Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Mortality and Neurologic Injury After Surgical Repair With Hypothermic Circulatory Arrest in Acute and Chronic Proximal Thoracic Aortic Pathology: Effect of Age on Outcome
- Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease
- Peroxisome Proliferator-Activated Receptor Pathway Gene Polymorphism Associated With Extent of Coronary Artery Disease in Patients With Type 2 Diabetes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial
- Heart Disease May Be a Risk Factor for Pulmonary Embolism Without Peripheral Deep Venous Thrombosis
- Exercise Oscillatory Ventilation in Systolic Heart Failure: An Indicator of Impaired Hemodynamic Response to Exercise
- Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction Are Associated With Exercise Intolerance in Adults and Adolescents With Homozygous Sickle Cell Anemia in the United States and United Kingdom
- Long-Term Outcome of Patients With Isolated Thin Discrete Subaortic Stenosis Treated by Balloon Dilation: A 25-Year Study
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Mortality and Neurologic Injury After Surgical Repair With Hypothermic Circulatory Arrest in Acute and Chronic Proximal Thoracic Aortic Pathology: Effect of Age on Outcome
The aim of this study was to determine whether advanced age affects mortality and incidence of neurological injury in patients undergoing surgical repair with hypothermic circulatory arrest in acute and chronic thoracic aortic pathology. Between 2005 and 2010, 523 patients underwent surgical repair with hypothermic circulatory arrest for repair of acute and chronic proximal thoracic aortic pathology at our institution. Our results show that age is not associated with increased risk for mortality and neurological injury in patients undergoing surgical repair for acute and chronic thoracic aortic pathology with hypothermic circulatory arrest. Extended hypothermic circulatory arrest times, reflecting the extent of disease, and redo surgery predict mortality; emergency surgery and extracardiac arteriopathy predict neurological injury. These data should encourage clinicians to refer elderly patients with acute and chronic thoracic aortic pathology for surgical therapy because the risk for mortality and neurological injury is consistently low even in patients with advanced age. See p 1407.
Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease
There is no angiographically demonstrable obstructive coronary artery disease in a substantial proportion of patients with myocardial infarction, particularly women. Plaque rupture has long been hypothesized to be a cause of myocardial infarction with nonobstructive coronary artery disease. We sought to determine the mechanism(s) of myocardial infarction in this setting using intravascular ultrasound during angiography and cardiac magnetic resonance imaging performed within 1 week. Fifty women were enrolled with median worst coronary angiographic stenosis of 20% and median peak troponin of 1.60 ng/mL. Plaque disruption (rupture and/or ulceration) was found on blinded core laboratory intravascular ultrasound review in 38% of patients tested. Late gadolinium enhancement (LGE) was identified in 39% and abnormal T2 signal in 53% of women undergoing cardiac magnetic resonance imaging. The most common LGE pattern was ischemic (transmural/subendocardial). Nonischemic (midmyocardial/subepicardial) and mixed LGE patterns were also observed. T2 signal hyperintensity was common and LGE was infrequent among patients with plaque disruption. We hypothesize that vasospasm of, embolism to, or flush occlusion of a branch vessel caused myocardial infarction in patients with an ischemic LGE pattern but without plaque disruption. Intravascular ultrasound and cardiac magnetic resonance imaging provided complementary information in this cohort and together revealed abnormalities in 35 of 50 patients (70%). In this study, the first prospective evaluation using intravascular ultrasound and cardiac magnetic resonance imaging in women with acute myocardial infarction and without obstructive coronary artery disease at angiography, we have demonstrated that plaque disruption is a frequent finding. We have also shown that LGE commonly identifies the location and pattern of myocardial damage and that acute myocardial edema is frequently present in these patients. See p 1414.
Peroxisome Proliferator-Activated Receptor Pathway Gene Polymorphism Associated With Extent of Coronary Artery Disease in Patients With Type 2 Diabetes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial
In patients with diabetes mellitus, atherosclerosis is more extensive and rapidly progressive. The reasons for this are not known but may relate in part to genetic variation that influences vascular disease severity. Using microarray technology to interrogate >3000 tagged single nucleotide polymorphism markers of peroxisome proliferator-activated receptor pathway genes, we have discovered a polymorphism in the TLL1 gene that is significantly associated with angiographic extent of coronary artery disease among patients with type 2 diabetes mellitus. This genetic polymorphism explains more variance of the phenotype than previously determined clinical factors. This association was initially observed in white patients with type 2 diabetes mellitus in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial and then validated specifically in the diabetic subgroups of 2 other independent white patient cohorts with quantitatively coronary imaging. TLL1 encodes a metalloproteinase that regulates procollagen processing and the metabolism of inhibitors of bone morphogenetic proteins involved with atherosclerotic calcification. These observations identify a novel putative genetic contributor to the biology of diabetic coronary atherosclerosis and suggest that targeting the TLL1/bone morphogenetic proteins pathway may afford specific therapeutic intervention for diabetic vascular disease. See p 1426.
