A prospective randomized controlled trial of the natural history of idiopathic scoliosis versus treatment with the SpineCor brace. Sosort Award 2011 winner.

AIM: The purpose of this randomized controlled trial was to evaluate the efficacy of the Dynamic SpineCor brace for early idiopathic scoliosis (15°-30°) compared to the natural evolution of the disease. 68 patients participated in this study (32 treated and 36 controls) with at least 5 years follow-up. METHODS: The inclusion criteria were: 1) high risk of evolution: family history and/or proven progressive; 2) no significant pathological malformation of the spine; 3) initial Cobb angle between 15° and 30°; 4) risser 0, 1 or 2. Assessment of brace efficacy included the percentage of patients who have 5º or less curve progression and the percentage of patients who have 6º or more progression at skeletal maturity. RESULTS: At five-year follow-up a correction was achieved in 50% of treated patient and only in 9.5% of controls, stabilization in 42.3% treated and 47.7% in controls and progression in 26.9% for the treated group and 42.8% for controls. For the control patients we considered as a failure if the Cobb angle worsened by more then 5° from the original angle and the patient then received treatment. CONCLUSION: The results 5 years after the treatment suggested that the SpineCor brace reduced the probability of the progression of early idiopathic scoliosis comparing with its natural history. Moreover, the positive outcome appears to be maintained in the long term.

Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study.

OBJECTIVES: This study investigated the prognostic value of left ventricular (LV) mass at echocardiography in uncomplicated subjects with essential hypertension. BACKGROUND: Only a few single-center studies support the prognostic value of LV mass in uncomplicated hypertension. METHODS: The MAssa Ventricolare sinistra nell'Ipertensione study was a multicenter (45 centers) prospective study. The prespecified aim was to explore the prognostic value of LV mass in hypertension. Admission criteria included essential hypertension, no previous cardiovascular events, and age > or =50. There was central reading of echocardiographic tracings. Treatment was tailored to the single subject. RESULTS: Overall, 1,033 subjects (396 men) were followed for 0 to 4 years (median, 3 years). Mean age at entry was 60 years, and systolic/diastolic blood pressure was 154/92 mm Hg. The rate of cardiovascular events (x100 patient-years) was 1.3 in the group with normal LV mass and 3.2 in the group (28.5% of total sample) with LV mass > or =125 g/body surface area (p = 0.005). After adjustment for age (p < 0.01), diabetes (p < 0.01), cigarette smoking (p < 0.01) and serum creatinine (p = 0.03), LV hypertrophy was associated with an increased risk of events (RR [relative risk] 2.08; 95% CI [confidence interval]: 1.22 to 3.57). For each 39 g/m(2) (1 SD) increase in LV mass there was an independent 40% rise in the risk of major cardiovascular events (95% CI: 14 to 72; p = 0.0013). CONCLUSIONS: Our findings show a strong, continuous and independent relationship of LV mass to subsequent cardiovascular morbidity. This is the first study to extend such demonstration to a large nationwide multicenter sample of uncomplicated subjects with essential hypertension.

[Epidural spinal stimulation in the treatment of refractory angina pectoris. Its clinical efficacy, complications and long-term mortality. An Italian multicenter retrospective study]. / La stimolazione spinale epidurale nel trattamento dell'angina pectoris refrattaria. Efficacia clinica, complicanze e mortalità a lungo termine. Studio retrospettivo multicentrico Italiano.

BACKGROUND: Spinal cord stimulation has been used for many years in the treatment of refractory angina pectoris. Its anti-anginal and anti-ischemic effect has been well documented in several studies, but the long-term efficacy, safety and survival rate are not well known. The aim of this study was to carry out a retrospective analysis of a series of patients from the Italian Multicenter Registry, the data of which were collected in five centers, by means of a questionnaire. METHODS: One hundred and thirty patients (83 males, 47 females, mean age 74.8 +/- 9.8 years) were submitted to spinal cord stimulator implantation for refractory angina pectoris in the period 1988-1995 and controlled during a mean follow-up of 31.4 +/- 25.9 months. A previous myocardial infarction had already occurred in 69.3% of patients, whereas in 67.6% multivessel coronary artery disease was documented. A left ventricular dysfunction (ejection fraction < 0.40) was present in 34% of patients; bypass surgery and coronary angioplasty were performed in 49.6% and in 27% of patients respectively. In 96.3% of cases revascularization procedures were not advisable. RESULTS: A complete follow-up of 116 patients (89.2%) was available. The spinal cord stimulator induced a significant reduction in NYHA functional class from 2.5 +/- 1.2 to 1.5 +/- 0.9 (p < 0.01). During the follow-up 41 patients (35.3%) died, and in 14.2% a new acute myocardial infarction developed. The total percentage of minor spinal cord stimulation-related complications was 6.8%. No major complications occurred. The annual total mortality rate was 6.5%, whereas the cardiac mortality rate was 5%. Compared to the survivors, patients who died showed a higher incidence of left ventricular dysfunction, previous myocardial infarction and bypass surgery at implantation. CONCLUSIONS: In our experience, spinal cord stimulation is an effective therapy in patients affected by refractory angina pectoris and who cannot undergo revascularization procedure. The complication rate is low, with the total and cardiac mortality showing a trend as that reported for patients with similar coronary disease.

