Giorgio Binetti

Idiopathic restrictive cardiomyopathy in the young: report of two cases

Two cases of idiopathic restrictive cardiomyopathy in young age are reported. This rare kind of restrictive cardiomyopathy is characterized by the absence of specific histologic features of myocardial abnormalities. In both cases (aged 12 and 9 years at diagnosis), the clinical picture was characterized by severe and slowly progressive congestive heart failure. The electrocardiogram showed biventricular hypertrophy, right bundle branch block and pseudoinfarctional Q waves. Echocardiography revealed moderate pericardial effusion, biatrial enlargement, and normal or nearly normal biventricular dimensions and systolic function. Cardiac catheterization disclosed the typically restrictive filling pattern. Right ventricular endomyocardial biopsy demonstrated moderate interstitial fibrosis and cellular hypertrophy without any evidence of infiltrative or storage myocardial disease or endocardial pathology. One patient underwent cardiac transplantation, whereas in the other, transplantation was contraindicated because of longstanding pulmonary hypertension and liver cirrhosis. The knowledge of this rare entity may correctly orient the diagnostic process in children suspected of having restrictive myocardial disease. Heart, or even heart-lung, transplantation must be considered in cases with congestive heart failure before irreversible damage occurs in many organs.

Usefulness of nicorandil in congestive heart failure.

Rest and exercise hemodynamic and hormonal effects of nicorandil, a nicotinamide-nitrate vasodilator, were assessed in 9 patients with New York Heart Association class II or III congestive heart failure (CHF) and left ventricular ejection fraction less than or equal to 40%. Single oral doses of placebo and 40 and 60 mg of nicorandil were given in a double-blind, randomized trial. Hemodynamic measurements were assessed at rest, up to 8 hours after dose and at peak exercise performed on an upright cycloergometer 1 hour after the dose. Forearm blood flow and venous capacitance were measured by plethysmography 45 minutes after dose. Plasma noradrenaline and plasma renin activity were assessed 1 hour and 2 hours after dose, respectively. Data were analyzed by analysis of variance. Peak effects were observed between 30 and 60 minutes after dose. Mean blood pressure decreased from 86 +/- 7 mm Hg after placebo to 78 +/- 7 mm Hg after 40 mg (p less than 0.05) and to 78 +/- 7 mm Hg after 60 mg (p less than 0.05) of nicorandil. Mean pulmonary artery pressure decreased from 24 +/- 11 to 15 +/- 17 mm Hg (p less than 0.05) and to 17 +/- 7 mm Hg (p less than 0.05) and mean pulmonary wedge pressure decreased from 15 +/- 8 to 9 +/- 4 mm Hg (p less than 0.05) and to 10 +/- 5 mm Hg (p less than 0.05). The changes were significant up to 6 to 8 hours after both doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic heterogeneity of hypertrophic cardiomyopathy

We studied the pattern of inheritance of hypertrophic cardiomyopathy among 111 first-degree relatives of 30 patients with the disease. Results of segregation analysis suggest a genetic heterogeneity for hypertrophic cardiomyopathy in that both autosomal dominant and autosomal recessive mode of inheritance can occur.

Echocardiographic evaluation of the response to afterload stress test in young asymptomatic patients with chronic severe aortic regurgitation: sensitivity of the left ventricular end-systolic pressure-volume relationship.

The detection of myocardial depression is an important goal in the management of patients with chronic severe aortic regurgitation but may be quite difficult at an early stage by the conventional basal measures of contractility. The response to afterload stress determined by angiotensin challenge and the end-systolic pressure-volume relationship was evaluated echocardiographically in 16 asymptomatic or mildly symptomatic patients with chronic severe aortic regurgitation, ages 15 to 56 years (mean 32 +/- 12). Nine normal subjects, ages 25 to 41 years (mean 31 +/- 5), served as a control group. In the group with aortic regurgitation, end-systolic dimensions were greater than 55 mm in five of 16 patients and fractional shortening was 25% or less in two of 16. In the control group angiotensin caused a decrease of stroke volume index in six out of nine patients (15% at the most) and a mild increase in three. In the group with aortic regurgitation stroke volume index decreased by 15% or more of the basal value in nine of 16 patients and increased or decreased by less than 15% in seven of 16. Ejection fraction decreased in both groups, from 61 +/- 6% to 52 +/- 7% in the control group and from 56 +/- 6% to 45 +/- 5% in the group with aortic regurgitation. Ventricular function curves were derived by relating end-diastolic volume index to stroke work index; seven of 16 patients had abnormal responses reflecting an afterload mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of felodipine in congestive heart failure

