Kirkwood F. Adams

Relation Between Gender, Etiology and Survival in Patients With Symptomatic Heart Failure

OBJECTIVES This study investigated the relation between gender, etiology and survival in patients with symptomatic heart failure. BACKGROUND Previous work provides conflicting results concerning the relation between gender, clinical characteristics and survival in patients with heart failure. METHODS We examined the relation of these factors in 557 patients (380 men, 177 women) who had symptomatic heart failure, predominantly nonischemic in origin (68%) and typically associated with severe left ventricular dysfunction. RESULTS Follow-up data were available in 99% of patients (mean follow-up period 2.4 years, range 1 day to 10 years) after study entry, and 201 patients reached the primary study end point of all-cause mortality. By life-table analysis, women were significantly less likely to reach this primary end point than men (p < 0.001). A significant association was found between female gender and better survival (p < 0.001), which depended on the primary etiology of heart failure (p = 0.008 for the gender-etiology interaction) but not on baseline ventricular function. Women survived longer than men when heart failure was due to nonischemic causes (men vs. women: relative risk [RR] 2.36, 95% confidence interval [CI] 1.59 to 3.51, p < 0.001). In contrast, outcome appeared similar when heart failure was due to ischemic heart disease (men vs. women: RR 0.85, 95% CI 0.45 to 1.61, p = 0.651). CONCLUSIONS Women with heart failure due to nonischemic causes had significantly better survival than men with or without coronary disease as their primary cause of heart failure.

Lack of effect of low levels of carboxyhemoglobin on cardiovascular function in patients with ischemic heart disease.

We studied 30 patients 38-75 yr of age who had ischemic heart disease to assess the effect of acute elevation of carboxyhemoglobin (COHb) concentration. Patients were nonsmokers with ischemia defined by exercise-induced ST depression (ST decreases)--25/30, angina--23/30, or abnormal ejection fraction (EF) response--18/30. After an initial familiarization and exercise session patients were exposed to air (carboxyhemoglobin [COHb] = 1.5 +/- 0.05%) and to carbon monoxide (CO) (100 ppm-COHb-average = 3.8 +/- 0.1%) on successive days in a double blind, randomized fashion. There was no significant difference in time to onset of angina (air = 312 sec, CO = 306 sec), maximal exercise time (air = 711 sec, CO = 702 sec), maximal ST decreases (1.5 mm for both), or time to significant ST decreases (air = 474 sec, CO = 475 sec). Double product at ST decreases and maximal double products were similar for both conditions. Resting ejection fraction was slightly but nonsignificantly higher after CO exposure (air = 53.9%, CO = 55.2%). Maximal ejection fraction was similar for both conditions (air = 57.4%, CO = 57.1%). Change in ejection fraction was slightly lower for CO exposure (air = 3.5%, CO = 2%), p = .049. In conclusion, there is no clinically significant effect of 3.8% COHb (representing a 2.2% increase from resting values) on the cardiovascular system in this study.

Reactive hyperemia is associated with adverse clinical outcomes in heart failure

INTRODUCTION Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients. METHODS Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (± SD) = 56.2 (±12.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period. RESULTS Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors. CONCLUSION The association of reduced hyperemic flow with increased risk of adverse clinical outcomes suggests that micro-vascular function may be an important prognostic marker in patients with HF.

Developing clinical practice guidelines for heart failure : Creative process and practice implications

The rapid growth of medical knowledge has created many advances in therapeutics related to chronic disease. Translation of these advances into everyday care of patients with chronic disease has proven problematic. Guideline development offers a principal strategy to improve use of new and existing therapeutic modalities of proven benefit. To be effective, practice guidelines must not only deal with which therapies are efficacious but attempt to consider the many practical aspects necessary in the actual care of patients. In this way both the art and science of medicine can be employed to obtain optimal patient outcomes in many chronic diseases that have been associated with severe mortality, morbidity, and poor quality of life. The logical process of guideline development and its use in one specific chronic disease, heart failure, is examined.

Current perspectives on β-receptor antagonists in the treatment of symptomatic ventricular dysfunction

Even though therapeutic advances have occurred, heart failure is still associated with significant morbidity and mortality. Digitalis, diuretics, and angiotensin‐converting enzyme inhibitors have proven effective, but in many patients still do not prevent progressive and debilitating heart failure. Many hormonal factors are involved, but two, the renin‐angiotensin‐aldosterone (RAA) axis and the autonomic nervous system, apparently are critical in the pathophysiology of progressive ventricular dysfunction. Pharmacologic suppression of the RAA system is associated with significant clinical benefit, suggesting that antagonism of sympathetic nervous activity with β‐receptor‐blocking agents might also be efficacious. Major alterations of the autonomic nervous system are characteristic of heart failure, with excessive sympathetic activity one of the earliest adaptations to the condition, and important in promoting the heart failure state and the progression of ventricular dysfunction. Certain β‐antagonists administered early by careful and slow up‐titration from small starting dosages proved effective in small trials. Large‐scale, randomized, placebo‐controlled studies continue to document that β‐blockers improve ventricular function and symptoms, and preliminary results suggest mortality and morbidity reductions as well. Although intolerance to β‐antagonism does occur, the majority of patients can be successfully treated with these agents.

Influence of calcium administration on the short-term hemodynamic and anti-ischemic effects of nifedipine

This prospective study investigated whether pretreatment with intravenously administered calcium would influence the effect of nifedipine on rest hemodynamics and treadmill performance in patients with ischemic heart disease. Seventeen patients were studied after undergoing a qualifying treadmill exercise test that revealed ST segment depression indicative of ischemic heart disease. Study subjects performed three additional treadmill tests as part of the protocol. One treadmill test was obtained from each patient to provide baseline measurements without a preceding intravenous infusion and in the absence of all antianginal drugs including nifedipine; two additional exercise tests were preceded by an infusion and 10 mg of bite-and-swallow nifedipine. The infusions, administered in a randomized, double-blind, crossover fashion, consisted of either 10 ml of 10% calcium chloride (13.6 mEq) in 50 ml of 5% dextrose in water or 5% dextrose in water alone. Rest systolic blood pressure (134 +/- 4.6 mm Hg) was unchanged after placebo infusion (135 +/- 4.6 mm Hg) but decreased to 124 +/- 4.1 mm Hg (p less than 0.01) 25 min after nifedipine administration. Rest systolic blood pressure increased after calcium infusion (from 139 +/- 4.3 to 148 +/- 4.8 mm Hg, p less than 0.01) and then decreased significantly 25 min after nifedipine administration to 135 +/- 4.2 mm Hg (p less than 0.01). Despite a decrease at the time of peak nifedipine effect after either infusion, systolic blood pressure was significantly lower after administration of nifedipine alone than after administration of calcium and nifedipine (124 +/- 4.1 vs. 135 +/- 4.2 mm Hg, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)