Temporal variations in hematocrit values in patients with left ventricular dysfunction: Relationship with cause-specific mortality and morbidity and optimal monitoring--further insights from SOLVD

BACKGROUND

Anemia is associated with an increased risk of death in heart failure (HF) patients. Currently, the relationship between temporal variations in hematocrit and specific causes of mortality and morbidity, as well as the most appropriate way to monitor changes in hematocrit, is unknown.

OBJECTIVE

To evaluate the prognostic value of changes in hematocrit during follow-up on specific causes of mortality and morbidity in the Studies Of Left Ventricular Dysfunction (SOLVD).

METHODS

A retrospective analysis of the SOLVD trials was conducted. Changes in hematocrit were evaluated in two ways: hematocrit as an absolute value at baseline and at each visit, and relative hematocrit variations compared with baseline.

RESULTS

Low absolute hematocrit values during follow-up were associated with cardiovascular (CV), non-CV and HF mortality, HF and non-CV hospitalizations, and cardiac ischemic events (P<0.05 for all end points). Decreases in hematocrit during follow-up compared with baseline were associated with HF hospitalizations (P<0.05) and non-CV death in patients receiving placebo (P=0.01 for interaction).

CONCLUSIONS

Hematocrit values during follow-up provide independent prognostic information in patients with HF for both CV and non-CV events. Absolute values of hematocrit are more closely related with outcomes and are therefore more clinically relevant to monitor than relative variations.     

Heart failure mortality in Southeast Asian patients with left ventricular systolic dysfunction

BackgroundPrognostic indicators and mortality in multiethnic Southeast Asian patients with heart failure (HF) may be different.Methods and ResultsThe study population comprised 225 inpatients with HF with a left ventricular ejection fraction of 40% or less who were discharged alive. Five years later, survival and causes of death were determined. Proportionally, more Malay and Indian patients were admitted compared with Chinese patients (P < .001). There were 55.6% in New York Heart Association (NYHA) class III or IV. Ischemic heart disease was the most common cause (85.8%). At 5 years, 152 patients (67.5%) had died. Angiotensin-converting enzyme inhibitors were prescribed to 79.1% of patients on discharge. Cardiovascular causes accounted for 69.7% of deaths. Predictors of mortality include female gender (P = .046), age 70 years or more (P = .017), renal impairment (P = .008), NYHA class III or IV (P = .03), and non-use of angiotensin-converting enzyme inhibitors (P = .005). On multivariate analysis, increasing age (P = .001) and renal impairment (P = .019) were independent predictors of all-cause mortality. Cardiovascular death was more likely with NYHA class III or IV (P = .004) and renal impairment (P = .012).ConclusionMortality is unusually high in this group of patients despite treatment. Greater use of evidence-based therapies in HF-management programs may arrest this trend.     

Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators.

BACKGROUND. In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure. METHODS AND RESULTS. We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo. CONCLUSIONS. In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.     

Assessment of heart failure and left ventricular systolic dysfunction after cardiac pacing in patients with preserved left ventricular systolic function

BACKGROUND: There is an accumulating data suggesting the deleterious effects of right ventricular pacing on left ventricular performance. Such pacing mimics left bundle branch block resulting in a prolonged QRS duration and causes ventricular asynchrony. AIMS: The purpose of this study is to assess heart failure and left ventricular systolic function after cardiac pacemaker implantation in patients with atrioventricular block and preserved systolic left ventricular function. Secondly, we sought to search for predictive factors of developing left ventricular dysfunction after pacing. METHODS: In this prospective study, we included patients who had been implanted for at least six months. They underwent medical history and examination, 12 leads electrocardiogram and echocardiography before pacemaker implantation and when attending to routine pacemaker follow up. RESULTS: Forty-three patients (22 men and 21 women, age 71+/-12 years) were included in this study. Twenty-nine patients had DDD pacing and 14 VVI pacing. The ventricular lead was implanted in the apex in all patients. After a median follow up of 18+/-11 months, 11 patients (25%) developed signs of congestive heart failure. NYHA was higher after implantation (1.64+/-0.7 versus 2.27+/-0.8, p>0.00001). Left ventricular ejection fraction decreased significantly during follow up (60+/-6% versus 51+/-13%, p=0.0002). Eleven (25%) patients developed left ventricular dysfunction. We compared patients who had left ventricular ejection fraction (LV EF) less or equal to 40% (group A) and patients having LV EF greater than 40% (group B) after implantation. Patients in group A had a paced QRS width significantly larger than group B (181+/-32 ms versus 151+/-26 ms, p=0.002), a significantly prolonged intra left ventricular electromechanical delay (115+/-59 ms versus 45+/-35 ms, p<0.0001) and interventricular delay (44+/-29 ms versus 27+/-18 ms, p=0.02). Age, sex, diabetes hypertension, pacing mode and percentage of ventricular pacing were similar in both groups. A paced QRS width of 180 ms had the best sensitivity and specificity for detecting left ventricular dysfunction: sensitivity=54% and specificity=93%, p=0.01, area under the curve=0.75. CONCLUSION: Patients with atrioventricular block and preserved left ventricular systolic function at baseline decrease significantly left ventricular ejection fraction after pacing. Induced ventricular asynchronism plays a major role in the deterioration of left ventricular function. Prolonged paced QRS width is a good predictor of left ventricular dysfunction after pacing. Larger prospective studies are needed to confirm these data.     

