Publications by authors named "Daniel L Dries"

The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients.

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We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process.

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Background: The compensatory actions of the endogenous natriuretic peptide system require adequate processing of natriuretic peptide pro‐hormones into biologically active, carboxyl‐terminal fragments. Natriuretic peptide pro‐peptide processing is accomplished by corin, a transmembrane serine protease expressed by cardiomyocytes. Brain natriuretic peptide (BNP) processing is inadequate in advanced heart failure and is independently associated with adverse outcomes; however, the molecular mechanisms causing impaired BNP processing are not understood.

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Objective: To characterise the trends in the left ventricular assist device (LVAD) implantation rates and outcomes between 2004 and 2011 in the Medicare population. Since the approval of the HeartMate II in 2008, the use of LVADs has steadily climbed. Given the increase in LVAD use, issues around discharge disposition, post-implant hospitalisations and costs require further understanding.

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High-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strongly predict heart failure (HF) in the general population. However, the interpretation of levels of these biomarkers as predictors of HF is uncertain among patients with CKD. Here, we investigated whether hsTnT and NT-proBNP are associated with incident HF among patients with CKD.

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Background: Chronic kidney disease is associated with an increased risk of heart failure (HF). We aimed to evaluate the role of large artery stiffness, brachial, and central blood pressure as predictors of incident hospitalized HF in the Chronic Renal Insufficiency Cohort (CRIC), a multiethnic, multicenter prospective observational study of patients with chronic kidney disease.

Methods And Results: We studied 2602 participants who were free of HF at baseline.

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Background: Although noninvasive positive pressure ventilation (NIPPV) for patients with acute decompensated heart failure was introduced almost 20 years ago, the variation in its use among hospitals remains unknown. We sought to define hospital practice patterns of NIPPV use for acute decompensated heart failure and their relationship with intubation and mortality.

Methods And Results: We conducted a cross-sectional study using a database maintained by Premier, Inc.

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Hyperacute rejection is a rare but potentially catastrophic complication after cardiac transplantation. We describe an unusual case of hyperacute rejection due to preformed anti-donor antibodies despite a negative preoperative panel-reactive antibody (PRA) screen. An excellent outcome was achieved in this case and our strategy involving the use of CentriMag ventricular assist devices (VADs) for biventricular support during treatment with rituximab, intravenous immunoglobulin (IVIG), and plasmapheresis is illustrated.

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Background: Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study.

Methods And Results: Among 6765 African Americans, we related age, sex, height, and weight-adjusted residuals for 9 cardiac phenotypes (assessed by echocardiogram or magnetic resonance imaging) to 2.5 million single-nucleotide polymorphisms genotyped using Genome-wide Affymetrix Human SNP Array 6.

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Cardiomyocytes release atrial natriuretic peptide (ANP) and B-type natriuretic peptide to stimulate processes that compensate for the failing heart by activating guanylyl cyclase (GC)-A. C-type natriuretic peptide is also elevated in the failing heart and inhibits cardiac remodeling by activating the homologous receptor, GC-B. We previously reported that GC-A is the most active membrane GC in normal mouse ventricles while GC-B is the most active membrane GC in failing ventricles due to increased GC-B and decreased GC-A activities.

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Background: Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin-converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we investigated the relative early WRF-associated mortality rates in subjects randomized to ACE-I or placebo.

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The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry.

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Background: Soluble ST2 reflects activity of an interleukin-33-dependent cardioprotective signaling axis and is a diagnostic and prognostic marker in acute heart failure. The use of ST2 in chronic heart failure has not been well defined. Our objective was to determine whether plasma ST2 levels predict adverse outcomes in chronic heart failure in the context of current approaches.

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Background: An increased minute ventilation (VE)/carbon dioxide production (VCO2) relationship, an expression of ventilatory inefficiency (VI), is associated with increased morbidity and mortality in patients with left ventricular systolic dysfunction (LVSD). A direct link between VI and a specific cardiac abnormality has not been established.

Methods: We analyzed cardiopulmonary exercise test (CPET) data from patients (N=83) with severe LVSD (ischemic and nonischemic; left ventricular ejection fraction [LVEF] 19%±7%) and at least moderate exercise intolerance.

