Transient cardiac apical ballooning syndrome: prevalence and clinical implications of right ventricular involvement.
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Adult↗
Biomedical subjects
Amir Lerman
Publications and source records attributed to Amir Lerman.
Women and cardiovascular heart disease: clinical implications from the Women's Ischemia Syndrome Evaluation (WISE) Study. Are we smarter?
Review of the trend in cardiovascular disease mortality for males and females clearly demonstrated that whereas the trend shows a decline in males this decline is not observed in females. Multiple important reports emerged from the initial phases of the Women's Ischemic Syndrome Evaluation (WISE) study that may have significant clinical implications for our approach to cardiovascular disease in women. The data derived from the WISE study certainly provided important information to our understanding of the approach to women with cardiovascular disease. The clinical presentation may be different, and a gender-oriented questionnaire may enhance our diagnosis. In a multivariable model, low hemoglobin was associated with significantly higher risk of adverse outcomes. The risk factor assessment and the risk factor profiles in women that are associated with coronary artery disease may be different. Based on the studies from the WISE study, metabolic syndrome is a leading and a major risk factor in women. Moreover, the data further support the concept that the mechanism of ischemia in women may be localized in the microvascular coronary arteries. Therefore, the diagnoses of coronary microvascular dysfunction or endothelial dysfunction should be considered in women with chest pain who do not have obstructive coronary artery disease. It may be advantageous to add such diagnostic tests when the conventional tests are nondiagnostic. A revised clinical approach to cardiovascular disease in women may be designed and tested based on these findings.
Cardiovascular Diseases↗
Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease.
Coronary heart disease is the leading cause of death and disability in the U.S., but recent advances have not led to declines in case fatality rates for women. The current review highlights gender-specific issues in ischemic heart disease (IHD) presentation, evaluation, and outcomes with a special focus on the results derived from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In the second part of this review, we will assess new evidence on gender-based differences in vascular wall or metabolic alterations, atherosclerotic plaque deposition, and functional expression on worsening outcomes of women. Additionally, innovative cardiovascular imaging techniques will be discussed. Finally, we identify critical areas of further inquiry needed to advance this new gender-specific IHD understanding into improved outcomes for women.
Atherosclerosis↗
Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies.
Despite a dramatic decline in mortality over the past three decades, coronary heart disease is the leading cause of death and disability in the U.S. Importantly, recent advances in the field of cardiovascular medicine have not led to significant declines in case fatality rates for women when compared to the dramatic declines realized for men. The current review highlights gender-specific issues in ischemic heart disease presentation, evaluation, and outcomes with a special focus on the results published from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. We will present recent evidence on traditional and novel risk markers (e.g., high sensitivity C-reactive protein) as well as gender-specific differences in symptoms and diagnostic approaches. An overview of currently available diagnostic test evidence (including exercise electrocardiography and stress echocardiography and single-photon emission computed tomographic imaging) in symptomatic women will be presented as well as data using innovative imaging techniques such as magnetic resonance subendocardial perfusion, and spectroscopic imaging will also be discussed.
Female↗
Chronic antioxidant supplementation impairs coronary endothelial function and myocardial perfusion in normal pigs.
Experimental studies have shown the beneficial effects of antioxidant supplementation on endothelial function in the presence of increased endogenous oxidative stress, whereas limited data are available under normal conditions. The present study tested the hypothesis that in normal pigs long-term antioxidants would have deleterious effects on the cardiovascular system. Normal domestic pigs (V, n=6) were studied 12 weeks after dietary supplementation with vitamin E (100 IU/kg per day) and vitamin C (1 g/day) and compared with normal controls (C, n=7). Myocardial perfusion and permeability index were evaluated by electron beam computed tomography after intravenous adenosine and dobutamine. Coronary endothelial function was evaluated in vitro by organ chamber and coronary tissue studied by immunoblotting and staining. Myocardial perfusion response was lower in V than in C after adenosine (10.1+/-4.5 versus 53.4+/-5.2%; P<0.01) and dobutamine (V, 78.4+/-8.1; C, 193.0+/-39.0%; P<0.05). The permeability index increased in V after adenosine (48.8+/-5.1%) and dobutamine (59.9+/-13.6%) and did not change in C. Coronary vasodilation to bradykinin and substance P was lower in V than in C. Moreover, in V, coronary nitrotyrosine and superoxide content was significantly higher than in C. The groups had similar total monomer expression of endothelial nitric oxide synthase, whereas the dimerized form, reflecting coupled enzyme, was lower in V. These findings suggest that long-term experimental antioxidant vitamin supplementation in normal pigs impairs myocardial perfusion and coronary endothelial function via an increased level of oxidative stress in the arterial wall, which may be partly related to the uncoupling of endothelial nitric oxide synthase and/or the direct prooxidant effect of vitamin radicals.
