Left ventricular remodeling and mechanics after successful repair of aortic coarctation.

Forty normotensive patients (mean age 12.3 +/- 6.5 years) followed up after a successful repair of aortic coarctation (mean age at coarctectomy 5.1 +/- 4.8 yrs) were studied by echo-Doppler to (1) evaluate left ventricular (LV) remodeling and endocardial and midwall mechanics, and (2) identify factors that might predispose to persistent abnormalities. Sex- and age-specific cutoff levels for LV mass/height2.7 and relative wall thickness were defined to assess LV geometry. To adjust for age-and growth-related changes in ventricular mechanics, all echocardiographic variables were expressed as a Z-score relative to the normal distribution. In addition, the smallest diameter of the aorta was assessed by magnetic resonance imaging and calculated as percent narrowing compared with the diameter of the aorta at the diaphragmatic level. In the study group, 24 of 40 patients (60%) had normal LV geometry. Among the 16 patients (40%) with abnormal LV geometry, 5 (12.5%) had a pattern of concentric remodeling and 11 (27.5%) an eccentric hypertrophy. LV hypertrophy was marked (LV mass index >51 g/m2.7) in 5 of these patients. No patient had a pattern of concentric hypertrophy. LV contractility was increased (Z-score >95th percentile) in 28 patients (70%) as assessed using the endocardial stress-velocity index. In contrast, LV contractility assessed using midwall stress-velocity index remained elevated (Z-score >95th percentile) in 15 patients (37.5%). The stepwise multiple logistic regression analysis was not able to detect any significant independent predictor of abnormal LV remodeling, including sex, age at surgical repair, length of postoperative follow-up, heart rate, body mass index, systolic and diastolic blood pressure, and smallest diameter of the aorta, as well as indexes of LV geometry (shape, mass, volume, mass/ volume ratio) and function (preload, afterload, pump function, and myocardial contractility). Thus, normotensive patients after surgical repair of aortic coarctation may be in an LV hyperdynamic cardiovascular state (more frequent in those who have undergone late repair) and have multiple patterns of LV geometry.

[Syndrome X and microvascular angina]. / Sindrome X ed angina microvascolare.

The term X syndrome is used to indicate a group of patients who present anginous symptoms and ischemic-type electrocardiographic alterations which appear during exercise tolerance tests, dipiridamol tests or Holter's dynamic monitoring where coronary ultrasonography reveals no evident coronary lesions, vasospastic angina, arterial hypertension and/or diabetes mellitus, block of the left branch when resting or exercising, cardiomyopathy or valvulopathy. The highest incidence is in females with a mean age of around 50. A reduced reserve of coronary flow, highlighted both in response to vasodilatators or rapid stimulation and by positron emission tomography (PET), underlies this syndrome. It is thought to be caused by a dysfunction of the coronary microcirculation which consists in a deficit of the endothelium-dependent vasodilatory mechanisms, probably also owing to the accumulation of vasoconstrictive type substances, like endothelin-1. In addition to a dysfunction of the coronary microcirculation, one widely backed hypothesis concerns the existence of an altered perception of painful symptoms in patients with X syndrome: the anomalous constriction of prearteries might cause an increased release of adenosine, able to provoke angina despite the scarce signs of myocardial ischemia in terms of the metabolic or functional profile. From a therapeutic point of view, treatment of these patients is often ineffective: treatment should be based on the use of nitrates, calcium-antagonists or beta-blockers, if necessary moving on to other forms of therapy (aceinhibitors, xanthine methylate, estrogens, alphablockers, imipramine); the simultaneous use of tranquillizers may be useful in view of the anxious personality often characteristic of these patients.

[Acute hepatitis following amiodarone administration]. / Epatite acuta dopo somministrazione di amiodarone.

A 61 year old man, treated with amiodarone since 1993 for resistant supraventricular arrhythmias, developed acute hepatitis after an intravenous amiodarone administration. Kidney and liver function tests were performed and pointed out abnormal results. Symptoms ascribable to hepatotoxicity were absent. These changes returned to normal levels within 20 days from withdrawal of the drug. Amiodarone hepatotoxicity can be related to prolonged therapy with a high dose. Intravenous amiodarone may cause acute hepatic disease, but it is suggested that polysorbate 80, a solvent added to the intravenous infusion, is a more likely cause of this complication.

Efficacy of carvedilol on complex ventricular arrhythmias in dilated cardiomyopathy: double-blind, randomized, placebo-controlled study.

