• Cardiology - Board Certified by Colombian Association of Medical Faculties (ASCOFAME), Santa Fe de Bogotá (Colombia) • MD Title validated in US by the Educational Commission for Foreign Medical Graduates, 1996 after completing successfully the USMLE step I, step II and step III exams.
Licensure includes:
• Licensed as a Doctor in Medicine and Surgery by resolution # 8778 of the Colombian Minister of Health, Colombia, 1979
ACADEMIC ACHIEVEMENTS
SCHOOL OF PUBLIC HEALTH-EPIDEMIOLOGY DIVISION UNIVERSITY OF MINNESOTA, Minneapolis, MN. (September 1999 - August 2002) Post-Doctoral Fellowship in Cardiovascular Epidemiology
SCHOOL OF PUBLIC HEALTH-EPIDEMIOLOGY DIVISION UNIVERSITY OF MINNESOTA, Minneapolis, MN. (September 1999 - June 2003) Master Degree in Public Health (MPH)- Major in Epidemiology
ALTON OCHSNER MEDICAL INSTITUTION-HYPERTENSION SECTION New Orleans, LA. Fellowship in Hypertension Research (October 1993 - October 1996)
THE NATIONAL INSTITUTE OF CARDIOLOGY “IGNACIO CHAVEZ” UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO, Mexico City, Mexico Fellowship in Cardiology (March 1981 - February 1984)
SAN JOSE HOSPITAL UNIVERSITY HOSPITAL, Bogotá, Colombia. Internship (December 1976 - December 1977)
EDUCATION
COLEGIO MAYOR DE NUESTRA SEñORA DEL ROSARIO, Bogotá, Colombia Doctor in Medicine & Surgery (January 1971 - December 1976)
PROFESSIONAL EMPLOYMENT
WYETH RESEARCH Collegeville, PA. (January 8, 2008 – August 14, 2009) Assistant Director of Epidemiology [Global Safety, Surveillance and Epidemiology (GSSE)]
GLAXOSMITHKLINE-WWW EPIDEMIOLOGY Collegeville, PA. (August 2004 – January 2, 2008) Principal Epidemiologist (Cardiovascular Therapeutic Area)
VALENCIA UNIVERSITARY HOSPITAL Valencia, Spain (August 2000 – Present) Adjunctive Professor in Cardiovascular Epidemiology (Honorary position)
UNIVERSITARY HOSPITAL OF BARRANQUILLA Barranquilla, Colombia (June 1984 - August 1991) CLINICAL CARDIOLOGIST
CEDIUL - CENTER OF ULTRASONOGRAPHY Barranquilla, Colombia (June 1985 - September 1993) Cardiology and echocardiography consultation.
PRIVATE PRACTICE Barranquilla, Colombia (June, 1984 - September, 1993) Internist-Cardiologist
TEACHING EXPERIENCE
LIBRE UNIVERSITY, Barranquilla, Colombia (June 1984 - August 1991) Professor of Internal Medicine
AWARDS
“Excellence in Cardiology” Colombian Society of Cardiology, Bogotá, Colombia (November 27, 1993)
“Merck Young Investigators Award” Excellence in High Blood Pressure Research Council for High Blood Pressure Research (AHA - September 18, 1996)
Abstract: OBJECTIVE: We sought to determine the relationship between the lowest lymphocyte count (lymphocyte(min))obtained within the first 96 h of symptoms onset and the risk of postdischarge recurrent spontaneous myocardial infarction (re-MI) in patients admitted with ST-segment elevation MI (STEMI). METHODS: We analyzed 549 consecutive patients admitted with STEMI from a single academic hospital. Lymphocyte counts were determined at admission and routinely during the first 96 h. Lymphocyte(min) was selected as the main exposure. Patients with inflammatory or infectious diseases, in-hospital death, or reinfarction were excluded from the analysis (final sample= 426 patients). Lymphocyte(min) was divided into quartiles (Q) and their association with re-MI was assessed by competing risk analysis. Postdischarge death and coronary revascularization were considered competing events. RESULTS: During a median follow-up of 36 months, 53 re-MI (12.4%) were registered. The re-MI crude rate was significantly higher in patients in the lowest lymphocyte(min) quartile (Q1r1045 cells/ml) compared with Q2-Q4: 22.4, 9.4, 8.4, 9.4%, respectively; P =0.005. In a multivariate setting, Q1 was also associated with a significant increased risk of re-MI compared with Q2-Q4 (hazard ratio: 2.04, 95% confidence interval: 1.11-3.76; P = 0.021). CONCLUSION: Low lymphocyte count obtained within the first 96 h of a STEMI predicts the risk of re-MI.
Abstract: AIMS: To evaluate the relationship between systolic blood pressure (SBP) and long-term mortality in patients with acute heart failure (AHF) stratified by ejection fraction (LVEF): reduced (< or =40%) vs. preserved (> or =50%). METHODS AND RESULTS: We studied 1049 consecutive patients admitted with AHF. Systolic blood pressure was determined in the emergency department. Left-ventricular ejection fraction was categorized as < or =40% (n = 288), 41-49% (n = 174), or > or =50% (n = 587). Cox regression analysis was used for multivariable analysis. Mean age and SBP were 73 +/- 11 years and 150 +/- 36 mmHg, respectively. During a median follow-up of 18 months, 290 deaths (33.1%) were identified. Higher SBP was associated with lower mortality. In multivariable analysis, a differential effect of SBP across LVEF status was documented (P-value for interaction = 0.036). In linear models, SBP was shown to be inversely related with mortality in both groups (per 10 mmHg decrease): HR((LVEF > or = 50%)): 1.06, CI 95% = 1.01-1.11; P = 0.016, and HR((LVEF < or = 40%)): 1.16, 95% CI = 1.08-1.25; P < 0.001). When SBP was modelled with restrictive cubic splines, an inverse and almost linear relationship with mortality was shown in patients with LVEF < or =40% (P < 0.001), whereas in patients with LVEF > or =50%, SBP followed a J-shape curve. CONCLUSION: In patients with AHF, SBP showed a differential prognostic effect on mortality according to LVEF status; when LVEF was < or =40%, SBP was linearly and inversely associated with mortality. Conversely, in patients with LVEF > or =50% this relationship showed a J-shape pattern.
Abstract: OBJECTIVE: Risk stratification of patients with acute chest pain, non-diagnostic electrocardiogram and normal troponin (ACPneg) remains a challenge, partly because no standardized set of biomarkers with prognostic ability has been identified in this population. Lymphopenia has been associated with atherosclerosis progression and adverse outcomes in cardiovascular diseases; although its prognostic value in ACPneg is unknown. We sought to determine the relationship between the lymphocyte count obtained in the Emergency Department (ED) and the risk of the long-term all-cause mortality or myocardial infarction (MI) in patients with ACPneg. METHODS: We analyzed 1030 consecutive patients admitted with ACPneg in our institution. Lymphocyte count was determined in the ED as a part of a routine diagnostic workup to rule out an acute coronary syndrome. Patients with inflammatory, infectious diseases, or active malignancy were excluded (final sample=975). The independent association between lymphocyte count and the composite endpoint (death/MI) was assessed by survival analysis for competing risk events (revascularization procedures). RESULTS: During a median follow-up of 36 months, 139 (14.3%) patients achieved the combined endpoint, with rates increasing monotonically across lymphocyte quartiles (6.2%, 10%, 20.6% and 24.1% for Q4, Q3, Q2 and Q1 (p<0.001), respectively). In a multivariable analysis, patients in lymphocytes' Q1 and Q2 as compared with those in Q4 had an increased risk for the combined endpoint: HR=2.45 (CI 95% 1.25-4.79, p=0.008) and HR=2.56 (CI 95% 1.30-5.07, p=0.007), respectively. CONCLUSION: In patients with ACPneg, low lymphocytes count was associated with an increased risk for developing the combined endpoint of death or MI.
