Prognostic implications of evaluation of contractile reserve in akinetic and hypokinetic segments during low dose dobutamine echocardiography in patients with acute myocardial infarction.

BACKGROUND: Previous studies have reported the prognostic value of myocardial viability (MV) detected using low-dose dobutamine echocardiography (DbE). However, viability was frequently evaluated as improvement in regional wall motion score index, which includes increased function in hypokinetic segments, in which viable myocardium is necessarily present. It is not known whether an evaluation focusing on akinetic segments, in which the possible presence of viable myocardium is unknown, might have more prognostic value. The aim of this study was to compare the prognostic value of the improvement of myocardial function during dobutamine infusion in akinetic and hypokinetic regions in patients with acute myocardial infarction (AMI). METHODS: 191 patients with uncomplicated AMI and at least one akinetic segment were retrospectively selected from those consecutively examined at our echo-laboratory to evaluate MV using DbE. Myocardial viability was evaluated both as an increment in RWMSI (Delta RWMSI), which takes into consideration improvement in both akinetic and hypokinetic regions, and as an improvement of function in akinetic (Delta akinetic) and hypokinetic (Delta hypokinetic), segments considered separately. Follow-up evaluation was performed at 30+/-13 months. RESULTS: On the basis of the Delta RWMSI, 94/191 patients were judged to have myocardial viability, whereas considering myocardial viability in akinetic segments only, 72/191 patients showed viability. At follow-up 18 patients had died (six viable considering Delta RWMSI; three viable considering Delta akinetic). The presence of a previous AMI, the site of AMI, RWMSI and the number of akinetic segments, and Delta RWMSI and Delta akinetic were related to mortality at univariate Cox analysis. At multivariate stepwise Cox regression analysis Delta akinetic, but not Delta hypokinetic proved to be significantly related to mortality. The Kaplan-Meier survival curves were no different in patients with or without viable myocardium evaluated as Delta RWMSI, while they were significantly different considering patients with or without viability in akinetic segments (P=0.04). CONCLUSION: In conclusion our study confirms the prognostic importance of the evaluation of myocardial viability in infarcted patients. However, it points out that it is the presence of viability in akinetic segments that affects long-term survival in these patients. This supports the hypothesis that other mechanisms, above and beyond the effect on regional wall motion, are involved in the beneficial effects of myocardial viability.

Relationship between mitral regurgitation and myocardial viability after acute myocardial infarction: their impact on prognosis.

Mitral regurgitation (MR) after acute myocardial infarction (AMI) is an important prognostic factor. Although its mechanisms are still debated, ventricular remodeling probably plays an important role. Because myocardial viability (MV) in the infarct zone reduces infarct expansion and ventricular remodeling, it is also possible that its presence counteracts the development of mitral regurgitation in infarcted patients. To evaluate this issue 191 patients with uncomplicated AMI, wall motion abnormalities (akinesis) and semiquantitative evaluation of MR were retrospectively selected from those consecutively examined at our echo-laboratory to evaluate MV using low-dose dobutamine echocardiography (DbE). Follow-up evaluation was performed at 30+/-13 months. Seventy-nine patients had no MR; 86 patients had grade 1 MR, 11 patients had grade 2 MR, nine patients had grade 3 MR, and six patients had grade 4 MR. Patients with significant MR (>grade 1) were older (63+/-7 vs. 59+/-10 years, P=0.03), had lower reduction of RWMSI (DeltaRWMSI) during DbE (0.08+/-0.11 vs. 0.22+/-0.28, P=0.01), more stenotic vessels at coronary angiography (2.35+/-0.93 vs. 1.67+/-1.12, P=0.01), and more frequently had anterior-inferior AMI (P<0.0001); they also had a non-significant tendency to higher RWMSI (2.04+/-0.38 vs. 1.92+/-0.28, P=0.06). In a multivariate regression analysis, DeltaRWMSI proved to be significantly related to the grade of MR (P=0.02). Eighteen patients died during follow-up. Death was more frequent in patients with MR (10/165 vs. 8/26, P=0.0003). At multivariate stepwise Cox regression analysis both the extent of ventricular dysfunction and the presence of MR were significantly related to mortality (P<0.0001 and P=0.01, respectively); DeltaRWMSI showed a non-significant tendency to influence mortality (P=0.09). When MR was excluded from the multivariate analysis, DeltaRWMSI remained significantly related to mortality (P=0.05). In conclusion our study suggests that the presence of MV in infarcted patients influences the development of MR. This reduction of MR may be one of the mechanisms by which MV affects mortality after AMI and should be considered in all studies that evaluate MV after myocardial infarction.

Role of growth hormone in chronic heart failure: therapeutic implications.

Chronic heart failure is a multi-etiological cardiovascular disorder with high prevalence and poor prognosis. Medical treatment of dilated cardiomyopathy is aimed at alleviating heart failure symptoms. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and very recently, beta-blockers have been shown to have favorable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The role of GH and IGF-1 as modulators of myocardial structure and function is well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, while IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases; impaired cardiac efficiency can also be observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by hemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is due to ventricular dilation with inadequate wall thickening that leads to impaired cardiac performance; therefore, based on previous evidence we would expect beneficial effects from the use of GH in these patients. Several papers have highlighted the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small open studies, acute and chronic GH treatment has demonstrated beneficial effects in patients with heart failure due to ischemic or idiopathic cardiomyopathy. Recently, two randomized, placebo-controlled studies did not show any significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance might be an important feature of severe heart failure and explain the diverse responses to GH therapy observed in different patients. Whether GH treatment will finally find a place in the treatment of heart failure, and with which modalities, remains to be established.