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Background Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) are potential novel therapies after myocardial infarction (MI). We first established the optimal and clinically applicable dosages of these drugs in mobilizing hematopoietic stem cells (HSC), and then tested the efficacy of monotherapy and combination therapy post-MI. Methods and Results Optimal doses were established in enhanced green fluorescent protein (eGFP) + chimeric mice (n = 30). Next, mice underwent MI and randomized into 4 groups (n = 18/group): 1) GCSF; 2) EPO; 3) EPO+GCSF; and 4) control. Left ventricular (LV) function was analyzed pre-MI, at 4 hours and at 28 days post-MI. Histological assessment of infarct size, blood vessels, apoptotic cardiomyocytes, and engraftment of eGFP+ mobilized cells were analyzed at day 28. LV function in the control group continued to deteriorate, whereas all treatments showed stabilization. The treatment groups resulted in less scarring, increased numbers of mobilized cells to the infarct border zone (BZ), and a reduction in the number of apoptotic cardiomyocytes. Both EPO groups had significantly more capillaries and arterioles at the BZ. Conclusion We have established the optimal doses for EPO and GCSF in mobilizing HSC from the bone marrow and demonstrated that therapy with these agents, either as monotherapy or combination therapy, led to improvement of cardiac function post-MI. Combination therapy does not seem to have additive benefit over monotherapy in this model.

Objectives In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Results Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: −4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Conclusions Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).

Short QT syndrome (SQTS) is an uncommon genetic channelopathy that predisposes to sudden cardiac death (SCD). Management of this condition in asymptomatic individuals is controversial. A 22-year-old man presented with a 6-month history of atypical chest pain. His medical history was unremarkable.

Although 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. From 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. In 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.

We aimed to assess the utility of changes in systolic and diastolic function by isoproterenol challenge in predicting symptom resolution post-myectomy in selected patients with hypertrophic cardiomyopathy (HCM) and labile obstruction.In a subset of symptomatic HCM patients without resting/provocable obstruction on noninvasive assessment, isoproterenol challenge during hemodynamic catheterization may elicit labile left ventricular outflow tract (LVOT) obstruction, and demonstrate the effect of obstruction on diastolic function. These changes may determine whether patients achieve complete symptom resolution post-myectomy.Between February 2003 and April 2009, 18 symptomatic HCM patients without LVOT obstruction on noninvasive testing underwent isoproterenol provocation and septal myectomy due to presence of provocable gradient and were followed for 4 (IQR 3-7) years.Thirteen (72.2%) had complete symptom resolution, while 5 (27.8%) had improved, but persistent symptoms. Those with provoked gradient100 mm Hg or increase in left atrial pressure (LAP) with isoproterenol had symptom resolution.Symptomatic HCM patients without LVOT gradient on noninvasive testing may demonstrate labile obstruction with isoproterenol. With isoproterenol, patients with high LVOT gradient or increase in LAP concomitant with an increase in gradient achieved complete symptom resolution post-myectomy. Thus, improved diastolic filling as well as outflow gradient production in patients with HCM may predict symptom response to myectomy. © 2016 Wiley Periodicals, Inc.

Background Normal endothelial function is central to physiologic anticoagulation mechanisms. Endothelial dysfunction may predispose to venous thromboembolism (VTE). We aimed to investigate if coronary endothelial dysfunction (CED) predicts development of VTE in patients presenting with coronary atherosclerosis without critical stenoses. Methods Coronary microvascular function was evaluated in 502 patients with coronary atherosclerosis without critical stenoses by administration of intracoronary acetylcholine at the time of diagnostic study. After a median follow-up of 6.3 years, patients were assessed for the development of VTE by administration of a questionnaire. Coronary microvascular endothelial dysfunction was defined as ≤ 50% increase in coronary blood flow from baseline in response to maximal dose of acetylcholine. Results The median age was 53 years (IQR: 45, 62) 68% were female and CED occurred in 279 (56%) patients. Hypertension (40.8%), diabetes (8.4%), and hyperlipidemia (58.3%) were common risk factors. There were no differences in baseline characteristics between those with and without CED. There were 9 VTE events (6 unprovoked) among patients with CED compared to no events in the control group (P = 0.01). Discussion CED was associated with the development of VTE. Endothelial injury by causing disruption of vascular hemostasis may play a role in predisposing patients to VTE.

