-blocker [bisoprolol, carvedilol, or metoprolol succinate], angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, angiotensin receptor-neprilysin inhibitor, mineralocorticoid receptor antagonist, and hydralazine plus nitrate) and ICD. Treatment rates for guideline-directed medical therapies and ICDs were calculated within 6 months of the index HFrEF date using medication fills, procedural codes for implantation and monitoring, and diagnosis codes. Risk-adjusted mortality was calculated after adjusting for baseline patient characteristics. For both treatment rates and risk-adjusted mortality, we evaluated the change over 3 periods (period 1: July 1, 2013, to June 30, 2015; period 2: July 1, 2015, to June 30, 2017; and period 3: July 1, 2017, to June 30, 2019) and variation across VA facilities. The final cohort comprised 144 074 eligible patients with incident HFrEF that was diagnosed between July 1, 2013, and June 30, 2019. The cohort had a mean (SD) age of 71.0 (11.4) years and was mostly composed of men (140 765 [97.7%]). Overall, changes in medical therapy rates were minimal over time, with the use of a guideline-recommended β-blocker increasing from 64.2% in 2013 to 72.0% in 2019. Rates for mineralocorticoid receptor antagonist therapy increased from 23.9% in 2013 to 26.9% in 2019, and rates for hydralazine plus nitrate therapy remained stable at 24.2% over the study period. Rates for angiotensin receptor-neprilysin inhibitor therapy increased since its introduction in 2015 but only to 22.6% in 2019. Among patients with an ICD indication, early use rates decreased over time. Substantial variation in medical therapy rates persisted across VA facilities. Risk-adjusted mortality decreased over the study period from 19.9% (95% CI, 19.6%-20.2%) in July 1, 2013, to June 30, 2015, to 18.4% (95% CI, 18.0%-18.7%) in July 1, 2017, to June 30, 2019 (OR, 0.96 per additional year; 95% CI, 0.96-0.97). This study found only marginal improvement between 2013 and 2019 in the guideline-recommended therapy and mortality rates among patients with recent-onset HFrEF. New approaches to increase the uptake of evidence-based HFrEF treatment are urgently needed and could lead to larger reductions in mortality.

Clinical Profiles and Outcomes of Heart Failure in Five African Countries: Results from INTER-CHF Study.

Background:A wide knowledge gap exists on the clinical profiles and outcomes of heart failure (HF) in sub-Saharan Africa.Objectives:To determine the clinical profiles and outcomes of HF patients from five African countries.Methods:The INTERnational Congestive Heart Failure Study (INTER-CHF) is a prospective, multicenter cohort study. A total of 1,294 HF patients were consecutively recruited from Nigeria (383 patients), South Africa (169 patients), Sudan (501 patients), Uganda (151patients), and Mozambique (90 patients). HF was defined according to the Boston criteria for diagnosis. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) score.Results:Of the 1294 patients, 51.4% were recruited as out-patients, 53.7% had HF with reduced ejection fraction (EF), 30.1% had HF with mid-range EF and 16.2% had HF with preserved EF (16.2%). The commonest etiologies of HF were hypertensive heart disease (35%) and ischemic heart disease (20%). The mean MoCA score was highest in Uganda (24.3 ± 1.1) and lowest in Sudan (13.6 ± 0.3). Prescriptions for guideline-recommended HF therapies were poor; only 1.2% of South African patients received an Implantable Cardioverter Defibrillator, and none of the patients received Cardiac Resynchronised Therapy. The composite outcome of death or HF hospitalization at one year among the patients was highest in Sudan (59.7%) and lowest in Mozambique (21.1%). Six variables were associated with higher mortality risk, while digoxin use (adjusted hazard ratio [aHR]: 0.69; 95% confidence interval [CI]: 0.49–0.97; p = 0.034) and 10mmHg unit increase in systolic blood pressure (aHR 0.86; 95%CI 0.81–0.93; p < 0.001) were associated with lower risk for mortality.Conclusions:This is the largest HF study in Africa that included in- and out-patients from the West, East, North, Central and South African sub-regions. Clinically relevant differences, including cognitive functional impairment, were found between the involved countries.