Abstract: BACKGROUND: Hyperuricemia is a prevalent condition in chronic heart failure (CHF), describing increased oxidative stress and inflammation. Although there is evidence that serum uric acid (UA) predicts mortality in CHF, its role as a prognostic biomarker in acute heart failure (AHF) has not yet been well assessed. The aim of this study was to determine if UA levels predict all-cause mortality. Additionally, as a secondary endpoint we sought the clinical predictors of UA serum level in this population. METHODS: We analyzed 560 consecutive patients with AHF admitted in a single university center. UA (mg/dl) was measured during early hospitalization. Patient survival status was followed up after discharge (median follow-up: 330 days). The independent association of UA level with all-cause mortality was analyzed using Cox regression analysis. RESULTS: During follow-up 165 (29.5%) deaths were identified. Patients with UA levels above the median value (>or=7.7 mg/dl) exhibited higher mortality rates (21.1 vs. 37.9%; p<0.001). In multivariable analysis, after adjusting for recognized prognostic factors and potential confounders, UA>or=7.7 mg/dl and per change in 1 mg/dl of UA was associated with an increased risk of mortality (HR 1.45, CI 95%=1.03-2.44; p=0.03 and HR 1.08, CI 95%=1.01-1.15; p=0.03, respectively). CONCLUSION: UA serum levels is an independent predictor of all-cause mortality in an unselected patients admitted with AHF.
Abstract: BACKGROUND: Depression is a risk factor of excessive morbidity and mortality in heart failure. We examined in-hospital treatment and postdischarge outcomes in hospitalized heart failure patients with a documented history of depression from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure. METHODS: We identified patient factors associated with depression history and evaluated the association of depression with hospital treatments and mortality, and early postdischarge mortality, emergency care, and rehospitalization. RESULTS: In 48,612 patients from 259 hospitals, depression history was present in 10.6% and occurred more often in females, whites, and those with common heart failure comorbidities, including chronic pulmonary obstructive disease (36% vs 27%), anemia (27% vs 16.5%), insulin-dependent diabetes mellitus (20% vs 16%), and hyperlipidemia (38% vs 31%), all P <.001. Patients with depression history were less likely to receive coronary interventions and cardiac devices, all P <.01; or be referred to outpatient disease management programs, P <.001. Length of hospital stay was longer with depression history (7.0 vs 6.4 days, P <.001). In 5791 patients followed-up at 60-90 days postdischarge, those with depression history had higher mortality (8.8% vs 6.4%; P=.025). After multivariable modeling, depression history remained a predictor of length of hospital stay, P <.001 and postdischarge mortality, P=.02. CONCLUSIONS: Depression history at heart failure hospitalization may be a predictor of prolonged length of hospital stay, less use of cardiac procedures and postdischarge disease management, and increased 60-90 day mortality. Patients with depression might represent a vulnerable group in which improved use of evidence-based treatment should be considered.
Abstract: BACKGROUND: Low lymphocyte count (LLC), a surrogate for inflammation, has emerged as a potential risk factor for cardiovascular outcomes, especially new ischemic events. To identify patients with non-ST segment elevation acute coronary syndromes (NSTEACS) who benefit from an invasive revascularization strategy remains a challenge. We sought to determine if patients with high-risk NSTEACS who exhibited LLC have a greater reduction in long-term post-discharge myocardial infarction (MI) when managed under a revascularization invasive strategy (RIS) as compared with conservative strategy (CS). METHODS: Nine hundred seventy two consecutive patients with high-risk NSTEACS were treated under two revascularization strategies (RS): 1) CS, from January 2001 to October 2002 (345 patients; 35.5%) and 2) RIS, from November 2002 to May 2005 (627 patients; 64.5%). LLC was defined as lymphocytes count < or =1200 cells/ml (1 vs. 2-4 quartiles). The association between the type of RS and MI was stratified by lymphocyte count status and assessed by Cox regression adapted for competing events. RESULTS: At 3-year follow-up, 145 deaths (14.9%), 135 MI (13.9%) and 76 revascularization procedures (7.8%) were registered. In a multivariable setting, LLC patients exhibited a greater MI risk reduction when managed under RIS (HR: 0.40; 95% CI=0.22-0.72, p=0.003). Conversely, when LLC was not present, no difference in the rate of MI was detected between the two RS. CONCLUSIONS: LLC identifies a subgroup of patients with greater reduction in the risk of postdischarge MI when a RIS is applied.
Abstract: BACKGROUND: Most patients hospitalized for acute heart failure syndromes (AHFS) carry a diagnosis of coronary artery disease (CAD), but coronary angiography is infrequently performed. This purpose of this study was to determine the influence of coronary angiography on use of therapeutics and early postdischarge outcomes in patients with AHFS. METHODS: The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure program enrolled 48,612 patients admitted with AHFS at 259 academic and community hospitals throughout the United States Inhospital treatments and outcomes were tracked in all patients and postdischarge outcomes in a prespecified 10% sample. Outcome data were prospectively collected and analyzed according to whether coronary angiography was performed during the index hospitalization and whether a patient had CAD. RESULTS: Overall, 8.7% of all patients underwent inhospital angiography. Among patients with CAD who underwent angiography, 27.5% underwent inhospital myocardial revascularization. At the time of discharge, patients with CAD who underwent angiography were significantly more likely to be receiving aspirin (68.9% vs 50.3%, P < .0001), statins (56.6% vs 40.6%, P < .0001), beta-blockers (78.6% vs 67.5%, P < .0001), and angiotensin-converting enzyme inhibitors (64.9% vs 51.5%, P < .0001). In patients with AHFS and CAD, the use of inhospital angiography was associated with significantly lower mortality and rehospitalization risk in the first 60 to 90 days post hospital discharge after adjustment for multiple comorbidities and patient factors: mortality (HR 0.31 [95% CI 0.14-0.70], P = .004) and death or rehospitalization (OR 0.65 [95% CI 0.50-0.86], P = .003). There were no significant differences in any of these outcomes in patients with AHFS and a nonischemic etiology based the performance of inhospital angiography. CONCLUSIONS: The performance of inhospital angiography on patients with AHFS and CAD is associated with an increased use of aspirin, statins, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and myocardial revascularization. This corresponded with significantly lower rates of death, rehospitalization, and death or rehospitalization at 60 to 90 days post discharge.
