Epicardial fat, rather than pericardial fat, is independently associated with diastolic filling in subjects without apparent heart disease.

BACKGROUND AND AIM: Epicardial and pericardial fat are separate fat depots surrounding the heart. Previous studies found epicardial fat to be associated with diastolic dysfunction, but they had some limitations. Pericardial fat association with diastolic dysfunction was not examined. Our aim was to assess the relation of epicardial and pericardial fat with diastolic filling. METHODS AND RESULTS: In 73 volunteers without known heart disease or complaints, using echocardiography, we measured epicardial and pericardial fat thickness from long(LAX) and short(SAX) axis views and assessed diastolic filling: mitral inflow (E/A ratio, E wave deceleration time[DT]), pulmonary vein flow (systolic/diastolic ratio [S/D], systolic filling fraction[SFR], late retrograde velocity[Ar]), color M-mode flow propagation velocity [Vp], and tissue Doppler derived mitral early annular velocities at the septum [e' sep] and lateral wall [e'-lat]. By Spearman's correlation, epicardial fat from LAX had a weak, but statistically significant correlations with several diastolic filling indices (SFR{rs = 0.29, P = 0.02}, Ar{rs = 0.3, P = 0.01}, Vp{rs = -0.3, P = 0.01}, e' sep{rs = -0.23, P = 0.04}, e' lat{rs = -0.26, P = 0.03}). In multivariate logistic regression model adjusting for age, gender, diabetes, systolic blood pressure and left ventricle mass index, epicardial fat thickness from LAX (and not from SAX) was the only independent predictor of e' [e' sep < 8: OR = 1.8, 95%CI = 1.1-2.9; e' lat<10: OR = 1.6, 95%CI = 1.01-2.6]. After adjustment, Pericardial fat measured from LAX was independent predictor of e' lat only[e' lat < 10:OR = 1.3, 95% CI 1.03-1.6). CONCLUSIONS: Epicardial fat measured from LAX is an independent predictor of myocardial relaxation. Pericardial fat independent association with diastolic filling is uncertain.

Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease.

The most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is coronary artery disease (CAD), not chronic liver disease. Fatty liver increases cardiovascular risk by classical (dyslipidemia, hypertension, diabetes) and by less conventional mechanisms. Common pathways involved in the pathogenesis of fatty liver and CAD includes hepatic insulin resistance and sub clinical inflammation. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased FFA, which causes lipotoxicity and impairs endothelium-dependent vasodilatation, increases oxidative stress, and has a cardio toxic effect. Additional metabolic risk factors include leptin, adiponectin, pro inflammatory cytokines [such as IL-6, C-reactive protein and plasminogen activator inhibitor-1 (PAI-1)], which together lead to increased oxidative stress and endothelial dysfunction, finally promoting coronary artery disease (CAD). When classical risk factors are superimposed on fatty liver accumulation, they may further increase the new metabolic risk factors, exacerbating CAD. The clinical implication is that patients with NAFLD are at higher risk (steatohepatitis, diabetes, obesity, atherogenic dyslipidemia) and should undergo periodic cardiovascular risk assessment including the Framingham score, cardiac effort test, and measurement of intimae-media thickening of the carotids arteries. This may improve risk stratification for CAD.

Validation of a novel method to determine non-invasively the rate of central aortic pressure changes.

INTRODUCTION: One of the most sensitive indices of myocardial contractility is represented by the rate of increase of intraventricular pressure during isovolumetric contraction (dP/dt) and (dP/dt(ejc)), which represents the rate of change of pressure during ejection. Today these parameters can be obtained only by invasive catheterization methods. We developed a novel technique that leads to the non-invasive reconstruction of the central aortic pressure. The technique is based on the concept of applying multiple successive occlusive pressures on the brachial artery from peak systole to diastole using an inflatable cuff and plotting the values against time intervals. The hypothesis is that the time intervals required for the aortic pressure wave to overcome a given occlusive brachial pressure applied by a sphyngomanometer on the arm are equal to time needed to reach the same pressure in the central aorta plus the propagation time to the brachial point, which is constant in the same patient throughout the measurements. METHODS AND RESULTS: We tested the hypothesis using an animal experiment. The new non-invasive device was mounted on the left forelimb of the animal. A Millar pressure transducer catheter was inserted to the aorta and the aorta pressure was recorded at time intervals of 1 ms. A second catheter was inserted into the coronary arteries and used to create controlled occlusion of the arteries using a balloon inflated to 10 atm. Measurements were obtained before the intervention was started, and throughout the sequence of repeated occlusions and deflations. At the end of the sequence, IV dobutamine was administered and results were monitored for 10 min while the heart rate and blood pressure were rising. Non-invasive dP/dt(ejc) was reduced typically by 20% in response to balloon inflation. In long occlusion periods, stabilization and sometimes recovery of dP/dt(ejc) is observed. By plotting dP/dt(ejc) measured by the new non-invasive device versus catheter measurements a correlation factor of 0.843 was found. CONCLUSION: A newly developed method of non-invasive measurement of central dP/dt has been found to correlate to invasive measurements in an animal model.

