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Abstract

Summary:The initial diagnosis of new nonacute heart failure is as difficult as it is important, especially in settings where more advanced diagnostic tests, notably echocardiography, are not readily available. This diagnostic study demonstrates the importance of history taking and, in particular, physical examination in a large cohort of 721 patients suspected of having nonacute heart failure, 207 (28.7%) of whom were diagnosed with heart failure. When a primary care physician is confronted with a patient suspected of having nonacute heart failure, a diagnostic rule including age, objective evidence of prior coronary artery disease, use of a loop diuretic, displaced apex beat, basal or more pulmonary rales, irregularly irregular pulse, heart murmur suggestive of mitral regurgitation, pulse rate, and elevated jugular venous pressure, plus a single additional test, the NT-proBNP plasma level, can accurately predict the presence or absence of heart failure numerically. The rule had comparable performance in 2 validation datasets. Chest x-ray or ECG can be used in addition to or instead of the NT-proBNP measurement depending on local availability and other patient characteristics. It remains important for diagnosticians to maintain basic physical examination skill. Conclusions:In this study, we estimated the quantitative diagnostic contribution of elements of the history and physical examination in the diagnosis of heart failure in primary care outpatients, which may help to improve clinical decision making. The largest additional quantitative diagnostic contribution to those elements was provided by measurement of NT-proBNP. For daily practice, a diagnostic rule was derived that may be useful to quantify the probability of heart failure in patients with new symptoms suggestive of heart failure. 1 Sildenafil and B-Type Natriuretic Peptide Acutely Phosphorylate Titin and Improve Diastolic Distensibility In VivoSummary: Reduced left ventricular diastolic compliance contributes to the pathophysiology of heart failure with preserved ejection fraction, a disease entity with no effective therapy. In vitro studies suggest that cGMP may have favorable effects on diastolic function, in part via activation of cGMP-dependent protein kinase and titin phosphorylation. Phosphodiesterase-5A degrades cGMP, whereas nitric oxide and natriuretic peptides enhance cGMP production. We studied the effects of short-term treatment with sildenafil (a phosphodiesterase-5A inhibitor) and brain natriuretic peptide on diastolic function in vivo (pressure-volume analysis) and on skinned cardiomyocyte passive stiffness and myofilament protein phosphorylation (serial myocardial biopsies) in a canine model of heart failure with preserved ejection fraction (elderly dogs with experimental hypertension) and young normal controls. In vivo, plasma cGMP levels and left ventricular diastolic and systolic capacitance increased and ex vivo measurements of cardiomyocyte passive stiffness decreased during serial treatment with sildenafil and with brain natriur...