Alessandro Salvi

Left ventricular involvement in right ventricular dysplasia

Right ventricular dysplasia, a heart muscle disease of unknown cause, anatomically characterized by variable replacement of myocardial muscle with adipose or fibroadipose tissue, is usually considered a selective disorder of the right ventricle. However, concomitant left ventricular involvement has been noted in a few cases. The aim of this study was to evaluate the prevalence and characteristics of left ventricular involvement in right ventricular dysplasia, as well as possible progression of the disease. Thirty-nine patients with right ventricular dysplasia were studied by M-mode and two-dimensional echocardiography; 28 of them also underwent cardiac catheterization, and in 25 endomyocardial biopsy was performed. On first examination the left ventricle was normal in 25 patients, whereas in the remaining 14 right ventricular abnormalities were associated with left ventricular involvement, characterized by asynergic areas (12 patients) or diffuse mild hypokinesis (two patients). During follow-up (27 patients, 84.1 +/- 66.1 months) 10 patients showed worsening of right ventricular function; in nine the appearance or worsening of left ventricular abnormalities was observed. Five patients died (four in congestive heart failure and one suddenly). Results of postmortem examination (available in two patients) showed atrophy of myocells and a massive fatty and fibrous infiltration of the right ventricular wall, associated with degenerative changes and fibrosis of the left ventricle. In conclusion, right ventricular dysplasia may be associated with left ventricular involvement and the disorder appears to be progressive in some instances.

Induction of Functional Neovascularization by Combined VEGF and Angiopoietin-1 Gene Transfer Using AAV Vectors

Vectors based on the adeno-associated virus (AAV) deliver therapeutic genes to muscle and heart at high efficiency and maintain transgene expression for long periods of time. Here we report about the synergistic effect on blood vessel formation of AAV vectors expressing the 165 aa isoform of vascular endothelial growth factor (VEGF165), a powerful activator of endothelial cells, and of angiopoietin-1 (Ang-1), which is required for vessel maturation. High titer AAV-VEGF165 and AAV-Ang-1 vector preparations were injected either alone or in combination in the normoperfused tibialis anterior muscle of rats. Long term expression of VEGF165 determined massive cellular infiltration of the muscle tissues over time, with the formation of a large set of new vessels. Strikingly, some of the cells infiltrating the treated muscles were found positive for markers of activated endothelial precursors (VEGFR-2/KDR and Tie-2) and for c-kit, an antigen expressed by pluripotent bone marrow stem cells. Expression of VEGF165 eventually resulted in the formation of structured vessels surrounded by a layer of smooth muscle cells. Presence of these arteriolae correlated with significantly increased blood perfusion in the injected areas. Co-expression of VEGF165 with angiopoietin-1-which did not display angiogenic effect per se-remarkably reduced leakage of vessels produced by VEGF165 alone.

Ventricular arrhythmias in dilated cardiomyopathy: Efficacy of amiodarone

Sixty-five patients with dilated cardiomyopathy were studied by means of 24-hour ECG monitoring. Ventricular arrhythmias were present in 62 (95.4%), of whom 52 (80%) showed a complex form (multiform ventricular extrasystoles, pairs, and ventricular tachycardia). Forty-one patients, presenting with complex ventricular arrhythmias, received antiarrhythmic treatment with amiodarone (600 mg/day in the first week, 400 mg/day in the second week, and 200 to 400 mg/day chronically), and were then controlled with periodic 24-hour ambulatory monitoring. A significant reduction in the number of ventricular extrasystoles was seen in over 70% of patients during a 3-year period. There was also a significant decrease in the incidence of complex ventricular arrhythmias (particularly of ventricular tachycardia). Adverse effects were noted in 23 patients, but only four had to stop treatment. During the follow-up period, 19 patients died: 14 of heart failure, four of sudden death, and one of a noncardiac cause; all patients who died suddenly were not treated with amiodarone (p = 0.022). Complex ventricular arrhythmias are frequent in dilated cardiomyopathy and it is suggested that amiodarone is effective in short- and long-term control of these arrhythmias.

