Showing papers in "Circulation-heart Failure in 2010"
TL;DR: Euvolemic patients with exertional dyspnea, normal brain natriuretic peptide, and normal cardiac filling pressures at rest may have markedly abnormal hemodynamic responses during exercise, suggesting that chronic symptoms are related to heart failure.
Abstract: Background—When advanced, heart failure with preserved ejection fraction (HFpEF) is readily apparent. However, diagnosis of earlier disease may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and hemodynamic indicators of volume overload may be absent at rest. Methods and Results—Patients with exertional dyspnea and ejection fraction >50% were referred for hemodynamic catheterization. Those with no significant coronary disease, normal brain natriuretic peptide assay, and normal resting hemodynamics (mean pulmonary artery pressure <25 mm Hg and pulmonary capillary wedge pressure [PCWP] <15 mm Hg) (n=55) underwent exercise study. The exercise PCWP was used to classify patients as having HFpEF (PCWP ≥25 mm Hg) (n=32) or noncardiac dyspnea (PCWP <25 mm Hg) (n=23). At rest, patients with HFpEF had higher resting pulmonary artery pressure and PCWP, although all values fell within normal limits. Exercise-induced elevation in PCWP in HFpEF was confirmed by greater incre...
880 citations
TL;DR: National mean and RSRR distributions among Medicare beneficiaries discharged after hospitalization for heart failure have not changed in recent years, indicating that there was neither improvement in hospital readmission rates nor in hospital variations in rates over this time period.
Abstract: Background— In July 2009, Medicare began publicly reporting hospitals’ risk-standardized 30-day all-cause readmission rates (RSRRs) among fee-for-service beneficiaries discharged after hospitalization for heart failure from all the US acute care nonfederal hospitals. No recent national trends in RSRRs have been reported, and it is not known whether hospital-specific performance is improving or variation in performance is decreasing.Methods and Results— We used 2004–2006 Medicare administrative data to identify all fee-for-service beneficiaries admitted to a US acute care hospital for heart failure and discharged alive. We estimated mean annual RSRRs, a National Quality Forum-endorsed metric for quality, using 2-level hierarchical models that accounted for age, sex, and multiple comorbidities; variation in quality was estimated by the SD of the RSRRs. There were 570 996 distinct hospitalizations for heart failure in which the patient was discharged alive in 4728 hospitals in 2004, 544 550 in 4694 hospitals...
436 citations
TL;DR: In patients with HCM, presence of LGE on CE-MRI was common and more prevalent among gene-positive patients, but LGE was not associated with severe symptoms and remained a significant associate of subsequent SCD and/or ICD discharge after controlling for other variables.
Abstract: Background— Myocardial late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (CE-MRI) of patients with hypertrophic cardiomyopathy (HCM) has been suggested to represent intramyocardial fibrosis and, as such, an adverse prognostic risk factor. We evaluated the characteristics of LGE on CE-MRI and explored whether LGE among patients with HCM was associated with genetic testing, severe symptoms, ventricular arrhythmias, or sudden cardiac death (SCD).Methods and Results— Four hundred twenty-four patients with HCM (age=55±16 years [range 2 to 90], 41% females), without a history of septal ablation/myectomy, underwent CE-MRI (GE 1.5 Tesla). We evaluated the relation between LGE and HCM genes status, severity of symptoms, and the degree of ventricular ectopy on Holter ECG. Subsequent SCD and appropriate implanted cardioverter defibrillator (ICD) therapies were recorded during a mean follow-up of 43±14 months (range 16 to 94). Two hundred thirty-nine patients (56%) had LGE on CE-MRI, r...
370 citations
TL;DR: In this paper, a randomized, attention-controlled, single-blind study of medically supervised ET (3 days per week) on exercise intolerance and QOL in 53 elderly patients (mean age, 70±6 years; range, 60 to 82 years; women, 46) with isolated heart failure with reduced ejection fraction (HFPEF) was conducted.
Abstract: Background—Heart failure (HF) with preserved left ventricular ejection fraction (HFPEF) is the most common form of HF in the older population. Exercise intolerance is the primary chronic symptom in patients with HFPEF and is a strong determinant of their reduced quality of life (QOL). Exercise training (ET) improves exercise intolerance and QOL in patients with HF with reduced ejection fraction (EF). However, the effect of ET in HFPEF has not been examined in a randomized controlled trial. Methods and Results—This 16-week investigation was a randomized, attention-controlled, single-blind study of medically supervised ET (3 days per week) on exercise intolerance and QOL in 53 elderly patients (mean age, 70±6 years; range, 60 to 82 years; women, 46) with isolated HFPEF (EF ≥50% and no significant coronary, valvular, or pulmonary disease). Attention controls received biweekly follow-up telephone calls. Forty-six patients completed the study (24 ET, 22 controls). Attendance at exercise sessions in the ET grou...
