Prognostic value of left ventricular hypertrophy and geometry in patients with a first, uncomplicated myocardial infarction.

BACKGROUND: The prognostic impact of left ventricular (LV) geometry on cardiovascular risk for patients with a first, uncomplicated acute myocardial infarction (AMI), and echocardiographic ejection fraction > or =50% has not been well described. METHODS AND RESULTS: Accordingly, 111 AMI consecutive patients (mean age 59.3+/-10 years) performed echocardiographic examination at predischarge. LV mass was calculated by means of Devereux's formula and subsequently indexed by body surface area. Fifty-three patients had LV hypertrophy and 58 patients had normal LV mass. The two groups were homogeneous for demographic, clinical and angiographic variables as well as for the incidence of residual ischemia on predischarge stress testing. During follow-up period there were 24 cardiac events (cardiac death, unstable angina and non-fatal reinfarction) in the 53 patients with LV hypertrophy and only four events in the remaining 58 patients without LV hypertrophy (RR=2.45; CI=1.76-3.41; P<0.0001). The patients with concentric LV hypertrophy showed a higher incidence of events (64%) than patients with eccentric LV hypertrophy (32%, P<0. 05) and patients with normal geometry and mass (6%, P<0.0001). Multivariate Cox regression model identified concentric geometry as the most powerful predictor of combined end-points (chi(2)=32.7, P<0. 0001). CONCLUSIONS: An increased LV mass and concentric geometry resulted important independent markers of an adverse outcome in patients with a first, uncomplicated myocardial infarction and good LV function.

[Multiple rhabdomyomas in a newborn infant. A clinical case report]. / Rabdomiomi multipli in età neonatale. Descrizione di un caso clinico.

Rhabdomyoma is a rare primary benign cardiac tumor usually diagnosed in newborn and infancy. The authors report a case of multiple and completely asymptomatic rhabdomyoma, diagnosed by echocardiography.

Usefulness of the severity and extent of wall motion abnormalities as prognostic markers of an adverse outcome after a first myocardial infarction treated with thrombolytic therapy.

The prognostic value of wall motion score index (WMSI), assessed at predischarge after a first acute myocardial infarction (AMI) in the thrombolytic era, is still not well known. One-hundred forty-four consecutive patients with a first AMI treated with thrombolytic therapy underwent exercise testing and echocardiography at rest before discharge and were followed-up for a mean period of 18 months. During follow-up, there were 32 cardiac events (12 patients had cardiac deaths, 8 had unstable angina pectoris, 1 had nonfatal reinfarction, and 11 patients had congestive heart failure). The patients who experienced any cardiac event had a higher WMSI (1.67+/-0.15 vs. 1.30+/-0.16, p<0.0001), a higher end-systolic volume (75.1+/-34 vs. 59.5+/-22 ml, p<0.01), and a lower ejection fraction (47+/-16% vs. 55+/-10%, p<0.001) at predischarge than patients without events. The incidence of a positive predischarge exercise testing did not differ between patients with and without cardiac events (22% vs. 24%, p = NS). Multivariate Cox regression analysis, including clinical, exercise results, and echocardiographic parameters, showed that the most powerful predictor of a subsequent event was a resting WMSI > or =1.50 before discharge (chi-square 17.8, p<0.0001). Thus, in patients with a first AMI who underwent thrombolysis, the severity and extent of echocardiographically detected wall motion abnormalities are important independent predictors of cardiac events.

Low-dose dipyridamole infusion acutely increases exercise capacity in angina pectoris: a double-blind, placebo controlled crossover stress echocardiographic study.

OBJECTIVES: The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND: Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS: Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS: In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs. dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS: Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity A1 myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals.

C-reactive protein as a marker for cardiac ischemic events in the year after a first, uncomplicated myocardial infarction.