Long-Term Evolution and Prognostic Stratification of Biopsy-Proven Active Myocarditis

Background— Active myocarditis is characterized by large heterogeneity of clinical presentation and evolution. This study describes the characteristics and the long-term evolution of a large sample of patients with biopsy-proven active myocarditis, looking for accessible and valid early predictors of long-term prognosis. Methods and Results— From 1981 to 2009, 82 patients with biopsy-proven active myocarditis were consecutively enrolled and followed-up for 147±107 months. All patients underwent clinical and echocardiographic evaluation at baseline and at 6 months. At this time, improvement/normality of left ventricular ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points or presence of LVEF≥50%, was assessed. At baseline, left ventricular dysfunction (LVEF<50%) and left atrium enlargement were independently associated with long-term heart transplantation–free survival, regardless of the clinical pattern of disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of patients. Persistence of New York Heart Association III to IV classes, left atrium enlargement, and improvement/normality of LVEF at 6 months emerged as independent predictors of long-term outcome. Notably, the short-term reevaluation showed a significant incremental prognostic value in comparison with the baseline evaluation (baseline model versus 6 months model: area under the curve 0.79 versus 0.90, P=0.03). Conclusions— Baseline left ventricular function is a marker for prognosis regardless of the clinical pattern of disease onset, and its reassessment at 6 months appears useful for assessing longer-term outcome.

Arrhythmias in dilated cardiomyopathy.

Sixty-five patients with dilated cardiomyopathy underwent 24 hour electrocardiographic monitoring: 62 (95.4%) showed ventricular arrhythmias and 52 (80%) complex ventricular arrhythmias (multiform ventricular extrasystoles, paired ventricular extrasystoles and ventricular tachycardia). Complex ventricular arrhythmias correlated significantly with some haemodynamic indices of ventricular dysfunction: patients with multiform and paired ventricular extrasystoles and with ventricular tachycardia had lower values of ejection fraction (31.9 +/- 11.8%, P = 0.002) and of cardiac index (2.9 +/- 0.7 litres/min/m2, P = 0.029) than the others (41.1 11.1% and 3.5 +/- 0.9 litres/min/m2 respectively). Patients were followed for a period of 30 +/- 18 months (20 days to 64 months). During follow-up 19 died and mortality was higher among patients with multiform and paired ventricular extrasystoles and/or ventricular tachycardia. Complex ventricular arrhythmias are frequent in dilated cardiomyopathy: ventricular tachycardia and multiform and paired ventricular extrasystoles seem to be related to a more depressed ventricular function and to a poor prognosis. The importance of antiarrhythmic treatment in these patients has still to be evaluated.

Contrast-induced nephropathy in patients undergoing primary percutaneous coronary intervention without acute left ventricular ejection fraction impairment.

The prognostic relevance of direct contrast toxicity in patients treated with primary percutaneous coronary intervention remains unclear, owing to the confounding hemodynamic effect of acute left ventricular ejection fraction (LVEF) impairment on kidney function estimation. In the present study, 644 consecutive patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were prospectively enrolled. Contrast-induced nephropathy (CIN) was defined as an increase in serum creatinine >25% or a decrease in the estimated glomerular filtration rate (eGFR) <25% from baseline in the first 72 hours. The primary end point of the study was major adverse cardiovascular events at 1 year (composite of death, myocardial infarction, target lesion revascularization, and bleeding). Among the global population, the interaction between the LVEF and eGFR at admission to define CIN was statistically significant (p <0.001). When only the 385 patients without acute LVEF impairment (i.e., those with LVEF ≥40%) were considered, 27 (7%) developed postprocedural CIN that was associated with increased major adverse cardiovascular events rate at 1 year of clinical follow-up (38% vs 9%; p <0.001). On adjusted Cox multivariate analysis, CIN was an independent predictor of worse outcomes, both when defined according to creatinine (hazard ratio 3.81, 95% confidence interval 1.71 to 8.48, p = 0.001) or eGFR (hazard ratio 3.77, 95% confidence interval 1.53 to 9.28, p = 0.004) variations. In conclusion, in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, LVEF has a significant interaction with eGFR. When only patients without acute LVEF impairment were considered, CIN confirmed its negative prognostic effect on the 1-year clinical outcomes.

