Search

Elevation of resting high-sensitivity troponin (hs-Tn) holds prognostic value in heart failure (HF), but its pathophysiological meaning is unclear. We aimed to investigate hs-Tn elevation after maximal exercise in patients with systolic HF and its neurohormonal and hemodynamic correlates: 30 patients diagnosed with systolic HF (left ventricular ejection fraction 32 ± 8%, mean ± SD), on guideline-directed medical therapy and not recognized inducible ischemia, underwent maximal cardiopulmonary stress test, with assay of plasma N-terminal proB-type natriuretic peptide (NT-proBNP), norepinephrine (NE), and hs-TnT (hs-TnT) at baseline, peak, and 1 and 4 hours after exercise. Cardiac output (CO) was measured during effort, with a rebreathing technique. The natural logarithm of the ratio between percentage (%) increase in CO and NT-proBNP (ln[CO%/NT-proBNP% increase]) was evaluated, as a noninvasive estimate of Frank-Starling adaptation to effort, with NT-proBNP variation considered as a surrogate of end-diastolic left ventricular pressure variation. Hs-TnT increased during exercise with a 4-hour peak (p = 0.001); 10 patients had hs-TnT increase >20%. Patients with Hs-TnT increase >20% were more symptomatic at rest (p = 0.039) and showed greater NE at peak exercise (p = 0.003) and less ln[CO%/NT-proBNP% increase] (p = 0.034). A lower ln[CO%/NT-proBNP% increase] correlated with greater NE at peak exercise (r = -0.430, p = 0.018). In conclusion, acute troponin elevation after maximal exercise was detected in 1/3 of this series. The association of troponin release with NE, CO, and NT-proBNP changes after effort suggests a pathophysiological link among transient hemodynamic overload, adrenergic activation, and myocardial cell damage, likely identifying a clinical subset at greater risk for HF progression. [ABSTRACT FROM AUTHOR]

Heart failure (HF) with reduced left ventricular (LV) ejection fraction (HFrEF) is regarded as an independent risk factor for poor outcomes after coronary artery bypass grafting (CABG). However, the impact of HF with preserved EF (HFpEF) still has been unclear. We identified 1,877 patients who received isolated CABG of 15,939 patients who underwent first coronary revascularization enrolled in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) Registry Cohort-2. Of them, 1,489 patients had normal LV function (LVEF >50% without a history of HF; Normal group), 236 had HFrEF (LVEF =50% with HF), and 152 had HFpEF (LVEF >50% with HF). Preoperative LVEF was the lowest in the HFrEF group (62 ± 12%, 36 ± 9%, and 61 ± 7% for the Normal, HFrEF, and HFpEF groups, respectively; p <0.001). Unadjusted 30-day mortality rate was the highest in the HFrEF group (0.5%, 3.0%, and 0.7%; p = 0.003). However, cumulative incidences of all-cause death at 5-year was the highest in the HFpEF group (14%, 27%, and 32%, respectively; p <0.001). After adjusting confounders, the risk of all-cause death in the HFpEF group was greater than the Normal group (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.02 to 1.97; p = 0.04). The risk of all-cause death was not different between the HFpEF and the HFrEF groups (HR 0.88; 95% CI 0.61 to 1.29; p = 0.52). In addition, the risks of cardiac death and sudden death in the HFpEF group were greater than the Normal group (HR 2.14, 95% CI 1.32 to 3.49, p = 0.002; and HR 3.60, 95% CI 1.55 to 8.36, p = 0.003, respectively), and the risks of those end points were not different between the HFrEF and the HFpEF groups. Despite low 30-day mortality rate after CABG in patients with HFpEF, HFpEF was associated with high risks of long-term death and cardiovascular events. Patients with HFpEF, as well as HFrEF, should be carefully operated and followed up. [ABSTRACT FROM AUTHOR]

Medication nonadherence is a common precipitant of heart failure (HF) hospitalization and is associated with poor outcomes. Recent analyses of national data focus on long-term medication adherence. Little is known about adherence of patients with HF immediately after hospitalization. Hospitalized patients with HF were identified from the Atherosclerosis Risk in Communities study. Atherosclerosis Risk in Communities data were linked to Medicare inpatient and part D claims from 2006 to 2009. Inclusion criteria were a chart-adjudicated diagnosis of acute decompensated or chronic HF; documentation of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), ß blocker (BB), or diuretic prescription at discharge; and Medicare part D coverage. Proportion of ambulatory days covered was calculated for up to twelve 30-day periods after discharge. Adherence was defined as =80% proportion of ambulatory days covered. We identified 402 participants with Medicare part D: mean age 75, 30% men, and 41% black. Adherence at 1, 3, and 12 months was 70%, 61%, and 53% for ACEI/ARB; 76%, 66%, and 62% for BB; and 75%, 68%, and 59% for diuretic. Adherence to any single drug class was positively correlated with being adherent to other classes. Adherence varied by geographic site/race for ACEI/ARB and BB but not diuretics. In conclusion, despite having part D coverage, medication adherence after discharge for all 3 medication classes decreases over 2 to 4 months after discharge, followed by a plateau over the subsequent year. Interventions should focus on early and sustained adherence. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) modify outcome in patients with heart failure (HF). We aimed to analyze the risk for death, HF alone, combined end point HF/death, and ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with mild HF without DM and in those with DM, further stratified by the presence of insulin treatment. We determined whether cardiac resynchronization therapy with defibrillator (CRT-D) versus implantable cardioverter defibrillator improves clinical outcomes in these 3 subgroups. Cox proportional hazards regression models were used to analyze 1,278 patients with left bundle branch block in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy trial. Treatment with CRT-D versus implantable cardioverter defibrillator was associated with 76% risk reduction in all-cause mortality (hazard ratio 0.24; 95% confidence interval 0.08 to 0.74, p = 0.012) in subgroup of diabetic patients treated with insulin only (interaction p = 0.043). Significant risk reduction in HF alone, HF/death, and the VT/VF after CRT-D was observed across investigated groups and similar left ventricular reverse remodeling to CRT-D. In conclusion, patients with mild HF with DM treated with insulin derive significant risk reduction in mortality, in HF, and VT/VF after implantation of CRT-D. Diabetic patients not receiving insulin benefit from CRT-D by reduction of HF events. [ABSTRACT FROM AUTHOR]

Heart failure (HF) hospitalization length of stay (LOS) has been associated with the risk of subsequent readmission and mortality. We identified 19,927 hospitalized patients with HF who were discharged alive from 2008 to 2011 from 3 Kaiser Permanente regions. In adjusted Cox models using LOS 3 to 4 days as the reference category, shorter LOS was not significantly associated with hospital readmissions. LOS of 5 to 10 days was associated with 17% greater risk of readmission within 30 days (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.07 to 1.28) and 9% greater risk within 1 year (HR 1.09, 95% CI 1.03 to 1.15). LOS of 11 to 29 days was associated with increased readmission risk of 52% at 30 days (HR 1.52, 95% CI 1.30 to 1.76) and 25% at 1 year (HR 1.25, 95% CI 1.16 to 1.35). Mortality risk within 30 days among those with LOS of 1 day was 47% lower (HR 0.53, 95% CI 0.43 to 0.65) and 32% lower at 1 year (HR 0.68, 95% CI 0.62 to 0.74). LOS of 2 days was associated with lower mortality risk of 17% (HR 0.83, 95% CI 0.76 to 0.90) at 1 year. At LOS 5 to 10 days, 30-day and 1-year risk of mortality was increased by 52% (HR 1.52, 95% CI 1.30 to 1.76) and 25% (HR 1.25, 95% CI 1.16 to 1.35), respectively. LOS of 11 to 29 days was associated with 171% higher mortality risk at 30 days (HR 2.71, 95% CI 2.19 to 3.35) and 73% at 1 year (HR 1.73, 95% CI 1.53 to 1.97). Longer LOS during the index HF hospitalization was associated with readmission and mortality within 30 days and 1 year independent of co-morbidities and cardiovascular risk factors. These results suggest that LOS may be a proxy for the severity of HF during the index hospitalization. [ABSTRACT FROM AUTHOR]

Patients with chronic heart failure (CHF) at risk of sudden cardiac death (SCD) are often treated with implantable cardiac defibrillators (ICDs). However, current criteria for device use that is based largely on left ventricular ejection fraction (LVEF) lead to many patients receiving ICDs that never deliver therapy. It is of clinical significance to identify patients who do not require ICDs. Although cardiac I-123 meta-iodobenzylguanidine (MIBG) imaging provides prognostic information about CHF, whether it can identify patients with CHF who do not require an ICD remains unclear. We studied 81 patients with CHF and LVEF <35%, assessed by cardiac MIBG imaging at enrollment. The heart-to-mediastinal ratio (H/M) in delayed images and washout rates were divided into 6 grades from 0 to 5, according to the degree of deviation from control values. The study patients were classified into 3 groups: low (1 to 4), intermediate (5 to 7), and high (8 to 10), according to the MIBG scores defined as the sum of the H/M and washout rate scores. Sixteen patients died of SCD during a follow-up period. Patients with low MIBG score had a significantly lower risk of SCD than those with intermediate and high scores (low [n = 19], 0%; intermediate [n = 37], 19%; high [n = 25], 36%; p = 0.001). The positive predictive value of low MIBG score for identifying patients without SCD was 100%. In conclusion, the MIBG score can identify patients with CHF and LVEF <35% who have low risk of developing SCD. [ABSTRACT FROM AUTHOR]

Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5 ± 12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level ≥5.00 μU/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p = 0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p = 0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, p <0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p = 0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation. [ABSTRACT FROM AUTHOR]

Despite important progress in recent decades, mortality remains high for patients with chronic heart failure. Risk stratification may be refined by the use of biomarkers for different pathophysiological processes that established mortality risk factors do not directly reflect. Biomarkers that are currently available can provide information about at least 7 pathobiological processes operative in HF, help to identify the specific processes involved in individual patients, and aid in constructing management plans. However, the additional prognostic information gained by any biomarker over a clinical risk model plus other biomarkers needs to be determined with adequate statistical tools. A major problem in selecting a biomarker profile is the proportional increase in economic burden; thus, the addition of any biomarker to a profile should be justified by adequate discrimination, calibration, reclassification, and likelihood analyses. Three studies that implemented such rigorous analyses have assessed a multimarker panel in chronic heart failure that incorporated the biomarker ST2: the Penn HF Study, the Barcelona Study, and the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) biomarker substudy. In all 3 studies, a multimarker panel appeared to provide significant information over conventional risk stratification. The latter 2 reports proposed that ST2 might be superior to natriuretic peptides. The Barcelona Bio-HF calculator (www.bcnbiohfcalculator.cat) is a novel risk calculator that considers clinical variables, treatment, and biomarkers (i.e., N terminal pro-brain natriuretic peptide [NT-proBNP], ST2, and high sensitivity troponin T [hsTnT]). The optimal panel of markers, the change in these markers over time, and how these changes might help guide therapeutic interventions remain to be defined. [ABSTRACT FROM AUTHOR]

Among patients with chronic heart failure (HF), it is known that soluble concentrations of the interleukin receptor family member ST2 (sST2) are prognostic for adverse outcome, including risk for progression of HF and death. Considerably less was known about the merits of serial testing of sST2 and whether such testing provides incremental information beyond single measurements; additionally, the influence of HF therapies on sST2 concentrations and whether sST2 values predicted benefit of therapy changes remained unclear. Recently, several studies indicate that serial testing for sST2 increases the prognostic information gained compared with a single measurement. When measured in patients with chronic HF, concentrations of sST2 appear to predict worsening left ventricular remodeling, and serial measurements of sST2 appear particularly useful for predicting HF events, such as worsening HF and risk for either hospitalization or death from HF. Values for sST2 are lower in those treated with several HF therapies; in turn, sST2 concentrations may predict benefit from specific HF therapy changes. Using an upper reference limit of 35 ng/ml, serial testing for sST2 in chronic HF thus appears useful. The promising role of sST2 for serial chronic HF therapy monitoring will be discussed. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensitymatched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m², those on no-ACEi/ ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m² and with neutral effect in those with GFR <30 ml/min/1.73 m². [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) has a symptomatic and survival benefit for patients with heart failure (HF), but the percentage of nonresponders remains relatively high. The aims of this study were to assess the clinical significance of baseline tricuspid regurgitation (TR) or worsening TR after implantation of a CRT device on the response to therapy. This is a multicenter retrospective analysis of prospectively collected databases that includes 689 consecutive patients who underwent implantation of CRT. The patients were divided into groups according to baseline TR grade and according to worsening TR within 15 months after device implantation. Outcome was assessed by clinical and echocardiographic response within 15 months and by estimated survival for a median interquartile range follow-up time of 3.3 years (1.6, 4.6). TR worsening after CRT implantation was documented in 104 patients (15%). These patients had worse clinical and echocardiographic response to CRT, but worsening of TR was not a significant predictor of mortality (p = 0.17). According to baseline echocardiogram, 620 patients (90%) had some degree of TR before CRT implant. Baseline TR was an independent predictor of worse survival (p <0.001), although these patients had significantly better clinical and echocardiographic response compared with patients without TR. In conclusion, worsening of TR after CRT implantation is a predictor of worse clinical and echocardiographic response but was not significantly associated with increased mortality. Baseline TR is associated with reduced survival despite better clinical and echocardiographic response after CRT implantation. [ABSTRACT FROM AUTHOR]

A spiral phenomenon is sometimes noted in the plots of CO2 output (VCO2) against O2 uptake (VO2) measured during cardiopulmonary exercise testing (CPX) in patients with heart failure with oscillatory breathing. However, few data are available that elucidate the clinical significance of this phenomenon. Our group studied the prevalence of this phenomenon and its relation to cardiac and cardiopulmonary function. Of 2,263 cardiac patients who underwent CPX, 126 patients with a clear pattern of oscillatory breathing were identified. Cardiopulmonary indexes were compared between patients who showed the spiral phenomenon (n = 49) and those who did not (n = 77). The amplitudes of VO2 and VCO2 oscillations were greater and the phase difference between VO2 and VCO2 oscillations was longer in the patients with the spiral phenomenon than in those without it. Patients with the spiral phenomenon also had a lower left ventricular ejection fraction (43.4 ± 21.4% vs 57.1 ± 16.8%, p <0.001) and a higher level of brain natriuretic peptide (637.2 ± 698.3 vs 228.3 ± 351.4 pg/ml, p = 0.002). The peak VO2 was lower (14.5 ± 5.6 vs 18.1 ± 6.3, p = 0.002), the slope of the increase in ventilation versus VCO2 was higher (39.8 ± 9.5 vs 33.6 ± 6.8, p <0.001), and end-tidal PCO2 both at rest and at peak exercise was lower in the patients with the spiral phenomenon than in those without it. In conclusion, the spiral phenomenon in the VCO2-versus-VO2 plot arising from the phase difference between VCO2 and VO2 oscillations reflects more advanced cardiopulmonary dysfunction in cardiac patients with oscillatory breathing. [ABSTRACT FROM AUTHOR]

Physician practice patterns in the management of hospitalized acute decompensated heart failure (ADHF) patients may vary by specialty; comparative practice patterns in ADHF management and clinical outcomes as a function of provider type have not been well reported. We studied a total of 496 patients discharged with the principal diagnosis of ADHF to analyze practice patterns among 3 provider types (cardiologists, hospitalists, and nonhospitalists). We examined outcomes of death and rehospitalization for HF and adherence to the Joint Commission HF performance core measures. Cardiologists had the highest adherence in all 4 HF core measures compared with hospitalists and nonhospitalists. At 6 months, 6.0% of the patients cared by cardiologists died compared with 10.9% and 11.4% cared by hospitalist and nonhospitalists (p = 0.12). Patients cared for by cardiologists had a significantly lower 6-month ADHF readmission rate (16.2%) compared with hospitalists (40.1%) and nonhospitalists (34.9%, p <0.001). In multivariate analysis, both hospitalist and nonhospitalist provider types were an independent predictor for 6-month ADHF-related readmission (hospitalists vs cardiologists, hazard ratioadjusted 3.01; 95% confidence interval 1.84 to 4.89, p <0.001; and nonhospitalists vs cardiologists, hazard ratioadjusted 2.07; 95% confidence interval 1.24 to 3.46, p = 0.005). In conclusion, cardiologist-delivered ADHF care is associated with greater adherence to HF core measures and with significantly lower rates of adverse outcome compared with noncardiologists. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the heterogeneity of the association of a preserved or reduced ejection fraction (EF) with the increased risk of outcomes among patients with acute heart failure syndromes. Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry in Japan, 4,720 patients were evaluated to investigate the association of EF and clinical features or co-morbidities with all-cause mortality after admission. The median follow-up period after admission was 519 (388 to 781) days. The all-causemortality rate did not differ between the reduced EF and preserved EF groups (24.9% and 24.5%, respectively). To evaluate the heterogeneity of the influence of a preserved or reduced EF on all-cause mortality, subgroup analyses were performed. As a result, there were significant interactions in the association of a preserved or reduced EF with all-cause mortality when the patients were stratified by an ischemic cause, a hypertensive cause, previous hospitalization for heart failure, diabetes mellitus, and anemia. The influence of a nonischemic cause, a hypertensive cause, or new-onset heart failure on the risk of all-cause mortality was significantly greater in patients with preserved EF than in those with reduced EF. In contrast, the influence of diabetes mellitus or anemia on the risk of all-cause mortality was significantly greater in patients with reduced EF than in those with preserved EF. In conclusion, the present analysis demonstrated that the association of a preserved or reduced EF with the clinical outcome differs markedly in relation to the clinical features or co-morbidities of these patients. [ABSTRACT FROM AUTHOR]