Treatment patterns and clinical outcomes among patients

Data regarding patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF) following a worsening HF event (WHFE) are largely driven by findings from elderly patients. Younger patients are not well studied. The aim of this study was to evaluate treatment patterns and clinical outcomes in commercially insured chronic HFrEF patients <65 years old during 1-year periods before and after a WHFE. A retrospective claims analysis was performed using the IBM® MarketScan® Commercial Database on HFrEF patients aged <65 years during the year before and after a WHFE, defined as HF hospitalization or outpatient intravenous diuretic use. Treatment patterns, rehospitalizations, health care resource utilization, and costs were assessed. A total of 4460 HFrEF patients with WHFE were included. Guideline-recommended HF therapy was initially underutilized, increased pre-WHFE, and peaked 0-3months post-WHFE. The proportions of patients using dual and triple therapy were 31.5% and 9.8% pre-WHFE, 41.5% and 17.4% 0-3months post-WHFE, and 34.6% and 13.9% 10-12 months post-WHFE, respectively. Within 30 and 90 days after a WHFE, 12% and 23% of patients had HF-related and 16% and 30% had all-cause rehospitalizations, respectively. HF-related and all-cause hospitalizations and outpatient visits peaked 0-3months post-WHFE, whereas emergency department visits peaked 0-3months pre-WHFE. Use of HF medications increased pre-WHFE but decreased post-WHFE, despite recurrent hospitalizations. These findings suggest that age and insurance status may not totally explain the suboptimal treatment of HFrEF patients before and after a WHFE. Reasons for these trends need further study.

Atrial fibrillation in chronic heart failure patients with reduced ejection fraction: The CHECK-HF registry

BackgroundAtrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy. MethodsWe analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines. Results2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07). ConclusionIn this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF.

Physicians’ guideline adherence is associated with long-term heart failure mortality in outpatients with heart failure with reduced ejection fraction: The QUALIFY international registry

Physicians’ adherence to guideline-recommended therapy is associated with short-term clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). However, its impact on longer-term outcomes is poorly documented. In this analysis we assessed the longer-term association of physicians’ adherence with clinical outcomes, including mortality and unplanned hospitalisations, at 18-month follow-up of the QUALIFY registry (Clinical trial registration ISRCTN87465420) Data at 18 months were available for 6118 ambulatory HFrEF patients from this international prospective observational survey. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed with regard to five classes of recommended HF medications and dosages. Most deaths were cardiovascular (CV) (228/394) and HF-related (191/394) and the same was true for unplanned hospitalisations (1175 CV and 861 HF-related hospitalisations, out of a total of 1541). According to univariable analysis, CV and HF deaths were significantly associated with physician adherence to guidelines. In multivariable analysis, HF death was associated with adherence level [subdistribution hazard ratio (SHR) 0.93, 95% confidence interval (CI) 0.87–0.99 per 0.1 unit adherence level increase; P = 0.034] as was composite of HF hospitalisation or CV death (SHR 0.97, 95% CI 0.94–0.99 per 0.1 unit adherence level increase; P = 0.043), whereas unplanned all-cause, CV or HF hospitalisations were not (all-cause: SHR 0.99, 95% CI 0.9–1.02; CV: SHR 0.98, 95% CI 0.96–1.01; and HF: SHR 0.99, 95% CI 0.96–1.02 per 0.1 unit change in adherence score; P = 0.52, P = 0.2, and P = 0.4, respectively). These results suggest that physicians’ adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians’ adherence to guidelines.

Physicians' guideline adherence is associated with long-term heart failure mortality in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry.

Physicians' adherence to guideline-recommended therapy is associated with short-term clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). However, its impact on longer-term outcomes is poorly documented. Here, we present results from the 18-month follow-up of the QUALIFY registry. Data at 18 months were available for 6118 ambulatory HFrEF patients from this international prospective observational survey. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed for five classes of recommended HF medications and dosages. Most deaths were cardiovascular (CV) (228/394) and HF-related (191/394) and the same was true for unplanned hospitalizations (1175 CV and 861 HF-related hospitalizations, out of a total of 1541). According to univariable analysis, CV and HF deaths were significantly associated with physician adherence to guidelines. In multivariable analysis, HF death was associated with adherence level [subdistribution hazard ratio (SHR) 0.93, 95% confidence interval (CI) 0.87-0.99 per 0.1 unit adherence level increase; P = 0.034] as was composite of HF hospitalization or CV death (SHR 0.97, 95% CI 0.94-0.99 per 0.1 unit adherence level increase; P = 0.043), whereas unplanned all-cause, CV or HF hospitalizations were not (all-cause: SHR 0.99, 95% CI 0.9-1.02; CV: SHR 0.98, 95% CI 0.96-1.01; and HF: SHR 0.99, 95% CI 0.96-1.02 per 0.1 unit change in adherence score; P = 0.52, P = 0.2, and P = 0.4, respectively). These results suggest that physicians' adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians' adherence to guidelines.

