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L E Rohde

Publications and source records attributed to L E Rohde.

At least 19 recordsLinked to original sources

The role of adrenergic receptor polymorphisms in heart failure.

The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of beta-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.

Cardiac Output, Low↗

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis.

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (< 100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (> 280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Adolescent↗

Right heart catheterization and cardiac complications in patients undergoing noncardiac surgery: an observational study.

CONTEXT: Right heart catheterization (RHC) is commonly performed before high-risk noncardiac surgery, but the benefit of this strategy remains unproven. OBJECTIVE: To evaluate the relationship between use of perioperative RHC and postoperative cardiac complication rates in patients undergoing major noncardiac surgery. DESIGN: Prospective, observational cohort study. SETTING: Tertiary care teaching hospital in the United States. PATIENTS: Patients (n = 4059 aged >/=50 years) who underwent major elective noncardiac procedures with an expected length of stay of 2 or more days between July 18, 1989, and February 28, 1994. Two hundred twenty one patients had RHC and 3838 did not. MAIN OUTCOME MEASURE: Combined end point of major postoperative cardiac events, including myocardial infarction, unstable angina, cardiogenic pulmonary edema, ventricular fibrillation, documented ventricular tachycardia or primary cardiac arrest, and sustained complete heart block, classified by a reviewer blinded to preoperative data. RESULTS: Major cardiac events occurred in 171 patients (4.2%). Patients who underwent perioperative RHC had a 3-fold increase in incidence of major postoperative cardiac events (34 [15.4%] vs 137 [3.6%]; P<.001). In multivariate analyses, the adjusted odds ratios (ORs) for postoperative major cardiac and noncardiac events in patients undergoing RHC were 2.0 (95% confidence interval [CI], 1.3-3.2) and 2.1 (95% CI, 1.2-3.5), respectively. In a case-control analysis of a subset of 215 matched pairs of patients who did and did not undergo RHC, adjusted for propensity of RHC and type of procedure, patients who underwent perioperative RHC also had increased risk of postoperative congestive heart failure (OR, 2.9; 95% CI, 1.4-6.2) and major noncardiac events (OR, 2.2; 95% CI, 1.4-4.9). CONCLUSIONS: No evidence was found of reduction in complication rates associated with use of perioperative RHC in this population. Because of the morbidity and the high costs associated with RHC, the impact of this intervention in perioperative care should be evaluated in randomized trials.

Aged↗

Impact of age on perioperative complications and length of stay in patients undergoing noncardiac surgery.

BACKGROUND: Major surgical procedures are performed with increasing frequency in elderly persons, but the impact of age on resource use and outcomes is uncertain. OBJECTIVE: To evaluate the influence of age on perioperative cardiac and noncardiac complications and length of stay in patients undergoing noncardiac surgery. DESIGN: Prospective cohort study. SETTING: Urban academic medical center. PATIENTS: Consecutive sample of 4315 patients 50 years of age or older who underwent nonemergent major noncardiac procedures. MEASUREMENTS: Major perioperative complications (cardiac and noncardiac), in-hospital mortality, and length of stay. RESULTS: Major perioperative complications occurred in 4.3% (44 of 1015) of patients 59 years of age or younger, 5.7% (93 of 1646) of patients 60 to 69 years of age, 9.6% (129 of 1341) of patients 70 to 79 years of age, and 12.5% (39 of 313) of patients 80 years of age or older (P < 0.001). In-hospital mortality was significantly higher in patients 80 years of age or older than in those younger than 80 years of age (0.7% vs. 2.6%, respectively). Multivariate analyses indicated an increased odds ratio for perioperative complications or in-hospital mortality in patients 70 to 79 years of age (1.8 [95% CI, 1.2 to 2.7]) and those 80 years of age or older (OR, 2.1 [CI, 1.2 to 3.6]) compared with patients 50 to 59 years of age. Patients 80 years of age or older stayed an average of 1 day more in the hospital, after adjustment for other clinical data (P = 0.001). CONCLUSIONS: Elderly patients had a higher rate of major perioperative complications and mortality after noncardiac surgery and a longer length of stay, but even in patients 80 years of age or older, mortality was low.

Age Factors↗

Usefulness of transthoracic echocardiography as a tool for risk stratification of patients undergoing major noncardiac surgery.

