Abstract Higher red cell distribution width (RDW) has been associated with poor prognosis in patients with heart failure (HF). RDW is also closely associated with iron deficiency. However, the ...mechanism underlying this association is unclear. The relationship between left ventricular end-diastolic pressure (LVEDP) and RDW has not been studied, especially in those without HF. We examined the relationship between LVEDP and RDW in 1,084 consecutive stable patients who underwent elective coronary angiography. We observed that 38% had high LVEDP (>16mmHg) and 29% had history of HF. The median RDW was 13.4%, which was higher with increasing LVEDP (p<0.0001) and significantly higher among patients with HF (p<0.0001). Baseline RDW were independently associated with high LVEDP even after multivariable logistic regression analysis (adjusted odds ratio OR per unit change: 1.14, 95% CI: 1.0-1.29, p=0.044). Interestingly, result were stronger in non-HF cohort (adjusted OR per unit change: 1.37, 95% CI: 1.13-1.67, p=0.001). In addition, elevated (third versus first tertiles) RDW levels were independently a predictor of high LVEDP and were associated with a 4.8-fold increased 5-year mortality risk (adjusted hazard ratio: 4.11, 95% CI: 2.12-7.96, p<0.0001), even with the addition of B-type natriuretic peptide to the model (adjusted OR for LVEDP: 2.25, 95% CI: 1.0-5.05, p=0.05; adjusted HR for mortality: 3.79, 95% CI: 1.033-13.89, p=0.044, respectively). In conclusion, high RDW levels were observed in patients with or without HF and independently associated with high LVEDP and with mortality.
Abstract Background Cardiac troponin (cTn) levels offer prognostic information for patients with heart failure. Highly sensitive assays detect levels of cTn much lower than the 99th percentile of ...standard cTn assays. We hypothesize that cardiac troponin levels measured by a high-sensitivity assay provide better prognostic value compared with cTn levels measured by a standard assay in patients with chronic heart failure. Methods We measured high-sensitivity cTnT (hs-cTnT) and standard cardiac troponin I (cTnI) levels, as well as amino-terminal pro B-type natriuretic peptide (NT-proBNP) in 504 sequential stable patients with a history of heart failure who underwent elective coronary angiography, without acute coronary syndrome, and with 5-year follow-up of all-cause mortality. Results The median hs-cTnT level was 21.2 (interquartile range 12.3-40.9) ng/L and 170 subjects died over 5 years. In a head-to-head overall comparison, hs-cTnT provided increased prognostic utility compared with cTnI (area under the curve AUC 66.1% and AUC 69.4%, respectively, P = .03; 9.0% integrated discrimination improvement, P < .001; and 13.6% event-specific reclassification, P < .001), and was independent of NT-proBNP and renal function. Even within the subset of patients where cTn levels by both assays were above the limit of quantification, higher hs-cTnT is associated with a 2-fold increase in 5-year mortality risk after adjusting for traditional risk factors (tertile 1 vs 3: hazard ratio 95% confidence interval 2.0 1.3-3.2; P = .0002). Conclusion Cardiac troponin can be detected by the high-sensitivity assay in more patients with chronic heart failure than the standard assay, and may yield independent and better prognostic accuracy for mortality prediction than standard assay.
Highlights • Binding of albumin to diuretics are key to delivery to the nephron, and low albumin levels diminish intravascular oncotic pressures necessary to maintain intravascular volume for ...effective diuresis. • Based on prospectively collected data from two acute heart failure clinical trials (DOSE-AHF and ROSE-AHF), this may not be the case in acute heart failure populations largely free of nephrotic syndrome or cirrhosis. • Our data from two well characterized cohorts of patients with acute heart failure suggest that serum albumin may not be a helpful tool to guide decongestion strategies or determine effectiveness of therapy.
