Search

Background Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an underappreciated cause of heart failure that results from misfolded TTR (prealbumin) protein. Diflunisal is an approved non-steroidal anti-inflammatory drug that stabilizes TTR, with limited data available regarding effects on cardiac structure and function. Methods and Results ATTR-CM patients (n=81, 41% treated with 250 mg twice-daily diflunisal by clinical practice) were retrospectively identified with baseline and follow-up (median interval 1 year) serum biomarker and echocardiographic data compared, including global longitudinal strain (GLS). Chi-squared and Wilcoxon tests assessed differences between subjects, divided by treatment group, and univariable and multivariable linear regression was performed. At baseline, patients treated with diflunisal were younger (68 vs 77 years, P = .0001), with lower B-type natriuretic peptide (BNP; 249 vs 545 pg/mL, P = .009) and serum creatinine (1.1 vs 1.2 mg/dL, P = .04), but similar TTR concentration (P = .31), cardiac troponin I (P = .06), and GLS (P = .67). At follow-up, diflunisal untreated versus treated patients showed differences in TTR concentration (19 vs 33 mg/dL, P = .01) and favorable differences in left atrial volume index (+4.6 vs −1.4 mL/m2, P = .002) and cardiac troponin I (+0.03 vs −0.01 ng/mL, P = .01) for the entire cohort. Among the subset with wild-type ATTR (n=53), diflunisal treatment was associated with differences in GLS (+1.2% untreated vs +0.1% treated, P = .03). Changes in wall thickness (P = .2), left ventricular ejection fraction (P = .71), and BNP (P = .42) were similar between groups. Conclusions In ATTR-CM, diflunisal treatment resulted in measurable differences in some parameters of cardiac structure and function after only 1 year of administration. Further longer-term analysis is warranted.

The global prevalence of atrial fibrillation (AF) and heart failure (HF) is rising. Population-based studies have observed that AF and HF often coexist, predispose to each other, and share risk factors. Age is the most potent risk factor for both AF and HF, but race plays an important role. Although AF and HF share common risk factors, adjusting for these risk factors does not explain the higher risk of AF patients developing HF and vice versa. Common pathophysiologic mechanisms may explain this linkage. The morbidity and mortality outcomes with combined AF and HF are substantial and warrant improved preventive strategies.

Introduction: Hereditary transthyretin amyloid cardiomyopathy (pV142I hATTR-CM) is an under-recognized cause of heart failure (HF) in elderly patients of African origin. While we have previously demonstrated that the endogenous TTR ligand retinol binding protein 4 (RBP4) identifies patients with hATTR-CM, its capacity to predict outcomes is unexplored. Further, comparative data are lacking describing clinical outcomes in hATTR-CM vs. matched patients with HF. Hypothesis: Reduced survival is associated with pV142I hATTR-CM when compared to an age, race, sex matched patients with HF. Methods: Retrospective, single center, cohort study of self-reported African American patients ≥ 60 years of age with normal TTR genotype, HF, and LV wall thickness ≥ 12mm (n=84) were compared to a cohort with biopsy-proven pV142I hATTR-CM (n=30). Patients did not receive ATTR-specific therapies, as study occurred prior to FDA approvals. Baseline laboratory values were measured. All-cause mortality was estimated and compared between groups based on a median followup of 45.4 months. Analyses were conducted with Fisher Exact, Kruskal Wallis, and Kaplan-Meier with log-rank testing. Results: hATTR-CM patients were slightly older but less likely to have concomitant HTN or DM (Table 1). Baseline RBP4 concentration was lower while troponin level higher in patients with hATTR-CM (Table 1). hATTR-CM patients had a higher hazard of all-cause mortality after adjusting for age (HR=3.5, 95% CI: 1.8 – 6.7, p Conclusions: Patients pV142I hATTR-CM demonstrate significantly reduced survival (a 3.5-fold increased risk of death, 43% 4-year survival) compared to control subjects with HF in the absence of amyloidosis. Baseline RBP4 concentration did not associate with survival. These data suggest that hATTR-CM recognition is essential to permit implementation of available therapies that can improve survival.

Relief of congestion is the primary goal of initial therapy for acute decompensated heart failure (ADHF). Early measurement of urine sodium concentration (UNa) may be useful to identify patients with diminished response to diuretics. The aim of this study was to determine if the first spot UNa after diuretic initiation could select patients likely to require more intensive therapy during hospitalization.At the time of admission, 103 patients with ADHF were identified prospectively, and UNa was measured after the first dose of intravenous diuretic. Clinical outcomes were compared for patients with UNa60 mmol/L and UNa of ≤60 mmol/L, with the primary outcome of a composite of death at 90 days, mechanical circulatory support during admission, and requirement of inotropic support at discharge.Patients with UNa ≤60 had lower admission blood pressure, had less chronic neurohormonal antagonist prior to admission, and were more than twice as likely to experience the primary end point (hazard ratio 2.40, 95% CI 1.02-5.66, P = .045), which was marginally significant after adjusting for renal function and baseline home loop diuretic. Worsening renal function was significantly more common in patients with UNa60 (23.6% vs 6.5%, P = .05). Although the initial assessment of congestion was similar at admission, patients with low early UNa had a longer length of stay (11 vs 6 days, P .006) than patients with UNa60.Assessment of spot UNa after initial intravenous loop diuretic administration may facilitate identification and triage of a population of HF patients at increased risk for adverse events and prolonged hospitalization.