336 citations
TL;DR: Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI, and functional improvements after BMC therapy may persist for at least 2 years.
Abstract: Background— The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI).Methods and Results— Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow–derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P=0.015). Intraco...
307 citations
TL;DR: AI progresses over time in LVAD-supported patients, and as the authors move toward an era of long-term cardiac support, more studies are needed to determine the clinical significance of these findings.
Abstract: Background—Aortic insufficiency (AI) following left ventricular assist device (LVAD) placement can affect device performance. The aim of this study was to examine AI development following LVAD implantation. Methods and Results—Echocardiograms (n=315) from 78 subjects undergoing HeartMate-XVE (n=25 [32%]) or HeartMate-II (n=53 [68%]) implantations from 2004 to 2008 were reviewed. Studies were obtained preoperatively and at 1, 3, 6, 12, 18, and 24 months after surgery. AI was graded on an interval scale (0=none, 0.5=trivial, 1=mild, 1.5=mild-moderate, 2=moderate, 2.5=moderate-severe, 3=severe), and the change in AI at follow-up was analyzed with significance tests. Kaplan–Meier estimates for freedom from moderate or worse AI at follow-up were generated. Mixed-model linear regression was used to identify correlates of AI progression during LVAD support. The median (25th, 75th percentile) duration of LVAD support was 239 (112, 455) days, and preoperative AI grade was 0.0 (0.0, 0.0). At 6 months, 89±4% of subj...
295 citations
TL;DR: A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding.
Abstract: Background—Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy. Methods and Results—Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (n=12) and after a median of 15.5 months in ongoing patients (n=11). In all patients on devices, severe impairment of platele...
263 citations
TL;DR: Dichloroacetate (DCA), a compound known to enhance glucose oxidation, increased energy reserves and glucose uptake, improved cardiac function and the survival of the animals and activated the pentose phosphate pathway in the rat heart.
Abstract: Background—Congestive heart failure (CHF) is associated with a change in cardiac energy metabolism. However, the mechanism by which this change is induced and causes the progression of CHF is unclear. Methods and Results—We analyzed the cardiac energy metabolism of Dahl salt-sensitive rats fed a high-salt diet, which showed a distinct transition from compensated left ventricular hypertrophy to CHF. Glucose uptake increased at the left ventricular hypertrophy stage, and glucose uptake further increased and fatty acid uptake decreased at the CHF stage. The gene expression related to glycolysis, fatty acid oxidation, and mitochondrial function was preserved at the left ventricular hypertrophy stage but decreased at the CHF stage and was associated with decreases in levels of transcriptional regulators. In a comprehensive metabolome analysis, the pentose phosphate pathway that regulates the cellular redox state was found to be activated at the CHF stage. Dichloroacetate (DCA), a compound known to enhance gluc...
244 citations
TL;DR: Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency and was not seen on timed up and go testing, subjective measures of function, daily activity, or tumor necrosis factor.
Abstract: Background— Low 25-hydroxyvitamin D levels, commonly found in older patients with heart failure, may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance. We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life.Methods and Results— In a randomized, parallel group, double-blind, placebo-controlled trial, patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels <50 nmol/L (20 ng/mL) received 100 000 U of oral vitamin D2 or placebo at baseline and 10 weeks. Outcomes measured at baseline, 10 weeks, and 20 weeks were 6-minute walk distance, quality of life (Minnesota score), daily activity measured by accelerometry, Functional Limitations Profile, B-type natriuretic peptide, and tumor necrosis factor-α. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks (22.9 versus 2.3 nmol...
213 citations
TL;DR: Twelve weeks of ET in patients with advanced CHF is associated with augmented regenerative capacity of CPCs, enhanced flow-mediated dilation suggestive of improvement in endothelial function, skeletal muscle neovascularization, and improved LV function.
Abstract: Background—Attenuated peripheral perfusion in patients with advanced chronic heart failure (CHF) is partially the result of endothelial dysfunction. This has been causally linked to an impaired endogenous regenerative capacity of circulating progenitor cells (CPC). The aim of this study was to elucidate whether exercise training (ET) affects exercise intolerance and left ventricular (LV) performance in patients with advanced CHF (New York Heart Association class IIIb) and whether this is associated with correction of peripheral vasomotion and induction of endogenous regeneration. Methods and Results—Thirty-seven patients with CHF (LV ejection fraction 24±2%) were randomly assigned to 12 weeks of ET or sedentary lifestyle (control). At the beginning of the study and after 12 weeks, maximal oxygen consumption (Vo2max) and LV ejection fraction were determined; the number of CD34+/KDR+ CPCs was quantified by flow cytometry and CPC functional capacity was determined by migration assay. Flow-mediated dilation w...
188 citations
TL;DR: The results suggest that contemporary asymptomatic patients with HIV manifest mild functional and morphological cardiac abnormalities, which are independently associated with HIV infection.
