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Biomedical subjects

Barry M Massie

Publications and source records attributed to Barry M Massie.

At least 19 recordsLinked to original sources

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Heart Failure Validation Study: diagnosis and prognosis.

BACKGROUND: ALLHAT, a randomized, double-blind, active-controlled hypertension treatment trial in 42,418 patients, reported that a thiazide-type diuretic (chlorthalidone) was superior to a calcium channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha1-blocker (doxazosin) in preventing the new onset of heart failure (HF). However, questions have been raised regarding the validity of the HF diagnosis. METHODS: The ALLHAT HF Validation Study was designed to validate and elucidate the significance of HF events in ALLHAT. Records for 2778 HF hospitalizations in 1935 patients were centrally reviewed using several prespecified algorithms (based on ALLHAT and Framingham criteria) and reviewers' global clinical judgment. Percent agreement with diagnoses assigned by ALLHAT site physicians, relative risks across randomized comparisons, incidence rates, and mortality after HF hospitalization were evaluated for first events validated by each of the criteria sets. RESULTS: Percent agreements with site physician diagnoses were 71%, 80%, and 84% for ALLHAT, Framingham, and reviewers' judgment, respectively. Using these 3 criteria, relative risks (95% CI) for new-onset HF compared with chlorthalidone were, respectively, 1.46 (1.27-1.68), 1.42 (1.25-1.62), and 1.45 (1.28-1.64) for amlodipine; 1.18 (1.02-1.28), 1.13 (0.99-1.30), and 1.15 (1.01-1.32) for lisinopril; and 1.79 (1.51-2.11), 1.71 (1.46-2.00), and 1.80 (1.55-2.10) for doxazosin. CONCLUSIONS: An independent review of source documentation showed a high degree of agreement with the HF diagnoses assigned by site physicians and confirmed the higher risk of HF associated with first-step therapy using amlodipine, lisinopril, or doxazosin compared with chlorthalidone. Thiazide-type diuretics should be the preferred first-step therapy for prevention of HF in high-risk patients with hypertension.

Adrenergic alpha-Antagonists↗

The utility of gestures in patients with chest discomfort.

PURPOSE: Patient gestures are thought to be useful in determining the etiology of chest discomfort. We sought to determine the utility of certain patient gestures in the diagnosis of ischemic chest discomfort or myocardial infarction. METHODS: We performed a prospective observational study of 202 patients admitted with chest discomfort. Patients were observed for the Levine Sign (clenched fist to the chest), the Palm Sign (palm of the hand to the chest), the Arm Sign (touching the left arm), and, as an indicator of nonischemic chest discomfort, the Pointing Sign (pointing with 1 finger). RESULTS: Prevalences of the Levine, Palm, Arm, and Pointing Signs were 11%, 35%, 16%, and 4%, respectively. Using troponin levels and results of functional studies and coronary angiograms as reference standards, none of the sensitivities of the signs exceeded 38%. Specificities of the Levine and Arm Signs ranged between 78% and 86%, but the positive predictive values did not exceed 55%. The Pointing Sign had a specificity of 98% for evidence of nonischemic chest discomfort, and the positive predictive value of a negative troponin was 88%. The diameter of discomfort significantly correlated with certain gestures. Larger chest pain diameters were associated with evidence of myocardial ischemia. CONCLUSIONS: Although certain gestures are exhibited by patients presenting with chest discomfort, they generally have poor test characteristics. The Pointing Sign has a high specificity for nonischemic chest discomfort, but a low prevalence. The gestures may communicate the size of the chest discomfort, with larger areas suggestive of ischemia.

Biomarkers↗

Predictors of clinical outcomes in patients given carvedilol for heart failure.

Risk factors for outcomes in heart failure (HF) were derived from populations in clinical trials, at hospital discharge, or in localized geographic or socioeconomic strata before the widespread use of beta blockers. This study observed 4,280 patients in a community-based HF registry for 1 year after completing carvedilol titration. Independent risk factors for death, hospitalization for HF, or hospitalization for cardiovascular reasons other than HF were first identified by age-, gender-, and race-adjusted analyses, then by multivariate analysis adjusted simultaneously for all factors. Over this period, 7% of patients died, 11% were hospitalized for HF, 12% were hospitalized for other cardiovascular reasons, and 27% had > or =1 of these events. The most significant outcome predictors were New York Heart Association class III or IV, history of hospitalization for HF or other cardiovascular reasons, and angina pectoris, all associated with increased odds of having an adverse outcome (all p < or =0.001). The left ventricular ejection fraction was not a significant outcome predictor by multivariate analysis. The odds ratio for an adverse outcome was significantly reduced for patients with hypertensive or idiopathic causes of HF and for those whose physicians had graduated from medical school > or =24 years earlier compared with <14 years earlier (all p <0.005). In conclusion, easily obtained historical information predicts clinical outcomes in patients with HF in the year after initiating carvedilol. In this unselected community population, these historical factors were better predictors of risk than the left ventricular ejection fraction.