Abstract: OBJECTIVE: To investigate the safety of discharge of patients deemed at low risk of cardiac events after evaluation in a chest pain unit and to determine the prognostic effect of revascularization of patients deemed at high risk. PATIENTS AND METHODS: The study population consisted of 1088 patients presenting at the emergency department from January 15, 2001, to September 1, 2006, with chest pain but without ischemia on electrocardiography or troponin elevation. Patients were managed by a chest pain unit protocol that included early exercise testing. Three groups of patients were distinguished: (1) those discharged after exercise testing (424 [39%]); (2) those in whom unstable angina was ruled out after in-hospital evaluation (208 [19%]); and (3) those in whom unstable angina was confirmed or not ruled out (456 [42%]). Of the 456 patients in group 3, 183 (40%) were revascularized at the index episode. The primary end point was the occurrence of myocardial infarction or death within 1 year. Adjustments were made for patient characteristics and a propensity score for revascularization (c statistic [0.83]). RESULTS: Groups 1 and 2 showed lower rates of the primary end point than group 3 (group 1: 7 [1.7%]; group 2: 1 [0.5%]; group 3: 62 [13.6%]; P=.001). In group 3, revascularization at the index episode did not reduce the primary end point in the univariate (22 [12%] vs 29 [11%]; P=.80) and multivariate (hazard ratio, 1.4; 95% confidence interval, 0.7-2.5; P=.40) analyses. In-hospital revascularization decreased the need for postdischarge revascularization (hazard ratio, 0.3; 95% confidence interval, 0.1-0.7; P=.01). CONCLUSION: Chest pain unit protocols are associated with safe patient discharge. Although early revascularizations may decrease the need for postdischarge revascularizations, they may not improve 1-year outcomes by reducing the number of myocardial infarctions or deaths.
Abstract: BACKGROUND: Differences in hospital staffing may influence outcomes for patients with acute conditions, including heart failure (HF), depending on which day of the week the patients are admitted. This study examined the relationship between the day of the week patients are hospitalized for HF and death rate, length of stay (LOS), and rehospitalization rate. METHODS AND RESULTS: A total of 259 US hospitals participating in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) submitted data on 48 612 patients with HF. Sixty- to 90-day postdischarge follow-up data were collected prospectively in a prespecified 10% sample. We analyzed day of admission and discharge, demographic, medical history, medication use, laboratory, and in-hospital procedure data for their association with hospital LOS and death rate. Patient characteristics were similar for weekday and weekend presentation. LOS was a median of 4.0 days and a mean of 5.7+/-5.7 days; in-hospital death rate was 3.8%. In-hospital and postdischarge risk of death were similar for each day of the week in the hospital and follow-up cohorts, respectively. LOS, however, was significantly influenced by day of admission, even after adjustment for other LOS risk factors. The shortest LOS by admission day of the week was Tuesday (5.39 days), and the longest was Friday (5.88 days; P<0.001). CONCLUSIONS: No differences in death rate by day of admission or discharge for HF hospitalizations were evident. Hospitalizations for HF on Thursday and Friday were associated with prolonged LOS. Understanding the factors responsible for the increased LOS and potential adjustments in staffing to facilitate weekend discharges may improve the efficiency of HF hospital care.
Abstract: Neutrophil to lymphocyte ratio (N/L) has been associated with poor outcomes in patients who underwent cardiac angiography. Nevertheless, its role for risk stratification in acute coronary syndromes, specifically in patients with ST-segment elevation myocardial infarction (STEMI), has not been elucidated. We sought to determine the association of N/L maximum value (N/L max) with mortality in the setting of STEMI and to compare its predictive ability with total white blood cell maximum count (WBC max). We analyzed 515 consecutive patients admitted with STEMI to a single university center. White blood cells (WBC) and differential count were measured at admission and daily for the first 96 hours afterward. Patients with cancer, inflammatory diseases, or premature death were excluded, and 470 patients were included in the final analysis. The association between N/L max and WBC max with mortality was assessed by Cox regression analysis. During follow-up, we registered 106 deaths (22.6%). A positive trend between mortality and N/L max quintiles was observed; 6.4%, 12.4%, 11.7%, 34%, and 47.9% of deaths occurred from quintiles 1 to 5 (p <0.001), respectively. In a multivariable setting, after adjusting for standard risk factors, patients in the fourth (Q4 vs Q1) and fifth quintile (Q5 vs Q1) showed the highest mortality risk (hazard ratio 2.58, 95% confidence interal 1.06 to 6.32, p = 0.038 and hazard ratio 4.20, 95% confidence interal 1.73 to 10.21, p = 0.001, respectively). When WBC max and cells subtypes were entered together, N/L max remained as the only WBC parameter; furthermore, the model with N/L max showed the most discriminative ability. In conclusion, N/L max is a useful marker to predict subsequent mortality in patients admitted for STEMI, with a superior discriminative ability than total WBC max.
Abstract: AIMS: Cigarette smoking is a well-established risk factor for cardiovascular disease yet several studies have shown lower mortality after acute coronary syndromes in smokers compared with non-smokers, the so called 'smoker's paradox'. This study aimed to ascertain the relationship between smoking and clinical outcomes in patients hospitalized with heart failure (HF). METHODS AND RESULTS: OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) collected data on 48 612 patients from 259 hospitals. Characteristics, treatments, and outcomes were compared for current/recent smokers vs. those without current/recent smoking, and multivariable regression analyses with adjustment for hospital clustering were performed. There were 7743 (15.9%) smokers, 39 126 (80.5%) non-smokers, and 1743 (3.6%) missing. Smokers were younger, had similar renal function, but lower ejection fraction. The risk of in-hospital mortality was less in smokers (2.3 vs. 3.9%, P < 0.001). After extensive covariate adjustment, smokers still had lower in-hospital mortality risk OR (odds ratio) 0.70, 95% CI (confidence interval) 0.56-0.88, P = 0.002. Post-discharge, smokers (n = 998) had similar mortality risk (6.7 vs. 8.4%, P = 0.29) compared with those without current/recent smoking. CONCLUSION: Smokers hospitalized with HF had lower risk adjusted in-hospital mortality and similar early post-discharge mortality compared with non-smokers. The residual association of smoking and better prognosis, the 'smoker's paradox', was not fully explained by measured covariates.
Abstract: BACKGROUND: Coronary artery disease (CAD) is frequent among patients hospitalized with acute heart failure syndromes (AHFS). AIMS: To describe the influence of coronary revascularization status on survival in patients with AHFS. METHODS AND RESULTS: OPTIMIZE-HF enrolled 48,612 patients with AHFS from 259 U.S. hospitals. In-hospital data were obtained for all patients and post-discharge 60-90 day follow-up in a pre-specified 10% sample. CAD was associated with higher in-hospital (3.7% vs. 2.9%, OR 1.14, 95% CI 1.00-1.31) and post-discharge mortality (9.2% vs. 6.9%, HR 1.37, 95% CI 1.03-1.81) compared to no CAD. Post-discharge, patients with CAD who were not revascularized had higher mortality compared to patients without CAD (10.6% vs. 6.9%, HR 1.56, 95% CI 1.15-2.11). This association was similar in patients with left ventricular systolic dysfunction (EF <40%, adjusted HR 1.52, 95% CI 0.98-2.35) and preserved systolic function (EF > or =40%, adjusted HR1.58, 95% CI 1.05-2.39). Patients with CAD who were revascularized had similar mortality to patients without CAD (HR 1.06, 95% CI 0.62-1.80 for PSF, HR 1.13, 95% CI 0.71-1.80 for LVSD). CONCLUSIONS: In AHFS, patients with CAD have a higher 60-90 day post-discharge mortality compared to no-CAD patients. However, patients with CAD who are revascularized appear to have similar post-discharge mortality when compared to the no-CAD group. This suggests that revascularization status may confer a survival advantage in this high risk population.