Abstract: Background— Patients with HIV have increased risk for cardiovascular disease, but the underlying mechanisms remain unknown. The purpose of this study was to determine the prevalence of echocardiogr...
TL;DR: In this paper, the authors compared the efficacy of adaptive servo-ventilation (ASV) to continuous positive airway pressure (CPAP) in patients with chronic heart failure (CHF).
Abstract: Background— In patients with chronic heart failure (CHF), the presence of sleep-disordered breathing, including either obstructive sleep apnea or Cheyne-Stokes respiration-central sleep apnea, is associated with a poor prognosis. A large-scale clinical trial showed that continuous positive airway pressure (CPAP) did not improve the prognosis of such patients with CHF, probably because of insufficient sleep-disordered breathing suppression. Recently, it was reported that adaptive servo-ventilation (ASV) can effectively treat sleep-disordered breathing. However, there are no specific data about the efficacy of flow-triggered ASV for cardiac function in patients with CHF with sleep-disordered breathing. The aim of this study was to compare the efficacy of flow-triggered ASV to CPAP in patients with CHF with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea.
Methods and Results— Thirty-one patients with CHF, defined as left ventricular ejection fraction <50% and New York Heart Association class ≥II, with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea, were randomly assigned to either CPAP or flow-triggered ASV. The suppression of respiratory events, changes in cardiac function, and compliance with the devices during the 3-month study period were compared. Although both devices decreased respiratory events, ASV more effectively suppressed respiratory events (ΔAHI [apnea-hypopnea index], −35.4±19.5 with ASV; −23.2±12.0 with CPAP, P <0.05). Compliance was significantly greater with ASV than with CPAP (5.2±0.9 versus 4.4±1.1 h/night, P <0.05). The improvements in quality-of-life and left ventricular ejection fraction were greater in the ASV group (ΔLVEF [left ventricular ejection fraction], +9.1±4.7% versus +1.9±10.9%).
Conclusions— These results suggest that patients with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea may receive greater benefit from treatment with ASV than with CPAP.
Received April 2, 2009; accepted November 13, 2009.
TL;DR: In this article, the authors examined the long-term outcome of ASA among patients with obstructive hypertrophic cardiomyopathy, and found that the 1-, 5-, and 8-year survival-free from the primary end point was 96, 86, and 67%, respectively in ASA patients versus 100%, 96, an...
Abstract: Background—The impact of alcohol septal ablation (ASA)-induced scar is not known. This study sought to examine the long-term outcome of ASA among patients with obstructive hypertrophic cardiomyopathy. Methods and Results—Ninety-one consecutive patients (aged 54±15 years) with obstructive hypertrophic cardiomyopathy underwent ASA. Primary study end point was a composite of cardiac death and aborted sudden cardiac death including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia/ventricular fibrillation. Secondary end points were noncardiac death and other nonfatal complications. Outcomes of ASA patients were compared with 40 patients with hypertrophic cardiomyopathy who underwent septal myectomy. During 5.4±2.5 years, primary and/or secondary end points were seen in 35 (38%) ASA patients of whom 19 (21%) patients met the primary end point. The 1-, 5-, and 8-year survival-free from the primary end point was 96%, 86%, and 67%, respectively in ASA patients versus 100%, 96%, an...
TL;DR: The pathophysiology of the disorder is multifactorial, with a central role of myocardial iron overload and the significant contribution of immunoinflammatory mechanisms, and patients' management is demanding and requires a multidisciplinary approach, preferably in specialized centers.
Abstract: Beta-thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia that typically requires life-long transfusion therapy. Although traditionally prevalent in the Mediterranean basin, Middle East, North India, and Southeast Asia, immigration of those populations to North America and Western Europe has rendered beta-thalassemia a global health problem. Cardiac complications represent the primary cause of mortality and one of the major causes of morbidity in those patients. Heart disease is mainly expressed by a particular cardiomyopathy that progressively leads to heart failure and death. The beta-thalassemia cardiomyopathy is mainly characterized by 2 distinct phenotypes, a dilated phenotype, with left ventricular dilatation and impaired contractility and a restrictive phenotype, with restrictive left ventricular filling, pulmonary hypertension, and right heart failure. The pathophysiology of the disorder is multifactorial, with a central role of myocardial iron overload and the significant contribution of immunoinflammatory mechanisms. Patients' management is demanding and requires a multidisciplinary approach, preferably in specialized centers.
TL;DR: In this article, the chronotropic response to exercise and heart rate recovery after exercise in a carefully phenotyped group of patients with heart failure with preserved left ventricular ejection fraction (HfpEF) and a control group of similar age and gender distribution was assessed.
Abstract: Background— This study assessed the chronotropic response to exercise and heart rate (HR) recovery after exercise in a carefully phenotyped group of patients with heart failure with preserved left ventricular ejection fraction (HfpEF) and a control group of similar age and gender distribution.
