Search

IntroductionNearly one-quarter of patients discharged from the hospital with heart failure (HF) are readmitted within 30 days, placing a significant burden on patients, families and health systems. The objective of the ‘UsingMobileIntegratedHealth andTelehealth to support transitions of care among patients withHeartfailure’ (MIGHTy-Heart) study is to compare the effectiveness of two postdischarge interventions on healthcare utilisation, patient-reported outcomes and healthcare quality among patients with HF.Methods and analysisThe MIGHTy-Heart study is a pragmatic comparative effectiveness trial comparing two interventions demonstrated to improve the hospital to home transition for patients with HF: mobile integrated health (MIH) and transitions of care coordinators (TOCC). The MIH intervention bundles home visits from a community paramedic (CP) with telehealth video visits by emergency medicine physicians to support the management of acute symptoms and postdischarge care coordination. The TOCC intervention consists of follow-up phone calls from a registered nurse within 48–72 hours of discharge to assess a patient’s clinical status, identify unmet clinical and social needs and reinforce patient education (eg, medication adherence and lifestyle changes). MIGHTy-Heart is enrolling and randomising (1:1) 2100 patients with HF who are discharged to home following a hospitalisation in two New York City (NY, USA) academic health systems. The coprimary study outcomes are all-cause 30-day hospital readmissions and quality of life measured with the Kansas City Cardiomyopathy Questionnaire 30 days after hospital discharge. The secondary endpoints are days at home, preventable emergency department visits, unplanned hospital admissions and patient-reported symptoms. Data sources for the study outcomes include patient surveys, electronic health records and claims submitted to Medicare and Medicaid.Ethics and disseminationAll participants provide written or verbal informed consent prior to randomisation in English, Spanish, French, Mandarin or Russian. Study findings are being disseminated to scientific audiences through peer-reviewed publications and presentations at national and international conferences. This study has been approved by: Biomedical Research Alliance of New York (BRANY #20-08-329-380), Weill Cornell Medicine Institutional Review Board (20-08022605) and Mt. Sinai Institutional Review Board (20-01901).Trial registration numberClinicaltrials.gov,NCT04662541.

Introduction Heart failure accounts for 1-2% of overall healthcare costs. While the link between re-hospitalization and mortality is unclear, care pathways that standardize inpatient management and establish outpatient follow-up improve patient outcomes and reduce morbidity. Aim To implement a comprehensive interdisciplinary care pathway for heart failure patients with the goal of optimizing inpatient management and improving transitions of care. Methods To address this clinical need, New York-Presbyterian Brooklyn Methodist Hospital (NYP-BMH) identified resources needed to optimize patient care, developed an inpatient admission order set (so-called "power plan"), and implemented a multidisciplinary clinical care pathway. The Plan-Do-Study-Act cycle addressed the implementation obstacles. Interdisciplinary rounds guided day-to-day management and addressed barriers. Our team developed a sustainable care pathway, and measured the utilization of pharmacy, nutrition, physical therapy, case management, and social work resources; outpatient appointments were made prior to discharge. We used the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guidelines to guide our planning and evaluation of this quality improvement initiative. Results Our intervention markedly increased the number of heart failure hospitalizations that were identified on admission, and the use of pharmacy/nutrition services was greater after the intervention. The utilization of our "power plan" promoted adherence to a series of evidence-based best practices, but these measures had no significant impact on readmissions as a whole. The involvement of the case management support team increased outpatient appointments made for patients prior to discharge and aided in the transition of care from inpatient to outpatient management. Conclusion The management of heart failure patients starts in the hospital and continues in the community. Patients who are treated in a standardized dedicated care pathway have reduced morbidity and better outcomes. Identifying these patients early, involving a comprehensive team, and transitioning their care to the outpatient setting improves the quality of care in these patients.