Transthoracic echocardiography (TTE) is frequently ordered before noncardiac surgery, although its ability to predict perioperative cardiac complications is uncertain. To evaluate the incremental information provided by TTE after consideration of clinical data for prediction of cardiac complications after noncardiac surgery, 570 patients who underwent TTE before major noncardiac surgery at a university hospital were studied. Preoperative clinical data and clinical outcomes were collected prospectively according to a structured protocol. TTE data included left ventricular (LV) function, hypertrophy indexes, and Doppler-derived measurements. In univariate analyses, preoperative systolic dysfunction was associated with postoperative myocardial infarction (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.1 to 7.0), cardiogenic pulmonary edema (OR 3.2, 95% CI 1.4 to 7.0), and major cardiac complications (OR 2.4, 95% Cl 1.3 to 4.5). Moderate to severe LV hypertrophy, moderate to severe mitral regurgitation, and increased aortic valve gradient were also associated with major cardiac events (OR 2.3, 95% CI 1.2 to 4.6; OR 2.2, 95% CI 1.1 to 4.3; OR 2.1, 95% CI 1.0 to 4.5, respectively). In logistic regression analysis, models with echocardiographic variables predicted major cardiac complications significantly better than those that included only clinical variables (c statistic 0.73 vs 0.68; p <0.05). Echocardiographic data added significant information for patients at increased risk for cardiac complications by clinical criteria, but not in otherwise low-risk patients. In conclusion, preoperative TTE before noncardiac surgery can provide independent information about the risk of postoperative cardiac complications in selected patients.

Aged↗

Three-dimensional return map: a new tool for quantification of heart rate variability.

BACKGROUND: Several methods are used to study heart rate variability, but they have limitations, which might be overcome by the use of a three-dimensional return map. OBJECTIVES: To evaluate the performance of three-dimensional return map-derived indices to detect (1) sympathetic and parasympathetic modulation to the sinus node and (2) autonomic dysfunction in diabetic patients. METHODS: Six healthy subjects underwent partial and total pharmacological autonomic blockade in a protocol that incorporated vagal and sympathetic predominance. Twenty-two patients with type 2 diabetes mellitus and 12 normal controls participated in the subsequent validation experiment. Three-dimensional return maps were constructed by plotting RRn intervals versus the difference between adjacent RR intervals [(RRn+1)-(RRn)] versus the number of counts, and four derived indices (P1, P2, P3, MN) were created for quantification. RESULTS: Both indices P1 and MN were significantly increased after sympathetic blockade with propranolol, while all indices except P1 were modified after parasympathetic blockade (P < 0.05). During the validation experiments, P1 and MN detected differences between normal controls, and diabetic patients with and without autonomic neuropathy. The overall accuracy of most three-dimensional indices to detect autonomic dysfunction, estimated by the area under the ROC curve, was significantly better than traditional time domain indices. Three-dimensional return map-derived indices also showed adequate reproducibility on two different recording days (intra-class correlation coefficients of 0.69 to 0.82; P < 0.001). CONCLUSIONS: Three-dimensional return map-derived indices are reproducible, quantify parasympathetic as well as sympathetic modulation to the sinus node, and are capable of detecting autonomic dysfunction in diabetic patients.

1-Propanol↗

Ten-year trends in hospital care for congestive heart failure: improved outcomes and increased use of resources.