Abstract: The prognostic value of brain natriuretic peptide (BNP) measurement in patients with acute heart failure is not well understood. The aim of this study was to investigate the relationship between the BNP level and mortality and readmission for acute heart failure. We studied 569 consecutive patients who were admitted with a diagnosis of acute heart failure. The BNP level was measured after the patient became clinically stable. The relationship between the BNP level and mortality was assessed by Cox regression analysis, and the relationship with readmission, by competing risks regression analysis. During a median follow-up period of 9 (range, 3-18) months, 156 deaths (27.4%) and 140 readmissions (24.6%) occurred. Multivariate analysis demonstrated a positive linear association between the risk of death and the BNP quintile. In contrast, the BNP level did not predict readmission for acute heart failure, mainly because of the effect of death as a competing outcome.
Abstract: BACKGROUND AND OBJECTIVE: The relation between left ventricular ejection fraction (LVEF) and prognosis in patients with heart failure is controversial. The aim of this study was to determine the relation of LVEF in long-term mortality and readmissions for acute heart failure in a non-selected population of patients admitted with acute heart failure (AHF). PATIENTS AND METHOD: We included 507 patients admitted consecutively for AHF in a cardiology department of a single-centre. LVEF was assessed with transthoracic echocardiography during hospitalization. All-cause mortality and readmission for AHF were selected as primary and secondary endpoints, respectively. The independent association between LVEF and endpoints was assessed with traditional Cox regression analysis for all-cause mortality and Cox regression for competing risks for readmission for AHF. RESULTS: 47% of patients exhibited LVEF > or = 50%. During a median follow-up of one year, 151 (30%) deaths and 139 (27%) readmissions for AHF were observed. Mortality rates were higher in patients with LVEF < 50% (34 vs 25%; p = 0.028) and no differences were observed for readmissions for AHF (26 vs 29%, p = 0.510). In multivariate analysis, after adjustment for traditional risk factors, patients with LVEF < 50% did not show higher risk of mortality (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 0.76-1.57; p = 0.645) or readmissions for AHF (HR = 1.00; 95% CI, 0.68-1.47; p = 1). CONCLUSIONS: Patients with preserved LVEF constitute a substantial proportion of patients with AHF, exhibiting similar mortality and readmissions risks compared with patients with depressed LVEF.
Abstract: OBJECTIVE: To assess whether circulating levels of carbohydrate antigen 125 (CA125) predict subsequent 6-month all-cause mortality in patients after the index hospitalisation for acute heart failure (HF). DESIGN AND SETTING: Prospective cohort study at a single teaching centre in Spain. METHODS: 529 consecutive patients with acute HF admitted in a single university centre were analysed. In addition to the traditional clinical information, CA125 (U/ml) was measured during the early course of hospitalisation. The independent association between baseline CA125 and mortality was assessed with Cox regression analysis. The follow-up was limited to 6 months. RESULTS: 349 (66%) patients showed serum levels of CA125 >35 U/ml (established cut-off point value). At a 6-month follow-up, 89 (16.8%) deaths were identified. A positive trend between mortality and CA125 quartiles was observed; 3.8%, 15.2%, 22% and 26.5% of deaths occurred from quartile 1 to 4 of CA125 (p<0.001). Likewise, a monotonic, ascending trend in the risk ratios was estimated from the multivariable Cox model. Compared with the first quartile of CA125, the HRs (95% CI) for the second, third and fourth quartiles were 3.25 (1.20 to 8.79), 4.91 (1.88 to 12.85) and 8.41 (3.24 to 21.79), respectively. CONCLUSIONS: Serum levels of CA125 obtained in patients admitted with a diagnosis of acute HF was shown to be an independent predictor of mortality up to the 6-month follow-up.
Abstract: BACKGROUND: The optimal revascularization strategy for non-ST elevation acute coronary syndromes (NSTE-ACS) remains controversial, especially in a real world context. The objective of this work was to assess differences at 1 year in all-cause mortality and the composite endpoint of mortality or acute myocardial infarction (MI) between two management strategies for NSTE-ACS: a conservative strategy (CS) versus a routine invasive strategy (RIS). METHODS: Of 799 consecutive patients admitted to our institution, 369 were treated with CS (from January 2001 to October 2002); 430 patients admitted with the same diagnosis were treated with RIS (from November 2002 to November 2004). A propensity score (PS) matched sample was created and included 694 patients (87% of the original population). The event rate was compared between each paired member of the PS-matched sample, one receiving RIS and the other CS, and their differences were tested by Cox proportional analysis. RESULTS: No significant differences in baseline characteristics were noted between the two management cohorts. By design, the rate of in-hospital catheterization and revascularization procedures increased in RIS compared with CS. The mortality rate was lower, but not significant, in RIS (HR: 0.76, 95% CI=0.51-1.11; p=0.155). For the composite of death or MI, RIS showed a relative risk reduction of 29% (HR: 0.71, 95% CI=0.53-0.94); p=0.018) compared with CS, differences that become non-significant (p=0.680) if we adjust for differences in rate of revascularization procedures and changes in medication prescription. CONCLUSIONS: RIS was associated with a 1-year lower risk of the combined endpoint of all-cause death and MI in patients with NSTE-ACS, attributable to changes in frequency of revascularization procedures and in medical treatment.
Abstract: PURPOSE: The present study was designed to assess, 1) the independent prognostic effect of renal dysfunction on all-cause mortality in the setting of acute myocardial infarction with ST-segment elevation (STEMI), and 2) to determine if such effect varies based upon the presence of heart failure (HF) on admission. METHODS: 549 consecutive patients admitted with the diagnosis of STEMI were prospectively recruited in a teaching hospital in Spain. Serum creatinine (sCr) and glomerular filtration rate (GFR) were obtained on admission, together with other relevant information used for risk stratification. The independent effect of sCr and GFR on long-term mortality was determined by Cox regression analysis. Main outcome was all-cause mortality, with a median follow-up of 1 year. RESULTS: In a multivariate analysis the degree of renal impairment was a strong predictor of mortality in patients without clinical evidence of HF at admission (HR=1.15; 95% CI 1.10 to 1.19 and HR=1.58; 95% CI 1.30 to 1.81) for sCr (per 0.1 mg/dl) and GFR (per decreasing 10 ml/min/1.73 m2), respectively. In the group with HF, the effect was less pronounced (HR=1.03; 95% CI 1.01 to 1.04 and HR=1.17; 95% CI 1.02 to 1.37) for sCr and GFR, respectively. CONCLUSIONS: In the setting of STEMI, renal dysfunction estimates showed a differential prognostic effect depending on HF status, with a greater impact seen in patients without clinical evidence of HF.