Background: Coronary endothelial dysfunction(CED) may reflect loss of vascular integrity and permeability. We aimed to test the hypothesis that CED may be associated with increased risk of bleeding events. Methods: Coronary vascular reactivity was evaluated in 444 patients with non-obstructive coronary arteries by administration of intracoronary acetylcholine during angiography. CED was defined as a ≤ 50% increase in coronary blood flow (CBF) from baseline in response to maximal dose of acetylcholine. After a median follow-up of 7 years, patients were assessed for the occurrence of any significant bleeding events. Results: Of 444 patients, 70.7% (314) were female. Average age was 52.3 years. Of 252 patients with CED, 7.9% (20) developed bleeding events compared to 2.1% (4 of 192) without CED (p=0.004). Patients who developed bleeding events had a lower percent change in CBF vs. those who did not median: (IQR) 14.1 (-28.1, 98.7) vs. 40.0 (-11.0, 103.5); p=0.03 (Figure 1). CED was significantly associated with the development of bleeding in univariate analysis(p=0.004, relative risk: 3.81 CI, 1.32, 10.96). In multivariate analysis CED was an independent predictor of development of bleeding (p=0.01) Conclusions: CED is associated with increased risk of bleeding events. This can be explained by the altered vascular function that is inherent to CED. This study underscores the systemic involvement of the endothelium in vascular disease, and the concept of the ‘vulnerable patient’.

Introduction: Venous thromboembolism (VTE) is a cause of significant morbidity and mortality. The vascular endothelium may be involved in the pathogenesis of both VTE and arterial thrombosis, as endothelial injury and dysfunction may disrupt normal anticoagulation mechanisms. We aimed to test the hypothesis that coronary endothelial dysfunction (CED) is associated with development of VTE in prospective follow-up. Methods: Coronary vascular reactivity was evaluated in 502 patients with non-obstructive coronary artery disease by administration of intracoronary acetylcholine during diagnostic angiography. Microvascular CED was defined as ≤50% increase in coronary blood flow (CBF) from baseline in response to maximal dose of acetylcholine. After median follow-up of 6.3 years (IQR 3.5, 10.7), patients were assessed by standardized questionnaire, phone-call and review of medical records for development of VTE. Results: Median age of the population was 53 years (IQR 45, 62); 68% were females. Hypertension was prevalent in 40.8%, diabetes in 8.4%, and hyperlipidemia in 58.3% of patients. Of 502 patients, 279 had CED. There were no significant differences in baseline characteristics including cardiovascular and VTE risk factors between patients with and without CED (p>0.05). Eighty-nine percents of patients who developed VTE had CED. Patients who developed spontaneous or provoked VTE both had significantly lower % change in CBF than patients who did not develop VTE (p Conclusion: We found a seven-fold increased risk of VTE with CED, suggesting a link between the two. Endothelial injury disrupting vascular homeostasis may predispose patients to VTE.