Detection of chest pain of non-cardiac origin at the emergency room by a new non-invasive device avoiding unnecessary admission to hospital.

Recent advances in the treatment of acute coronary syndromes has raised awareness that prompt presentation for chest pain may be life saving. Most patients presenting with chest discomfort have a non-ischaemic ECG on presentation, but are routinely admitted to hospital because of diagnostic uncertainty for occult MI or ischaemia. We tested a new non-invasive device that measures central aortic pressure changes (dP/dtejc): an accepted index of myocardial performance that could be added to the diagnostic triage of ischaemia in the ER avoiding unnecessary admissions. We followed 85 patients presenting at the ER with acute chest pain. In 72 patients, negative ECG and myocardial enzyme dynamics ruled out coronary origin during the first 24 h after admission. In 8 of the 72 patients, coronary catheterisation found normal coronary arteries. In this group, average dP/dtejc was 163 (range 92-232). In 35 patients in whom the new non-invasive cardiac performance index dP/dtejc was above a threshold of >150, acute MI was ruled out. In 13 patients, acute chest pain had coronary origin confirmed by ECG and/or positive enzymes. The average dP/dtejc in this group was 117 (range 61-149). The dP/dtejc values were found to be significantly higher in patients without acute MI (p<0.001). Preliminary findings suggest that nearly 40% of patients presenting with acute chest pain could be spared the risks and costs of unnecessary hospital admission and more invasive cardiac testing by simply adding a easy to use, immediately obtained, test to the diagnostic protocol, and using a threshold of dP/dtejc>150 to rule out heart attack.

Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steep decrease in blood pressure in patients with congestive heart failure.

OBJECTIVE: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction. METHODS: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h(-1)) to 38 CHF (NYHA class III) patients with ejection fraction or=15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean arterial blood pressure [(MAP-right atrial pressure)/cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure x flow (MAP x CI), where MAP represents pressure and CI represents cardiovascular flow. RESULTS AND DISCUSSION: Compared to the placebo, tezosentan induced a dose-dependent decrease in SVRi (-32%), an increase in Cpi (+20%) and a small decrease in MAP (-9%). By contrast, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increase in Cpi leading to a steep decrease in MAP. CONCLUSIONS: The use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a useful alternative characterization of the complex influences of vasodilators on cardiac function in patients with CHF.

Endothelin release: a marker for the severity of exercise-induced ischemia.

Elevated endothelin-1 levels were found in exercise-induced ischemia. To our knowledge, no attempt has been made to correlate the presence of the elevated endothelin levels with severity of ischemia. In the present study, we attempt to correlate the severity of ischemia, quantified using a bullseye visual display of scintigraphic ischemic score on SPECT technetium 99m sestamibi, with presence of endothelin at peak exercise. Twenty seven patients with documented effort angina were included in the study. All subjects underwent stress technetium 99m sestamibi and ischemic scores were evaluated on the polar map image divided into 13 segments. Endothelin levels were measured at baseline and at peak exercise. In 13 patients with elevated endothelin-1 levels, there were 88 ischemic segments, 26 of which showed severe ischemia. In the remaining 14 patients with no endothelin-1 elevation, there were 80 ischemic segments of which only four showed severe ischemia. The amount of severe ischemic segments per patient was 2+/-2.2 in the elevated endothelin positive group and 0.28+/-0.6 in the endothelin negative (P< or =0.011). When looking at ischemia as detected by sestamibi SPECT as a gold standard, we found that of 331 segments, 168 were without ischemia, 143 had mild to moderate ischemia, and 30 has severe ischemia. Endothelin levels were 1.2+/-0.6, 2.2+/-0.5, 6.2+/-0.7 pg/l (P<0.01), respectively. Thus, endothelin-1 is a marker of severity of ischemia rather than ischemia itself, and as such, may have prognostic value.

Outcome of patients with post acute myocardial infarction ischemia hospitalized in intensive cardiac care units with and without on-site catheterization laboratories.