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Background: The epidemiology of atrial fibrillation (AF) has been mainly investigated in patients with end-stage renal disease, with limited data on less advanced chronic kidney disease (CKD) stages.

Methods: A total of 3,267 adult participants (50% non-Hispanic blacks, 46% women) with CKD from the Chronic Renal Insufficiency Cohort were included in this study. None of the study participants had been on dialysis.

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Background: B-type natriuretic peptide (BNP) is produced as a biologically inactive prohormone (proBNP(1-108)), processed, and released as an inactive amino acid N-terminal fragment (proBNP(1-76)) and a biologically active carboxyl-terminal fragment (proBNP(77-108) or BNP32). We hypothesized that simultaneous assessment of proBNP(1-108) and active BNP32, as an index of natriuretic peptide processing efficiency, would improve risk stratification in patients with chronic systolic heart failure.

Methods And Results: We quantified plasma proBNP(1-108) and BNP32 in 756 participants in the Penn Heart Failure Study, a prospective cohort of outpatients with predominantly systolic heart failure.

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Left-ventricular hypertrophy (LVH) is one of the strongest independent predictors of cardiovascular morbidity and mortality in the general population. Although hypertension and obesity are well-established, independent risk factors for the development of LVH, they explain less than 25% to 50% of the variance of left ventricular mass (LVM) in humans. A substantial body of evidence suggests that there is a genetic basis to the observed inter-individual variability in the susceptibility to the development of LVH.

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Background: Corin, a transmembrane serine protease expressed in cardiomyocytes, cleaves pro-atrial natriuretic peptide and pro-brain natriuretic peptide (BNP) into biologically active peptide hormones. The minor corin I555(P568) allele, defined by the T555I and Q568P mutations, is common in persons of African ancestry and associated with increased risk for hypertension and cardiac concentric hypertrophy. The corin gene product containing the T555I and Q568P mutations has significantly reduced natriuretic peptide processing capacity.

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Associated with technological progress in deoxyribonucleic acid and messenger ribonucleic acid profiling, advances in basic biology have led to a more complete and sophisticated understanding of interactions among genes, environment, and affected tissues in the setting of complex and heterogeneous conditions such as heart failure (HF). Ongoing identification of mutations causing hereditary hypertrophic and dilated cardiomyopathies has provided both pathophysiological insights and clinically applicable diagnostics for these relatively rare conditions. Genotyping clinical trial participants and genome-wide association studies have accelerated the identification of much more common disease- and treatment-modifying genes that explain patient-to-patient differences that have long been recognized by practicing clinicians.

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Left ventricular ejection fraction (EF) is used to assess patients with heart failure (HF); however, frequent measurements are not cost-effective. Impedance cardiography (ICG) is a low-cost, noninvasive test that measures systolic time intervals and may be a method for detecting impaired vs intact EF. This study evaluated the relationship between EF by echocardiography or gated nuclear ventriculography and systolic time ratio (STR) by ICG in outpatients with chronic HF.

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Corin is a cardiac serine protease that acts as the pro-atrial natriuretic peptide (ANP) convertase. Recently, 2 single-nucleotide polymorphisms (SNPs) (T555I and Q568P) in the human corin gene have been identified in genetic epidemiological studies. The minor I555/P568 allele, which is more common in African Americans, is associated with hypertension and cardiac hypertrophy.

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Background: The objective of the study was to evaluate racial differences in the prevalence of left ventricular (LV) dysfunction. Few data compare the relative frequency of reduced LV ejection fraction (EF) (LVEF) in blacks and whites. Because of the higher prevalence of risk factors for heart failure in blacks, including hypertension, obesity, and LV hypertrophy, we hypothesized that LV dysfunction would also be more common in this ethnic group.

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Heart failure and cardiac hypertrophy.

Curr Treat Options Cardiovasc Med

August 2007

Left ventricular failure is the final common pathway for a wide spectrum of myocardial insults, including systemic hypertension and myocardial infarction. Although left ventricular hypertrophy is an adaptive response to pressure and volume overload, this process becomes maladaptive if left untreated and pathologic cardiac hypertrophy then becomes an important and independent risk factor for the development of heart failure. Despite its importance, the transition from hypertrophy to heart failure in humans is poorly understood.

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