AIMS: The aim of the present study was to investigate whether the addition of carvedilol to conventional therapy in dilated cardiomyopathy patients is associated with further benefits in the treatment of complex non-sustained ventricular arrhythmias (Lown class III, IV or V). METHODS AND RESULTS: We recruited 168 patients with ischaemic or idiopathic dilated cardiomyopathy, with complex ventricular arrhythmias. Patients able to tolerate low doses of carvedilol were randomized to treatment with carvedilol or placebo for 6 months. Carvedilol treatment improved ventricular function and reduced the incidence of arrhythmic episodes. Notably, by the end of the first month of treatment, the antiarrhythmic efficacy of the drug was significantly greater in patients with ischaemic than in those with idiopathic dilated cardiomyopathy, an effect that could probably be attributed to the anti-ischaemic properties of carvedilol. After 3 months, at a time when ejection fraction was significantly improved in all treated patients, the antiarrhythmic efficacy of carvedilol was similar in the two study groups. CONCLUSIONS: Carvedilol antiarrhythmic efficacy was paralleled by the improvement in ejection fraction, independent of the aetiology of heart failure. The possibility of adding to an already 'optimized' conventional therapy a drug able to reduce the incidence of complex non-sustained ventricular arrhythmias is a therapeutic option that should be considered in the treatment of these patients.

[Incremental doses of diltiazem in patients with coronary artery disease in end-stage renal failure maintained on hemodialysis: which is the optimal dose?]. / Diltiazem a dosaggi crescenti in pazienti uremici emodializzati con cardiopatia ischemica: qual è il dosaggio ottimale?

End-stage renal disease patients on maintenance hemodialysis suffering from coronary artery disease probably receive too low doses of calcium-antagonists, because the attempt to avoid adverse effects prevails the well-documented antianginal activity of the drug. The aim of our study was to assess the safety and efficacy of incremental doses of diltiazem in treating angina pectoris in hemodialyzed patients with coronary artery disease, to identify the optimal dose. Ninety-four chronic hemodialyzed patients (59 males and 35 females; mean age 55.2 +/- 3.3 years; on periodic dialysis for 80.3 +/- 25.6 months) with coronary artery disease and more than 5 min of transient myocardial ischemia during 48 hours of Holter monitoring were included in the study. A double-blind, randomized, placebo-controlled trial design was used. Incremental doses of diltiazem (from 120 to 240 mg/day) were administered in 4 months. At doses of 120 and 180 mg/day it was observed a statistically significant reduction in the number and duration of total and symptomatic ischemic episodes in 48 hours, compared with baseline (p < 0.001). Instead, the number and the duration of silent ischemic episodes did not significantly change (NS). The efficacy on silent myocardial ischemia was obtained only with the dosage of 240 mg/day (p < 0.001). If this dosage was obtained with a sustained-release formulation (120 mg twice a day), the efficacy was similar to the administration of 4 tablets/day of 60 mg, but the tolerability was better, especially during dialysis. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours, one from 6.00 to 9.00 a.m. and another from 4.00 to 8.00 p.m., just during the dialysis. Both peaks were reduced only with 240 mg/day. In conclusion, this study demonstrates that sustained-release diltiazem (120 mg twice a day) is greatly useful in patients with coronary artery disease on maintenance dialysis because it reduces the frequency of silent ischemic episodes, has a good tolerability, and modifies the circadian pattern of ischemic episodes, reducing both peaks during the day.

[Complex ventricular arrhythmias and carvedilol: efficacy in hemodialyzed uremic patients]. / Aritmie ventricolari complesse e carvedilolo: efficacia in pazienti uremici emodializzati.

