Search PubMed⌕ Search

Biomedical subjects

Scott D Solomon

Publications and source records attributed to Scott D Solomon.

At least 91 records · Page 5Linked to original sources
PubMed2004

Effect of candesartan on cause-specific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure. We assessed the effect of candesartan on cause-specific mortality in patients enrolled in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program. METHODS AND RESULTS: The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure: CHARM-Alternative (n=2028; LVEF<=40% [corrected] and ACE intolerant), CHARM-Added (n=2548; LVEF<=40%, [corrected] already on ACE inhibitors), and CHARM-Preserved (n=3023; LVEF >40%). Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months. All deaths were reviewed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation. The number and rate of deaths by cause were calculated for each of the component trials and the overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of progressive heart failure. Candesartan reduced both sudden death (HR 0.85 [0.73 to 0.99], P=0.036) and death from worsening heart failure (HR 0.78 [0.65 to 0.94], P=0.008). These reductions were most apparent in the patients with LVEF<=40% [corrected]. CONCLUSIONS: Candesartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure, although this reduction was most apparent in patients with systolic dysfunction.

Aged↗
PubMed2004

Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.

BACKGROUND: The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. METHODS: As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups. RESULTS: The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment. CONCLUSIONS: Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction.

Aged↗
PubMed2004

Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial.

BACKGROUND: A prior diagnosis of diabetes mellitus is associated with adverse outcomes after acute myocardial infarction (MI), but the risk associated with a new diagnosis of diabetes in this setting has not been well defined. METHODS AND RESULTS: We assessed the risk of death and major cardiovascular events associated with previously known and newly diagnosed diabetes by studying 14,703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Patients were grouped by diabetic status: previously known diabetes (insulin use or diagnosis of diabetes before MI, n=3400, 23%); newly diagnosed diabetes (use of diabetic therapy or diabetes diagnosed at randomization [median 4.9 d after infarction], but no known diabetes at presentation, n=580, 4%); or no diabetes (n=10,719). Patients with newly diagnosed diabetes were younger and had fewer comorbid conditions than did patients with previously known diabetes. At 1 year after enrollment, patients with previously known and newly diagnosed diabetes had similarly increased adjusted risks of mortality (hazard ratio [HR] 1.43; 95% confidence interval [CI], 1.29 to 1.59 and HR, 1.50; 95% CI, 1.21 to 1.85, respectively) and cardiovascular events (HR, 1.37; 95% CI, 1.27 to 1.48 and HR, 1.34; 95% CI, 1.14 to 1.56). CONCLUSIONS: Diabetes mellitus, whether newly diagnosed or previously known, is associated with poorer long-term outcomes after MI in high-risk patients. The poor prognosis of patients with newly diagnosed diabetes, despite having baseline characteristics similar to those of patients without diabetes, supports the idea that metabolic abnormalities contribute to their adverse outcomes.

Aged↗
PubMed2004

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

Animals↗
PubMed2004

Effect of antecedent systemic hypertension on subsequent left ventricular dilation after acute myocardial infarction (from the Survival and Ventricular Enlargement trial).

Whether antecedent systemic hypertension influences the risk of subsequent left ventricular (LV) dilation in patients after an acute myocardial infarction with LV systolic dysfunction is unclear. We assessed echocardiographic evidence of ventricular remodeling from baseline (mean +/- SD 11 +/- 3 days) to 2 years after an acute myocardial infarction in 122 hypertensive (defined as a history of treated hypertension, baseline systolic blood pressure > or =140 or baseline diastolic blood pressure > or =90 mm Hg) and 334 nonhypertensive patients in the Survival and Ventricular Enlargement echocardiographic substudy. Compared with nonhypertensives, baseline heart size, defined as the sum of the average short- and long-axis LV cavity areas, was similar (70.1 +/- 11.9 vs 68.8 +/- 11.2 cm(2), p = 0.33 at end-diastole; 50.1 +/- 11.3 vs 48.8 +/- 10.8 cm(2), p = 0.31 at end-systole), but short-axis LV myocardial area (24.7 +/- 4.3 vs 25.7 +/- 5.0 cm(2), p = 0.043) and wall thickness (1.15 +/- 0.16 vs 1.21 +/- 0.17 cm, p = 0.004) at end-diastole were greater among hypertensives. The myocardial infarct segment lengths were similar in the 2 groups (p = 0.22). Although LV cavity areas increased significantly in the 2 groups from baseline to 2 years (p < or =0.001), the increase was significantly greater in hypertensives than in nonhypertensives (+5.6 +/- 11.5 vs +2.2 +/- 10.7 cm(2), p = 0.005 at end-diastole; +6.23 +/- 12.75 vs +2.94 +/- 11.4 cm(2), p = 0.012 at end-systole). There was no concomitant difference in the change in LV myocardial area or LV wall thickness between the 2 groups (p >0.30). After adjusting for known confounders, antecedent hypertension was associated with a doubling of the risk of LV dilation (50.8% vs 37.7%, odds ratio 2.09, 95% confidence interval 1.27 to 3.45, p = 0.004). This association was not modified by diabetes mellitus, myocardial infarct segment length, or captopril use (all p values for interaction >0.10). We conclude that antecedent hypertension is associated with subsequent LV dilation in patients after acute myocardial infarction with LV systolic dysfunction.

