Prognostic value of pulmonary venous flow Doppler signal in left ventricular dysfunction: contribution of the difference in duration of pulmonary venous and mitral flow at atrial contraction.

OBJECTIVES: We assessed the contribution of difference in duration of pulmonary venous and mitral flow at atrial contraction (ARd-Ad) for prognostic stratification of patients with left ventricular (LV) systolic dysfunction. BACKGROUND: Although pulmonary venous flow (PVF) variables may supplement mitral flow patterns in evaluating left ventricular (LV) diastolic function, their value to the prognostic stratification of patients has not been investigated. METHODS: Pulsed wave Doppler mitral and PVF velocity curves were recorded in 145 patients (mean age: 70 years) with LV systolic dysfunction secondary to ischemic or nonischemic cardiomyopathy who were followed for 15 +/- 8 months. In 38% of patients, PVF signal was enhanced by the intravenous (IV) administration of a galactose-based echo-contrast agent. Based on E-wave deceleration time < or = or >130 ms and ARd-Ad, patients were grouped into restrictive (group 1, n = 40), nonrestrictive with ARd-Ad > or =30 ms (group 2, n = 55) and nonrestrictive with ARd-Ad <30 ms (group 3, n = 50). RESULTS: During follow-up, 29 patients died from cardiac causes and 28 were hospitalized for worsening heart failure (HF). On multivariate Cox model, ARd-Ad > or =30 ms provided important prognostic information with regard to cardiac mortality and emerged as the single best predictor of cardiac events (cardiac mortality, hospitalization). The 24-month cardiac event-free survival was best (86.3%) for group 3; it was intermediate (37.9%) for group 2; and it was worst (22.9%) for group 1 (p < 0.0002 group 1 vs. 3; p < 0.0005 group 2 vs. 3; p < 0.0003 group 1 vs. group 2). CONCLUSIONS: Assessment of ARd-Ad exhibited an independent value in the prognostic evaluation of patients with LV systolic dysfunction. Moreover, it contributed to identify patients at low, intermediate and high risk of cardiac events.

Coronary vasodilation by nitrates is not mediated by the prostaglandin system: a quantitative cineangiographic study.

The possible role of prostaglandins in mediating large coronary artery vasodilation by nitrates was investigated by quantitative magnification coronary angiography. The effects of aspirin (1 g systemically and 100 mg intracoronary) in preventing large coronary artery vasodilation induced by intracoronary isosorbide dinitrate was investigated in 16 patients. Of these, 5 received 0.3 mg (Group 1A) and 11 received 3 mg (Group 1B) intracoronary isosorbide dinitrate, before and 15 minutes after aspirin. Relative to control, 0.3 mg isosorbide dinitrate induced a 19 +/- 9% (mean +/- SD) (p less than 0.01) and 19.5 +/- 11% (p less than 0.01) increase in coronary diameter before and after aspirin, respectively (p = NS). Changes after 3 mg isosorbide were 23 +/- 12% (p less than 0.01) and 26.5 +/- 14% (p less than 0.01), respectively, before and after aspirin (p = NS). In 10 additional patients (Group 2), the effect of the same dose of aspirin on rest coronary artery tone was assessed: changes relative to control were 0.9 +/- 5.5% (p = NS) minutes after aspirin. The intracoronary administration of 3 mg isosorbide dinitrate produced a 24.7 +/- 11% increase in coronary diameter (p = NS versus pre- and postaspirin isosorbide in Group 1B). Urinary 6-ketoprostaglandin-F1 alpha values in urine samples collected in the 8 hours before and the 8 hours after the study in five patients in Group 1B and five patients of Group 2, revealed a 36 +/- 14% (mean +/- SD) reduction in excretion of prostacyclin (p less than 0.01). These data rule out a role for prostaglandins both in mediating dilation of large coronary arteries by nitrates and in affecting their vascular tone at rest.

Prognostic value of dipyridamole echocardiography early after myocardial infarction in elderly patients. Echo Persantine Italian Cooperative (EPIC) Study Group.