BACKGROUND: This study addresses the impact of availability of on-site catheterization laboratories on the 1-year survival of patients with post-acute myocardial infarction ischemia (P-AMI-I), a high-risk subgroup of AMI patients. METHODS: A prospective 5 month national survey was conducted in 1996 in all operating intensive care units (ICCUs) in Israel (N=26) and included 2377 patients. Four hundred and three (17%) had P-AMI-I, 317 of them were admitted to 18 ICCUs with on-site catheterization laboratories (CATH+) and 86 patients to 8 ICCUs without such facilities (CATH-). A retrospective analysis was performed comparing the in-hospital course and 7 day, 1 month and 1 year mortality data of CATH+ vs. CATH- patients. RESULTS: Patient characteristics in both groups were similar with regard to age, gender AMI location, risk factors, hemodynamic parameters on admission and rate of thrombolytic therapy. Of patients in CATH+, 79% were catheterized before hospital discharge vs. 42% in CATH- (P<0.0001), 45 vs. 15% had PTCA (P<0.0001) and 19 vs. 9% had CABG (P<0.05). At 30 days, patients in CATH+ still had significantly more revascularization procedures (71 vs. 48%, P<0.001). Patients hospitalized in ICCUs with CATH+ and CATH- facilities had similar cardiac mortality rates at 7 days (2.0 vs. 2.3%), 30 days (5.7 vs. 4.7%) and at 1 year (7.6 vs. 7.0%). CONCLUSIONS: Despite a more invasive strategy used during the index hospitalization of patients with P-AMI-I hospitalized in CATH+ ICCUs, their survival was similar to CATH- patients at 7 days, 30 days and at 1 year follow-up.

Effect of mibefradil, a T-type calcium channel blocker, on morbidity and mortality in moderate to severe congestive heart failure: the MACH-1 study. Mortality Assessment in Congestive Heart Failure Trial.

BACKGROUND: Calcium antagonists have proved disappointing in long-term congestive heart failure (CHF) studies. Mibefradil, a new calcium antagonist that selectively blocks T-type calcium channels, has been shown to be an effective antihypertensive, antianginal, and anti-ischemic agent, and because of its different mechanism of action, it may be beneficial as adjunct therapy in CHF patients. METHODS AND RESULTS: This multicenter, randomized, double-blind study compared mibefradil with placebo as adjunct to usual therapy in 2590 CHF patients (NYHA class II to IV; left ventricular fraction <35%). The initial 50-mg daily dose of mibefradil was uptitrated to 100 mg after 1 month and continued up to 3 years. Patients were monitored at 1 week; 1, 2, and 3 months; and every 3 months thereafter. All-cause mortality, cardiovascular mortality, and cardiovascular morbidity/mortality were analyzed by use of the log-rank test (alpha=0.05). Substudies included exercise tolerance, plasma hormone and cytokines, echocardiography, and quality of life. Total mortality was similar between mibefradil- and placebo-treated patients (P=0.151). The 14% increased risk of mortality with mibefradil in the first 3 months was not statistically significant (P=0.093). Treatment groups had similar cardiovascular mortality (P=0.246), cardiovascular morbidity/mortality (P=0.783), and reasons for death or hospitalization. Patients comedicated with mibefradil and antiarrhythmics (class I or III), including amiodarone, had a significantly increased risk of death. Substudies demonstrated no significant differences between treatments. CONCLUSIONS: When used as adjunct therapy, mibefradil did not affect the usual outcome of CHF. The potential interaction with antiarrhythmic drugs, especially amiodarone, and drugs associated with torsade de pointes may have contributed to poor outcomes early in the study.

Familial idiopathic dilatation of the right atrium with complete atrio-ventricular block: a new syndrome?

Familial occurrence of idiopathic dilatation of the right atrium is extremely rare. This is the first description of a family in which 2 siblings had a syndrome of idiopathic dilatation of the right atrium associated with complete atrio-ventricular block. The family workup did not show other family members to be affected, and the question we raise is whether or not this might be a new syndrome.

Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina.

Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides stable plasma concentrations over the entire 24 h dosing interval. Two-hundred and one patients with Canadian Cardiovascular Society class II to III angina who were on 50 mg of atenolol yet still experiencing angina symptoms were randomized to receive either placebo or nifedipine GITS 30, 60 or 90 mg/day. After four weeks of treatment, the changes in time from baseline to onset of 1 mm ST segment depression in the 183 eligible patients were 26.7+/-10.2 s, 40.9+/-11.3 s, 63.2+/-12.9 s and 70.3+/-12.6 for the placebo, and 30, 60 and 90 mg/day groups, respectively. These differences were significant (P<0.05) for the 60 and 90 mg/day groups compared with placebo and for the 60 mg/day group compared with the 30 mg/day group. The times to onset of pain and termination of exercise showed similar prolongation but did not achieve statistical significance. During the one-year open label phase of the study, patients exhibited statistically significant improvements in the time to onset of ST segment depression, time to anginal pain and time to termination of exercise at a mean dose of 52.3 mg/day of nifedipine GITS. Adverse events were primarily vasodilatory in nature. This study supports the use of nifedipine GITS in patients with chronic stable angina inadequately controlled on beta-blocker alone.

Treatment and outcome of patients with acute myocardial infarction and prior cerebrovascular events in the thrombolytic era: the Israeli Thrombolytic National Survey.

BACKGROUND: Patients with a history of stroke presenting with acute myocardial infarction (MI) are often excluded from thrombolytic therapy owing to fear of intracranial hemorrhage. Few data, however, are available on the risks vs the benefits of thrombolysis in patients with an acute MI and a prior cerebrovascular event (PCE). METHODS: Data were derived from 2 nationwide surveys of 2012 consecutive patients with acute MI admitted to all 25 coronary care units in Israel during 1992 and 1994. Thrombolytic therapy was given to patients with a PCE at the discretion of the treating physicians. Outcomes were compared between patients with an acute MI with and without a PCE and between patients with a PCE treated with or excluded from thrombolysis. RESULTS: Patients with a PCE (n = 115 [6%]) were older, with higher rates of atherosclerotic risk factors and in-hospital complications than their counterparts without a prior event (n = 1897). They were treated less often with thrombolysis or mechanical reperfusion. The 1-year mortality rates were higher among patients with a PCE (28% vs 19%, P<.01), but not after multivariate adjustments for clinical characteristics (adjusted hazard ratio, 1.08; 95% confidence interval, 0.75-1.55). Patients with an acute MI and a PCE who were treated with thrombolysis (n = 29 [25%]) were compared with 46 patients found ineligible for thrombolysis primarily because of their PCE. The timing of the PCE was comparable in both groups (one fifth in the preceding year), while prior transient ischemic attacks were more prevalent among patients who had undergone thrombolysis. The patients who were treated with thrombolysis (n = 29) were older, had a higher rate of anterior infarction, and, while in the hospital, received aspirin, anticoagulants, and beta-blockers more often than their counterparts (n= 46). In-hospital intracranial hemorrhage did not occur in either group. The 1-year mortality rates were 2-fold higher among patients who had not undergone thrombolysis compared with those who had (33% vs 18%; adjusted hazard ratio, 2.44; 95% confidence interval, 0.78-7.64). CONCLUSIONS: These findings, derived from 2 nationwide surveys of consecutive patients with acute MI, suggest that patients with PCEs have an adverse outcome attributed to their older age and less favorable risk profile. Thrombolytic therapy, however, based on our preliminary data, may be beneficial in selected patients with an acute MI with a nonrecent PCE.

Adding the new calcium antagonist mibefradil to patients receiving long-term beta-blocker therapy results in improved antianginal and antiischemic efficacy.

OBJECTIVE: The objective of this study was to evaluate the efficacy, tolerability, and safety of mibefradil, a new selective T-type calcium channel blocker, in patients with chronic stable angina pectoris receiving concomitant beta-blocker therapy. DESIGN: This was a multicenter, double-blind, placebo-controlled study. METHODS: Ninety-five patients receiving a stable dose of beta-blockers, which was not changed for the purpose of the study, were administered either 50 mg mibefradil once daily for 2 weeks, then 100 mg once daily for 2 weeks, or matching placebo. Efficacy was evaluated by treadmill exercise tolerance testing 24 hours after dose and by diary registration of anginal episodes and nitroglycerin consumption. RESULTS: Two weeks of treatment with 50 mg mibefradil resulted in a significant increase in symptom-limited exercise duration and a significant delay in the onset of persistent 1 mm ST-segment depression (placebo-corrected treatment effect: 23.2 and 51.7 seconds, respectively). Treatment with the 100 mg dose for 2 additional weeks resulted in a larger improvement in treadmill exercise tolerance testing duration and onset of ischemia (placebo-corrected treatment effect: 52.7 and 75.8 seconds, respectively). In addition, a significant decrease in weekly anginal episodes was observed with the 100 mg dose of mibefradil compared with the effect in the placebo group (-53% vs - 12%, p = 0.037). CONCLUSIONS: The combined treatment of mibefradil and beta-blockers was well tolerated, and the overall incidence of adverse events was no different from that with beta-blockers alone. The results indicate that adding mibefradil to chronic beta-blocker treatment is associated with significant improvement in efficacy, which is not achieved at the expense of tolerability.

