Antonio Nicolino

Left ventricular diastolic filling in diabetes mellitus with and without hypertension

Left ventricular diastolic filling by Doppler echocardiography was investigated in 84 diabetic patients without evidence of heart disease and in 84 normotensive nondiabetic age- and sex-matched control subjects. Diabetic patients were subdivided into two groups on the basis of the presence of arterial hypertension. Group 1 comprised 41 normotensive diabetic patients (19 men, 22 women, mean age 63.7 +/- 9.1 years); Group 2 comprised 43 hypertensive diabetics (15 men, 28 women, mean age 65.6 +/- 9.6 years). Doppler measures of diastolic filling were significantly altered in the two groups as compared with control subjects. Peak atrial flow velocity, velocity integral for the atrial filling period, and atrial filling fraction were increased, whereas the ratio of peak early to peak atrial flow velocity and the ratio of flow velocity integrals were decreased, especially in Group 2 patients. Thirteen patients in Group 1 (32%) and 17 in Group 2 (40%) had evidence of diastolic dysfunction, as assessed by the presence of at least two independent abnormal indices (outside age-corrected 95% confidence interval). In each group, patients with altered diastolic filling differed slightly from diabetic patients with normal Doppler indices, tending to increased wall thickness and left ventricular mass. In conclusion, diastolic filling of the left ventricle is frequently altered in diabetic patients and is adversely affected by arterial hypertension whose coexistence further impairs left ventricular relaxation.

Effect of beta-adrenoceptor blockade on dipyridamole-induced myocardial asynergies in coronary artery disease.

Twenty-one patients with angiographic evidence of significant coronary artery disease, and positive dipyridamole echocardiographic test results at basal condition and after 7 days of placebo treatment were prospectively studied to see whether beta blockade modifies the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to propranolol (120 mg/day) or placebo treatment in 3 divided doses for 7 days, after which each patient crossed over to the alternate regimen. Dipyridamole-echocardiographic testing was repeated at the end of each treatment. Propranolol abolished new mechanical signs of transient dipyridamole-induced ischemia (new wall motion abnormalities or an increase in degree of basal asynergies, or both) in 13 of 21 patients. The remaining 8 patients had positive results on dipyridamole echocardiographic testing after the propranolol treatment period. At basal conditions both heart rate and rate-pressure product were significantly reduced with propranolol; there was also a significant decrease in these parameters at peak dipyridamole infusion. At peak dipyridamole infusion heart rate and rate-pressure product were significantly lower in patients with negative than in those with positive echocardiographic test results after propranolol. Our data show that administration of beta blockade significantly reduces the development of transient dipyridamole-induced myocardial asynergies, the earliest markers of acute myocardial ischemia, detected with 2-dimensional echocardiography.

Six-minute walking test but not ejection fraction predicts mortality in elderly patients undergoing cardiac rehabilitation following coronary artery bypass grafting

Background: Age-related effects on the ability of 6-min walking test (6MWT) and ejection fraction (EF) to predict mortality in coronary artery bypass grafting (CABG) patients undergoing cardiac rehabilitation (CR) is still debated. Design and methods: In order to verify the role of 6MWT and EF on all-cause mortality in patients undergoing CR following CABG, 882 CABG patients undergoing CR stratified in adults (<65 years) and elderly (≥65 years) were studied. Results: At the admission, EF was 52.6 ± 9.1% in adults and 51.3 ± 8.9% in elderly (p = 0.234, NS) while 6MWT was 343.8 ± 93.5 m in adults and 258.9 ± 95.7 m in elderly (p < 0.001). After 42.9 ± 14.1 months follow up, mortality was 8.2% in adults and 10.9% in elderly (p = 0.176, NS). Cox regression analysis shows that EF ≥ 50% and 6MWT ≥300 m are protective on mortality in all CABG patients before CR. However, EF ≥50% in adults (HR 0.18, 95% CI 0.06–0.49, p < 0.005) but not in elderly (HR 1.16, 95% CI 0.45–3.42, p = 0.354, NS) and 6MWT ≥300 m in elderly (HR 0.34, 95% CI 0.10–0.79, p = 0.033) but not in adults (HR 0.76, 95% CI 0.31–2.12, p = 0.654, NS) exert a protective role on mortality. Conclusions: Our results indicate that both EF ≥ 50% and 6MWT ≥ 300 m independently protect against mortality in CABG patients before CR. However, their protective role is age dependent. In fact, EF ≥ 50% is protective in adults but not in elderly while 6MWT ≥ 300 m is protective in elderly but not in adult patients.