Animals↗
Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis.
AIMS: Coronary endothelial dysfunction (CED) precedes atherosclerosis and is associated with cardiovascular events. Both CED and erectile dysfunction (ED) are partly mediated by impairment in the nitric oxide pathway. ED is associated with established coronary atherosclerosis, but its relationship with early coronary atherosclerosis and CED is unknown. This study was designed to test the hypothesis that CED is associated with ED in men with early coronary atherosclerosis. Moreover, the role of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) was investigated; ADMA is a novel endogenous competitive inhibitor of nitric oxide synthase and has been shown to be an independent marker for cardiovascular disease. METHODS AND RESULTS: Fifty-six men without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing were studied. ADMA levels were determined and all men were asked to complete the International Index of Erectile Function-5 questionnaire to assess erectile function. Patients were divided according to the presence (n = 32) or absence (n = 24) of CED. Men with CED had significant impairment of erectile function (P = 0.008) and significantly higher ADMA levels (0.50 +/- 0.06 vs. 0.45 +/- 0.07 ng/mL, P = 0.017) compared with men with normal endothelial function. Erectile function positively correlated with coronary endothelial function. This correlation was independent of age, body mass index, high-density lipoprotein, C-reactive protein, homeostasis model assessment of insulin resistance index, and smoking status. CONCLUSION: CED is independently associated with ED and plasma ADMA concentration in men with early coronary atherosclerosis. This study further supports the role of the endothelium in systemic vascular diseases and the role of ADMA in the systemic manifestations of endothelial dysfunction.
Arginine↗
Endothelial function and cerebrovascular disease: implications for diagnosis and treatment.
Cerebrovascular disease remains one of the most common causes of morbidity and mortality in the United States. There is strong evidence to implicate endothelial dysfunction in the initiation and progression of atherosclerosis and its complications. It is now well known that endothelial dysfunction represents a systemic syndrome involving multiple vascular beds, including the cerebral vasculature. Currently, no gold standard treatment for endothelial dysfunction exists. Nonetheless, several treatment strategies have been found to be helpful in improving endothelial function. A few of these strategies have been implicated in stroke risk reduction as well, adding another line of evidence to the relationship between endothelial function and cerebrovascular disease.
Journal Article↗
Myocardial perfusion in apical ballooning syndrome correlate of myocardial injury.
BACKGROUND: The pathophysiology of the apical ballooning syndrome (ABS) is poorly understood. This study evaluated myocardial perfusion abnormalities at the time of presentation in patients with ABS and examined whether abnormal microvascular blood flow predicts the extent of myocardial injury. METHODS: We evaluated 42 consecutive patients, all women, with a diagnosis of ABS and technically adequate angiograms for the assessment of the TIMI myocardial perfusion grade (TMPG), an index of myocardial perfusion. RESULTS: Abnormal myocardial perfusion was present in 29 (69%) patients. There were no differences in age, frequency of conventional coronary atherosclerosis risk factors, left ventricular ejection fraction at either presentation or follow-up, congestive heart failure at presentation, or length of hospital stay between patients with normal versus those with abnormal TMPG. Patients with abnormal TMPG had higher peak troponin level compared with patients with normal TMPG (0.84 +/- 0.68 vs 0.42 +/- 0.33 ng/mL, P = .047). Similarly, ST elevation or deep T-wave inversion on the electrocardiogram was more common in patients with abnormal perfusion (86% vs 46%, P = .006). CONCLUSION: Impaired myocardial perfusion due to abnormal microvascular blood flow is frequently present in patients with ABS and correlates with the extent of myocardial injury. Microvascular dysfunction likely play a pivotal role in the pathogenesis of myocardial stunning in ABS.