Abstract: In recent years, numerous studies have validated the role of inflammation in the pathogenesis of atherosclerosis. Several of such studies have produced compelling evidence that inflammation participates in both, the initiation and perpetuation of the atherosclerotic process. Furthermore, epidemiological observations have found basal white blood cell (WBC) count is strongly associated with future cardiovascular disease (CVD), highlighting the participation of leukocytes in the pathogenesis of the ischemic damage that occurred during an acute coronary event, in particularly during the acute myocardial infarction (MI). Fundamentally, an acute MI triggers a systemic response to a necrotic insult characterized by leukocytosis and acute-phase protein synthesis. In this setting, elevated WBC count plays a central role in the reparative process that takes place to replace the necrotic tissue for collagen. In addition to be a proxy for the intensity of the peri-infarction inflammatory response, recent evidence has also shown that an elevated WBC counts, measured during the acute phase of MI, to be associated with adverse outcomes. This relationship holds true even when adjusting for classical prognostic variables some of which are surrogates for the extension of the infarcted-area. WBC count prognostic value in absence of necrosis marker elevation (like unstable angina), however, remains unclear and controversial. Additionally, and essentially due to its simplicity, cost-effectiveness and wide availability, WBC count has drawn the attention of researchers as a potential stratification tool in acute coronary syndromes (ACS). However, a formal comparison is needed between WBC count with other inflammatory markers such high-sensitive C-reactive protein to fully characterize its diagnostic accuracy.
Abstract: The distribution of echocardiographic left ventricular (LV) mass differs among ethnicities. Because ethnic-specific echocardiographic criteria for LV hypertrophy (LVH) are not established, we determined whether threshold values derived from overwhelmingly white populations are appropriate for blacks, a subgroup having more LVH. Between 1992 and 1994, LV mass was measured echocardiographically in the Jackson, Mississippi, black cohort of the Atherosclerosis Risk in Communities study. Participants free of prevalent cardiovascular disease (CVD) (n=1616; mean+/-SD, age 59+/-5.7; 65% women and 57% with hypertension) were included. The optimal LVH threshold value was selected from the continuum of LV mass index (LVMI=LV mass/height(2.7)) using 3 methods: (1) the best operating point from the area under the resulting receiver-operating characteristic (ROC) curve predicting incident CVD; (2) the value with the smallest probability value associated with incident CVD; and (3) visual inspection of functions of LVMI and CVD in the general additive model (GAM) plot. At a median follow-up of 6.8 years, there were 192 events (coronary heart disease=87, stroke=62, and congestive heart failure=43; incidence=17.6/1000 person-years). The best operating point from the resulting ROC analysis was 51.2 g/m(2.7) for sensitivity (53.4%) and specificity (61.5%). The Cox and GAM models adjusted for age, gender, systolic blood pressure, hypertension, diabetes, smoking, total cholesterol-to-high-density lipoprotein ratio, LVH by ECG criterion, and socioeconomic status found 50 to 51 g/m(2.7) as the optimal threshold for LVH in middle-aged blacks, corresponding to a minimum probability value and to a log-hazard ratio of zero, respectively. Because these values are close to the 51 g/m(2.7) established from predominantly white populations, this cutpoint is appropriate for both groups.
Abstract: INTRODUCTION AND OBJECTIVES: The Charlson comorbidity index (CCI), an indicator of comorbidity, has been used as an adjusting variable in multivariate models. Because of its prognostic value per se for cardiovascular complications after acute myocardial infarction (AMI), we sought to determine the predictive value of the CCI for all-cause mortality and recurrent AMI 30 days and 1 year after the index event. PATIENTS AND METHOD: We analyzed 1035 consecutive patients admitted with the diagnosis of AMI (ST elevation=508 and non-ST elevation=527). The composite endpoint was determined after 30 days (13.9%) and 1 year (26.3%) of follow-up. The CCI was calculated on admission, and other variables with prognostic value were also recorded. CCI was stratified in 4 categories: 1: CCI=0 (control), 2: CCI=1, 3: CCI=2,4: CCI> or =3. Cox proportional risks analysis was used for the multivariate analysis, and the C-statistic was calculated to assess the discriminative power of the models. RESULTS: Hazard ratios (95% CI) estimated for each category of CCI were: 2=1.69 (1.10-2.59), 3=1.78 (1.08-2.92) and 4=1.57 (0.87-2.83) at 30 days; 2=1.62 (1.18-2.23), 3=2.00 (1.39-2.89) and 4=2.24 (1.50-3.36) at 1 year. Comparisons with the C-statistic between the nested multivariate models (with and without CCI) yielded values of 0.765 vs 0.750 after 30 days, and 0.751 vs 0.735 after 1 year. CONCLUSIONS: Our data indicate that CCI is an independent predictor of mortality or recurrent AMI 30 days and 1 year after the index AMI.
Abstract: Echocardiographically determined left ventricular (LV) hypertrophy may be a stronger risk factor of cardiovascular disease (CVD) for women than for men, although it is unclear whether reported gender differences are real or attributable to confounding. We evaluated echocardiographic LV hypertrophy (defined as LV mass/height(2.7) >/=51 g/m(2.7)) collected from the African-American population of the Atherosclerosis Risk in Communities Study. Incident CVD events (57 in men, 62 in women) were determined during a median follow-up of 4.9 years (interquartile range 4.3 to 5.6) and included nonfatal myocardial infarction, cardiac death, coronary revascularization, and stroke. We conducted 2 analyses. First, we created matched samples of 340 men and 812 women who had LV hypertrophy based on propensity score and estimated the gender-specific incidence rate ratios and population-attributable risks. Second, we evaluated the complete cohort (604 men and 1,113 women) with Poisson's regression after adjusting for age, body mass index, hypertension, diabetes mellitus, ratio of total cholesterol to high-density lipoprotein cholesterol, current smoking, and education level. LV hypertrophy was significantly predictive of incident CVD, and the association shown by analyses of matched propensity scores was similar in men and women (incidence rate ratio 1.88 vs 1.92, p = 0.97 for men, population-attributable risk 0.22 vs 0.26, p <0.07 for women). In the multivariate analysis, we found comparable effect estimates for LV hypertrophy (incidence rate ratio 1.66 vs 2.09, p = 0.55 for men; population-attributable risk 0.24 vs 0.32, p <0.07 for women). Thus, LV hypertrophy is a strong predictor of CVD in African-Americans, and the effect of LV hypertrophy on CVD is similar in men and women.
Abstract: BACKGROUND: It is suspected that effective therapies are often underutilized in black compared with white patients with coronary artery disease (CAD). HYPOTHESIS: We hypothesized that an unfavorable bias may exist against black patients in the medical management of heart failure. METHODS: In 566 consecutive adult subjects who were discharged alive from the hospital with a principal discharge diagnosis of heart failure, we assessed the effect of patient race on utilization of classes of medications (angiotensin-converting enzyme inhibitors [ACEI], digitalis, diuretic agents) and combinations of medications (effective vasodilators, i.e., ACEI or combined hydralazine and nitrate; effective combination therapy, i.e., effective vasodilator with digitalis and diuretic) known to be beneficial in symptomatic heart failure. RESULTS: Compared with black patients (n = 182), white patients were older, had a higher incidence of coronary artery disease, lower incidence of hypertension, and lower serum creatinine and left ventricular end-diastolic diameter. In crude analyses, the utilization of all medications was similar between white and black patients. After adjustment for clinical differences, black patients were more likely to receive ACEI (adjusted odds ratio [OR] = 1.84; 95% confidence interval [CI] 1.13-3.01), effective vasodilators (OR = 1.97; CI 1.20-3.23), and effective combination therapy (OR = 1.66; CI 1.02-2.69) than white patients at the time of discharge from the hospital. No multivariate association was seen between patient race and use of digoxin or diuretics. In an analysis of subsets of patients with ejection fraction < 45% (n = 260), no association was seen between patient race and utilization of effective medical therapy. CONCLUSION: Our results show no unfavorable bias against black patients with decompensated heart failure.