BACKGROUND: Scarce data are available on long-term trends in hospital mortality, length of stay (LOS), and costs in congestive heart failure (CHF). OBJECTIVE: To assess 10-year trends in the outcomes of patients hospitalized with CHF. METHODS: We studied all 6676 patients with a primary discharge diagnosis of CHF hospitalized from January 1, 1986, through July 31, 1996, at an academic tertiary care center. Hospital mortality, LOS, and costs were adjusted for sociodemographic characteristics, comorbidities, invasive procedures, hospital disposition, and LOS where appropriate. RESULTS: The mean (+/- SD) age of patients was 70+/-13 years; 54.1% were male; 87.0% were white. There was a significant increasing trend in heart failure severity as assessed by a CHF-specific risk-adjustment index. The proportion of patients who underwent invasive procedures (e.g., cardiac catheterization, coronary angioplasty, coronary artery bypass surgery, defibrillator and pacemaker implantation) was significantly higher in the 1994-1996 period. The standardized mortality ratio (observed mortality/predicted mortality) progressively fell during the study period. Compared with patients admitted before 1991, those admitted after 1991 had a 24% lower observed than predicted mortality. Adjusted LOS exhibited a downward trend, ie, 7.7 days in 1986-1987 to 5.6 days in 1994-1996 (P<.001). Unadjusted cost peaked during 1992-1993 and declined thereafter. Adjusted costs in 1994-1996 were not significantly different from those in 1990-1991. CONCLUSIONS: After risk adjustment for sociodemographic characteristics, comorbidities, and disease severity, a significant decrease in in-hospital mortality was observed during the study decade. This decline in hospital mortality occurred in parallel with decreasing LOS and increasing use of cardiac procedures and costs.

Aged↗

Circulating endothelin-1 and tumor necrosis factor-alpha: early predictors of mortality in patients with septic shock.

OBJECTIVES: To determine the predictive value of early determination of tumor necrosis factor (TNF)-alpha, TNF-alpha 1 and 2 soluble receptors (sTNFR1 and sTNFR2) and endothelin-1 (ET-1) for mortality in patients with septic shock. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-one patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients with septic shock had a pulmonary artery catheter inserted and blood samples drawn at time zero, 6, 12 and 24 h, simultaneously with hemodynamic assessments. Plasma levels of all markers were measured by ELISA. All patients were followed up to hospital discharge or death. Age and APACHE II scores were significantly higher in nonsurvivors (n = 11) than in survivors (n = 10). Hemodynamic assessments did not aid in the discrimination between the two groups of patients (P > 0.05). Levels of TNF-alpha were higher in nonsurvivors than in survivors at all time-points. sTNFR1 and sTNFR2 were also significantly elevated in nonsurvivors, but not in all measurements. Endothelin-1, however, was significantly higher in nonsurvivors than in survivors only at 6 h (P = 0.02). When both TNF-alpha and ET-1 were increased at early time-points, the best predictive values for mortality were obtained [positive and negative predictive values of 72 and 100% at 6 h, odds ratio 3.0, 95% CI (1.2-7.6)]. CONCLUSIONS: Increased levels of TNF-alpha were consistently higher at all time-points in nonsurvivors with septic shock. ET-1 levels, however, appeared also to be an early and sensitive predictor of mortality. Very early determination of TNF-alpha and ET-1 in septic shock may help to identify patients at higher risk for adverse outcome.

APACHE↗

Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction.

Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial infarction (MI). We tested the hypothesis that mice with targeted deletion of MMP9 have less left ventricular (LV) dilation after experimental MI than do sibling wild-type (WT) mice. Animals that survived ligation of the left coronary artery underwent echocardiographic studies after MI; all analyses were performed without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had significantly smaller increases in end-diastolic and end-systolic ventricular dimensions at both midpapillary and apical levels, compared with infarcted WT mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less collagen accumulation in the infarcted area than did WT mice, and they showed enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV dilation after experimental MI in mice. The decrease in collagen accumulation and the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role in extracellular matrix remodeling after MI.

Animals↗

Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men.

Several prospective studies have demonstrated a direct association between C-reactive protein (CRP) levels and the risks of developing cardiovascular disease. Few studies, however, have explored the interrelations between CRP levels and other risk factors for cardiovascular disease. We evaluated the relation of CRP with several cardiovascular risk factors in a cross-sectional survey of 1,172 apparently healthy men. There were significant positive associations between CRP levels and age, number of cigarettes smoked per day, body mass index, systolic and diastolic blood pressure, total cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, tissue-type plasminogen activator antigen, D-dimers, total homocysteine, and fibrinogen (all p values <0.05). Significant inverse associations were observed for exercise frequency, high-density lipoprotein cholesterol, and apolipoprotein A-I and A-II (all p values <0.02). In multivariate analysis, age, smoking status, and serum levels of tissue-type plasminogen activator antigen, fibrinogen, lipoprotein(a), and total homocysteine were independent correlates of CRP levels. Finally, in an analysis controlled either for all the independent correlates or for several usual risk factors, we observed progressive increases in levels of CRP with increasing prevalence of risk factors (p for trend <0.001 for independent correlates and <0.01 for usual risk factors). In conclusion, in a large cohort of apparently healthy men, CRP levels were associated with several cardiovascular risk factors. These data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease.