Adrenergic beta-Antagonists↗

Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study.

BACKGROUND: Previous studies have associated reduced hemoglobin levels with increased adverse events in heart failure. It is unclear, however, whether this relation is explained by underlying kidney disease, treatment differences, or associated comorbidity. METHODS AND RESULTS: We examined the associations between hemoglobin level, kidney function, and risks of death and hospitalization in persons with chronic heart failure between 1996 and 2002 within a large, integrated, healthcare delivery system in northern California. Longitudinal outpatient hemoglobin and creatinine levels and clinical and treatment characteristics were obtained from health plan records. Glomerular filtration rate (GFR; mL.min(-1).1.73 m(-2)) was estimated from the Modification of Diet in Renal Disease equation. Mortality data were obtained from state death files; heart failure admissions were identified by primary discharge diagnoses. Among 59,772 adults with heart failure, the mean age was 72 years and 46% were women. Compared with that for hemoglobin levels of 13.0 to 13.9 g/dL, the multivariable-adjusted risk of death increased with lower hemoglobin levels: an adjusted hazard ratio (HR) of 1.16 and 95% confidence interval (CI) of 1.11 to 1.21 for hemoglobin levels of 12.0 to 12.9 g/dL; HR, 1.50 and 95% CI, 1.44 to 1.57 for 11.0 to 11.9 g/dL; HR, 1.89 and 95% CI, 1.80 to 1.98 for 10.0 to 10.9; HR, 2.31 and 95% CI, 2.18 to 2.45 for 9.0 to 9.9; and HR, 3.48 and 95% CI, 3.25 to 3.73 for <9.0 g/dL. Hemoglobin levels > or = 17.0 g/dL were associated with an increased risk of death (adjusted HR, 1.42; 95% CI, 1.24 to 1.63). Compared with those with a GFR > or = 60 mL . min(-1).1.73 m(-2), persons with a GFR <45 mL.min(-1).1.73 m(-2) had an increased mortality risk: adjusted HR, 1.39 and 95% CI, 1.34 to 1.44 for 30 to 44; HR, 2.28 and 95% CI, 2.19 to 2.39 for 15 to 29; HR, 3.26 and 95% CI, 3.05 to 3.49 for <15; and HR, 2.44 and 95% CI, 2.28 to 2.61 for those on dialysis. Relations were similar for the risk of hospitalization. The findings did not differ among patients with preserved or reduced systolic function, and hemoglobin level was an independent predictor of outcomes at all levels of kidney function. CONCLUSIONS: Very high (> or = 17 g/dL) or reduced (<13 g/dL) hemoglobin levels and chronic kidney disease independently predict substantially increased risks of death and hospitalization in heart failure, regardless of the level of systolic function. Randomized trials are needed to evaluate whether raising hemoglobin levels can improve outcomes in chronic heart failure.

Adult↗

Utility of impedance cardiography for the identification of short-term risk of clinical decompensation in stable patients with chronic heart failure.

OBJECTIVES: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation.

Adult↗

Evidence-based use of levosimendan in different clinical settings.

Levosimendan is a new calcium sensitizer and K-ATP channel opener. Compared with other inodilators, it improves myocardial contractility without increasing oxygen requirements and induces peripheral and coronary vasodilation with a potential anti-stunning, anti-ischaemic effect. The documentation regarding levosimendan is one of the largest ever on the safety and efficacy of a new pharmacological agent in acute heart failure syndromes. Recent experiences in small-scale studies and randomized clinical trials have led to greater interest in the use of this drug for the support of impaired cardiac function also in patients with ischaemic heart disease and cardiogenic or septic shock. It is also demonstrated that this drug could be used as bridge therapy for the peri-operative phase of cardiac surgery in both adult and paediatric populations. This review summarizes the evidence from published scientific literature regarding the use of levosimendan in various clinical settings.

Administration, Oral↗

Aspirin use in chronic heart failure: what should we recommend to the practitioner?

There has been ongoing controversy as to whether aspirin should be used in patients with chronic heart failure (CHF). The argument for aspirin is that many patients have underlying coronary disease, and aspirin prevents reinfarction and other vascular events. Arguments against the routine use of aspirin are that many CHF patients do not have underlying coronary disease, and that the benefit of aspirin lessens after the first 6 to 12 months after infarction. Also, several analyses suggest that aspirin may actually worsen outcomes in CHF patients, possibly because it inhibits prostaglandins, with resulting adverse hemodynamic and renal effects. Two recent prospective randomized studies have found that aspirin is associated with more frequent hospitalizations for worsening heart failure, although it did not have an adverse effect on vascular events. These results suggest that aspirin should not be routinely used in CHF patients and be avoided in those with refractory CHF, but that it may be beneficial in patients with recent infarction or multiple vascular risk factors.