Carvedilol has been shown to be effective in systemic hypertension and coronary artery disease in patients with end-stage renal disease, on maintenance hemodialysis. The aim of our study was to assess the effects of carvedilol on ventricular arrhythmias in these patients. Ninety-eight uremic patients maintained on hemodialysis, with complex ventricular arrhythmias (class III, IV and V of Lown's classification), not only during dialysis, were included in the study. They were divided into two groups, with mild-to-moderate hypertension or coronary artery disease. The efficacy and safety of carvedilol (50 mg/day) was compared to placebo in a 6-week randomized, double-blind study. Carvedilol significantly reduced, in both hypertensive and ischemic patients, total ventricular premature contractions (82.7 +/- 11.3 vs 358.1 +/- 73.9, p < 0.001; 88.3 +/- 24.4 vs 369.9 +/- 77.8, p < 0.001), repetitive ventricular premature contractions (1.3 +/- 1.3 vs 6.3 +/- 3.5, p < 0.001; 1.2 +/- 0.7 vs 6.9 +/- 2.6, p < 0.001) and episodes of ventricular tachycardia (1.1 +/- 1.2 vs 11.8 +/- 7.5, p < 0.001; 1.4 +/- 1.2 vs 14.0 +/- 8.3, p < 0.001). In placebo-treated patients, instead, these parameters were not significantly changed (329.1 +/- 76.5 vs 361.7 +/- 71.7, NS, and 324.6 +/- 79.7 vs 359.3 +/- 58.1, NS; 6.2 +/- 3.7 vs 7.3 +/- 3.7, NS, and 4.9 +/- 2.2 vs 6.1 +/- 3.2, NS; 9.8 +/- 6.3 vs 13.3 +/- 8.0, NS, and 9.0 +/- 6.2 vs 12.4 +/- 7.8, NS). Carvedilol confirmed a significant effect on myocardial ischemia and systemic hypertension. No significant side effects were reported. Ventricular arrhythmias are frequent in patients with end-stage renal disease maintained on hemodialysis. They are often due to an underlying cardiac disease, namely systemic hypertension with left ventricular hypertrophy and coronary artery disease. The results of our study show that the antiarrhythmic effect of carvedilol is linked, at least partly, to an improvement of the underlying cardiac disease. Uremic patients have a chronic increase in adrenergic tone, with a direct correlation between norepinephrine plasmatic concentration and frequence of premature ventricular contractions. Beta-blockers are very important in these patients because of their modulation on the adrenergic system. They also reduce potassium flow, from extracellular to intracellular fluid. Therefore carvedilol can affect the sudden hypokalemia occurring in the first phase of hemodialysis treatment, that may be an important cause of intradialytic arrhythmias.

[Efficacy of diltiazem in uremic hemodialyzed patients with isolated diastolic dysfunction and dialysis hypotensive crisis]. / Efficacia del diltiazem in pazienti uremici emodializzati con disfunzione diastolica isolata e crisi ipotensive intradialitiche.

The aim of our study was to assess the effects of diltiazem on diastolic function, left ventricular mass and intradialytic hypotension, in uremic patients on maintenance hemodialysis. Forty-eight uremic patients on maintenance hemodialysis (mean age 46 +/- 5 years) with diastolic heart failure and normal systolic function (ejection fraction > 40%), although hemodialysis had been correctly performed, were included in the study. All patients had left ventricular hypertrophy. Diltiazem was given at the dosage of 60 mg, twice a day, for 3 months. At the end of this period, significant improvement of Doppler echocardiographic filling pattern and clinical symptomatology were observed, but left ventricular mass index was unchanged. Episodes of intradialytic hypotension were significantly reduced. We conclude that diltiazem improves symptoms and left ventricular diastolic filling in uremic patients with diastolic heart failure, without modifying left ventricular mass index; impaired diastolic function has an important role in recurrent dialysis hypotension.

[Effectiveness and tolerability of bisoprolol vs. nifedipine in uremic patients with ischemic cardiopathy in dialysis treatment]. / Efficacia e tollerabilità di bisoprololo e nifedipina in pazienti uremici con cardiopatia ischemica in trattamento dialitico.

The effects of bisoprolol on transient myocardial ischemia have been compared with those of nifedipine in patients with coronary artery disease in end-stage renal failure maintained on haemodialysis. We also evaluated the tolerability of both drugs. Sixty patients (42 males, 18 females, mean age 52 +/- 4 years) in renal failure maintained on haemodialysis, with coronary artery disease and more than four significant episodes of transient myocardial ischemia (> or = 1 min) during 48-hour Holter monitoring, were included in the study. All cardiovascular drugs were discontinued > or = 6 days before this 48-hour ambulatory ECG monitoring, with the exception of sublingual nitrates allowed for relief of anginal attacks. Patients were then randomized to receive either bisoprolol or nifedipine for 2 weeks. After a 15-day wash-out period, they were crossed over to receive either bisoprolol or nifedipine for other 2 weeks. Statistical analysis was carried out using the Student's t test. A p value < 0.01 was considered significant. Both bisoprolol and nifedipine reduced number and duration of transient ischemic episodes as well as the total ischemic burden. Reductions were statistically significant for both antianginal drugs. Only bisoprolol was effective in silent ischemia (p < 0.001). It also reduced heart rate (p < 0.001), while nifedipine raised it (p < 0.001). Both drugs reduced systolic and diastolic blood pressure. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours. Both peaks were reduced with bisoprolol. Nifedipine brought a clear overall reduction in the number of episodes but the circadian pattern was unchanged. During the study, 10 patients taking bisoprolol and 12 patients taking nifedipine had drug adverse effects. No one of them had to be withdrawn from treatment. In conclusion, bisoprolol seems to be more useful than nifedipine because its effects, in transient ischemic episodes, are greatly superior to those of nifedipine, and because it is effective also in silent ischemia. Both drugs showed a good tolerability in these patients. Bisoprolol, reducing the two daily peaks of ischemic episodes frequency, has a protective role towards mortality due to coronary artery disease.

