Scognamiglio R

Aortic root dilatation in young men with normally functioning bicuspid aortic valves

OBJECTIVE To evaluate the dimensions of the aortic root in a selected population of young males with isolated normally functioning bicuspid aortic valve. DESIGN AND SETTING Echocardiographic and Doppler evaluation of conscripts with bicuspid aortic valve at the time of military pre-enrolment screening in two military hospitals. SUBJECTS AND METHODS 66 consecutive young men with a normally functioning bicuspid aortic valve were studied to assess aortic size at four aortic levels: annulus, sinuses of Valsalva, supra-aortic ridge, and proximal ascending aorta; 70 consecutive normal young subjects, matched for age and body surface area, were used as controls. RESULTS In men with a bicuspid aortic valve, the diameter of the aortic root was significantly larger than in controls at the sinuses (3.16 (0.37)v 2.87 (0.31) cm, p < 0.001), at the supra-aortic ridge (2.64 (0.46) v 2.47 (0.28) cm, p = 0.01), and at the level of the proximal ascending aorta (3.12 (0.48) v 2.69 (0.28) cm, p < 0.001). The prevalence of aortic root dilatation was 7.5% at the annulus (5/66), 19.6% at the sinuses (13/66), 15% at the supra-aortic ridge (10/66), and 43.9% at the ascending aorta (29/66); 32 subjects (48%) had aortic root dimensions comparable with controls, while 34 (52%) had definitely abnormal aortic root dimensions. CONCLUSIONS Aortic root enlargement in people with a bicuspid aortic valve occurs independently of haemodynamic abnormalities, age, and body size. However, there appear to be different subgroups of young adults with bicuspid aortic valves, one of which is characterised by aortic dilatation, possibly caused by a congenital abnormality of the aortic wall.

Familial occurrence of right ventricular dysplasia: A study involving nine families

Right ventricular pathologic involvement, with autopsy evidence of fibrous and fatty infiltration of the right ventricle, was investigated in members of families in which cases of juvenile sudden death had occurred. Seventy-two subjects from nine families were studied. Sixteen died at a young age and 56 are living. Postmortem investigation in 11 cases (mean age at death 24 years) revealed massive replacement of the right ventricular free wall by fat or fibrous tissue. In the 56 living patients clinical examination included an electrocardiogram (ECG) at rest, ambulatory ECG recording, posteroanterior and lateral chest roentgenograms, M-mode and two-dimensional echocardiograms and exercise stress tests. In 14 patients, hemodynamic, angiographic and electrophysiologic studies were also carried out; right ventricular endomyocardial biopsy was performed in four. Structural and dynamic right ventricular impairment was detected in 30 living patients (mean age 25 years), and concomitant mild left ventricular abnormalities were present in 4. In eight of the nine families studied at least two members were affected. Ventricular arrhythmias (Lown grade greater than or equal to 4a) were recorded in more than half of the cases. The data reveal that right ventricular dysplasia shows a familial clustering and causes electrical instability that may place affected subjects at risk of sudden death. The mean age of these subjects suggests that the disease is manifested at a young age with a polymorphic clinical and arrhythmic profile. Finally, because this disease is a primary disorder of the ventricular myocardium, it should be included among the cardiomyopathies.

Ventricular fibrillation without apparent heart disease: Description of six cases

Since 1977, six patients (five males and one female), aged 14 to 35 years, resuscitated from ventricular fibrillation, were referred to our department for detailed evaluation, after exclusion of major cardiac pathologic conditions. Four patients had a family history of heart disease. Basic ECGs showed sinus rhythm in all of them. PR interval was prolonged in one. Two patients had complete and one had incomplete right bundle branch block. One patient had inverted t waves in V1-3 and late potentials. Three had an upsloping ST-T segment elevation in V1-2. The cardiothoracic index was less than 0.5 in five and 0.50 in one. In one of the five patients studied, the clinical episode of ventricular fibrillation was reproduced by stimulation of the right ventricular outflow tract during electrophysiologic study. Results of cross-sectional echocardiography and angiography showed predominantly structural and wall motion abnormalities of the right ventricle in five patients and slight wall motion abnormalities of the left ventricle in two. Two patients also had mitral and tricuspid valve prolapse. Coronary arteries were normal in all five patients examined. Results of endomyocardial biopsy showed no abnormalities in one patient, fibrosis in two, and fibrolipomatosis in one. Two patients died during follow-up: autopsy was performed in one and results showed right ventricular cardiomyopathy. Thus in five of these selected patients with apparent idiopathic ventricular fibrillation, some abnormalities, predominantly of the right ventricle, were documented only after detailed investigation; however, clinical history and some nonspecific ECG abnormalities were factors in the diagnostic procedure.

Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function

BACKGROUND Vasodilator therapy with nifedipine reduces left ventricular volume and mass and increases the ejection fraction in asymptomatic patients with severe aortic regurgitation. METHODS To assess whether vasodilator therapy reduces or delays the need for valve replacement, we randomly assigned 143 asymptomatic patients with isolated, severe aortic regurgitation and normal left ventricular systolic function to receive either nifedipine (20 mg twice daily, 69 patients) or digoxin (0.25 mg daily, 74 patients). RESULTS By actuarial analysis, we determined that after six years a mean (+/- SD) of 34 +/- 6 percent of the patients in the digoxin group had undergone valve replacement, as compared with only 15 +/- 3 percent of those in the nifedipine group (P < 0.001). In the digoxin group, valve replacement (in a total of 20 patients) was performed because of left ventricular dysfunction (ejection fraction < 50 percent) in 75 percent, left ventricular dysfunction plus symptoms in 10 percent, and symptoms alone in 15 percent. In the nifedipine group, all six patients who underwent valve replacement did so because of the development of left ventricular dysfunction. In addition, all the patients in both groups who underwent aortic-valve replacement had an increase of 15 percent or more in the left ventricular end-diastolic volume index. After aortic-valve replacement, 12 of the 16 patients (75 percent) in the digoxin group and all six patients in the nifedipine group who had had an abnormal left ventricular ejection fraction before surgery had a normal ejection fraction. CONCLUSIONS Long-term vasodilator therapy with nifedipine reduces or delays the need for aortic-valve replacement in asymptomatic patients with severe aortic regurgitation and normal left ventricular systolic function.

Postprandial Myocardial Perfusion in Healthy Subjects and in Type 2 Diabetic Patients

Background—In diabetic patients, postprandial hyperglycemia is a more powerful risk factor for cardiovascular disease than fasting hyperglycemia itself. A negative influence of acute hyperglycemia on systemic endothelial function (brachial artery) has been shown. However, myocardial perfusion during postprandial hyperglycemia has not been investigated. Methods and Results—We evaluated the effects of a standardized mixed meal on myocardial perfusion in 20 healthy subjects and 20 consecutive patients with type 2 diabetes mellitus without macrovascular or microvascular complications. Myocardial perfusion was assessed in fasting and postprandial states by myocardial contrast echocardiography. Fasting myocardial flow velocity (&bgr;, 0.65±0.27 versus 0.67±0.24; P=NS), myocardial blood volume (MBV; 8.3±1.2 versus 8.4±2; P=NS), and myocardial blood flow (5.4±1.5 versus 5.6±2; P=NS) did not differ between control subjects and diabetic patients. In the postprandial state, &bgr; (0.67±0.24 versus 0.92±0.35; P<0.01), MBV (8.4±2 versus 10.9±2.7; P<0.01), and myocardial blood flow (5.6±2 versus 9.9±2.8; P<0.01) increased significantly in control subjects. In diabetic patients, &bgr; increased (0.65±0.27 versus 0.8±0.24; P<0.01) but MBV (8.3±1.2 versus 4.3±1.3; P<0.01) and myocardial blood flow (5.4±1.5 versus 3.4±0.9; P<0.01) decreased significantly. Changes in MBV (expressed as [(MBVpostprandial−MBVfasting)/MBVfasting]×100) were significantly correlated with postprandial glycemia levels in diabetic patients. Conclusions—Postprandial hyperglycemia determines myocardial perfusion defects in type 2 diabetic patients. They are secondary to deterioration in microvascular function causing a decrease in MBV. In diabetic patients without microvascular or macrovascular complications, postprandial myocardial perfusion defects may represent an early marker of the atherogenic process in the coronary circulation; hence, its reversal constitutes a potential goal of treatment.

Arrhythmogenic right ventricular cardiomyopathy in young versus adult patients : similarities and differences

OBJECTIVES This study was designed to evaluate and compare the patterns of arrhythmogenic right ventricular cardiomyopathy in young people and adults. BACKGROUND Few data are available on this cardiomyopathy in young people because clinical and morphologic findings considered pathognomonic are normally based on observations in adults. However, a familial occurrence with a probable genetic transmission led to the study of children and to early detection of this disease, in which sudden death has been reported even in young people. METHODS Seventeen young patients with arrhythmogenic right ventricular cardiomyopathy diagnosed at a mean age +/- SD of 14.9 +/- 4.9 years were studied. Clinical, electrocardiographic, echocardiographic, cineangiographic and biopsy findings were compared with those of 19 adult patients whose condition was diagnosed at a mean age of 38.1 +/- 13.4 years. RESULTS Syncope occurred in 23.5% of the young patients but in none of the adults (odds ratio of familial sudden death 5.54, p = 0.1). Ventricular couplets (odds ratio 16.0, p = 0.004) and subtricuspid bulging on echocardiography (odds ratio 5.95, p = 0.036) were prevalent in the young group. Cineangiographic data in the two groups were similar, except that more hypokinetic areas were found in adults (odds ratio 4.44, p = 0.05). Morphometric analysis of biopsy sections showed a greater amount of fibrous tissue in the young patients (p = 0.04) and a prevalence of fatty tissue in the adults (odds ratio 12, p = 0.005). During an equivalent follow-up time (mean 7 years), two young patients died suddenly, and two had ventricular fibrillation in the absence of antiarrhythmic therapy. CONCLUSIONS The pathognomonic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy in adults are also valid for young people. Sudden or aborted death occurred frequently in young untreated patients.