SummaryThe hemodynamic effects of increasing dosages of felodipine, a new calcium antagonist with selective vasodilator properties, were studied in 13 patients with chronic cardiac failure. A Swan-Ganz thermodilution catheter was positioned in the pulmonary artery and hemodynamic parameters were monitored from 9 am to 6 pm for five days. On the first and the fifth day patients received placebo (P) and on the second, third, and fourth day patients received felodipine 5, 10, and 20 mg, respectively. Symptom-limited exercise tests with a bicycle ergometer were performed on both days of P and on the fourth day. A marked reduction of systemic vascular resistance (SVR) and a significant increase of cardiac index without increments of heart rate (HR) were observed after felodipine at rest. A dose response effect could be demonstrated. During exercise a significant increment of cardiac index and decrease of pulmonary wedge pressure was observed after felodipine. Felodipine showed a potent vasodilator action on systemic circulation with significant changes on both stroke volume and filling pressures at rest and during exercise without side effects.

Assessing the role of eptifibatide in patients with diffuse coronary disease undergoing drug-eluting stenting: The INtegrilin plus STenting to Avoid myocardial Necrosis Trial

BACKGROUND The optimal antiplatelet regimen in elective patients undergoing complex percutaneous coronary interventions (PCIs) is uncertain. We aimed to assess the impact of glycoprotein IIb/IIIa (GpIIb/IIIa) inhibition with eptifibatide in clinically stable subjects with diffuse coronary lesions. METHODS Patients with stable coronary artery disease undergoing PCI by means of implantation of >33 mm of drug-eluting stent were single-blindedly randomized to heparin plus eptifibatide versus heparin alone. The primary end point was the rate of abnormal post-PCI creatine kinase-MB mass values. Secondary end points were major adverse cardiovascular events (MACEs) (ie, cardiac death, myocardial infarction, or urgent revascularization) and MACE plus bailout GpIIb/IIIa inhibitor use. RESULTS The study was stopped for slow enrollment and funding issues after including a total of 91 patients: 44 were randomized to heparin plus eptifibatide, and 47, to heparin alone. Analysis for the primary end point showed a trend toward lower rates of abnormal post-PCI creatine kinase-MB mass values in the heparin-plus-eptifibatide group (18 [41%]) versus the heparin-alone group (26 [55%], relative risk 0.74 [95% CI 0.48-1.15], P = .169). Similar nonstatistically significant trends were found for rates of MACE, their components, or MACE plus bailout GpIIb/IIIa inhibitors (all P > .05). Notably, heparin plus eptifibatide proved remarkably safe because major bleedings or minor bleeding was uncommon and nonsignificantly different in both groups (all P > .05). CONCLUSIONS Given its lack of statistical power, the INSTANT study cannot definitively provide evidence against or in favor of routine eptifibatide administration in stable patients undergoing implantation of multiple drug-eluting stent for diffuse coronary disease. However, the favorable trend evident for the primary end point warrants further larger randomized studies.