OBJECTIVE Metabolic syndrome (MetS) can lead to myocardial fibrosis, diastolic dysfunction, and eventual heart failure. This study evaluated alterations in myocardial microstructure in people with MetS by using a novel algorithm to characterize ultrasonic signal intensity variation. METHODS Among 254 participants without existing cardiovascular disease (mean age 42 ± 11 years, 75% women), there were 162 with MetS, 47 with obesity without MetS, and 45 nonobese controls. Standard echocardiography was performed, and a novel validated computational algorithm was used to investigate myocardial microstructure based on sonographic signal intensity and distribution. The signal intensity coefficient (SIC [left ventricular microstructure]) was examined. RESULTS The SIC was significantly higher in people with MetS compared with people with (P

Background Heart Failure (HF) the most frequent MS-DRG resulting in 30 day readmission is a major focus of readmission reduction initiatives. Achieving meaningful and sustained reductions in HF readmissions in a Safety Net Hospital is particularly challenging. Boston Medical Center achieved this goal through designing a robust slate of multidisciplinary interventions tapping existing institutional resources in new ways. Objectives Design a slate of multidisciplinary interventions that lower BMC’s average 30 day Medicare HF readmission to less than 19% by May 2019. Methods Using PDSA methodology a multidisciplinary team implemented interventions addressing care processes, co-morbidities and social determinants of health. Effectiveness was monitored through automated performance dashboards. Interventions included (1) Inpatient HF Consult Criteria patients not on Cardiology teams; (2) Standardized RN Teach Back and EPIC smart phrases discharge documentation; (3) VNA support HF home discharges, preferential respite admission when homelessness; (4) HF Clinic Nurse Practitioner follow up appointments within 7–14 days discharge ;(5) Scripted call day prior Cardiology appointment to mitigate barriers to arrival;(6) Concurrent Renal consultation CKD IV or V patients not on hemodialysis. Results In the six month prior to QI initiative, BMC’s Medicare 30 day HF readmission rate averaged 26.85% which decreased to 15.2% (12/1/18–6/30/19) as the slate of interventions fully activated. Total HF readmissions showed similar decrease from 23.9% to 17.2%. Conclusions BMC demonstrates that meaningful Heart Failure readmission reductions can be achieved Safety Net Hospitals by tapping into existing institutional resources in new ways. Planning permanent accountable team, automated dashboards and robust feedback loops insure reductions seen are sustained.

The review’s main focus centers on the genetics of hereditary cardiac amyloidosis, highlighting the opportunities and challenges posed by the widespread availability of genetic screening and diagnostic cardiac imaging. Advancements in cardiac imaging, heightened awareness of the ATTR amyloidosis diagnosis, and greater access to genetic testing have all led to an increased appreciation of the prevalence of ATTR cardiac amyloidosis. Elucidation of the TTR molecular structure and effect of mutations on TTR function have allowed for novel TTR therapy development leading to clinical implementation of transthyretin stabilizers and transthyretin gene silencers. The transthyretin amyloidoses are a diverse group of protein misfolding disorders with cardiac and peripheral/autonomic nervous system manifestations due to protein deposition. Genetic screening allows for the early identification of asymptomatic TTR mutation carriers. With the advent of TTR-specific therapeutics, clinical guidance is necessary for the management of individuals with mutations in the TTR gene without evidence of disease.

The global prevalence of atrial fibrillation (AF) and heart failure (HF) is rising. Population-based studies have observed that AF and HF often coexist, predispose to each other, and share risk factors. Age is the most potent risk factor for both AF and HF, but race plays an important role. Although AF and HF share common risk factors, adjusting for these risk factors does not explain the higher risk of AF patients developing HF and vice versa. Common pathophysiologic mechanisms may explain this linkage. The morbidity and mortality outcomes with combined AF and HF are substantial and warrant improved preventive strategies.

