Megha Prasad

Coronary Artery Tortuosity in Spontaneous Coronary Artery Dissection Angiographic Characteristics and Clinical Implications

Background—Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute coronary syndrome. The angiographic characteristics of SCAD are largely undetermined. The goal of this study was to determine the prevalence of coronary tortuosity in SCAD and whether it may be implicated in the disease. Methods and Results—Patients with confirmed SCAD (n=246; 45.3±8.9 years; 96% women) and 313 control patients without SCAD or coronary artery disease who underwent coronary angiography were included in this case–control study. Angiograms were reviewed for coronary tortuosity and assigned a tortuosity score. Tortuosity was common in patients presenting with their first SCAD event (78% versus 17% in controls; P<0.0001; tortuosity score, 4.41±1.73 versus 2.33±1.49 in controls; P<0.0001) despite a low prevalence of hypertension (34%). Recurrent SCAD (n=40) occurred within segments of tortuosity in 80% of cases. Severe tortuosity (≥2 consecutive curvatures ≥180°) was associated with a higher risk of recurrent SCAD (hazard ratio, 3.29; 95% confidence interval, 0.99–8.29; P=0.05). Tortuosity score >5 was associated with a trend toward higher risk of recurrent SCAD (P=0.16). Prespecified angiographic markers of tortuosity including corkscrew appearance and multivessel symmetrical tortuosity were associated with extracoronary vasculopathy including fibromuscular dysplasia (P<0.05 for both). Conclusions—Coronary artery tortuosity is highly prevalent in the SCAD population and is associated with recurrent SCAD. Recurrent SCAD most often occurs within segments of tortuosity. Angiographic features of SCAD are associated with extracoronary vasculopathy, including fibromuscular dysplasia. These findings suggest that coronary tortuosity may serve as a marker or potential mechanism for SCAD.

Rates and severity of perforation from implantable cardioverter-defibrillator leads: A 4-year study

IntroductionAlthough recent case reports and one small single-year observational study report a substantially increased rate of perforation with the St. Jude Riata series defibrillator lead, these results have not been externally validated.Methods and ResultsFrom 2004 to 2007, 593 implantable cardioverter-defibrillator (ICD) implants were performed by six faculty and 13 fellows at four University of California, San Francisco, CA, USA and affiliate hospitals. An electronic medical records system was systematically searched to identify clinically significant cases of ICD lead dislodgment or perforation. Of 307 (56%) St. Jude leads (all Riata series 6.3- and 7.3-French leads), 188 (29%) Medtronic leads (including 99 Sprint Fidelis 6.6 French leads), and 98 (15%) Guidant/Boston Scientific leads, there were three perforations in 593 cases (0.51%). One perforation occurred with a Medtronic Sprint Fidelis 6949 lead (0.53%), and two with a St. Jude Riata 1581 lead (0.65%). There were no statistically significant differences in perforation or dislodgement rates between manufacturers or lead models (p = NS for all). In both cases of perforation with the St. Jude Riata leads, the lead tip perforated through the pericardium into the pleural space.ConclusionsIn our 4-year series of ICD implants, perforation and dislodgement rates were low, similar across all lead makes and models, and well below published and accepted complication rates. Our findings contradict previously-reported higher rates of perforation with the Riata lead. Registry and product performance reports should also classify complications by severity and outcome to provide a more complete assessment of product safety.

A novel application of CT angiography to detect extracoronary vascular abnormalities in patients with spontaneous coronary artery dissection

BACKGROUND Spontaneous coronary artery dissection (SCAD) is associated with extracoronary vascular abnormalities, which depending on type and location may warrant treatment or provide additional diagnostic or prognostic information about this uncommon entity. Fibromuscular dysplasia (FMD), aneurysms, and dissections have been detected in multiple vascular territories by magnetic resonance angiography, CT angiography (CTA), and catheter angiography. The optimal modality to detect extracoronary vascular abnormalities is unknown. We highlight the technique and feasibility of a novel CTA protocol to detect extracoronary vascular abnormalities in these patients, incorporating patient safety and convenience. METHODS The complete CTA protocol consisting of a single CTA of the neck, chest, abdomen, and pelvis was performed on 39 SCAD outpatients. All examinations were performed with 200 mL of low-osmolar contrast agent and used radiation dose modulation techniques. Average volume CT dose index was 9 mGy for the chest, abdomen, and pelvis portions and 21 mGy for the neck portion. Studies were independently reviewed by 2 senior vascular radiologists. RESULTS Two patients had nondiagnostic CTA neck evaluation because of technical acquisition errors. Extracoronary vascular abnormalities were detected in 27 of 39 patients (69%). Catheter angiography detected brachial artery FMD in 1 patient, a vascular bed not included in the SCAD CTA protocol. Extracoronary vascular abnormalities were common, including FMD, aneurysms, dissection, and aortic tortuosity, and were seen in the iliac (36%), carotid and/or vertebral (31%), splanchnic (10%), and renal (26%) arteries and in the thoracic and/or abdominal aorta (10%). CONCLUSIONS The frequency of extracoronary vascular abnormalities and extent of territories identified the CTA protocol in our cohort are high. A tailored CTA may be the optimal imaging technique for detecting extracoronary vascular abnormalities in patients with suspected underlying vasculopathy. Although the clinical significance of extracoronary vascular abnormalities remains unclear, detection of these abnormalities has identified patients in whom cerebral imaging and serial monitoring have been recommended.

