Sex, the heart, and heart failure.

In the modern era of pharmacologic treatment of erectile dysfunction, men with heart disease increasingly approach their physicians regarding the possibility of restoring sexual activity. At the same time, patients are also frequently aware of public figures that have reportedly died during coitus, often in the arms of their mistresses or prostitutes. Added to this is the perception of patients, and oftentimes their physicians, that coitus and orgasm are associated with a near maximal or even "supermaximal" cardiac workload and therefore may be hazardous for a diseased heart. Accordingly, knowledge of the cardiovascular effects of sexual activity, the risks of triggering a cardiovascular event, and the potential risks inherent in the use of drug therapy of male impotence is important to properly advise patients and their spouses regarding this sensitive issue.

Prolonged oxygen uptake kinetics during low-intensity exercise are related to poor prognosis in patients with mild-to-moderate congestive heart failure.

STUDY OBJECTIVE: To investigate the prognostic value of oxygen uptake (O(2)) kinetics during low-intensity exercise in patients with congestive heart failure. DESIGN: Prospective cohort study. SETTING: Tertiary care center. PATIENTS: One hundred forty-six consecutive patients (128 men) with chronic heart failure, followed up for a mean (+/- SD) duration of 25 +/- 15 months. MEASUREMENTS: A treadmill exercise test was performed with "breath by breath" gas-exchange monitoring. VO(2) kinetics were defined as the VO(2) deficit (ie, Delta VO(2) x time[rest to steady state] - Sigma VO(2)[rest to steady state]) and mean response time (MRT) [ie, VO(2) deficit/Delta VO(2)]. Cardiac death, urgent cardiac transplantation, and hospitalization due to worsening heart failure were considered as the end points. RESULTS: Thirty patients (21%) died, 11 patients (8%) underwent urgent transplantation, and 32 patients (22%) were hospitalized. In univariate analysis, MRT was the most powerful predictor of survival, survival free of urgent transplantation, and survival free of hospitalization (hazard ratios [HRs] per 10 s, 1.65, 1.72, and 1.61, respectively; all p < 0.0001). The predictive value of MRT exceeded that of peak VO(2) (HR per mL/kg/min, 0.90; p = 0.02, 0.91; p = 0.007, and 0.95; p = 0.08, respectively). In multivariate analysis, MRT (HR per 10 s, 1.73; p = 0.0002), resting systolic BP (HR per 10 mm Hg, 0.65; p = 0.003), and the slope of the ventilatory response to exercise (HR per 10 U, 1.68; p = 0.02) were independent predictors of survival. CONCLUSIONS: Our results suggest that VO(2) kinetics are strongly related to outcome in heart failure patients. Since it has several additional advantages over peak exercise testing (eg, less time-consuming, less demanding for the patients, less dependent on motivation, and applicable in patients with limitations other than cardiopulmonary disease), it has the potential to become a prognostic test for the assessment of heart failure patients.

Combining low-intensity and maximal exercise test results improves prognostic prediction in chronic heart failure.

OBJECTIVES: This study investigated the combination of maximal and low-intensity exercise testing in predicting prognosis in chronic heart failure (CHF), using one single exercise test (two-step protocol). BACKGROUND: Risk assessment based on any single factor has limited accuracy and reproducibility. METHODS: Treadmill exercise testing was performed in 202 consecutive CHF patients (174 male; mean age 52 +/- 11 years) using "breath-by-breath" gas exchange monitoring. Oxygen uptake (VO(2)) kinetics were defined as oxygen deficit (DeltaVO(2) x time [rest to steady state] - Sigma VO(2) [rest to steady state]) and mean response time (MRT = oxygen-deficit/DeltaVO(2)). Peak VO(2) (VO(2)max) was defined as the highest VO(2). Mean follow-up was 873 +/- 628 days. The primary end point was cardiac mortality and the need for urgent heart transplantation. RESULTS: Forty-four patients (22%) died and 15 (7%) were urgently transplanted. In both univariate and multivariate analyses, MRT >50 s was the most powerful predictor of the primary end point (hazard ratio [HR] 4.44), followed by predicted VO(2)max <50% (HR 3.50) and resting systolic blood pressure <105 mm Hg (HR 2.49, all p < 0.001). A majority (n = 130 [64%]) had one or none of these risk factors, with a one-year event rate of only 3%. Patients with two risk factors (n = 45 [22%]) were at medium risk (one-year event rate of 33%). Twenty-seven patients (13%) had all three risk factors, with a one-year event rate of 59%. The area under the curve, using the number of risk factors, was 0.86 +/- 0.04 for the primary end point at one year. These results were independent of medication, in particular, beta-blockade. CONCLUSIONS: A combination of low-intensity and maximal exercise test results improves assessment of prognosis in patients with CHF.