We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) £40%, with specific focus on gender, race, and renal function based interactions. In 3,955 of 4,133 patients (96%) with baseline sUA data, clinical characteristics and outcomes were compared across sUA quartiles. The primary end points were all-cause mortality and a composite of cardiovascular mortality or heart failure hospitalization. Interaction analyses were performed for gender, race, and baseline renal function. Median follow-up was 9.9 months. Mean sUA was 9.1 ± 2.8 mg/dl and was higher in men than in women (9.3 ± 2.7 vs 8.7 ± 3.0 mg/dl, p <0.001) and in blacks than in whites (10.0 ± 2.7 vs 9.0 ± 2.8 mg/dl, p <0.001). Higher sUA was associated with lower systolic blood pressure and EF, higher natriuretic peptides, and more impaired renal function. After accounting for 24 baseline covariates, in patients with enrollment estimated glomerular filtration rate ≥30 ml/min/1.73 m2, sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p <0.001) and the composite end point (hazard ratio 1.44,95% confidence interval 1.26 to 1.64, p <0.001). However, in patients with estimated glomerular filtration rate <30 ml/min/1.73 m2, sUA was not related with either end point (both p >0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction. [ABSTRACT FROM AUTHOR]

In 2006, there were >1 million hospital admissions for heart failure (HF), and the estimated cost to the United States in 2009 was >$37.2 billion. Better models to target aggressive therapy to patients at the highest risk for readmission are clearly needed. We studied 3,413 consecutive admissions for HF based on discharge diagnosis codes from October 2007 to August 2011 from a single academic center. We randomly generated derivation and validation sets in a 3:1 ratio. We used generalized estimating equations to develop our models, accounting for repeated hospitalizations and the Hosmer-Lemeshow test to examine model calibration. The 30-day readmission rate was 24.2% in the derivation set. Of 25 candidate variables, the best fitting model included creatinine, troponin, hematocrit, and hyponatremia at discharge; race; zip code of residence; discharge hour; and number of hospitalizations in the previous year. Insignificant variables included intravenous diuretic use on day of discharge, discharge service, diabetes, atrial fibrillation, age, and gender. The risk of 30-day readmission increased with increasing decile of predicted risk in both the validation and derivation cohorts. The area under the receiver operating characteristic curve for the model was 0.69 in the derivation set and 0.66 in the validation set. In conclusion, we derived and validated a simple model relating discharge-specific characteristics at risk of 30-day readmission. Application of this approach may facilitate targeted intervention to reduce the burden of rehospitalization in patients with HF, but our results suggest that the best readmission models may require incorporation of both clinical and local system factors for optimal prediction. [ABSTRACT FROM AUTHOR]

Postpericardiotomy syndrome (PPS) may be associated with tamponade and pericardial constriction that may require procedural intervention. The aim of this study was to identify clinical features associated with adverse events requiring procedural intervention in patients with PPS. A total of 239 patients who developed PPS after cardiac surgery were monitored for 12 months. PPS was diagnosed if 2 of the 5 following findings were present: fever without infection, pleuritic pain, friction rub, pleural effusion, and pericardial effusion (<60 days after surgery). The primary end point was the development of pericardial effusion or pericardial constriction requiring procedural intervention. Among 239 patients with PPS, 75 (31%) required procedural intervention. In a univariate analysis, the odds of a procedural intervention were decreased with older age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96 to 0.99) and with colchicine used in combination with anti-inflammatory agents (OR 0.45, 95% CI 0.26 to 0.79). However, the odds were increased in patients with preoperative heart failure (OR 1.84, 95% CI 1 to 3.39) and early postoperative constrictive physiology (OR 5.77, 95% CI 2.62 to 12.7). After multivariate adjustment, treatment with colchicine along with anti-inflammatory agents was associated with lower odds of requiring intervention (OR 0.43, 95% CI 0.95 to 0.99). Independent positive predictors of procedural intervention included age (OR 0.97,95% CI 0.95 to 0.99), time to PPS (OR 0.97,95% CI 0.95 to 0.99), and early postoperative constrictive physiology (OR 6.23, 95% CI 2.04 to 19.07). In conclusion, younger age, early-onset PPS, and postoperative constrictive physiology were associated with the need for procedural intervention in patients with PPS, whereas colchicine was associated with reduced odds of adverse events and procedural intervention. [ABSTRACT FROM AUTHOR]

Increased combined free light chains (cFLCs) are strongly prognostic of death in general populations and in patients with chronic kidney disease, but scarce data are available on cFLC in heart failure (HF). The aim of this study was to assess the dynamics and prognostic significance of cFLC levels in patients after admission with acute HF (AHF). cFLC measurements were compared in 49 patients with AHF, 37 patients with stable HF, 43 patients with stable coronary artery disease and without HF ("disease controls"), and 37 healthy controls. The association of cFLC with death and/or rehospitalization was assessed. Patients with AHF had significantly elevated cFLC levels, compared with other groups (p <0.001). Patients with stable HF showed higher levels of cFLCs than healthy controls. In patients with AHF, cFLC levels were correlated with cystatin C (Spearman's r = 0.63, p <0.001) and creatinine (Spearman's r = 0.47, p = 0.002). During 3-month follow-up, brain natriuretic peptide was reduced significantly (p = 0.017), but cFLCs did not change significantly. In a multivariate Cox regression analysis, the higher quartiles of cFLCs were significantly associated with death or readmission (hazard ratio 8.34, 95% confidence interval 2.38 to 29.22, p = 0.0009) after adjustment for age, gender, brain natriuretic peptide and cystatin C levels. Higher quartiles of cFLCs were prognostic for death alone (hazard ratio 14.0, 95% confidence interval 1.72 to 113.8, p = 0.014). In conclusion, increased serum cFLC concentrations in patients with AHF were independently associated with prognosis. In patients with AHF, elevated cFLC levels persist long after clinical stabilization, which may reflect immune disturbances and/or the reduced capacity of (perhaps functionally impaired) kidneys and the endothelium to eliminate them. [ABSTRACT FROM AUTHOR]

Peripheral vascular disease (PVD) portends increased morbidity and mortality in patients with heart failure. In those with advanced heart failure, heart transplantation (HT) is the only causative therapy to increase survival. However, little is known about the impact of symptomatic PVD on survival of HT recipients in large multicenter cohorts. The aim of this study was to investigate an association between recipient symptomatic PVD and survival after HT. We analyzed 20,297 patients from the United Network of Organ Sharing data set. Survival analysis using a control cohort established by propensity matching was performed. There was an increased prevalence of traditional cardiovascular risk factors in 711 patients with symptomatic PVD compared with 19,586 patients without PVD. Patients with pretransplant symptomatic PVD had increased post-transplant mortality compared with those without PVD (1-, 5- and 10-year survival rate 91.5% vs 94.9%, 74.8% vs 82.6%, 48.6% vs 54.7%, respectively, log-rank p <0.001). On multivariate analysis based on the propensity matching, factors associated with a lower survival rate were presence of PVD (hazard ratio 1.20, 95% confidential interval 1.02 to 1.42, p = 0.030), and female gender (hazard ratio 1.22, 95% confidence interval 1.02 to 1.47, p = 0.034). In conclusion, patients with symptomatic PVD have a lower survival rate after HT. Symptomatic PVD should be considered an independent risk factor for poor prognosis in patients undergoing HT evaluation. [ABSTRACT FROM AUTHOR]

There are limited data integrating findings on right-sided cardiac catheterization and cardiopulmonary exercise testing in ambulatory patients with heart failure. In this study, 187 outpatients with HF referred to the Duke Medical Center for consideration of advanced HF therapies were retrospectively evaluated. All patients had undergone right-sided cardiac catheterization and cardiopulmonary exercise testing; the median cardiac index (CI) was 2.0 L/min/m2 (interquartile range 1.7 to 2.3), and the median peak oxygen consumption was 11.3 ml/kg/min (interquartile range 9.2 to 13.8). Despite aggressive medical therapy, medical management had failed in 97 patients (52%) at 18 months, defined as left ventricular assist device implantation, cardiac transplantation, or death. After multivariate adjustment, factors associated with failure of optimal medical management included percentage achieved of predicted peak oxygen consumption, low CI (i.e., <2 L/min/m2), left ventricular size, and exercise time. Patients with discordant findings on right-sided cardiac catheterization and cardiopulmonary exercise testing were common, occurring in 88 patients (47%). The most common profile was preserved CI but reduced functional capacity, and these patients remained at high risk for requiring advanced therapies, whereas patients with reduced CIs but preserved exercise capacity were uncommon. In conclusion, low CI was independently associated with higher rates of death, transplantation, and left ventricular assist device implantation in this study. Also, patients with preserved CIs at rest but poor functional capacity, so-called cardiac insufficiency, were commonly encountered and had poor outcomes with medical management. [ABSTRACT FROM AUTHOR]