Methods and Results— We studied 41 patients with HfpEF, 41 healthy controls, and 16 hypertensive controls. None were taking HR-limiting medications. All study participants had clinical examination, 12-lead ECG, pulmonary function test, echocardiogram, and metabolic exercise test with HR monitoring throughout exercise. Chronotropic response was measured by the percentage of the HR reserve used during maximal exercise and the peak exercise HR as a percentage of predicted maximal HR. Patients with HfpEF were generally women (70%), overweight, aged 69±8 years. Controls were of similar gender (63%) and age (67±6 years). Patients with HfpEF had significantly reduced peak VO2 compared with controls (20±4 mL · kg−1 · min−1 versus 31±6 mL · kg−1 · min−1, P <0.001) and greater minute ventilation-carbon dioxide production relationship (Ve/Vco2 slope) (33±6 versus 29±4, P <0.001). Chronotropic incompetence was significantly more common in patients with HfpEF compared with matched healthy controls as measured by the percentage of the HR reserve used during maximal exercise (63% versus 2%, <0.001) and percentage of predicted maximal HR (34% versus 2%, <0.001). In addition, abnormal HR recovery 1-minute after exercise (defined as the reduction in the HR from peak exercise 1-minute after exercise) was also significantly more common in patients with HfpEF compared with controls (23% versus 2%, P =0.01). Hypertensive controls showed similar chronotropic response to peak exercise and HR recovery after exercise as healthy controls.
Conclusions— Patients with HfpEF have impaired chronotropic incompetence during maximal exercise and abnormal HR recovery after exercise.
Received May 5, 2009; accepted August 21, 2009.
TL;DR: The results show that UA lowering by uricosuric treatment without XO inhibition may not have an effect on hemodynamic impairment in CHF pathophysiology, and suggests that upregulated XO activity rather than UA itself is actively involved in hemodynamics impairment inCHF.
Abstract: Background— Hyperuricemia is common in chronic heart failure (CHF), and it is a strong independent marker of prognosis. Upregulated xanthine oxidase (XO) activity and impaired renal excretion have been shown to account for increased serum uric acid (UA) levels in CHF. Therapeutic interventions with allopurinol to reduce UA levels by XO inhibition have been shown to be beneficial. Discussions are ongoing whether UA itself is actively involved or it is a mere marker of upregulated XO activity within CHF pathophysiology. Therefore, the aim of this study was to test the effect of lowering UA by uricosuric treatment without XO inhibition on hemodynamic and metabolic characteristics of CHF. Impaired renal excretion of UA was taken into account.
Methods and Results— Serum UA (SUA), urinary UA (uUA) excretion, and renal clearance test for UA (ClUA) were measured in 82 patients with CHF. SUA was significantly increased compared with controls of similar age (control, 5.45±0.70 mg/dL; New York Heart Association I, 6.48±1.70 mg/dL; New York Heart Association II, 7.34±1.94 mg/dL; New York Heart Association III, 7.61±2.11 mg/dL; P <0.01). Patients with CHF showed lower uUA excretion and ClUA. On multivariate analysis, insulin, brain natriuretic peptide ( P <0.01), and creatinine levels ( P =0.05) showed independent correlation with SUA. The treatment effect of the uricosuric agent benzbromarone was tested in 14 patients with CHF with hyperuricemia in a double-blind, placebo-controlled, randomized crossover study design. Benzbromarone significantly decreased SUA ( P <0.01). Brain natriuretic peptide, left ventricular ejection fraction, and dimensions in echocardiographic assessment did not change after benzbromarone therapy. In contrast, fasting insulin (placebo, 18.8±8.9 μU/mL; benzbromarone, 11.0±6.2 μU/mL; P <0.05), homeostasis model assessment of insulin resistance index (placebo, 5.4±2.6; benzbromarone, 3.0±1.7; P <0.05), and tumor necrosis factor-α (placebo, 2.59±0.63 pg/mL; benzbromarone, 2.14±0.51 pg/mL; P <0.05) improved after benzbromarone, and the changes in tumor necrosis factor-α levels were correlated with reduction of SUA ( P <0.05).
Conclusions— These results show that UA lowering without XO inhibition may not have an effect on hemodynamic impairment in CHF pathophysiology. To the extent that these data are correct, this finding suggests that upregulated XO activity rather than UA itself is actively involved in hemodynamic impairment in CHF.
Clinical Trial Registration— clinical trials.gov. Identifier: [NCT00422318][1].
Received March 26, 2009; accepted November 3, 2009.
[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00422318&atom=%2Fcirchf%2F3%2F1%2F73.atom
TL;DR: Cardiac dysfunction in long-term AAS users appears to be more severe than previously reported and may be sufficient to increase the risk of heart failure.
