Mary A. Woo

The relationship between obesity and mortality in patients with heart failure.

OBJECTIVES The study aimed to evaluate the role of obesity in the prognosis of patients with heart failure (HF). BACKGROUND Previous reports link obesity to the development of HF. However, the impact of obesity in patients with established HF has not been studied. METHODS We analyzed 1,203 patients with advanced HF followed in a comprehensive HF management program. The patients were subclassified into categories of body mass index (BMI) defined as: underweight BMI <20.7 (n = 164), recommended BMI 20.7 to 27.7 (n = 692), overweight BMI 27.8 to 31 (n = 168) and obese BMI >31 (n = 179). This sample size allows the detection of small effects (0.02), with a power of 0.80 and an alpha level of 0.05 for comparing one-year survival between BMI groups. RESULTS The four BMI groups had similar profiles in terms of ejection fraction (mean 0.22), sodium, creatinine and smoking. The obese and overweight groups had significantly higher rates of hypertension and diabetes, as well as higher levels of cholesterol, triglycerides and low density lipoprotein cholesterol. The four BMI groups had similar survival rates. Ejection fraction, HF etiology and angiotensin-converting enzyme inhibitor use predicted survival on univariate analysis (p < 0.01), although BMI did not. On multivariate analysis, cardiopulmonary exercise tests, pulmonary capillary wedge pressure and serum sodium were strong predictors of survival (p < 0.05). Higher BMI was not a risk factor for increased mortality, but was associated with a trend toward improved survival. CONCLUSIONS In a large cohort of patients with advanced HF of multiple etiologies, obesity is not associated with increased mortality and may confer a more favorable prognosis. Further studies need to delineate whether weight loss promotion in medically optimized patients with HF is a worthwhile therapeutic goal.

Impact of a comprehensive heart failure management program on hospital readmission and functional status of patients with advanced heart failure.

OBJECTIVES To assess the impact of a comprehensive heart failure management program, functional status, hospital readmission rate and estimated hospital costs were determined and compared for the 6 months before and the 6 months after referral. BACKGROUND The course of advanced heart failure is characterized by progressive clinical deterioration reflected in frequent hospital admissions, which comprise the major financial cost. METHODS Over a 3-year period, 214 patients were accepted for heart transplantation and discharged after evaluation, which included adjustments in medical therapy and intensive patient education. Patients were in New York Heart Association functional class III or IV (94 and 120 patients, respectively), with a mean left ventricular ejection fraction of 0.21, peak oxygen consumption of 11 ml/kg per min and a total of 429 hospital admissions in the previous 6 months (average 2.0 per patient). Changes in the medical regimen included a 98% increase in angiotensin-converting enzyme inhibitor dose and a flexible diuretic regimen after 4.2-liter net diuresis, with counseling also regarding diet and progressive exercise. RESULTS During the 6 months after referral, there were only 63 hospital readmissions (85% reduction), with 0.29/patient (p < 0.0001). Functional status improved as assessed by functional class (p < 0.0001) and peak oxygen consumption (15.2 vs. 11.0 ml/kg per min, p < 0.001). The same results were seen after excluding the 35 patients without full 6-month follow-up (9 deaths, 14 urgent transplant procedures during hospital readmission, 12 elective transplant procedures from home); 34 hospital admissions occurred after referral, compared with 344 before referral. Even when adding in the initial hospital admission after referral for these 179 patients, there was a 35% decrease in total hospital admissions in the 6-month period. The estimated savings in hospital readmission costs after subtracting the initial hospital costs for management was

Patterns of beat-to-beat heart rate variability in advanced heart failure

9,800 per patient. CONCLUSIONS Comprehensive heart failure management led to improved functional status and an 85% decrease in the hospital admission rate for transplant candidates discharged after evaluation. The potential to reduce both symptoms and costs suggests that referral to a heart failure program may be appropriate not only for potential heart transplantation, but also for medical management of persistent functional class III and IV heart failure.

Improving survival for patients with advanced heart failure : a study of 737 consecutive patients

Diminished heart rate variability is associated with high sympathetic tone and an increased mortality rate in heart failure cases. We constructed Poincaré plots of each sinus R-R interval plotted against the subsequent R-R interval from 24-hour Holter recordings of 24 healthy subjects (control group) and 24 patients with heart failure. Every subject in the control group had a comet-shaped Poincaré plot resulting from an increase in beat-to-beat dispersion as heart rate slowed. No patient with heart failure had this comet-shaped pattern. Instead, three distinctive patterns were identified: (1) a torpedo-shaped pattern resulting from low R-R interval dispersion over the entire range of heart rates, (2) a fanshaped pattern resulting from restriction of overall R-R interval ranges with enhanced dispersion, and (3) complex patterns with clusters of points characteristic of stepwise changes in R-R intervals. Poincaré pattern could not be predicted from standard deviations of R-R intervals. This first use of Poincaré plots in heart rate variability analysis reveals a complexity not readily perceived from standard deviation information. Further study is warranted to determine if this method will allow refined assessment of cardiac-autonomic integrity in heart failure, which could help identify patients at highest risk for sudden death.

