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Biomedical subjects

M Viganò

Publications and source records attributed to M Viganò.

At least 19 recordsLinked to original sources

Successful treatment of aortic dissection after heterotopic heart transplantation.

Heterotopic heart transplantation is a valid option when there is a large donor-recipient size mismatch. However, the presence of the diseased native heart can jeopardize the medium-term and long-term outcome. The problems stemming from this most commonly described in the literature are thromboembolism, angina, and arrhythmias. In this report, we describe the case of a type A aortic dissection in the native aorta that occurred 30 months after heterotopic heart transplantation and the surgical technique successfully applied for its repair. We also discuss some of the alternative techniques.

Aortic Dissection

Efficacy and pharmacokinetics of simvastatin in heart transplant recipients.

OBJECTIVE: To evaluate the efficacy and safety of simvastatin administered to a group of heart transplant patients receiving triple-drug immunosuppressive therapy. We also assessed the potential pharmacokinetic interaction between simvastatin and cyclosporine by comparing mean plasma concentrations of simvastatin beta-hydroxy acid, the major metabolite of the drug, in a group of heart transplant patients treated with cyclosporine and in a control group of patients who had not received heart transplants. Both groups received long-term (> 6 wk) simvastatin therapy. DESIGN: We monitored hyperlipidemia in 20 hypercholesterolemic heart transplant patients receiving simvastatin 10 mg/d and triple-drug immunosuppressive therapy. Changes in laboratory results before and after 4 months of simvastatin therapy were considered. The same laboratory data were monitored in a control group of 20 nonhypercholesterolemic heart transplant patients who were not treated with simvastatin but were receiving triple-drug immunosuppressive therapy. Plasma concentrations of simvastatin beta-hydroxy acid were measured in 14 hypercholesterolemic patients, 7 of whom had received heart transplants and 7 who had not. SETTING: The Division of Cardiology and the First Medical Clinic for the clinical study, as well as the Department of Pharmacology for the pharmacokinetic analysis. PARTICIPANTS: Forty heart transplant patients and 7 hypercholesterolemic nontransplant patients. MAIN OUTCOME MEASURES: Effectiveness of simvastatin was determined by comparing cholesterol and lipoprotein plasma concentrations in 20 patients who underwent heart transplant and were treated with simvastatin for 4 months. The safety of the drug was determined by analyzing changes in laboratory results in the treated group and in the control group, both those who had received heart transplants and those who had received immunosuppressive therapy. RESULTS: After 4 months of simvastatin therapy, total cholesterol decreased by 12.5% and low-density lipoprotein cholesterol decreased by 21.3%. The only statistically significant laboratory change was an increase of 28.7% in the alanine aminotransferase concentrations. Plasma concentrations of simvastatin beta-hydroxy acid were higher in heart transplant patients than in those who had not received heart transplants, the control group. CONCLUSIONS: Low-dosage simvastatin treatment seems to be safe and sufficiently effective to decrease cholesterol concentrations. Concomitant treatment with immunosuppressive therapy (primarily cyclosporine) in heart transplant patients appeared to cause a reduced metabolic clearance of simvastatin from the plasma. More extensive studies on the interaction between simvastatin and cyclosporine are needed to understand the marked variability found in the response to simvastatin.

Adult

[The MELAS syndrome and dilated-hypertrophic cardiomyopathy: a case report].

We describe a case of a 34-year-old male patient first hospitalized in February '93 for stroke (concomitant dilated-hypertrophic cardiomyopathy was noted), and then in April '93 for congestive heart failure. The presence of myopathy, encephalopathy, lactic acidosis and stroke episode allows for the diagnosis of MELAS syndrome, proven by a specific point mutation in mitochondrial DNA. In this case we were able to observe not only the electrocardiographic and echocardiographic features of hypertrophic cardiomyopathy, previously described in mitochondrial encephalomyopathies, but we were also able to monitor the rapid evolution of this cardiomyopathy towards the hypokinetic dilated form with severe impairment of systolic function; this transition was due to changes in the heart anatomy and structure with reduction in the left ventricular (LV) wall thickness and dilatation of all chambers. The remodeling of LV geometry seems to be not definite and capable of dynamic evolution, as suggested by clinical and echocardiographic findings evaluated six months after the hospitalization. In this patient, we obtained a mid-term favourable clinical outcome using inotropic drugs and Ubiquinone (coenzyme Q), an intermediate substrate of the energetic metabolism, which seems to be poorly synthetized because of the early enzymatic defects in the mitochondrial respiratory chain.