The prognostic role of C-reactive protein levels in patients with a first acute myocardial infarction, an uncomplicated in-hospital course, and the absence of residual ischemia on a predischarge ergometer test and with an echocardiographic ejection fraction > or = 50% has not been described. C-reactive protein was determined during hospitalization in 64 patients (55 men, mean age 64.6 +/- 10.4 years). The patients were followed up for 13 +/- 4 months and the following cardiac events were recorded: cardiac death, new-onset angina pectoris, and recurrent myocardial infarction. Patients who developed cardiac events during the follow-up period had significantly higher C-reactive protein values than patients without events (3.61 +/- 2.83 vs 1.48 +/- 2.07 mg/dl, p <0.001). The probability of cumulative end points was: 6%, 12%, 31%, and 56% (p = 0.006; RR 3.55; confidence interval 1.56 to 8.04), respectively, in patients stratified by quartiles of C-reactive protein (< 0.45, 0.45 to 0.93, 0.93 to 2.55 and > 2.55 mg/dl). In the Cox regression model, only increased C-reactive protein levels were independently related to the incidence of subsequent cardiac events (chi-square 9.8, p = 0.001). Thus, increased C-reactive protein levels are associated with a worse outcome among patients with a first acute myocardial infarction, an uncomplicated in-hospital course without residual ischemia on the ergometer test, and with normal left ventricular function.

Left origin of the atrial esophageal signal as recorded in the pacing site.

Clear atrial depolarizations from inside the esophagus have always been recorded in electrocardiology, but their precise origin is still under discussion. Though atrial signals are recorded along most of the esophagus, pacing of the atria is possible only in a short tract, probably where the esophagus is in contact with the posterior left atrium wall. In order to ascertain which portion of atria gives rise to the esophageal atrial signal recorded in the atrial pacing segment, we examined 37 patients with normal P waves on the standard ECG by inserting esophageal and endocavitary catheters. The interval between the earliest start of the P wave and the bipolar atrial deflection, was measured both through the esophagus (PA-Eso) and the Hisian region (PA-His) (the latest depolarization of interatrial septum). The former was longer than the latter (P < 0.001) in 36 of 37 patients, showing that the esophagus recorded atrial signal, at the site of effective pacing, originates outside the interatrial septum. As the atrial depolarization recorded through the esophagus is significantly delayed compared with the Hisian region recording, a pure left origin of the esophageal signal can be hypothesized. This is supported by the well-known delayed depolarization, during sinus rhythm, of the left atrium posterior wall compared with the right atrium and interatrial septum. Measuring the interval between the standard ECG P wave and atrial depolarization recorded through esophagus in the site of effective pacing, provides a reliable noninvasive estimate of interatrial time conduction.

Combined therapy with benazepril and amlodipine in the treatment of hypertension inadequately controlled by an ACE inhibitor alone.

In a multicenter, randomized, double-blind, placebo-controlled study, we evaluated the efficacy and tolerability of the combination of benazepril, 10 mg, and amlodipine, 2.5 or 5 mg once daily, compared with benazepril, 10 mg, monotherapy in patients with hypertension inadequately controlled with angiotensin-converting enzyme (ACE)-inhibitor monotherapy. After a 2-week placebo and 4-week single-blind benazepril, 10 mg once daily, run-in period, 448 patients, 213 men and 235 women, aged 24-73 years (mean, 55 years), with mean diastolic blood pressure (DBP) > or =95 and < or =120 mm Hg at the end of the benazepril run-in period, were randomized to receive one of the following treatments once daily for 8 weeks: (a) benazepril, 10 mg, plus placebo (BZ10); (b) benazepril, 10 mg, plus amlodipine, 2.5 mg (BZ10/AML2.5); or (c) benazepril, 10 mg, plus amlodipine, 5 mg (BZ10/AML5). Before the patients were admitted to the trial, at the end of the placebo run-in and the benazepril run-in period and at the end of weeks 4 and 8 of the treatment period, sitting and standing blood pressure (BP), heart rate (HR), and body weight were measured 22-26 h after the intake of the trial medication. Both BZ10/AML2.5 and BZ10/AML5 combinations showed better antihypertensive activity than did BZ10 monotherapy at the terminal visit as demonstrated by (a) the 24-h postdosing sitting and standing systolic BP (SBP) and DBP values, which were statistically lower with combination therapy than with BZ10; (b) the success rate, which was statistically higher with both the combinations (69.2% in the BZ10/AML2.5 and 65.8% in the BZ10/AML5 group) compared with the BZ10 group (40.5%). The tolerability was good in the three treatment groups. No significant abnormal laboratory data were detected. There was no difference in efficacy and safety/tolerability between the BZ10/AML2.5 and BZ10/AML5 groups.

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine.

