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Periodic leg movements during sleep (PLMs) are a disorder characterized by regularly recurring movements of the legs during sleep. Although PLMs are common in patients with heart failure (HF), their clinical significance is unknown. The aim of this study was to determine whether, in patients with HF, PLMs are associated with increased mortality risk. In a prospective cohort study, 218 consecutive patients with systolic HF newly referred to an HF clinic from 1997 to 2004 who underwent overnight polysomnography, regardless of symptoms or signs of sleep disorders, were enrolled. The frequency of PLMs per hour of sleep was quantified as the PLM index (PLMI). Patients were classified as either normal (PLMI

Chronic heart failure is characterized by increased renal extraction of endothelin (ET)-1 and unaltered handling of big ET-1. The renal extraction of ET-1 in patients with heart failure is closely related to elevations in pulmonary artery and pulmonary capillary wedge pressures.

concentrations of ET-1 have been found in the coronary sinus in other cardiovascular conditions and it is believed to be associated with increased ET-1 production. 10 ‐12 In the present study, we examine the transcardiac plasma ET-1 gradient in patients with normal left ventricular (LV) function and those with chronic CHF. We hypothesize that there would be an increase in coronary sinus ET-1 concentration in CHF because myocardial content and production may be increased in this setting. ••• A total of 64 subjects, divided into 2 groups were studied (Table 1). Group I consisted of 34 patients with no history of CHF and normal LV function (by echocardiography or ventriculography). Within this group there were 12 patients with angiographically normal coronary arteries and 22 patients with evidence of coronary artery disease (CAD). None of the patients in group 1 had undergone coronary artery bypass grafting (CABG). Group 2 consisted of patients with chronic CHF secondary to LV systolic dysfunction (ejection fraction ,35%) Within this group, there were 15 patients with angiographically normal coronary arteries and no history of myocardial infarction and 15 patients with ischemic cardiomyopathy. Five of the 15 patients with ischemic heart disease had undergone CABG. Patients with CHF were treated with combinations of digoxin, diuretics, and angiotensin-converting enzyme inhibitors. Patients with normal LV function were generally treated with nitrates, calcium channel antagonists, and b blockers for management of chest pain syndrome. All medications were discontinued on the morning of the study. This study was approved by the Ethical Review Committee for Human Experimentation of the University of Toronto. Written informed consent was obtained from all patients. Studies were performed after diagnostic cardiac catheterization. An arterial sheath (Cordis Laboratories) was left in the femoral artery for continuous monitoring of blood pressure and blood sampling. In patients with CHF, a pulmonary artery catheter was also left in place. A 7Fr Sidewinder angiographic catheter (Cordis Laboratories, Miami, Florida) was inserted into the coronary sinus. Blood samples for ET-1 were drawn simultaneously from the coronary sinus and femoral artery. Blood was collected into prechilled tubes containing ethylenediaminetetraacetic acid (1 mg/ml) and aprotinin (500 KIU/mL) and placed in ice. ET-1 was measured with an enzyme immunoassay kit as described previously.13 Differences between arterial and coronary sinus concentrations of ET-1 were evaluated using a paired t test. Between group comparisons were performed with an unpaired t test. Simple linear regression was used to examine the relation between the transcardiac ET-1 gradient and other variables. Groups were well matched in terms of age. The 2 groups of patients with CHF were similar in terms of disease severity (Table 1). In those with normal LV function, arterial and coronary sinus ET-1 levels were similar (0.98 6 0.06 in the artery and 0.95 6 0.05 pg/ml in the coronary sinus). Similar results were observed in the presence and absence of CAD. In those with normal LV function and normal coronary arteries, ET-1 concentrations were 1.11 6 0.14 in the artery and 0.98 6 0.10 in the coronary sinus (p 5 NS). Similarly, in those with normal LV function and CAD, there was no difference in the arterial and coronary sinus ET-1 concentrations (0.91 6 0.06 vs 0.94 6 0.06, respectively; p 5 NS). In patients with CHF, ET-1 levels in the coronary sinus were lower than those observed in arterial plasma, indicating significant net extraction of ET-1 across the heart (2.23 6 0.21 vs 1.74 6 0.15 pg/ml, arterial vs coronary sinus; p ,0.01). A significant transcardiac gradient of ET-1 was observed in both the nonischemic and ischemic cardiomyopathy groups. In those with CHF and normal coronary arteries, plasma ET-1 was 1.77 6 0.2 pg/ml in the artery and 1.43 6 0.16 pg/ml in the coronary sinus (p 5 0.02). In those with ischemic cardiomyopathy, arterial and coronary sinus ET-1 levels were 2.69 6 0.35 and 2.05 6 0.23 pg/ml, respectively (p 5 0.01). There was a significant relation between the transcardiac ET-1 gradient and both mean pulmonary ar

The hemodynamic and antianginal effects of the organic nitrates are greatly reduced during therapy designed to provide 24-hour protection throughout each day. Although the mechanisms of tolerance are not clearly understood, it is likely that tolerance is related to a combination of reduced sulfhydryl groups in vascular smooth muscle and neurohormonal activation. These changes would reduce nitrate-induced vasodilation and induce sodium and water retention with an increase in plasma volume. These reflex neurohormonal changes would reduce the hemodynamic effect of any given degree of nitrate-induced vasodilation. Although preliminary studies suggest that diuretic therapy or the use of converting enzyme inhibitors may reduce or abolish tolerance, further clinical studies are required to confirm these findings.