Symptom-oriented nitrate administration and survival after acute myocardial infarction. Israeli Thrombolytic Survey Group.

The effect of nitrates during evolving myocardial infarction is controversial. While previous studies showed that nitrates improve left ventricular function and have a beneficial effect on survival, two recent randomized megatrials showed that nitrates did not alter mortality after acute myocardial infarction (AMI). The present study analyzes the use of nitrates in clinical practice and their impact on mortality in a cohort of unselected consecutive AMI patients admitted to all 25 coronary care units operating in Israel during 2 months in 1994. Among 966 patients in Killip class I-III on admission, 81% (n = 783) received nitrate therapy by intravenous infusion or orally. Baseline characteristics of patients treated with or without nitrates were quite similar. Seven-day mortality was markedly reduced in the nitrate-treated group (5 and 11 %, p < 0.001) in comparison with those who did not receive nitrates. After adjustment for pertinent variables the 7-day relative risk (RR) of mortality was 0.51 [95% confidence interval (CI) 0.25-1.07; p = 0.08], whereas, the 7-day to 1-year mortality after AMI was not altered by nitrate use (RR = 0.97; 95% CI 0.56-1.68; p = 0.92). Nitrate therapy remains a widespread and a valid symptom-oriented therapeutic approach, especially early after AMI, in the community.

Prognostic value of noninvasively obtained left ventricular contractile reserve in patients with severe heart failure.

OBJECTIVES: The present study sought to evaluate the prognostic value of contractile reserve measured noninvasively during dobutamine infusion in patients with severe heart failure. BACKGROUND: In patients with severe heart failure there is a great need for objective criteria to define candidates for heart transplantation or intensive medical treatment. Cardiac pumping performance reserve has been shown to have excellent prognostic value in patients with cardiogenic shock. METHODS: Cardiac peak power, an afterload-independent contractility index, was measured noninvasively at rest and at peak dobutamine inotropic stimulation. Contractile reserve was defined as the difference between maximal cardiac power at peak dobutamine dose and baseline value. Maximal cardiac power was calculated from the maximal product of validated central arterial pressure and aortic flow. RESULTS: Results were obtained from 52 subjects (42 patients, 10 control subjects). Twenty-two patients were in New York Heart Association functional classes III and IV. Of nine patients with a contractile reserve < 1.5 W/ml, eight died during the 3-year follow-up period. In contrast, all survivors had a contractile reserve > 1.5 W/ml. Using multiple logistic regression analysis, contractile reserve was shown to be the only predictor of survival. CONCLUSIONS: Contractile reserve measured noninvasively during dobutamine infusion is a valuable prognostic indicator in patients with severe heart failure, with added value to ejection fraction.

Safety of prostaglandin E1 for the treatment of peripheral arterial occlusive disease in patients with congestive heart failure. The Alprostadil Investigators.

OBJECTIVES: To confirm the safety of prostaglandin E ( 1 ) (PGE ( 1 ) ) when administered in 100 mL normal saline to patients with severe peripheral occlusive disease (PAOD; Fontaine class III or IV) and concomitant compensated chronic congestive heart failure (CHF) and to explore possible hemodynamic benefits of PGE ( 1 ) in CHF. BACKGROUND: PGE ( 1 ) has been found to be effective in the treatment of severe PAOD. The agent may beneficially affect left ventricular performance or hemodynamics in patients with CHF. However, it must be administered intravenously (in saline diluent, adding potential hazard in patients with volume CHF). METHODS: In a randomized, double-blinded protocol, 50 patients received intravenous (i.v.) infusion of either 60 microg PGE ( 1 ) or placebo, each dissolved in 100 mL saline solution administered over 2 hours each day for 14 days. During the succeeding 14 days, i.v. PGE ( 1 ) was administered to all patients in open-label fashion. Safety was assessed by clinical evaluation of symptoms and signs of CHF or other adverse events, by catheter-based and echocardiographic search for objective cardiac functional influences, and by echocardiogram monitoring for cardiac rhythm. PAOD status also was defined. RESULTS: No evidence of clinical or objective cardiac functional influence was detected. With the usual dosage approved in PAOD, no significant influence on cardiac performance was observed. CONCLUSION: PGE ( 1 ) is safe for treatment of PAOD in patients with concomitant chronic, compensated CHF.