OBJECTIVE: To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, amlodipine. METHODS: One hundred sixty-eight adult outpatients with mild to moderate hypertension were randomly allocated in double-blind fashion and equal number to receive 80 mg valsartan or 5 mg amlodipine for 12 weeks. After 8 weeks of therapy, in patients whose blood pressure remained uncontrolled, 5 mg amlodipine was added to the initial therapy. Patients were assessed at 4, 8, and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure at 8 weeks. Secondary variables included change in sitting systolic blood pressure and responder rates. RESULTS: Both valsartan and amlodipine were effective at lowering blood pressure at 4, 8, and 12 weeks. Similar decreases were observed in both groups, with no statistically significant differences between the groups for any variable analyzed. For the primary variable the difference was 0.5 mm Hg in favor of valsartan (p = 0.68; 95% confidence interval, -2.7 to 1.7). Responder rates at 8 weeks were 66.7% for valsartan and 60.2% for amlodipine (p = 0.39). Both treatments were well tolerated. The incidence of drug-related dependent edema was somewhat higher in the amlodipine group, particularly at a dose of 10 mg per day (2.4% for 80 mg valsartan; 3.6% for 5 mg amlodipine; 0% for valsartan plus 5 mg amlodipine; 14.3% for 10 mg amlodipine). CONCLUSIONS: The data show that valsartan is at least as effective as amlodipine in the treatment of mild to moderate hypertension. The results also show valsartan to be well tolerated and suggest that it is not associated with side effects characteristic of this comparator class, dihydropyridine calcium antagonists.

Twenty-four-hour antihypertensive efficacy of felodipine 10 mg extended-release: the Italian inter-university study.

We assessed the 24-h antihypertensive efficacy of an extended-release (ER) 10-mg formulation of the dihydropyridine felodipine in mild-to-moderate essential hypertension [World Health Organization (WHO) stage I-II]. Thirty patients, 23 men and 7 women, aged 37-70 years (mean 53 +/- 9 years) participated in a double-blind, randomized, cross-over study of felodipine 10 mg ER versus placebo. An ambulatory daytime diastolic blood pressure (DBP) >90 mm Hg at the end of a 4-week run-in period was necessary to enter the 10-week treatment phase. Twenty-nine patients completed the treatment phase. Twenty-two underwent a 2-day single-blind placebo follow-up to assess residual drug effects. All patients underwent ambulatory BP monitoring (ABPM) by Spacelabs 90207 recorders. Recorders were programmed to make automatic BP and heart rate (HR) measurements every 15 min throughout the 24 h. Felodipine 10 mg ER significantly (p < 0.01) reduced ambulatory systolic BP (SBP) and DBP values throughout the 24-h, day (7 a.m. to 11 p.m.) and night (11 p.m. to 7 a.m.) periods, but not influencing average ambulatory HR values. Trough-to-peak (T/P) ratios, calculated on the average ambulatory BP values measured in the 7-9 a.m. 2-h interval of the second day of ABPM (before the new drug administration: trough) and in the 10 a.m. to 12 noon 2-h interval of the first day of ABPM (peak BP-lowering effect), were 0.71 and 0.58 for SBP and DBP, respectively. Individual T/P calculations, after post hoc selection of nonresponders, gave superimposable results, the consistency of which was judged on mean, median, and confidence intervals (CI). However, the wide variability of the individual T/P ratios suggests that this method cannot be the only means to evaluate the duration of action of an antihypertensive drug by ABPM. The long-acting BP-lowering drug effect was clearly shown by the ABPM performed in the follow-up when SBP and DBP average values of the 24-h, day, and night periods were still reduced. Felodipine 10 mg ER effectively reduced BP in patients with mild-to-moderate hypertension, showing prolonged duration of its antihypertensive action beyond the time of the next dose.

Leucocytes and free radicals in stable angina pectoris.

Bicycle ergometer exercise was used to induce ischemia in 20 patients with stable angina pectoris (SAP). Superoxide dismutase (SOD) blood concentrations, free radical generation (by the SOD-inhibitable reaction of ferricytochrome C), malondialdehyde (MDA) plasma concentrations, the unfractionated leucocyte filterability rate and the filterability rates of the granulocyte and mononuclear sub-fractions (using a positive pressure filtration system and 5 mu diameter Nuclepore filters), were monitored before and after exercise in the patients and in 18 matched controls. At the onset of ischemia a significant increase in the level of MDA plasma concentrations and significant decreases in both SOD blood concentrations and the SOD-inhibitable reduction of ferricytochrome C indicated oxygen free radicals had been released in the SAP patients. These changes were associated with significant impairments of granulocyte and unfractionated leucocyte filterabilities and with morphological evidence of granulocyte activation.

