Objectives This study sought to examine the ability of left ventricular (LV) global longitudinal strain (GLS) to assess disease severity in patients with chronic systolic heart failure (HF). ...Background Left ventricular GLS is a sensitive measure of LV mechanics. Its relationship with standard clinical markers and long-term adverse events in chronic systolic HF is not well established. Methods In 194 chronic systolic HF patients, we performed comprehensive echocardiography with assessment of GLS by velocity vector imaging averaged from apical 4-chamber and 2-chamber views. Death, cardiac transplantation, and HF hospitalization were tracked for 5 years. Results In our study cohort (age 57 ± 14 years, left ventricular ejection fraction LVEF 26 ± 6%, median N-terminal pro-B-type natriuretic peptide NT-proBNP 1,158 pg/ml), the mean GLS was −7.1 ± 3.3%. The GLS worsened with increasing New York Heart Association functional class (rank-sum p < 0.0001) and higher NT-proBNP (r = 0.42, p < 0.0001). The GLS correlated with LV cardiac structure (LV mass index: r = 0.35, p < 0.0001; LV end-diastolic volume index: r = 0.43, p < 0.0001) and LVEF (r = −0.66, p < 0.0001). A lower magnitude of GLS was associated with worsening LV diastolic function (E/e' septal: r = 0.33, p < 0.0001), right ventricular (RV) systolic function (RV s': r = −0.30, p < 0.0001), and RV diastolic function (RV e'/a': r = 0.16, p = 0.033). GLS predicted long-term adverse events (hazard ratio: 1.55, 95% confidence interval: 1.21 to 2.00; p < 0.001). Worsening strain (GLS ≥−6.95%) predicted adverse events after adjustment for age, sex, ischemic etiology, E/e' septal, and NT-proBNP (hazard ratio: 2.04, 95% confidence interval: 1.09 to 3.94; p = 0.025) and age, sex, ischemic etiology, and LVEF (hazard ratio: 2.15, 95% confidence interval: 1.19 to 4.02; p = 0.011). Conclusions In chronic systolic HF, worsening LV GLS is associated with more severe LV diastolic dysfunction and RV systolic and diastolic dysfunction, and provides incremental prognostic value to LVEF.
Abstract Lower serum chloride (Cl) levels are strongly associated with increased long-term mortality after admission for acute heart failure (AHF). However, the therapeutic implications of serum Cl ...levels during AHF are unknown. We sought to determine the short-term clinical response and post-discharge outcomes associated with serum Cl levels in AHF. Serum Cl was measured at randomization (N=358) and during hospitalization from patients with AHF in the in the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) trial. Outcomes included diuretic response and renal function at 72 hours and death and rehospitalization at 60 and 180-days. Baseline Cl tertiles were: 84-98 meq/L; 99-102 meq/L; and 103-117 meq/L. Baseline Cl level was associated with diuretic efficiency (P<.001), but not change in cystatin C (P=0.30) at 72 hours; and was associated with 60-day death (HR 0.86, P=0.029), 60-day death and rehospitalization (HR 0.90, P=0.01), and 180-day death (HR 0.91, P=0.049). These associations were attenuated with additional adjustment for loop diuretic dose (P>0.05). Chloride change correlated with weight change (rho 0.18, P=0.001), cystatin C change (rho -0.35, P<.001), and cumulative sodium excretion (rho -0.21, P<.001), but was not associated with any clinical outcomes (P>0.05 for all). In conclusion, serum Cl levels in AHF were inversely associated with loop diuretic response and were prognostic. However, changes in Cl levels were associated with parameters of decongestion, but not with clinical outcomes.