Left ventricular outflow tract obstruction (LVOTO) can be caused by multiple factors. One of the rare causes of LVOTO is preserved anterior mitral valve leaflet and chordal apparatus after mitral valve replacement. We describe a case of a patient with worsening chronic congestive heart failure secondary to LVOTO from systolic anterior motion of residual native anterior mitral leaflet. In this patient, LVOTO was surgically corrected by excision of anterior leaflet and chordal apparatus through the aortic root.

Background Patients undergoing consideration for venoarterial extracorporeal membrane oxygenation (VA-ECMO) require an immediate risk profile assessment in the setting of incomplete information. A number of survival prediction models for critically ill patients and patients undergoing elective cardiac surgery or institution of VA-ECMO support have been designed. We assess the ability of these models to predict outcomes in a cohort of patients undergoing institution of VA-ECMO for cardiogenic shock or cardiac arrest. Methods Fifty-one patients undergoing institution of VA-ECMO support were retrospectively analyzed. APACHE II, SOFA, SAPS II, Encourage, SAVE, and ACEF scores were calculated. Their ability to predict outcomes were assessed. Results Indications for ECMO support included postcardiotomy shock (25%), ischemic etiologies (39%), and other etiologies (36%). Pre-ECMO arrest occurred in 73% and 41% of patients underwent cannulation during arrest. Survival to discharge was 39%. Three survival prediction model scores were significantly higher in nonsurvivors to discharge than surivors; the Encourage score (25.4 vs 20; p = .04), the APACHE II score (23.6 vs 19.2; p = .05), and the ACEF score (3.1 vs 1.8; p = .03). In ROC analysis, the ACEF score demonstrated the greatest predictive ability with an AUC of 0.7. Conclusions A variety of survival prediction model scores designed for critically ill ICU and VA-ECMO patients demonstrated modest discriminatory ability in the current cohort of patients. The ACEF score, while not designed to predict survival in critically ill patients, demonstrated the best discriminatory ability. Furthermore, it is the simplest to calculate, an advantage in the emergent setting.

Background Endocardial catheter ablation has been shown to be effective in patients with paroxysmal atrial fibrillation (AF), and significantly less effective in patients with persistent AF (PAF). Lately, there is a trend toward a hybrid approach in the treatment of PAF that may be a more durable treatment for patients with PAF. In this manuscript we report our experience with the convergent ablation procedure in a PAF cohort. Methods This is a single center retrospective analysis of 31 patients with PAF who underwent the convergent procedure. All patients underwent surgical epicardial ablation of the posterior left atrial through a subxiphoid approach, followed by radiofrequency endocardial ablations on the same day. Patients were followed at 6 months intervals with static electrocardiograms or implanted devices. Results Sinus rhythm was achieved intraoperatively in all patients. Recurrence was defined according to Hearlt Rhythm Society definitions. At a median follow up of 17.7 months (IQR 11-24), the recurrence of atrial tachyarrhythmia (AF and atrial flutter) by Kaplan-Meier event free survival analysis occurred in 9 (29%) patients at 1-year follow up and 15 (48%) patients at 2-year follow up with or without the use of antiarrhythmic drugs. Recurrence of AF alone occurred in 4 (13%) patients at 1-year follow up and 9 (29%) patients at 2-year follow up patients. Complication rate in perioperative period was 12.9%. Conclusion Our experience showed the hybrid procedure is a relatively safe and effective option for patients with PAF. Further studies are needed to better determine its long-term outcomes.

Patients undergoing consideration for venoarterial extracorporeal membrane oxygenation (VA ECMO) require an immediate risk profile assessment in the setting of incomplete or no information. A retrospective cohort study of 100 patients undergoing VA ECMO placement at three institutions was carried out. Variables strongly associated with survival to discharge were used to calculate a risk stratification score. Indications for VA ECMO support included postcardiotomy shock (24%), ischemic etiologies (33%), nonischemic cardiomyopathy (32%), and other etiologies (11%). Pre–VA ECMO arrest occurred in 69%, and 30% of patients underwent cannulation during arrest. Survival to discharge was 38%. Three variables demonstrated a strong trend toward predicting survival to discharge: lactate >10 mmol/L (p = .054), albumin