OBJECTIVES: This study was conducted to assess the feasibility, safety and prognostic value of dipyridamole echocardiography in elderly patients recovering from an uncomplicated acute myocardial infarction in a subset analysis performed on the patients entered in the subproject "residual ischemia" of the Echo Persantine Italian Cooperative Study (EPIC). BACKGROUND: Coronary heart disease accounts for two thirds of all deaths in the age group > 65 years, and > 50% of all patients admitted to the hospital with acute myocardial infarction are > 65 years old. The prognostic value of dipyridamole-induced left ventricular dysfunction was clearly established in patients evaluated early after acute infarction. METHODS: In a subgroup analysis of the Echo Persantine Italian Cooperative Study (EPIC), we assessed the value of dipyridamole echocardiography in predicting cardiac events in 190 elderly (> or = 65 years) patients (age 68.4 +/- 3.3 years, range 65 to 78; 147 men and 43 women) evaluated early (mean 10 days) after uncomplicated acute myocardial infarction and followed up for 14 +/- 9.8 months. RESULTS: There was no major side effect during dipyridamole echocardiography. A positive test result occurred in 85 patients (44.7%). During follow-up, there were 62 events (14 cardiac deaths, 7 nonfatal reinfarctions, 21 cases of class III or IV angina and 20 revascularization procedures). Of these 62 events, 44 occurred among 85 patients with positive dipyridamole echocardiography and 18 among 105 patients with negative dipyridamole echocardiography (52% vs. 17%, p < 0.001). Spontaneous events (death, reinfarction, angina) occurred in 31 patients with positive and in 11 with negative dipyridamole echocardiography (36% vs. 10%, p < 0.001). Hard events (myocardial infarction or death) occurred in 14 patients with positive and 7 with negative dipyridamole echocardiography (16% vs. 6%, p < 0.05). Death occurred in 11 patients with positive and in 3 with negative dipyridamole echocardiography (13% vs. 3%, p < 0.01). The positive predictive value of positive dipyridamole echocardiography and negative predictive value of negative dipyridamole echocardiography as related to the occurrence of all events in the follow-up period (death, reinfarction, angina, revascularization procedures) were 52% and 83%, respectively. The relative risk (that is, the relative risk of occurrence of future cardiac events in the group with positive dipyridamole echocardiography compared with that in those with negative dipyridamole echocardiography) was 3 for all events and 4.4 for death. CONCLUSIONS: Dipyridamole echocardiography was well tolerated by elderly patients and proved to be very effective in prognostic stratification early after uncomplicated acute myocardial infarction, even when only survival was considered.

Myocardial washout of sonicated iopamidol reflects coronary blood flow in the absence of autoregulation.

OBJECTIVES: The aim of the study was to evaluate the relation between measurements derived from myocardial contrast echocardiography and coronary blood flow. BACKGROUND: Contrast echocardiography has the potential for measuring blood flow. METHODS: In six open chest anesthetized dogs, the left circumflex coronary artery was cannulated and perfused with blood drawn from the left femoral artery. While adenosine was infused into the circuit, circumflex flow was generated by a calibrated roller pump to the point of abolishing coronary autoregulation. At each of 25 levels of coronary blood flow, paired bolus injections of sonicated iopamidol were performed proximal to a mixing chamber. The perfused area of the left circumflex coronary artery was labeled by radioactive microspheres injected into the perfusion line. Two-dimensional echocardiographic images of the left ventricular short axis were digitized off-line, and myocardial videodensity was measured in the area perfused by the left circumflex coronary artery to generate time-intensity curves. RESULTS: The washout slope of curves showed a good correlation with coronary blood flow, ranging from 0.5 to 12.5 ml/min per g of tissue. This correlation was good both in individual dogs (correlation coefficient [r] ranging from 0.78 to 0.96) and in the group of animals as a whole (r = 0.85). Washout slope also showed a good correlation with coronary diastolic pressure (r = 0.80), which ranged from 23 to 114 mm Hg, suggesting a possible primary effect of pressure on contrast washout. However, coronary blood flow appeared to be a stronger predictor of washout slope (partial F = 26.5, p < 0.001) than did perfusion pressure (partial F = 5.9, p < 0.05 by multiple regression). The injection to injection variability in myocardial washout slope appeared to be high (24%). The gamma variate fitting of curves did not improve the correlation with coronary flow (r = 0.78). CONCLUSIONS: Myocardial washout of sonicated iopamidol reflects coronary blood flow in a model in which coronary autoregulation is abolished.

Chronic oral dipyridamole as a 'novel' antianginal drug: the collateral hypothesis.