Antihypertensive Agents↗
PubMed2004

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction.

OBJECTIVES: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BACKGROUND: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. METHODS: The Survival And Ventricular Enlargement (SAVE) trial randomized 2231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. RESULTS: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. CONCLUSIONS: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.

Alcohol Drinking↗
PubMed2004

Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism.

BACKGROUND: We investigated the prognostic role of right ventricular enlargement on multidetector-row chest CT in acute pulmonary embolism (PE). METHODS AND RESULTS: We studied 63 patients with CT-confirmed PE who underwent echocardiography within the ensuing 24 hours. Adverse clinical events, defined as 30-day mortality or the need for cardiopulmonary resuscitation, mechanical ventilation, pressors, rescue thrombolysis, or surgical embolectomy, were present in 24 patients. We performed off-line CT measurements of right and left ventricular dimensions (RV(D), LV(D)) with axial and 2-dimensional reconstructed 4-chamber (4-CH) views. The proportion of patients with RV(D)/LV(D)>0.9 on the axial view was similar in patients with (70.8%) and those without adverse events (71.8%; P=0.577). In contrast, RV(D)/LV(D)>0.9 on the 4-CH view was more common in patients with (80.3%) than without (51.3%; P=0.015) adverse events. The area under the curve of RV(D)/LV(D) from the axial and 4-CH views for predicting adverse events was 0.667 and 0.753, respectively. Sensitivity and specificity of RV(D)/LV(D)>0.9 for predicting adverse events were 37.5% and 92.3% on the axial view and 83.3% and 48.7% on the reconstructed 4-CH view, respectively. RV(D)/LV(D)>0.9 on the 4-CH view was an independent predictor for adverse events (OR, 4.02; 95% CI, 1.06 to 15.19; P=0.041) when adjusted for age, obesity, cancer, and recent surgery. CONCLUSIONS: Right ventricular enlargement on the reconstructed CT 4-CH views predicts adverse clinical events in patients with acute PE. Ventricular CT measurements obtained from 4-CH views are superior to those from axial views for identifying high-risk patients.

Acute Disease↗
PubMed2004

Angina pectoris prior to myocardial infarction protects against subsequent left ventricular remodeling.

OBJECTIVES: To investigate the hypothesis that prior angina pectoris confers protection from remodeling occurring after myocardial infarction (MI), we analyzed echocardiograms from the Healing and Early Afterload Reducing Therapy (HEART) trial. BACKGROUND: Ischemia occurring before MI has been shown to reduce infarct size in experimental models and to improve outcomes in patients. The extent to which ischemia occurring before MI influences subsequent changes in ventricular size and function is unclear. METHODS: We studied 283 patients enrolled in the HEART trial who had echocardiograms at days 1 and 90 after MI. Left ventricular (LV) dilation from days 1 to 90 was used as a measure of LV remodeling. We explored the relationship between symptomatic angina occurring before infarction and subsequent LV remodeling. RESULTS: In patients who reported angina (n = 111) during the three months preceding MI, LV volume change was -0.73 +/- 2.6 ml over the 90-day post-MI period, compared with 6.8 +/- 2.6 ml for patients (n = 172) without angina (p = 0.017). In contrast, there were no differences in changes in ejection fraction based on prior angina. Maximal creatine kinase was significantly lower in patients with prior angina (2,119 +/- 1,729 vs. 2,701 +/- 2,088, p = 0.016). In a multivariate model, prior angina remained protective for ventricular remodeling after adjusting for age, gender, baseline ejection fraction, Killip class, baseline end-diastolic volume, and drug treatment group (p = 0.042). However, the protective effect of pre-infarction angina appeared to be attenuated in diabetic patients. CONCLUSIONS: Ischemic symptoms occurring before MI may protect against LV remodeling. These protective effects may be secondary to recruitment of collaterals or ischemic preconditioning of the myocardium, and they appear to be attenuated in diabetic patients.