Background Biomarker-evidenced myocardial injury is common among patients with COVID-19 infection and confers an increased risk of mortality Prevalence and incremental prognostic impact of myocardial dysfunction is unknown Methods Consecutive COVID-19 patients undergoing clinical echocardiography during their index hospitalization at three New York City hospitals were studied Images were analyzed by a central core lab blinded to all clinical data LV dysfunction was defined as LVEF < 55% and RV dysfunction as TAPSE

About a fourth of acute decompensated heart failure (ADHF) patients develop renal dysfunction during their admission. To date, the association of ADHF treatment with the development of worsening renal function (WRF) remains contentious. Thus, we examined the association of WRF with changes in BNP levels and with mortality.We performed retrospective chart review of patients admitted with ADHF who had BNP, eGFR, creatinine and blood urea nitrogen (BUN) values measured both on admission and discharge. Survival analysis was conducted using Cox proportional hazards model and correlation was measured using Spearman's rank correlation test.358 patients admitted for ADHF were evaluated. WRF was defined as20% reduction in eGFR from admission to discharge and response to treatment was assessed by ΔBNP. There was a statistically significant reduction in BNP and increase in BUN during the admission. ΔBNP did not correlate with either ΔGFR or ΔBUN. Patients who developed WRF and those who did not, had a similar reduction in BNP. On univariate survival analysis, ΔBUN, but not ΔeGFR, was associated with 1-year mortality. In multivariate Cox proportional hazards model, BUN at discharge was associated with 1-year mortality (HR: 1.02, p0.001), but ΔeGFR and ΔBUN were not associated with the primary endpoint.During ADHF treatment, ΔBNP was not associated with changes in renal function. Development of WRF during ADHF treatment was not associated with mortality. Our study suggests that development of WRF should not preclude diuresis in ADHF patients in the absence of volume depletion.

Background Elevated troponin at baseline is associated with higher mortality in heart failure (HF) patients, but the prognostic role of recurrently elevated troponin is not well described. Methods and results We performed chart reviews of 196 HF patients without acute coronary syndrome, with at least three Troponin I (TnI) measurements on different admissions. For the analyses, three sets of TnI values closest to baseline, one year and two years were selected for each patient. Based on the three sets of TnI, the lowest value of TnI ( minimum ), the highest value of TnI ( maximum ), median value of TnI and delta TnI (3rd TnI–baseline TnI) were derived for each patient. The study population of 196 patients had 632 person-year follow-up, consisted predominantly of elderly (68±10years) male patients (99%) with mean ejection fraction of 26±13%. Using multivariate Cox proportional hazards model only minimum TnI, but not the maximum , median or delta of TnI values, was significantly associated with mortality (HR: 13.7, 95% CI: 3.7 to 50.8, p minimum TnI value of >0.04ng/ml was also independently associated with mortality (p=0.01, HR=1.6, 95% CI: 1.1 to 2.3). Conclusions In HF patients without acute coronary syndrome, the persistence of TnI elevation, even at low levels, is associated with a worse survival than sporadic TnI elevations of higher magnitude or any single elevation in TnI; and a recurrent elevation of TnI >0.04ng/ml portends a poor prognosis.

BACKGROUND Right Atrial Volume Index (RAVI) measured by echocardiography is an independent predictor of morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). The aim of this study is to evaluate the predictive value of RAVI assessed by cardiac magnetic resonance (CMR) for all-cause mortality in patients with HFrEF and to assess its additive contribution to the validated Meta-Analysis Global Group in Chronic heart failure (MAGGIC) score. METHODS AND RESULTS We identified 243 patients (mean age 60 ± 15; 33% women) with left ventricular ejection fraction (LVEF) ≤ 35% measured by CMR. Right atrial volume was calculated based on area in two- and four -chamber views using validated equation, followed by indexing to body surface area. MAGGIC score was calculated using online calculator. During mean period of 2.4 years 33 patients (14%) died. The mean RAVI was 53 ± 26 ml/m2; significantly larger in patients with than without an event (78.7±29 ml/m2 vs. 48±22 ml/m2, p

