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Objectives: We characterized a large cohort of children who had a Fontan procedure, with measures of functional health status, ventricular size and function, exercise capacity, heart rhythm, and brain natriuretic peptide (BNP). Background: The characteristics of contemporary Fontan survivors are not well described. Methods: We enrolled 546 children (age 6 to 18 years, mean 11.9 years) and compared them within pre-specified anatomic and procedure subgroups. History and outcome measures were obtained within a 3-month period. ... 
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Objectives: The aim of this study was to describe exercise performance during the first 2 decades of life in Fontan survivors by a cross-sectional study and to identify factors that influence exercise performance. Background: Exercise performance after the Fontan procedure is reduced relative to performance in healthy subjects. Data on pre-adolescents are limited, and the patterns of exercise performance in different ages are unexplored. Methods: Ramp cycle ergometry was performed with expired gas. Data were analyzed for the entire study population and for subpopulations ...
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Objectives: The aim of this study was to prospectively examine the effects of elective Fontan fenestration closure upon exercise capacity and ventilatory abnormalities. Background: For patients undergoing Fontan procedures as palliation of single ventricle physiology, the addition of a fenestration to the procedure mitigates perioperative morbidity. Although some fenestrations may close spontaneously, many remain patent and subject patients to arterial hypoxemia and risk for paradoxical emboli. For these reasons fenestration closure is routinely performed ...
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Objectives: This study investigated the prevalence and electrocardiographic and electrophysiologic characteristics of aortic root ventricular arrhythmias (VAs). Background: Idiopathic VAs originating from the ostium of the left ventricle may be ablated at the base of the aortic cusps. Methods: We studied 265 patients with idiopathic VAs with an inferior QRS-axis morphology. Results: The successful ablation site was within (or below) the aortic cusps in 44 patients (16.6%). The site of the origin ...
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Objectives: The aim of this study was to characterize the relationship between impaired sympathetic innervation and arrhythmia with noninvasive biologic imaging in an animal model of post-infarct ventricular tachycardia (VT). Background: Innervation might be abnormal in the normally perfused borderzone of myocardial infarction, contributing to myocardial catecholamine overexposure and arrhythmogenic risk. Methods: Myocardial infarction was induced by mid-left anterior descending coronary artery balloon occlusion in 11 pigs. Positron ...
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Background Because plasma levels of adenosine are increased in patients with chronic heart failure (CHF), we examined adenosine concentrations in the plasma and heart and assessed the activity of ecto-5′-nucleotidase in the plasma and ventricular myocardium in patients with CHF.Methods and Results We studied 36 patients with CHF (New York Heart Association Class I/II/III/IV, 9/8/12/7). Twenty-five subjects without CHF were used as controls. Both plasma adenosine levels and ecto-5′-nucleotidase activity were significantly higher in patients with CHF (219 ± 28 nmol/L and 0.72 ± 0.03 nmoL/mg protein/min, ...
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Background Although the fourth heart sound (S4) is thought to be associated with a stiff left ventricle, this association has never been proven. Recently, single-beat estimation of the end-diastolic pressure volume relationship (EDPVR) has been characterized (P = αVβ), allowing the estimation of EDPVR in larger groups of patients. We hypothesized that the S4 is associated with an upward- and leftward-shifted EDPVR, indicative of elevated end-diastolic stiffness.Methods and Results Ninety study participants underwent acoustic cardiographic ...
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Objective Plasma brain natriuretic peptide (BNP) is an important parameter of severity in congestive heart failure (CHF). We analyzed if BNP might stratify 6-month clinical outcome in outpatients with CHF with restrictive mitral filling pattern.Methods All subjects with New York Heart Association (NYHA) class II to IV and restrictive filling pattern were enrolled at hospital discharge after an acute decompensation. NYHA class, BNP, and echocardiogram for the evaluation of left ventricular ejection fraction (LVEF) and diastolic function were analyzed. ...