Abstract: Background— Although illicit anabolic-androgenic steroid (AAS) use is widespread, the cardiac effects of long-term AAS use remain inadequately characterized. We compared cardiac parameters in weightlifters reporting long-term AAS use to those in otherwise similar weightlifters without prior AAS exposure.
Methods and Results— We performed 2D tissue-Doppler and speckle-tracking echocardiography to assess left ventricular (LV) ejection fraction, LV systolic strain, and conventional indices of diastolic function in long-term AAS users (n=12) and otherwise similar AAS nonusers (n=7). AAS users (median [quartile 1, quartile 3] cumulative lifetime AAS exposure, 468 [169, 520] weeks) closely resembled nonusers in age, prior duration of weightlifting, and current intensity of weight training. LV structural parameters were similar between the two groups; however, AAS users had significantly lower LV ejection fraction (50.6% [48.4, 53.6] versus 59.1% [58.0%, 61.7%]; P =0.003 by two-tailed Wilcoxon rank sum test), longitudinal strain (16.9% [14.0%, 19.0%] versus 21.0% [20.2%, 22.9%]; P =0.004), and radial strain (38.3% [28.5%, 43.7%] versus 50.1% [44.3%, 61.8%]; P =0.02). Ten of the 12 AAS users showed LV ejection fractions below the accepted limit of normal (≥55%). AAS users also demonstrated decreased diastolic function compared to nonusers as evidenced by a markedly lower early peak tissue velocity (7.4 [6.8, 7.9] cm/s versus 9.9 [8.3, 10.5] cm/s; P =0.005) and early-to-late diastolic filling ratio (0.93 [0.88, 1.39] versus 1.80 [1.48, 2.00]; P =0.003).
Conclusions— Cardiac dysfunction in long-term AAS users appears to be more severe than previously reported and may be sufficient to increase the risk of heart failure.
TL;DR: It is demonstrated that chronic infusion of the cardiac myosin activator, omecamtiv mecarbil, improves LV function in sHF without the limitations of progressive desensitization and increased MVO2.
Abstract: Background—Therapy for chronic systolic heart failure (sHF) has improved over the past 2 decades, but the armamentarium of drugs is limited and consequently sHF remains a leading cause of death and disability In this investigation, we examined the effects of a novel cardiac myosin activator, omecamtiv mecarbil (formerly CK-1827452) in 2 different models of heart failure Methods and Results—Two different models of sHF were used: (1) pacing-induced sHF after myocardial infarction (MI-sHF) and (2) pacing-induced sHF after 1 year of chronic pressure overload left ventricular hypertrophy (LVH-sHF) Omecamtiv mecarbil increased systolic function in sHF dogs, chronically instrumented to measure LV pressure, wall thickness, and cardiac output Omecamtiv mecarbil, infused for 24 hours, induced a sustained increase without desensitization (P<005) in wall thickening (25±62%), stroke volume (44±65%) and cardiac output (22±28%), and decreased heart rate (15±30%) The major differences between the effect of omec
TL;DR: Patients with HF who are discharged from the emergency department (ED) have substantial risks of early death, which, in some cases, may exceed that of hospitalized patients.
Abstract: Background— Although approximately one third of patients with heart failure (HF) visiting the emergency department (ED) are discharged home, little is known about their care and outcomes.Methods and Results— We examined the acute care and early outcomes of patients with HF who visited an ED and were discharged without hospital admission in Ontario, Canada, from April 2004 to March 2007. Among 50 816 patients (age, 76.4±11.6 years; 49.4% men) visiting an ED for HF, 16 094 (31.7%) were discharged without hospital admission. A total of 4.0% died within 30 days from admission, and 1.3% died within 7 days of discharge from the ED. Although multiple (≥2) previous HF admissions (odds ratio [OR], 1.64; 95% CI, 1.14 to 2.31), valvular heart disease (OR, 1.37; 95% CI, 1.00 to 1.84), peripheral vascular disease (OR, 1.41; 95% CI, 1.00 to 1.93), and respiratory disease (OR, 1.33; 95% CI, 1.08 to 1.63) increased the risk of 30-day death among those discharged from the ED, presence of these conditions did not increase ...
TL;DR: The role of “coordinated adaptation,” an energy-conserving strategy to maximize efficiency in a damaged system, will be examined in the development of the skeletal myopathy in all of these chronic diseases.
Abstract: In chronic heart failure (HF) from systolic cardiac dysfunction, the degree of exercise intolerance is not directly related to the degree of cardiac weakness.1–5 Somewhat surprisingly symptoms that typify HF, including shortness of breath and fatigue, are often directly related to the abnormalities of the skeletal musculature in HF. Our understanding of the features of skeletal myopathy is evolving as therapy for HF is changing and improving. Understanding the skeletal myopathy of HF is important for 2 reasons: (1) therapies, including heart transplantation, only directed at improving cardiac function, will not immediately and may never improve exercise capacity in HF, and (2) with greater understanding of the mechanisms underlying the skeletal myopathy of HF, specific therapies targeting these abnormalities can be developed.