There is currently no reliable method of predicting the success of weaning from intra-aortic balloon pumping (IABP). The aim of this study was to investigate the ability of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level to predict the success of weaning from IABP. Consecutive patients scheduled for weaning from IABP were prospectively enrolled. NT-proBNP levels were measured at baseline (before the start of weaning) and cessation (just before cessation of IABP). Changes in NT-proBNP level between baseline and cessation were analyzed in 2 groups of patients: those who were successfully weaned and those who were not successfully weaned for any reason, including a decision to discontinue weaning, worsening of pulmonary edema after cessation of IABP, or unstable hemodynamics after cessation of IABP. A total of 30 patients were enrolled (mean age 66 - 12 years, 16 men, 16 with acute myocardial infarctions, and 14 with acute exacerbation of chronic heart failure). Median (interquartile range) baseline NT-proBNP levels were not significantly different between the successful and unsuccessful weaning groups (4,200 [1,400 to 8,752] pg/ml vs (5,620 [2,035 to 13,950] pg/ml, p = 0.30). In the unsuccessful weaning group, the median NT-proBNP level was significantly higher at cessation (9,995 [2,920 to 15,100] pg/ml) than at baseline (p = 0.008). All patients with decreases in NT-proBNP level between baseline and cessation were successfully weaned from IABP. In conclusion, these results show that NT-proBNP levels were useful for predicting the success of weaning from IABP. If the NT-proBNP level increases during weaning from IABP, more intense management should be considered. [ABSTRACT FROM AUTHOR]

Limited data exist about the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to ejection fraction (EF) findings. The primary objective of this population-based observational study was to characterize and compare trends in long-term prognosis after an episode of ADHF across 3 EF strata. Hospital medical records were reviewed for 3,604 residents of the Worcester, Massachusetts, metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004 and had EF measurements during their index hospitalizations. The average age of this population was 75 years, most were white, and 44% were men. Approximately 49% of the population had heart failure (HF) with preserved EF (EF ‡ 50%), 37% had HF with reduced EF (EF £40%), and 14% had HF with borderline EF (EF 41% to 49%). Patients with HF with preserved EF experienced higher postdischarge survival rates than patients with either HF with reduced EF or HF with borderline EF at 1, 2, and 5 years after discharge from all central Massachusetts medical centers. Although prognosis at 1 year after hospital discharge improved for all patient groups during the years under study, especially for those with HF with reduced EF and HF with preserved EF, these encouraging trends decreased with increasing duration of follow-up. In conclusion, although improvements in 1-year postdischarge survival were observed for patients in each of the 3 EF groups examined to varying degrees, the postdischarge prognosis of all patients with ADHF remains guarded. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) and heart failure (HF), common in older adults, are associated with poor outcomes. However, little is known about their impact, independent of each other. We studied 5,673 community-dwelling adults aged ⩾65 years in the Cardiovascular Health Study. Baseline prevalent AF and HF were centrally adjudicated, and 116 patients had AF only, 219 had HF only, 39 had both, and 5,263 had neither. The Cox proportional hazards model was used to estimate age-gender-race-adjusted hazard ratio (aHR) and 95% confidence intervals (CIs) for all-cause, cardiovascular (CV), and non-CV mortalities. Participants had a mean age of 73 years (±6 years), 58% were women, and 15% African-American. During 13 years of follow-up, all-cause mortality occurred in 43%, 66%, 74%, and 85% of those with neither, AF only, HF only, and both, respectively. Compared with neither, aHR (95% CIs) for all-cause mortality associated with AF only, HF only, and both was 1.36 (1.08 to 1.72), 2.31 (1.97 to 2.71), and 3.04 (2.15 to 4.29), respectively. Similar associations were observed with CV mortality, but HF only also had greater non-CV mortality (aHR 1.72, 95% CI 1.35 to 2.18). Compared with AF alone, aHR (95% CIs) associated with HF alone for all-cause, CV, and non-CV mortalities was 1.69 (1.29 to 2.23), 1.73 (1.20 to 2.51), and 1.64 (1.09 to 2.46), respectively. Compared with HF alone, those with both conditions had greater CV but not all-cause mortality. In conclusion, community-dwelling older adults with AF have greater mortality than those without but lesser than those with HF, and both conditions were associated with greater CV and all-cause mortalities, whereas only those with HF had greater non-CV mortality. [ABSTRACT FROM AUTHOR]

The current definition of peripartum cardiomyopathy (PC) is restricted to patients with left ventricular systolic dysfunction (ejection fraction [EF] <45%). Data on peripartum heart failure (HF) with normal EF are sparse. We describe clinical characteristics of patients with normal (≥55%) and patients with low (<45%) left ventricular ejection fractions (LVEFs). Electronic medical records (2006 to 2013) of our tertiary care center were retrospectively screened to identify peripartum HF with normal EF, defined as an entity meeting Framingham criteria for HF with symptom onset during the last month of pregnancy or up to 5months after delivery and with an EF of ≥55%.Clinical characteristics, echocardiographic parameters, and outcomes of these patients were compared with age-matched control patients with traditionally defined PC (EF <45%). A total of 25 patients with PC and EF ≥55% were identified. Exclusion of hypertension (n [ 9), preeclampsia (n [ 1), and diabetes mellitus (n [ 2) yielded 13 patients with PC and EF ≥55%. Age-matched patients with traditional PC (EF <45%) constituted controls (n [16). Compared with patients with PC and low LVEF, patients with PC and normal LVEF had lower B-type natriuretic peptide levels, systolic and diastolic left ventricular dimensions, left atrial size, and incidence of decompensated HF during delivery (p <0.05). Compared with historical age-matched controls, patients with normal LVEF exhibited attenuated E0 mitral annular velocities. On follow-up, these patients were associated with a lower New York Heart Association functional class. In conclusion, peripartum HF with normal LVEF appears to be a distinct entity. [ABSTRACT FROM AUTHOR]

Hyponatremia portends a poor prognosis in patients with heart failure (HF). The aim of this study was to evaluate prognostic implication of hyponatremia on adverse events in patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of improvement of hyponatremia after CRT device implantation was also evaluated. In this retrospective analysis, we included patients in whom a CRT device was implanted between April 2004 and April 2010 at our institution and had a baseline sodium level obtained within 72 hours of implantation. The patients were followed up for 3 years after implantation for subsequent primary composite end points, that is, hospitalization for HF, left ventricular assist device or heart transplant, and all-cause death. Sodium levels were followed up at 3 to 6 months after device implantation. Hyponatremia was defined as a serum sodium level of <135 mmol/L. A total of 402 patients were included (age 68.7 ± 12.3 years, women 20.9%). One hundred seventy-nine adverse events were noted in this period. In a Cox proportional hazards univariate model, hyponatremia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.113 to 2.131, p = 0.009), creatinine (HR 1.267, 95% CI 1.156 to 1.389, p <0.001), and diuretics (HR 2.652, 95% CI 1.401 to 5.019, p = 0.003) were associated with occurrence of the composite end point. A total of 57.9% of patients with hyponatremia at baseline had the composite end point compared with 40.7% of those with normal sodium concentration (p = 0.004). Kaplan-Meier curve showed that hyponatremic patients fared worse. Also, patients in whom hyponatremia resolved after CRT device implantation had lower incidence of the composite end point compared with patients who had normal pre-CRT sodium levels but developed hyponatremia later. In conclusion, baseline hyponatremia is associated with poor prognosis in patients with HF. CRT can resolve hyponatremia in some patients after device implantation. Patients with postimplantation hyponatremia (either newly developed or persistent from baseline) have a poor clinical outcome. Post-CRT improvement of hyponatremia is associated with improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality among selected patients with left ventricular systolic dysfunction and severe heart failure symptoms despite guideline-directed medical therapy (GDMT). Contemporaneous guidelines provided clear recommendations regarding selection of patients for CRT, including that all patients should first receive GDMT with β blockers and renin-angiotensin axis antagonists. Prevalence of GDMT among real-world patients receiving CRT defibrillators (CRT-D) has not been well studied. We identified 45,392 patients in the National Cardiovascular Data Registry Implantable Cardioverter-Defibrillator Registry who underwent first CRT-D implantation for primary prevention of sudden death from January 2006 to June 2008. We calculated the proportion of patients with contemporaneous class I guideline indications for CRT-D, the proportion receiving GDMT for heart failure, and the proportion receiving GDMT who had class I guideline indications for CRT-D. Among patients without contraindications, 87% were prescribed β blockers, 78% an angiotensin-converting enzyme inhibitor or an angiotensin II receptor inhibitor, and 70% both a β blocker and an angiotensin-converting enzyme or angiotensin II receptor inhibitor at discharge. Finally, 50% of patients met class I guideline indications and were prescribed GDMT at discharge; 9% neither met class I indications nor were prescribed GDMT at discharge. The major limitation of this study is the lack of dosage information in the Implantable Cardioverter-Defibrillator Registry and lack of prescribing information at times other than discharge. In conclusion, many patients receiving CRT-D are not receiving GDMT at discharge. Ensuring that all patients receiving CRT-D are also receiving GDMT appears to be a quality improvement target. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether a scoring system integrating clinical, electrocardiographic, and echocardiographic measurements can predict left ventricular reverseremodeling after cardiac resynchronization therapy (CRT). The derivation cohort consistedof 162 patients with heart failure implanted with a CRT device. Baseline clinical, electrocardiographic, and echocardiographic characteristics were entered into univariate and multivariate models to predict reverse remodeling as defined by a ≥15% reduction in left ventricular end-systolic volume at 6 months (60%). Combinations of predictors were then tested under different scoring systems. A new 7-point CRT response score termed L2ANDS2: Left bundle branch block (2 points), Age >70 years, Nonischemic origin, left ventricular end-diastolic Diameter <40 mm/m², and Septal flash (2 points) was calculated for these patients. This score was then validated against a validation cohort of 45 patients from another academic center. A highly significant incremental predictive value was noted when septal flash was added to an initial 4-factor model including left bundle branch block (difference between area under the curve C statistics = 0.125, p <0.001). The predictive accuracy using the L2ANDS2 score was then 0.79 for the C statistic. Application of the new score to the validation cohort (71% of responders) gave a similar C statistic (0.75). A score >5 had a high positive likelihood ratio (DLR = 5.64), whereas a score <2 had a high negative likelihood ratio (LLR = 0.19). In conclusion, this L2ANDS2 score provides an easy-to-use tool for the clinician to assess the pretest probability of a patient being a CRT responder. [ABSTRACT FROM AUTHOR]