Adult↗

Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice.

BACKGROUND: Extracellular matrix synthesis and degradation contribute to the morphological changes that occur after myocardial infarction (MI). METHODS AND RESULTS: We tested the hypothesis that inhibition of matrix metalloproteinases (MMPs) attenuates left ventricular remodeling in experimental MI. Seventy-one male FVB mice that survived ligation of the left anterior coronary artery were randomized to a broad-spectrum MMP inhibitor (CP-471,474) or placebo by gavage. Echocardiographic studies were performed before randomization (within 24 hours of surgery) and 4 days later and included short-axis imaging at the midpapillary and apical levels. Infarction as defined by wall motion abnormality was achieved in 79% of the procedures (n=56), and mortality rate during the 4-day protocol was 23% (9 of 36 on treatment vs 7 of 35 on placebo; P=NS). Baseline end-diastolic and end-systolic dimensions and areas were similar (P=NS) between treated and placebo groups. At follow-up, infarcted mice allocated to MMP inhibitor had significantly smaller increases in end-systolic and end-diastolic dimensions and areas at both midpapillary and apical levels compared with infarcted mice allocated to placebo (all P<0.05). In addition, infarcted animals that received MMP inhibitor had no change in fractional shortening (-3+/-13%), whereas animals that received placebo had a decrease in fractional shortening (-12+/-12%) (P<0.05). In an analysis stratified by baseline end-diastolic area, the effects of MMP inhibition on the changes in end-systolic area and end-diastolic area were most prominent in animals that had more initial left ventricular dilatation (both P<0.05). CONCLUSIONS: -Administration of an MMP inhibitor attenuates early left ventricular dilation after experimental MI in mice. Further studies in genetically altered mice and other models will improve understanding of the role of MMPs in left ventricular remodeling.

Animals↗

Echocardiography-derived left ventricular end-systolic regional wall stress and matrix remodeling after experimental myocardial infarction.

OBJECTIVES: We tested the hypothesis that regional end-systolic left ventricular (ESLV) wall stress is associated with extracellular matrix remodeling activity after myocardial infarction (MI). BACKGROUND: Increased left ventricular (LV) wall stress is a stimulus for LV enlargement, and echocardiography can be used to estimate regional wall stress. A powerful validation of a noninvasive method of estimating wall stress would be predicting cellular responses after a MI. METHODS: Echocardiographic images were obtained in rats 1, 7, 14 or 21 days after coronary ligation (n = 11) or sham surgery (n = 5). End-systolic left ventricular wall stress was calculated by finite element analysis in three regions (infarcted, noninfarcted and border) from short-axis images. Matrix metalloproteinase-9 (MMP-9) and macrophage density were determined by immunohistochemistry, and positive cells were counted in high power fields (hpf). RESULTS: Average ESLV wall stress was higher in rats with MI when compared to shams irrespective of time point (p < 0.01), and ESLV wall stress in the infarcted regions increased with time (25.1 +/- 5.9 vs. 69.9 +/- 4.4 kdyn/cm2, day 1 vs. 21; p < 0.01). Matrix metalloproteinase-9 expression was higher in infarcted and border regions when compared to noninfarcted regions (22.1 vs. 25.7 vs. 0.10 cells/hpf, respectively; p < 0.01). Over all regions, ESLV wall stress was associated with MMP-9 (r = 0.76; p < 0.001), macrophage density (r = 0.72; p < 0.001) and collagen content (r = 0.67; p < 0.001). End-systolic left ventricular wall stress was significantly higher when MMP-9 positive cell density was greater than 10 cells/hpf (45+/-20 vs. 14+/-10 kdyn/cm2; p < 0.001). CONCLUSIONS: Regional increases in ESLV wall stress determined by echocardiography-based structural analysis are associated with extracellular matrix degradation activity.

Animals↗

Cross-sectional study of soluble intercellular adhesion molecule-1 and cardiovascular risk factors in apparently healthy men.