Aged↗
PubMed2003

Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. METHODS: Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. RESULTS: During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. CONCLUSIONS: Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.

Aged↗
PubMed2003

Value of the electrocardiogram in predicting left ventricular enlargement and dysfunction after myocardial infarction.

To identify electrocardiographic predictors of left ventricular enlargement or persistent dysfunction following a myocardial infarction. Baseline and predischarge 12-lead electrocardiograms (ECGs) from 272 patients with anterior myocardial infarction who were enrolled in the Healing and Early Afterload Reducing Therapy trial were evaluated and related to echocardiographic data obtained at baseline and day 90. ST-segment elevation, QRS score, and number of negative T waves were assessed at both time points. The majority of patients (87%; n = 237) received reperfusion therapy. Multivariate models were used to adjust for potential confounders, including maximal creatine kinase level and ejection fraction at baseline. None of the baseline electrocardiographic variables independently predicted ventricular enlargement or recovery of function. In contrast, the sum of ST- and maximum ST-segment elevation, and the number of leads with ST-segment elevation > or =1 mm in the predischarge ECG, were independent predictors of ventricular enlargement from baseline to day 90. Each lead with ST-segment elevation > or =1 mm was associated with 3.5 mL of ventricular enlargement (95% confidence interval [CI]: 1.6 to 5.5 mL; P <0.0001). Similarly, the sum of ST-segment elevation (odds ratio [OR] = 0.78; 95% CI: 0.69 to 0.89; P <0.0001), the maximum ST-segment elevation (OR = 0.25; 95% CI: 0.13 to 0.45; P <0.0001), and the number of leads with ST-segment elevation > or =1 mm (OR = 0.58; 95% CI: 0.45 to 0.74; P <0.0001) were independently associated with a lower likelihood of recovery of function at day 90. Predischarge ECG may be a useful tool for early identification of patients at risk of ventricular enlargement and persistent dysfunction following myocardial infarction.

Aged↗
PubMed2002

Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction.

BACKGROUND: We identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes and hypothesized that ST2 participates in the acute myocardial response to stress and injury. METHODS AND RESULTS: ST2 mRNA was induced in cardiac myocytes by mechanical strain (4.7+/-0.9-fold) and interleukin-1beta (2.0+/-0.2-fold). Promoter analysis revealed that the proximal and not the distal promoter of ST2 is responsible for transcriptional activation in cardiac myocytes by strain and interleukin-1beta. In mice subjected to coronary artery ligation, serum ST2 was transiently increased compared with unoperated controls (20.8+/-4.4 versus 0.8+/-0.8 ng/mL, P<0.05). Soluble ST2 levels were increased in the serum of human patients (N=69) 1 day after myocardial infarction and correlated positively with creatine kinase (r=0.41, P<0.001) and negatively with ejection fraction (P=0.02). CONCLUSIONS: These data identify ST2 release in response to myocardial infarction and suggest a role for this innate immune receptor in myocardial injury.

Angiotensin II↗
PubMed2002

Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction.