Prostaglandin E1 : electrophysiological safety in patients with congestive heart failure and peripheral arterial occlusive disease. The Alprostadil Investigators.

Prostaglandin E ( 1 ) (PGE ( 1 ) ), the active ingredient of the drug alprostadil-alpha-cyclodextrin, has been effective in mitigating the clinical manifestations of peripheral arterial occlusive disease (PAOD). PGE ( 1 ) often is administered to patients with the potential for developing serious arrhythmias, presenting potential safety hazards if the drug caused or potentiated arrhythmias. However, PGE ( 1 ) has antiadrenergic properties and, theoretically, might have an antiarrhythmic action. Therefore, the effect of PGE ( 1 ) on frequency and severity of atrial and ventricular arrhythmias was evaluated from 48-hour electrocardiographic recordings in patients receiving PGE ( 1 ) therapy for severe PAOD. No significant effects on arrhythmia frequency or severity, and no evidence of proarrhythmia, was apparent after PGE ( 1 ) administration.

Evaluation of contractile reserve by dobutamine echocardiography: noninvasive estimation of the severity of heart failure.

Functional status in chronic heart failure is evaluated in general by subjective means, such as the New York Heart Association class, or by invasive techniques difficult to use routinely. The aim of this study was to evaluate noninvasively the contractile reserve in cases of heart failure as a means to define the functional status of the patients. Cardiac peak power, a new noninvasively obtained afterload-independent index of contractility, was calculated from online Doppler and central arterial blood pressure estimated noninvasively in 35 patients with heart failure and 10 healthy subjects during dobutamine infusion. Cardiac output increased in all patients to the same extent, without differentiation among the functional classes. Contractile reserve, as assessed by peak power, was found to be a good marker of functional class: it was significantly higher in functional class 1 than in functional classes 2 through 4. A correlation of r = 0.99 and probability of p < 0.001 was found with the functional status. This new, noninvasive contractility index, peak power, allows an objective evaluation of the severity of heart failure.

Comorbidity and outcome in eating disorders.

This article reviews the data on comorbidity, course, and outcome in anorexia nervosa and bulimia nervosa. Recovery, relapse, the process of recovery, and predictors of outcome are reviewed. Although significant differences exist among outcome studies, the data suggest that patients with anorexia and bulimia tend to improve symptomatically over time. Anorexia nervosa and bulimia nervosa are associated with substantial rates of comorbidity. The relationship between eating disorders and depression, anxiety disorders, substance abuse, and personality disorders is discussed.

Acute myocardial infarction complicating viper bite.

An acute myocardial infarction was induced by Vipera palaestinea venom in a young patient. The diagnosis was confirmed by cardiac catheterization, which showed a segmental contraction abnormality but normal coronary arteries.

Differences in ischemic threshold and nitrate efficacy between normotensive and hypertensive patients with stable angina pectoris.

The coexistence of ischemic heart disease with hypertension makes antihypertensive therapy essential, since relief of hypertension may ameliorate the coronary disease. On the other hand, the effect of antianginal nitrate therapy in patients with stable angina pectoris and systemic arterial hypertension is not fully understood. This study assessed the effects of hypertension on the ischemic threshold and the time to moderate angina, measured as parameters of nitrate efficacy. In this double-blind, parallel-group study, 141 patients with stable angina pectoris were randomly assigned to receive 5 mg, 10 mg or 20 mg isosorbide-5-mononitrate or matching placebo bid for 21 days. Ninety-three normotensive and 48 hypertensive patients were compared with regard to the time to moderate anginal pain and the ischemic threshold before and after nitrate treatment on the first day of the study. The acute nitrate effect 2 h after drug administration was substantially attenuated in hypertensives at both 10 and 20 mg of isosorbide-5-mononitrate, with the time to moderate anginal pain being significantly shortened. Impaired vasodilatator response of the arterial vasculature to organic nitrates, probably due to impaired biotransformation of organic nitrates to nitric oxide in hypertensive patients, is suggested as a possible mechanism for the diminished nitrate effect. Thus, oral nitrate therapy does not have the same beneficial antianginal effect in hypertensive patients as it does in normotensives. Dose adjustment based on the pretreatment blood pressure, and the administration of higher doses of oral nitrates should therefore be considered in hypertensive patients suffering from stable angina pectoris.