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Background Despite recent advances in pharmacologic and device therapy, morbidity and mortality from heart failure (HF) remain high. Yoga combines physical and breathing exercises that may benefit patients with HF. We hypothesized that an 8-week regimen of yoga in addition to standard medical therapy would improve exercise capacity, inflammatory markers, and quality of life (QoL) in patients with HF.Methods and Results New York Heart Association Class I-III HF patients were randomized to yoga treatment (YT) or standard medical therapy (MT). Measurements included a graded ...
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Background Skeletal muscle microcirculation impairment in patients with chronic heart failure (CHF) seems to correlate with disease severity. We evaluated the microcirculation by near-infrared spectroscopy (NIRS) occlusion technique before and after inotropic infusion.Methods We evaluated 25 patients with stable CHF, 30 patients with end-stage CHF (ESCHF) receiving treatment with intermittent infusion of inotropic agents, and 12 healthy subjects. Thenar muscle tissue oxygen saturation (StO2%) was measured noninvasively by NIRS before, during, and after 3-minute occlusion ...
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Background The influence of myocardial function on plasma levels of cystatin C (CysC), a sensitive marker of renal function, in chronic systolic heart failure (HF) has not been well established.Methods We prospectively identified 139 subjects with stable, chronic HF (left ventricular ejection fraction ≤ 35%) and measured plasma levels of CysC. We prospectively tracked patients' long-term adverse clinical outcomes (death, cardiac transplantation, and HF hospitalizations).Results Plasma levels of CysC were elevated in 41% of patients ...
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Objective In chronic heart failure (HF), diuretic doses increase as the disease progresses, often after hospitalization for instability, and have been associated with worsening renal function and increased mortality.Methods and Results A prospective observational analysis of 183 patients in an advanced HF clinic stratified at baseline by diuretic dose (low dose ≤ 80 mg, high dose > 80 mg furosemide equivalent) was performed. All patients were followed for 1 year, and the primary outcome was a combined HF event of admission for HF, cardiac transplant, mechanical cardiac support, or ...
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Objective The New York Heart Association (NYHA) classification is recommended for grading symptoms of chronic heart failure and is a powerful prognostic marker. Patient-rated NYHA (Pa-NYHA) and physician-rated NYHA (Dr-NYHA) class have never been compared directly, and it is unknown whether they carry similar prognostic significance.Methods and Results NYHA class was rated independently by a physician and patient in 1752 patients referred with suspected heart failure. Pa-NYHA and Dr-NYHA varied by 1 class in 37.1% cases and by 2 classes in 12.8% cases. ...
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Background Racial differences in the epidemiology and outcomes of heart failure are well known. However, the association of race with the natural history of heart failure has not been previously studied in a propensity-matched population of chronic heart failure in which all measured baseline patient characteristics are well-balanced between the races.Methods and Results Of the 7788 patients with chronic systolic and diastolic heart failure in the Digitalis Investigation Group trial, 1128 were nonwhites. Propensity scores for being nonwhite ...
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Background Although previous studies of mechanical circulatory support devices (MCSDs) have used all-cause mortality as a primary end point, trends in device technology and implementation will increasingly necessitate the use of composite end points for MCSD studies. The ideal composite end point for studies of MCSDs is uncertain.Methods and Results We reviewed the advantages and disadvantages of traditional composite end points in MCSD studies from both a clinical and statistical perspective. Although composite end points may increase statistical power, ...
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Background Heart failure (HF) remains a major cause of morbidity and mortality in North America. With an aging population and an unmet clinical need by current pharmacologic and device-related therapeutic strategies, novel treatment options for HF are being explored. One such promising strategy is gene therapy to target underlying molecular anomalies in the dysfunctional cardiomyocyte. Prior animal and human studies have documented decreased expression of SERCA2a, a major cardiac calcium cycling protein, as a major defect found in HF.Methods and Results ...
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Objectives: The purpose of this study was to determine whether spironolactone use is associated with fractures in men with congestive heart failure (CHF). Background: In rats with aldosteronism, spironolactone preserves skeletal strength. However, in humans, the relationship of spironolactone to fractures is not known. Methods: The medical records of all male patients with CHF from 1999 to 2005 treated at the Veterans Affairs Medical Center, Memphis, Tennessee, were reviewed (n = 4,735). Odds ratios with 95% confidence intervals of ...