Abstract Background Patients with moderate-to-severe chronic kidney disease (CKD) are poorly represented in clinical trials of cardiac resynchronization therapy (CRT). Objectives This study sought to ...assess the real-world comparative effectiveness of CRT with defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) alone in CRT-eligible patients with moderate-to-severe CKD. Methods We conducted an inverse probability-weighted analysis of 10,946 CRT-eligible patients (ejection fraction <35%, QRS >120 ms, New York Heart Association functional class III/IV) with stage 3 to 5 CKD in the National Cardiovascular Data Registry (NCDR) ICD Registry, comparing outcomes between patients who received CRT-D (n = 9,525) versus ICD only (n = 1,421). Outcomes were obtained via Medicare claims and censored at 3 years. The primary endpoint of heart failure (HF) hospitalization or death and the secondary endpoint of death were assessed with Cox proportional hazards models. HF hospitalization, device explant, and progression to end-stage renal disease were assessed using Fine-Gray models. Results After risk adjustment, CRT-D use was associated with a reduction in HF hospitalization or death (hazard ratio HR: 0.84; 95% confidence interval CI: 0.78 to 0.91; p < 0.0001), death (HR: 0.85; 95% CI: 0.77 to 0.93; p < 0.0004), and HF hospitalization alone (subdistribution HR: 0.84; 95% CI: 0.76 to 0.93; p < 0.009). Subgroup analyses suggested that CRT was associated with a reduced risk of HF hospitalization and death across CKD classes. The incidence of in-hospital, short-term, and mid-term device-related complications did not vary across CKD stages. Conclusions In a nationally representative population of HF and CRT-eligible patients, use of CRT-D was associated with a significantly lower risk of the composite endpoint of HF hospitalization or death among patients with moderate-to-severe CKD in the setting of acceptable complication rates.
When stratifying thromboembolic risk to patients with atrial fibrillation (AF), left atrial appendage (LAA) thrombus is currently the only echocardiographic index that absolutely contraindicates ...cardioversion. The aim of this study was to identify the predictors of LAA "sludge" and its impact on subsequent thromboembolism and survival in patients with AF.
A total of 340 patients (mean age, 66 ± 12 years; 75% men) who underwent transesophageal echocardiography to exclude LAA thrombus before electrical cardioversion or radiofrequency pulmonary vein isolation) for AF were retrospectively studied. LAA sludge was defined as a dynamic, viscid, layered echodensity without a discrete mass, visualized throughout the cardiac cycle. Follow-up was obtained after a mean of 6.7 ± 3.7 years, and patients were analyzed according to LAA thrombus (n = 62 18%), sludge (n = 47 14%), or spontaneous echocardiographic contrast (n = 84 25%). Patients without these transesophageal echocardiographic characteristics served as controls (n = 147 43%).
LAA sludge was independently predicted by enlarged left atrial area (odds ratio, 4.54; 95% confidence interval CI, 2.38-8.67; P < .001), reduced LAA emptying velocity (odds ratio, 12.7; 95% CI, 6.11-26.44; P < .001), and reduced left ventricular ejection fraction (odds ratio, 2.11; 95% CI, 1.03-4.32; P < .001). Thromboembolic event and all-cause mortality rates in patients with sludge were 23% and 57%, respectively. Multiple logistic regression analyses identified the presence of LAA sludge to be independently associated with thromboembolic complications (adjusted hazard ratio, 3.43; 95% CI, 1.42-8.28; P = .006) and all-cause mortality (adjusted hazard ratio, 2.02; 95% CI, 1.22-3.36; P = .007).
Sludge within the LAA is independently associated with subsequent thromboembolic events and all-cause mortality in patients with AF.
Elevated Intra-Abdominal Pressure in Acute Decompensated Heart Failure: A Potential Contributor to Worsening Renal Function? Wilfried Mullens, Zuheir Abrahams, Hadi N. Skouri, Gary S. Francis, David ...O. Taylor, Randall C. Starling, Emil Paganini, W. H. Wilson Tang We measured intra-abdominal pressure (IAP) using a simple transvesical technique in 40 consecutive patients admitted for acute decompensated heart failure without overt abdominal symptoms. Among them, 60% had elevated IAP (≥8 mm Hg). Elevated IAP was directly associated with worse renal function, and intensive medical therapy resulted in improvement in both hemodynamic measures and IAP. However, reduction in IAP is better correlated with improvement in renal function than any hemodynamic variable, suggesting a potential contribution of elevated IAP in the pathophysiology of the cardiorenal syndrome.
Abstract Background Among various cardiac autoantibodies (AAbs), those recognizing the β1 -adrenergic receptor (β1 AR) demonstrate agonist-like effects and induce myocardial damage that can be ...reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction LVEF ≤0.40; <6 months). The presence of IgG and IgG3-β1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.
