Lynne Warner Stevenson

Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients.

BackgroundAtrial fibrillation is common in advanced heart failure, but its prognostic significance is controversial. Methods and ResultsWe evaluated the relation of atrial rhythm to overall survival and sudden death in 390 consecutive advanced heart failure patients. Etiology of heart failure was coronary artery disease in 177 patients (45%) and nonischemic cardiomyopathy or valvular heart disease in 213 patients (55%). Mean left ventricular ejection fraction was 0.19 ± 0.07. Seventy-five patients (19%o) had paroxysmal (26 patients) or chronic (49 patients) atrial fibrillation. Compared with patients with sinus rhythm, patients with atrial fibrillation did not differ in etiology of heart failure, mean pulmonary capillary wedge pressure on therapy, or embolic events but were more likely to be receiving warfarin and antiarrhythmic drugs and had a slightly higher left ventricular ejection fraction. After a mean follow-up of 236 ± 303 days, 98 patients died: 56 (57%) died suddenly, and 36 (37%) died of progressive heart failure. Actuarial 1-year overall survival was 68%, and sudden death-free survival was 79%. Actuarial survival was significantly worse for atrial fibrillation than for sinus rhythm patients (52% versus 71%, p =0.0013). Similarly, sudden death-free survival was significantly worse for atrial fibrillation than for sinus rhythm patients (69% versus 82%, p = 0.0013). By Cox proportional hazards model, pulmonary capillary wedge pressure on therapy, left ventricular ejection fraction, coronary artery disease, and atrial fibrillation were independent risk factors for total mortality and sudden death. For patients who had pulmonary capillary wedge pressure of less than 16 mm Hg on therapy, atrial fibrillation was associated with poorer 1-year survival (44% versus 83%, p = 0.00001); however, in the high pulmonary capillary wedge pressure group, atrial fibrillation did not confer an increased risk (58% versus 57%). ConclusionsAtrial fibrillation is a marker for increased risk of death, especially in heart failure patients who have lower filling pressures on vasodilator and diuretic therapy. Whether aggressive attempts to maintain sinus rhythm will reduce this risk is unknown. (Circulation 1991;84:40–48)

Diverse mechanisms of unexpected cardiac arrest in advanced heart failure.

To define the mechanisms of unexpected cardiac arrest in advanced heart failure, we reviewed the causes of cardiac arrest as established from electrocardiographic monitoring and from clinical and autopsy data in patients hospitalized for cardiac transplantation evaluation and management of advanced heart failure (mean left ventricular ejection fraction, 0.18 +/- 0.08) who were stable while on vasodilator and diuretic therapy such that hospital discharge to home was anticipated. Twenty-one cardiac arrests occurred in 20 of 216 (9%) such patients during a 4-year period. Heart failure was due to coronary artery disease with prior myocardial infarction in 13 patients and nonischemic cardiomyopathy in seven patients. The rhythm at the time of arrest was severe bradycardia or electromechanical dissociation (BA/EMD) in 13 (62%) patients. The precipitating cause of the BA/EMD arrest was coronary artery thrombosis or embolism in two patients, pulmonary embolism in one patient, hyperkalemia in two patients, and unexplained hypoglycemia in one patient. In seven of 13 (54%) patients, a precipitating cause of the bradycardia arrest could not be established. Only eight of 21 (38%) arrests were due to ventricular tachycardia or fibrillation (VT/VF), and all occurred in patients with prior myocardial infarction (p = 0.02 vs. BA/EMD arrests). Two VT/VF arrests were due to acute or recent infarction, and one patient had hyperkalemia. The patients who suffered a BA/EMD arrest were similar to those who had a VT/VF arrest in age, ventricular arrhythmia history, ventricular function, and serum potassium levels. Serum sodium levels were lower in patients with BA/EMD arrests (129 +/- 3 vs. 133 +/- 4 meq/l, p = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of hemodynamic response to therapy in predicting survival with ejection fraction ≤20% secondary to ischemic or nonischemic dilated cardiomyopathy