Dipyridamole is an adenosine transport blocker that produces elevation of tissue adenosine levels. The oral formulation has long been used as a 'coronary vasodilator', but inappropriate vasodilation can lead to a pro-ischemic effect. However, available evidence linking adenosine to angiogenesis raises the possibility of a therapeutically relevant anti-ischemic effect of the drug. Molecular biology data show that in a hypoxic milieu, increased interstitial adenosine increases proliferation of endothelial cells in culture by stimulating A1 and A2 adenosine receptors and induces vascular endothelial growth factor which leads to angiogenesis. Morphologic data indicate that chronic, intermittent dipyridamole administration increased endomyocardial capillary length density by 33% in hypertensive and 11% in normotensive rabbits. Experimental data suggest that chronic treatment with dipyridamole increases collateral flow and decreases exercise-induced left ventricular dysfunction in the territory dependent upon a critical coronary stenosis. Clinical data indicate that the meta-analysis of all published double-blind, placebo-controlled, randomized trials assessing the effect of dipyridamole as an antianginal agent showed a highly significant drug benefit (odds ratio = 0.299, confidence intervals = 0.202-0.443). Treatment duration (log time in days) was significantly correlated to the observed benefit (log odds) (r = -75, P = 0.0031), consistently with a structural change in the collateral coronary circulation requiring time to emerge. The available data support the 'adenosine collateral hypothesis' (i.e., a beneficial angiogenetic effect of chronic endogenous adenosine accumulation). The angiogenetic effect would be different from the coronary vasodilator effect in several respects: coronary anatomical target (mainly capillaries instead of arterioles); cellular target (mainly endothelium rather than smooth muscle cell); receptor target (A1 and A2 rather than A2 adenosine receptors); time required for effect (weeks or months rather than minutes or hours); clinical use (possibly therapeutic for angiogenesis; mainly diagnostic for vasodilator stress testing). Prospective, properly designed trials are needed to assess convincingly the efficacy of a drug used for 40 years and yet possibly prematurely discarded as an effective antianginal treatment.

Possibilities, limitations, and technique for the study of regional myocardial perfusion in man by Xenon-133.

The theoretical possibilities and the practical limitations of the Xenon-133 (133Xe) method for the study of regional myocardial perfusion in man are discussed. The techniques for data acqusition and processing developed over the past 5 years are described in detail. Illustrative examples of experimental findings are reported. The practical interpretation of the data, at the light of the influence of injection site, initial tracer distribution, constancy of counting geometry, spatial resolution, and Xenon retention in fat, is presented.

Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients.

PURPOSE: Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE. SUBJECTS AND METHODS: We examined 110 consecutive patients with suspected PE. The study protocol included assessment of clinical probability, echocardiography, and perfusion lung scanning. Pulmonary angiography was performed in all patients with abnormal scans. As echocardiographic criteria to diagnose acute PE, we used the presence of any two of the following: right ventricular (RV) hypokinesis, RV end-diastolic diameter >27 mm (without RV wall hypertrophy), or tricuspid regurgitation velocity >2.7 m/sec. Clinical estimates of PE served as pretest probabilities in calculating, after echocardiography, the posttest probabilities of PE. RESULTS: Pulmonary angiography confirmed PE in 43 (39%) of 110 patients. Echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. For pretest probabilities of 10%, 50%, and 90%, the posttest probabilities of PE conditioned by a positive echocardiogram were 38%, 85%, and 98%, respectively. The posttest probabilities of PE conditioned by a negative echocardiogram were 5%, 33%, and 81%, respectively. CONCLUSIONS: In unselected patients with suspected PE, transthoracic echocardiography fails to identify some 50% of patients with angiographically proven PE. Although echocardiographic findings of RV strain, paired with a high clinical likelihood, support a diagnosis of PE, the transthoracic echocardiography has to have a better sensitivity to be used as a screening test to rule out PE.

Equal antiplatelet effects of aspirin 50 or 324 mg/day in patients after acute myocardial infarction.