Patients with non-left bundle branch block (LBBB) morphologies are thought to derive less benefit from cardiac resynchronization therapy (CRT) than those with LBBB. However, some patients do exhibit ...improvement. The characteristics associated with a response to CRT in patients with non-LBBB morphologies are unknown. Clinical, electrocardiographic, and echocardiographic data were collected from 850 consecutive patients presenting for a new CRT device. For inclusion, all patients had a left ventricular ejection fraction of ≤35%, a QRS duration of ≥120 ms, and baseline and follow-up echocardiograms available. Patients with a paced rhythm or LBBB were excluded. The response was defined as an absolute decrease in left ventricular end-systolic volume of ≥10% from baseline. Multivariate models were constructed to identify variables significantly associated with the response and long-term outcomes. A total of 99 patients met the inclusion criteria. Of these 99 patients, 22 had right bundle branch block and 77 had nonspecific intraventricular conduction delay; 52.5% met the criteria for response. On multivariate analysis, the QRS duration was the only variable significantly associated with the response (odds ratio per 10-ms increase 1.23, 95% confidence interval 1.01 to 1.52, p = 0.048). During a mean follow-up of 5.4 ± 0.9 years, 65 patients died or underwent heart transplant or left ventricular assist device placement. On multivariate analysis, the QRS duration was inversely associated with poor long-term outcomes (hazard ratio per 10-ms increase 0.79, 95% confidence interval 0.66 to 0.94, p = 0.005). In patients with advanced heart failure and non-LBBB morphologies, a wider baseline QRS duration is an important determinant of enhanced reverse ventricular remodeling and improved long-term outcomes after CRT.
Abstract Background Inflammation is associated with progression of chronic heart failure (HF). Few data exist on high-sensitivity C-reactive protein (hsCRP) levels and their importance in acute HF. ...Methods and Results In this biomarker substudy of the ASCEND-HF trial, we measured hsCRP levels at admission (n = 794), 48–72 hours (n = 677), and 30 days (n = 581) and evaluated their association with outcomes. Levels of hsCRP were considerably elevated at admission (median 12.6 mg/L, interquartile range IQR 5.23–30.5) and 48–72 hours (median 11.0 mg/L, IQR 4.87–29.9) and declined only at 30 days (median 4.7 mg/L, IQR 1.83–13.1). Admission hsCRP was not associated with dyspnea improvement at 6 hours (74.1%) and 24 hours (86.2%), in-hospital death or worsening HF (n = 37; 4.7%), 30-day mortality or HF readmission (death: n = 25 3.2%; combined death and HF readmission: n = 95 12.0%), or 180-day mortality (n = 96; 12.1%). Hospital stay (median 5 days, IQR 3–7) was longer among patients with higher admission hsCRP levels (0.57 days per log2 -hsCRP in adjusted models; 95% confidence interval CI 0.33–0.81; P < .001). Levels of hsCRP at 48–72 hours did not predict 30-day mortality or HF readmission and were only marginally associated with 180-day mortality. However, higher hsCRP at 30 days among survivors was associated with higher 180-day mortality in models including admission hsCRP (adjusted hazard ratio HR per log2 -hsCRP: 1.23; 95% CI 1.04–1.45; P = .016). Patients with an hsCRP increase at day 30, defined as >10% increase over baseline value, had higher 180-day mortality risk compared with those with unchanged or decreased 30-day hsCRP (HR 2.29, 95% CI 1.16–4.52; P = .017). Conclusions Levels of hsCRP are elevated among patients with acute HF. Increasing levels at 30 days after discharge are associated with higher 180-day mortality.
MPO can use plasma levels of thiocyanate as a cosubstrate to generate cyanate and catalyze protein carbamylation. Because plasma levels of thiocyanate are heightened in smokers and in exposure to ...second-hand or work-place smoke, this pathway has been linked to heightened cardiovascular disease risks in subjects who smoke (2). ...it is important to point out that beyond carbamyllysine as a measurement of extent of carbamylation, other residues (e.g., cysteine) or nucleophilic groups (e.g., anionic lipids that contain reactive amine moieties) can also be targets of carbamylation. Because carbamylation is a conserved chemical pathway that links inflammation and uremia, the findings reported by Holy et al.
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