The early diastolic transmitral velocity/tissue Doppler imaging mitral annular early diastolic velocity (E/é) ratio is used to estimate left ventricular (LV) filling pressures at rest. However, there are only limited data that validate its use during exercise. Accordingly, the aim of this study was to test the ability of E/é to estimate pulmonary capillary wedge pressure (PCWP) during symptom-limited exercise in patients with LV systolic dysfunction. Forty patients with severe LV dysfunction and heart failure symptoms (54 ± 12 years, 28 men) underwent simultaneous Doppler assessment of E/é and right-sided cardiac catheterization at rest and during a symptom-limited exercise test, at steady state levels of 30%, 60%, and 90% of their maximal exercise capacity. During exercise, all 40 patients successfully completed stage 1, yielding 40 pairs of data for comparison. Eighteen patients also successfully completed stage 2, and 5 patients also made it through stage 3, yielding 23 additional data pairs. In total, there were thus 63 pairs of data available during exercise. With exercise, heart rate increased from 77 ± 14 to 112 ± 21 beats/min. Septal E/é at rest correlated well with PCWP at rest (r = 0.75, p <0.01). PCWP at rest also correlated with resting mitral deceleration time (r = 0.32, p <0.01) and with the transmitral E/A ratio (r = 0.74, p <0.01). During exercise, the correlation between septal E/é and PCWP was weaker (r = 0.57, p <0.01) and was shifted to the right. This rightward shift was observed in patients with both separated or merged E and A velocities. In conclusion, in patients with severe LV dysfunction, although E/é allows accurate estimation of PCWP at rest, it appears less reliable for estimating LV filing pressure during exercise. [ABSTRACT FROM AUTHOR]

Neopterin is synthesized by macrophages upon stimulation with gamma-interferon, and high neopterin production is associated with cellular immune activation and increased production of reactive oxygen species (oxidant stress), but the clinical utility of urine neopterin levels in patients with heart failure (HF) has not been explored. Fifty-three ambulatory patients with chronic systolic HF (left ventricular [LV] ejection fraction ≤40%) underwent comprehensive echocardiographic evaluation and cardiopulmonary exercise testing. Urine neopterin levels were quantified by liquid chromatography with tandem mass spectrometric analyses and corrected to urine creatinine (Cr) levels. In our study cohort, median urine neopterin level was 60 mmol/mol Cr (interquartile range 40 to 86). There were modest correlations between urine neopterin levels and abnormalities in cardiac structure and function by echocardiography: LV ejection fraction (r = L0.33, p = 0.017), indexed LV end-diastolic volume (r = 0.31, p = 0.029), indexed LV end-systolic volume (r = 0.32, p = 0.024), and E/septal Ea (r = 0.28, p = 0.041). Although there was no significant correlation between urine neopterin and maximal oxygen uptake (peak VO2: r = L0.25, p = 0.07), there was a modest correlation between urine neopterin and maximal ventilation/ carbon dioxide production ratio (VE/VCO2 max: r = 0.38, p = 0.005). In conclusion, increase in urine neopterin levels tracks with disease severity in patients with chronic systolic HF. [ABSTRACT FROM AUTHOR]

Patients with hypertrophic cardiomyopathy (HC) are reported to have a mortality rate of about 1.0% per year, and those patients without sudden death risk factors and with no or mild symptoms are generally considered to have a benign clinical presentation. However, the risk of sudden death and the outcome in this latter subgroup have not been investigated systematically and remain unresolved. We assessed the risk of sudden death and outcome in 653 consecutive patients with HC without risk factors and with no or mild symptoms. Over a median follow-up of 5.3 years, 35 patients (5.4%) died of HC-related causes. Mean age at death was 46 ± 20 years in patients who died suddenly and 66 ± 15 and 72 ± 9 years, respectively, in patients who died of heart failure or stroke. Event rate was 0.6% per year for sudden death, 0.2% per year for heart failure death, and 0.1% per year for stroke-related death. Sudden death risk was independently and inversely related to age, and risk of heart failure or stroke death was directly related to age (p = 0.020). At 10 years after the initial evaluation, sudden death risk was 5.9%, with sudden death rate being the lowest (0.3% per year) in patients with normal left atrial dimension (≤40 mm). In conclusion, in patients with HC without conventional risk factors and with no or mild symptoms, the risk of sudden death was not negligible, with an event rate of 0.6% per year. Heart failure and strokerelated death were less common and largely confined to older patients. These results underscore the need for a more accurate assessment of the sudden death risk in patients with HC. [ABSTRACT FROM AUTHOR]

Implanted devices can provide objective assessment of physical activity over prolonged periods. The purpose of this study was to investigate the prognostic value of devicemeasured physical activity data compared with a six-minute walk test (6MWT) in predicting clinical response to cardiac resynchronization therapy (CRT). This was a singlecenter study in which patients who underwent CRT for standard indications were evaluated. Daily physical activity and 6MWT were evaluated postimplant at 1, 3, and 6 months. The primary end point was a composite of heart failure hospitalization, transplant, left ventricular (LV) assist device, and all-cause death at 3 years. Echocardiographic response, defined as a ≥10% improvement in LV ejection fraction (LVEF), at 6 months was the secondary end point. About 164 patients were included: average age was 67.3 ± 12.9 years, 77% were men, baseline LVEF was 25% ± 7%. Kaplan-Meier curves showed superior freedom from the composite end point in the highest tertile of both 6MWT and physical activity compared with the lowest tertile (41 vs 23 cases, respectively, p <0.001) for 6MWT and for activity (22 vs 7 cases, respectively, p [ 0.001). In an adjusted multivariate model, independent predictors of improved clinical outcome included 1-month physical activity (hazard ratio 0.546, 95% confidence interval [CI] 0.361 to 0.824, p = 0.004) and 6MWT (hazard ratio 0.581, 95% CI 0.425 to 0.795, p = 0.001). An additional hour of higher activity at 1 month translated to a 1.38 times (95% CI 1.075 to 1.753, p = 0.011) higher likelihood of improved echocardiographic response. In conclusion, device-based measures of physical activity may be useful in predicting echocardiographic reverse remodeling and long-term clinical outcome in patients receiving CRT. [ABSTRACT FROM AUTHOR]

Echocardiography-guided left ventricular (LV) lead placement at the site of latest mechanical activation improves heart failure outcomes in patients receiving a cardiac resynchronization therapy defibrillator (CRT-D). In this study, we test the hypothesis that a strategy of echocardiography-guided LV lead placement improves patient survival rate free from appropriate CRT-D therapy for ventricular arrhythmias. Patients enrolled in the prospective, randomized Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial and treated with a CRT-D device (108 with the echo-guided strategy and 75 with the routine strategy) were followed to the end point of death or first appropriate CRT-D therapy. Over a follow-up period of 3.7 ± 2.1 years, 62 patients (33%) died and 40 (22%) received appropriate CRT-D therapy. Compared with the routine group, patients in the echo-guided group had improved CRT-D therapy-free survival rate (hazard ratio = 0.64, 95% confidence interval = 0.42 to 0.98, p = 0.038). Patients randomized to the echoguided LV lead placement were more likely to resynchronize their LV compared with the routine group (72% vs 48%, respectively, p = 0.006). Patients whose LV did resynchronize after CRT-D had improved therapy-free survival rate compared with those whose LV did not resynchronize (hazard ratio = 0.49, 95% confidence interval = 0.28 to 0.86, p = 0.012). In conclusion, a strategy of echo-guided LV lead placement improved the patient survival rate free from defibrillator therapy in CRT-D recipients. [ABSTRACT FROM AUTHOR]