I will review the features of the skeletal myopathy of HF, as currently understood, based on state-of-the-art research in humans and animal models. I will then examine the mechanisms underlying the skeletal myopathy, which appears not to be unique to HF but are shared by other chronic diseases such as chronic obstructive pulmonary disease(COPD) and chronic renal disease.3 Specifically, the role of “coordinated adaptation,” an energy-conserving strategy to maximize efficiency in a damaged system, will be examined in the development of the skeletal myopathy in all of these chronic diseases.6 Further, I will present evidence supporting the concept that sympathetic nerve activation (SNA) initiates and maintains this systemic, coordinated adaptation. Finally, the impact of current and future pharmacological and nonpharmacological therapies will be related to the above pathophysiology of the skeletal myopathy of HF.
There are several features of the skeletal myopathy that have been described and confirmed by many different investigative groups. Patients with chronic HF on stable medical therapy have decreased muscle bulk compared with healthy humans.7,8 The …
TL;DR: Despite increased adiponectin expression in the skeletal muscle, patients with CHF are characterized by downregulation of AdipoR1 that is most probably linked to deactivation of the PPAR-&agr;/AMP-activated protein kinase pathway.
Abstract: Background— Adiponectin is an antiinflammatory, insulin-sensitizing, and antiatherogenic adipocytokine that plays a fundamental role in energy homeostasis. In patients with chronic heart failure (CHF), high circulating adiponectin levels are associated with inverse outcome. Recently, adiponectin expression has been identified in human skeletal muscle fibers. We investigated the expression of adiponectin, the adiponectin receptors, and genes involved in the downstream lipid and glucose metabolism in the skeletal muscle of patients with CHF.Methods and Results— Muscle biopsies (vastus lateralis muscle) were obtained from 13 patients with CHF and 10 healthy subjects. mRNA transcript levels of adiponectin, adiponectin receptors (AdipoR1 and AdipoR2), and downstream adiponectin-related enzymes were quantified by real-time reverse transcriptase polymerase chain reaction. Adiponectin expression in the skeletal muscle of patients with CHF was 5-fold higher than in healthy subjects (P<0.001), whereas AdipoR1 was d...
Durham University1, Northwestern University2, University of North Carolina at Chapel Hill3, University of Hull4, Duke University5, University of Bergen6, Stavanger University Hospital7, National and Kapodistrian University of Athens8, University of California, Los Angeles9, University of California, San Diego10, Pierre-and-Marie-Curie University11, Tufts University12, University of Toronto13, University of California, San Francisco14, University of Glasgow15, University of Maryland, Baltimore16, Case Western Reserve University17, Henry Ford Health System18, Baylor University Medical Center19, University of Upper Alsace20
TL;DR: Although substantial efforts in the last decade to develop improved AHFS therapies have yielded disappointing results, the scientific community is now better equipped to conduct future studies, and attempts to develop new short-term therapies for AHFS have largely been unsuccessful.
Abstract: Acute heart failure syndromes (AHFS) are characterized by a gradual or rapid onset of new or worsening signs and/or symptoms of heart failure (HF) requiring urgent therapy, usually resulting in hospitalization1,2 The societal burden of AHFS is substantial, with >1 million hospitalizations annually in the United States and similar relative numbers in Europe2–6 Ongoing epidemiological trends, such as the aging population, improved survival after myocardial infarction, and a decrease in sudden death due to defibrillator therapy, suggest that the prevalence of chronic HF resulting in hospitalization will continue to increase during the coming decades7 The prognosis after hospitalization for AHFS remains bleak, with rates of death or recurrent hospitalization at 6 months approaching 50%,8–10 outcomes that have changed little in recent years despite improvements in the management of chronic HF11 Hidden within these oft-cited statistics is a notable paradox—signs and symptoms of AHFS (dyspnea, edema, etc) are successfully treated in the majority of patients, but postdischarge outcomes remain dismal, and attempts to develop new short-term therapies for AHFS have largely been unsuccessful Since our initial publication in 2005,1 4 large, international phase III development programs—tezosentan,12 levosimendan,13 tolvaptan,14 and rolofylline15—have failed to convincingly demonstrate the safety and efficacy of these agents in AHFS Even for drugs approved for AHFS treatment (milrinone and nesiritide in the United States and levosimendan in parts of Europe), there have been persistent concerns about safety16–18 Broadly speaking, the pharmacological armamentarium for AHFS—loop diuretics, vasodilators, and inotropes—is largely unchanged from the 1970s19
Although substantial efforts in the last decade to develop improved AHFS therapies have yielded disappointing results, we believe that as a scientific community, we are now better equipped to conduct future studies Hospitalization for AHFS is now recognized as a critical clinical …
TL;DR: The Multidimensional Prognostic Index, calculated from information collected in a standardized comprehensive geriatric assessment, is useful to estimate the risk of 1-month mortality in older patients with heart failure.