Heart Disease May Be a Risk Factor for Pulmonary Embolism Without Peripheral Deep Venous Thrombosis
It is well established that heart diseases such as atrial fibrillation increase the risk of arterial embolism. However, whether heart diseases similarly increase the risk of pulmonary embolism without peripheral venous thrombosis is less certain. Using Danish medical databases, we conducted a nationwide population-based case-control study of 45 282 patients with embolism alone, 4680 patients with pulmonary embolism and lower-limb deep venous thrombosis, 59 790 with deep venous thrombosis alone, and 541 561 population controls. Myocardial infarction and heart failure in the preceding 3 months conferred remarkably high risks of apparently isolated pulmonary embolism, with odds ratios of 43.5 (95% confidence interval, 39.6–47.8) and 32.4 (95% confidence interval, 29.8–35.2), respectively. There was a particularly strong association of right-sided valvular disease with isolated pulmonary embolism (odds ratio, 74.6; 95% confidence interval, 28.4–195.8). We conclude that heart disease is associated with an increased short-term risk of venous thromboembolism, including isolated pulmonary embolism. Because common heart diseases may directly account for the development of pulmonary embolism, in patients with pulmonary embolism and no apparent deep venous thrombosis, cardiac sources of emboli should be considered and appropriate treatment instituted. See p 1435.
Exercise Oscillatory Ventilation in Systolic Heart Failure: An Indicator of Impaired Hemodynamic Response to Exercise
Cyclic fluctuations in minute ventilation during exercise, called exercise oscillatory ventilation (EOV), have been observed in 19% to 51% of patients with systolic heart failure (HF). When present, EOV potently predicts adverse outcomes in HF patients. However, mechanistic insights into EOV have been limited by the absence of studies relating EOV to invasive hemodynamic measurements and blood gases performed during exercise. Exercise oscillatory ventilation was present in 45% of HF subjects in this study and was closely related to elevated cardiac filling pressures and reduced cardiac index (CI) during exercise but not to Paco2 or Pao2. Multivariate logistic regression identified that low exercise CI is the strongest predictor of EOV (odds ratio, 1.39 for each 1.0-L · min · −1 · m−2 decrement in exercise CI; 95% confidence interval, 1.14–1.70; P=0.001). Among HF patients with EOV, exercise CI was also inversely related to the cycle length (R=−0.71) and amplitude (R=−0.60) of oscillations (both P<0.001). Exercise oscillatory ventilation cycle length and amplitude decreased proportionately to increases in CI in 11 HF patients with EOV who were treated with 12 weeks of sildenafil. Because EOV is an easily recognized, reproducible, noninvasive measurement than can be taken during submaximal exercise testing, it represents an attractive surrogate for exercise hemodynamic measurements, which are invasive and challenging to perform. By indicating an inadequate hemodynamic response to exercise (ie, impaired CI augmentation, increased filling pressures) independently of left ventricular ejection fraction, EOV may provide not only prognostic information but also an impetus to intensify therapy to optimize cardiac hemodynamics in HF subjects. See p 1442.
Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction Are Associated With Exercise Intolerance in Adults and Adolescents With Homozygous Sickle Cell Anemia in the United States and United Kingdom
Sickle cell disease, the most common inherited blood disorder in the United States, is a multisystem disease. It is characterized by episodes of acute illness; progressive organ damage in the spleen, joints, and kidneys as well as early mortality. Until recently, cardiopulmonary complications were not commonly recognized. With newer treatment options that prolong survival, clinical studies have shown that these patients also develop right and left heart dysfunction. Noninvasively measured elevations in pulmonary pressures and left ventricular diastolic dysfunction have been found to be independent predictors of mortality. In this observational study of 483 subjects with sickle cell disease, approximately one third had elevated pulmonary pressures by echocardiography. These patients had higher levels of hemolytic markers and serum erythropoietin and decreased renal function. Tissue Doppler–estimated filling pressures were used to assess diastolic dysfunction, and patients with a higher E/e′ ratio were older, had higher body mass index and systemic blood pressure, and had lower hemoglobin concentration. They also had higher pulmonary systolic pressure. Sickle cell disease patients can develop significant exercise limitations. In this cohort, women and older individuals were more likely to have a shorter 6-minute walk distance. Pulmonary pressure elevations and diastolic dysfunction were also independent predictors of a lower 6-minute walk distance. Both of these risk markers are now recognized as important parameters of poor outcome in sickle cell disease and may help target patients for future treatment studies. See p 1452.
Long-Term Outcome of Patients With Isolated Thin Discrete Subaortic Stenosis Treated by Balloon Dilation: A 25-Year Study
This study presents the longest follow-up analysis of a series of patients with isolated thin discrete subaortic stenosis treated by transluminal balloon tearing of the membrane. Selection of appropriate candidates for percutaneous treatment was an important issue, and only patients with a thin membrane at the outflow tract without a fibromuscular component were included. After a mean follow-up time of 16±6 years, 11 patients (15%) developed restenosis, 3 patients (4%) progressed to muscular obstructive disease, 1 patient (1.3%) developed a new distant obstructive membrane, and 4 patients (5%) underwent surgery at a mean of 3±2 years after their first treatment. Fifty-eight patients (77%) remained alive and free of redilation or surgery at follow-up. Larger annulus diameter and thinner membranes were independent factors associated with better long-term results. These findings, together with current improvements in image techniques for better delineation of the outflow tract, could help in the selection of patients who can benefit from an interventional procedure as a first-choice treatment. The recurrence rate in this selected group of patients may be similar to that observed in surgical patients, and both are probably influenced by the progressive nature of the disease. If restenosis of the membrane develops, balloon dilation can be repeated successfully in most patients. With this strategy, surgery for a thin membrane may be delayed or even avoided. See p 1461.
- © 2011 American Heart Association, Inc.
- Heart Disease May Be a Risk Factor for Pulmonary Embolism Without Peripheral Deep Venous Thrombosis
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