Improving survival for patients with atrial fibrillation and advanced heart failure

OBJECTIVES This study sought to determine whether survival and risk of sudden death have improved for patients with advanced heart failure referred for consideration for heart transplantation as advances in medical therapy were systematically implemented over an 8-year period. BACKGROUND Recent survival trials in patients with mild to moderate heart failure and patients after a myocardial infarction have shown that angiotensin-converting enzyme inhibitors are beneficial, type I antiarrhythmic drugs can be detrimental, and amiodarone may be beneficial in some groups. The impact of advances in therapy may be enhanced or blunted when applied to severe heart failure. METHODS One-year mortality and sudden death were determined in relation to time, baseline variables and therapeutics for 737 consecutive patients referred for heart transplantation and discharged home on medical therapy from 1986 to 1988, 1989 to 1990 and 1991 to 1993. Medical care was directed by a single team of physicians with policies established by consensus. From 1986 to 1990, the hydralazine/isosorbide dinitrate combination or angiotensin-converting enzyme inhibitors were the initial vasodilators, and class I antiarrhythmic drugs were allowed. After 1990, captopril was the initial vasodilator, given to 86% of patients compared with 46% of patients before 1989. After mid-1989, class I agents were routinely withdrawn, and amiodarone was used for frequent ventricular ectopic beats or atrial fibrillation (53% of patients after 1990 vs. 10% before 1989). RESULTS The total 1-year mortality rate decreased from 33% before 1989 to 16% after 1990 (p = 0.0001), and sudden death decreased from 20% to 8% (p = 0.0006). Adjusted for clinical and hemodynamic variables in multivariate proportional hazards models, total mortality and sudden death were lower after 1990. CONCLUSIONS The large reduction in mortality, particularly in sudden death, from advanced heart failure since 1990 may reflect an enhanced impact of therapeutic advances shown in large randomized trials when they are incorporated into a comprehensive approach in this population. This improved survival supports the growing practice of maintaining potential heart transplant candidates on optimal medical therapy until clinical decompensation mandates transplantation.

Complex heart rate variability and serum norepinephrine levels in patients with advanced heart failure

OBJECTIVES We attempted to determine whether changes in heart failure therapy since 1989 have altered the prognostic significance of atrial fibrillation. BACKGROUND Atrial fibrillation occurs in 15% to 30% of patients with heart failure. Despite the recognized potential for adverse effects, the impact of atrial fibrillation on prognosis is controversial. METHODS Two-year survival for 750 consecutive patients discharged from a single hospital after evaluation for heart transplantation from 1985 to 1989 (Group I, n = 359) and from 1990 to April 1993 (Group II, n = 391) was analyzed in relation to atrial fibrillation. In Group I, class I antiarrhythmic drugs and hydralazine vasodilator therapy were routinely allowed. In Group II, amiodarone and angiotensin-converting enzyme inhibitors were first-line antiarrhythmic and vasodilating drugs. RESULTS A history of atrial fibrillation was present in 20% of patients in Group I and 24% of those in Group II. Patients with atrial fibrillation in the two groups had similar clinical and hemodynamic profiles. Among patients with atrial fibrillation, those in Group II had a markedly better 2-year survival (0.66 vs. 0.39, p = 0.001) and sudden death-free survival (0.84 vs. 0.70, p = 0.01) than those in Group I. In each time period, survival was worse for patients with than without atrial fibrillation in Group I (0.39 vs. 0.55, p = 0.002) but not in Group II (0.66 vs. 0.75, p = 0.09). CONCLUSIONS The prognosis of patients with advanced heart failure and atrial fibrillation is improving. These findings support the practice of avoiding class I antiarrhythmic drugs in this group and may reflect recent beneficial changes in heart failure therapy.

Heart Rate Variability in Congenital Central Hypoventilation Syndrome

OBJECTIVES This study was designed to examine the relation of the Poincaré plot heart rate variability pattern to sympathetic nervous system activity as assessed by serum norepinephrine. BACKGROUND Poincaré plots demonstrate a complexity of beat to beat behavior not readily detected by other heart rate variability measures. Previous studies have described two abnormal Poincaré patterns in patients with heart failure: a torpedo pattern with reduced beat to beat variability and a complex pattern with clustering of points. METHODS To assess the relation of these plots to sympathetic activity, plasma norepinephrine at rest and a standard deviation measure of heart rate variability were analyzed in 21 patients with heart failure (mean left ventricular ejection fraction [+/- SD] 0.22 +/- 0.05). RESULTS Eleven subjects had a torpedo-shaped and 10 subjects had a complex Poincaré plot pattern. These two groups did not differ significantly in age, functional class, disease etiology, left ventricular ejection fraction, heart rate, ventricular ectopic activity or in a standard deviation measure of heart rate variability. However, patients with a complex Poincaré plot pattern had higher norepinephrine levels (722 +/- 373 pg/ml) than patients with torpedo-shaped plots (309 +/- 134 pg/ml) (p = 0.003). Patients with a complex pattern also had more severe hemodynamic decompensation, as evidenced by their higher levels of pulmonary capillary wedge and mean pulmonary artery pressures and lower values for cardiac index than those of patients with a torpedo-shaped plot. CONCLUSIONS Complex Poincaré plots are associated with marked sympathetic activation and may provide additional prognostic information and insight into autonomic alterations and sudden cardiac death in patients with heart failure.