Abstract: Background— Multidimensional impairment of older patients may influence the clinical outcome of diseases. The aim of this study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment predicts short-term mortality in older patients with heart failure.Methods and Results— In this prospective study with a 1-month follow-up, 376 patients aged 65 and older with a diagnosis of heart failure were enrolled. A standardized comprehensive geriatric assessment that included information on functional (activities of daily living and instrumental activities of daily living), cognitive (Short Portable Mental Status Questionnaire), and nutritional status (Mini Nutritional Assessment), as well as on risk of pressure sore (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale Index), medications, and social support network, was used to calculate the MPI for mortality using a previously validated algorithm. The New York Heart Association, the Enhanced Feed...
TL;DR: In this paper, the authors used an ELISA-based method to measure the plasma corin levels in patients with heart failure (HF) and acute myocardial infarction (AMI) and found that the corin deficiency may contribute to the pathogenesis of heart failure.
Abstract: Background— Corin is a transmembrane protease that processes natriuretic peptides in the heart. Like many membrane proteins, corin is shed from the cell surface.
Methods and Results— In this study, we obtained plasma samples from healthy controls and patients with heart failure (HF) and acute myocardial infarction. Soluble corin levels in plasma were measured by an ELISA method. In healthy adults (n=198), plasma corin levels were 690 pg/mL (SD, 260 pg/mL). The corin levels did not differ significantly among different age groups. In patients with HF (n=291), plasma corin levels were significantly lower compared with that of healthy controls (365 pg/mL [SD, 259]; P 0.05).
Conclusions— Soluble corin was detected in human plasma. Plasma corin levels were reduced significantly in patients with HF but not in those with acute myocardial infarction. Our results indicate that corin deficiency may contribute to the pathogenesis of HF and that plasma corin may be used as a biomarker in the diagnosis of HF.
Received August 21, 2009; accepted December 10, 2009.
TL;DR: Despite current management, many patients with advanced HF live on a plateau of high filling pressures from which later events occur, and this risk is progressively higher with higher chronic ambulatory pressures.
Abstract: Background—Intracardiac pressures in heart failure (HF) have been measured in patients while supine in the hospital but change at home with posture and activity. The optimal level of chronic ambulatory pressure is unknown. This analysis compared chronic intracardiac pressures to later HF events and sought a threshold above which higher pressures conferred worse outcomes. Methods and Results—Median pressures were measured every 24 hours from continuous 8-minute segments for 6 months after implantation of hemodynamic monitors in 261 patients with New York Heart Association class III-IV HF in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure Study. Baseline and chronic daily medians of estimated pulmonary artery diastolic, right ventricular systolic, and right ventricular end-diastolic pressures were compared with HF event rate. The group median for chronic 24-hour estimated pulmonary artery diastolic pressure was 28 mm Hg (excluding 7 days before and after events)...
TL;DR: In a follow-up study, the effect of enalapril on peak exercise oxygen consumption was small (0.7%; 95% CI, 4.2% to 5.6%) as mentioned in this paper.
Abstract: Background— Exercise intolerance is the primary symptom in older patients with heart failure and preserved ejection fraction (HFPEF); however, little is known regarding its mechanisms and therapy.
Methods and Results— Seventy-one stable elderly (70±1 years) patients (80% women) with compensated HFPEF and controlled blood pressure were randomized into a 12-month follow-up double-blind trial of enalapril 20 mg/d versus placebo. Assessments were peak exercise oxygen consumption; 6-minute walk test; Minnesota Living with HF Questionnaire; MRI; Doppler echocardiography; and vascular ultrasound. Compliance by pill count was excellent (94%). Twenty-five patients in the enalapril group versus 34 in the placebo group completed the 12-month follow-up. During follow-up, there was no difference in the primary outcome of peak exercise oxygen consumption (enalapril, 14.5±3.2 mL/kg/min; placebo, 14.3±3.4 mL/kg/min; P =0.99), or in 6-minute walk distance, aortic distensibility (the primary mechanistic outcome), left ventricle mass, or neurohormonal profile. The effect size of enalapril on peak exercise oxygen consumption was small (0.7%; 95% CI, 4.2% to 5.6%). There was a trend toward improved Minnesota Living with HF Questionnaire total score ( P =0.07), a modest reduction in systolic blood pressure at peak exercise ( P =0.02), and a marginal improvement in carotid arterial distensibility ( P =0.04).