Mitral insufficiency and morbidity and mortality in left ventricular dysfunction

BACKGROUND: Mitral insufficiency is known to occur in a substantial proportion of patients with heart failure. Its relationship with morbidity and mortality is poorly described. METHODS: The mortality and hospitalization for heart failure were retrospectively examined in patients who underwent baseline echocardiography in the Studies Of Left Ventricular Dysfunction (SOLVD) treatment and prevention trials. The presence and grade of mitral insufficiency was assessed, and patients with and without mitral insufficiency were compared. RESULTS: Patients with left ventricular dysfunction and mitral insufficiency had greater than twofold increased risk of death or admission for heart failure over two years (RR 2.38, 95% CI 1.43 to 3.97). This excess risk persisted after adjustment for the severity of heart failure, etiology and differences in treatment (RR 1.82, 95% CI 1.04 to 3.17; P=0.04). The presence of moderate mitral insufficiency versus no insufficiency was associated with even greater independent risk (RR 2.20, 95% CI 1.01 to 4.80; P=0.05). Results were consistent with binary and ordinal analysis of mitral insufficiency. CONCLUSION: The presence of mitral insufficiency in patients with left ventricular dysfunction is independently associated with adverse outcomes, including death and hospitalization for heart failure. This has potentially important clinical implications for the assessment and management of patients with heart failure.     

Effectiveness of preload reserve as a determinant of clinical status in patients with left ventricular systolic dysfunction. The SOLVD Investigators.

The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined training in patients with systolic left ventricular dysfunction

The objective of the work was to evaluate the effect of eight-week combined training on the performance, aerobic capacity and basic haemodynamic parameters in patients with systolic dysfunction of the left ventricle and to assess its safety. The investigation comprised 26 patients, men mean age (x +/- SD) 61.8 +/- 11.1 years with coronarographically verified chronic ischaemic heart disease and with a left ventricular ejection fraction lower than 40% (EF 35 +/- 4%). Before the beginning and after completion of the rehabilitation programme (eight weeks) a spiroergometric examination was made, up to the symptom-limited maximum. Fitness elements were included after 2 weeks of aerobic training. The lesson lasted 60 mins. and included warming up (10 mins.), aerobic load on an ergometer with an intensity of the load at the level of the anaerobic threshold (20 mins.), the stage of fitness training on a combined training machine (20 mins) and the relaxation stage (10 mins). In the fitness stage the patients started to exercise at the 30% level, after two weeks at the 60% level 1-RM (one repetition maximum) The results showed after eight-week combined training a significant (p < 0.05) increase of the maximum achieved performance (from 104 +/- 27 to 132 +/- 32 W) in patients with systolic left ventricular dysfunction. There was a significant increase in the capacity of the transport system expressed by the value of the maximum oxygen uptake (from 1545 +/- 312 to 1740 +/- 359 ml.min-1) and MET (from 5.3 +/- 1.3 to 6.0 +/- 1.4). There was a significant decrease of the blood pressure at rest, systolic and diastolic, and of the baseline value of the heart rate at rest and of the "product rate, pressure"--RPP. Changes in the EF were not significant.     

Cardiac rehabilitation and survival in patients with left ventricular systolic dysfunction.