Immunosuppressive treatment in myocarditis

Twenty patients (13 males and seven females) with a biopsy-proven diagnosis of myocarditis underwent a period of treatment with prednisone and azathioprine. The primary objective of the study was the observation of histologic changes which occur during treatment and after treatment withdrawal. The secondary objective was the detection, if any, of changes in left ventricular ejection fraction. Multiple endomyocardial biopsies were obtained and the treatment was adjusted in order to achieve complete disappearance of the myocardial inflammation. The histologic status was improved in all patients, although complete disappearance of the signs of active disease was seen in 15 patients only. Two patients died during the observation period. A clear relationship between histologic status and immunosuppression was established in some patients (50% of all cases showed a worsening after withdrawal from the treatment). An overall improvement of the ejection fraction was observed (from 0.37 +/- 0.14 to 0.46 +/- 0.17), but a direct effect of the treatment on the recovery of ventricular function cannot be stated. In some patients, however, a direct relationship between the histological changes and the changes in ejection fraction was seen. These data suggest that treatment with prednisone and azathioprine may be beneficial in some patients with biopsy-proven myocarditis and depressed ventricular function.

Acute rickettsial myocarditis and advanced atrioventricular block: diagnosis and treatment aided by endomyocardial biopsy

A case of acute advanced atrioventricular block in a young patient is described. An endomyocardial biopsy performed to confirm myocarditis showed findings compatible with rickettsial endomyocarditis. Treatment with tetracycline was therefore started and a rapid remission of the atrioventricular block was observed. Healing of the disease was subsequently documented by a second endomyocardial biopsy. The rickettsial etiology was confirmed by the results of serial serum titers against Proteus OX-19. Endomyocardial biopsy may be clinically indicated for the diagnosis of advanced atrioventricular block in young patients and may help in their optimal treatment.

Endomyocardial biopsy in dilated cardiomyopathy and myocarditis: which role?

Biopsy of the heart had been limited for many years by the difficulties of reaching the organ and by the fear of serious complications. The introduction of the transvascular endomyocardial bioptome by Konno and Sakakibara in 1962 [l] may, therefore, be considered an important improvement in the diagnosis of diseases of heart muscle. Endomyocardial biopsy spread in subsequent years due to the availability of new and better devices, to the improved skill of the operators, and to the development of new and more sophisticated methods of diagnosis. The diffusion of the technique, nonetheless, was mainly conditioned by the possibility of diagnosing diseases which could be medically cured. The use of endomyocardial biopsy has certainly increased in recent years in many countries. A survey recently conducted by Mason and O’Connell [2], with the help of a questionnaire sent to all 821 cardiac catheterization laboratories in the U.S.A. (with a 60% response) showed that in 310 laboratories, 6292 endomyocardial biopsies were performed by 734 cardiologists with a mean of 22

Percutaneous mitral valve repair: The last chance for symptoms improvement in advanced refractory chronic heart failure?

BACKGROUND The role of percutaneous mitral valve repair (PMVR) in patients with end-stage heart failure (HF) and functional mitral regurgitation (FMR) is unclear. METHODS Seventy-five consecutive patients with FMR grade≥3+ and severe HF symptoms despite optimal medical therapy and resynchronization therapy underwent PMVR with the MitraClip system (Abbott, Abbott Park, IL, USA) at 3 centers. Clinical evaluation, echocardiography and pro-BNP measurement were performed at baseline and at 6-month. RESULTS Mean age was 67±11years, logistic EuroSCORE=23±18%, left ventricle ejection fraction (LVEF) 30±9%. In 6 patients (8%) PMVR was performed as a bridge to heart transplant; many patients were dependent from iv diuretics and/or inotropes. Rate of serious adverse in-hospital events was 1.3% (1 patient who died after conversion to cardiac surgery). Sixty-three patients (84%) were discharged with MR≤2+. At 6-month, 4 patients died (5%), 80% had MR≤2+ and 75% were in New York Heart Association class ≤II. Median pro-BNP decreased from 4395pg/ml to 2594pg/ml (p=0.04). There were no significant changes in LV end-diastolic volume (222±75ml vs. 217±79, p=0.19), end-systolic volume (LVESV, 154±66ml vs. 156±69, p=0.54) and LVEF (30±9% vs. 30±12%, p=0.86). Significant reverse remodeling (reduction of LVESV≥10%) was observed in 25%, without apparent association with baseline characteristics. The number of hospitalizations for HF in comparison with the 6months before PMVR were reduced from 1.1±0.8 to 0.3±0.6 (p<0.001). CONCLUSIONS In extreme risk HF patients with FMR, PMVR improved symptoms and reduced re-hospitalization and pro-BNP levels at 6months, despite the lack of LV reverse remodeling.