This study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 324 mg aspirin or placebo, daily for 21 days. Compared with placebo, bleeding time was significantly and similarly prolonged with both aspirin doses (+ 71 +/- 22% and + 69 +/- 20%, mean +/- S.D.). Aspirin 50 mg/day suppressed arachidonate-induced platelet aggregation and secondary phase aggregation after ADP and adrenaline. Collagen aggregation was inhibited by 44 +/- 15%. In no case were differences in the antiplatelet effects of the two doses observed. The effects of 50 mg/day persisted without attenuation during the observation period. Platelet thromboxane B2 generation during arachidonate-induced aggregation was inhibited by 95 +/- 2 and 99 +/- 1% compared to placebo group after 50 and 324 mg/day, respectively (P between doses less than 0.05). No change was observed with any treatment in coagulation time, prothrombin time or plasma thromboplastin time. Thus, in patients with acute myocardial infarction, the antiplatelet effects of aspirin 50 mg/day are stable over time and superimposable on those of 324 mg/day. The antithrombotic efficacy of aspirin 50 mg/day remains to be tested clinically.

Clinical features and prognostic implications of myocardial ischemia at rest in patients with exertional angina pectoris.

The prognosis of patients with coronary artery disease (CAD) is mainly influenced by organic factors such as cardiac muscle loss and extent of CAD. The aim of this study was to investigate whether a functional factor--reversible myocardial ischemia at rest--plays an independent prognostic role. Thus, 2 groups of patients were studied and followed up for 46 +/- 32 months: 1 group (483 patients) had ischemic electrocardiographic changes only on effort and another group (224 patients) both on effort and at rest. The 2 groups did not differ significantly as to age, gender, coronary risk factors, baseline electrocardiographic abnormalities, incidence of previous myocardial infarction, angiographic left ventricular dysfunction, and extent of coronary stenoses (> or = 50% diameter reduction). There were 65 deaths (40 of which were from cardiac causes) during the 5-year follow-up. Despite the similar incidence of known predictors of prognosis, Kaplan-Meier survival analysis revealed a significantly lower 5-year survival rate in patients with mixed (84.4%) rather than exertional (92.1%) ischemia (p < 0.05 by Mantel-Haenszel test). If only cardiac causes of deaths were considered, the 5-year survival rate was still lower in patients with mixed (89.6%) rather than exertional (93.9%) ischemia. Finally, reversible ischemia at rest was an independent predictor of survival by Cox multivariate regression analysis, preceded only by the extent of CAD and left ventricular dysfunction. Thus, reversible ischemia at rest plays an independent negative role in the long-term clinical outcome of patients with CAD and positive exercise stress test results.

Usefulness of pirenzepine, an M1 antimuscarinic agent, for effort myocardial ischemia.

This study evaluated the effect of pirenzepine, an M1 antimuscarinic agent, on exercise duration and ischemic threshold in patients with angiographically documented coronary artery disease and clear-cut ST depression (greater than 0.2 mV, 0.08 second after the J point) during ergometric stress testing. Twenty-five patients, mean age 56 +/- 8 years, underwent 3 randomized multistage bicycle exercise stress tests after intravenous administration of saline solution (2 ml), isosorbide dinitrate (1 mg) and pirenzepine (2 mg). Isosorbide dinitrate, an endothelium-independent coronary dilating agent, was used as a reference drug. Compared with saline, both pirenzepine and isosorbide dinitrate significantly improved time to ischemia (0.15 mV ST-segment depression) from 6.5 +/- 2 to 7.8 +/- 2 and 8.6 +/- 2 minutes and rate-pressure product at ischemia from 21,498 +/- 4,903 to 24,083 +/- 6,692 and 24,547 +/- 5,390 mm Hg.beats/min, respectively. Compared with saline, pirenzepine did not induce significant changes in blood pressure either at rest or during exercise, whereas it decreased resting heart rate from 71 +/- 9 to 60 +/- 11 beats/min (p less than 0.01) and induced a significant increment of heart rate during ischemia from 117 +/- 18 to 126 +/- 21 beats/min (p less than 0.05). Compared with saline, isosorbide dinitrate reduced systolic blood pressure at rest from 132 +/- 12 to 112 +/- 12 mm Hg, increased heart rate at rest from 71 +/- 10 to 84 +/- 16 beats/min and heart rate at ischemia from 117 +/- 18 to 132 +/- 16 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term prognosis of transient acute myocardial ischemia at rest.