Abstract: BACKGROUND: The Tei index (TI) is a new echocardiographic/Doppler index of combined systolic and diastolic function, calculated as isovolumic relaxation time plus isovolumic contraction time divided by ejection time. This purpose of this study was to explore the prognostic value of TI in patients with heart failure from left ventricular (LV) systolic dysfunction. METHODS: Of 105 randomly selected participants with LV ejection fraction less than 30% and at least 1 hospitalization for heart failure, we included 60 patients in whom assessment of the TI was technically feasible. Using the patients' medical records, we collected information on several clinical and echocardiographic variables. We monitored patients for a mean duration of 24 +/- 19 months from the time of the echocardiogram. The study outcome was the composite of death from any cause or emergency heart transplant. RESULTS: The median value (interquartile range) of TI was 0.79 (0.54, 1.14). Of 57 patients (95%) with complete follow-up, 28 (49%) died, and 2 (3.5%) underwent emergency heart transplant at a mean duration of 17 +/- 14 months. Kaplan-Meier survival curves showed a higher cumulative incidence of the study end point among patients in the highest quartile of TI, compared with the other 3 quartiles (log rank P =.002). After adjustment for potential clinical confounders, TI in the highest quartile (TI > 1.14) was a significant independent predictor of the composite end point (odds ratio 5.3, 95% confidence interval 1.9 to 14.9, P =.0018). CONCLUSION: Prolonged TI (>1.14) is a powerful and independent predictor of poor clinical outcome in patients with symptomatic heart failure and severe LV systolic dysfunction.
Abstract: Left ventricular geometry is suspected to affect heterogeneity of myocardial repolarization; therefore, it is plausible but unproven that increased sphericity of the left ventricle is associated with greater QT interval dispersion. In 60 patients with dilated cardiomyopathy with left ventricular ejection fraction < or = 30%, we found that spherical distortion of the left ventricle was associated with increased QT dispersion, implying increased heterogeneity of myocardial repolarization.
Abstract: An adverse interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors is suspected in patients with heart failure, but the effect of combined therapy with these agents on hospital readmission rates is unknown. Our study found that combining aspirin with ACE inhibitors is associated with higher early readmission rates than use of ACE inhibitors alone, particularly in patients with depressed ejection fraction and in those without coronary artery disease.
Abstract: INTRODUCTION: The purpose of this study was to ascertain the presence of gender bias in the medical management of heart failure, and to assess its association with the specialty of the caregiver physician. METHODS: In 309 patients with documented left ventricular systolic dysfunction (ejection fraction <45%) and at least one hospitalization for heart failure, we assessed the frequency of use of effective medical therapy for heart failure among male (n=187) and female (n=122) patients at the time of hospital discharge. We constructed multivariate models relating patient gender and caregiver specialty to utilization of each class of medications (angiotensin-converting enzyme inhibitors, effective vasodilator therapy (i.e., angiotensin-converting enzyme inhibitors or hydralazine-nitrate therapy), diuretics, digoxin), and combination therapy (i.e., vasodilator plus diuretic plus digoxin). RESULTS: In crude analyses, we did not find any difference in utilization of medications between male and female patients. Multivariate analyses involving adjustment for age, race, coronary artery disease, ejection fraction, and other relevant variables, revealed higher utilization of combination therapy by cardiologists in male versus female patients (adjusted odds ratios=2.07; 95%CI=1.09-3.95), and higher utilization of digoxin therapy by non-cardiologists in female versus male patients (adjusted odds ratio=5.5; 95%CI=1.4-22.2). No gender or caregiver specialty differences were seen in models relating to the other classes of medications. CONCLUSIONS: Our findings suggest the presence of gender bias in the medical management of heart failure, and identify an interesting interaction between caregiver specialty and gender bias.
Abstract: BACKGROUND: Left ventricular (LV) shape tends to become spherical in patients with dilated cardiomyopathy of diverse etiology. Clinical and echocardiographic factors which affect the degree of LV spherical distortion and the impact of altered LV shape on prognosis have not been studied adequately. HYPOTHESIS: This study was undertaken to investigate the prognostic implications of altered LV shape on clinical outcome in dilated cardiomyopathy. METHODS: In 112 patients with depressed LV ejection fraction (19 +/- 9%) and symptomatic heart failure, and in 10 age- and gender-matched normal controls, we performed 2-dimensional echocardiography to assess LV shape using the eccentricity index. Eccentricity index was defined as the ratio of the LV long axis to the LV transverse diameter, measured at end systole and end diastole in the apical four-chamber view. We sought univariate and multivariate clinical and echocardiographic correlates of LV shape. Further, we sought correlations between eccentricity index and clinical outcomes (death and composite outcome of death or emergent heart transplant). RESULTS: Compared with controls, patients with cardiomyopathy had significantly lower systolic (2.04 vs. 1.56; p = 0.001) and diastolic (1.75 vs. 1.53; p = 0.003) eccentricity index, implying a more spherical LV shape. Of all clinical and echocardiographic variables tested, mitral regurgitation, right ventricular dysfunction, and increased LV mass were independently associated with spherical LV shape. At a follow-up period of 17 +/- 12 months, no correlation was found between eccentricity index and the occurrence of death or the combined endpoint of death or emergent heart transplant, in univariate or multivariate analysis. CONCLUSIONS: In patients with dilated cardiomyopathy, the degree of spherical distortion of the LV does not correlate with prognosis.
Abstract: OBJECTIVES: We sought to assess whether the adjustment of peak oxygen consumption (PkVO2) to lean body mass would yield a more accurate discriminator of outcomes in the chronic heart failure population. BACKGROUND: Peak oxygen consumption is traditionally used to risk stratify patients with congestive heart failure (CHF) and to time cardiac transplantation. There is, however, considerable variability in body fat content, which represents metabolically inactive mass. METHODS: In 225 consecutive patients with CHF, the percentage of body fat was determined by the sum of skinfolds technique. All underwent CPX using a ramping treadmill protocol. Mean follow-up duration was 18.9+/-11.3 months. RESULTS: There were 14 cardiovascular deaths and 15 transplants. Peak oxygen consumption lean, both as a continuous variable and using a cutoff of < or =19 ml/kg/min, was a better predictor of outcome than unadjusted PkVO2 (p = 0.003 vs. 0.027 for the continuous variables and p = 0.0006 vs. 0.055 for < or =19 ml/kg/min and < or =14 ml/kg/min unadjusted body weight, respectively). Using partial correlation index R statistics, the Cox model using PkVO2 lean < or =19 ml/kg/min, in addition to age and etiology of CHF as covariates, yielded the strongest predictive relationship to the combined end point (chi-square value 24.32). Especially in the obese patients and in women, there was considerably better correlation of PkVO2 lean with outcome than the unadjusted PkVO2. CONCLUSIONS: The adjustment of PkVO2 to lean body mass increases the prognostic value of cardiopulmonary stress testing in the evaluation of patients with chronic heart failure. The use of <19 ml O2/kg of lean body mass/min as a cutoff in PkVO2 should be used for timing transplantation, particularly in women and the obese.