We hypothesized that the response to cardiac resynchronization therapy with a defibrillator (CRT-D) in patients with mildly symptomatic heart failure (HF) is more favorable than the commonly referenced figure of 70%. This study involves the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study population in which paired echocardiograms from baseline and 1-year follow-up were available in 621 implantable cardioverter-defibrillatoretreated patients and 749 patients treated with CRT-D. We prespecified CRT-D responders as the patients who at 1-year follow-up had a reduction in left ventricular end-systolic volume (LVESV) that corresponded to the top (best) quintile of LVESV reduction in the implantable cardioverter-defibrillatoretreated patients, that is, a ≥17% reduction in LVESV. Using this metric, 88% of patients treated with CRT-D and 91% of the patients treated with CRT-D with left bundle branch block (LBBB) were identified as cardiac resynchronization therapy responders. Landmark multivariate Cox model analyses revealed a significant interaction (p [ 0.038) involving LVESV (responders vs nonresponders) and LBBB (present vs not present) in risk reduction for HF or death. The interaction finding indicates that cardiac resynchronization therapy responders with LBBB have a significantly lower risk for HF or death (hazard ratio [HR] 0.24) than patients without LBBB (HR 0.62). In the patients treated with CRT-D, LVESV response was associated with reduction in the risk of death (HR 0.20, p <0.001). An increasing percent reduction in LVESV was associated with progressively lower rates of HF or death, a finding consistent with a dose-response relation. In conclusion, approximately 90% of CRT-Detreated patients in MADIT-CRT had a significant and meaningful reduction in LVESV, and these LVESV responders had reduced rates of cardiac events during long-term follow-up. [ABSTRACT FROM AUTHOR]

The aim of this study was to use T2* cardiac magnetic resonance (CMR) imaging to quantify myocardial iron content in patients with heart failure (HF) and to investigate the relation between iron content, cardiac function, and the cause of HF. CMR data were analyzed from 167 patients with nonischemic and 31 with ischemic HF and 50 patients with normal ventricular function. Short-axis T2* imaging was accomplished using 3-T scanner andmultiecho gradient-echo sequence. Myocardial T2* value (M-T2*) was calculated by fitting the signal intensity data for the mideleft ventricular (LV) septum to a decay curve. Patients with nonischemic HF were categorized into patients with LV ejection fraction (LVEF) <35% or ‡35%. The relation between nonischemic HF with LVEF <35% and the risk for major adverse cardiac events was analyzed by multivariate logistic regression analysis using M-T2* and HF biomarkers. M-T2* was significantly greater for patients with nonischemic HF (LVEF <35%: 29 – 7 ms, LVEF ‡35%: 26 – 5 ms) than for patients with normal LV function (22 – 3 ms, p <0.0001) or ischemic HF (22 – 4 ms, p <0.001). The odds ratio was 1.21 for M-T2* (p <0.0001) and 1.0015 for brain natriuretic peptide (p <0.0001) in relation to nonischemic HF with LVEF <35%. Furthermore, this value was 0.96 for systolic blood pressure (p[0.012) and 1.02 for MT2* (p [ 0.03) in relation to the risk for major adverse cardiac events in patients with nonischemic HF. In conclusion, T2* CMR demonstrated the robust relation between myocardial iron deficiency and nonischemic HF. M-T2* is a biomarker that can predict adverse cardiac function in patients with nonischemic HF. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is associated with poor prognosis in patients with heart failure (HF). Although platelets play an important role in rendering a prothrombotic state in AF, the exact mechanism by which the effect is mediated is still debated. MicroRNAs (miRNAs), which have been shown to be involved in a variety of cardiovascular conditions, are abundant in platelets and in a cell-free form in the circulation. In the present study, we performed a genome-wide screen for miRNA expression in platelets of patients with systolic HF and in controls without cardiac disease, in pursuit of specific miRNAs that are associated with the presence of AF. MiRNA expression was measured in platelets from 50 patients with systolic HF and 50 controls, of which, samples from 41 patients with HF and 35 controls were used in the final analysis because of a quality control process. MiR-150 expression was 3.2-fold lower (p[0.0003) in platelets of patients with HF with AF relative to those without AF. A similar effect was seen in serum samples from the same patients, in which miR-150 levels were 1.5- fold lower (p[0.004) in patients with HF with AF. Furthermore, the serum levels of miR-150 were correlated to platelet levels in patients with AF (r [ 0.65, p [ 0.0087). In conclusion, miR-150 expression levels in platelets of patients with systolic HF with AF are significantly reduced and correlated to the cell-free circulating levels of this miRNA. [ABSTRACT FROM AUTHOR]

The contribution of postimplant optimization of device settings to the beneficial effect of cardiac resynchronization therapy (CRT) in heart failure is uncertain. We performed a meta-analysis to investigate the impact of CRT optimization on the improvement of left ventricular function, exercise capacity, and quality of life. We undertook a systemic review of the evidence from a search of relevant controlled clinical studies in the MEDLINE and EMBASE databases. Changes in left ventricular ejection fraction (LVEF), 6-minute walk distance, and Minnesota Living with Heart Failure score at follow-up were assessed; the primary outcome was ejection fraction. A random-effects model was used to combine weighted mean difference (WMD) and 95% confidence intervals (CIs). A metaregression was undertaken to assess the impact of potential covariates. Data were collated from 13 studies enrolling 1,431 patients (919 optimized and 669 controls). Pooled analysis demonstrated that the optimization procedure resulted in a significant increase in LVEF (WMD 2.6%, 95% CI 0.8 to 4.4, p [ 0.001) as compared with a nonoptimized CRT. No improvements with the optimization of CRT were seen in 6-minute walk distance and quality of life (WMD 12 m, 95% CI 23 to 48, p [ 0.49, and 3.6, 95% CI 2.2 to 9.5, p [ 0.22, respectively); however, this part of the analysis was performed using limited data. Thus, these collated data suggest that the optimization of CRT leads to a significant but small improvement in LVEF in patients with heart failure. Additional, adequately powered studies are needed to evaluate the effects of this procedure on exercise tolerance and quality of life. [ABSTRACT FROM AUTHOR]

Despite significant advances in therapies for patients with heart failure with reduced ejection fraction (HFrEF), there are no evidence-based therapies for heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure (HF). Differences in pathophysiologic mechanisms are touted as to why patients with HFpEF purportedly do not derive similar therapeutic benefits compared with HFrEF. Similarly, the relative frequencies of HFpEF and HFrEF may differ between hospitalized and ambulatory settings. There are limited data on the prevalence, characteristics, treatment, and short-term outcomes of patients hospitalized with HFpEF. We sought to investigate these in patients hospitalized with HFpEF in an urban, hospitalized setting using the Get With The Guidelines registry. We retrospectively reviewed all consecutive discharges (n = 1,701) with a diagnosis of acute decompensated HF from December 1, 2006 to September 30, 2008. Patients with HFpEF (n = 499) were older, overweight, predominantly women, and had underlying hypertension and dyslipidemia. Presenting blood pressure and levels of creatinine were higher, with lower brain natriuretic peptide levels compared with patients with HFrEF (n [ 598). Length of stay and 30-day mortality were comparable between patients with HFpEF and HFrEF. Thirty-day readmission was initially lower in patients with HFpEF. However 30-day mortality from any cause after the index HF hospitalization and survival curve at 1-year was no different between patients with HFpEF and HFrEF. In conclusion, lower 30-day readmissions do not translate into improved long-term outcome in patients with HFpEF. [ABSTRACT FROM AUTHOR]