Objectives Our aim was to determine the feasibility and value of a protocol-driven approach to patients with cardiac resynchronization therapy (CRT) who did not exhibit a positive response long after ...implant. Background Up to one-third of patients with advanced heart failure do not exhibit a positive response to CRT. Methods A total of 75 consecutive ambulatory patients with persistent advanced heart failure symptoms and/or adverse reverse remodeling and CRT implanted >6 months underwent a comprehensive protocol-driven evaluation to determine the potential reasons for a suboptimal response. Recommendations were made to maximize the potential of CRT, and adverse events were documented. Results All patients (mean left ventricular LV ejection fraction 23 ± 9%, LV end-diastolic volume 275 ± 127 ml) underwent evaluation. Eighty-eight percent of patients had significantly better echocardiographic indexes of LV filling and LV ejection with optimal setting of their CRT compared with a temporary VVI back-up setting. Most patients had identifiable reasons for suboptimal response, including inadequate device settings (47%), suboptimal medical treatment (32%), arrhythmias (32%), inappropriate lead position (21%), or lack of baseline dyssynchrony (9%). Multidisciplinary recommendations led to changes in device settings and/or other therapy modifications in 74% of patients and were associated with fewer adverse events (13% vs. 50%, odds ratio: 0.2 95% confidence interval: 0.07 to 0.56, p = 0.002) compared with those in which no recommendation could be made. Conclusions Routine protocol-driven approach to evaluate ambulatory CRT patients who did not exhibit a positive response is feasible, and changes in device settings and/or other therapies after multidisciplinary evaluation may be associated with fewer adverse events.
Abstract Background Cardiac dysfunction influences candidate selection for kidney transplantation. There is a paucity of data regarding predictors of myocardial recovery following kidney ...transplantation and long-term outcomes. Objectives The purpose of this study was to identify the extent of reverse remodeling in our kidney transplant population and the predictors of such changes, and to assess outcomes in these patients. Methods We reviewed 232 patients who underwent kidney transplantation at the Cleveland Clinic from 2003 to 2013 and who had baseline and post-transplant echocardiograms; patients with simultaneous heart transplantation were excluded. Results Post-transplantation mean left ventricular ejection fraction (LVEF) improved in those with LV dysfunction (increased from 41% to 50%; p < 0.0001; n = 66). There was significant improvement in other parameters, including diastolic function, LV end-diastolic dimension, LV mass, and right ventricular systolic pressure. After adjusting for multiple clinical variables, increased hemoglobin following transplantation was associated with an improved LVEF (odds ratio: 1.50; 95% confidence interval CI: 1.07 to 2.14; p = 0.016) and reduced mortality (hazard ratio HR: 0.65; 95% CI: 0.49 to 0.87; p = 0.004). An improved LVEF ≥10% predicted survival independently of a pre-transplantation LVEF (HR: 0.46; 95% CI: 0.21 to 0.93; p = 0.031). Conclusions Kidney transplantation is associated with improved cardiac structure and function. A rise in post-transplantation hemoglobin was a significant factor associated with such changes, in addition to conferring a survival advantage.
Abstract Background Net fluid and weight loss are used ubiquitously to monitor diuretic response in acute decompensated heart failure research and patient care. However, the performance of these ...metrics has never been evaluated critically. The weight and volume of aqueous fluids such as urine should be correlated nearly perfectly and with very good agreement. As a result, significant discrepancy between fluid and weight loss during the treatment of acute decompensated heart failure would indicate measurement error in 1 or both of the parameters. Methods The correlation and agreement (Bland-Altman method) between diuretic-induced fluid and weight loss were examined in 3 acute decompensated heart failure trials and cohorts: (1) Diuretic Optimization Strategies Evaluation (DOSE) (n = 254); (2) Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) (n = 348); and (3) Penn (n = 486). Results The correlation between fluid and weight loss was modest (DOSE r = 0.55; ESCAPE r = 0.48; Penn r = 0.51; P < .001 for all), and the 95% limits of agreement were wide (DOSE −7.9 to 6.4 kg-L; ESCAPE −11.6 to 7.5 kg-L; Penn −14.5 to 11.3 kg-L). The median relative disagreement ranged from ±47.0% to 63.5%. A bias toward greater fluid than weight loss was found across populations (−0.74 to −2.1 kg-L, P ≤ .002). A consistent pattern of baseline characteristics or in-hospital treatment parameters that could identify patients at risk of discordant fluid and weight loss was not found. Conclusions Considerable discrepancy between fluid balance and weight loss is common in patients treated for acute decompensated heart failure. Awareness of the limitations inherent to these commonly used metrics and efforts to develop more reliable measures of diuresis are critical for both patient care and research in acute decompensated heart failure.