[The Study Group of Quinapril in Arterial Hypertension. The Steering Committee]. / Gruppo di studio del quinapril nell'ipertensione arteriosa. Steering Committee.

The efficacy and safety of the treatment of arterial hypertension with the ACE-inhibitor quinapril, were evaluated in a multicentre study conducted in Italy. The study, lasting 14 weeks, after a preliminary wash-out period, allowed response-based titration of quinapril dose from 10 mg to 40 mg once a day, with provision to combine additional hydrochlorothiazide (12.5 to 25 mg), in case of persistently high diastolic pressure levels. The efficacy sample included 1267 patients: at therapy week 14, 78.6% of patients were treated with quinapril alone. Global response rate (intent-to-treat) was 83.3%, with a mean reduction of diastolic pressure of 15.8 mmHg (95% confidence interval from 15.5 to 16.2 mmHg). 91 patients reported 126 associated adverse events (7.0%); the most frequently reported event was cough (2.7%). First-dose hypotension was rarely reported (1.3%), even in elderly and diabetic patients.

[Recent findings on the physiopathology of hypertension]. / Recenti acquisizioni in tema di fisiopatologia dell'ipertensione.

The numerous pathophysiological theories in the field of essential hypertension are often conflicting, and till now a comprehensive model is not available. The aetiology of human hypertension is probably multifactorial, the control mechanisms of hypertension are strictly interdependent, and the alteration of one induces readjustment of the others, so that it is very difficult to discriminate the "primum movens" from its consequences. In this review the recent acquisitions in the aetiology and the pathophysiology of arterial hypertension are analysed, with particular regard to the role of inheritance, of renal mechanisms of sodium retention, ions transport, humoral factors, central nervous system and of enhanced vascular reactivity. The activation of some of these pathophysiological factors induces the rise in peripheral vascular resistance, which is the final common pathway in the development of essential hypertension.

[Abnormal origin of the left coronary artery from the pulmonary artery. Description of a rare case in adulthood]. / Origine anomala della coronaria sinistra dall'arteria polmonare. Descrizione di un raro caso in età adulta.

The anomalous origin of the left coronary artery from the pulmonary artery is a rare and usually fatal congenital malformation. The Authors present a case of anomalous left coronary artery arising from the pulmonary artery diagnosed in an adult patient.

Verapamil 240 SR versus verapamil 120 SR in arterial hypertension. A randomized double-blind, placebo-controlled study with 24-hour ambulatory blood pressure monitoring.

Fifteen patients (6 males, 9 females), age range 36-70 years, were enrolled in a randomized, double-blind, placebo-controlled study according to a Latin-square design, with the aim of comparing 24-hour blood pressure profiles after three 15-day treatment periods with placebo, verapamil SR 120 mg (V120 SR) given twice daily (bid), and verapamil SR 240 mg (V240 SR) given once daily (od). All of the patients were diagnosed as mild or moderate essential hypertensives on the basis of standard casual recordings. Noninvasive 24-hour ambulatory blood pressure (BP) monitoring was performed with an ICR Spacelab 5200 automatic device. In comparison with placebo, a clinically and statistically significant reduction in both systolic and diastolic BP over 24 hours was obtained with both active treatments. Comparison of the two active treatments shows that V240 SR led to a greater reduction in systolic and diastolic BP than V120 SR. No changes in heart rate were observed. Both treatments were well tolerated. In conclusion, both verapamil regimens proved to be effective and safe in treating essential hypertensives, with V240 SR giving better 24-hour BP control.

[Simvastatin versus gemfibrozil in the treatment of primary hypercholesterolemia in hypertensive patients treated with hydrochlorothiazide]. / Simvastatina versus gemfibrozil nel trattamento dell'ipercolesterolemia primaria in pazienti ipertesi in trattamento con idroclorotiazide.