Adult↗
Bosentan preserves endothelial function in mice overexpressing APP.
This study was designed to test the hypothesis that Alzheimer's disease (AD) is associated with endothelial dysfunction and that chronic endothelin-1 antagonism preserves endothelial function in mice overexpressing the AD amyloid precursor protein (APP). Three groups of mice were studied: C57BL/6 (normal control, n = 6), transgenic mice overexpressing APP (Tg2576, n = 5), and Tg2576 mice fed Bosentan (100 mg/(kg day)(-1)), a combined endothelin A and B receptor antagonist, for 4 months (Tg2576+Bosentan, n = 5). Mice were sacrificed at the age of 7 months. In vitro, the endothelium-dependent aortic vasorelaxation was significantly attenuated in Tg2576 mice as compared to C57BL/6 and Tg2576+Bosentan mice. In contrast, Tg2576+Bosentan and C57BL/6 mice showed similar endothelium-dependent aortic vasorelaxation. Similarly, endothelium-dependent carotid vasorelaxation was significantly attenuated in Tg2576 mice compared to C57BL/6 and Tg2576+Bosentan mice. There was no difference between the three groups in the response to nitroprusside. The current study demonstrates the presence of endothelial dysfunction in both carotid and aortic arteries in mice overexpressing APP and suggests a pathophysiological role for the endogenous endothelin system in AD.
Alzheimer Disease↗
Plasma 8-iso-prostaglandin F2alpha, a marker of oxidative stress, is increased in patients with acute myocardial infarction.
BACKGROUND: Oxidative stress has been implicated in the pathogenesis of atherogenesis. The aim of our study is to examine whether the plasma 8-iso-prostaglandin F(2alpha) level, a marker of oxidative stress, is elevated in patients with acute myocardial infarction. METHODS: Three groups of patients were enrolled: (1) patients with no or minimal coronary artery disease (CAD) (n = 15); (2) patients with stable CAD (n = 31); (3) patients with acute myocardial infarction (n = 13). RESULTS: Plasma 8-iso-prostaglandin F(2alpha) levels were significantly elevated (p < 0.001) in patients with acute myocardial infarction (290.7 +/- 73.9 pg/ml) as compared to patients with stable CAD (182.0+75.7 pg/ml) and patients with no significant CAD (118.9 +/- 85.5 pg/ml). This remained significant after correcting for coronary atherosclerosis risk factors, age, extent of atherosclerosis, and C-reactive protein (CRP) level. CONCLUSION: Plasma 8-iso-prostaglandin F(2alpha) levels are elevated in patients with acute myocardial infarction. Endogenous oxidative stress may contribute to the pathogenesis of atherosclerosis and its complications, namely myocardial infarction.
Acute Disease↗
Death during coronary angiography in a woman with cardiac amyloidosis.
Amyloidosis is a well-recognized systemic disease entity. Patients with cardiac amyloidosis have a poor prognosis; the median survival time after development of congestive heart failure is 4 months. We describe a 72-year-old woman with unsuspected cardiac amyloidosis who died during diagnostic coronary angiography. To our knowledge, this is the first report of this complication.
Aged↗
Variable response of conductance and resistance coronary arteries to endothelial stimulation in patients with heart failure due to nonischemic dilated cardiomyopathy.