To identify patients with left ventricular ejection fractions less than 20% who are likely to survive on tailored medical therapy after referral to transplantation, this study of 152 patients addressed the hypotheses that (1) severely elevated filling pressures initially measured at referral would not necessarily predict poor outcome, (2) survival would be best when low pulmonary wedge pressures could be achieved with therapy tailored for hemodynamic goals, and (3) coronary artery disease would be an independent risk factor for early mortality. Despite an average initial ejection fraction of 0.15, cardiac index of 2.0 liters/min/m2 and pulmonary artery wedge pressure of 28 mm Hg, the actuarial survival with tailored therapy was 63% at 1 year, with 34 of 41 (83%) deaths occurring suddenly. Survival was not related to initial filling pressure elevation, but was best predicted by the pulmonary artery wedge pressures during therapy; patients achieving pressure of less than or equal to 16 mm Hg had 1-year survival of 83 vs 38% (p = 0.0001). The other independent predictors were serum sodium and coronary artery disease. Patients with high filling pressures during therapy and coronary artery disease had 21% survival at 1 year. Survival after referral to transplantation with an ejection fraction less than or equal to 20% is better than previously described. Patients in whom left ventricular filling pressures cannot be adequately reduced by tailored therapy, particularly if coronary artery disease is present, should be considered for early transplantation.

Syncope in advanced heart failure: High risk of sudden death regardless of origin of syncope

OBJECTIVES The purpose of this study was to assess the importance of syncope as a warning sign for sudden death in advanced heart failure and to determine the relative importance of cardiac syncope and syncope from other causes. BACKGROUND Despite remarkable advances in the pharmacologic approach to advanced heart failure, 20% to 40% of patients with advanced heart failure will die each year. In such patients, the relation between sudden death and the etiology of syncope has not been evaluated. METHODS The relation of syncope to sudden death was evaluated in 491 consecutive patients with advanced heart failure (New York Heart Association functional class III or IV), no history of cardiac arrest and a mean left ventricular ejection fraction of 0.20 +/- 0.07. Patients were evaluated for the presence and origin of syncope. The severity of heart failure was assessed from serum sodium levels, ejection fraction, functional class and echocardiographic and hemodynamic variables. RESULTS Sixty patients (12%) had a history of syncope; the condition had a cardiac origin in 29 (48%) and was due to other causes in 31 (52%). The origin of heart failure was coronary artery disease in 234 patients (48%) and dilated cardiomyopathy in 253 (51%) and its severity was similar in patients with and without syncope. During a mean follow-up interval of 365 +/- 419 days, 69 patients (14%) died suddenly and 66 patients (13%) died of progressive heart failure. The actuarial incidence of sudden death by 1 year was significantly greater in patients with (45%) than in those without (12%, p < 0.00001) syncope. In the Cox proportional hazards model, syncope predicted sudden death independent of atrial fibrillation, serum sodium, cardiac index, angiotensin-converting enzyme inhibition and patient age. The actuarial risk of sudden death by 1 year was similarly high in patients with either cardiac syncope or syncope from other causes (49% vs. 39%, p = NS). CONCLUSIONS Patients with advanced heart failure are at especially high risk for sudden death regardless of the etiology of syncope.

Exercise capacity for survivors of cardiac transplantation or sustained medical therapy for stable heart failure.