Aspirin↗

Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study.

BACKGROUND: Endothelin receptor antagonism produces favorable short-term hemodynamic effects in heart failure, but the clinical effects of longer term therapy have not been evaluated. METHODS AND RESULTS: Three hundred and seventy patients with symptoms of heart failure at rest or on minimal exertion and a left ventricular ejection fraction <35% were randomly assigned (double-blind) to placebo (n = 126) or the endothelin receptor antagonist bosentan, titrated slowly (n = 121) or rapidly (n = 123) to a target dose of 500 mg twice daily. Treatment with the study drug was to be maintained for 26 weeks, whereas background medications for heart failure were kept constant. Safety concerns led to early termination of the trial when only 174 patients had had an opportunity to complete 26 weeks of therapy. Bosentan exerted no apparent benefit when all randomized patients were analyzed (P = .709). However, in the first 174 patients who were recruited at least 26 weeks before study termination and who could therefore be followed for the planned duration of the trial, patients in the bosentan groups were more likely to be improved (26% versus 19%) and were less likely to be worse (28% versus 43%), P = .045. When compared with placebo-treated patients, bosentan-treated patients had a increased risk of heart failure during the first month of treatment but a decreased risk of heart failure during the fourth, fifth, and sixth months of therapy. The major noncardiac adverse effects of bosentan included an increase in hepatic transaminases (in 15.6% of patients) and a decrease in hemoglobin (of about 1 g/L). CONCLUSION: Although bosentan exerted no favorable effects in the overall study, our findings suggest that the clinical responses to endothelin antagonism with bosentan in patients with severe chronic heart failure may be dependent on the duration of treatment.

Aged↗

Silent cerebral infarction in heart failure: vascular or thromboembolic?

Silent cerebral infarction in heart failure as reported by Siachos et al is significantly higher than reports of symptomatic cerebral infarction. Are we underestimating the occurrence of silent cerebral infarction, or can this finding be accounted for by concomitant conditions?

Fibrinolytic Agents↗

The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design.

BACKGROUND: Although 40% to 50% of patients with chronic heart failure (HF) have relatively preserved systolic function (PSF), few trials have been conducted in this population and treatment guidelines do not include evidence-based recommendations. METHODS AND RESULTS: The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) is enrolling 4100 subjects with HF-PSF to evaluate whether 300 mg irbesartan is superior to placebo in reducing mortality and prespecified categories of cardiovascular hospitalizations. The principal inclusion criteria are age > or =60 years, heart failure symptoms, an ejection fraction > or =45%, and either hospitalization for heart failure within 6 months or corroborative evidence of heart failure or the substrate for diastolic heart failure. Additional secondary end points include cardiovascular mortality, cause-specific mortality and morbidity, change in New York Heart Association functional class, quality of life, and N-terminal pro-BNP measurements. Follow-up will continue until 1440 patients experience a primary end point. Substudies will evaluate changes in echocardiographic measurements and serum collagen markers. CONCLUSION: I-PRESERVE is the largest trial in this understudied area and will provide crucial information on the characteristics and course of the syndrome, as well as the efficacy of the angiotensin receptor blocker irbesartan.

Angiotensin II Type 1 Receptor Blockers↗

Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure.

OBJECTIVES: The goal of this study was to determine the prevalence of worsening renal function (WRF) among hospitalized heart failure (HF) patients, clinical predictors of WRF, and hospital outcomes associated with WRF. BACKGROUND: Impaired renal function is associated with poor outcomes among chronic HF patients. METHODS: Chart reviews were performed on 1,004 consecutive patients admitted for a primary diagnosis of HF from 11 geographically diverse hospitals. Cox regression model analysis was used to identify independent predictors for WRF, defined as a rise in serum creatinine of >0.3 mg/dl (26.5 micromol/l). Bivariate analysis was used to determine associations of development of WRF with outcomes (in-hospital death, in-hospital complications, and length of stay). RESULTS: Among 1,004 HF patients studied, WRF developed in 27%. In the majority of cases, WRF occurred within three days of admission. History of HF or diabetes mellitus, admission creatinine > or =1.5 mg/dl (132.6 micromol/l), and systolic blood pressure >160 mm Hg were independently associated with higher risk of WRF. A point score based on these characteristics and their relative risk ratios predicted those at risk for WRF. Hospital deaths (adjusted risk ratio [ARR] 7.5; 95% confidence intervals [CI] 2.9, 19.3), complications (ARR 2.1; CI 1.5, 3.0), and length of hospitalizations >10 days (ARR 3.2, CI 2.2, 4.9) were greater among patients with WRF. CONCLUSIONS: Worsening renal function occurs frequently among hospitalized HF patients and is associated with significantly worse outcomes. Clinical characteristics available at hospital admission can be used to identify patients at increased risk for developing WRF.

Aged↗