The ratio of early transmitral blood flow velocity over tissue Doppler early diastolic mitral annulus velocity (E/e') was found unreliable for estimating pulmonary capillary wedge pressure (PCWP) in patients with decompensated systolic heart failure (HF). The objective of this study was to test its reliability in stable HF. Therefore, 130 consecutive patients with a left ventricular (LV) ejection fraction of <35% and stable HF underwent right-sided cardiac catheterization and transthoracic echocardiography with measurement of transmitral flow velocities (E, A) and mitral annulus velocities during systole (s0) and diastole (e'). Mean age was 56 ± 11 years and mean LV ejection fraction was 28 ± 8%; 48% had PCWP of >15 mm Hg. E/e'septal correlated more strongly with PCWP (r = 0.53) compared with E/e'lateral (r = 0.41) and E/e'mean (r = 0.50; all p values <0.001). The area under the receiver operating characteristic curve (AUC) of E/e' ratios for PCWP estimation was 0.79 (95% confidence interval [CI] 0.70 to 0.87) for E/e'septal, 0.72 (95% CI 0.63 to 0.82) for E/elateral, and 0.79 (95% CI 0.70 to 0.87) for E/emean (all p values <0.0001). AUCs of E/eseptal and E/emean did not vary with s'septal, QRS width, or resynchronization. Using a cutoff of 8, negative predictive value of E/e'septal was 89% and negative likelihood ratio of 0.15. E/e'lateral showed good diagnostic performance only in patients with s'lateral of >4.5 cm/s (n = 77, 59%; AUC = 0.82; 95% CI 0.71 to 0.92; s'lateral of ≤4.5 cm/s: AUC = 0.54; 95% CI 0.38 to 0.70; p = 0.005). In conclusion, e' is useful for estimating LV filling pressure in stable severe systolic HF. E/e'septal showed good diagnostic performance for detecting normal filling pressures. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) is often deferred in dialysis-dependent patients with heart failure (HF) because of a perceived lack of benefit and potentially higher risks, although the outcomes associated with CRT in dialysis have not been reported. We therefore studied our center's experience with CRT in dialysis-dependent patients. We constructed a descriptive assessment of these patients (n = 15) and performed a casecontrol analysis matching for age, gender, bundle branch morphology, diabetes mellitus, cardiomyopathy origin, and β-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. Baseline and 6-month echocardiograms were assessed for evidence of reverse remodeling. No periprocedural or long-term complications were observed among dialysis patients. Heterogenous improvement in ejection fraction (+3.1 ± 9.2%) was noted and 2 patients derived absolute improvements of 8% and 22%, respectively. Dialysis patients demonstrated the following 3-year event rates: HF hospitalization, 31%; all-cause hospitalization, 100%; mortality, 73%; and HF hospitalization or death, 82%. In the case-control analysis, controls demonstrated superior reverse remodeling (+9.2 ± 9.5% increase in ejection fraction), decreased mortality (73% vs 44%, p = 0.038), and allcause hospitalizations (76% vs 100%, p = 0.047), with no difference in HF hospitalizations (p = 0.39), compared with dialysis patients. In conclusion, at our center, the dialysisdependent patients with HF who underwent CRT implantation did so safely and no serious complications were observed. Certain dialysis patients demonstrated compelling improvement after device implantation. Compared with matched controls, dialysis patients were at increased risk for adverse events and worsened echocardiographic outcomes. [ABSTRACT FROM AUTHOR]

The occurrence of heart failure (HF) and its clinical features after a great disaster have not been rigorously examined. We retrospectively examined the effect of the Great East Japan Earthquake on the occurrence of decompensated HF. The number of patients admitted for treatment of decompensated HF and their clinical features were compared between 2 periods, March 11, 2011 to September 10, 2011 (after the earthquake) and the same period in the previous year. The number of admissions increased from 55 in 2010 to 84 in 2011. A comparison of the clinical features showed that the patients admitted after the earthquake had (1) older age (p [ 0.031), (2) greater systolic blood pressure (p [ 0.039), (3) a greater incidence of new-onset HF due to valvular heart disease (p [ 0.040), (4) interruption of drugs (p [ 0.001), (5) a greater incidence of infection (p [ 0.019), (6) greater B-type natriuretic peptide (p[0.005) and C-reactive protein (p[0.003) levels, (7) a lower estimated glomerular filtration rate (p [ 0.048) and lower albumin levels (p [ 0.021), and (8) a larger diameter of the inferior vena cava (p [ 0.008). In conclusion, these results suggest that the earthquake increased the incidence of HF in association with high blood pressure, interruption of drugs, inflammation, malnutrition, and fluid retention. Taking appropriate measures to control blood pressure, nutritional status, and hygiene environment might decrease the occurrence of HF in future disasters. [ABSTRACT FROM AUTHOR]

A head-to-head evaluation of the effect of ramipril and zofenopril on the cardiovascular mortality rate of patients with chronic heart failure (HF) in the setting of clinical practice is not yet available. We prospectively enrolled 224 patients with all-cause HF, who were untreated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. These patients were then assigned to zofenopril 15 to 30 mg/day or ramipril 5 to 10 mg/day on the basis of a prospective, randomized, open, blinded, end point trial. The primary outcome of the trial was patient survival during the follow-up period. The groups were similar in a large number of clinical parameters. The mean follow-up of this cohort was 6.1 - 1.2 years. Overall, during the follow-up period, we observed 45 deaths in the zofenopril- treated group and 48 in the ramipril-treated group (p = 0.251). Zofenopril and ramipril appears to be equivalent regarding the effects on cardiovascular mortality in the entire sample. Zofenopril was a significant predictor of better survival in patients who were the median age or older (odds ratio 0.56, 95% confidence interval 0.35 to 0.91), in men (odds ratio 0.57, 95% confidence interval 0.30 to 0.98), and in patients with a lower ejection fraction (odds ratio 0.52, 95% confidence interval 0.26 to 0.97). In conclusion, in the clinical practice setting, ramipril and zofenopril seem to have similar effects on cardiovascular mortality. However zofenopril might be more efficacious in elderly patients, male patients, and patients with a lower ejection fraction. [ABSTRACT FROM AUTHOR]

failure (HF), however not well studied in Japan. The aims of this study were to characterize hyponatremic hospitalized patients with HF and to clarify the relations between hyponatremia and detailed in-hospital outcomes in Japan. Among 4,837 hospitalized patients with HF enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, patient characteristics and in-hospital mortality in those with hyponatremia were examined. Hyponatremia (sodium <135 mEq/L) was observed in 11.6% of patients. Patients with hyponatremia were of similar age, included fewer men, and had a higher proportion of previous hospitalizations for HF compared to those with normonatremia. On admission, lower heart rates and blood pressures and higher brain natriuretic peptide levels were observed in patients with hyponatremia. During hospitalization, inotrope levels and mechanical device use were significantly higher in patients with hyponatremia. Rates of allcause and cardiac death were significantly higher in patients with hyponatremia, 15.0% and 11.4%, respectively, compared to 5.3% and 3.6%, respectively, in those with normonatremia. In hyponatremic hospitalized patients with HF, cardiac death accounted for 76.2% of all-cause death. In conclusion, the present study demonstrates that in Japan hyponatremia in patients hospitalized with HF is relatively common and is associated with a very high in-hospital mortality. [ABSTRACT FROM AUTHOR]

In patients with heart failure (HF) with chronic obstructive pulmonary disease (COPD), concerns exist regarding β blockers, particularly noncardioselective β blockers, precipitating bronchospasm or attenuating the benefit of inhaled β2 agonists. The aim of this study was to test the hypothesis that noncardioselective β blockers would not be associated with worse outcomes compared with cardioselective β blockers in patients with concomitant COPD in a large HF registry. A retrospective analysis of patients from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) who had systolic dysfunction, documentation of β-blocker status, and follow-up information available after index hospitalization (n = 2,670) was performed. The associations between cardioselective and noncardioselective β blockers and the end points of 60- to 90-day mortality and mortality or rehospitalization in patients with (n = 722) and without (n [ 1,948) COPD were analyzed using regression modeling. The models were adjusted for covariate predictors of β-blocker use at discharge and clinical predictors of outcomes. Noncardioselective and cardioselective β blockers were associated with lower risk-adjusted mortality in patients with and without COPD. There was no evidence that β-blocker selectivity was associated with a difference in outcomes between patients with and those without COPD (p for interaction >0.10 for both outcomes). In conclusion, despite concerns regarding β blockers in patients with HF with COPD, there was no evidence that β-blocker selectivity was associated with differences in outcomes for patients with HF with COPD versus those without. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate whether diagnostic data collected after a heart failure (HF) hospitalization can identify patients with HF at risk of early readmission. The diagnostic data from cardiac resynchronization therapy defibrillator (CRT-D) devices can identify outpatient HF patients at risk of future HF events. In the present retrospective analysis of 4 studies, we identified patients with CRT-D devices, with a HF admission, and 30-day postdischarge follow-up data. The evaluation of the diagnostic data for impedance, atrial fibrillation, ventricular heart rate during atrial fibrillation, loss of CRT-D pacing, night heart rate, and heart rate variability was modeled to simulate a review of the first 7 days after discharge on the seventh day. Using a combined score created from the device parameters that were significant univariate predictors of 30-day HF readmission, 3 risk groups were created. A Cox proportional hazards model adjusting for age, gender, New York Heart Association class, and length of stay during the index hospitalization was used to compare the groups. The study cohort of 166 patients experienced a total of 254 HF hospitalizations, with 34 readmissions within 30 days. Daily impedance, high atrial fibrillation burden with poor rate control (>90 beat/min) or reduced CRT-D pacing (<90% pacing), and night heart rate >80 beats/min were significant univariate predictors of 30-day HF readmission. Patients in the "high"-risk group for the combined diagnostic had a significantly greater risk (hazard ratio 25.4, 95% confidence interval 3.6 to 179.0, p=0.001) compared to the "low"-risk group for 30-day readmission for HF. In conclusion, device-derived HF diagnostic criteria evaluated 7 days after discharge identified patients at significantly greater risk of a HF event within 30 days after discharge. [ABSTRACT FROM AUTHOR]