Adult

[The noninvasive demonstration of functional reinnervation after heart transplantation].

Although RR interval variability appears to be an ideal method for assessing reinnervation after heart transplantation, it has been shown that respiratory sinus arrhythmia is caused by the mechanical effect of respiration on the right atrium. The neck-suction induces heart rate changes only by means of nervous reflex and its hemodynamic effect is local and hence appears as a useful method for assessing reinnervation. We tested the presence of autonomic reinnervation in 18 heart transplant recipients, compared to 12 donor-age-matched controls. We measured the power of RR interval low- (LF, around 0.1 Hz) and respiratory fluctuations (HF) before and during rhythmic neck-suction stimulation at 0.1 Hz and at a frequency (0.20 Hz) similar to, but distinct from, that of respiration (controlled at 0.25 Hz), before and during 0.04 mg/kg atropine infusion, using autoregressive spectral analysis of RR interval, respiration and neck pressure signals. The relationship between pairs of signals at each frequency was quantitatively assessed by bivariate coherence function. All transplanted subjects showed low-amplitude HF, related to respiration. Detectable LF (whose power was lower than in controls: 1.15 +/- 0.39 versus 6.08 +/- 0.27 1n-ms2, p < 0.001), non coherent with respiration, were present in 11/18 transplanted subjects, and correlated with months since transplantation (r = +0.59, p < 0.05). HF neck suction induced the presence of a 0.20 Hz fluctuation in 12/12 controls, distinct from and greater than the 0.25 Hz respiratory component (7.28 +/- 0.26 versus 6.69 +/- 0.74 1n-ms2, p < 0.01); this was not seen in any of the transplanted subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[The ergometric test after a heart transplant: its usefulness and limits].

Aim of this study was to analyze the cardiovascular response to graded physical exercise in patients who have undergone cardiac transplantation and to assess the ability of exercise stress testing in early detection of coronary artery disease. We studied 114 transplanted subjects (100 men and 14 women, mean age 46.6 +/- 11.3 years), who performed exercise stress testing 6 months after bypass and then every 6 (+/- 1) months during a 5-year follow-up. Variations of hearth rate (HR), systolic blood pressure (SBP), heart rate-pressure product (RPP) values and exercise stress tolerance were studied both in basal and maximum workload conditions. Mean HR values at basal conditions (103.9 +/- 11.3 b/min at 6 months and 89 +/- 12.7 b/min at 60 months, p < 0.05) and maximum workload tolerance (67.7 +/- 20.4 W at 6 months and 100 +/- 17 W at 60 months, p < 0.05) were significantly different at the beginning and at the end of follow-up. SBP values both at basal conditions and at peak exercise had always been constant. Exercise was stopped for leg muscle fatigue in 92% and dyspnea in 7% of the subjects; isolated T-wave and ST segment changes were found in 29.8% and in 10.5% of the patients respectively, whereas 11.4% exhibited both ST-T variations. Angiographic examination (performed in 80/114 patients) showed significant coronary disease (stenosis > 50%) in 8, coronary atherosclerosis (CAD) of minor degree in 4 and provoked spasm in 2 subjects. In this subgroup exercise stress testing induced ischemic ECG changes (ST segment depression > or = 1 mm) without angina in 1 patient, ST-T segment variations only in 5 and no electrocardiographic alterations (negative tests) in 2 patients. Four subjects with CAD and 1 with coronary spasm induced by angiography showed isolated ST segment and T-wave changes. Our work demonstrated that exercise stress testing plays a relevant role in the study of the denervated heart response to dynamic exercise. The rise in workload tolerated, observed in our population, seems to be related to time elapsed from surgery, improvement in clinical conditions, psychological stability and patient's confidence in his own abilities. The tolerance to exercise 6 months after graft seems to predict the quality of performance in the following tests. Our angiographic results reveal a low sensitivity of the exercise stress test in detecting CAD in this population according to traditional electrocardiographic criteria for myocardial ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Expression of proliferating cell markers in normal and diseased human hearts.