Objective Female sex is a known risk factor for cardiac surgery, and tricuspid valve (TV) disease is more common in women. There are few data on sex-stratified surgical outcomes for isolated TV surgery. An administrative database was used to compare acute in-hospital outcomes between men and women undergoing isolated TV surgery. Methods Patients aged >18 who underwent TV repair or replacement from 2004 to 2013 were identified using the National Inpatient Sample. Patients were excluded if they had congenital heart disease, endocarditis, or were undergoing concomitant cardiac surgeries except coronary bypass. Results were weighted to represent national averages. Sex-stratified analysis was performed using propensity score matching to compare in-hospital mortality, postoperative complications and hospital costs. Results Over 10 years, women represented 58% of the 5005 TV surgeries performed. With propensity matching, hospital mortality (7.9% vs 7.7%; P=0.99) and median length of stay (11 vs 11 days; P=0.99) were similar between men and women. However, median hospital charges were higher for men ($166 000 vs $155 000; P=0.04). Conclusion Isolated TV surgery is rare, but women more commonly undergo the procedure. In-hospital mortality was similar between men and women after propensity matching, but remains markedly high for both men and women in comparison to that reported for left-sided isolated valve surgery.

Background: Serum uric acid is a marker of oxidative stress, and may predict cardiovascular events/outcomes. We aimed to determine whether elevated serum uric acid levels were predictive of worse outcomes in women undergoing percutaneous coronary intervention(PCI). Methods: We retrospectively

Autoimmune rheumatic diseases can affect the cardiac vasculature, valves, myocardium, pericardium, and conduction system, leading to a plethora of cardiovascular manifestations that can remain clinically silent or lead to substantial cardiovascular morbidity and mortality. Although the high risk of cardiovascular pathology in patients with autoimmune inflammatory rheumatological diseases is not owing to atherosclerosis alone, this particular condition contributes substantially to cardiovascular morbidity and mortality-the degree of coronary atherosclerosis observed in patients with rheumatic diseases can be as accelerated, diffuse, and extensive as in patients with diabetes mellitus. The high risk of atherosclerosis is not solely attributable to traditional cardiovascular risk factors: dysfunctional immune responses, a hallmark of patients with rheumatic disorders, are thought to cause chronic tissue-destructive inflammation. Prompt recognition of cardiovascular abnormalities is needed for timely and appropriate management, and aggressive control of traditional risk factors remains imperative in patients with rheumatic diseases. Moreover, therapies directed towards inflammatory process are crucial to reduce cardiovascular disease morbidity and mortality. In this Review, we examine the multiple cardiovascular manifestations in patients with rheumatological disorders, their underlying pathophysiology, and available management strategies, with particular emphasis on the vascular aspects of the emerging field of 'cardiorheumatology'.

Aims Metabolic syndrome has been associated with increased risk of cardiovascular disease. We aimed to determine the effectiveness of a community-based screening program in identifying cardiovascular risk factors in healthy young South Asian population. Materials and Methods Between 2006 and 2011, 3314 patients of all ages were recruited as a part of a prospective cohort study investigating cardiovascular risk in South Asians. We analyzed 1537 patients between the ages of 18 and 40. Demographic and baseline characteristics including baseline laboratory markers and blood pressures were obtained at initial visit. Results The total cohort of 1537 patients was 66.5% male, and the mean age was 35 ± 5 years. Among participants who denied a history of hypercholesterolemia, 62% had elevated LDL-C (>100 mg/dL), and 8% had markedly elevated LDL-C (>160 mg/dL). Overall, diabetes was present in 4%, hypertension was present in 12% and hyperlipidemia was present in 46%. Low HDL-C (50% of men, 52% of women) and elevated triglycerides (44% of men, 18% of women) were the most prevalent components of metabolic syndrome. Metabolic syndrome was present in 14% of men and 8% of women and one-third (30%) of men and one-fifth (19%) of women had at least two component risk factors. Conclusions This is the largest study to date assessing effectiveness of a community based screening program aiming to identify cardiovascular risk in young South Asians. We note significant modifiable risk at a young age. Such community based interventions can be effective at detecting and managing risk factors early in this vulnerable population.

Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome, often occurring in young women. The utility of comprehensive imaging and clinical significance of detected vascular abnormalities have yet to be determined. We hypothesized that extracoronary vascular abnormalities (EVAs) are common in SCAD and aimed to study the prevalence and distribution of these findings. We enrolled 115 patients with confirmed SCAD who were evaluated at the Mayo Clinic SCAD Clinic from February 2010 to May 2014 and prospectively underwent comprehensive computed tomography angiography imaging of the neck, chest, abdomen, and pelvis (SCAD computed tomography angiography protocol, n = 95) or had retrospective review of outside studies (n = 20) including head imaging (n = 40). Follow-up was determined by last clinical visit or study correspondence and included review of recurrent SCAD or myocardial infarction, congestive heart failure, and death. We reported EVAs in 66% of patients with SCAD, most frequently in the abdomen (36%), pelvis (28%), and neck (27%). Only 1 patient had EVA in the chest (aortic dissection and Marfan's). Fibromuscular dysplasia (FMD) (exclusively multifocal) was the most common type of EVA (45%). Vascular abnormalities in those with head imaging included intracranial aneurysms (n = 9) and FMD (n = 3). There were no deaths at median follow-up of 21 months (Q1 to Q3 7.7 to 55). The presence of FMD was not associated with SCAD recurrence (relative risk [RR] 1.2; confidence interval [95% CI] 0.60, 2.5), congestive heart failure (RR 0.66; 95% CI 0.20, 2.3), or myocardial infarction (RR 1.34; 95% CI 0.69, 2.6). In conclusion, EVAs including FMD, dissections, aneurysms, and dilation are common in patients with SCAD and occur in a wide anatomic distribution. The presence of EVAs and/or FMD did not correlate with the risk of subsequent clinical events, but future studies with increased power and longer follow-up will be important to further assess the role of EVAs in patients with SCAD.

To determine the feasibility of automated co-registration of angiography and intravascular ultrasound (IVUS) to facilitate integration of these two imaging modalities in a synchronous manner.IVUS provides cross-sectional imaging of coronary arteries but lacks overview of the vascular territory provided by angiography. Co-registration of angiography and IVUS would increase utility of IVUS in the clinical setting.Forty-nine consecutive patients undergoing surveillance for cardiac allograft vasculopathy with angiography and IVUS of the left anterior descending artery (LAD) were enrolled. A pre-IVUS angiogram of the LAD was performed followed by an ECG-triggered fluoroscopy (ECGTF) during IVUS pullback at 0.5 mm/s using an automatic pullback device. ECGTF was used to track the IVUS catheter during pullback and establish a spatial relationship to the pre-IVUS angiogram. Angio-IVUS co-registration was performed with a research prototype (Siemens Healthcare, Germany) and accuracy was evaluated by distance mismatch between angiography and IVUS images at vessel bifurcations.Median age was 54 (44.5, 67) years. The population was 82.6% male with minimal risk factors. The median (IQR) co-registration distance mismatch measured at 108 bifurcations in 42 (85%) patients was 0.35 (0.00-1.16) mm. Seven patients were excluded due to inappropriate data acquisition (n = 3) and failure of tracking (n = 4), e.g., due to overlapping sternal wires. Estimated effective radiation dose for ECGTF was 0.09 mSv.This study demonstrates the feasibility of angio-IVUS co-registration which may be used as a clinical tool for localizing IVUS cross-sections along an angiographic roadmap. © 2015 Wiley Periodicals, Inc.

Megha Prasad, Martin Reriani, Sundeep Khosla, Mario Gössl, Ryan Lennon, Rajiv Gulati, Abhiram Prasad, Lilach O Lerman, Amir Lerman Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA 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. Keywords: coronary artery disease, endothelial dysfunction, endothelial progenitor cells, low bone mass, screening