Dual chamber pacing with optimal AV delay in congestive heart failure: a randomized study.

AIM: A prospective randomized trial was set up to evaluate contractile parameters and quality of life in patients with congestive heart failure. METHODS AND RESULTS: We describe the results from 38 patients in sinus rhythm and with chronic heart failure due to congestive cardiomyopathy, prospectively randomized to optimal medical therapy (Group 1, 19 patients) or optimal medical therapy plus dual chamber pacemaker programmed to optimal AV delay (Group 2, 19 patients). At a 6 month follow-up, 7/19 patients in Group 1 had died compared with 5/19 patients in Group 2. During follow-up, there were few significant changes in evaluated parameters except for mitral regurgitation time, which was prolonged in Group 1 and shortened in Group 2. The systolic left ventricular diameter shortened significantly only in Group 2. An energy and activity questionnaire showed that the effect of DDD pacing in the latter patient population was beneficial. CONCLUSIONS: From these results we may conclude that at the 6 month follow-up DDD pacing with echo-optimized AV interval programming can improve quality of life without affecting survival.

Multicenter, randomized, placebo-controlled, double-blind study of the safety and efficacy of oral delapril in patients with congestive heart failure.

A total of 101 patients (67 delapril, 34 placebo) with congestive heart failure, New York Heart Association (NYHA) classes II and III, entered a multicenter, randomized (2:1), double-blind, placebo-controlled study to determine the minimum effective and maximum tolerated doses of delapril. Patients received placebo or increasing doses of delapril. After a 2-week run-in period on placebo, patients were randomly assigned to delapril or placebo. The dose of delapril was 7.5 mg twice daily for 2 weeks, 15 mg twice daily for another 2 weeks, followed by 30 mg twice daily for 4 weeks. The dose was increased only if the patient did not present any symptoms of orthostatic hypotension. If such symptoms developed, the code was broken and an open treatment was continued on the minimum effective dose (delapril group). Patients with symptoms of orthostatic hypotension in the placebo group were withdrawn. At the end of the 8-week treatment, 36 (54.5%) patients in the delapril group completed the study on 30 mg twice daily, 12 (18.2%) on 15 mg twice daily, and 18 (27.3%) on 7.5 mg twice daily. Seven patients on placebo were withdrawn because of insufficient therapeutic response; one patient on delapril was lost to follow-up. There was a significant improvement (p < 0.01) in bicycle ergometric performance involving an increase in the exercise duration and the maximum workload tolerated in those patients completing the study on delapril 30 mg twice daily and those finishing on 15 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension and ischemic heart disease. Role of dipyridamole echocardiography test.

The aim of this study is to try to evaluate the relationship between arterial hypertension and ischemic heart disease (IHD) in the light of the physiopathologic response pattern to the dipyridamole echocardiography test (DET) in hypertensive patients, in pharmacologic washout, without any electrocardiographic ST segment depression during exercise tests or at rest. Sixty patients affected by mild to moderate asymptomatic essential arterial hypertension were studied: the subjects had a sitting diastolic blood pressure > or = 95 < or = 114 mmHg; there were 38 men and 22 women with a mean age of 49.8 +/- 7.6 years (range twenty-nine to sixty-eight). All patients had undergone high-dose DET (0.84 mg/kg in ten minutes). No patients developed side effects or asynergy in cardiac contractility during the test. In the absence of any significant coronary artery obstruction assessed angiographically, 18 patients (30%) showed ST segment depression > 1.0 mV during DET, sometimes with the presence of ventricular and/or supraventricular extrasystoles. In this group of patients the left ventricular mass index (LVMI) and duration of hypertension (in months) were higher as compared with those of the other 42 patients (respectively: 160.2 +/- 5.1 vs 129.2 +/- 9.2 g/m2, P < 0.02; and 30 +/- 4.8 vs 9 +/- 5.4 months, P < 0.007). In conclusion it is reasonable to speculate from these data that the ischemic-like" dipyridamole-induced ST segment depression, like that shown by patients affected by Syndrome X, might involve a worse prognosis in hypertensive patients. This may be because of increased coronary resistance due to structural modification or anatomic background.

Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR.

Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose).

[The prevention of nitrate tolerance in angina patients treated with transdermal nitroglycerin: a comparison of 2 therapeutic regimens (therapeutic outlook versus dosage reduction)]. / Prevenzione della tolerance ai nitrati in pazienti anginosi trattati con nitroglicerina per via transdermica: confronto di due schemi terapeutici (finestra terapeutica verso riduzione di dosaggio).

We studied the long-term antianginal and anti-ischemic effects of two dosage regimens designed to prevent tolerance to transdermal nitroglycerin (TNTG): (1) 10 mg TNTG applied for 16 h with a 'nitrate-free' interval of 8 h; (2) 10 mg TNTG applied for 16 h followed by a 'nitrate-low' interval of 5 mg applied for 8 h. 129 patients completing a 3-month study period were evaluated by repeated exercise tests. Both regimens significantly increased maximum exercise duration at 3 months, from 699.1 +/- 23.4 to 833 +/- 21.9 s and from 686.1 +/- 20 to 789.6 +/- 22.6 s, respectively, reduced the number of patients with 1 mm S-T segment depression and increased the time duration to 1 mm S-T segment depression. Marked reductions in anginal attacks was observed in both groups: from 6.5 to 0.15 attacks per week and from 6.0 to 0.15 attacks per week, respectively. No statistically significant differences were found between the groups, and both regimens were well tolerated. In conclusion, our results demonstrate sustained antianginal efficacy, without tolerance, of either 'nitrate-free' of 'nitrate-low' interval therapy with transdermal nitroglycerin.

[Changes in the left ventricular function in hemodialyzed patients. Role of Doppler echocardiography]. / Modifiche della funzione ventricolare sinistra in pazienti emodializzati. Ruolo dell'ecocardiografia Doppler.

The aim of this study was to provide a further contribution to the study on the alterations of left ventricular diastolic function induced by dialysis, using simple indexes of diastolic function obtained with Doppler. The study is conduced in 15 patients with renal failure aged between 22 and 51 years old by means of echocardiography M-2D a pulsed Doppler analysis of the left ventricular refilling flow, evaluated before and after dialysis. By the results is risen up that the dLA has had a significant reduction (p = 0.032), the dSLV have undergone a reduction that is not being significant, while the dDLV has had a significant reduction (p = 0.029), shortening fraction is improved even if in a not significant manner. Also the Doppler indexes has had a behaviour homogeneous in the group of studied patients. Early ventricular refilling is reduced, as showed by the reduction of E, consequence of the reduction preload, while the diastolic late refilling has showed a little increment, expressed by the increase af the peak A. The variations of these indexes, even if not statistically significant, express an alteration of pattern diastolic Doppler caused by both the reduction of preload and the alteration of ventricular relaxation. Besides this alteration, to our notice, is not to consider expression of myocardial compromise in this group studied patients. It would be however useful enlargement of the study to greater number of patients with follow-up for better comprehension of this cardiopathy and makes a more individual treatment of these patients.

[The role of Doppler echocardiography in assessing left ventricular diastolic function. Case histories]. / Ruolo dell'ecocardiografia Doppler nella valutazione della funzione diastolica ventricolare sinistra. Contributo casistico.

