- Benefits and Risks of Corticosteroid Prophylaxis in Adult Cardiac Surgery: A Dose-Response Meta-Analysis
- Early Diagnosis and Treatment of Atrioventricular Block in the Fetus Exposed to Maternal Anti-SSA/Ro-SSB/La Antibodies: A Prospective, Observational, Fetal Kinetocardiogram–Based Study
- Baseline Risk of Major Bleeding in Non–ST-Segment–Elevation Myocardial Infarction: The CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Bleeding Score
- Prognostic Value of Changes in the Electrocardiographic Strain Pattern During Antihypertensive Treatment: The Losartan Intervention for End-Point Reduction in Hypertension Study (LIFE)
- Four Blood Pressure Indexes and the Risk of Stroke and Myocardial Infarction in Japanese Men and Women: A Meta-Analysis of 16 Cohort Studies
- Elevated Admission Glucose and Mortality in Elderly Patients Hospitalized With Heart Failure
- Kidney Androgen-Regulated Protein Transgenic Mice Show Hypertension and Renal Alterations Mediated by Oxidative Stress
- Reduced Myocardial Creatine Kinase Flux in Human Myocardial Infarction: An In Vivo Phosphorus Magnetic Resonance Spectroscopy Study
- Molecular Imaging of Innate Immune Cell Function in Transplant Rejection
- Abciximab in Patients With Acute ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention After Clopidogrel Loading: A Randomized Double-Blind Trial
- Transgenic Overexpression of Aldehyde Dehydrogenase-2 Rescues Chronic Alcohol Intake–Induced Myocardial Hypertrophy and Contractile Dysfunction
- Fatal and Nonfatal Cardiovascular Disease and the Use of Therapies for Secondary Prevention in a Rural Region of India
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Benefits and Risks of Corticosteroid Prophylaxis in Adult Cardiac Surgery: A Dose-Response Meta-Analysis
Corticosteroid prophylaxis in cardiac surgery has been studied extensively for >30 years, but its potential benefits and risks remain inconclusive. Small sample sizes and a wide range of doses of corticosteroid used in different studies are the major confounders affecting the interpretation of these studies. We assessed the dose-response relationship of corticosteroid in adult on-pump cardiac surgery by meta-analyzing a total of 3323 patients from 50 randomized controlled trials. Corticosteroid prophylaxis was effective in reducing serum inflammatory markers, atrial fibrillation, and length of stay in the intensive care unit and hospital compared with placebo. The number of patients needed to treat to prevent 1 atrial fibrillation was estimated to be 10. No additional benefits were found on all outcomes beyond a total dose of 1000 mg hydrocortisone or equivalent. The use of corticosteroid prophylaxis was not associated with a change in hospital mortality or an increased risk of all-cause infection. The sample size of this meta-analysis has a power of 80% to exclude a 3.5% increase in infection risk if the infection rate of the control group is 5%. Hyperglycemia requiring insulin infusion, however, was common after corticosteroid prophylaxis, and very high doses of corticosteroid (>10 000 mg hydrocortisone or equivalent) were associated with prolonged mechanical ventilation. The current evidence suggests that low-dose corticosteroid, <1000 mg hydrocortisone, is safe and effective in reducing the risk of atrial fibrillation after on-pump adult cardiac surgery. Large randomized controlled studies are needed to confirm the cost-effectiveness of corticosteroid in adult cardiac surgery. See p 1853.
Early Diagnosis and Treatment of Atrioventricular Block in the Fetus Exposed to Maternal Anti-SSA/Ro-SSB/La Antibodies: A Prospective, Observational, Fetal Kinetocardiogram–Based Study
Fetal exposure to maternal anti-SSA/Ro or anti-SSB/La antibodies (or both) results in a 2% to 5% risk of complete AV block, with up to 30% risk of intrauterine mortality; thus, detection of the first signs of AV conduction prolongation (first-degree AV block) is mandatory. We used a tissue velocity–based fetal kinetocardiogram for accurate measurement of AV conduction time. We assessed AV conduction in 109 normal fetuses to define the range for normal fetal AV conduction and measured AV conduction from gestational weeks 13 to 40 in 70 fetuses exposed to maternal anti-SSA/Ro and/or SSB/La antibodies. Median acquisition and measurement time was 3 minutes. First-degree AV block, defined as >2 z-score prolongation of AV conduction, was found in 6 exposed fetuses (8.6%). Dexamethasone was administered to their mothers. Fetal AV conduction returned to normal within 4 to 14 days. All fetuses, including these 6, were normal after delivery. None had or developed AV block at 2 to 7 years of follow-up. We believe that tissue velocity imaging is a robust and accurate method for early diagnosis of first-degree AV block in fetuses. Although dexamethasone appeared to have a positive effect on the 6 affected fetuses, the effect of dexamethasone was not the purpose of the present study. Further prospective studies are needed to assess of the role of dexamethasone in the treatment of fetal AV block. See p 1867.