Background Interfering with angiogenesis is an effective, widely used approach to cancer therapy, but antiangiogenic therapies have been associated with important systemic cardiovascular toxicities ...such as hypertension, left ventricular dysfunction, heart failure, and myocardial ischemia and infarction. As the use of vascular endothelial growth factor signaling pathway (VSP) inhibitors broadens to include older patients and those with existing cardiovascular disease, the adverse effects are likely to be more frequent, and cardiologists will increasingly be enlisted to help oncologists manage patients who develop adverse cardiovascular effects. Methods The Cardiovascular Toxicities Panel of the National Cancer Institute reviewed the published literature and abstracts from major meetings, shared experience gained during clinical development of VSP inhibitors, and contributed extensive clinical experience in evaluating and treating patients with cancer with cardiovascular disease. This report was edited and approved by the National Cancer Institute Investigational Drug Steering Committee. It presents the panel's expert opinion on the current clinical use and future investigation for safer, more expansive use of these drugs. Results and Conclusions The panel recommends that physicians (1) conduct and document a formal risk assessment for existing cardiovascular disease and potential cardiovascular complications before VSP inhibitor treatment recognizing that preexisting hypertension and cardiovascular disease are common in patients with cancer, (2) actively monitor for blood pressure elevations and cardiac toxicity with more frequent assessments during the first treatment cycle, and (3) aggressively manage blood pressure elevations and early symptoms and signs of cardiac toxicity to prevent clinically limiting complications of VSP inhibitor therapy.
Galectin-3 plays an important role in fibroblast activation and fibrosis in animal models. Increased galectin-3 levels are associated with poor long-term survival in heart failure (HF). We examined ...the relation between plasma galectin-3 levels and myocardial indexes of systolic HF. We measured plasma galectin-3 in 133 subjects with chronic HF and 45 with advanced decompensated HF using echocardiographic and hemodynamic evaluations. In the chronic HF cohort, median plasma galectin-3 level was 13.9 ng/ml (interquartile range 12.1 to 16.9). Higher galectin-3 was associated with more advanced age (r = 0.22, p = 0.010), poor renal function (estimated glomerular filtration rate, r = −0.24, p = 0.007; cystatin C, r = 0.38, p <0.0001) and predicted all-cause mortality (hazard ratio 1.86, 95% confidence interval 1.36 to 2.54, p <0.001). In multivariate analysis, galectin-3 remained an independent predictor of all-cause mortality after adjusting for age, estimated glomerular filtration rate, left ventricular (LV) ejection fraction, and mitral early diastolic myocardial relaxation velocity at septal mitral annulus (hazard ratio 1.94, 95% confidence interval 1.30 to 2.91, p = 0.001). However, galectin-3 did not predict the combined end point of all-cause mortality, cardiac transplantation, or HF hospitalization (p >0.05). Furthermore, there were no relations between galectin-3 and LV end-diastolic volume index (r = −0.05, p = 0.61), LV ejection fraction (r = 0.10, p = 0.25), or LV diastolic function (mitral early diastolic myocardial relaxation velocity at septal mitral annulus, r = 0.06, p = 0.52; left atrial volume index, r = 0.08, p = 0.41). In the advanced decompensated HF cohort, we did not observe any relation between galectin-3 and echocardiographic or hemodynamic indexes. In conclusion, high plasma galectin-3 levels were associated with renal insufficiency and poorer survival in patients with chronic systolic HF. However, we did not observe a relation between galectin-3 and echocardiographic or hemodynamic indexes.
