Carlo Montemartini

A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice.

BackgroundImaging of the flow convergence region (FCR) proximal to a regurgitant orifice has been shown to provide a method for quantifying the regurgitant flow rate. According to the continuity principle, the FCR is constituted by concentric hemispheric isovelocity surfaces centered at the orifice. The flow rate is constant across all isovelocity surfaces and equals the flow rate through the orifice. For any isovelocity surface the flow rate (Q) is given by: Q = 2n−r2 Vr, where 2wrr2 is the area of the hemisphere and Vr is the velocity at the radial distance (r) from the orifice. Methods and ResultsWe studied 52 consecutive patients with mitral regurgitation (mean age, 49 years; age range, 21–66 years) verified by left ventricular angiography using color flow mapping. The FCR r was measured as the distance between the first aliasing limit-at a Nyquist limit obtained by zero-shifting the velocity cutoff to 38 cm/sec and the regurgitant orifice. Seven patients without evidence of an FCR had only grade 1 + mitral regurgitation angiographically. There was a significant relation between the Doppler-derived maximal instantaneous regurgitant flow rate and the angiographic degree of mitral regurgitation in the other patients (rs = 0.91, p < 00.001). The regurgitant flow rate by Doppler also correlated with the angiographic regurgitant volume (r = 0.93, SEE = 123 ml/sec) in the 15 patients in normal sinus rhythm and without other regurgitant lesions in whom it could be measured. The correlation between regurgitant jet area within the left atrium and the angiographic grade was only fair (rs = 0.75, p < 0.001). ConclusionsColor flow Doppler provides new velocity information about the proximal FCR in patients with mitral regurgitation. According to the continuity principle, the maximal instantaneous regurgitant flow rate, obtained with the FCR method, may provide a quantitative estimate of the severity of mitral regurgitation, which is relatively independent of technical factors.

Coronary arterial spasm as a cause of exercise-induced ST-segment elevation in patients with variant angina.

Four patients with variant angina pectoris exhibited reproducible exercise-induced chest pain ST-segment elevation. Coronary arterial spasm was documented with arteriography during exerciseinduced ST-segment elevation (three patients) or after intravenous administration of ergonovine maleate (one patient). Our observations show that in patients with variant angina exercise can trigger coronary arterial spasm, thus inducing anginal pain ST-segment elevation.

Clinical significance of exercise-induced silent myocardial ischemia in patients with coronary artery disease.

Exercise-induced silent myocardial ischemia is a frequent feature in patients with coronary artery disease. The purpose of this study was to compare the clinical and angiographic characteristics of 269 patients who complained of chest pain during an exercise test (group I) with those of 204 who developed exercise-induced silent myocardial ischemia (group II). Group I patients more frequently had anginal symptoms of class III and IV of the Canadian Cardiovascular Society than did group II patients, who had milder symptoms (p less than 0.001). The only angiographic difference observed between the two groups was a slightly but significantly higher left ventricular end-diastolic pressure in group II patients (p less than 0.05), who also showed a longer exercise duration (p less than 0.01) with a higher heart rate-systolic pressure product (p less than 0.01) and more pronounced ST segment depression at peak exercise (p less than 0.001). Moreover, ventricular ectopic beats during exercise were more frequently observed in group II patients (p less than 0.05). Coronary bypass surgery was performed in 45% of patients of group I and in 24% of patients of group II (p less than 0.05). Survival curves of medically treated patients did not show any statistically significant difference between the two groups. Thus, although patients with a defective anginal warning system may have more pronounced signs of myocardial ischemia and a greater incidence of ventricular arrhythmias during exercise, their long-term prognosis is not different from that of patients who are stopped by angina from the activity that is inducing myocardial ischemia.