Diffuse Idiopathic Skeletal Hyperostosis Prevalence in Subjects With Severe Atherosclerotic Cardiovascular Diseases

Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of different entheseal sites. Several metabolic factors have been suggested to be involved in DISH development. We assessed the prevalence of DISH and its relationship to traditional vascular risk factors in a cohort of patients diagnosed with cardiovascular diseases.

Failure of protective effect of Captopril and Enalapril on exercise and dipyridamole-induced myocardial ischemia

Fifteen patients with angiographic evidence of significant coronary artery disease, exertional myocardial ischemia, and positive dipyridamole echocardiographic test results at basal conditions and after 7 days of placebo treatment were prospectively studied to see whether captopril (containing sulfhydryl) and enalapril (nonsulfhydryl) modify myocardial ischemia induced by exercise testing and the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to captopril (150 mg/day in 3 separate doses) or enalapril (20 mg/day) for 1 week. At the end of this period each patient crossed over to the alternate regimen after a washout period of 7 days. Exercise stress testing and dipyridamole echocardiographic testing were repeated at the end of each treatment period. Neither captopril nor enalapril had a significantly greater anti-ischemic effect than placebo in any patient. Exercise duration, time to onset of ST-segment depression, maximal workload, degree of ST-segment depression, and rate-pressure product were not affected by either drug. Neither captopril nor enalapril improved dipyridamole-induced mechanical dysfunction or ST-segment depression.

Left ventricular diastolic filling in elderly hypertensive patients

Objective: To evaluate the effects of mild to moderate hypertension and of LVH on diastolic filling and other Doppler indices in the elderly.

Echo-dipyridamole stress test evaluation of isosorbide-5-mononitrate efficacy and tolerance in patients with coronary heart disease: interplay with sympathetic activity.

In 22 patients with stable myocardial ischemia, we prospectively studied the short- and long-term effects of isosorbide-5-mononitrate (5-ISMN) on dipyridamole-induced myocardial ischemia, the ability of dipyridamole-stress echocardiography to evaluate nitrate tolerance, and the role of activation of the neurohumoral system in nitrate tolerance development, assessed by modifications of catecholamines plasma levels and heart rate variability. After brief treatment with 5-ISMN, dipyridamole-stress echocardiography was negative in 19 of 22 patients (p < 0.001 vs. placebo). During the sustained phase, dipyridamole-stress echocardiography was positive after both placebo and active drug (p = NS vs. placebo). Heart rate variability showed significantly higher values in power of the low frequency (LF) band and low- to high-frequency ratio (L/H), as well as significantly lower values of the power of the high-frequency (HF) band (all p < 0.001) during brief but not during sustained administration of 5-ISMN. Norepinephrine plasma levels were significantly higher (p < 0.001) during short-term 5-ISMN administration but not during the sustained phase. Our results indicate that short-term administration of 5-ISMN antagonizes dipyridamole-induced myocardial ischemia and show the loss of antiischemic efficacy in 95% of patients during sustained treatment, demonstrating that dipyridamole-stress echocardiography is a useful tool to assess the presence of nitrate tolerance. Spectral analysis of heart rate variability and norepinephrine values confirm that brief nitrate administration increases sympathetic activity, a possible crucial trigger event in the development of nitrate tolerance, whereas prolonged nitrate treatment is not associated with prolonged neurohumoral activation.

Effects of delapril in combination with indapamide on blood pressure and left ventricular mass in elderly hypertensive patients.