A medical approach to treatment was adopted in 652 patients with documented myocardial ischemia at rest during both the acute and follow-up phases. No patient underwent coronary revascularization during hospitalization and only 86 patients (13%) underwent coronary bypass surgery within 8 months from discharge. During hospitalization 13 patients died. In the remaining group (639 patients), the likelihood of death in the 10-year period after discharge was 28% for all patients and 20% for cardiac causes only. A series of factors studied during the acute stage were assessed in an effort to predict long-term outcome. The following noninvasive characteristics, listed in decreasing order of statistical significance, were found to be significant univariate predictors of survival: abnormal basal electrocardiogram, duration of coronary artery disease, previous myocardial infarction, pattern of ST-T changes during episodes of ischemia at rest, age and systemic hypertension. The average annual mortality rate for patients with T-wave changes, ST-segment elevation and ST-segment depression was 0.9, 1.8 and 3%, respectively. The Cox survival analysis identified abnormal basal electrocardiogram, duration of coronary artery disease and pattern of ST-T changes as significant, independent predictors of death. When invasive characteristics were entered in the model, number of greater than or equal to 50% narrowed coronary arteries, left ventricular ejection fraction, abnormal basal electrocardiogram and smoking habit were found to be independent and additive prognostic variables. Thus, long-term prognosis of patients with ischemia at rest is related to the severity of anatomic impairment, independent of the pattern of ST-T changes observed during the acute phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of myocardial ischemic electrocardiographic changes during dipyridamole stress echocardiography.

The aim of this study was to assess the diagnostic and prognostic value of the presence and characteristics of ischemic electrocardiographic (ECG) changes during dipyridamole stress echocardiography. The ECG response in 178 patients with echocardiographic evidence of myocardial ischemia during dipyridamole stress testing was analyzed. ECG changes occurred in 105 patients (59%). Patients with ECG changes had a higher incidence of echocardiographic signs of ischemia at a low dose than patients with an unchanged electrocardiogram (50% vs 23%; p = 0.0002). Three-vessel and/or left main coronary artery disease (CAD) was found in 41% of patients with and in 21% of patients without ECG changes (p = 0.029). During follow-up (33 +/- 19 months), 30 cardiac events occurred: 10 deaths, 6 infarctions, and 14 unstable anginas. Coronary revascularization was performed in 48 patients with and in 17 patients without ECG changes (p = 0.0022). The univariate predictors of cardiac events were: presence of ischemia in > or =4 ECG leads (p = 0.0004), echocardiographic evidence of ischemia at a low dose (p = 0.0062), ST-segment shift on precordial leads (p = 0.0094), family history of CAD (p = 0.0115), coexistence of > or =3 cardiovascular risk factors (p = 0.0156), ST-segment depression (p = 0.0172), and ECG changes during testing (p = 0.0335). At Cox analysis, occurrence of ischemia at a low dose (odds ratio 3.0; 95% confidence interval 1.3 to 6.8) and the presence of ischemia in > or =4 ECG leads (odds ratio 3.5; 95% confidence interval 1.3 to 9.3) had an independent prognostic importance. In conclusion, the presence and characteristics of ischemic ECG changes are associated with more extensive CAD and worse prognostic outlook than are echocardiographic changes alone during dipyridamole stress echocardiography.

Electrocardiographic manifestations and in-hospital prognosis of transient acute myocardial ischemia at rest.

From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST-segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome.

Comparison of verapamil and propranolol therapy for angina pectoris at rest: a randomized, multiple-crossover, controlled trial in the coronary care unit.

The effects of oral verapamil (V), 400 mg/day, oral propranolol (P), 300 mg/day, and placebo were compared in 10 patients admitted to the coronary care unit because of frequent attacks of angina at rest. Testing was done according to a randomized, double-blind, multiple-crossover, placebo-controlled trial, consisting of 8 consecutive 48-hour treatment periods with V or P or placebo. Three patients had variant angina, 5 had episodes of both ST-segment elevation and depression and 2 had only ST-segment depression. One patient had no critical coronary stenoses, 1 had 1-vessel disease, 7 had 2-vessel disease and 1 had 3-vessel disease. Electrocardiographic monitoring and tape recording were continued during the 16 days of the trial. A total of 1,602 episodes of transient diagnostic ST shift were recorded during the trial (1,309 episodes of ST-segment elevation, 293 of ST-segment depression); 43% were painless. Mean blood levels of V and P at the end of the active phases were 161 +/- 89 and 120 +/- 45 ng/ml, respectively. In the group as a whole, the average number of diagnostic ischemic ST-segment shifts per 24 hours was significantly reduced relative to corresponding placebo periods during V (2.6 +/- 2.4 vs 11.9 +/- 8.6; p less than 0.01) but not during P treatment (11.9 +/- 8.6 vs 12.0 +/- 7.3). Similar statistically significant reductions were observed in the number of anginal attacks and nitroglycerin tablets consumed. Considering individual patients, V reduced ischemic episodes during both active phases in all patients, whereas P was effective only in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Findings from long-term electrocardiographic monitoring of patients with variant angina in a coronary care unit.