The intent of this American Heart Association (AHA) scientific statement is to summarize our current understanding of dilated cardiomyopathies. There is special emphasis on recent developments in diagnostic approaches and therapies for specific cardiomyopathies. Recommendations in this document are based on published studies, published practice guidelines from the American College of Cardiology (ACC)/AHA1 and other organizations,2,3 and the multidisciplinary expertise of the writing group. Existing evidence in epidemiology, classification, diagnosis, and management of specific cardiomyopathies is usually derived from nonrandomized observational studies, registries, case reports, or expert opinion based on clinical experience, not large-scale randomized clinical trials or systematic reviews. Therefore, in this document, rather than using the standard ACC/AHA classification schema of recommendations and level of evidence,4 we have included key management strategies at the end of each section and categorized our recommendations according to the level of consensus. Although the format of our recommendations might resemble the ACC/AHA classification of recommendations used in the ACC/AHA practice guidelines, because of the preponderance of expert opinion or level of evidence C evidence in our document, we elected to use different terminology to provide a distinction from the practice guidelines, in which stronger levels and quality of evidence with randomized clinical trials or meta-analyses are usually present.4 The levels of evidence follow the AHA and ACC methods of classifying the level of certainty of the treatment effect.4 The term dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders that are characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease.5 In clinical practice, the pathogenesis of heart failure (HF) has often been placed into 2 categories: ischemic and nonischemic cardiomyopathy. The term nonischemic cardiomyopathy has been interchangeably used with DCM. Although this …

The comorbidities of hypertension, diabetes mellitus, obesity, hyperlipidemia, and metabolic syndrome are common in patients with heart failure (HF) and affect clinical outcomes.1–3 Interestingly, although these comorbidities are associated with the development of incident HF in the general population, in patients with established HF, their contributory roles to clinical outcomes are not predictable, and their management is quite challenging. Recent American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines have addressed the role of lifestyle modification,4 treatment of blood cholesterol,5 and management of overweight and obesity6 in the general population and in patients with increased cardiovascular risk, and a recent report from the Eighth Joint National Committee addressed the management of hypertension.7 However, these guidelines did not specifically address the management of such comorbidities in patients with HF. Similarly, the most recent ACCF/AHA HF practice guidelines8 in 2013 addressed the overall management of comorbidities in patients with HF in broad terms, but again, specific and detailed recommendations on how to manage hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome are lacking. The intent of this AHA scientific statement is to summarize data relevant to contributory risk and to provide guidance on the management of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in the development and prognosis of HF to provide recommendations (Table 1) and to foster communication between physicians and other healthcare professionals and patients on the management of these comorbidities. Recommendations in this document are based on published studies and the multidisciplinary expertise of the writing group and harmonized with published practice guidelines from the ACC/AHA4–6,8–12 and other organizations.7,13–15 View this table: Table 1. Applying Classification of Recommendations and Level of Evidence Hypertension is a worldwide epidemic; in many countries, 50% of …

The initial observation of functional recovery in dysfunctional myocardium following revascularization led to the introduction of the concept of hibernating myocardium. Since then, the pathophysiologic basis of hibernating myocardium has been well described. Multiple imaging modalities have been utilized to prospectively detect viable myocardium and thus predict its functional recovery following revascularization. It has been hypothesized that viability imaging will be instrumental in the selection of patients with ischemic cardiomyopathy likely to benefit from revascularization. Multiple observational studies built a large body of evidence supporting this concept. However, data from prospective studies failed to substantiate utility of viability testing. This review aims to summarize the current literature and describe the role of viability imaging in current clinical practice as well as future directions.