Mortality in patients with chronic heart failure (CHF) is high and associated with body mass. However, the best method of assessing nutritional status in patients with CHF is not clear. We sought to demonstrate the prognostic use of a nutritional risk index (NRI) in ambulatory patients with CHF. Consecutive patients attending their first quarterly review appointment in the HF clinic were recruited. All patients had systolic left ventricular (LV) dysfunction. An NRI was calculated as: (1.5 × serum albumin [grams per liter]) + (current body weight/ideal weight). Patients were followed up every 4 months. Of the 538 patients enrolled in the study 75% were men. The patients'' age was 71 ± 10 years (mean ± SD) and total median follow-up in survivors was 68 months (interquartile range 54 to 74). New York Heart Association classes II and III accounted for 60% and 27%, respectively, with 80% having moderate LV impairment or worse. Based on the NRI 23% of patients were at risk of malnutrition. Severely malnourished patients were older. There was no relation between NRI and LV function. The NRI was a univariable predictor of mortality (chi-square 25, p <0.001) and was an independent predictor of outcome in multivariable analysis (chi-square 12, p <0.001). In conclusion, the NRI is useful as a prognostic marker in patients with CHF in an outpatient setting. NRI might be of use as a surrogate marker for nutritional status in trials of dietary supplementation in CHF. [Copyright &y& Elsevier]

Elevated uric acid (UA) levels have been associated with cardiovascular disease in epidemiologic studies. The relation between UA levels and long-term outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention is not known. Data from 2,249 consecutive patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were evaluated. Patients were divided into 2 groups with high or low UA using upper limits of normal of 6 mg/dl for women and 7 mg/dl for men. There were 1,643 patients in the low-UA group (mean age 55.9 ± 11.6 years, 85% men) and 606 patients in the high-UA group (mean age 60.5 ± 12.6 years, 76% men). Serum UA levels were 8.0 ± 1.5 mg/dl in the high-UA group and 5.2 ± 1.0 mg/dl in the low-UA group (p <0.001). The in-hospital mortality rate was significantly higher in patients with high UA levels (9% vs 2%, p <0.001), as was the rate of adverse outcomes in patients with high UA. The mean follow-up time was 24.3 months. Cardiovascular mortality, reinfarction, target vessel revascularization, heart failure, and major adverse cardiac events were all significantly higher in the high-UA group. In a multivariate analyses, high plasma UA levels were an independent predictor of major adverse cardiac events in the hospital (odds ratio 2.03, 95% confidence interval 1.25 to 3.75, p = 0.006) and during long-term follow-up (odds ratio 1.64, 95% confidence interval 1.05 to 2.56, p = 0.03). In conclusion, high UA levels on admission are independently associated with in-hospital and long-term adverse outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

There are few data on the incidence and clinical outcomes of patients with atrial fibrillation (AF) treated in the era of percutaneous coronary intervention (PCI). We analyzed 30-day clinical outcomes in 3,307 consecutive patients with and without AF (sinus rhythm) undergoing PCI from January 2007 through December 2008 enrolled in a multicenter Australian registry. Periprocedural AF was present in 162 patients (4.9%). AF was associated with older age (74.1 ± 8.9 vs 63.9 ± 11.9 years, p <0.001), higher baseline serum creatinine (0.13 ± 0.14 vs 0.10 ± 0.13 mmol/L, p = 0.01), and lower left ventricular ejection fraction (49.5 ± 13.2% vs 53.4% ± 11.6%, p <0.001). Significantly more patients with AF had a history of heart failure and cerebrovascular and peripheral arterial diseases (p ≤0.01 for all comparisons). Periprocedural glycoprotein IIb/IIIa inhibitor (31.5% vs 31.4%, p = 0.98) and antithrombin use were not different between groups, but in-hospital bleeding complications were higher in patients with AF (5.0% vs 2.1%, p = 0.015). Fewer patients with AF received drug-eluting stents (p = 0.004). AF was associated with a greater than fourfold increase in 30-day mortality (9.9% vs 2.2%, p <0.0001) and readmission rates at 30 days (p = 0.01). Fewer patients with AF were on dual antiplatelet therapy at 30 days (86.3% vs 94.3%, p <0.0001), although 28.1% of patients with AF were on triple therapy (dual antiplatelet therapy plus oral anticoagulation). In conclusion, patients with periprocedural AF represent a very high-risk group. Excess 30-day morbidity and mortality after PCI may be due to the higher incidence of co-morbidities, bleeding complications, and suboptimal antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Heart failure with preserved left ventricular ejection fraction (HFpEF) is implicitly attributed to diastolic dysfunction, often recognized in elderly patients with hypertension, diabetes, and renal dysfunction. In these patients, left ventricular circumferential and longitudinal shortening is often impaired despite normal ejection fraction. The aim of this prospective study was to analyze circumferential and longitudinal shortening and their relations in patients with nonischemic HFpEF. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S′) were measured in 60 patients (mean age 73 ± 13 years) with chronic nonischemic HFpEF in stable New York Heart Association functional class II or III and compared to the values in 120 healthy controls and 120 patients with hypertension without HFpEF. Sc-MS was classified as low if <89% and S′ as low if <8.5 cm/s (the 10th-percentile values of healthy controls). Isolated low sc-MS was detected in 46% of patients with HFpEF, 27% of patients with hypertension, and 2% of controls; isolated low S′ was detected in 11% of patients with HFpEF, 7% of patients with hypertension, and 5% of controls; and combined low sc-MS and low S′ was detected in 26% of patients with HFpEF, 9% of patients with hypertension, and 5% of controls (HFpEF vs others, all p values <0.001). Thus, any alteration of systolic function was found in 83% of patients with HFpEF. The relation between sc-MS and S′ was nonlinear (cubic). Changes in S′ within normal values corresponded to negligible variations in sc-MS, whereas the progressive decrease below 8.5 cm/s was associated with substantial decrease in sc-MS. In conclusion, circumferential and/or longitudinal systolic dysfunction is present in most patients with HFpEF. Circumferential shortening normalized by wall stress identifies more patients with concealed left ventricular systolic dysfunction than longitudinal shortening. [Copyright &y& Elsevier]

There is uncertainty and debate regarding whether ischemic mitral regurgitation (MR) is a secondary epiphenomenon resulting from left ventricular (LV) dysfunction or confers an independent effect on exercise capacity and outcomes. We tested whether ischemic MR negatively affects exercise capacity and cardiovascular morbidity and mortality in patients with coronary artery disease (CAD) and those with inferior wall motion abnormality independent of LV dysfunction. Clinical follow-up over 5 years was obtained in 77 patients (64 ± 10 years old, LV ejection fraction 54 ± 11%) with at least mild ischemic MR from CAD and evidence of inferior wall motion abnormality who had exercise stress testing with perfusion imaging within 24 hours of echocardiography. Patients with active heart failure, ischemia, intrinsic valve disease, pulmonary and vascular diseases were excluded. Exercise capacity (METs, peak double product) was tested for relation to MR (vena contracta [VC] and jet area), LV size and function, and pulmonary pressures. Cox proportional hazards analysis assessed whether MR predicted cardiovascular events including hospitalization for heart failure, acute coronary syndrome, and myocardial infarction and cardiovascular and total mortalities. Univariate correlation identified MR with VC (r = −0.674, p <0.0001) and MR jet area (r = −0.575, p <0.0001) as determinants of decreased functional capacity evaluated by METs, with VC the stronger predictor. MR VC >2 mm (moderate ischemic MR) and age were independent predictors of cardiovascular events and death (hazard ratio 6.72 for MR, p = 0.04). In conclusion, in patients with CAD and LV inferior wall motion abnormality, MR negatively affects exercise capacity and is associated with increased cardiovascular morbidity and mortality. This effect appears independent of degree of LV dysfunction. [Copyright &y& Elsevier]

The aim of this study was to evaluate the mode of death and hospitalizations in advanced heart failure (HF) patients with renal dysfunction and to examine the rate of concordance between events reported by the clinical events committee and site investigators (using case report forms) in the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Little is known about the cause of death and hospitalization in patients with advanced HF. FUSION II was a randomized, double-blind, placebo-controlled trial evaluating outpatient nesiritide infusions versus placebo, with 911 patients with advanced HF (New York Heart Association class III or IV) and renal dysfunction enrolled. There were 151 deaths and 1,041 hospitalizations at 24 weeks. The clinical events committee classified events as cardiac, renal, cardiorenal, other or noncardiovascular, or unknown. Kappa statistics and McNemar tests were used to assess agreement (overall and by individual modes of death and hospitalization indications). In conclusion, the most common cause of death or hospitalization was cardiac related, with 70% of deaths and 60% of hospitalizations due to cardiac causes. There was 74% agreement (26% disagreement) on cardiac cause of death (κ = 0.40, McNemar p = 0.001) and 75% agreement (25% disagreement) between the investigators and the clinical events committee on cardiac classification for hospitalization (κ = 0.49, McNemar p <0.0001). [ABSTRACT FROM AUTHOR]