Thrombin Activity and Early Outcome in Unstable Angina Pectoris

BACKGROUND The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome. METHODS AND RESULTS Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A (P<.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring (P<.0001), the presence of intracoronary thrombosis at angiography (P=.016), and abnormal fibrinopeptide A plasma levels (P=.038). CONCLUSIONS Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

Dental pain threshold and angina pectoris in patients with coronary artery disease

One hundred eight consecutive patients with proved coronary artery disease and reproducible exercise-induced myocardial ischemia were studied. During repeated exercise testing, 52 patients (Group I) had myocardial ischemia in the absence of pain (silent ischemia) whereas 56 patients (Group II) experienced anginal symptoms in the presence of electrocardiographic signs of ischemia. A pulpal test was carried out in all patients using an electrical dental stimulator commonly used in dentistry. Electrical current was delivered in increasing intensity from 10 to 500 mA, and the dental pain threshold and the reaction of the patients to maximal stimulation were determined. During the pulpal test, 71.2% of the patients in Group I did not experience pain, even at maximal stimulation (threshold 0), 11.5% were sensitive at threshold I (10 to 200 mA) and 17.3% felt pain at threshold II (210 to 500 mA). In Group II, 69.7% of the patients complained of dental pain at the low intensity test current (threshold I), 10.7% at threshold II and 19.6% at threshold 0. In Group I, 71.2% of patients did not have discomfort (reaction -), even at maximal stimulation, 21.1% had a mild reaction (reaction +) and 7.7% had an intense painful reaction (reaction ++). In Group II, 80.4% of patients were sensitive to the pulpar test (67.9% reported intense painful sensation at maximal stimulation, 12.5% had a mild reaction); 19.6% of patients had no reaction. The two groups of patients were similar with respect to age, sex and angiographic features.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between beta-endorphin plasma levels and anginal symptoms in patients with coronary artery disease

To verify whether beta-endorphin plasma levels influence the presence of anginal symptoms, 74 consecutive male patients were studied. All patients had previously documented coronary artery disease and reproducible exercise-induced myocardial ischemia. Thirty-five patients (Group I) had a history of angina and reported anginal symptoms during exercise stress testing; 39 patients (Group II) were asymptomatic and had documented silent myocardial ischemia during exercise. Baseline beta-endorphin plasma levels were measured in blood samples taken before exercise stress testing and analyzed by beta-endorphin-I125-RIA Kit-NEN (a radioimmunoassay method). The mean baseline beta-endorphin plasma level was 22.5 +/- 19 pg/ml in patients with anginal symptoms compared with 43.7 +/- 28 pg/ml in asymptomatic patients (p less than 0.001). Baseline blood pressure and heart rate-systolic pressure (rate-pressure) product at baseline and at ischemia threshold (1 mm ST segment depression) were similar in the two groups. Group II patients had a longer exercise duration (p less than 0.01), more pronounced ST segment depression (p less than 0.001) and a higher peak rate-pressure product (p less than 0.01). The extent of coronary artery disease, ejection fraction and left ventricular end-diastolic pressure were similar in the two groups. These data suggest that higher baseline beta-endorphin plasma levels may play a role in the decreased sensitivity to pain in patients with silent myocardial ischemia. In addition, different beta-endorphin levels can be associated with a different sensitivity to pain.

Hemodynamics of volume loading compared with dobutamine in severe right ventricular infarction

To compare the hemodynamic effect of volume loading with that of dobutamine infusion in severe ischemic right ventricular (RV) dysfunction, 11 patients with inferior and RV infarction complicated by low cardiac output syndrome and important hemodynamic derangement (systolic blood pressure < 100 mm Hg, cardiac index < 2.0 liters/min/m2, right atrial pressure > 10 mm Hg) were prospectively studied within 48 hours of symptom onset. After right heart catheterization, volume loading (mean 400 ml saline solution) and dobutamine infusion (5 and 10 micrograms/kg/min over 10 minutes) were performed according to a randomized, crossover design. Volume loading resulted in increased right atrial (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) and pulmonary capillary (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) pressures, without increasing cardiac index, heart rate, aortic pressure, or right and left ventricular stroke work index. Dobutamine (5 micrograms/kg/min) increased cardiac index (from 1.5 +/- 0.3 to 1.9 +/- 0.5 liters/min/m2, p < 0.05), incrementing both heart rate (from 61 +/- 12 to 70 +/- 13 beats/min, p < 0.05) and stroke volume index (from 25 +/- 6 to 27 +/- 5 ml/beat/m2, p < 0.05), as well as right (from 1.4 +/- 1.6 to 2.3 +/- 2.2 g.m/m2, p < 0.05) and left (from 21 +/- 7 to 27 +/- 10 g.m/m2, p < 0.05) stroke work indexes; right and left ventricular filling pressures did not decrease. Dobutamine (10 micrograms/kg/min) significantly improved myocardial performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nifedipine on coronary hemodynamic findings during exercise in patients with stable exertional angina.