Estimation of mitral valve area (MVA) in the cardiac catheterization laboratory is prone to pitfalls because of the time required for calculations and inaccuracies in the measurement of cardiac output. Because the rate of decrease in the mitral gradient directly correlates with the severity of mitral stenosis, an on-line estimate of MVA at the time of catheterization may be possible with regression analysis of digitized pressure recordings. A total of 61 comparisons of mitral gradient measurements and MVA were obtained in 37 patients at diagnostic catheterization and in 24 patients after balloon mitral valvotomy. Linear and nonlinear regression parameters yielded pressure half-time values and empiric constants similar to those used in Doppler echocardiography for estimation of MVA. The correlations derived from linear analysis were as good as those obtained from nonlinear analysis: from linear analysis, MVAregression = 0.79 · MVAGrolin − 0.03; r2 = 0.64, p = 0.0001; and from double exponential analysis, MVAregression = 0.86 · MVAGorlin − 0.07; r2 = 0.74; p = 0.0001. The correlations were not significantly affected by the presence of mild to moderate mitral regurgitation or whether they were obtained after balloon valvotomy. In summary, linear regression analysis yields accurate estimates of MVA despite the theoretical superiority of nonlinear methods. On-line digital analysis of mitral gradient tracings may thus be useful at the time of diagnostic cardiac catheterization or balloon mitral valvotomy to assess the severity of mitral stenosis and the response to interventions.

The response of left ventricular (LV) geometry to altered loading conditions after mitral valvuloplasty has been incompletely described. Therefore, 15 patients with rheumatic mitral stenosis were studied using quantitative 2-dimensional echocardiography a mean of 1 +/- 2 months before and 11 +/- 5 months after percutaneous balloon mitral valvuloplasty. Mitral valve area (Gorlin) increased in all patients, from 1.0 +/- 0.3 to 1.9 +/- 0.5 cm2 (p less than 0.01). Mitral regurgitation (1+/4+) developed in 3 patients, and increased by 1 grade in 1 patient as a consequence of mitral valvuloplasty. After valvuloplasty, there were significant increases in LV end-diastolic volume (69 +/- 22 to 82 +/- 26 ml, p less than 0.01), stroke volume (34 +/- 13 to 46 +/- 19 ml, p less than 0.05) and mass (181 +/- 46 to 200 +/- 42 ml, p less than 0.005). LV end-systolic volume and ejection fraction did not change significantly. LV mass-to-volume ratio was unchanged (5.6 +/- 1.5 to 5.8 +/- 1.4 g/ml, p = not significant). Quantitatively similar results were obtained when these changes were indexed to body surface area. Thus, successful mitral valvuloplasty was associated with significant increases in LV end-diastolic volume and mass. These findings suggest that increased preload may be a stimulus to myocardial growth.

The transdermal application of nitroglycerin has been used as a model of nitrate tolerance to study the effects of diuretic therapy. The administration of amiloride and hydrochlorothiazide did not prevent the development of tolerance in a group of volunteers. A further study, in patients with stable angina pectoris, showed that diuretic therapy had an antianginal effect that was independent of that of transdermal nitroglycerin therapy. The mechanisms of these antianginal effects are presently unknown and further work is needed to confirm the role of diuretic therapy in the management of patients with angina pectoris

Chronic heart failure (CHF) is an increasingly common cardiovascular disorder. Many patients who have CHF report moderate to marked decreases in the frequency of sexual activity, and up to 75% of patients report erectile dysfunction (ED). There are few controlled clinical data on the efficacy and safety of sildenafil citrate in men who have ED and CHF; thus, we evaluated these parameters in patients who had stable CHF. This was a double-blind, placebo-controlled, flexible-dose study. Men who had ED and stable CHF were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function. Secondary outcomes included the 5 functional domains of the International Index of Erectile Function, 2 global efficacy assessment questions, intercourse success rate, the Erectile Dysfunction Inventory of Treatment Satisfaction, and the Life Satisfaction Checklist. By week 12, patients who received sildenafil (n = 60) showed significant improvements on questions 3 and 4 compared with patients who received placebo (n = 72; p