Cardiac transplantation is predicted to improve survival for patients with severe symptoms of heart failure and ejection fraction of 20% or less, but the exercise capacity after cardiac transplantation is less than normal. Patients responding to vasodilators and diuretics have progressive improvement in exercise capacity despite low ejection fraction. We hypothesized that among patients currently considered appropriate for transplantation who could nonetheless subsequently be stabilized on medical therapy tailored to hemodynamic goals, survivors after 6 months of sustained medical therapy would demonstrate exercise capacity comparable to that of survivors of transplantation. Of 146 patients referred, 118 (81%) were discharged on tailored therapy without transplantation, and 88 (60%) were stable for at least 1 month. Stability after discharge was more likely in patients with lower right atrial pressures and better renal function on therapy. Of the 88 stable patients, 45 patients were listed for transplant, and 43 were ineligible or unwilling. From these patients, 42 survivors for more than 6 months follow-up after cardiac transplantation or tailoring of medical therapy underwent exercise testing. Baseline functional and hemodynamic status and left ventricular ejection fraction (15 +/- 4%) were not different between the transplant and sustained medical survivor groups at the time of initial evaluation. After 14 +/- 6 months, left ventricular ejection fraction had increased to 62 +/- 7% after transplantation (p less than 0.01) and only 22 +/- 9% after sustained medical therapy (p less than 0.05). However, there were no significant differences in the maximum workload, oxygen uptake, anaerobic threshold, or maximum oxygen pulse between survivors of cardiac transplantation and survivors on sustained medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered thyroid hormone metabolism in advanced heart failure

To determine the prevalence and significance of abnormal thyroid hormone metabolism in congestive heart failure, free thyroxine (T4) index, free triiodothyronine (T3) index, reverse T3 and thyrotropin levels were obtained in 84 hospitalized patients with chronic advanced heart failure. Free T4 index was normal in all patients. Free T3 index was reduced or reverse T3 elevated, or both, leading to a low free T3 index/reverse T3 ratio in 49 (58%) of the 84 patients. A low free T3 index/reverse T3 ratio was associated with higher right atrial, pulmonary artery and pulmonary capillary wedge pressures and lower ejection fraction, cardiac index, serum sodium, albumin and total lymphocyte count. In multivariate analysis, the free T3 index/reverse T3 ratio was the only independent predictor of poor 6 week outcome (p less than 0.001); the actuarial 1 year survival rate was 100% for patients with a normal ratio and only 37% for those with a low ratio (p less than 0.0001). A low free T3 index/reverse T3 ratio is associated with poor ventricular function and nutritional status and is the strongest predictor yet identified for short-term outcome in patients with advanced heart failure.

Impact of left ventricular cavity size on survival in advanced heart failure.

Although left ventricular (LV) dilation has been assumed to be deleterious, the physiologic significance of severe LV dilation in advanced heart failure and its impact on survival have not been defined. LV end-diastolic dimension was measured by M-mode echocardiography in 382 patients with class III or IV heart failure symptoms (mean LV ejection fraction 20 +/- 8%) referred for evaluation for cardiac transplantation. All patients underwent right-sided heart catheterization, and received vasodilator and diuretic therapy adjusted to hemodynamic goals. Although 183 patients with massive LV dilation by LV index > 4 cm/m2 (LV index = LV end-diastolic dimension/estimated body surface area) had a similar severity of hemodynamic impairment to that of 199 patients with only moderate dilation (LV index < or = 4 cm/m2), with baseline mean cardiac index of 2 liters/m/m2 and mean pulmonary arterial wedge pressure of 26 mm Hg in both groups, their actuarial 2-year survival without transplantation was much lower (49 vs 75%; p = 0.004). In the Cox proportional-hazards model, LV index predicted total and sudden death, independent of etiology of heart failure, ejection fraction and other parameters of disease severity. Follow-up echocardiograms (mean 13 +/- 6 months) in 80 heart failure survivors without transplantation showed an increase in mean LV ejection fraction (22 +/- 8% to 26 +/- 13%), but no change in mean LV index in either the massive or moderately dilated groups. Thus, massive LV dilation is an independent contributor to poor outcome in patients with advanced heart failure, and may be stabilized by aggressive vasodilator and diuretic therapy.