Background Long-term heart failure (HF) treatment has been shown to result in reverse chamber remodeling. However, it is unknown whether sizes of cardiac chambers acutely change during HF therapy and whether these changes are associated with favorable clinical outcomes. Methods and Results Using the Evaluation Study of Congestive Heart Failure and Pulsmonary Artery Catheterization Effectiveness (ESCAPE) trial database, echocardiographic parameters at baseline and discharge, changes from baseline to discharge, and their association with the combined endpoint of death or HF rehospitalization (HFH) at 6 months were evaluated in patients admitted with acute decompensated HF (ADHF). Also, the correlation between changes in invasive hemodynamic parameters compared with changes in echocardiographic parameters was analyzed. During the treatment of ADHF, right atrium, right ventricle, and inferior vena cava (IVC) sizes decreased acutely. Mitral regurgitation severity and mitral inflow parameters also improved significantly. However, the majority of acute changes in echocardiographic parameters did not have an impact on clinical outcome, except for the reduction in left ventricular (LV) end-diastolic and end-systolic volumes, which was associated with a reduction in the combined outcome of HFH or death. The change in invasive hemodynamics that best correlated with change in echocardiographic parameters was change in pulmonary capillary wedge pressure with change in IVC diameter and IVC collapsibility. Conclusions This is the first study to identify the echocardiographic parameters that change during the treatment of ADHF and the echocardiographic parameters that most reliably correlate with invasive hemodynamic changes. Most changes in echocardiographic parameters were not associated with clinical outcomes, except for the reduction in LV volume, which was associated with a reduction in HFH or death.

Kumudha Ramasubbu1, Anita Deswal1, Cheryl Herdejurgen2, David Aguilar1, Adaani E Frost21Section of Cardiology, Michael E DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas, USA; 2Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USABackground: Pulmonary hypertension (PH), a disease which carries substantial morbidity and mortality, has been reported to occur in 25%–45% of dialysis patients. No prospective evaluation of the prevalence or clinical significance of PH in chronic dialysis patients in the United States (US) has been undertaken.Methods: Echocardiograms were performed prospectively in chronic hemodialysis patients prior to dialysis at a single dialysis center. PH was defined as a tricuspid regurgitant jet ≥2.5 m/s and “more severe PH” as ≥3.0 m/s. Clinical outcomes recovered were all-cause hospitalizations and death at 12 months.Results: In a cohort of 90 patients, 42 patients (47%) met the definition of PH. Of those, 18 patients (20%) met the definition of more severe PH. At 12 months, mortality was significantly higher in patients with PH (26%) compared with patients without PH (6%). All-cause hospitalizations were similar in patients with PH and without PH. Echocardiographic findings suggesting impaired left ventricular function and elevated pulmonary capillary wedge pressure were significantly associated with PH.Conclusion: This prospective cross-sectional study of a single dialysis unit suggests that PH may be present in nearly half of US dialysis patients and when present is associated with increased mortality. Echocardiographic findings demonstrate an association between elevated filling pressures, elevated pulmonary artery pressures, and higher mortality, suggesting that the PH may be secondary to diastolic dysfunction and compounded by volume overload.Keywords: renal failure, pulmonary hypertension, diastolic dysfunction

The non-lipid-lowering or pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been hypothesized to beneficially alter mechanisms involved in heart failure. Retrospective analyses of heart failure trials as well as small prospective trials with nonmortality clinical and surrogate end points appeared to confirm this presumption. However, two recently published, large, prospective randomized trials did not demonstrate any significant clinical benefit of statins in heart failure patients. This review outlines the proposed biologic effects of statins in heart failure syndrome and clinical evidence of statin use in heart failure patients.