An elevated plasma concentration of the soluble intercellular adhesion molecule-1 (sICAM-1) is associated with increased risk for future coronary events. However, data exploring the interrelations of sICAM-1 with known cardiovascular risk factors are sparse. We determined sICAM-1 levels in 948 middle-aged men with no prior history of cardiovascular disease. sICAM-1 levels increased with age (P<0.001) and were significantly associated with smoking (P<0.001), hypertension (P<0.05), and frequent alcohol consumption (P=0.006). Positive correlations were observed between sICAM-1 and triglycerides (r=0.15; P<0.001), fibrinogen (r=0.21; P<0.001), tissue-type plasminogen activator antigen (r=0.17; P<0.001), and total homocysteine (r=0.09; P=0.02); whereas a negative correlation was observed for high density lipoprotein cholesterol (r=-0.15; P<0. 001). Overall, plasma concentrations of sICAM-1 increased with increasing prevalence of usual cardiovascular risk factors; mean plasma concentrations were 231, 236, 245, 257, and 312 ng/mL for those subjects with 0, 1, 2, 3, and >4 risk factors, respectively (P<0.01 for trend). In multivariate analysis, age, smoking status, diabetes, systolic blood pressure, positive family history of coronary disease, and serum levels of total homocysteine and fibrinogen were all independently associated with sICAM-1 levels (all P</=0.05). sICAM-1 levels are associated with several established cardiovascular risk factors. Further studies will be needed to evaluate whether these associations reflect the role of sICAM-1 as a marker of preclinical atherosclerosis, and whether such interrelations might have a causal basis.

Age Factors↗

Plasma concentrations of interleukin-6 and abdominal aortic diameter among subjects without aortic dilatation.

Previous studies suggest that cytokine-induced tissue inflammation may participate in the pathogenesis of abdominal aortic aneurysms. Serum inflammatory markers may reflect arterial inflammation in asymptomatic phases of the aneurysmal disease. We studied 120 outpatients (62 men; age, 65+/-9 years) by ultrasound evaluation of the abdominal aorta to evaluate the association of circulating levels of interleukin-6 (IL-6) with abdominal aortic diameter in subjects with normal aortic size. Aortic diameter was measured at the infrarenal level and indexed for body surface area. Seven patients with abdominal aortic dilatation (indexed aortic diameter, >1.3 cm/m2) were also identified. Plasma concentrations of IL-6, serum amyloid A (SAA), C-reactive protein (CRP), total homocysteine, and lipids were measured. Among the 113 subjects without aortic dilatation, indexed aortic diameter was positively associated with serum levels of IL-6 (P<0.01), SAA (P<0.01), and total homocysteine (P=0.01). IL-6 levels increased in a stepwise fashion among dichotomized groups of aortic size (low and high aortic diameters) and peaked in patients with aortic dilatation (2.3+/-1.2 versus 2. 7+/-0.9 versus 3.2+/-0.9 pg/mL, respectively; P for trend=0.039). None of the serum lipid measurements correlated with abdominal aortic diameter. Although CRP levels were associated with SAA levels (r=0.60; P<0.001), associations between CRP and aortic diameter were nonsignificant. In multivariate analysis, levels of IL-6 (P=0.02), SAA (P=0.001), and total homocysteine (P<0.001) were independent correlates of indexed aortic diameter. In conclusion, circulating levels of IL-6, SAA, and total homocysteine may reflect processes involved in the early phases of abdominal aortic aneurysm formation, before dilation of the abdominal aorta is established. These data support a role for chronic inflammation in the progression of asymptomatic aortic disease.

Aged↗

Sympathetic nervous system representation in time and frequency domain indices of heart rate variability.