Baseline Risk of Major Bleeding in Non–ST-Segment–Elevation Myocardial Infarction: The CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Bleeding Score
With renewed emphasis in the American College of Cardiology/American Heart Association non–ST-segment–elevation acute coronary syndrome practice guidelines on patient risk stratification and an expanding array of antithrombotic therapies with varying bleeding hazards, consideration of both safety and efficacy may improve selection of optimal treatment strategies for patients with non–ST-segment elevation myocardial infarction. The Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) bleeding score complements existing ischemic risk stratification tools by providing an assessment of baseline bleeding risk. The CRUSADE bleeding score combines 8 readily available variables (baseline hematocrit, creatinine clearance, female sex, diabetes, peripheral vascular disease, signs of heart failure, systolic blood pressure, and heart rate on admission) into a validated bleeding risk score (range 1 to 100 points). This score stratifies baseline bleeding risk across quintiles: Very low risk (score ≤20), low risk (21 to 30), moderate risk (31 to 40), high risk (41 to 50), and very high risk (>50). In CRUSADE, observed rates of major in-hospital bleeding across quintiles of risk were 3.1% (very low risk), 5.5% (low risk), 8.6% (moderate risk), 11.9% (high risk), and 19.5% (very high risk). By providing an estimation of baseline risk of bleeding, application of the CRUSADE bleeding score will better equip providers to consider the safety and efficacy implications of various treatment strategies for a patient with non–ST-segment–elevation myocardial infarction. See p 1873.
Prognostic Value of Changes in the Electrocardiographic Strain Pattern During Antihypertensive Treatment: The Losartan Intervention for End-Point Reduction in Hypertension Study (LIFE)
This study demonstrates that development of a new ECG strain pattern of lateral ST depression and T-wave inversion in lead V5 or V6 between baseline and year 1 during the LIFE study (Losartan Intervention For End-point reduction in hypertension) identifies patients at increased risk of cardiovascular morbidity and mortality, sudden cardiac death, and all-cause mortality in the setting of antihypertensive therapy associated with substantial decreases in both systolic and diastolic pressure. The increased risk associated with new ECG strain was independent of the improved prognosis with losartan therapy and with regression of ECG left ventricular hypertrophy in the LIFE study and persisted after adjustment for the greater baseline severity and prevalence of ECG left ventricular hypertrophy and the higher prevalence of other cardiovascular disorders associated with ECG strain. The independent relation of new ECG strain to increased risk in the LIFE study despite aggressive blood pressure reduction suggests that the development of new strain on the ECG may be used to identify hypertensive patients with ECG left ventricular hypertrophy who require more aggressive antihypertensive therapy aimed at further risk reduction. Further research will be required to determine whether additional treatment in patients with new ECG strain will improve prognosis in this high-risk group of hypertensive patients. See p 1883.
Four Blood Pressure Indexes and the Risk of Stroke and Myocardial Infarction in Japanese Men and Women: A Meta-Analysis of 16 Cohort Studies
Information has been sparse on the comparison of 4 blood pressure (BP) indexes (systolic BP, diastolic BP, pulse pressure, and mean BP) in relation to long-term incidence of stroke and myocardial infarction, particularly in middle-aged and older Asians. The present meta-analysis of 16 cohort studies investigated >1000 stroke events and 200 myocardial infarction events from >400 000 person-years of follow-up in middle-aged and older Japanese men and women. For predicting all stroke, ischemic stroke, and myocardial infarction, mean BP or systolic BP was generally the strongest and pulse pressure was the weakest in any of the age-sex groups. For hemorrhagic stroke, mean BP was the strongest predictor in both sexes, and in men, diastolic BP was more important than systolic BP. Pulse pressure was not the strongest of the 4 BP indexes for any subtype of stroke in any of the age-sex groups, including older people. For the primary prevention of cardiovascular diseases in East Asian populations, the long-term risk of stroke and myocardial infarction should be assessed mainly by systolic BP. Diastolic BP should also be given careful consideration for its independent relationship to stroke risk. Emphasis on pulse pressure should be avoided even in older people for the prediction of future cardiovascular disease risk. Although mean BP was important in addition to systolic BP, use of this index may not be practical in daily clinical and public health practice at present. See p 1892.