Purpose of reviewDilated cardiomyopathy is a disease of the heart muscle, characterized by ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions or ischemic heart disease. Dilated cardiomyopathy may be viewed as a progressive disorder that is initi

Ability to predict response to cardiac resynchronization therapy (CRT) has been one of the challenges in the treatment of heart failure (HF). Although CRT has been associated with significant clinical improvement in large clinical trials ([1–3][1]), approximately 30% of the patients do not

Objective: We report an 11-year-old boy presenting with splenomegaly, chronic thrombocytopenia and concordant neutropenia. Results: In contrast to autoantibodies against platelets, there were no detectable neutrophil-specific autoantibodies present in this patient. Extensive serologic investigations revealed increased IgM- and IgG-antibody titers against parvovirus B19. A nested polymerase chain reaction (PCR) showed parvovirus B19-specific sequences in the patient's bone-marrow cells but not in the serum. Specific antibodies against the structural proteins VP1 and VP2 in addition to those against non-structural protein NS1 of parvovirus B19 were detected by Western blot analysis. Thrombocytopenia and neutropenia responded to immunosuppressive therapy and subsequent splenectomy, the latter being necessary due to severe side-effects of steroid medication. Conclusion: Autoimmune thrombocytopenia/neutropenia may have been triggered and/or sustained by a chronic parvovirus B19 infection. Patients with this very rare disorder should be screened for this virus.

Several retrospective studies have suggested that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may benefit patients with ischemic and nonischemic cardiomyopathy ([1–5][1]). However, there are limited prospective data to suggest that statins are beneficial once

Immunohistochemical colocalization of the α-subunit of neutrophil NADPH oxidase and ecto-5′-nucleotidase in kidney and liver.In kidney and liver, fibroblasts and fibroblast-like cells, respectively, are sources of erythropoietin (Epo) formation, and these cells also bear a number of other similarities. Renal Epo expression is localized in peritubular type I fibroblasts of the cortical labyrinth, and in the liver, apart from parenchymal cells, transcription is found in Ito cells. Both the renal peritubular cells and Ito cells contain ecto-5′-nucleotidase (5′NT). It had been suggested that 5′NT is involved in the oxygen sensing mechanism via a hydrolysis of AMP to adenosine, which in turn may stimulate EPO synthesis. However, the molecular mechanism of the cellular response to hypoxia is currently not well understood. Based on the notion that a heme protein probably acts as the oxygen sensor, it has recently been proposed that a b-type cytochrome as part of the neutrophil NADPH oxidase may influence intracellular superoxide levels depending on local oxygen tension. Superoxide levels were otherwise shown to determine the EPO production in hepatoma cell lines. By double immunofluorescence labeling the α-sub-unit of cytochrome b558 (α-SU) and 5′NT were simultaneously localized in rat kidney and liver, and in the kidney Epo mRNA and α-SU were double-labeled. Positive signal for α-SU was found in the majority of renal peritubular fibroblasts in the cortex and outer medulla, and in Ito cells. In both organs, the cells that coexpress 5′NT and Epo mRNA also contain an immunoreactivity for α-SU. In these cells, cytochrome b558 as part of an NADPH oxidase may be involved in a presumptive oxygen sensing mechanism using H2O2 as a possible second messenger for EPO gene regulation.

A 36-year-old man was admitted to the hospital for heart failure symptoms. He had initially presented to the emergency room 3 months prior to admission for shortness of breath and a low-grade fever. At that time, he was diagnosed with possible pneumonia and started on antibiotics. Despite this, his symptoms progressed over the next few months. At presentation, he experienced dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and lower extremity edema. The patient's past medical history was …