Interaction of sildenafil with cAMP-mediated vasodilation in vivo.

Sildenafil inhibits cGMP breakdown by phosphodiesterase 5. In vitro, increased cGMP levels inhibit cAMP breakdown by phosphodiesterase 3. It is uncertain, however, whether sildenafil increases biological effects of interventions increasing cAMP levels in vivo. The objective of the present study in 40 healthy male volunteers was to determine the existence and extent of interactions with sildenafil and vasodilators acting via cGMP or cAMP or independently from these mediators on the arterial tone of the human forearm. Forearm blood flow (FBF) responses (plethysmography) to brachial artery infusions of 3 doses each of nitroglycerin, which increases cGMP levels; of isoprenaline and milrinone, which increase cAMP levels; and of verapamil as a control were assessed at baseline and 80 minutes after 50 mg oral sildenafil in 10 volunteers each. Sildenafil increased FBF (2.5+/-0.1 to 3.5+/-0.2 mL/min per 100 mL, P<0.001; n=40). At equipotent vasodilator dosages, sildenafil increased FBF from 7.5+/-1.0 to 9.8+/-1.2 mL/min per 100 mL for nitroglycerin, from 8.3+/-1.0 to 10.4+/-1.4 mL/min per 100 mL for isoprenaline, and from 8.1+/-1.0 to 10.3+/-1.2 mL/min per 100 mL for milrinone and slightly decreased FBF from 7.7+/-1.3 to 7.1+/-1.2 mL/min per 100 mL for verapamil. ANOVA for repeated measures revealed a significant interaction between sildenafil and the type of vasodilator on FBF (P<0.01). The responses of FBF to nitroglycerin, milrinone, and isoprenaline after sildenafil were similarly increased compared with the response to verapamil (P<0.01). Sildenafil markedly enhanced the arterial vasodilator response to nitroglycerin, milrinone, and isoprenaline. The response to milrinone and isoprenaline is compatible with an interaction between cGMP and phosphodiesterase 3 or an enhancement of the NO component of cAMP-mediated vasodilation, and raises the possibility of enhanced biological effects of interventions leading to increases of cAMP in the presence of sildenafil.

Noninvasive assessment of cardiac pumping capacity during exercise predicts prognosis in patients with congestive heart failure.

BACKGROUND: Prognostic parameters in patients with congestive heart failure (CHF) are important for guiding therapeutic options. Maximal oxygen uptake (O(2)max) is a widely used parameter for prognostic assessment in patients with CHF and correlates with exercise cardiac output; however, afterload is not taken into account. METHODS: The concept of a noninvasive surrogate of cardiac power output combines exercise systolic BP (SBP), as an estimate of afterload, with O(2)max, as an estimate of exercise cardiac output neglecting preload. Thus, a variable termed exercise cardiac power (ECP) is defined as the product of O(2)max (expressed as a percent predicted value) and SBP (ECP, expressed as %mm Hg, is the product of O(2)max, expressed as percentage of predicted maximum, times systolic pressure. The prognostic value of ECP obtained during routine treadmill ergospirometry was assessed in patients referred to our heart failure clinic. Patients undergoing heart transplantation were censored at the time of transplantation. RESULTS: One hundred fifty-four patients were followed prospectively for a mean (+/- SE) duration of 625 +/- 32 days. Thirty-two patients (21%) died. ECP was the most powerful predictor of mortality, was the combined end point of mortality or hospitalization for worsening heart failure (all p < 0.001), and was an independent predictor in multivariate analysis. An ECP of < 5,000 %mm Hg indicated a poor prognosis with a 1-year mortality rate of 37%, whereas only 2% of the patients having an ECP of > 9,000 %mm Hg died during the first year. CONCLUSION: The integration of afterload and O(2)max improves the prognostic value of each indicator, and provides an easily available and independent predictor of mortality and morbidity in CHF patients. This integrative concept of cardiac hydraulic performance is superior to O(2)max and can be used in routine ergospirometry.