Elevated Admission Glucose and Mortality in Elderly Patients Hospitalized With Heart Failure
Although some professional societies recommend target-driven glucose control for all hospitalized patients, the association between elevated glucose and adverse outcomes has not been well established in patients hospitalized with heart failure. We studied 50 532 elderly patients hospitalized with heart failure in the United States from April 1998 to June 2001. Multivariable Cox proportional-hazards regression models were used to examine the relationship between admission glucose and all-cause mortality at 30 days and 1 year. We found no significant relationship between glucose levels and mortality at either 30 days or 1 year. This lack of association between admission glucose and mortality was similar across various patient subgroups, including those with and without diabetes mellitus. These findings suggest that the relationship between hyperglycemia and adverse outcomes seen in acute myocardial infarction cannot be automatically extended to patients hospitalized with other cardiovascular conditions. See p 1899.
Kidney Androgen-Regulated Protein Transgenic Mice Show Hypertension and Renal Alterations Mediated by Oxidative Stress
These data demonstrate for the first time a key role of the kidney androgen-regulated protein (KAP) in the regulation of responses outside the kidney, and they link the function of KAP with hypertension. The present study provides one of the first mechanistic insights to explain the higher prevalence of hypertension in a sexually dimorphic manner on the basis of a molecule expressed exclusively in kidney that is also able to affect the cardiovascular system. It also connects KAP with oxidative stress, another key mechanism of cardiovascular disease and hypertension. In summary, these data may shed some light on the gender-related molecular mechanisms underlying essential hypertension, an increasingly prevalent disease in highly developed countries that remains elusive at the pathophysiological level, and they suggest KAP as a possible target for therapeutic interventions. See p 1908.
Reduced Myocardial Creatine Kinase Flux in Human Myocardial Infarction: An In Vivo Phosphorus Magnetic Resonance Spectroscopy Study
Contractile dysfunction in patients with myocardial infarction (MI) may be due to cell loss, abnormal metabolism in surviving tissue, or a mix of both. The creatine kinase (CK) reaction serves as the major energy reserve of the heart, providing adenosine triphosphate (ATP) via phosphocreatine (PCr) to fuel contractile function. The CK forward pseudo–first-rate constant for generating ATP is a measure of intracellular metabolism and is independent of the number of myocytes. To determine whether intracellular CK metabolism is preserved after MI, we used, for the first time, a new magnetic resonance spectroscopy technique to directly measure the CK reaction rate constant, forward CK flux, PCr, and ATP concentrations in patients with prior anterior MI. We found that the primary effect of MI on CK metabolism is a reduction in PCr and ATP, which reduces the forward CK flux for generating ATP in the infarcted area. However, the CK reaction rate constant and the PCr/ATP ratio remain essentially intact. The results are consistent with metabolite loss in infarcted areas but preservation of near-normal intracellular metabolism in residual noninfarcted tissue. Importantly, the results support therapies that primarily ameliorate the effects of tissue loss on metabolite depletion and those that reduce energy demand after MI rather than those that affect energy transfer, which does not appear to be significantly depressed in surviving myocytes, or those that increase the energy demand on the surviving tissue. See p 1918.
Molecular Imaging of Innate Immune Cell Function in Transplant Rejection
Since the advent of effective immunosuppressive regimens, cardiac transplantation has become a routine treatment of end-stage heart failure. Acute rejection episodes occur in most heart transplant recipients during the first year after surgery, and their severity and frequency seem to predict the long-term survival of the graft. Thus, rapid and precise detection of graft rejection is vital. Repetitive invasive endomyocardial biopsies remain the most commonly performed diagnostic test but are invasive, increase morbidity, and have a considerable sampling error. The development of a noninvasive yet quantitative diagnostic tool to identify graft rejection would significantly improve the care of heart transplant recipients. Assessing macrophage-host responses by the use of recently developed molecular and cellular imaging techniques could provide a noninvasive alternative. As a result of the uncertainty about which macrophage functions provide the most useful markers for detecting parenchymal rejection, we compared 2 imaging probes reporting on key macrophage functions, protease activity and phagocytosis. In vivo imaging with both probes provided a functional 3-dimensional map of macrophage accumulation, with the signal intensity correlated to the severity of graft rejection. The imaging approaches described here could advance the investigation of novel therapeutic strategies and the longitudinal assessment of individualized immunosuppressive regimens, and their application may well facilitate the monitoring of transplant recipients. See p 1925.