BACKGROUND: Exercise training, the major component of cardiac rehabilitation (CR), has been shown in previous trials to improve many pathophysiologic changes found in patients with left ventricular systolic dysfunction. It remains unproven whether exercise training improves survival. METHODS: By using the Duke Databank for Cardiovascular Disease, we identified patients with an ejection fraction < or = 40% and no recent myocardial infarction, congenital heart disease, or primary valvular disease who survived > or = 30 days after a cardiac catheterization (n = 1902). Participation in CR (n = 70) was identified through computer billing records. We developed a multivariable Cox proportional hazards regression model to estimate survival by using variables known to be independent predictors of survival in patients with systolic dysfunction. RESULTS: Patients participating in CR were less likely to be female or black and more likely to have a history consistent with ischemic cardiomyopathy. Participation in CR was associated with significantly improved survival after adjustment for baseline characteristics (hazard ratio, 0.39; 95% confidence interval, 0.15 to 0.62, P < .0001). Survival increased when patients participated in > 6 CR sessions (hazard ratio, 0.10; 95% confidence interval, 0.03 to 0.39; P < .0001). CONCLUSIONS: Participation in CR was associated with improved survival for patients with cardiomyopathy. There appears to be a dose response with improved survival benefit for patients with left ventricular systolic dysfunction participating in cardiac rehabilitation.     

Relationship of current and past smoking to mortality and morbidity in patients with left ventricular dysfunction

OBJECTIVES: The aim of this study was to evaluate the impact of smoking in patients with left ventricular dysfunction. BACKGROUND: The impact of smoking in patients with left ventricular dysfunction has not been well-studied. METHODS: We compared the incidence of death, hospitalization due to heart failure and myocardial infarction (MI) in current smokers to ex-smokers of < or =2 years and ex-smokers of >2 years duration to never-smokers among participants of the Study Of Left Ventricular Dysfunction (SOLVD) Prevention and Intervention trials. Participants all had left ventricular ejection fraction (LVEF) <35% and follow-up was over a mean of 41 months. RESULTS: Complete smoking status and outcome data were available in 6,704 subjects. There were 1,562 current smokers, 1,317 ex-smokers of < or =2 years, 2,354 ex-smokers of >2 years and 1,471 never-smokers. After adjusting for baseline differences of age, LVEF, race and etiology of heart failure, current smoking was associated with a significantly increased all-cause mortality (relative risk [RR]: 1.41, 95% confidence interval [CI]: 1.25 to 1.58, p < 0.001) compared with ex-smokers and never-smokers. The incidence of death or recurrent congestive heart failure requiring hospitalization or MI was significantly greater (RR: 1.39, 95% CI: 1.26 to 1.52, p < 0.001) in current smokers compared with ex-smokers and never-smokers. There were no significant differences in the number of deaths or hospitalizations due to heart failure between ex-smokers and never-smokers. This effect was consistent across both the SOLVD Prevention and Treatment trials. CONCLUSIONS: Current smoking is a powerful independent predictor of morbidity (recurrent heart failure and MI) and mortality in patients with left ventricular dysfunction. Quitting smoking appears to have a substantial and early effect (within two years) on decreasing morbidity and mortality in patients with left ventricular dysfunction, which is at least as large as proven drug treatments recommended in patients with left ventricular dysfunction.     

Epicardial fat volume in patients with left ventricular systolic dysfunction

Epicardial adipose tissue has been linked to cardiovascular metabolism and inflammation and has been shown to predict prevalence and progression of coronary artery disease. Only limited data are available on the role of epicardial fat in patients with heart failure (HF). We analyzed cardiac adiposity and its relation to markers of morbidity and clinical outcome in patients with normal and impaired left ventricular (LV) function. Epicardial fat volume (EFV) and coronary artery calcium were measured in 381 patients (210 women and 171 men, mean age 55 ± 10 years) who underwent low-dose computed tomography. HF was defined by LV ejection fraction (EF) <55%. Three hundred twenty-one patients had an EF >55% (mean 63 ± 6) and 60 patients had an EF <55% (mean 41 ± 12). Subgroup analysis was performed according to degree of LV dysfunction in patients with HF (LVEF 35% to 55% or <35%). Mean EFVs were 114.5 ± 98.5 cm(3) in patients with normal EF and 83.5 ± 67.1 cm(3) in those with decreased EF (p <0.05). Mean EFVs were 96.1 ± 73.9 cm(3) in patients with moderate HF and 52.2 ± 29.7 cm(3) in patients with severe HF (p <0.05). Subgroup analysis revealed a persistently smaller EFV in patients with HF regardless of coronary artery calcium scores, markers of renal function, lipid metabolism, fasting blood glucose, or body mass index. In conclusion, our data demonstrate a stepwise decrease in EFV in patients with impaired cardiac function.