Conclusions— In stable, older patients with compensated HFPEF and controlled blood pressure, 12 months of enalapril did not improve exercise capacity or aortic distensibility. These data, combined with those from large clinical event trials, suggest that angiotensin inhibition does not substantially improve key long-term clinical outcomes in this group of patients. This finding contrasts sharply with observations in HF with reduced EF and highlights our incomplete understanding of this important and common disorder.
TL;DR: In this article, the effects of hypokalemia on outcomes in patients with chronic heart failure (HF) and chronic kidney disease were studied. But, little is known about the effects on outcomes.
Abstract: Background— Little is known about the effects of hypokalemia on outcomes in patients with chronic heart failure (HF) and chronic kidney disease.Methods and Results— Of the 7788 patients with chronic HF in the Digitalis Investigation Group trial, 2793 had chronic kidney disease, defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2. Of these, 527 had hypokalemia (serum potassium <4 mEq/L; mild) and 2266 had normokalemia (4 to 4.9 mEq/L). Propensity scores for hypokalemia were used to assemble a balanced cohort of 522 pairs of patients with hypokalemia and normokalemia. All-cause mortality occurred in 48% and 36% of patients with hypokalemia and normokalemia, respectively, during 57 months of follow-up (matched hazard ratio when hypokalemia was compared with normokalemia, 1.56; 95% CI, 1.25 to 1.95; P<0.0001). Matched hazard ratios (95% CIs) for cardiovascular and HF mortalities and all-cause, cardiovascular, and HF hospitalizations were 1.65 (1.29 to 2.11; P<0.0001), 1.82 (1.28 to 2.57; P<...
TL;DR: Children with biopsy-confirmed or probable myocarditis had similar proportions of death, transplantation, and echocardiographic normalization 3 years after presentation and better outcomes than those of children with idiopathic dilated cardiomyopathy.
Abstract: Background—Myocarditis is a cause of a new-onset dilated cardiomyopathy phenotype in children, with small studies reporting high rates of recovery of left ventricular (LV) function. Methods and Results—The presenting characteristics and outcomes of children with myocarditis diagnosed clinically and with biopsy confirmation (n=119) or with probable myocarditis diagnosed clinically or by biopsy alone (n=253) were compared with children with idiopathic dilated cardiomyopathy (n=1123). Characteristics at presentation were assessed as possible predictors of outcomes. The distributions of time to death, transplantation, and echocardiographic normalization in the biopsy-confirmed myocarditis and probable myocarditis groups did not differ (P≥0.5), but both groups differed significantly from the idiopathic dilated cardiomyopathy group (all P≤0.003). In children with myocarditis, lower LV fractional shortening z-score at presentation predicted greater mortality (hazard ratio, 0.85; 95% confidence interval, 0.73 to ...
TL;DR: In a clinically stable, well-treated population of patients with mild-to-moderate HF symptoms and LV dysfunction, 36 weeks of treatment of aldosterone antagonism with eplerenone at a dose of 50 mg daily had no detectable effect on parameters of LV remodeling.
Abstract: Background—Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in patients with post-myocardial infarction and left ventricular (LV) dysfunction with HF symptoms. Few data are available on effects of aldosterone antagonism in patients with mild-to-moderate HF. Methods and Results—In a multicenter, randomized, double-blind, placebo-controlled study in patients with mild-to-moderate HF and LV systolic dysfunction, patients with New York Heart Association class II/III HF and LV ejection fraction (EF) ≤35% were randomly assigned to receive eplerenone 50 mg/d versus placebo in addition to contemporary background therapy. Quantitative radionuclide ventriculograms to assess LV volumes and ejection fraction were performed at baseline and again after 9 months of double-blind treatment and were analyzed in a central core laboratory, blinded to treatment. The primary efficacy analysis was the between-group comparison of the change in LV end-diastolic volume index. Secondary ...
TL;DR: Increased end-diastolic static ventricular stiffness relative to age-matched controls was not a universal finding, Nevertheless, patients with HFPEF, even when well compensated, had elevated filling pressures, reduced distensibility, and increased diastolic wall stress compared with controls.
Abstract: Background—Congestive heart failure in the setting of a preserved left ventricular (LV) ejection fraction is increasing in prevalence among the senior population. The underlying pathophysiologic abnormalities in ventricular function and structure remain unclear for this disorder. We hypothesized that patients with heart failure with preserved ejection fraction (HFPEF) would have marked abnormalities in LV diastolic function with increased static diastolic stiffness and slowed myocardial relaxation compared with age-matched healthy controls. Methods and Results—Eleven highly screened patients (4 men, 7 women) aged 73±7 years with HFPEF were recruited to participate in this study. Thirteen sedentary healthy controls (7 men, 6 women) aged 70±4 years also were recruited. All subjects underwent pulmonary artery catheterization with measurement of cardiac output, end-diastolic volumes, and pulmonary capillary wedge pressures at baseline; cardiac unloading (lower-body negative pressure or upright tilt); and card...