Abstract: BACKGROUND: The outcome of patients with diabetes after myocardial infarction (MI) has traditionally been worse than in their nondiabetic counterparts before and during the thrombolytic therapy era. Whether the fate of patients with diabetes might improve with mechanical intervention, particularly with primary stenting, has not previously been studied. METHODS: We compared the angiographic and clinical outcome of 76 nondiabetic patients (aged 61 +/- 14 years; 66% male) and 28 patients with diabetes (aged 65 +/- 12 years; 64% male) consecutively treated with primary stenting for acute MI. Coronary Thrombolysis In Myocardial Infarction grade 3 flow was restored in 96% of diabetic and 97% of nondiabetic patients. RESULTS: Angiographic results after stent deployment were similar in the 2 groups. At 1-month follow-up, all patients in both groups were alive. Patients with diabetes had a much higher incidence of stent thrombosis (18% vs 1%; P =.003), which accounted for the majority of the major cardiac events at 1 month (21% vs 4%; P =.009). At a mean follow-up of 315 +/- 13 days, 99% of nondiabetic and 89% of patients with diabetes were alive (P =.04). Overall freedom from a major cardiac event (death, MI, target vessel revascularization) at 315 +/- 13 day follow-up was 88% for nondiabetics and 54% for patients with diabetes (P =.0003). By multivariate analysis, diabetes mellitus was the most important predictor for development of 1-month (RR 9.89; 95% confidence interval, 1.6-30) and late major cardiovascular events (RR 8.39; 95% confidence interval, 2.93-24). CONCLUSIONS: Primary stenting in acute MI is highly effective in restoring immediate TIMI 3 coronary flow in nondiabetic patients and patients with diabetes. This procedure may improve benefit in terms of mortality rate to both groups, particularly in patients with diabetes, compared with previous reports with thrombolytic therapy. Nevertheless, stent thrombosis and major cardiovascular events at 1 month and late follow-up are more frequent in patients with diabetes.
Abstract: BACKGROUND: While depressed left ventricular ejection fraction is clearly associated with poor long-term outcome in heart failure (HF), the effect of ejection fraction on short-term outcomes and resource utilization following hospitalization for HF remains unclear. HYPOTHESIS: We evaluated the independent effect of depressed ejection fraction (< or = 40%) on short-term outcomes and resource utilization following hospitalization for HF. METHODS: The study population included 443 consecutive patients hospitalized for DRG 127 (HF and shock) with known ejection fraction. For each patient, we assessed the hospitalization cost (1995 US$), length of stay, in-hospital mortality, 30-day mortality, and 30-day readmission rates. RESULTS: Despite similar disease severity at admission, patients with ejection fraction < or = 40% (Group 1) had longer length of stay (4.0 vs. 3.7 days; p = 0.03), a tendency toward higher hospitalization cost ($3,054 vs. $2,770; p = 0.08), more readmissions for any cause (0.4 vs. 0.3; p = 0.05) and for HF (0.2 vs. 0.1; p = 0.01), but similar in-hospital (2.5 vs. 2.6%) and 30-day mortality (4.0 vs. 4.6%) compared with patients with ejection fraction > 40% (Group 2). In multivariate analyses, Group 1 patients were more likely to have higher than median hospitalization cost [odds ratio (OR) = 1.98; 95% confidence intervals (CI) = 1.02-3.91] and longer than median hospital stay (OR = 1.68; CI = 1.08-3.91); they were also more likely to be readmitted for any cause (OR = 2.07; CI = 1.15-3.78) or for HF (OR = 5.71; CI = 1.64-21.94), and they tended to have a higher 30-day incidence of death or readmission (OR = 1.65; CI = 0.96-2.84). CONCLUSIONS: Depressed left ventricular ejection fraction is associated with higher resource utilization and readmission rates following hospitalization for HF. Greater focus on patients with depressed ejection fraction may increase cost savings from HF disease management programs.
Abstract: The aim of the study was to determine if a hypercoagulable state that may persist for several months after an acute myocardial infarction may contribute to an increased incidence of stent thrombosis. Primary stenting was performed in 104 consecutive patients with acute myocardial infarction using 147 coronary stents. Twenty-eight patients (27%) were diabetic and 55 patients (53%) were smokers. A single stent was placed in 63%, two stents in 33%, and more than two stents in 4% of the patients. Procedural success was obtained in 97% of the patients. All stents were deployed using high-pressure balloon inflation. The reference vessel diameter and minimal lumen diameter after stent deployment were 3.30 +/- 0.42 and 3.23 +/- 0.42 mm, respectively. Six patients (5.7%) developed stent thrombosis within 1 month after the procedure complicated by reinfarction in five of the six patients. At 1-month follow-up, all patients remained alive. On multivariate analysis, independent predictors of stent thrombosis were diabetes mellitus (relative risk [RR] 5.2; 95% confidence interval [CI] 1.8, 25.1), tobacco use (RR 4.5; 95% CI 1.3, 24.5), number of stents: 1 vs. > 1 (RR 3.7; 95% CI 1.1, 15.9), minimal lumen diameter poststent placement (RR 0.03; 95% CI 0.0002, 0.74), and duration of chest pain before intervention (RR 1.1; 95% CI 1.01, 1.25). Stent thrombosis had not been associated with diabetes mellitus and tobacco use previously but is in agreement with the enhanced platelet aggregability, coagulation factor abnormalities, and impaired fibrinolysis characteristic of these patients.
Abstract: In 111 patients with left ventricular ejection fraction < or =30% who required hospitalization for heart failure, we examined the association between outpatient dose of diuretic agents and all-cause mortality. In comparison to patients who were not on treatment with diuretics prior to hospitalization, patients being treated with 'low' doses of diuretics (<80 mg/day of furosemide) and those being treated with 'high' doses of diuretics (> or =80 mg/day of furosemide) were more likely to die during follow-up after adjustment for other clinical parameters (adjusted relative risks, RR, 3.1 and 4.6).
Abstract: OBJECTIVE: To delineate hypertension-related and age-related changes in coronary hemodynamics and to assess the role of myocardial (i.e. left ventricular) hypertrophy and cardiac fibrosis in inducing progressive deterioration of coronary flow reserve associated both with hypertension and with aging. METHODS: Systemic and coronary hemodynamics (using radionuclide-labeled microspheres), right ventricular, left ventricular, and aortic mass indexes, and ventricular hydroxyproline concentrations (an estimate of collagen) in normotensive Wistar-Kyoto and spontaneously hypertensive rats aged 22, 35, and 65 weeks were determined. RESULTS: Spontaneously hypertensive rats of all ages had greater left ventricular and aortic masses, greater collagen concentrations in both ventricles, a lower coronary flow reserve, and greater minimal coronary vascular resistance after administration of dipyridamole than did Wistar-Kyoto rats. Despite spontaneously hypertensive rats having only left ventricular hypertrophy, coronary hemodynamics were impaired to the same extent in both ventricles. Progressive increases in myocardial collagen concentration, decreases in coronary flow reserve, and increases in minimal coronary vascular resistance were observed in rats of both strains with aging. A positive correlation and linear regression between myocardial collagen concentration and minimal vascular resistance were found for both ventricles of rats of both strains. CONCLUSIONS: Both aging and hypertension adversely affected the coronary circulation; furthermore, these effects appeared to be additive. Cardiac fibrosis, but not hypertrophy, might play a role in progressive deterioration of coronary hemodynamics in aging and hypertension and could provide an explanation for the diastolic dysfunction encountered clinically in older patients with hypertension.