Device-based Therapy for Mitral Regurgitation and Ventricular Reshaping

ABSTRACTBackground: A clinically effective treatment for functional mitral regurgitation (fMR) due to left ventricular (LV) remodeling may need to address both annular and LV dilation to improve symptoms of heart failure (HF). Here we describe the effects of a device intended to reduce mitral annular dimensions and also reduce the radius of curvature of the LV to improve function.Methods: Patient 202–051 is a 79-year-old man with ischemic cardiomyopathy and 3-to-4+ fMR treated with guideline recommended HF therapies. Echocardiography showed an effective regurgitant orifice (ERO) of 0.36 cm2, a regurgitant stroke volume of 69 ml, an LVEF of 14% and an LV diastolic diameter of 6.2 cm. The patient underwent percutaneous implantation of the Ancora Heart device which consists of a series of intramyocardial anchors connected via a cinching cable implanted into the LV free wall below the mitral annulus and behind the papillary muscles. Tension applied to the cable resulted in an acute ~15% decrease of the circumferential distance between the first and last anchors. Cinching was maintained with a locking mechanism placed at the end of the cable.Results: Echocardiographic follow up performed over the course of 1 year showed that ERO decreased to 0.12 cm2, regurgitant stroke volume to 23 ml, LV dimension to 5.6 cm and EF improved to 34%. ntPro-BNP decreased from 3440 to 1450 pg/ml.Conclusion: These findings provide proof-of-concept that a percutaneously deployable, sub-valvular intramyocardial implant that cinches the myocardial wall below the mitral annulus has the potential to reduce the severity of fMR and improve LV function.

Abstract 12707: HIV Infection and Heart Failure Outcomes in Women

Introduction: Women with HIV have an increased risk of incident heart failure (HF). Whether HF outcomes differ by HIV status in women has not been established. Methods: We performed a US health care system-based cohort study analyzing data from 1388 HIV-infected women initially matched 1:10 on age, race/ethnicity with uninfected women. The presence of HF was ascertained by ICD-9-CM codes and adjudicated by physicians blinded to HIV status. After adjudication, cohorts were re-matched 1:3 so that age, race/ethnicity would be similar in the final cohort. The primary outcome was incident HF hospitalization rate. Secondary outcomes included HF hospitalization length of stay, all cause and cardiovascular mortality. Results: The final HF cohort consisted of 34 HIV-infected and 102 uninfected women (mean age 59 years). There were no significant differences in the LVEF (54±15 vs. 52±14%, HIV+ vs. HIV-, p=0.48) or prevalence of HFrEF (EF&lt;50%) (29 vs. 35%, HIV+ vs. HIV-, p=0.67). HIV-infected women with HF had more cocaine use (23 vs. 6%, p=0.006), lower BMI (28±5 vs. 33±8 kg/m 2 , p=0.002), increased QRS (113±19 vs. 97±20 msec, p &lt;0.0001) and higher PASP (49±10 vs. 35±10 mmHg, p&lt;0.0001). Over a median follow-up of 5 years (IQR 4.0-7.5), HIV-infected women with HF had 2.5 times the rate of incident HF hospitalization, adjusted for age, HTN, DM, sleep apnea, CAD, ACE I/ARB and LVEF (HR: 2.5 (1.54-4.29), p&lt;0.0001) (Figure). HIV-infected women with HF also had an increased HF hospitalization length of stay (8 vs. 5 days, p&lt;0.001), and higher all-cause (53 vs. 21%, p&lt;0.001) and cardiovascular mortality (83 vs. 33%, p&lt;0.006). In sub-group analysis, HIV-infected women with HFrEF had lower use of guideline-recommended HF therapy (40 vs. 83%, p=0.01). Conclusions: As compared with matched uninfected women with HF, HIV-infected women with HF had a lower use of HF therapies, increased HF hospitalization rate, HF hospitalization length of stay, and all-cause and cardiovascular mortality.

Adherence Rates of Guideline-Recommended Therapies for Heart Failure in Outpatients: Primary Results of the IMPROVE HF Japan Pilot Study

Adherence Rates of Guideline-Recommended Therapies for Heart Failure in Outpatients: Primary Results of the IMPROVE HF Japan Pilot Study

Effects of JNJ-54452840, an Anti-β1 Receptor Antibody Cyclopeptide in Heart Failure Patients: A Randomized, Double-blind, Parallel-group, Phase-2 Pilot Study