Heart-failure phenotypes include pulmonary and systemic venous congestion. Traditional heart-failure classification systems include the Forrester hemodynamic subsets, which use 2 indices: pulmonary capillary wedge pressure (PCWP) and cardiac index. We hypothesized that changes in PCWP and central venous pressure (CVP), and in the phenotypes of heart failure, might be better evaluated by cardiovascular modeling. Therefore, we developed a lumped-parameter cardiovascular model and analyzed forms of heart failure in which the right and left ventricles failed disproportionately (discordant ventricular failure) versus equally (concordant failure). At least 10 modeling analyses were carried out to the equilibrium state. Acute discordant pump failure was characterized by a "passive" volume movement, with fluid accumulation and pressure elevation in the circuit upstream of the failed pump. In biventricular failure, less volume was mobilized. These findings negate the prevalent teaching that pulmonary congestion in left ventricular failure results primarily from the "backing up" of elevated left ventricular filling pressure. They also reveal a limitation of the Forrester classification: that PCWP and cardiac index are not independent indices of circulation. Herein, we propose a system for classifying heart-failure phenotypes on the basis of discordant or concordant heart failure. A surrogate marker, PCWP-CVP separation, in a simplified situation without complex valvular or pulmonary disease, shows that discordant left and right ventricular failures are characterized by differences of ≥ 4 and ≤ 0 mmHg, respectively. We validated the proposed model and classification system by using published data on patients with acute and chronic heart failure.

In ambulatory patients with heart failure with reduced ejection fraction (HFrEF), high systolic blood pressure (SBP) is associated with better outcomes. However, it is not known whether there is a ceiling beyond which high SBP has a detrimental effect. Thus, our aim was to assess the linearity of association between SBP and mortality.We used the External Peer Review Program (EPRP) and Digitalis Investigation Group (DIG) trial databases of HFrEF patients. Linearity of association of SBP with mortality was assessed by plotting Martingale residuals against SBP. To assess the patterns of relationship of SBP with mortality, we used restricted cubic spline analysis with Cox proportional hazards model.In patients with mild-to-moderate left ventricular systolic dysfunction (LVSD) (30% ≤ LVEF50%), SBP had a nonlinear association with mortality in both EPRP (n = 3,693) and DIG (n = 3,263) databases. In these patients, SBP had a significant U-shaped association with mortality in EPRP and a trend toward U-shaped relationship in DIG database. In patients with severe LVSD (LVEF30%), SBP had a linear association with mortality in both EPRP (n = 2,906) and DIG (n = 3,537) databases, with lower SBP being associated with increased mortality.Systolic blood pressure has a complex nonlinear association with mortality in patients with heart failure. Whereas it has a U-shaped association in patients with mild-to-moderate LVSD, it has a linear association with mortality in patients with severe LVSD. Recognition of this pattern of association of blood pressure profile may help clinicians in providing better care for their patients and help improve existing prediction models.

Digoxin has been shown to reduce heart failure (HF) hospitalizations with no overall effect on mortality in HF patients. We used cluster analysis to delineate the clinical characteristics of HF patients in whom digoxin therapy was associated with improved or worsened clinical outcomes.The Digitalis Investigation Group (DIG) database was partitioned into 20 clusters. Multivariate Cox regression analyses was used, to identify clusters in which digoxin was associated with either an increase (Mortality(dig)HR1), decrease (Mortality(dig)HR1), or no association with all cause mortality (Mortality(dig)HR-NS); and separately, with an increase (HFA(dig)HR1), decrease (HFA(dig)HR1), or no association (HFA(dig)HR-NS) with HF admissions (HFA).We identified 938 patients in the Mortality(dig)HR1 group, 6818 patients in the Mortality(dig)HR-NS group, and none in Mortality(dig)HR1 group. The Mortality(dig)HR1 group had a higher prevalence of females, diabetes mellitus, hypertension, higher age, systolic blood pressure (SBP), heart rate and ejection fraction (EF), compared to the Mortality(dig)HR-NS group. Similarly, 6325 patients clustered in the HFA(dig)HR1 group, 1431 patients in the HFA(dig)HR-NS group, and none in the HFA(dig)HR1 group. The HFA(dig)HR-NS group had a higher prevalence of females and hypertension, higher SBP, body mass index and EF; and lower prevalence of peripheral edema and third heart sound, compared with the HFA(dig)HR1 group.Thus, the baseline characteristics of patients who did not have reduction in HF hospitalization or who had increased mortality were very similar and included females with hypertension, higher EF and higher SBP. Thus, use of digoxin in patients with this profile may need to be avoided.

