Broad population studies of patients with stable ambulatory heart failure have associated female gender with better age-adjusted survival. This study investigated whether there are gender-specific ...differences in clinical presentation, response to intensive medical therapy, and outcomes in patients admitted with advanced (cardiac index <2.4 L/min/m2 ) decompensated heart failure (ADHF). We reviewed 278 consecutive patients (age 54 ± 12 years, cardiac index 1.7 ± 0.4 L/kg/m2 , pulmonary capillary wedge pressure 26 ± 9 mm Hg, serum creatinine 1.4 ± 0.8 mg/dl) with ADHF treated with intensive medical therapy guided by pulmonary artery catheter in a dedicated heart failure intensive care unit from 2000 to 2006. Compared with men (n = 226), women (n = 52) had similar baseline characteristics with the exception of a higher prevalence of nonischemic cause. No differences in medical therapy on admission, during intensive medical therapy, or at discharge were observed. Intensive medical therapy was associated with significant hemodynamic improvement independent of gender. All-cause mortality and heart failure rehospitalization rates were similar between genders. However, adjusted for cause, women with ischemic cardiomyopathy had higher all-cause mortality rates (50% vs 37%, hazard ratio 1.95, 95% confidence interval 0.98 to 3.90, p = 0.05) and those with nonischemic cardiomyopathy had lower all-cause mortality rates (19% vs 40%, hazard ratio 0.40, 95% confidence interval 0.17 to 0.96, p = 0.01) than men. In conclusion, women presenting with ADHF had baseline characteristics and response to therapy similar to men. Overall outcomes were similar between men and women, although subgroup analysis suggested better survival for women with a nonischemic cause.
Anemia is being increasingly recognized as an important comorbidity in patients with heart failure. Despite wide variations in defining anemia, approximately one-fifth to one-third of patients with ...heart failure may experience anemia at a given time. The prevalence may increase to more than half of patients in the setting of severe heart failure, and it may differ with different settings. Meanwhile, up to a fifth of patients may experience new-onset anemia, even though most cases may resolve over time. Different factors contribute to the development of anemia, including increasing age, renal insufficiency, hemodilution, chronic inflammation, and increasing heart failure disease severity.
Acute heart failure syndrome (AHFS) is prevalent and costly, and clinical development of pharmacologic therapy remains challenging. Relieving congestion is still the central goal in the decompensated ...states, although the predominant approach remains the use of intravenous loop diuretics. Newer agents such as vasopressin receptor antagonists have yet to show incremental benefits. A resurgence of interest in vasodilator therapy has been supported by a better understanding of the pathophysiology of AHFS and the availability of nesiritide and other natriuretic peptides, but long-term clinical outcomes data are lacking and highly debated. Several promising drugs are currently undergoing clinical development for the treatment of AHFS, although many of the clinical challenges remain unresolved.
Abstract Background The ratio of peak transmitral pulsed Doppler early velocity to early diastolic tissue Doppler velocity (TDI) of the lateral or septal mitral annulus (E/Ea) is considered a ...reliable estimation of LV filling pressure. We aim to examine the impact of left ventricular (LV) dimensions on the relationship between lateral and septal E/Ea in the determination of diastolic dysfunction patterns in the setting of chronic systolic heart failure (HF). Methods and Results In 207 patients with chronic systolic HF (LV ejection fraction ≤40%, New York Heart Association Classes I-IV), comprehensive transthoracic echocardiography was performed and long-term outcomes followed up to a median of 40 months. The median lateral and septal Ea (interquartile range) were 7.0 (4.7 to 9.5) cm/s and 4.5 (3.5 to 5.6) cm/s, respectively. The median E/lateral Ea, E/septal Ea, and E/average Ea (interquartile range) were 10.8 (7.1 to 15.1), 16.1 (11.1 to 23.0), and 12.7 (8.8 to 17.7), respectively. In the first 2 tertiles of indexed left ventricular end-diastolic volume (LVEDVi) (<92 mL/m2 and 92 to 130 mL/m2 ), all 3 E/Ea indices rise with increasing diastolic stage (all P < .001). However, in the highest tertile of indexed LVEDVi (≥130 mL/m2 ), E/average Ea and E/septal Ea (but not E/lateral Ea) increased with increasing diastolic stage, and only E/septal Ea correlated with natriuretic peptide levels ( r = 0.38, P = .018) and adverse cardiac events (Hazard ratio 1.91, 95% confidence interval 1.25 to 2.96, P = .003). Conclusions In the setting of chronic systolic heart failure with extensive cardiac remodeling, septal TDI measurements may be more reliable and clinically relevant than lateral TDI measurements in the assessment of diastolic dysfunction.
Right ventricular (RV) global longitudinal strain (RV strain) is a sensitive measure of RV mechanics. Its relationship with standard clinical markers and long-term events in chronic systolic heart ...failure is not well established. The aim of this study was to examine the ability of RV strain to provide incremental prognostic value to left ventricular (LV) ejection fraction (LVEF) in patients with chronic systolic heart failure.
In 171 patients with chronic systolic heart failure (LVEF ≤ 35%), a retrospective substudy of RV strain was performed using Velocity Vector Imaging to analyze previously recorded, comprehensive echocardiographic images. Death, cardiac transplantation, and heart failure hospitalization were tracked for 5 years.