The aim of this study was to provide a further contribution to evaluate the alterations induced by age on a number of simple Doppler indexes of left ventricular diastolic function. A population of 48 healthy subjects aged between 15 and 78 years old was examined using pulsed Doppler analysis of the left ventricular refilling flow. Linear regression analysis revealed a significant inverse correlation between age and peak speed during rapid refilling (r = -0.80); between age and the ratio between peak speed during rapid refilling and peak during atrial systole (r = -0.92); between age and deceleration time of peak E wave speed, although on the contrary the peak speed of diastolic refilling flow during the atrial systole (r = 0.81) increased significantly with age. Variance analysis showed that indexes of left ventricular diastolic function and age continued on the contrary to be significant n the population as a whole and in both sexes. From these findings it is clear that in the different age groups (15-29, 30-49, 50-65, and over 65) the peak speed of rapid refilling flow was significantly lower in over-65-year-olds than in elderly, middle-aged and young subjects (55 +/- 0.8, 60 +/- 0.5, 65 +/- 0.7 and 75 +/- 0.6 respectively; p < 0.001). The ratio between the peak speed of rapid refilling and that during the atrial systole was lower in over-65-year-olds compared to elderly subjects, middle-aged subjects or the youngest age group (0.94 +/- 0.09, 1.05 +/- 0.13, 1.96 +/- 0.21 and 2.68 +/- 0.50 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine versus nifedipine retard in the treatment of chronic ischemic heart disease.

The efficacy of amlodipine, a long half-life dihydropyridine calcium antagonist, at the dosage of 5-10 mg/day in a single daily administration, has been compared with that of nifedipine R, a short half-life dihydropyridine, at the dosage of 20-40 mg b.i.d. in 29 patients with chronic ischemic heart disease. After a one week placebo period, patients were assigned to the treatment with amlodipine or nifedipine R, according to a randomized sequence and a cross-over, single-blind design, for two control periods of four weeks and without a wash-out interval between these two phases. During the stress test, a significant increase from baseline in test duration and in time to onset of ischemia and of angina have been obtained with both treatments; moreover amlodipine increased significantly the time to onset of ST segment deviation (-1 mm) and the time to maximum ST segment deviation compared with nifedipine R changes. Also with Holter monitoring and in the angina diary there was a significant reduction of anginal episodes. As regards safety profile, amlodipine treatment was associated with a significantly lower incidence of side effects compared with nifedipine R. This is probably due to the particular pharmacokinetics of amlodipine which, besides the long half-life which allows a single daily administration, shows a retarded peak (between the 6th and the 12th hour) with consequent reduction of phenomena connected with fast and excessive peripheral vasodilatation. In conclusion, amlodipine was as effective in reducing the signs of ischemia as nifedipine R, but compliance was better due to the single daily administration and so was tolerability.

[Multiparameter analysis of the ergometric test. Significance of the failure of systolic blood pressure to decrease during recovery phase as an index of coronary disease]. / Analisi poliparametrica del test ergometrico. Significato del mancato decremento della pressione arteriosa sistolica in fase di recupero come indice di coronaropatia.

Ergometric tests were performed in 27 patients who had previously undergone coronarography following instrumental findings and/or symptoms which seemed highly indicative of ischemic cardiopathy. The aim of the study was to assess the diagnostic importance of the failure of systolic blood pressure to decrease during the third minute of the recovery phase of the test as an index of coronary disease. In particular, as reported by other studies, the ratio between systolic blood pressure at the third minute of recovery and maximum systolic blood pressure during the test was also assessed values above 0.7 were considered pathological. Sixteen out the 27 patients examined showed lesions which were hemodynamically significant, whereas 11 patients were free of lesions and 9 had previous myocardial necrosis. The level of the above ratio in subjects without significant coronary lesions was 0.66 +/- 0.05, whereas it was 0.85 +/- 0.04 (p less than 0.01) in patients with coronary disease. Sensitivity, specificity, and positive and negative prognostic values were respectively 91.6%, 62%, 64.7% and 90.9%. In patients with lesions to the three main arteries both the sensitivity and the specificity were 100%. In the same patients, the ST criteria were 85.7%, 50%, 81.8% and 74.3%.

[Evaluation of acute cardiotoxicity from the combination cyclophosphamide-mitoxantrone-5-fluorouracil (CMF) with Holter ECG]. / Valutazione della cardiotossicità in acuto dell'associazione ciclofosfamide-novantrone-5-fluorouracile (CNF) mediante ecg di Holter.