Abstract: We describe a patient with a clinical presentation of moderate renal dysfunction, recurrent hospitalizations for congestive heart failure, and an episode of abrupt-onset pulmonary edema (flash pulmonary edema). Diagnostic angiography revealed triple-vessel coronary artery disease (CAD) and bilateral severe renal artery stenosis. This patient underwent successful bilateral renal artery stent implantation with marked improvement in his functional class without further recurrence of pulmonary edema.
Abstract: Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-angiotensin system (RAS) inhibitor would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 microns radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total peripheral resistance. The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Although enalapril did not improve coronary flow reserve (CFR), it diminished minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. In conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.
Abstract: The cardiovascular effects of a combination of trandolapril and verapamil were evaluated in 14 patients with mild to moderate essential hypertension. This combination therapy decreased arterial pressure mainly through a decrease in total peripheral resistance without causing an increase in heart rate or cardiac output: left ventricular mass was significantly reduced, cardiac systolic function improved, and plasma volume and renal blood flow remained unchanged.
Abstract: The present study was designed to compare the effects of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists-the two drug classes thought to be most effective in reducing left ventricular hypertrophy-on arterial pressure, left ventricular structure and function in patients with essential hypertension. After a placebo period of 4 weeks, a population of 96 patients were treated either with one of five different ACE inhibitors or one of six different calcium antagonists. Cardiac structure and function was assessed by 2D-guided M-mode echocardiography. Whereas both drug classes lowered arterial pressure to the same extent, ACE inhibitors had a more pronounced effect on posterior and septal wall thickness and left ventricular mass index than calcium antagonists. Diastolic function, as measured by peak filling rate and duration of rapid filling, improved in both treatment groups to the same extent. However, systolic performance, as assessed by midwall fractional fibre shortening, was significantly improved by ACE inhibitors only. Myocardial contractility (end-systolic wall stress/end-systolic volume index) showed no significant change in the ACE inhibitor group but decreased after treatment with calcium antagonists. We conclude that both calcium antagonists and ACE inhibitors lower arterial pressure and increase left ventricular filling to the same extent. However, compared with calcium antagonists, ACE inhibitors had a more pronounced effect on left ventricular mass and improved systolic ventricular performance in patients with essential hypertension.
Abstract: Systemic and regional (including coronary) hemodynamics were studied in spontaneously hypertensive and normotensive Wistar Kyoto rats after 3 weeks of treatment with one of the three doses of the angiotensin converting enzyme inhibitor, ramipril. The effects of respective treatments on cardiovascular mass and systemic, coronary, and regional hemodynamics (at rest, during maximal treadmill exercise, and during dipyridamole infusion) then were evaluated in conscious rats using radiomicrosphere techniques. Low-dose ramipril (10 micrograms/kg/day by gavage) neither decreased arterial pressure nor reduced cardiac mass. However, medium (100 micrograms/kg/day) and high (1 mg/kg/day) doses reduced total cardiac and left ventricular masses to the same extent in spontaneously hypertensive rats, despite a much greater fall in arterial pressure with a high dose. Resting cardiac index, and myocardial and all other organ blood flows remained unchanged in both strains. When compared with Wistar Kyoto rats, coronary circulation was impaired in untreated spontaneously hypertensive rats (ie, reduced coronary flow and flow reserve and increased minimal coronary vascular resistance during dipyridamole infusion). This remained unchanged by ramipril. Furthermore, significant (and comparable) increases in cardiac index and myocardial blood flow and decreases in coronary vascular resistance were produced by maximal treadmill exercise in both strains. This also was unaffected by ramipril. These data showed that angiotensin converting enzyme inhibition with suboptimal and optimal hypotensive doses of ramipril reversed left ventricular hypertrophy in spontaneously hypertensive rats, but coronary flow, flow reserve, and minimal coronary vascular resistance remained unchanged despite left ventricular hypertrophy reversal.
Abstract: OBJECTIVES: To evaluate the effects of losartan administration on cardiovascular mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and dipyridamole infusion) and on resting regional hemodynamics in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. RESULTS: Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventricular mass at the higher dose in WKY rats and with both doses in SHR, only the higher dose reduced arterial pressure in SHR. Losartan administration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in cardiac index and coronary flow and decreases in coronary vascular resistance were observed during exercise in both strains and these responses were not affected by losartan administration. Compared with those in WKY rats, coronary flow and flow reserve (dipyridamole) were decreased and minimal coronary vascular resistance was increased in untreated SHR. Administration of a higher losartan dose increased coronary flow reserve and decreased minimal coronary vascular resistance (measured during dipyridamole infusion) in SHR. CONCLUSIONS: These data demonstrated that losartan administration reduced left ventricular mass, a response that did not seem to be solely dependent on afterload. Furthermore, cardiac and stroke indices and coronary flow reserve were not changed in SHR during maximal treadmill exercise after hypertrophy reversal, even with the lower dose of losartan and when the ventricular afterload was similar to that of untreated SHR.
Abstract: We studied the effect of chronic (7 days) angiotensin II (Ang II) infusion in nonpressor and pressor doses on cardiovascular mass and expression of alpha- and beta-myosin heavy chain genes in the left ventricle in normotensive Wistar rats. An increased left ventricular mass was observed in rats receiving non-pressor and pressor doses of Ang II, but only high doses increased arterial pressure. Normalization of arterial pressure during Ang II infusion by losartan, a specific Ang II receptor antagonist, or hydralazine had different effects on left ventricular mass. Losartan prevented the increased left ventricular mass, and hydralazine did not affect left ventricular mass. Northern blot analysis showed that the switch in left ventricular myosin isoform mRNA from the adult to the fetal pattern occurred only in rats given the pressor Ang II dose. Both losartan and hydralazine, in parallel with the normalization of arterial pressure, prevented this myosin isoform switch. Thus, these data suggest that the Ang II-induced increase in left ventricular mass was not dependent on pressure overload, but the switch in myosin isoform mRNA from the adult to the fetal pattern was dependent on pressure overload.
Abstract: Evidence from in vivo, in vitro, and genetic studies suggests that the reversal as well as the development of left ventricular hypertrophy do not depend solely on hemodynamic load; other factors are involved. Several humoral agents that may affect mitogenesis of cardiac myocytes and nonmyocitic elements have been identified, including the local renin-angiotensin system, norepinephrine, endothelins, transforming growth factor beta, insulin-like growth factor, bradykinin, prostaglandins, and nitric oxide. Animal studies using various models of left ventricular hypertrophy are beginning to suggest that reversal of hypertrophy may decrease mortality, improve coronary flow reserve, and maintain cardiac performance. Studies in humans are less supportive, and more are needed before it may be concluded that reduction of left ventricular mass decreases the cardiovascular morbidity and mortality associated with cardiac hypertrophy.
Abstract: Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hydralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action.