Eleven patients with frequent episodes of variant angina underwent 24-hour electrocardiographic monitoring in a coronary care unit for a total of 70 days to assess circadian variation in ischemic episodes and its correlation with circadian heart rate (HR) rhythm. In each patient a series of 4 to 13 consecutive days, in the absence of therapy, with 8 or more ischemic episodes per day were analyzed. Harmonic regression models were fitted to the hourly number of ischemic episodes and the hourly values of HR. Out of 54 days, with 8 or more episodes per day for a total of 1,357 episodes, a circadian rhythm was observed for 34 days (64%), in at least 1 day in all patients and during the entire period of observation in only 3. Its presence was independent of the number of episodes; the peak of periodic functions occurred at 2.9 +/- 2.7 AM. A cadian rhythm for HR was observed in 61 of the 70 days (87%), consistently in 7 patients; the nadir occurred at 2.4 +/- 1.5 AM; simultaneous cycling in HR and transient ischemia was found on 32 days. The intrapatient difference between the peak and the nadir of the ischemic and the HR function was, on average, 2.6 +/- 3.3 hours. Thus, a circadian rhythm of ischemic episodes was present in all patients although it was not consistently present; simultaneous occurrence of circadian variation in ischemic episodes and HR was observed only in 60% of the days with a sufficiently high number of attacks and when this occurred, a significant phase shift was observed; occasional loss of HR cycling was observed in some patients, without an apparent cause.

Impact of blunted pulmonary venous flow on the outcome of patients with left ventricular systolic dysfunction secondary to either ischemic or idiopathic dilated cardiomyopathy.

The intravenous administration of echo contrast agents enhances the Doppler signal and makes the study of pulmonary venous flow (PVF) easily achievable by transthoracic echocardiography. The aim of this study was to evaluate whether PVF patterns play a role in predicting the outcome of patients with left ventricular (LV) systolic dysfunction. Thus, 115 patients (79 men, mean age 69 years) with LV dysfunction (ejection fraction [EF] <45%) due to either ischemic or idiopathic dilated cardiomyopathy were studied and followed-up for 1 year. A quantitative interrogation of all components of PVF was feasible in 69% of patients at standard transthoracic examination; after contrast enhancement, anterograde and retrograde flow velocities were measurable in 100% and 92% of patients, respectively. A blunted PVF (defined by a systolic-to-diastolic peak velocity ratio <1) was identified in 48 patients (42%), who had a worse clinical status, a lower LVEF, and a more severe pulmonary hypertension. Thirty-six patients had cardiac events at follow-up: sudden death in 4, progressive heart failure in 12, and hospitalization for worsening heart failure in 20 patients. Multivariate Cox proportional-hazards analysis revealed that advanced New York Heart Association class, male gender, and older age were independent predictors of mortality. However, blunted PVF, reduced LVEF, older age, and increased heart rate in descending order of power were independent predictors of heart failure hospitalizations and deaths from end-stage heart failure. In conclusion, the assessments of PVF may effectively contribute to the characterization of patients with LV dysfunction and to the prediction of their outcome.

Echo-Doppler assessment of left ventricular filling in borderline hypertension.