UNLABELLED: Attenuation of endothelial-dependent coronary vasodilation has been reported in idiopathic dilated cardiomyopathy and anatomically normal coronaries; however, data are insufficient for understanding the incidence and extent of this finding. The response of conductance and resistance coronary arteries to endothelial stimulation with acetylcholine was examined in 25 patients. Coronary blood flow had a variable response to acetylcholine and suggested coronary endothelial dysfunction in approximately half of the patients. Abnormal endothelial dysfunction involved the large conductance epicardial coronary arteries and the small resistance vessels. Abnormal endothelial response of coronary blood flow to acetylcholine could not be predicted by demographic and hemodynamic data. CONCLUSIONS: Coronary artery endothelial function is heterogeneous in patients with idiopathic dilated cardiomyopathy. Endothelial dysfunction is present in approximately half of the cases and involves both resistance as well as conductance coronary blood vessels. Furthermore, coronary endothelial function cannot be predicted by demographic and hemo-dynamic parameters or left ventricular ejection fraction.
Acetylcholine↗
Feasibility of a pressure wire and single arterial puncture for assessing aortic valve area in patients with aortic stenosis.
BACKGROUND: Determination of a transvalvular pressure gradient for measurement of aortic valve area (AVA) by hemodynamic cardiac catheterization usually requires 2 catheters and 2 arterial access sites. We assessed the feasibility of using a single arterial puncture and a 0.014 inch pressure wire for evaluation of aortic stenosis. METHODS: Eighteen patients (mean age, 76 years; 10 men) underwent hemodynamic catheterization for assessment of AVA. Cardiac output was determined by thermodilution (using a pulmonary artery catheter), and the transvalvular pressure gradient was obtained from simultaneous pressure recordings (using a pressure wire to measure left ventricular pressure and a 5 Fr catheter to measure ascending aortic pressure). RESULTS: This novel technique was technically feasible in all patients. Calibration of the pressure wire with the pressure of the fluid-filled catheter was possible and accurate in the left ventricle and aorta. The method required 36.4 +/- 9.6 minutes from injection of a local anesthetic to completion of AVA measurement; 53.3 +/- 18.6 minutes were required to finish all catheterization procedures, including coronary angiography. Measurements of AVA (mean, 1.01 +/- 0.43 cm2) and pressure gradients (mean, 27.5 +/- 10.5 mmHg) taken by a pressure wire were similar to measurements taken by Doppler echocardiography (1.07 +/- 0.58 cm2 and 32.9 +/- 12.1 mmHg, respectively); the correlation was significant (r = 0.856; p < 0.001, and r = 0.741; p < 0.001, respectively). CONCLUSIONS: Our findings suggest that a single arterial approach using a pressure wire is feasible, safe, accurate and rapid for the invasive assessment of aortic stenosis.
Aged↗
Dietary reversal of experimental hypercholesterolemia improves endothelial dysfunction of epicardial arteries but not of small coronary vessels in pigs.
Endothelial dysfunction is characterized by impaired vasodilation, increase of oxidative stress and inflammation. The current study was designed to test the hypothesis that reversal of hypercholesterolemic diet alone does not normalize all the parameters of endothelial dysfunction. After 10 weeks on a high-cholesterol diet, female juvenile pigs were randomized to normal diet (n=5, "Reversals") or continued on the same diet (n=6, "HC") for another 6 weeks. A control group of 11 pigs received a normal diet ("C"). Coronary epicardial and arteriolar endothelial function was tested in vitro. NFkappaB and p47phox expression was analyzed in epicardial arteries and myocardium, respectively. P47phox localization in coronary arteries was demonstrated with immunohistochemistry. Lipid levels normalized in Reversal pigs. Epicardial arteries of Reversals showed a normalized relaxation and NFkappaB expression compared to HC (p<0.05). Small vessel relaxation remained attenuated, and expression of p47phox in myocardial tissue was elevated in Reversals compared to C (p<0.05). Dietary lowering of serum cholesterol and LDL improves vascular function of epicardial arteries but neither of small vessels nor vascular oxidative stress within this time frame. Hence, dietary normalization of serum lipid levels alone may not be synonymous to normalization of the components of endothelial dysfunction.
Analysis of Variance↗
Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs.