Safety and Efficacy of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Refractory Angina Pectoris

OBJECTIVE To assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris. PATIENTS AND METHODS A single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires. RESULTS Fifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10). CONCLUSION In this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.

coronary microvascular endothelial dysfunction is an independent predictor of development of osteoporosis in postmenopausal women

Background A growing body of evidence links coronary artery atherosclerosis and calcification to osteoporosis in women. The endothelium plays a critical role in maintaining vascular integrity and may play a role in bone metabolism. We aimed to determine whether early coronary atherosclerosis, as detected by coronary microvascular endothelial dysfunction (CMED), predicts the development of osteoporosis in postmenopausal women. Methods Coronary vascular reactivity was evaluated in 194 postmenopausal women greater than 50 years of age and with non-obstructive coronary arteries by administration of intracoronary acetylcholine during diagnostic angiography. CMED was defined as ≤50% increase in coronary blood flow from baseline in response to maximal dose. After a median follow-up of 7.0±0.3 years, patients were assessed by a questionnaire for development of osteoporosis. Results The average age of the cohort was 60.9±7.4 years. Women with CMED were twice as likely to develop osteoporosis compared with women without endothelial dysfunction after adjustment for potential confounders (relative risk, 2.4; 95% confidence interval [CI], 1.1, 5.6, P=0.02). Epicardial endothelial dysfunction was not associated with development of osteoporosis. Discussion Early coronary atherosclerosis with endothelial dysfunction is an independent marker for increased risk of developing osteoporosis in postmenopausal women greater than 50 years of age without obstructive coronary artery disease. The current study supports a link between coronary atherosclerosis and osteoporosis.

Prevalence of Metabolic Syndrome in South Asians Residing in the United States

AIMS/HYPOTHESIS The aim of this study was to define the prevalence of the metabolic syndrome and its component risk factors among individuals of South Asian origin living in the United States. METHODS We analyzed baseline data from 1,445 participants enrolled in a cohort study investigating risk factors for cardiovascular disease in South Asians. We defined the metabolic syndrome using the International Diabetes Federation criteria for waist circumference (>90 cm for men; >80 cm, women), triglycerides (>150 mg/dL), high-density lipoprotein cholesterol (HDL-C) (<40 mg/dL (men), < mg/dL (women)), blood pressure (>135/80 mmHg), and fasting glucose (>100 mg/dL). RESULTS The mean age was 43 +/-10 years, and 30% of participants were women. The prevalence of metabolic syndrome was 27% (31% men vs. 17% women, P < 0.05). Fifty-nine percent of the cohort had high waist circumference (58% men vs. 62% women, P = not significant [N.S.]), 47% had low HDL-C [46% men vs. 48% women (NS)], 19% had elevated triglycerides (23% men vs. 8% women, P < 0.05), 14% had hypertension (16% men vs. 9% women, P < 0.05), and 13% had elevated fasting glucose (18% men vs. 11% women, P < 0.05). The most common metabolic syndrome phenotype is low HDL-C with elevated triglycerides. CONCLUSIONS Although the prevalence of the metabolic syndrome is lower than previous reports of South Asians, the prevalence is still unacceptably high despite the presence of protective demographic factors.

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

Background Endothelial dysfunction is an early stage of atherosclerosis. Single‐nucleotide polymorphisms (SNPs) have been associated with vascular dysfunction, cardiac events, and coronary artery remodeling. We aimed to detect SNPs associated with endothelial dysfunction and determine whether these associations are sex specific. Methods and Results Six hundred forty‐three subjects without significant obstructive coronary artery disease underwent invasive coronary endothelial function assessment. We collected data from 1536 SNPs that had previously been associated with vasoreactivity, angiogenesis, inflammation, artery calcification, atherosclerotic risk factors, insulin resistance, hormone levels, blood coagulability, or with coronary heart disease. Coronary vascular reactivity was assessed by the percent change in coronary artery diameter ≤ −20% after an intracoronary bolus injection of acetylcholine on invasive coronary physiology study. SNPs significantly associated with coronary epicardial endothelial dysfunction were ADORA1,KCNQ1, and DNAJC4 in the whole cohort, LPA, MYBPH, ADORA3, and PON1 in women and KIF6 and NFKB1 in men (P<0.01). Conclusions We have identified several significant SNPs that are associated with an increased risk of coronary endothelial dysfunction. These associations appear to be sex specific and may explain gender‐related differences in development of atherosclerosis.

Microvascular endothelial dysfunction predicts the development of erectile dysfunction in men with coronary atherosclerosis without critical stenoses.