Objectives The goal of this study was to examine the relative impact of QRS morphology and duration in echocardiographic responses to cardiac resynchronization therapy (CRT) and clinical outcomes. ...Background At least one-third of all patients treated with CRT fail to derive benefit. Patients without left bundle branch block (LBBB) or patients with smaller QRS duration (QRSd) respond less or not at all to CRT. Methods We retrospectively assessed baseline characteristics, clinical and echocardiographic response , and outcomes of all patients who received CRT at our institution between December 2003 and July 2007. Patients were stratified into 4 groups according to their baseline QRS morphology and QRSd. Results A total of 496 patients were included in the study; 216 (43.5%) had LBBB and a QRSd ≥150 ms, 85 (17.1%) had LBBB and QRSd <150 ms, 92 (18.5%) had non-LBBB and a QRSd ≥150 ms, and 103 (20.8%) had non-LBBB and QRSd <150 ms. Echocardiographic response (change in ejection fraction) was better in patients with LBBB and QRSd ≥150 ms (12 ± 12%) than in those with LBBB and QRSd <150 ms (8 ± 10%), non-LBBB and QRSd ≥150 ms (5 ± 9%), and non-LBBB and QRSd <150 ms (3 ± 11%) (p < 0.0001). In a multivariate stepwise model with change in ejection fraction as the dependent variable, the presented classification was the most important independent variable (p = 0.0003). Long-term survival was better in LBBB patients with QRSd ≥150 ms (p = 0.02), but this difference was not significant after adjustment for other baseline characteristics (p = 0.15). Conclusions QRS morphology is a more important baseline electrocardiographic determinant of CRT response than QRSd.
Iron deficiency is prevalent in heart failure with reduced ejection fraction and relates to symptomatic status, readmission, and all-cause mortality. The relation between iron status and response to ...cardiac resynchronization therapy (CRT) remains insufficiently elucidated. This study assesses the impact of iron deficiency on clinical response and reverse cardiac remodeling and outcome after CRT. Baseline characteristics, change in New York Heart Association functional class, reverse cardiac remodeling on echocardiography, and clinical outcome (i.e., all-cause mortality and heart failure readmissions) were retrospectively evaluated in consecutive CRT patients who had full iron status and complete blood count available at implantation, implanted at a single tertiary care center with identical dedicated multidisciplinary CRT follow-up from October 2008 to August 2015. A total of 541 patients were included with mean follow-up of 38 ± 22 months. Prevalence of iron deficiency was 56% at implantation. Patients with iron deficiency exhibited less symptomatic improvement 6 months after implantation (p value <0.001). In addition, both the decrease in left ventricular end-diastolic diameter (−3.1 vs −6.2 mm; p value = 0.011) and improvement in ejection fraction (+11% vs +15%, p value = 0.001) were significantly lower in patients with iron deficiency. Iron deficiency was significantly associated with an increased risk for heart failure admission or all-cause mortality (adjusted hazard ratio 1.718, 95% confidence interval 1.178 to 2.506), irrespectively of the presence of anemia (Hemoglobin <12 g/dl in women and <13 g/dl in men). In conclusion, iron deficiency is prevalent and affects both clinical response and reverse cardiac remodeling after CRT implantation. Moreover, it is a powerful predictor of adverse clinical outcomes in CRT.
Abstract Diabetic cardiomyopathy is the presence of myocardial dysfunction in the absence of coronary artery disease and hypertension. Hyperglycemia seems to be central to the pathogenesis of ...diabetic cardiomyopathy and to trigger a series of maladaptive stimuli that result in myocardial fibrosis and collagen deposition. These processes are thought to be responsible for altered myocardial relaxation characteristics and manifest as diastolic dysfunction on imaging. Sophisticated imaging technologies also have permitted the detection of subtle systolic dysfunction in the diabetic myocardium. In the early stages, these changes appear reversible with tight metabolic control, but as the pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients independently of common comorbidities, such as coronary artery disease and hypertension. Therapeutic agents specifically targeting processes that lead to these pathophysiologic changes are in the early stages of development. Although glycemic control and early administration of neurohormonal antagonists remain the cornerstones of therapeutic approaches, newer treatment targets are currently being explored.
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