The Virtual histology In CaroTids Observational RegistrY (VICTORY) study: A European prospective registry to assess the feasibility and safety of intravascular ultrasound and virtual histology during carotid interventions☆

BACKGROUND Carotid occlusive disease is the most common determinant of thromboembolic stroke. However, limited insights in vivo into the pathophysiology and pathology of carotid plaques are available. We designed a prospective multicenter registry to appraise the safety and feasibility of intravascular ultrasound (IVUS) and IVUS-virtual histology (IVUS-VH) imaging before and immediately after carotid stenting. METHODS Symptomatic and asymptomatic patients scheduled for carotid stenting were included. IVUS-VH pullbacks were performed before and after stenting. Angiographic, IVUS and IVUS-VH analyses were performed. The primary objective was to appraise feasibility and safety of IVUS-VH, and secondary objectives were to correlate plaque composition and plaque type derived from IVUS-VH with acute and 30-day complications. RESULTS A total of 119 patients were enrolled. IVUS-VH could be performed in all cases (100%), with additional runs after completion of the stenting procedure in 85%. Most plaques were stable by IVUS-VH, with vulnerable ones at minimum lumen area in 7%. Conversely, vulnerable plaques were significantly more common elsewhere in the internal carotid artery (ICA, 24% of patients, p<0.001). Acute and 30-day adverse events were uncommon (2 strokes, 1 transient ischemic attack), with no significant association between these and IVUS-VH features. CONCLUSIONS IVUS and IVUS-VH examinations during carotid interventions are feasible and safe, and provide important insights on qualitative and quantitative compositions of carotid plaques. Whether carotid IVUS-VH can predict clinical events remains uncertain, awaiting long-term follow-up of the VICTORY study and additional clinical trials.

Severe postcardiac-transplant rejection associated with recurrence of giant cell myocarditis

Giant cell myocarditis is a disease of unknown etiology with several controversial aspects: clinical course, therapeutic management, recurring risk after heart transplantation, and histopathological factors. We report a case of giant cell myocarditis that recurred after orthotopic heart transplantation and an uneventful postoperative period. The myocardial inflammatory process in this patient showed various evolutive phases: an acute onset of diffuse giant cell myocarditis, an evolution into a granulomatous form of inflammation within the explanted heart, and a recurrence with multiple giant cell inflammatory infiltrates in the transplanted heart. Moreover, the patient presented a severe clinical course after surgery with precocious and continuous acute rejections despite the repeated immunosuppressive treatments. In this article we discuss the morphological aspects of the disease and the postoperative course of this case in relation to the possible immune dysregulation of patients affected by myocarditis before heart transplantation.

Medical treatment of eng-stage heart failure

SummaryCongestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Myocardial, coronary, and peripheral effects of xamoterol (ICI 118,587) in open-chest pigs.

SummaryThe hemodynamic and coronary effects of increasing doses of xamoterol, a beta-adrenoceptor partial agonist, were assessed in an anesthetized pig preparation in which cardiovascular reflexes were abolished and sympathetic tone was modified by infusion of noradrenaline (NA). Xamoterol, in basal conditions, increased heart rate (HR) from 104±12 to 120±13 beats/min (p<.001); systolic, diastolic, and mean blood pressure, respectively, from 77±8 to 103±17 mmHg (p<.01), from 48±7 to 70±12 mmHg (p<.01), and from 58±7 to 84±14 mmHg (p<.01); left ventricular dP/dT max from 2098±564 to 4205±937 mmHg/sec (p<.001); and systemic vascular resistance (SVR) from 1745±564 to 2270±739 dynes sec cm−5 (p<.01). The increase in HR and dP/dT max brought about by xamoterol was about 37% and 56%, resectively, of the maximum increase produced by NA. At the highest level of sympathetic tone, xamoterol reduced HR from 148±11 to 122±11 beats/min (p<.001) and no significant change was observed in dP/dT max. The increase in blood pressure and SVR induced by xamoterol was maintained at each level of sympathetic tone. On the contrary, SVR did not change after NA, as expected, since receptors were fully blocked. For a given inotropic effect, xamoterol and NA produced a similar increase in coronary blood flow and myocardial O2 consumption.In conclusion, the results indicate that, in the areflexic pig, xamoterol acts as a partial beta1-agonist, with a more potent positive inotropic than chronotropic effect in basal conditions. At the highest level of sympathetic tone, it does antagonize the chronotropic, but not the inotropic, effect of NA. Xamoterol increases peripheral resistance and blood pressure possibly through a beta2 vascular blocking action, and the increase in contractility induced by xamoterol is paralleled by an increase in myocardial O2 consumption. No direct effects on coronary circulation are observed.