Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease.

BACKGROUND: Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs) in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE) in men with coronary artery disease. METHODS: We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. RESULTS: All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E'), consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red), or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyl)lysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. CONCLUSIONS: Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the myocardial microvascular structure, or increased myocardial expression of Nε-(carboxymethyl)lysine or RAGE. These findings suggest that the increased myocardial fibrosis and AGE expression, cardiomyocyte hypertrophy, and altered microvasculature structure described in diabetic heart disease were a consequence, rather than an initiating cause, of cardiac dysfunction.

Factors Affecting Emergency Department Crowding.

Emergency department crowding is a multifactorial issue with causes intrinsic to the emergency department and to the health care system. Understanding that the causes of emergency department crowding span this continuum allows for a more accurate analysis of its effects and a more global consideration of potential solutions. Within the emergency department, boarding of inpatients is the most appreciable effect of hospital-wide crowding, and leads to further emergency department crowding. We explore the concept of emergency department crowding, and its causes, effects, and potential strategies to overcome this problem.

Effects of eliminating routine use of oral contrast for computed tomography of the abdomen and pelvis: A pilot study.

INTRODUCTION: Computed tomography (CT) of the abdomen and pelvis using only intravenous contrast has been shown to have a high degree of accuracy in evaluating abdominal pain. The aim of this study was to determine the effect on time to completion of study, time to radiologist read, and length of stay in the emergency department (ED) of implementing a protocol that stopped the routine use of oral contrast for CT of the abdomen and pelvis. METHODS: This was a single-center, retrospective cohort study. All patients ≥18 years of age who presented to the ED and required a CT of the abdomen and pelvis during the hours 0700-1500 were included. There were two one-month study periods, before and after implementing a protocol that specified oral contrast should only be used for CT scans of the abdomen and pelvis if body mass index <25 kg/m2 or age < 30 years, or if there was history of inflammatory bowel disease, gastrointestinal surgery, or suspected bowel malignancy. RESULTS: During the pre- and post-implementation periods, there were 93 and 83 patients, respectively, with mean times to CT completion of 158 min and 135 min, representing a reduction of 23 min (15%). The mean lengths of stay in the pre- and post-implementation periods were 365 min and 336 min, a decrease of 29 min (8%). CONCLUSION: A protocol without the routine use of oral contrast for CT of the abdomen and pelvis can result in improved time to completion and ED length of stay.

Bedside echocardiography for undifferentiated hypotension: diagnosis of a right heart thrombus.

A free-floating right heart thrombus is often a harbinger of a massive pulmonary embolism and must be diagnosed and treated rapidly in order to avoid significant adverse sequelae. We present the case of an 84-year-old female who presented with two days of dyspnea and was hypotensive on arrival. Bedside ultrasound was performed by the emergency physician and showed a large, mobile right heart thrombus leading to immediate administration of a thrombolytic. In this case, bedside ultrasound was utilized to help further delineate clinical care in a progressively worsening patient, leading to a potentially lifesaving treatment.

Obesity is associated with lower coronary microvascular density.

BACKGROUND: Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure. METHODS: We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy. RESULTS: Non-obese (body mass index, BMI, ≤ 30 kg/m(2), n=33) and obese patients (BMI >30 kg/m(2), n=24) did not differ with respect to myocardial total, interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte width. Obese patients had lower capillary length density (1145 ± 239, mean ± SD, vs. 1371 ± 333 mm/mm(3), P=0.007) and higher diffusion radius (16.9 ± 1.5 vs. 15.6 ± 2.0 µm, P=0.012), in comparison with non-obese patients. However, the diffusion radius/cardiomyocyte width ratio of obese patients (0.73 ± 0.11 µm/µm) was not significantly different from that of non-obese patients (0.71 ± 0.11 µm/µm), suggesting that differences in cardiomyocyte width explained in part the differences in capillary length density and diffusion radius between non-obese and obese patients. Increased BMI was associated with increased pulmonary capillary wedge pressure (PCWP, P<0.0001), and lower capillary length density was associated with both increased BMI (P=0.043) and increased PCWP (P=0.016). CONCLUSIONS: Obesity and its accompanying increase in left ventricular filling pressure were associated with lower coronary microvascular density, which may contribute to the lower maximal myocardial blood flow, impaired myocardial metabolism, diastolic dysfunction and higher risk of heart failure in obese individuals.

Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction.

BACKGROUND: Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. METHODS: We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. RESULTS: Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. CONCLUSIONS: Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers.

Diastolic dysfunction of aging is independent of myocardial structure but associated with plasma advanced glycation end-product levels.

BACKGROUND: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. METHODS: We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. RESULTS: The patients were aged 43-78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e' (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e' was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e' (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e' remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate. CONCLUSIONS: Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.

Differences in myocardial structure and coronary microvasculature between men and women with coronary artery disease.

Women younger than 75 years with stable angina or acute coronary syndrome have higher cardiac mortality than similarly aged men, despite less obstructive coronary artery disease. To determine whether the myocardial structure and coronary microvasculature of women differs from that of men, we performed histological analysis of biopsies from nonischemic left ventricular myocardium from 46 men and 11 women undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation, or furosemide therapy. The 2 patient groups had similar clinical characteristics, apart from a lower body surface area (BSA) in women (P = 0.0015). Women had less interstitial fibrosis than men (P = 0.019) but similar perivascular fibrosis. Arteriolar wall area/circumference ratio, a measure of arteriolar wall thickness, was 47% greater in women than men (P = 0.012). Cardiomyocyte width and diffusion radius were positively correlated, and capillary length density was negatively correlated with BSA (P < 0.05). Whereas cardiomyocyte width, capillary length density, diffusion radius, and cardiomyocyte width/BSA ratio were similar for men and women, women had a greater diffusion radius/BSA ratio (P = 0.0038) and a greater diffusion radius/cardiomyocyte width ratio (P = 0.027). Women also had lower vascular endothelial growth factor (VEGF) receptor-1 levels (P = 0.048) and VEGF receptor-1/VEGF-A ratio (P = 0.024) in plasma. We conclude that women with extensive coronary artery disease have greater arteriolar wall thickness and diffusion radius relative to BSA and to cardiomyocyte width than men, which may predispose to myocardial ischemia. Additional studies of larger numbers of women with less extensive coronary artery disease are required to confirm these findings.

Surgical treatment of ruptured metastatic pleomorphic leiomyosarcoma.

A rare case of primary cardiac leiomyosarcoma was diagnosed in a 21-year-old man who presented with a groin mass thought to be a sebaceous cyst. Histopathology revealed a high-grade pleomorphic leiomyosarcoma. Combined positron-emission and computed tomography showed a large metabolically active left atrial mass with multiple metastases. Major debulking resection was undertaken, followed by radiation and chemotherapy. At 13 months postoperatively, limited spread has been detected, and the patient had no limitation in daily life.

Resection of right atrial metastatic large-cell neuroendocrine carcinoma.

The incidence of cardiac metastases is rising due to increasingly sensitive diagnostic investigations and longer patient survival as a result of improved treatment for malignancies. We report a rare case of right atrial metastasis from a large cell neuroendocrine carcinoma successfully resected with cardiopulmonary bypass. The surgical management of advanced cardiac malignancy is discussed. In appropriately selected cases surgical resection of cardiac metastases can be beneficial, allowing improvement in quality of life, and prolongation of life.