The aim of this study was to evaluate left ventricular anatomy and diastolic function in borderline essential hypertension. To this aim, 16 borderline hypertensive patients underwent echocardiographic and pulsed-wave Doppler evaluation. As control groups, 20 normotensive controls and 20 patients with established hypertension were evaluated by the same procedure. By the Doppler assessment of transmitral blood flow, the following indices of left ventricular diastolic function were obtained: early (E) and late (A) peak flow velocity, late to early velocity ratio (A/E), early filling fraction (EFF) and acceleration and deceleration times of early and late flow peaks. Borderline hypertensives had an interventricular septum and posterior wall thickness significantly higher than normotensives and lower than established hypertensives. As regards the diastolic indexes, borderline hypertensive patients had significantly higher A peaks (P less than .02) and A/E ratios (P = .05) and lower EFF (P less than .02) as compared to normotensive controls. No significant differences were on the other hand observed with established hypertensive patients. This resultant diastolic pattern was independent of age, as indicated by the analysis of age-matched subgroups. The presence of diastolic function changes in borderline hypertension confirms the early appearance of this kind of abnormality in hypertensive heart disease. On the other hand, the finding of increased left ventricular wall thickness in borderline hypertensives does not allow us to conclude that, as suggested by other authors, diastolic function changes in the early stage of hypertension are independent on anatomical modifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced cardiovascular efficiency and increased reactivity during exercise in borderline and established hypertension.

In this study, exercise capacity was evaluated in patients with borderline and established, uncomplicated, essential hypertension as compared to normal subjects. To this aim, the response of blood pressure, heart rate and cardiac work to a multi-stage exercise test was investigated by analyzing the results of linear regression fitting of cardiovascular parameters (ie, heart rate, systolic blood pressure and rate-pressure product (RPP)) versus time of exercise. Compared to normal patients, both essential and borderline hypertensive patients had a shorter average duration of exercise test (ie, a decreased exercise capacity), always negative for transient myocardial ischemia. This was in spite of a mild increment of maximal RPP (+19% and +10% v normal patients, respectively). Reduction of exercise duration in borderline and established hypertensive patients was related to the higher RPP at rest (+26% and +56% related to normal patients, respectively) and to the steeper slopes (rates of increment) of heart rate systolic pressure and RPP during exercise. Interestingly, in the overall population of normal and hypertensive subjects, the slopes of heart rate and RPP were directly correlated with basal blood pressure. In conclusion, these data indicate a decreased exercise tolerance in both established and borderline hypertensive patients without documented myocardial ischemia. This abnormality, which appears to be due to a disproportional increment during exercise not only of systolic pressure but also of heart rate, could reflect abnormalities in the autonomic control of heart function.

Uric acid levels and platelet function in humans. An in-vivo ex-vivo study.

Platelet function (aggregation by ADP, adrenaline, collagen and circulating platelet aggregates) before, during and after dietary induction of hyperuricemia (ribonucleic acid, 3 g/day) was studied in five healthy volunteers to assess the relationship between uric acid level and platelet function. In the same subjects, during a second period of ribonucleic acid diet, the acute and chronic effects of a hypo-uricemizing agent, allopurinol, were assessed. No significant correlation was detected between platelet function and uricemia either in the absence or in the presence of pharmacological treatment with allopurinol. On the basis of these results, the well known relationship between uric acid levels and ischemic heart disease does not appear to be mediated by an exaggerated platelet function.

Elective response to propranolol or verapamil in ischemia on effort.

Twenty-four patients with effort angina and positive exercise stress test performed four control exercise stress tests, two tests while taking propranolol (240 mg/day) and two tests while taking verapamil (320 mg/day), in a randomized crossover sequence. For each test the following parameters were measured: time and rate-pressure product at ischemia; intercept and slope of the linear regression between rate-pressure product and minutes of exercise. Group analysis showed that both drugs improved time to ischemia significantly and to the same extent. However, eight patients responded preferentially to verapamil in contrast to 12 patients on propranolol. The remaining four patients responded equally to both drugs. In verapamil responders, verapamil increased time to ischemia by decreasing intercept and increasing rate-pressure product at ischemia. In these patients, propranolol did not increase time to ischemia because of a marked decrease in rate-pressure product at ischemia. In propranolol responders the significant increase in time to ischemia during propranolol was the result of a decrease in intercept and slope. The ineffectiveness of verapamil in these patients was related to a slight decrease in intercept without any increase in rate-pressure product at ischemia. The preferential response to one of the two drugs could not be predicted on the basis of clinical and angiographic features. In conclusion, in patients with effort angina, medical treatment should be personalized and based on a direct and objective verification of a drug's efficacy since different mechanisms can modulate exercise tolerance.