Previous clinical trials have shown that alpha(1)-adrenergic antagonists are not effective in subjects with heart failure (HF) and might increase HF rates when used for hypertension. However, alpha(1)-adrenergic antagonists may be prescribed to subjects with HF who have symptomatic benign prostatic hyperplasia. We sought to determine any association between alpha(1)-adrenergic antagonist use, commonly prescribed for benign prostatic hyperplasia, and the clinical outcomes of subjects with HF receiving contemporary therapy. An existing database of 388 subjects with decompensated HF admissions from 2002 to 2004 at the Veterans Affairs Hospital was analyzed according to the use of alpha(1)-adrenergic antagonists at discharge. Covariate-adjusted Cox proportional hazard models were used to examine any association with future admissions for decompensated HF and total mortality. Alpha-1-adrenergic antagonist therapy was prescribed in 25% of our HF population, predominantly for benign prostatic hyperplasia, and was not associated with significant increases in the combined risk of all-cause mortality and rehospitalization for HF (hazard ratio 1.24, 95% confidence interval 0.93 to 1.65, p = 0.14), HF hospitalization (hazard ratio 1.20, 95% confidence interval 0.85 to 1.70, p = 0.31), or all-cause mortality (hazard ratio 1.10, 95% confidence interval 0.78 to 1.56, p = 0.57). In patients not receiving beta-blocker therapy, alpha(1)-adrenergic antagonist therapy was significantly associated with increased HF hospitalizations (hazard ratio 1.94, 95% confidence interval 1.14 to 3.32, p = 0.015). In conclusion, in patients with chronic HF, the use of alpha(1)-adrenergic antagonists was significantly associated with more HF hospitalizations when prescribed without concomitant beta blockade. Thus, background beta-blocker therapy appears to be protective against the potential harmful effects of alpha(1)-adrenergic antagonist therapy in patients with HF.

The syndrome of heart failure is characterized by increased levels of circulating inflammatory mediators, which have been implicated in the pathogenesis of heart failure. Recently, a number of studies have suggested that statins may exert salutary effects in patients who have heart failure by virtue of their pleiotropic (non–lipid lowering) actions. This article focuses on the non–lipid lowering effects of statins, with an emphasis on the anti-inflammatory properties of these agents.

Previous trials have shown that digoxin was beneficial in patients with heart failure (HF). However, these studies were conducted before the incorporation of beta blockers as standard therapy for patients with HF. The purpose of this study was to determine the effect of digoxin in patients with HF on a contemporary regimen of renin-angiotensin inhibition and beta blockade. In 347 almost exclusively men, data pertaining to the index hospitalization and occurrence of all-cause mortality or readmission for HF were collected. Cox proportional hazard modeling was used. Patients on digoxin therapy had a lower left ventricular (LV) ejection fraction (EF), higher prevalence of previous hospitalizations for HF and atrial fibrillation, and lower prevalence of hypertension. After adjustment for age, LVEF, history of HF hospitalizations, New York Heart Association class, presence of chronic renal insufficiency, presence of atrial fibrillation, and prescriptions for beta blockers and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, HF hospitalizations (hazard ratio 1.08, 95% confidence interval [CI] 0.77 to 1.50, p = 0.66), total mortality (hazard ratio 1.03, 95% CI 0.78 to 1.35, p = 0.85), or the combined end point of HF hospitalization and total mortality (hazard ratio 1.11, 95% CI 0.81 to 1.53, p = 0.52) were not different in patients using digoxin compared with those not using digoxin. Clinical outcomes were not different in subgroups of patients with EFor =25%, New York Heart Association class III or IV, atrial fibrillation, heart rateor =60 beats/min, or patients on beta-blocker therapy. In conclusion, digoxin use was not associated with a decrease in HF hospitalizations or overall mortality rates in a cohort of hospitalized patients with HF with LV systolic dysfunction on contemporary background HF treatment including angiotensin-converting enzyme inhibitors and beta blockers.