BackgroundErectile dysfunction (ED) is associated with an increased risk for cardiovascular disease, stroke, and all-cause mortality, independent of conventional cardiovascular risk factors. Coronary endothelial dysfunction is independently associated with ED in men with early coronary atherosclerosis. We aimed to investigate whether coronary microvascular dysfunction predicts development of ED in patients presenting with coronary atherosclerosis without critical stenoses. Patients and methodsCoronary microvascular function was evaluated in 130 men with coronary atherosclerosis without critical stenoses by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4 years, patients were assessed for the development of ED by administration of a questionnaire. ResultsIn all, 68 (50%) men had microvascular endothelial dysfunction at baseline; 35 (51%) men with microvascular endothelial dysfunction developed ED on follow-up compared with 19 (31%) men without microvascular endothelial dysfunction. Men who developed ED had a lower coronary blood flow response (% [INCREMENT]CBF) compared with men who did not develop ED, with mean±SD of 25.4±71.3 versus 81.7±120 (P=0.003). In univariate analysis, microvascular endothelial dysfunction was a predictor for the development of ED, with relative risk of 2.4 (1.2–4.9) (P=0.016). In multivariate logistic regression adjusting for traditional cardiovascular risk factors (age, hypertension, hyperlipidemia, diabetes, vascular disease, and family history of coronary artery disease), only microvascular endothelial dysfunction (P=0.027) and age (P=0.044) remained significant predictors of development of ED. ConclusionCoronary microvascular dysfunction is a predictor of the development of ED in men with coronary atherosclerosis without critical stenoses. This study underscores the systemic involvement of the endothelial function in vascular disease.

Uric Acid Is Associated With Inflammation, Coronary Microvascular Dysfunction, and Adverse Outcomes in Postmenopausal Women

Uric acid is a risk factor for coronary artery disease in postmenopausal women, but the association with inflammation and coronary endothelial dysfunction (CED) is not well defined. The aim of this study was to determine the relationship of serum uric acid (SUA), inflammatory markers, and CED. In this prospective cohort study, SUA, high-sensitivity C-reactive protein levels, and neutrophil count were measured in 229 postmenopausal women who underwent diagnostic catheterization, were found to have no obstructive coronary artery disease, and underwent coronary microvascular function testing, to measure coronary blood flow response to intracoronary acetylcholine. The average age was 58 years (interquartile range, 52–66 years). Hypertension was present in 48%, type 2 diabetes mellitus in 5.6%, and hyperlipidemia in 61.8%. CED was diagnosed in 59% of postmenopausal women. Mean uric acid level was 4.7±1.3 mg/dL. Postmenopausal women with CED had significantly higher SUA compared with patients without CED (4.9±1.3 versus 4.4±1.3 mg/dL; P=0.02). There was a significant correlation between SUA and percent change in coronary blood flow to acetylcholine (P=0.009), and this correlation persisted in multivariable analysis. SUA levels were significantly associated with increased neutrophil count (P=0.02) and high-sensitivity C-reactive protein levels (P=0.006) among patients with CED, but not among those without CED. SUA is associated with CED in postmenopausal women and may be related to inflammation. These findings link SUA levels to early coronary atherosclerosis in postmenopausal women.

Extracorporeal shockwave myocardial therapy is efficacious in improving symptoms in patients with refractory angina pectoris a multicenter study

ObjectiveMedically refractory angina remains a significant health concern despite major advances in revascularization techniques and emerging medical therapies. We aimed to determine the safety and efficacy of extracorporeal shockwave myocardial therapy (ESMT) in managing angina pectoris. MethodsA single-arm multicenter prospective study was designed aiming to determine the safety and efficacy of ESMT. Patients of functional Canadian Cardiovascular Society class II–IV, despite stable and optimal medical management, with documented myocardial segments with reversible ischemia and/or hibernation on the basis of echocardiography/single-photon emission computerized tomography (SPECT) were enrolled from 2010 to 2012. A total of 111 patients were enrolled, 33 from Indonesia, 21 from Malaysia, and 57 from Philippines. Patients underwent nine cycles of ESMT over 9 weeks. Patients were followed up for 3–6 months after ESMT treatment. During follow-up, patients were subjected to clinical evaluation, the Seattle Angina Questionnaire, assessment of nitrate intake, the 6-min walk test, echocardiography, and SPECT. ResultsThe mean age of the population was 62.9±10.9 years. The summed difference score on pharmacologically induced stress SPECT improved from 9.53±17.87 at baseline to 7.77±11.83 at follow-up (P=0.0086). Improvement in the total Seattle Angina Questionnaire score was seen in 83% of patients (P<0.0001). Sublingual nitroglycerin use significantly decreased (1.14±1.01 tablets per week at baseline to 0.52±0.68 tablets per week at follow-up; P=0.0215). There were no changes in left ventricular function on echocardiography (0.33±9.97, P=0.93). The Canadian Cardiovascular Society score improved in 74.1% of patients. ConclusionThis multicenter prospective trial demonstrated that ESMT is both a safe and an efficacious means of managing medically refractory angina.