[Angiotensin-II receptor inhibitors in hemodialysed uremia patients with arterial hypertension: candesartan cilexitil versus losartan]. / Inibitori recettoriali dell'angiotensina II in pazienti uremici emodializzati con ipertensione arteriosa: candesartan cilexitil versus losartan.

BACKGROUND: The aim of this study was to evaluate, in patients with chronic renal failure in hemodialysis and arterial hypertension, the effectiveness of a new angiotensin II receptor antagonist, the candesartan cilexitil, comparing it with losartan, the first of this new class of drugs. METHODS: We have selected 128 patients with chronic renal failure (92 males and 36 females, mean age 56 +/- 6 years) and arterial hypertension, subjected to hemodialysis 3 times a week, with hemodialytic seniority of 90 +/- 10 months. The inclusion criteria in the study were given from the presence, after 15 days of pharmacological wash-out, of values of diastolic blood pressure (DBP) > or = 95 mmHg and systolic blood pressure (SBP) > or = 150 mmHg, despite a hemodialysis correctly performed. Patients were divided into two groups whether they received single blind randomized candesartan cilexitil 16 mg or losartan 50 mg at hour 8.00 for a period of 8 weeks at the end of which, after a period of pharmacological wash-out of 15 days, the drugs were administered to inverted groups for other 8 weeks. After 4 and 8 weeks of treatment an evaluation of the anti-hypertensive effectiveness by means of medical complete visit and measurement of blood pressure were made. The statistical analysis was made by means of Student's t test for paired data. RESULTS: All the patients concluded the study. After 4 weeks of treatment SBP and DBP were reduced in the group with candesartan cilexitil with regard to baseline values (SBP 151.8 +/- 6.3 vs 159.8 +/- 5.1 mmHg, p < 0.05; DBP 93.6 +/- 4.5 vs 98.1 +/- 3.7 mmHg, p < 0.05). In the losartan group (SBP 151.8 +/- 6.3 vs 158.7 +/- 5.5 mmHg, p < 0.05; DBP 93.6 +/- 4.5 vs 97.5 +/- 3.8 mmHg, p < 0.05) no significant reduction in blood pressure values was observed compared with baseline values (SBP 158.7 +/- 5.5 vs 159.8 +/- 5.1 mmHg, NS; DBP 97.5 +/- 3.8 vs 98.1 +/- 3.7 mmHg, NS). After 8 weeks of treatment in the candesartan cilexitil group (SBP 128.3 +/- 5.9 vs 159.8 +/- 5.1 mmHg, p < 0.05; DBP 81.5 +/- 4.1 vs 98.1 +/- 3.7 mmHg, p < 0.05) and in the losartan group (SBP 151.7 +/- 5.1 vs 159.8 +/- 5.1 mmHg, p < 0.05; DBP 92.7 +/- 3.9 vs 98.1 +/- 3.7 mmHg, p < 0.05) blood pressure values were reduced in the same manner as at baseline. By comparing the two drugs, candesartan cilexitil proved to have a better antihypertensive effectiveness (SBP 128.3 +/- 5.9 vs 151.7 +/- 5.1 mmHg, p < 0.05; DBP 81.5 +/- 4.1 vs 92.7 +/- 3.9 mmHg, p < 0.05). CONCLUSIONS: Our experience suggests that angiotensin II receptor antagonists may be a therapeutic remarkable option in patients with chronic renal failure in hemodialysis and arterial hypertension; the antihypertensive effect seems to be class-specific. Nevertheless, at least for our data, a better and more rapid antihypertensive results was obtained with candesartan cilexitil.