Abciximab in Patients With Acute ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention After Clopidogrel Loading: A Randomized Double-Blind Trial
Several previous randomized trials have shown that the glycoprotein IIb/IIIa receptor inhibitor abciximab can improve outcomes after primary percutaneous coronary interventions in patients with acute ST-segment–elevation myocardial infarction. A high loading dose of clopidogrel is increasingly being used before primary percutaneous coronary intervention. The role of abciximab has not been investigated in patients undergoing primary percutaneous coronary intervention if given after clopidogrel loading. The aim of the Bavarian Reperfusion Alternatives Evaluation-3 (BRAVE-3) trial was to assess whether upstream administration of abciximab reduces infarct size in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention after treatment with 600 mg clopidogrel. Left ventricular infarct size was measured by single-photon emission computed tomography with technetium-99m sestamibi performed before discharge. Of the 800 patients enrolled in this multicenter, double-blind, placebo-controlled randomized trial, 401 patients were assigned to receive abciximab plus a reduced dose of heparin and 399 patients to receive placebo plus a full dose of heparin. Full restoration of flow in the infarct-related artery was achieved in comparable proportions of patients in both groups. Administration of abciximab was not associated with a reduction in infarct size. In addition, this drug did not reduce the combined incidence of all-cause death, recurrent myocardial infarction, stroke, and urgent revascularization of the infarct-related artery over 30 days after randomization. Therefore, abciximab administration might not be needed in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention after loading with 600 mg clopidogrel. See p 1933.
Transgenic Overexpression of Aldehyde Dehydrogenase-2 Rescues Chronic Alcohol Intake–Induced Myocardial Hypertrophy and Contractile Dysfunction
Almost 1 of every 3 alcoholics displays some degree of heart problems, collectively known as alcoholic cardiomyopathy. The present study shows that the ALDH2 enzyme is capable of mitigating cardiac remodeling and myocardial dysfunction after chronic alcohol ingestion, possibly through facilitated acetaldehyde detoxification. Blood acetaldehyde levels are ≈10-fold higher in humans with defective ALDH2 (eg, Asians and blacks) than in normal individuals after alcohol ingestion. Allelic variation of ALDH genes, especially ALDH2 due to a point mutation in the active ALDH2*1 gene, significantly alters vulnerability for alcoholism and alcoholic complications; however, the jury is still out as to whether elevated acetaldehyde levels are directly involved in the origin of alcoholic cardiomyopathy or are simply the result of alcohol metabolism. The present study, which used transgenic mice with overexpression of ALDH2, provides the first evidence that facilitated acetaldehyde detoxification alone is sufficient to reverse the cardiac remodeling processes that lead to alcoholic cardiomyopathy. Results obtained in the present study support the conclusion that elevated acetaldehyde levels participate in cardiac remodeling and contractile defects, perhaps through NADPH oxidase–mediated oxidative stress and activation of hypertrophic signaling molecules. These data indicated that ALDH2 may be cardioprotective and counteract cardiac remodeling and myocardial dysfunction after chronic alcohol intake, thus providing its therapeutic potential in alcoholic and other forms of myocardial damage. Because convincing human case studies on the interaction between the ALDH2 gene polymorphism and heart function after chronic alcohol intake are lacking, caution must be exercised when evaluating the role of acetaldehyde and ALDH2 in the pathogenesis and management of alcoholic cardiomyopathy. See p 1941.
Fatal and Nonfatal Cardiovascular Disease and the Use of Therapies for Secondary Prevention in a Rural Region of India
India, the second most populous country in the world, is undergoing rapid epidemiological transition, and vascular disease is known to be a major health issue in urban areas. However, 70% of India’s population resides in rural regions where data about cardiovascular disease are scant. A comprehensive survey of mortality and morbidity in 53 villages in rural Andhra Pradesh showed that cardiovascular disease was the leading cause of mortality, responsible for at least 32% of all deaths. The average age at cardiovascular death was 65 years, and 51% of all cardiovascular deaths occurred in patients <70 years of age. The prevalence of coronary heart disease among adults ≥30 years of age was also high, estimated to be 4.8%. Prevalent cerebrovascular disease was present in a further 2.0%. Few individuals with a history of vascular disease were using proven preventive treatments; only 14% (95% CI, 10 to 18) were taking aspirin, 41% (95% CI, 36 to 47) were on a blood pressure–lowering medication, and 5% (95% CI, 3 to 7) were taking a cholesterol-lowering medication. Secondary prevention has been identified as a cost-effective vascular disease management strategy for low- and middle-income countries. The challenge now is to identify service delivery mechanisms that can provide these proven low-cost therapies to the very large number at risk. With access to healthcare facilities limited by both availability and capacity to pay, novel nonphysician-based approaches to vascular prevention that use existing facilities may have an important role to play. See p 1950.
- Elevated Admission Glucose and Mortality in Elderly Patients Hospitalized With Heart Failure
- Molecular Imaging of Innate Immune Cell Function in Transplant Rejection
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