Background: Metabolic syndrome has been associated with increased risk of cardiovascular disease.We aimed to determine the effectiveness of a community-based screening program in identifying cardiovascular risk factors in a healthy young South Asian population. Methods: Between 2006 and 2011, 3,314 patients of all ages were recruited as a part of a prospective cohort study investigating cardiovascular risk in South Asians. We analyzed 1537 patients between the ages of 18 and 40. Demographic and baseline characteristics including baseline laboratory markers and blood pressures were obtained at initial visit. Results: The total cohort of 1537 patients was 66.5% male, and the mean age was 35±5 years. Among participants who denied a history of hypercholesterolemia, 62% had elevated LDL-C (>100 mg/dL), and 8% had markedly elevated LDL-C (>160 mg/dL). Overall, diabetes was present in 4%, hypertension was present in 12% and hyperlipidemia was present in 46%. Low HDL-C (50% of men, 52% of women) and elevated triglycerides (44% of men, 18% of women) were the most prevalent components of metabolic syndrome. Metabolic syndrome was present in 14% of men and 8% of women and one-third (30%) of men and one-fifth (19%) of women had at least two component risk factors. Discussion: This is the largest study to date assessing effectiveness of a community based screening program aiming to identify cardiovascular risk in young South Asians. We note significant modifiable risk at a young age. Such community based interventions can be effective at detecting and managing risk factors early in this vulnerable population.

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.

To assess trainee physicians' ability to puncture at the femoral head and complication rates when obtaining access to the common femoral artery using fluoroscopy.The common femoral artery is the most common artery accessed during cardiac catheterization. Fluoroscopy can be used to visualize the femoral head and estimate the common femoral artery location. Puncture superior or inferior to the femoral head is associated with increased rates of retroperitoneal bleeding or thrombosis, respectively. Adequate training in groin puncture technique is essential in minimizing complications and upholding patient safety.Two consecutive samples of patients were retrospectively analyzed - one from Keck Medical Center (Keck) (n = 45), and one from Los Angeles County-University of Southern California (LAC-USC) (n = 100). An attending interventional cardiologist performed all groin punctures at Keck, and a trainee performed groin puncture at LAC-USC after detailed faculty instruction. A single reviewer retrospectively analyzed all angiograms. Puncture was recorded as occurring above, below, or at the femoral head.Percentage of punctures at the femoral head between LAC-USC vs Keck was not significantly different (93.0% vs 95.6%; P=.26). There was no significant difference in percentage of punctures below and above the femoral head between both groups, and no difference in complications.Femoral artery puncture at the femoral head is associated with improved outcomes. Our data show no significant difference between attending physicians' and trainees' ability to puncture at the level of the femoral head. Groin puncture using fluoroscopy can be taught to a high proficiency level with appropriate instruction.

Objectives: Although hyponatremia is a prognostic factor in acute heart failure (AHF), its influence on the acute clinical course of heart failure is unknown. Our objective was to evaluate the association of hyponatremia with diuretic response, renal function, and clinical outcomes in AHF. Methods: A retrospective study included 499 hospitalized AHF patients treated with intravenous loop diuretics for ≥48 h. Patients were grouped by nadir sodium concentrations (normonatremic, NN) ≥135 mEq/l, (mild hyponatremia, MHN) 130-134 mEq/l, and (moderate to severe hyponatremia, MSHN) Results: The incidence of hyponatremia was 54% (36% MHN, 18% MSHN). Maximum diuretic dose (furosemide equivalents: NN 84 ± 132 mg/day vs. MHN 114 ± 165 mg/day vs. MSHN 249 ± 450 mg/day, p < 0.001) and incidence of diuretic regimen escalation (NN 11% vs. MHN 16% vs. MSHN 44%, p < 0.001) were significantly higher in patients experiencing hyponatremia. Hyponatremia was also associated with a higher incidence of acute increases in serum creatinine (NN 27% vs. MHN 45% vs. MSHN 63%, p < 0.001), greater increases in blood urea nitrogen, longer hospital stay, and higher mortality. Outcome disparities to NN patients were similar whether hyponatremia was acute or present upon admission. Conclusions: Acute or admission hyponatremia, especially

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.