By making use of a twenty-four hour Holter monitoring, it as been possible to compute the acute cardiotoxicity of the cyclophosphamide + mitoxantrone + 5-fluorouracil (CNF) association in twenty oncologic patients (pts) each of whom being immune from organic cardiopathy emerging clinically and at their first cycle of chemotherapy. The following parameters have been computed: meaningful changes in the heart frequency; premature atrial and ventricular depolarizations, both as a first appearance and as a clear growth in the number; the ST dislocation entity; malignant ventricular arrhythmias. The administration of CNF at the doses of: 600 mg/m2 of cyclophosphamide, 12 mg/m2 of mitoxantrone and 600 mg/m2 of 5-fluorouracil , has caused a meaningful increase in the heart frequency on 6 pts (30%), an increase of premature atrial depolarization on 4 pts (20%) with an appearance ex novo on 2 pts (10%), an increase of premature ventricular depolarization, without any passing to superior Lown classes, on 2 pts (10%) with an appearance ex novo on 3 pts (15%). Although the results in the study point out a frequency percentage of simple hyperkinetic arrhythmias equal to the 55%, the lack of more serious hyperkinetic arrhythmias and of intense disorders of ventricular repolarization testified to a synergic effect as a determining factor on the acute cardiotoxicity of the previously discussed association, in our opinion.

[3 cases of gingival hyperplasia during nifedipine therapy]. / Su tre casi di iperplasia gengivale in corso di terapia con Nifedipina.

The authors report the cases of three male patients, aged 36, 54 and 52 years, who developed gingival hypertrophy during treatment with nifedipine at a dose of 40 mg/daily. Hypertrophy was the same as that observed in patients treated with anti-convulsive or cytostatic drugs, and may probably be due to interference with calcium ions and local factors. Full recovery was achieved by suspending nifedipine treatment in all patients.

[The diagnostic value of delta-R and delta-Q as positive criteria of the ergometry test in a group of patients with angina pectoris of effort]. / Valore diagnostico del delta-R e del delta-Q come criteri di positività del test ergometrico in un gruppo di pazienti con angina da sforzo.

ECG-exercise tests were performed in 29 patients affected by effort chest pain. All patients underwent coronary angiography and/or revealed positive results in the cycloergometer effort test. The aim of the study was to evaluate ultrasonic variations in the R and Q waves due to maximal effort, so as to increase the information provided by the effort ECG. In the coronary angiographic test, 21 out of 29 patients revealed significant hemodynamic coronary stenosis; 10 patients were affected by previous myocardial necrosis; 8 patients showed no hemodynamic coronary lesions (OV). In the OV patients a statistically significant increase was observed in the Q wave at maximal effort in comparison with average basal values; on the other hand, there was a decrease, although not significant, in voltage at peak effort in patients with coronary stenosis. R wave amplitude was smaller in comparison to basal values in OV patients, while a significant increase was observed in the 21 patients with coronary lesions.

Captopril at 50 mg as well as at 100 mg once a day reduces blood pressure for up to 24 h: a double-blind randomized crossover study in mild to moderate hypertensives.

The extent and the duration of the antihypertensive effect of captopril, given once a day at a dose of 50 mg, compared with placebo and with the 100 mg once daily dose was studied in 30 mild or moderate uncomplicated essential hypertensives (mean +/- s.e.m. age 52.0 +/- 1.5 years), who responded (mean blood pressure decrease greater than 10%) to a single oral dose (12.5 mg) of captopril. According to a randomized, double-blind, crossover design, they were given 50 mg captopril four times a day, 100 mg captopril four times a day or matched placebo for 1 month. At the end of each treatment period blood pressure and heart rate were measured every 30 min from 3 h before to 2 h after the last dose. Although the heart rate did not change, mean blood pressure after the 50- and 100-mg doses of captopril was consistently significantly (P less than or equal to 0.05) lower than after placebo. The hypotensive effect peaked at the second hour and was still significant 24 h after dosing without any significant differences between the 50- and the 100-mg doses. These findings indicate that captopril, given chronically once a day at a dose of 50 mg to mild to moderate hypertensive responders, exerts its hypotensive effect up to 24 h and that doubling the dose does not increase either the extent or the duration of its action.

[Digitalization of the arrhythmic heart patient]. / La digitalizzazione del cardiopaziente aritmico.

Digitalis combines a longstanding tradition with constant up-to-dateness. Kinetic maintenance therapy is very often required for heart patients with arrhythmia as one of their most striking clinical manifestations. The well-known questions of paroxystic tachycardia, flutter and atrial fibrillation are examined, and attention is concentrated on ventricular extrasystole, sinoatrial node disease, and Wolff-Parkinson-White syndrome. It is clear that combinations with recently introduced antiarrhythmic drugs, and administration of diuretics and electrolytes, and the employment of electrical stimulation have facilitated the long-term treatment of the chronic arrhythmic heart patient and brought about the better utilisation of digitalic substances. Their arrhythmogenic potential, however, cannot be overlooked.