Safety and Hemodynamic Effects of Intravenous Triiodothyronine in Advanced Congestive Heart Failure

Most patients with advanced congestive heart failure have altered thyroid hormone metabolism. A low triiodothyronine level is associated with impaired hemodynamics and is an independent predictor of poor survival. This study sought to evaluate safety and hemodynamic effects of short-term intravenous administration of triiodothyronine in patients with advanced heart failure. An intravenous bolus dose of triiodothyronine, with or without a 6- to 12-hour infusion (cumulative dose 0. 1 5 to 2.7 microg/kg), was administered to 23 patients with advanced heart failure (mean left ventricular ejection fraction 0.22 +/- 0.01). Cardiac rhythm and hemodynamic status were monitored for 12 hours, and basal metabolic rate by indirect calorimetry, echocardiographic parameters of systolic function and valvular regurgitation, thyroid hormone, and catecholamine levels were measured at baseline and at 4 to 6 hours. Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect. Acute intravenous administration of triiodothyronine is well tolerated in patients with advanced heart failure, establishing the basis for further investigation into the safety and potential hemodynamic benefits of longer infusions, combined infusion with inotropic agents, oral triiodothyronine replacement therapy, and new triiodothyronine analogs.

Predicting death from progressive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Data were retrospectively reviewed on 528 consecutive patients hospitalized for treatment of advanced heart failure (left ventricular ejection fraction 0.2 +/- 0.07) and cardiac transplant evaluation, who were stabilized with medical therapy and discharged home. Predictors of heart failure death or rehospitalization for urgent transplantation were identified using the Cox proportional-hazards model. Within 1 year, 59 patients (11%) died suddenly and 70 (13%) died of heart failure or required urgent transplantation. A serum sodium < or = 134 mEq/liter, pulmonary arterial diastolic pressure > 19 mm Hg, left ventricular diastolic dimension index > 44 mm/m2, peak oxygen consumption during exercise testing < 11 ml/kg/min and the presence of a permanent pacemaker were independent predictors of hemodynamic deterioration. In the absence of these risk factors the risk of hemodynamic deterioration within 1 year from this study was only 2%. This risk increased to > 50% in the presence of hyponatremia and any 2 additional risk factors. Thus, patients with advanced heart failure at highest risk for progressive hemodynamic deterioration can be identified from clinical variables that could aid in triaging such patients to earlier cardiac transplantation.

Prevalence and hemodynamic correlates of malnutrition in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Whereas cardiac cachexia is well recognized, the frequency and hemodynamic correlates of malnutrition in severe congestive heart failure (CHF) have not been established. Anthropometric and serum albumin assessment of nutritional status was compared with hemodynamic, echocardiographic and serum chemistry evaluation in 48 patients with severe CHF (ejection fraction 0.17 +/- 0.05). Malnutrition, as defined by decreases in percent body fat determined from skinfold thicknesses, weight/height index or serum albumin, was present in 24 of 48 (50%) patients, who did not differ from the 24 well-nourished patients in cardiac index (1.9 +/- 0.6 vs 2.1 +/- 0.6 liters/min/m2) and pulmonary artery wedge pressure (30 +/- 6 vs 27 +/- 10 mm Hg), but had higher right atrial pressure (16 +/- 5 vs 9 +/- 6 mm Hg, p less than 0.01) and more severe tricuspid regurgitation by semiquantitative Doppler grading on a 0 to 3 scale (2.0 +/- 0.9 vs 0.9 +/- 0.8, p less than 0.01). Right atrial pressure was the only independent hemodynamic predictor of malnutrition (p less than 0.0002). Malnourished patients had lower serum sodium (134 +/- 4 vs 139 +/- 4 mEq/liter, p less than 0.01) and total triiodothyronine levels (89 +/- 30 vs 115 +/- 26 ng/dl, p less than 0.01) and higher creatinine levels (1.6 +/- 0.7 vs 1.2 +/- 0.4, p less than 0.03). None of the other biochemical markers of nutritional status differed between the groups except lower serum triglyceride levels (115 +/- 73 vs 186 +/- 97 mg/dl, p less than 0.05) in malnourished patients. Malnutrition is common in patients with severe CHF and is associated with increased right atrial pressure and tricuspid regurgitation.