Background A growing body of evidence links coronary artery atherosclerosis and calcification to osteoporosis in women. Coronary endothelial dysfunction (CED) is associated with adverse cardiovascular events. We aimed to study the association of CED and development of osteoporosis. Methods Coronary vascular reactivity was evaluated in 225 women, greater than age 50, with non-obstructive coronary arteries, by administration of intracoronary acetylcholine during diagnostic angiography. CED was defined as Results The average age of the cohort was 60 years. Of 225 women, 60% (135) had CED. 18.2% (41 of 225 women) developed osteoporosis during follow-up. Women with CED were twice more likely to develop osteoporosis vs. women without CED (23% vs. 11.1%, p=0.024). Women who developed osteoporosis compared to those who did not had a markedly lower response (% change) in CBF: median (IQR)-4.3 (-28.3, 51.7) vs. 39.9 (-8.2, 106.0), p=0.007. In univariate analysis, CED was significantly associated with development of osteoporosis (p=0.024, relative risk 2.07, 95% CI: 1.07, 4.00). Multivariate analysis indicated CED as an independent predictor of osteoporosis (p=0.04). Discussion Endothelial dysfunction may account for or share similar mechanisms with development of osteoporosis in cardiac patients.

Author(s): Ye, Jianqin; Boyle, Andrew; Shih, Henry; Sievers, Richard E; Zhang, Yan; Prasad, Megha; Su, Hua; Zhou, Yan; Grossman, William; Bernstein, Harold S; Yeghiazarians, Yerem | Abstract: BackgroundEndogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI). However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs) have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear.Methodology/principal findingUsing "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+)CD45(-) cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1) in Sca-1(+)CD45(-) cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+)CD45(-) cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts.Conclusions/significanceThese studies demonstrate that cloned Sca-1(+)CD45(-) cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+)) precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

We compared therapeutic benefits of intramyocardial injection of unfractionated bone marrow cells (BMCs) versus BMC extract as treatments for myocardial infarction (MI), using closed-chest ultrasound-guided injection at a clinically relevant time post-MI. MI was induced in mice and the animals treated at day 3 with either: (i) BMCs from green fluorescent protein (GFP)-expressing mice (n = 14), (ii) BMC extract (n = 14), or (iii) saline control (n = 14). Six animals per group were used for histology at day 6 and the rest followed to day 28 for functional analysis. Ejection fraction was similarly improved in the BMC and extract groups versus control (40.6 +/- 3.4 and 39.1 +/- 2.9% versus 33.2 +/- 5.0%, P0.05) with smaller scar sizes. At day 6 but not day 28, both therapies led to significantly higher capillary area and number of arterioles versus control. At day 6, BMCs increased the number of cycling cardiomyocytes (CMs) versus control whereas extract therapy resulted in significant reduction in the number of apoptotic CMs at the border zone (BZ) versus control. Intracellular components within BMCs can enhance vascularity, reduce infarct size, improve cardiac function, and influence CM apoptosis and cycling early after therapy following MI. Intact cells are not necessary and death of implanted cells may be a major component of the benefit.

Background: A growing body of evidence links coronary artery atherosclerosis and calcification to osteoporosis in women. Coronary endothelial dysfunction (CED) is regarded as an early stage of coronary atherosclerosis. We aimed to study the association of CED and development of osteoporosis. Methods: Coronary endothelial function was evaluated in 194 postmenopausal women, greater than age 50, with non-obstructive coronary arteries, by administration of intracoronary acetylcholine during diagnostic angiography. CED was defined as

Although hyponatremia has prognostic implications in acute decompensated heart failure (ADHF), its influence on patient clinical course, including response to diuretics and renal function, has not been reported. Our objective was to evaluate the incidence of hyponatremia in ADHF and its association

Septal myectomy is the gold standard for medically-refractory patients with hypertrophic obstructive cardiomyopathy (HCM). There is a subset of patients who have severe exertional symptoms without a resting or provocable left ventricular outflow tract (LVOT) gradient on noninvasive testing. These