Background Obesity is a precursor to heart failure with preserved ejection fraction. Biomarkers that identify preclinical metabolic heart disease ( MHD ) in young obese patients would help identify high‐risk individuals for heart failure prevention strategies. We assessed the predictive value of GAL3 (galectin–3), FSTL3 (follistatin‐like 3 peptide), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) to identify stage B MHD in young obese participants free of clinically evident cardiovascular disease. Methods and Results Asymptomatic obese patients (n=250) and non‐obese controls (n=21) underwent echocardiographic cardiac phenotyping. Obese patients were classified as MHD positive ( MHD ‐ POS ; n=94) if they had abnormal diastolic function or left ventricular hypertrophy and had estimated pulmonary artery systolic pressure ≥35 mm Hg. Obese patients without such abnormalities were classified as MHD negative (MHD‐NEG; n=52). Serum biomarkers timed with echocardiography. MHD ‐ POS and MHD‐NEG individuals were similarly obese, but MHD ‐ POS patients were older, with more diabetes mellitus and metabolic syndrome. Right ventricular coupling was worse in MHD ‐ POS patients ( P GAL 3 levels were higher in MHD ‐ POS versus MHD ‐NEG patients (7.7±2.3 versus 6.3±1.9 ng/mL, respectively; P GAL 3 and FSTL 3 levels correlated with diastolic dysfunction and increased pulmonary artery systolic pressure but not with left ventricular mass. In multivariate models including all 3 biomarkers, only GAL 3 remained associated with MHD (odds ratio: 1.30; 95% CI , 1.01–1.68; P =0.04). Conclusions In young obese individuals without known cardiovascular disease, GAL 3 is associated with the presence of preclinical MHD . GAL 3 may be useful in screening for preclinical MHD and identifying individuals with increased risk of progression to obesity‐related heart failure with preserved ejection fraction.

Background How serum albumin levels are associated with risk for heart failure (HF) in the elderly is unclear. Methods We evaluated 2,907 participants without HF (age 73.6 ± 2.9 years, 48.0% male, 58.7% white) from the community-based Health ABC Study. The association between baseline albumin and incident HF was assessed with standard and competing risks proportional hazards models controlling for HF predictors, inflammatory markers, and incident coronary events. Results During a median follow-up of 9.4 years, 342 (11.8%) participants developed HF. Albumin was a time-dependent predictor of HF, with significance retained for up to 6 years (baseline hazard ratio [HR] per −1 g/L 1.14, 95% CI 1.06-1.22, P P = .001). This association persisted in models controlling for HF predictors, inflammatory markers, and incident coronary events (baseline HR per −1 g/L 1.13, 95% CI 1.05-1.22, P = .001; annual rate of HR decline 1.8%, 95% CI 0.5%-3.0%, P = .008) and when mortality was accounted for in adjusted competing risks models (baseline HR per −1 g/L 1.13, 95% CI 1.05-1.21, P = .001; annual rate of HR decline 1.9%, 95% CI 0.7%-3.1%, P = .002). The association of albumin with HF risk was similar in men (HR per −1 g/L 1.13, 95% CI 1.05-1.23, P = .002) and women (HR per −1 g/L 1.12, 95% CI 1.04-1.22, P = .005) and in whites and blacks (HR per −1 g/L 1.13, 95% CI 1.04-1.22, P Conclusions Low serum albumin levels are associated with increased risk for HF in the elderly in a time-dependent manner independent of inflammation and incident coronary events.

Background Metabolic disease can lead to intrinsic pulmonary hypertension in experimental models. The contributions of metabolic syndrome (MetS) and obesity to pulmonary hypertension and right ventricular dysfunction in humans remain unclear. We investigated the association of MetS and obesity with right ventricular structure and function in patients without cardiovascular disease. Methods and Results A total of 156 patients with MetS (mean age 44 years, 71% women, mean body mass index 40 kg/m 2 ), 45 similarly obese persons without MetS, and 45 nonobese controls underwent echocardiography, including pulsed wave Doppler measurement of pulmonary artery acceleration time ( PAAT ) and ejection time. Pulmonary artery systolic pressure was estimated from PAAT using validated equations. MetS was associated with lower tricuspid valve e′ (right ventricular diastolic function parameter), shorter PAAT , shorter ejection time, and larger pulmonary artery diameter compared with controls ( P PAAT was 42±12 mm Hg in participants with MetS compared with 32±9 and 32±10 mm Hg in obese and nonobese controls ( P for ANOVA PAAT (β=−20.4, SE=6.5, P =0.002 versus obese). This association persisted after accounting for left ventricular structure and function and after exclusion of participants with obstructive sleep apnea. Conclusions MetS is associated with abnormal right ventricular and pulmonary artery hemodynamics, as shown by shorter PAAT and subclinical right ventricular diastolic dysfunction. Estimated pulmonary artery systolic pressures are higher in MetS and preclinical metabolic heart disease and raise the possibility that pulmonary hypertension contributes to the pathophysiology of metabolic heart disease.