Recent pharmacological studies confirmed the role of hypercholesterolemia in the pathogenesis of coronary atherosclerosis. A 10% reduction in cholesterol levels can reduce the risk of coronary heart disease by 15%. However many hypercholesterolemic patients often suffer from arterial hypertension and drugs such as thiazide diuretics cause an imbalance in lipid metabolism. The efficacy and the tolerability of simvastatin (a inhibitor of HGM-CoA reductase) with that of gemfibrozil (a fibric acid derivative, which can reduce the VLDL level) were compared in a placebo-controlled study in 2 groups of patients with primary hypercholesterolemia and mild-to-moderate essential hypertension treated with hydrochlorothiazide. After 10 weeks standard hypolipidemic diet and hydrochlorothiazide (25 mg od) therapy, 30 patients whose cholesterol levels were still greater than or equal to 250 mg/100 ml and whose diastolic blood pressure was less than 95 mmHg were randomized to one of the following treatments: simvastatin, 20 mg od, gemfibrozil, 600 mg bid or placebo, while continuing dietetic and diuretic treatment. After 24 weeks treatment, simvastatin induced a 37% reduction in cholesterol plasma levels, a 9% increase of HDL and a 16% reduction of LDL. APO-A1 showed a 4% increase, while APO-B showed a 3% reduction. Gemfibrozil induced a 20% reduction in plasma triglycerides and a 13% decrease in plasma cholesterol, with a significant 19% increase in HDL and a 11% reduction in LDL. No significant variations in any of the lipid parameters monitored were observed in the placebo group. Treatment with simvastatin or gemfibrozil in hypertensive patients in hydrochlorothiazide monotherapy can reduce total cholesterol and LDL-cholesterol plasma levels, while significantly increasing HDL plasma levels compared to placebo. Simvastatin, however, resulted more efficient than gemfibrozil on total cholesterol or cholesterol fractions.

Stable angina pectoris and controlled ischemia: what causes the abnormalities in whole blood filterability?

The determinants of the altered whole blood filterability observed during coronary ischemia are still under discussion. Since no studies have been carried out to date on what exactly causes these alterations during the early stages of controlled ischemia in coronary heart disease, a model was set up using a bicycle ergometer test (with a 25 W increase every 2 minutes). Blood samples were taken from 48 stable angina pectoris patients and from a group of 28 matched controls before and immediately after exercise and 8 minutes later. Plasma viscosity, the filterability (through 5 microns diameter pore filters) of whole blood, erythrocytes, and polymorphonuclear and mononuclear leukocytes (separated by density gradient) were monitored. Alterations in whole blood filterability could be linked only to an impairment in polymorphonuclear cell filterability in those stable angina pectoris patients who reported chest pain and/or whose ST segment depression was greater than or equal to 2 mm.

Leucocyte rheology in controlled coronary ischaemia.

Since no studies have been carried out on the exact origin of the alterations in white blood cell rheology during the early stages of controlled ischaemia in coronary arterial disease, a model was set up using a cycle ergometer test (with a 25 watts increase every 2 minutes). Blood samples were taken (before and after exercise and again 8 minutes later at recovery) from 18 patients with stable angina pectoris and a group of 22 matched controls. The filterability (through 5 micrometer diameter pore filters) of the polymorphonuclear leucocyte sub-population (separated by density gradient), the monocyte and lymphocyte sub-fractions (separated by adhesion to Petri dishes) as well as leucocyte activation (observed under a light microscope) were monitored. Our results showed that the total leucocyte count in patients and controls rose after exercise and was accompanied by a differential shift from the polymorphonuclear to the lymphocyte cells. The polymorphonuclear filterability rate increased significantly in patients when compared to their basal values at rest, and to the controls after exercise (+ 19.58%; P less than 0.002 vs basal values at rest; + 18.72%; P less than 0.002 vs controls). This increase persisted throughout the recovery period (+ 19.86%; P less than 0.002 vs basal values; and + 23.52% P less than 0.001 vs controls), indicating that a reduced polymorphonuclear leucocyte filterability can be associated with the first signs of ischaemia.

[Doppler echocardiography in atrial myxoma]. / Ecocardiografia Doppler nel mixoma atriale.

Two-dimensional echocardiography is the technique of choice for the diagnosis of atrial myxoma. In fact the Echo study allows the recognition of the presence of the tumor, and can show its dimensions, shape, implantation site and motility. However, it is not clear the role of Doppler echocardiography in the evaluation of atrial myxoma. This technique could be useful to recognize patients with more severe obstruction to atrioventricular flow due to large tumors. In 4 patients with large atrial myxomas (3 left and 1 right atrial myxoma) Doppler analysis of atrioventricular flow showed an apparent correlation between variation of trans-mitral or trans-tricuspid diastolic flow and symptoms (syncopal attacks). Only patients with an obstruction to atrioventricular flow and severely restricted calculated mitral or tricuspid orifice had syncopal attacks, at variance with patients without flow obstruction. Further studies on larger population will verify this apparent relation between atrioventricular flow obstruction and clinical symptoms in patients with large atrial myxoma.