In this study cohort (mean age, 57 ± 14 years; mean LVEF, 25 ± 6%), mean RV strain was -11.6 ± 5.4%. More impaired RV strain was associated with increasing New York Heart Association class (rank-sums P < .0001) and greater LV volume (LV end-systolic volume index: r = 0.35, P < .0001). Worse RV strain was associated with reduced LVEF (r = -0.45, P < .0001), worse LV diastolic dysfunction (E/e' septal: r = 0.19, P = .017; left atrial volume index: r = 0.18, P = .031), and standard indices of RV systolic and diastolic dysfunction (RV s': r = -0.43, P < .0001; RV e'/a': r = 0.16, P = .0040; right atrial volume index: r = 0.20, P = .015). RV strain predicted long-term adverse events (hazard ratio, 1.30; 95% confidence interval, 1.02-1.70; P = .037). Furthermore, RV strain ≥ -14.8% predicted adverse events after adjustment for age, LVEF, RV s', E/e' septal, and right atrial volume index.
In patients with chronic systolic heart failure, worse RV strain provides prognostic value incremental to LV function.
Abstract Because hepatic dysfunction is common in patients with heart failure, the Model for End-Stage Liver Disease (MELD) may be attractive for risk-stratification. Although alternative scores such ...as the MELD-XI or MELD-Na may be more appropriate in heart failure populations, the short-term clinical implications of these in patients with acute heart failure (AHF) are unknown. The MELD-XI and MELD-Na were calculated at baseline in 453 patients with AHF in the DOSE-AHF and ROSE-AHF trials. The correlations and associations for each score with cardiorenal biomarkers, short-term endpoints at 72 hours including worsening renal function and clinical events to 60 days were determined. The median MELD-XI and MELD-Na was 16 and 17, respectively. Both were correlated with baseline cystatin C, NT-proBNP, and plasma renin activity (P<0.003 for all). MELD-XI≤16 and MELD-Na≤17 were associated with a slight increase in cystatin C (P<0.02 for both), higher diuretic efficiency (P<0.001 for both), but not with change in global VAS scores (P>0.05 for both) at 72 hours. Neither score was associated with CRS or worsening heart failure (P>0.05 for all). Similarly, both the MELD-XI and MELD-Na were not associated with 60-day death/any re-hospitalization and 60-day death/heart failure re-hospitalization in adjusted analyses when analyzes as a dichotomous or continuous variable (P>0.05 for all). The alternative MELD scores correlated with baseline cardiorenal biomarkers. In conclusion, lower baseline MELD scoring was associated with higher diuretic efficiency and a slight increase in cystatin C through 72 hours. However, MELD-Na and MELD-XI were not predictive of 60-day clinical events.
The transcription factor GATA2 was reported to associate with coronary artery disease (CAD) in the family-based Genecard sample (Connelly et al. in PLoS Genet 2:e139, 2006). We asked whether GATA2 ...associates with sporadic cases of CAD in the Ottawa Heart Genomics Study (OHGS) and Cleveland Clinic (CC) populations. We genotyped the lead single nucleotide polymorphism (SNP) from Genecard, rs2713604 which is located in intron 5-6 of GATA2 in 600 CAD cases and 625 controls, as well as a tag SNP rs1573949 (r ² = 0.87 in Caucasians of European ancestry in Utah from HapMap) in 1,136 cases and 1,162 controls in the OHGS1 population. A further 1,838 CAD cases and 913 controls derived from an independent sample combining genotypes from CC and OHGS2 populations were genotyped for rs1573949. Neither of the genotyped SNPs associates with CAD in the OHGS1 or CC/OHGS2 populations. Our data suggest that GATA2 does not contribute to the development of angiographic CAD among sporadic cases.
Abstract Background Intrathoracic impedance fluid monitoring has been shown to predict worsening congestive heart failure (CHF) in patients with implantable devices. We developed and externally ...validated a modified algorithm to identify worsening heart failure (HF) by using intrathoracic impedance. Methods and Results The modified algorithm was developed by using published data from 81 CHF subjects averaging 259 days of follow-up. Device-measured daily impedance was input to both the existing and the modified intrathoracic impedance fluid monitoring algorithms to determine a reference impedance and a fluid index (FI). Separate validation sets included 326 cardiac resynchronization therapy device (CRT-D) patients with an average 333 days of follow-up (group 1) and 104 CRT-D/implantable cardioverter/defibrillator (ICD) patients followed for an average of 520 days (group 2). Clinicians and patients in group 2 were blinded to impedance and FI data. HF events included adjudicated HF hospitalizations or emergency room visits. Sensitivity was defined as the percentage of HF events preceded by FI exceeding the predefined threshold (60 Ω-d) within the last 2 weeks. Unexplained detections were FI threshold crossing events not followed by a HF event within 2 weeks. The modified algorithm significantly decreased unexplained detections by 30% ( P = .01; GEE) in the development set, 30% ( P < .001) in the group 1 validation set, and 43% ( P < .001) in group 2. Sensitivity did not change significantly in any group. Simulated monthly review of FI threshold crossings identified subjects at significantly greater risk of worsening HF within the next 30 days. Conclusions A modified intrathoracic impedance based fluid detection algorithm lowered the number of unexplained FI threshold crossings and identified patients at significantly increased immediate risk of worsening HF.
A 66-year-old Chinese man developed corneal endothelial decompensation after intraocular lens (IOL) repositioning using intracameral epinephrine was performed. The presentation was compatible with ...toxic endothelial cell destruction syndrome, which is caused by prolonged, direct exposure of the corneal endothelium to relatively high concentrations of intracameral epinephrine. Despite its effective and immediate mydriatic effect, intracameral epinephrine is not recommended for intraoperative mydriasis in procedures such as IOL repositioning or secondary IOL implantation in which minimal irrigating solution is used.
Objectives This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying ...CAD. Background Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. Methods We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects. Results We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio OR: 1.31, 95% confidence interval CI: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele. Conclusions The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.
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