Brain Injury in Autonomic, Emotional, and Cognitive Regulatory Areas in Patients with Heart Failure

ABSTRACT: Heart rate variability was assessed in 12 patients with congenital central hypoventilation syndrome (CCHS) and in age- and sex-matched controls using SD of time intervals between R waves (R-R intervals), R-R interval histograms, spectral analysis, and Poincaré plots of sequential R-R intervals over a 24-h period using ambulatory monitoring. Mean heart rates in patients with CCHS were 103.3 ± 17.7 SD and in controls were 98.8 ± 21.6 SD (p > 0.5, NS). SD analysis of R-R intervals showed similar results in both groups (CCHS 102.2 ± 36.0 ms versus controls 126.1 ± 43.3 ms; p > 0.1, NS). Spectral analysis revealed that, for similar epochs sampled during quiet sleep and wakefulness, the ratios of low-frequency band to high-frequency band spectral power were increased for 11 of 12 patients with CCHS during sleep, whereas a decrease in these ratios was consistently observed in all controls during comparable sleep states (χ2 = 20.31; p < 0.000007). During wakefulness, the ratios of low-frequency band to high-frequency band spectral power were similar in both patients with CCHS and controls. Poincaré plots displayed significantly reduced beat-to-beat changes at slower heart rates in the CCHS patients (χ2 = 24.0; p < 0.000001). The scatter of points in CCHS Poincare plots was easily distinguished from controls. AH CCHS patients showed disturbed variability with one or more measures. The changes in moment-to-moment heart rate variability suggest that, in addition to a loss of ventilatory control, CCHS patients exhibit a dysfunction in autonomic nervous system control of the heart.

Improved Survival in Patients With Nonischemic Advanced Heart Failure and Syncope Treated With an Implantable Cardioverter-Defibrillator

BACKGROUND Heart failure (HF) is accompanied by autonomic, emotional, and cognitive deficits, indicating brain alterations. Reduced gray matter volume and isolated white matter infarcts occur in HF, but the extent of damage is unclear. Using magnetic resonance T2 relaxometry, we evaluated the extent of injury across the entire brain in HF. METHODS AND RESULTS Proton-density and T2-weighted images were acquired from 13 HF (age 54.6 +/- 8.3 years; 69% male, left ventricular ejection fraction 0.28 +/- 0.07) and 49 controls (50.6 +/- 7.3 years, 59% male). Whole brain maps of T2 relaxation times were compared at each voxel between groups using analysis of covariance (covariates: age and gender). Higher T2 relaxation values, indicating injured brain areas (P < .005), emerged in sites that control autonomic, analgesic, emotional, and cognitive functions (hypothalamus, raphé magnus, cerebellar cortex, deep nuclei and vermis; temporal, parietal, prefrontal, occipital, insular, cingulate, and ventral frontal cortices; corpus callosum; anterior thalamus; caudate nuclei; anterior fornix and hippocampus). No brain areas showed higher T2 values in control vs. HF subjects. CONCLUSIONS Brain structural injury emerged in areas involved in autonomic, pain, mood, language, and cognitive function in HF patients. Comorbid conditions accompanying HF may result from neural injury associated with the syndrome.

Relationship between obstructive sleep apnea severity and sleep, depression and anxiety symptoms in newly-diagnosed patients.

The purpose of this study was to assess whether in patients with syncope and heart failure due to nonischemic cardiomyopathy, treatment with an implantable cardioverter-defibrillator (ICD) compared with conventional medical therapy is associated with a reduction in sudden death and total mortality. Patients with advanced heart failure who have syncope have been shown to be at high risk for sudden death. Further risk stratification has been difficult in patients with nonischemic cardiomyopathy in whom inducibility on electrophysiologic study is not predictive of future risk. Of 639 consecutive patients with nonischemic cardiomyopathy referred for heart transplantation, 147 patients with history of syncope and no prior history of sustained ventricular tachycardia or cardiac arrest were identified. Outcomes were compared for the 25 patients managed with an ICD and 122 patients managed with conventional medical therapy. There were no differences in the baseline variables in the 2 groups of patients, including age, ejection fraction, and medical treatments for heart failure, but patients receiving an ICD were more likely to have had nonsustained ventricular tachycardia (56% vs. 15%, p = 0.001). During a mean follow-up of 22 months, there were 31 deaths, 18 sudden, in patients treated with conventional therapy, whereas there were 2 deaths, none sudden, in patients treated with an ICD. An appropriate shock occurred in 40% of the ICD patients. Actuarial survival at 2 years was 84.9% with ICD therapy and 66.9% with conventional therapy (p = 0.04). Thus, in patients with nonischemic cardiomyopathy and syncope, therapy with an ICD is associated with a reduction in sudden death and an improvement in overall survival.