Hypercholesterolemia (HC), a major risk factor for onset and progression of renal disease, is associated with increased oxidative stress, potentially causing endothelial dysfunction. One of the sources of superoxide anion is xanthine oxidase (XO), but its contribution to renal endothelial function in HC remains unclear. We tested the hypothesis that XO modulates renal hemodynamics and endothelial function in HC pigs. Four groups (n = 23) of female domestic pigs were studied 12 wk after either normal (n = 11) or HC diet (n = 12). Oxidative stress was assessed by plasma isoprostanes and oxidized LDL, and the XO system by plasma uric acid, urinary xanthine, and renal XO expression (by immunoblotting and immunohistochemistry). Renal hemodynamics and function were studied with electron beam-computed tomography before and after endothelium-dependent (ACh) and -independent (sodium nitroprusside) challenge, during a concurrent intrarenal infusion of either oxypurinol or saline (n = 5-6 in each group). HC showed elevated oxidative stress, higher plasma uric acid (23.8 +/- 3.8 vs. 6.2 +/- 0.8 microM/mM creatinine, P = 0.001), lower urinary xanthine, and greater renal XO expression compared with normal. Inhibition of XO in HC significantly improved the blunted responses to ACh of cortical perfusion (13.5 +/- 12.1 and 37.2 +/- 10.6%, P = 0.01 and P = not significant vs. baseline, respectively), renal blood flow, and glomerular filtration rate; restored medullary perfusion; and improved the blunted cortical perfusion response to sodium nitroprusside. This study demonstrates that the endogenous XO system is activated in swine HC. Furthermore, it suggests an important role for XO in regulation of renal hemodynamics, function, and endothelial function in experimental HC.
Animals↗
Coronary endothelial dysfunction following sirolimus-eluting stent placement: should we worry about it?
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Coronary Artery Disease↗
Lipoprotein-associated phospholipase A2 is an independent marker for coronary endothelial dysfunction in humans.
OBJECTIVE: The purpose of the current study was to determine whether lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans. METHODS AND RESULTS: Patients (172) with no significant coronary artery disease (<30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA2 were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow (63.8+/-73.2 and 32.0+/-71.7 versus 78.4+/-73.2%; P<0.001) and greater epicardial coronary artery vasoconstriction (-14.1+/-14.7 and -23.3+/-25.1 versus -9.5+/-15.2% mean diameter change; P<0.001) in response to acetylcholine. Patients with coronary endothelial dysfunction had significantly higher serum concentrations of Lp-PLA2 than those with normal endothelial function (246.2+/-71.6 versus 209+/-56.7 ng/mL; P=0.001). The odds ratio for coronary endothelial dysfunction in patients with Lp-PLA2 in the highest tertile was 3.3 (95% CI, 1.6 to 6.6). CONCLUSIONS: Lp-PLA2 is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension.
Advanced hypertension (HT), associated with left ventricular hypertrophy (LVH), impairs myocardial microvascular function and structure and leads to increased myocardial hypoxia and growth factor activation. However, the effect of HT on microvascular architecture and its relation to microvascular function, before the development of LVH (early HT), remains unclear. By way of method, pigs were studied after 12 wk of renovascular HT (n = 7) or control (n = 7) animals. Myocardial microvascular function (blood volume and blood flow at baseline and in response to adenosine) was assessed by using electron beam computed tomography (CT). Microvascular architecture was subsequently studied ex vivo using micro-CT, and microvessels (diameter, <500 microm) were counted in situ in three-dimensional images (40-microm on-a-side cubic voxels). Myocardial expression of vascular endothelial growth factor, basic fibroblast growth factor, and hypoxia-inducible factor-1alpha were also measured. By way of results, left ventricular muscle mass was similar between the groups. The blood volume response to intravenous adenosine was attenuated in HT animals compared with normal animals (+7.4 +/- 17.0 vs. +46.2 +/- 12.3% compared with baseline, P = 0.48 and P = 0.01, respectively). Microvascular spatial density in HT animals was significantly elevated compared with normal animals (246 +/- 26 vs. 125 +/- 20 vessels/cm2, P < 0.05) and correlated inversely with the blood volume response to adenosine. Growth factors expression was increased in HT animals compared with control animals. In conclusion, early HT elicits changes in myocardial microvascular architecture, which are associated with microvascular dysfunction and precede changes in muscle mass. These observations underscore the direct and early effects of HT on the myocardial vasculature.
Animals↗