We present a single-blinded, placebo-controlled trial of the effects on blood pressure and left ventricular mass and of the safety of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65–85 years (mean age, 69 ± 1) with sitting systolic/diastolic blood pressure of 160–200/95–115 mm Hg (at the end of the placebo period). After a 2-week placebo run-in, patients took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. Twenty-four-hour ambulatory blood pressure was monitored and M- and B-mode echo-cardiography were performed before and after 24 weeks of treatment. Blood pressure decreased from 156 ± 1.5/101 ± 1 mm Hg before treatment to 133 ± 1/73 ± 1 mm Hg after treatment. The total blood pressure burden also decreased; the percentage of measurements with a systolic blood pressure ≥ 140 mm Hg and a diastolic blood pressure ≥ 90 mm Hg decreased from 48.7% ± 5%/31.5% ± 4.3% to 23.5% ± 4%/20.5% ± 2.9% (p < 0.0005 and p > 0.05). The area under the curve of the 24-hour blood pressure decreased from 250 ± 41/103 ± 21 mm Hg to 97 ± 21/37 ± 8.5 mm Hg (p < 0.001 and p < 0.005). The left ventricular mass index (LVMI) in the 15 patients with pretreatment left ventricular hypertrophy was reduced after therapy from 167.5 ± 8.5 g/m2 to 152.2 ± 7.6 g/m2 (p < 0.05). A positive correlation was observed between percent changes of the area under the curve of the 24-hour diastolic blood pressure and percent changes of LVMI (r = 0.6; p < 0.05) in the 15 patients with left ventricular hypertrophy. Only 2 patients reported side effects: 1 developed skin rash and 1 developed headache. The safety of the treatment was confirmed by laboratory tests. In elderly hypertensive patients, the combination of delapril and indapamide at low doses reduced blood pressure and had favorable effects on LVMI with few side effects.

Acute dose-response, double-blind, placebo-controlled pilot study of lercanidipine in patients with angina pectoris

Abstract Objective The aim of this double-blind, placebo-controlled, parallel-group, dose-response, pilot study was to assess the acute hemodynamic and therapeutic effects of a single dose of lercanidipine in patients with angina pectoris. Background The calcium channel blocker lercanidipine is a new lipophilic, vasoselective dihydropyridine derivative with a slow onset and long duration of action that has been shown to be effective in hypertensive patients at a dosage of 10 to 20 mg/d. Methods Forty-five patients (42 males, 3 females) with chronic stable angina pectoris and angiographically documented coronary artery disease received a single oral dose of lercanidipine 5 mg (n = 7), 10 mg (n = 8), 20 mg (n = 7), 30 mg (n = 7), or 40 mg (n = 8) or of placebo (n = 8). Anti-ischemic and antianginal efficacy was assessed by a bicycle exercise test 3 and 8 hours after dosing. Systolic and diastolic blood pressures and heart rate were assessed both at rest and during exercise. Results Because of the small number of patients and high variability between the groups, no significant difference was seen compared with placebo. Nevertheless, a significant ( P Conclusions Our data indicated that the acute administration of lercanidipine 10 mg to 40 mg in patients with stable exercise-induced angina pectoris caused no unfavorable change in myocardial oxygen consumption and was well tolerated.

Efficacy of Transdermal Nitroglycerin Patches Evaluated by Dipyridamole-Induced Myocardial Ischemia in Patients with Coronary Artery Disease. Comparison Between Continuous and Intermittent Schedule

Nitrate tolerance remains a problem despite an enormous number of studies on this phenomenon. The aim of the present study was to compare the efficacy of nitroglycerin transdermal patches intermittently or continuously administered to patients with myocardial ischemia evaluated by the echocardiography dipyridamole stress test. We prospectively studied 34 coronary patients with stable myocardial ischemia. A double-blind, randomized, crossover study technique was used. After a run-in period (1 week) they underwent a dipyridamole stress test to evaluate nitrate responsiveness and then were randomized to 1 week of transdermal nitroglycerine 20 mg/24 h (two patches of 10 mg/24) administered either intermittently or continuously for 1 week. During the following week all patients were given placebo. In the final week, therapy was crossed over the alternate regimen. No significant changes in heart rate, systolic and diastolic blood pressure and rate-pressure product were observed at basal conditions and at peak of dipyridamole infusion among patients after placebo run-in period, after acute, 1 week of intermittent and 1 week of continuous nitroglycerine administration. At peak of dipyridamole infusion after acute administration of nitrate we observed a significant decrease in wall motion score index with respect to placebo. This pattern was similar during intermittent, but not continuous, patch therapy (p < 0.001). Our results suggest that transdermal nitroglycerin patches are an effective anti-ischemic medication, in reducing transient myocardial ischemia induced by dipyridamole. This anti-ischemic effect is lost when an overnight nitrate free dose interval is not used. Moreover the dipyridamole echocardiographic stress test, besides evaluating myocardial ischemia-induced wall motion abnormalities, is adequate to assess both the efficacy and the tolerance of transdermal nitrate therapy.