BACKGROUND: Diabetic patients are at increased risk for heart failure (HF) and other adverse events after myocardial infarction (MI). Left ventricular (LV) enlargement after MI is also associated with the same increased risk. We used data from the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy to test the hypothesis that diabetes was associated with increased LV enlargement after MI. METHODS AND RESULTS: Four hundred twelve nondiabetic and 100 diabetic patients underwent echocardiographic assessment at baseline and 3 months, 1 year, and 2 years after MI. HF developed in 30% of diabetic and 17% of nondiabetic patients during follow-up (P<0.001). Baseline LV diastolic size, ejection fraction, and infarct segment length were similar between diabetic and nondiabetic patients. Diabetic patients demonstrated less LV enlargement between baseline and 2 years than nondiabetic patients (0.9+/-11.1 cm2 versus 3.8+/-10.9 cm2, P=0.047). In patients who developed HF, LV diastolic dilatation (10.0+/-12.4 cm2 versus 3.7+/-13.1 cm2, P=0.06) and systolic dilatation (4.6+/-11.8 versus 0.91+/-12.1, P=0.017) were greater in nondiabetic than in diabetic patients. LV dilatation between baseline and 2 years was a predictor of HF in nondiabetic patients, but not in diabetic patients, even after excluding patients with recurrent MI and adjusting for history of hypertension, prior MI, age, treatment group, and smoking. Diabetes modified the relationship between ventricular enlargement and the risk of HF (P=0.011). CONCLUSIONS: The increased incidence of HF after MI in diabetic patients is not explained by a greater propensity for LV remodeling.

Diabetes Complications↗
PubMed2002

Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy.

BACKGROUND: Unexplained left ventricular hypertrophy (LVH) is considered diagnostic of hypertrophic cardiomyopathy (HCM) but fails to identify all genetically affected individuals. Altered diastolic function has been hypothesized to represent an earlier manifestation of HCM before the development of LVH; however, data regarding the clinical utility of imaging techniques that assess this parameter are limited. METHODS AND RESULTS: Echocardiographic studies including Doppler tissue imaging (DTI) were performed in a genotyped HCM population with beta-myosin heavy chain (beta -MHC) mutations. Genotype (+) individuals with LVH (G+/LVH+; n=18) and genotype (+) individuals without LVH (G+/LVH-; n=18) were compared with normal control subjects (n=36). Left ventricular ejection fraction (EF) was significantly higher in both genotype (+) groups (75+/-5% and 71+/-6%, respectively, versus 64+/- 5% in control subjects; P<0.0001). Mean early diastolic myocardial velocities (Ea) were significantly lower in both genotype (+) subgroups, irrespective of LVH (P<0.02). However, there was substantial overlap in Ea velocities between the G+/LVH- and control groups. An Ea velocity of < or =13.5 cm/s had 86% specificity and 75% sensitivity for identifying genotype-positive subjects. The combination of EF > or =68% and Ea velocity <15 cm/s was 100% specific and 44% sensitive in predicting affected genotype. CONCLUSIONS: Abnormalities of diastolic function assessed by Doppler tissue imaging precede the development of LVH in individuals with HCM caused by beta -MHC mutations. Although Ea velocity alone was not sufficiently sensitive as a sole diagnostic criterion, the combination of Ea velocity and EF was highly predictive of affected genotype in individuals without overt manifestations of HCM.

Adult↗
PubMed2002

Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction.

OBJECTIVES: The aim of this study was to determine the prognostic value of right ventricular (RV) function in patients after a myocardial infarction (MI). BACKGROUND: Right ventricular function has been shown to predict exercise capacity, autonomic imbalance and survival in patients with advanced heart failure (HF). METHODS: Two-dimensional echocardiograms were obtained in 416 patients with left ventricular (LV) dysfunction (ejection fraction [LVEF] < or = 40%) from the Survival And Ventricular Enlargement (SAVE) echocardiographic substudy (mean 11.1 +/- 3.2 days post infarction). Right ventricular function from the apical four-chamber view, assessed as the percent change in the cavity area from end diastole to end systole (fractional area change [FAC]), was related to clinical outcome. RESULTS: Right ventricular function correlated only weakly with the LVEF (r = 0.12, p = 0.013). On univariate analyses, the RV FAC was a predictor of mortality, cardiovascular mortality and HF (p < 0.0001 for all) but not recurrent MI. After adjusting for age, gender, diabetes mellitus, hypertension, previous MI, LVEF, infarct size, cigarette smoking and treatment assignment, RV function remained an independent predictor of total mortality, cardiovascular mortality and HF. Each 5% decrease in the RV FAC was associated with a 16% increased odds of cardiovascular mortality (95% confidence interval 4.3% to 29.2%; p = 0.006). CONCLUSIONS: Right ventricular function is an independent predictor of death and the development of HF in patients with LV dysfunction after MI.

Aged↗