To investigate the mechanism by which nifedipine improves exercise tolerance in patients with coronary artery disease, we studied 14 patients with stable exertional angina and left anterior descending artery disease by measuring great cardiac vein flow (GCVF) and calculating anterior regional coronary resistance (ARCR) during exercise before and after sublingual administration of 20 mg of nifedipine. After nifedipine seven patients (group I) had no increase in exercise capacity and showed a similar magnitude of ST segment depression at peak exercise, while another seven patients (group II) had prolonged exercise duration (p less than .001) with less ST segment depression at peak exercise (p less than .01). Such effects were achieved despite a significant increase in double product, an indirect index of myocardial oxygen consumption. In group I patients no significant change was induced by nifedipine in GCVF or in ARCR either at rest or at peak exercise. In contrast, in group II patients nifedipine significantly increased GCVF at rest (p less than .05) and at peak exercise (p less than .001). Moreover, resting ARCR was decreased (p less than .01) and remained significantly lower at peak exercise (p less than .01) compared with the prenifedipine values. These data show that nifedipine may increase GCVF and decrease ARCR at rest and at peak exercise in patients with left anterior descending artery disease. Such increase in myocardial oxygen supply seems the most likely mechanism by which nifedipine may improve exercise capacity in patients with stable exertional angina.

Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris.

OBJECTIVES This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris. BACKGROUND Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina. METHODS We assessed the efficacy of adding transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy in a randomized, double-blind, placebo-controlled trial involving 200 patients with unstable angina who were followed up for 4 months. RESULTS Outcome events--death, myocardial infarction or refractory angina requiring revascularization--occurred in 31% of patients receiving nitroglycerin, 42% of those receiving N-acetylcysteine, 13% of those receiving nitroglycerin plus N-acetylcysteine and 39% of those receiving placebo (p = 0.0052). Kaplan-Meier curves showed a higher probability (p < 0.01) of no failure of medical treatment in the group receiving both nitroglycerin and N-acetylcysteine than in those receiving placebo, N-acetylcysteine or nitroglycerin alone. The combination of nitroglycerin and N-acetylcysteine was associated with a high incidence of side effects (35%), mainly intolerable headache, which was almost twice as frequent as in patients receiving nitroglycerin alone. CONCLUSIONS The combination of nitroglycerin and N-acetylcysteine, associated with conventional medical therapy in the long-term treatment of patients with unstable angina, reduces the occurrence of outcome events. However, the high incidence of side effects limits the clinical applicability of this therapeutic strategy at least at the dosage used in the present study.

Beta-endorphins during coronary angioplasty in patients with silent or symptomatic myocardial ischemia

OBJECTIVES The aims of this study were to correlate beta-endorphin plasma levels and anginal pain in patients with ischemia induced by percutaneous transluminal coronary angioplasty and to detect eventual endorphin variations during balloon occlusion. BACKGROUND The opioid system appears involved in the absence of pain occurring in silent myocardial ischemia. METHODS Beta-endorphin plasma levels were measured 24 h before, just before, during and after coronary angioplasty (performed on the left anterior descending artery) in 53 men with documented coronary artery disease and exercise-induced myocardial ischemia. RESULTS Group 1 (33 patients) reported symptoms; group 2 (20 patients) was asymptomatic during angioplasty. In these patients, the prevalence of exercise-induced silent ischemia was 57%. The occurrence of angina during exercise or angioplasty was related to the frequency of angina during daily life when patients were subgrouped. The severity and distribution of coronary artery disease did not differ between the two groups. During angioplasty, the number of balloon inflations and the inflation time and pressure were similar in symptomatic and asymptomatic patients. In each group, no short-term variability of baseline beta-endorphin plasma levels was observed during 2 consecutive days. Corresponding beta-endorphin plasma levels (at baseline and during and after angioplasty) were significantly higher in Group 2. During balloon occlusion, the levels decreased significantly in the symptomatic group at the onset of angina but remained stable in the asymptomatic group. CONCLUSIONS Methodologic variables and the severity of coronary artery disease did not influence the presence of symptoms during angioplasty-induced ischemia. Beta-endorphin plasma levels were higher and more stable in patients with silent ischemia during angioplasty, suggesting that opiate levels and their variation during ischemia are associated with individual attitude toward anginal pain.