Proliferating cell nuclear antigen (PCNA) myocyte expression and histopathologic features related to its occurrence were investigated in normal and diseased hearts of adult humans using both immunohistochemical and Western blotting techniques. Ki67 Western blotting was also performed in the same samples used for PCNA blotting. Two hundred seventy-one endomyocardial biopsies, and 15 adult, 1 embryonic and 2 fetal hearts were studied. The biopsies were from normal donor hearts (n = 71), patients with cardiomyopathy and myocarditis (n = 64), and patients with transplantation with (n = 106) and without (n = 30) acute rejection of any grade. The 15 hearts were from 1 heart donor, and from patients with cardiomyopathy (n = 5), valvular heart disease (n = 2), ischemic heart disease (n = 4), amyloidosis (n = 1) and transplantation with acute rejection (n = 2). The PCNA labeling index was plotted against myocyte hypertrophy, inflammatory infiltrates and binucleation index. The PCNA labeling index ranged from 2 to 9% in embryonic and fetal hearts. PCNA was expressed by 1 to 2% of myocyte nuclei in 12% of normal heart biopsies, 1 to 5% of myocyte nuclei in 28% of cardiomyopathy and myocarditis biopsies, and by up to 8% of myocyte nuclei in 53% of biopsies of patients with transplantation, independently of the presence and degree of acute rejection. In the latter biopsies and in myocarditis, some inflammatory cells also showed PCNA expression. PCNA positive myocytes were both mono- and binucleated, and there was no correlation between binucleation and PCNA labeling indexes. Ki67 and PCNA blotting confirmed immunohistochemical results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[The complex origin of ventricular tachycardia after the total correction of tetralogy of Fallot].

Two patients underwent surgical treatment of ventricular tachycardia after repair of tetralogy of Fallot. Both patients had right bundle branch block, moderate pulmonary valve incompetence and right ventricular dilatation, and were refractory to electrophysiologically guided drug therapy. Both patients underwent intraoperative epicardial mapping, which located the arrhythmogenic focus on the right ventricular outflow tract, on the border of the previous ventriculotomy. In one patient removal of the previous scar and endocardial cryoablation was successful in ablating the arrhythmia. In the other, the same procedure was only temporarily effective. VT recurred and was subsequently identified at the superior border of the closed ventricular septal defect. It was ablated by means of transcatheter radiofrequency. While VT from foci located on the right ventricular free wall can be easily detected and ablated, septal origin of VT requires extensive preoperative and intraoperative electrophysiological evaluation and may necessitate combined surgical and transcatheter procedures.

Adolescent

Primary cardiac tumors. A clinical experience of 12 years.

From January 1980 through December 1992, we performed operations on 31 patients with primary cardiac tumors. There were 12 male and 19 female patients; the ages ranged from 7 to 71 years (mean, 47.7 +/- 18.3 years); 29 were adults and 2 were children. Twenty-six (83.9%) of the tumors were benign, and 5 were malignant. The most frequently encountered benign tumor was myxoma (22), and the most frequently encountered malignant tumor was fibrosarcoma (4). The most common symptoms at clinical presentation were those associated with cardiac insufficiency or embolization. Definition of the tumor was accomplished in all patients by echocardiography; cardiac angiography was performed in only 4 patients. All patients survived the operative procedure and were discharged from the hospital, but 4 patients with malignant disease died within 30 days. Follow-up for myxoma patients ranged from 16 to 151 months (mean, 68.5 +/- 36 months). Among the 26 patients with benign tumors, there was 1 death, 72 months after the surgical procedure, of right-heart failure due to recurrence of the myxoma.

Adolescent

Optimization of sampling time for cyclosporine monitoring in transplant patients.

Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were obtained from 22 patients before their morning dose of CsA and at 2, 4, 6, 8, 10, and 12 hours after the dose on the 7th and on the 21st day after heart transplantation. The plasma samples were assayed by both HPLC and FPIA. The Cmax for CsA was achieved over a period ranging from 2 to 6 hours (mean/median = 4.7/4.0) during the day 7 and the day 21 studies. The mean (+/- SD) half-life was 3.2 (1.0) hours on day 7 and 2.9 (1.1) hours on day 21, (P > 0.05); the mean apparent oral clearance was 276 (117) L/hr on the day 7 and 269 (209) L/hr on day 21, (P > 0.05). When CsA plasma concentration by either FPIA and HPLC was monitored, the drug concentration best correlated with AUC was found to correspond to the plasma samples taken 4 to 8 hours after drug administration. The authors conclude that through blood sampling for therapeutic drug monitoring of CsA is not optimal, and that further studies are necessary to correlate concentration monitoring during the dosing interval with pharmacologic and toxicologic parameters.

Adolescent

Left atrial isolation associated with mitral valve operations.

Surgical isolation of the left atrium was performed for the treatment of chronic atrial fibrillation secondary to valvular disease in 100 patients who underwent mitral valve operations. From May 1989 to September 1991, 62 patients underwent mitral valve operations (group I); 19, mitral valve operations and DeVega tricuspid annuloplasty (group II); 15, mitral and aortic operations (group III); and 4, mitral and aortic operations and DeVega tricuspid annuloplasty (group IV). Left atrial isolation was performed, prolonging the usual left paraseptal atriotomy toward the left fibrous trigone anteriorly and the posteromedial commissure posteriorly. The incision was conducted a few millimeters apart from the mitral valve annulus, and cryolesions were placed at the edges to ensure complete electrophysiological isolation of the left atrium. Operative mortality accounted for 3 patients (3%). In 79 patients (81.4%) sinus rhythm recovered and persisted until discharge from the hospital. No differences were found between the groups (group I, 80.7%; group II, 68.5%; group III, 86.7%; group IV, 75%; p = not significant). Three late deaths (3.1%) were registered. Long-term results show persistence of sinus rhythm in 71% of group I, 61.2% of group II, 85.8% of group III, and 100% of group IV. The unique risk factor for late recurrence of atrial fibrillation was found to be preoperative atrial fibrillation longer than 6 months. Due to the satisfactory success rate in recovering sinus rhythm, we suggest performing left atrial isolation in patients with chronic atrial fibrillation undergoing valvular operations.

Actuarial Analysis

Localization of brain and atrial natriuretic peptide in human and porcine heart.

We have compared the localization of brain and atrial natriuretic peptide-like immunoreactivity in human and porcine hearts, using immunohistochemical techniques at both the light and ultrastructural level and specific antisera to amino-(cardiodilatin) and carboxy-terminal regions of the atrial natriuretic precursor molecule and to brain natriuretic peptide. Atrial myocardial cells in human fetal, normal adult and failing explanted hearts, displayed immunoreactivity for both brain and atrial natriuretic peptide-like sequences. At the subcellular level, brain natriuretic peptide-, cardiodilatin- and alpha-atrial natriuretic peptide-like immunoreactivity were co-localized to secretory granules in atrial myocardial cells. Immunoreactivity was also detected in the left (64%) and right ventricular free walls (23%) of 22 failing explanted hearts, but not in donor cardiac tissues. A gradient of natriuretic peptide immunostaining was observed across ventricular free walls and immunoreactivity for both natriuretic peptide sequences co-localized to secretory granules in a subpopulation of myocardial cells, concentrated in subendocardial regions of the ventricular walls. Brain and atrial natriuretic peptide-like immunoreactivity were also demonstrated in porcine atrial myocardium and cells of the ventricular conduction system. The parallel distribution of cardiac brain and atrial natriuretic peptide-like immunoreactivity suggests a dual regulation and co-storage of the natriuretic peptides in human and porcine hearts.

Adolescent