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Objectives: This study sought to assess the prevalence and markers of left ventricular (LV) thrombus among patients with systolic dysfunction. Background: Prior studies have yielded discordant findings regarding prevalence and markers of LV thrombus. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) identifies thrombus on the basis of tissue characteristics rather than just anatomical appearance and is potentially highly accurate. Methods: Prevalence of thrombus by DE-CMR was determined in 784 consecutive patients with ...
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Objectives: This study sought to determine the effects of endogenous tetrahydrobiopterin (BH4) bioavailability on endothelial nitric oxide synthase (eNOS) coupling, nitric oxide (NO) bioavailability, and vascular superoxide production in patients with coronary artery disease (CAD). Background: GTP-cyclohydrolase I, encoded by the GCH1 gene, is the rate-limiting enzyme in the biosynthesis of BH4, an eNOS cofactor important for maintaining enzymatic coupling. We examined the associations between haplotypes of the GCH1 gene, GCH1 expression and biopterin levels, and the ...
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Objectives: We examined the hemodynamic, echocardiographic, and neurohormonal effects of intravenous istaroxime in patients hospitalized with heart failure (HF). Background: Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of Na/K adenosine triphosphatase (ATPase) and stimulation of sarcoplasmic reticulum calcium ATPase. Methods: One hundred twenty patients admitted with HF and reduced systolic function were instrumented with a pulmonary artery catheter within ...
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Objectives: This study assesses whether the relationship of lipoprotein(a) [Lp(a)] with cardiovascular risk may be modified by concurrent hormone replacement therapy (HT). Background: Prior studies indicate that HT decreases plasma levels of Lp(a), but few have been powered to assess whether it modifies the relationship of Lp(a) with cardiovascular disease (CVD). Methods: Lipoprotein(a) at baseline was measured among 27,736 initially healthy women, of whom 12,075 indicated active HT use at the time of blood draw at study initiation and 15,661 did not. ...
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Background Hypertrophic cardiomyopathy (HCM) shows increased myocardial collagen and disarray. Late gadolinium enhancement in cardiovascular magnetic resonance (CMR) is observed in regions of increased myocardial collagen. The extent of late gadolinium enhancement has been associated with higher prevalence of risk factors of sudden death. The aim of the present study was to describe the clinical characteristics and the presence of risk factors for sudden death in a series of patients from 2 referral centers for HCM in relation to late gadolinium enhancement in CMR.Methods and Results ...
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Emerging technologies based on mass spectrometry and nuclear magnetic resonance enable the monitoring of hundreds of metabolites from tissues or body fluids, that is, "metabolomics." Because metabolites change rapidly in response to physiologic perturbations, they represent proximal reporters of disease phenotypes. The profiling of low molecular weight biochemicals, including lipids, sugars, nucleotides, organic acids, and amino acids, that serve as substrates and products in metabolic pathways is particularly relevant to cardiovascular diseases. In addition to serving as disease biomarkers, circulating ...
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Objectives: The purpose of this study was to evaluate ethnic differences in left ventricular (LV) remodeling between highly-trained athletes of African/Afro-Caribbean (black) and Caucasian (white) athletes. Background: The upper limits of left ventricular hypertrophy (LVH) are established in white athletes and aid the differentiation of physiologic LVH from hypertrophic cardiomyopathy (HCM). However, there are few data regarding LV remodeling in black athletes, in whom deaths from HCM are more prevalent. Methods: Between 2003 and 2007, 300 ...
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Objectives: We studied the relation between presence and severity of microvascular obstruction (MO), measured by cardiovascular magnetic resonance (CMR) and intracoronary Doppler flow measurements, for assessment of myocardial reperfusion in patients with acute anterior myocardial infarction (MI) treated by primary percutaneous coronary intervention (PCI). Background: Cardiovascular magnetic resonance has been used to detect and quantify MO in patients after acute MI but has never been compared with coronary blood flow velocity patterns. Methods: ...
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