Usefulness of NT-proBNP in the assessment of patients with aortic or mitral regurgitation.

BACKGROUND: Recent application of brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in cardiac valvular disease is very promising. AIMS: To test the usefulness of NT-proBNP in the assessment of patients with aortic or mitral regurgitation. PATIENTS AND METHODS: Sixty-seven patients - 23 with aortic and 12 with mitral regurgitation vs. 32 controls - were examined by color Doppler echocardiography, cardiopulmonary exercise testing, Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and plasma NT-proBNP assay at rest (T0) and after maximal physical exercise (T1). RESULTS: NT-proBNP was significantly higher in patients than in controls, both at T0 (298 +/- 85 vs. 46 +/- 11 pg/ml; P < 0.01) and at T1 (366 +/- 106 vs. 50 +/- 12 pg/ml; P < 0.01). MLWHFQ score was significantly higher in patients (19 +/- 3 vs. 1 +/- 0.6; P < 0.001) with a significant inverse correlation with VO2max (r = -0.538, P < 0.001) and a direct correlation with NT-proBNP (T0: r = 0.415, P < 0.01; T1: r = 0.458, P < 0.01). NT-proBNP was inversely correlated with VO2max (T0: r = -0.444, P < 0.001; T1:r = -0.428, P < 0.001) and directly correlated with left atrial diameter (T0: r = 0.370, P < 0.01; T1: r = 0.409, P = 0.001), and left ventricular mass index (r = 0.279, P < 0.01, and r = 0.272, P < 0.01). No correlations were found between echocardiographic parameters of valvular disease severity and VO2max, NT-proBNP and MLWHFQ. CONCLUSIONS: NT-proBNP is useful in the assessment of the cardiac functional damage secondary to mitral and aortic regurgitation.

The GH/IGF-1 Axis and Heart Failure.

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis regulates cardiac growth, stimulates myocardial contractility and influences the vascular system. The GH/IGF-1 axis controls intrinsic cardiac contractility by enhancing the intracellular calcium availability and regulating expression of contractile proteins; stimulates cardiac growth, by increasing protein synthesis; modifies systemic vascular resistance, by activating the nitric oxide system and regulating non-endothelial-dependent actions. The relationship between the GH/IGF-1 axis and the cardiovascular system has been extensively demonstrated in numerous experimental studies and confirmed by the cardiac derangements secondary to both GH excess and deficiency. Several years ago, a clinical non-blinded study showed, in seven patients with idiopathic dilated cardiomyopathy and chronic heart failure (CHF), a significant improvement in cardiac function and structure after three months of treatment with recombinant GH plus standard therapy for heart failure. More recent studies, including a small double-blind placebo-controlled study on GH effects on exercise tolerance and cardiopulmonary performance, have shown that GH benefits patients with CHF secondary to both ischemic and idiopathic dilated cardiomyopathy. However, conflicting results emerge from other placebo-controlled trials. These discordant findings may be explained by the degree of CHF-associated GH resistance. In conclusion, we believe that more clinical and experimental studies are necessary to exactly understand the mechanisms that determine the variable sensitivity to GH and its positive effects in the failing heart.

Myocarditis and dilated cardiomyopathy: possible connections and treatments.

Myocarditis is an inflammatory heart muscle disease, resulting from various etiologies, both noninfectious and infectious, which may be associated or not with cardiac dysfunction. Its course is unpredictable: it may spontaneously resolve or evolve into dilated cardiomyopathy and heart failure. A possible connection between myocarditis and dilated cardiomyopathy has long been postulated, but the intimate mechanisms linking these two conditions are still poorly understood. Viral myocarditis could induce a dilated cardiomyopathy through viral persistence and/or by triggering an autoimmune process. Understanding the mechanisms underlying the relationship between myocarditis and dilated cardiomyopathy will help in identifying an effective strategy of treatment aimed to stop and prevent cardiac damage. Specifically, we need to (a) evaluate the potential role of autoantibodies in disease prevention and progression, and understand their importance as markers of disease progression; (b) clarify the role of immunoregulation in exacerbating the disease.

Effects of growth hormone on exercise capacity and cardiopulmonary performance in patients with chronic heart failure.

BACKGROUND: Because GH exerted beneficial effects in various experimental models of heart failure, we investigated the effects of GH on physical exercise capacity and cardiopulmonary performance in patients with dilated cardiomyopathy and chronic heart failure (CHF). METHODS: Twenty-two patients with CHF (New York Heart Association functional class II-III) underwent spirometry and a symptom-limited, cardiopulmonary exercise testing before and after 3 months of GH (n = 11; seven males; seven idiopathic; 57 +/- 11 yr; 4 IU sc every other day) or placebo (n = 11; eight males; six idiopathic; 54 +/- 10 yr) administration, in a randomized, double-blind trial. Background CHF therapy remained unchanged. RESULTS: GH, but not placebo, increased IGF-I serum concentration (from 144 +/- 35 to 293 +/- 58 ng/ml; P < 0.005) and improved New York Heart Association functional class (from 2.4 +/- 0.5 to 1.8 +/- 0.4; P < 0.005), exercise duration (from 831 +/- 273 to 925 +/- 266 sec; P < 0.005), peak power output (from 245 +/- 127 to 280 +/- 132 W; P < 0.05), peak minute ventilation (from 52.5 +/- 16.1 to 61.3 +/- 17.3 liters/min; P < 0.05), peak oxygen consumption (from 19.8 +/- 5.6 to 25.1 +/- 5.6 ml/kg.min; P < 0.005), and anaerobic threshold (from 14.9 +/- 4.8 to 20.0 +/- 4.5 ml/kg.min; P < 0.005) without affecting lung function parameters. Furthermore, the slope of the relationship between minute ventilation and pulmonary carbon dioxide production (ventilatory efficiency) decreased from 34.7 +/- 5.1 to 31.7 +/- 5.3 (P < 0.005), whereas the slope of the relation between percent predicted heart rate reserve used and percent observed metabolic reserve used (chronotropic index) rose from 0.57 +/- 0.20 to 0.69 +/- 0.18 (P < 0.005). CONCLUSION: Given the predictive value of physical exercise capacity and cardiopulmonary performance in CHF progression, these data provide additional insights into the mechanisms by which GH may potentially benefit CHF patients.