This study evaluated the contributions of sympathetic and parasympathetic modulation to heart rate variability during situations in which vagal and sympathetic tone predominated. In a placebo-controlled, randomized, double blind blockade study, six young healthy male individuals received propranolol (0.2 mg x kg(-1)), atropine (0.04 mg x kg(-1)), propranolol plus atropine, or placebo infusions over 4 days. Time-domain indices were calculated during 40 min of rest and 20 min of exercise at 70% of maximal exercise intensity. Spectrum analysis, using fast Fourier transformation, was also performed at rest and during the exercise. The time-domain indices standard deviation of R-R intervals, mean of the standard deviations of all R-R intervals for all 5-min segments, percentage of number of pairs of adjacent R-R intervals differing by more than 50 ms, and square root of the mean of the sum of squares of differences between adjacent R-R intervals were reduced after atropine and propranolol plus atropine. Propranolol alone caused no appreciable change in any of the time-domain indices. At rest, all spectrum components were similar after placebo and propranolol infusions, but following parasympathetic and double autonomic blockade there was a reduction in all components of the spectrum analysis, except for the low:high ratio. During exercise, partial and double blockade did not change significantly any of the spectrum components. Thus, time and frequency-domain indices of heart rate variability were able to detect vagal activity, but could not detect sympathetic activity. During exercise, spectrum analysis is not capable of evaluating autonomic modulation of heart rate.

Adult↗

Effect of partial arrhythmia suppression with amiodarone on heart rate variability of patients with congestive heart failure.

BACKGROUND: Some antiarrythmic agents that may increase mortality rates have been shown to reduce heart rate variability in patients with heart failure. Amiodarone is a potent antiarrhythmic agent that may reduce mortality rates in heart failure, but little is known about its effects on heart rate variability. METHODS AND RESULTS: The purpose of this study was to evaluate the effect of partial arrhythmia suppression by amiodarone on indexes of heart rate variability in patients with heart failure. Ten clinically stable patients in New York Heart Association class II-III received amiodarone during a 4-week period (600 mg every day for 14 days and 300 mg every day for 16 days), and 24-hour Holter recordings were performed before and after treatment. Heart rate variability indexes were calculated by a semiautomatic method that applies a 20% filter to the temporal series, excluding ectopy and compensatory pauses. After amiodarone administration, there was a significant reduction in pNN50 from 8% +/- 7% to 3% +/- 2% (p < 0.05) and there was a trend toward reduction in rMSSD (p = 0.06). Other time domain indexes did not change significantly. Spectral analysis demonstrated a significant reduction of low-frequency components (421 +/- 122 to 151 +/- 25 msec2; p < 0.05) and total power (1503 +/- 314 to 609 +/- 144 msec2, p < 0.05). Multivariate analysis showed that the observed reduction in pNN50 was strongly associated with the number and the reduction of ventricular premature contractions before and after amiodarone administration (r2 = 0.94; p < 0.01). CONCLUSIONS: These findings indicate that despite the use of software corrections for arrhythmia, short-term time domain indexes of heart rate variability may be affected by partial suppression of ectopy.

Amiodarone↗

A new casemix adjustment index for hospital mortality among patients with congestive heart failure.

OBJECTIVES: Comparative analysis of hospital outcomes requires reliable adjustment for casemix. Although congestive heart failure is one of the most common indications for hospitalization, congestive heart failure casemix adjustment has not been widely studied. The purposes of this study were (1) to describe and validate a new congestive heart failure-specific casemix adjustment index to predict in-hospital mortality and (2) to compare its performance to the Charlson comorbidity index. METHODS: Data from all 4,608 admissions to the Massachusetts General Hospital from January 1990 to July 1996 with a principal ICD-9-CM discharge diagnosis of congestive heart failure were evaluated. Massachusetts General Hospital patients were randomly divided in a derivation and a validation set. By logistic regression, odds ratios for in-hospital death were computed and weights were assigned to construct a new predictive index in the derivation set. The performance of the index was tested in an internal Massachusetts General Hospital validation set and in a non-Massachusetts General Hospital external validation set incorporating data from all 1995 New York state hospital discharges with a primary discharge diagnosis of congestive heart failure. RESULTS: Overall in-hospital mortality was 6.4%. Based on the new index, patients were assigned to six categories with incrementally increasing hospital mortality rates ranging from 0.5% to 31%. By logistic regression, "c" statistics of the congestive heart failure-specific index (0.83 and 0.78, derivation and validation set) were significantly superior to the Charlson index (0.66). Similar incrementally increasing hospital mortality rates were observed in the New York database with the congestive heart failure-specific index ("c" statistics 0.75). CONCLUSION: In an administrative database, this congestive heart failure-specific index may be a more adequate casemix adjustment tool to predict hospital mortality in patients hospitalized for congestive heart failure.

Aged↗