Background Galectin‐3 ( GAL ‐3), a β‐galactoside–binding protein, is a new clinical biomarker believed to reflect cardiac remodeling/fibrosis in patients with heart failure ( HF ). Plasma GAL ‐3 is inversely related to renal function. It is not known whether the relationship between renal function and GAL ‐3 is influenced by clinical decompensation, type of HF , or the presence or absence of clinical HF . Methods and Results Patients were prospectively categorized as having acute decompensated HF or stable HF on the basis of clinical status and as having HF with reduced left ventricular ejection fraction or HF with preserved left ventricular ejection fraction. Plasma GAL ‐3 was measured by enzyme‐linked immunosorbent assay in patients with HF (n=75), control patients without HF (n=32), and control patients without HF with moderate renal insufficiency (n=12). Compared to controls without HF (14±4 ng/mL), GAL ‐3 was higher in patients with both acute decompensated HF (23±11 ng/mL) and stable HF (22±10 ng/mL) ( P HF and stable HF ( P =0.75). Likewise, GAL ‐3 was elevated in both HF with preserved left ventricular ejection fraction (23±9 ng/mL) and HF with reduced left ventricular ejection fraction (22±11 ng/mL) ( P P =0.37). GAL ‐3 correlated strongly with estimated glomerular filtration rate, both in patients with HF ( r =−0.75, P HF ( r =−0.82, P HF . Conclusions Plasma GAL ‐3 is inversely related to renal function in patients with and without clinical HF . Concentrations of plasma GAL ‐3 do not seem to depend on the level of compensation or type of HF . Furthermore, the relationship between GAL ‐3 and renal function seems to be affected little or not at all by the presence or absence of clinical HF .

BackgroundAlthough there is evidence linking smoking and heart failure (HF), the association between lifetime smoking exposure and HF in older adults and the strength of this association among current and past smokers is not well known.MethodsWe examined the association between smoking status, pack-years of exposure, and incident HF risk in 2,125 participants of the Health, Aging, and Body Composition Study (age 73.6 ± 2.9 years, 69.7% women, 54.2% whites) using proportional hazard models.ResultsAt inception, 54.8% of participants were nonsmokers, 34.8% were past smokers, and 10.4% were current smokers. During follow-up (median 9.4 years), HF incidence was 11.4 per 1,000 person-years in nonsmokers, 15.2 in past smokers (hazard ratio [HR] vs nonsmokers 1.33, 95% CI 1.01-1.76, P = .045), and 21.9 in current smokers (HR 1.93, 95% CI 1.30-2.84, P = .001). After adjusting for HF risk factors, incident coronary events, and competing risk for death, a dose-effect association between pack-years of exposure and HF risk was observed (HR 1.09, 95% CI 1.05-1.14, P < .001 per 10 pack-years). Heart failure risk was not modulated by pack-years of exposure in current smokers. In past smokers, HR for HF was 1.05 (95% CI 0.64-1.72) for 1 to 11 pack-years, 1.23 (95% CI 0.82-1.83) for 12 to 35 pack-years, and 1.64 (95% CI 1.11-2.42) for >35 pack-years of exposure in fully adjusted models (P < .001 for trend) compared with nonsmokers.ConclusionsIn older adults, both current and past cigarette smoking increase HF risk. In current smokers, this risk is high irrespective of pack-years of exposure, whereas in past smokers, there was a dose-effect association.

Patients with heart failure (HF) develop metabolic derangements including increased adipokine levels, insulin resistance, inflammation and progressive catabolism. It is not known whether metabolic dysfunction and adipocyte activation worsen in the setting of acute clinical decompensation, or conversely, improve with clinical recovery.We assessed insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR), and measured plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), adiponectin, visfatin, resistin, leptin, and tumor necrosis factor (TNF) α in 44 patients with acute decompensated HF (ADHF) due to left ventricular (LV) systolic dysfunction and again early (1 wk) and late (6 mo) after clinical recovery, in 26 patients with chronic stable HF, and in 21 patients without HF. NT-proBNP was not increased in control subjects, mildly elevated in patients with stable HF, markedly elevated in patients with ADHF, and decreased progressively early and late after treatment. Compared to control subjects, plasma adiponectin, visfatin, leptin, resistin, and TNF-α were elevated in patients with chronic stable HF and increased further in patients with ADHF. Likewise, HOMA-IR was increased in chronic stable HF and increased further during ADHF. Adiponectin, visfatin, and HOMA-IR remained elevated at the time of discharge from the hospital, but returned to chronic stable HF levels. Adipokine levels were not related to body mass index in HF patients. HOMA-IR correlated positively with adipokines and TNF-α in HF patients.ADHF is associated with worsening of insulin resistance and elevations of adipokines and TNF-α, indicative of adipocyte activation. These metabolic abnormalities are reversible, but they temporally lag behind the clinical resolution of decompensated HF.