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus

BACKGROUND Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

Long-term nifedipine unloading therapy in asymptomatic patients with chronic severe aortic regurgitation

Vasodilating agents acutely reduce regurgitant volume and improve left ventricular performance in aortic regurgitation, but more information is necessary about their long-term efficacy. To evaluate the effects of 12 months of therapy with nifedipine, a randomized, double-blind, placebo-controlled trial was performed in 72 asymptomatic patients with severe aortic regurgitation. At 12 months, patients receiving nifedipine had a significant reduction in left ventricular end-diastolic volume index (110 +/- 19 versus 136 +/- 22 ml/m2, p less than 0.01) and mass (115 +/- 19 versus 142 +/- 16 g/m2, p less than 0.01) measured by two-dimensional echocardiography. They also had a reduction in left ventricular mean wall stress (360 +/- 27 versus 479 +/- 36 kdyne/cm2, p less than 0.001) and an increase in ejection fraction (72 +/- 8% versus 60 +/- 6%, p less than 0.05). These data show that the long-term unloading action of nifedipine is able to reverse left ventricular dilation and hypertrophy and suggest that such therapy has the potential to delay the need for valve replacement in asymptomatic patients.

Effects of Treatment With Sulfonylurea Drugs or Insulin on Ischemia-Induced Myocardial Dysfunction in Type 2 Diabetes

In patients with diabetes and coronary artery disease, the potential negative role of sulfonylurea drugs is under intensive investigation. We assessed the effects of treatment with glibenclamide or insulin on the extension of left ventricular myocardial dysfunction induced by acute ischemia. Nineteen consecutive patients with type 2 diabetes and coronary artery disease entered the study. Each patient was randomly assigned to either insulin or glibenclamide therapy. Treatment was crossed over after 12 weeks and maintained for another 12 weeks. At the end of each treatment, left ventricular myocardial function at rest and during dipyridamole infusion was studied by two-dimensional echocardiography under the same conditions of metabolic control. Glibenclamide or insulin treatment did not influence the rest values of left ventricular dimensions, left ventricular ejection fraction (LVEF), or wall motion score index (WMSI). Dipyridamole infusion, in patients receiving glibenclamide treatment, decreased LVEF (43 +/- 7 vs. 37 +/- 12%, P < 0.005) and increased WMSI (1.4 +/- 0.28 vs. 1.98 +/- 0.24, P < 0.001) compared with baseline values; during insulin treatment, LVEF (46 +/- 8 vs. 45 +/- 11%, NS) and WMSI (1.4 +/- 0.29 vs. 1.6 +/- 0.4, NS) did not change significantly. Peak stress LVEF was higher (45 +/- 11 vs. 37 +/- 12%, P < 0.001) and WMSI lower (1.6 +/- 0.4 vs. 1.98 +/- 0.24, P < 0.001) in patients receiving insulin. The results indicate that in patients with type 2 diabetes and coronary artery disease, ischemic myocardial dysfunction induced by dipyridamole infusion is less severe during treatment with insulin than with glibenclamide. Restitution of a preconditioning mechanism in insulin-treated patients may be the potential beneficial mechanism.

A polymorphic form of familial arrhythmogenic right ventricular dysplasia

Thirty-two members of a family were studied. Three of them died in their youth and had evidence of arrhythmogenic right ventricular (RV) dysplasia. The other 29 members underwent clinical examination, electrocardiography, chest x-ray and M-mode and 2-dimensional echocardiography. Fourteen patients found to have structural abnormalities of the right ventricle underwent 24-hour ambulatory electrocardiographic recording and symptom-limited bicycle stress testing. Hemodynamic and angiographic studies were performed in 6 of these patients. In this family the arrhythmogenic RV dysplasia showed a wide variation of abnormalities, ranging from mild, local alterations to generalized involvement of the right ventricle. The patients were separated into 3 groups on the basis of both the clinical profile and noninvasive/invasive studies: 3 subjects who died suddenly; 3 subjects who had severe ventricular arrhythmias; and 8 subjects in whom RV impairment was not associated with any significant arrhythmias. There was no close relation between the severity of the RV abnormality and presence of ventricular arrhythmias. The variability of the RV abnormality and the high prevalence of this condition in this family is consistent with a genetic pattern of autosomal dominance with incomplete penetrance.