Aim: JNJ-54452840 (COR-1) is a novel investigational cyclopeptide with proposed mechanism of action that decreases circulating anti-β1-adrenergic receptor antibodies (anti-β1-Abs) in heart failure patients. In a phase-2, double-blind, placebo-controlled pilot study, effects of JNJ-54452840 were investigated on cardiac function at rest in patients with Dilated Cardiomyopathy (DCM) when administered in addition to guideline-recommended heart failure therapy versus 6-months of guideline-recommended therapy alone. Methods: Patients with DCM and circulating anti-β1-Abs received treatment with placebo or JNJ-54452840 (6 doses of 20, 80 or 160 mg administered intravenously every 4 weeks) in addition to guideline-recommended heart failure therapy. Results: Thirty-six patients (Caucasian, mean age 59.6 years, mean LVEF 32%) were enrolled. An increase (+5.4%) in centrally-assessed Left Ventricular Ejection Fraction (LVEF) was observed in 80 mg JNJ-54452840 group compared to a decrease (-1.6%) in the placebo group (primary efficacy endpoint). Among secondary efficacy endpoints, locally-assessed LVEF values were similar to primary results, suggesting lack of treatment effect from baseline to month 9. NT-proBNP values varied considerably between patients but were not significantly improved in JNJ-54452840-treated groups versus placebo. Compared to baseline, both JNJ-54452840 and placebo groups demonstrated a numerical increase in 6-minute walk test from baseline to month 6. The most common adverse events reported among JNJ-54452840-treated patients were cardiac failure and nasopharyngitis (n=4 each), and cough, sinusitis, increased heart rate (n=3 each). Conclusion: Considering that this phase 2 trial, originally planned to recruit 160 patients was amended to a pilot study for strategic reasons, no definitive statements on the efficacy of JNJ-5445280 in DCM patients with circulating anti-β1-Abs can be made, although centrally-assessed LVEF appeared to improve in the 80 mg dose group. No compound-related safety or tolerability signals were observed.

Tolvaptan for treatment of decompensated heart failure patients with diuretic resistance and hyponatremia

Objective To assess the efficacy and safety of low dose short-term tolvaptan in treatment of decompensated heart failure patients with diuretic resistance and hyponatremia.Methods The clinical data of consecutive patients with decompensated heart failure,who were admitted to Changzheng Hospital from April 2012 to March 2014,were analyzed retrospectively.Patients were assigned to receiving tolvaptan(15 mg/d×7 d)or standard therapy(including 3%-4%hypertonic saline× 7 d).The efficacy endpoints were heart failure symptoms relief,serum sodium elevation during hospitalization and cardiovascular death at 180 dfrom discharge.The safety endpoint included adverse effect of thirsty,renal function impairment and symptoms of nervous system.Results A total of 37 patients met the inclusion criteria and were assigned to tolvaptan(n=16)or standard therapy(n=21).There were no significant differences between the 2groups at baseline.The elevation of serum sodium at day 7,reduction of body weight and NT-proBNP level before discharge,and the ratio of restoration to higher than NYHA classⅡin the tolvaptan group were all significantly more than those in the standard therapy group(P0.05).Tolvaptan,compared with standard therapy,significantly decreased the mean dose of furosemide,serum creatinine elevation and hospital stay(P0.05),but failed to lower the cardiovascular mortality at 180dfollow-up.Conclusion For Chinese patients with decompensated heart failure with diuretic resistance and hyponatremia,in addition to guideline-recommended therapies for heart failure,low dose short term tolvaptan is associated with more favorable in-hospital effects and less severe adverse effects,but not with long-term cardiovascular mortality.

Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study.

AimsWe explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial.Methods and resultsSHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximized β-blockade). In total, 1186 patients experienced at least one additional HF hospitalization during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Ivabradine was associated with fewer total HF hospitalizations [902 vs. 1211 events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), 0.65–0.87, P = 0.0002] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, 0.55–0.79, P < 0.001 and HR: 0.71, 95% CI, 0.54–0.93, P = 0.012, respectively]. Similar observations were made for all-cause and cardiovascular hospitalizations.ConclusionTreatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospitalizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs.

B-type natriuretic peptide assessment in ambulatory heart failure patients

B-type natriuretic peptide (BNP) levels provide diagnostic and prognostic information in heart failure. This study determined the frequency of BNP assessment and analyzed demographic characteristics, clinical variables and the utilization of guideline-recommended heart failure therapies by BNP level in outpatients with reduced left ventricular ejection fraction (LVEF). The IMPROVE HF registry (The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting) is a prospective cohort study of patients at least 18 years of age with a LVEF 35% or less and chronic heart failure or previous myocardial infarction (MI) presenting to cardiology and multispecialty practices. The medical records of 15,381 patients were reviewed. BNP was measured in 4213 (27.4%) patients and the median plasma BNP level was 384 pg/ml (interquartile range 158-877 pg/ml). Patients were stratified by plasma BNP measurements into the following tertiles: 219 pg/ml or less, more than 219 to 649 pg/ml, and more than 649 pg/ml. Jugular venous distension, pedal edema, rales and systolic murmur on physical examination and elevated renal function parameters were associated with higher BNP levels. BNP assessment and elevated BNP levels were not associated with greater use of any of the quality of care measures. However, patients with a BNP in the top tertile were less likely to be treated with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or aldosterone antagonists compared with patients with a BNP in the bottom tertile. Among practices participating in IMPROVE HF, BNP was not measured in most outpatients with reduced LVEF and chronic heart failure or previous MI. BNP assessment or the BNP level in patients with recorded measurements, with few exceptions, did not impact the utilization of guideline-recommended therapies.