Clinician perspectives regarding CYP2C19 genotype testing in patients with critical limb ischemia: A Delphi approach.

OBJECTIVES: Antiplatelet therapy is an essential element in the management of patients with arterial vascular disease. In peripheral arterial disease (PAD), dual antiplatelet therapy (DAPT), primarily clopidogrel and aspirin, is routinely prescribed following intervention. There is sparse data regarding the need for DAPT, the appropriate duration, or the heterogeneity of treatment effects for antiplatelet regimens across patients, leading to potential uncertainty and heterogeneity around treatment practices. An example of heterogeneity of treatment effects is a patients' metabolizer status for the use of clopidogrel. The aim of the study was to (1) assess clinicians' knowledge of and attitudes toward managing patients with CYP2C19 mutations, (2) identify barriers to implementation of CYP2C19 testing and management policies, and (3) reach consensus for CYP2C19 testing and management strategies for patients with PAD who undergo peripheral vascular interventions (PVI). METHODS: A modified Delphi method was used to establish consensus amongst PAD interventionalists around CYP2C19 testing. All practicing Yale New Haven Hospital PAD interventionalists with backgrounds in interventional cardiology, vascular surgery, or interventional radiology were approached by email for participation. Round 1 included the collection of baseline demographic questions, knowledge questions, and three statements for consensus. Knowledge questions were rated on a 0-10 Likert scale with the following anchors: 0 ("Not at all"), 5 ("Neutral), and 10 ("Very Much"). Participants were asked to rate the importance of the three consensus statements on a 9-point Likert scale from 1 ("Strongly Disagree") to 10 ("Strongly Agree"). In Round 2, participants were shown the same consensus statements, the median response of the group from the previous round, and their previous answers. Participants were instructed to revise their rating using the results from the previous round. This process was repeated for Round 3. RESULTS: Of the 28 experts invited to participate, 13 agreed (46%). Participants were predominantly male (92.3%) and white (61.5%) with representation from interventional cardiology (46.2%) and vascular surgery (53.8%). Most participants reported more than 10+ years in practice (61.5%). PAD interventionalists felt they would benefit from more education regarding CYP2C19 mutations (median score 8.0, interquartile range 5.0-8.5). They indicated some familiarity with CYP2C19 mutations (7.0, 6.0-9.5) but did not feel strongly that CYP2C19 was important to their practice (6.0, 5.5-7.5). In each round, the median responses for the three consensus statements were 5, 6, and 9, respectively. With each successive round the interquartile range narrowed indicative of evolving consensus but did not reach the prespecified interquartile range for consensus of 1 for any of the statements. CONCLUSIONS: PAD interventionalists practicing at an academic health system recognize the heterogenous response of their patients to clopidogrel therapy but are unsure when to leverage genetic testing to improve outcomes for their patients. Our study identified gaps regarding PAD interventionalists' knowledge, perceived barriers, and attitudes toward CYP2C19 testing in PAD. This information highlights the need for randomized data on genetic testing for clopidogrel responsiveness in peripheral vascular disease following intervention to help guide antiplatelet management.

Lower extremity symptoms and ankle-brachial index screening as predictors of cardiovascular outcomes in Black adults.

BACKGROUND: The prevalence of peripheral artery disease (PAD) and leg symptoms are higher in Black than White adults. We studied the effects of self-reported lower extremity symptoms and ankle-brachial indices (ABI) groups on outcomes. METHODS: Black participants in the Jackson Heart Study with baseline ABI and PAD symptom assessments (exertional leg pain by the San Diego Claudication questionnaire) were included. Abnormal ABI was < 0.90 or > 1.40. Participants were divided into (1) normal ABI, asymptomatic, (2) normal ABI, symptomatic, (3) abnormal ABI, asymptomatic, and (4) abnormal ABI, symptomatic to examine their associations with MACE (stroke, myocardial infarction, fatal coronary heart disease) and all-cause mortality, using Kaplan-Meier survival curves and stepwise Cox proportional hazard models adjusting for Framingham risk factors. RESULTS: Of 4586 participants, mean age was 54.6 ± 12.6 years, with 63% women. Compared with participants with normal ABI who were asymptomatic, participants with abnormal ABI and leg symptoms had highest risk of MACE (adjusted HR 2.28; 95% CI 1.62, 3.22) and mortality (aHR 1.82; 95% CI 1.32, 2.56). Participants with abnormal ABI without leg symptoms had higher risk for MACE (aHR 1.49; 95% CI 1.06, 2.11) and mortality (aHR 1.44; 95% CI 1.12, 1.99). Participants with normal ABI and no leg symptoms did not have higher risks. CONCLUSION: Among Black adults, the highest risk for adverse outcomes were in symptomatic participants with abnormal ABIs, followed by asymptomatic participants with abnormal ABIs. These findings underscore the need for further studies to screen for PAD and develop preventative approaches in Black adults with asymptomatic disease.

Fetal Growth Restriction and Clinical Parameters of Newborns from HIV-Infected Romanian Women.

Background and Objectives: The present study assessed the fetal growth restriction and clinical parameters of both human immunodeficiency virus (HIV)-negative and HIV-positive newborns from HIV-infected mothers in two HIV-acquired immunodeficiency syndrome regional centers (RCs) in Constanta and Craiova, Romania, in order to evaluate the adverse birth-related outcomes. Materials and Methods: These represent a retrospective study conducted between 2008 and 2019, in which 408 pregnant HIV-positive women, 244 from Constanta RC and 164 from Craiova RC, were eligible to participate in the study. Consecutive singleton pregnancies delivered beyond 24 weeks of pregnancy were included. Growth restriction in newborns was defined as the birth weight (BW) being less than the third percentile, or three out of the following: BW < 10th percentile; head circumference (HC) < 10th percentile; birth length (BL) < 10th percentile; prenatal diagnosis of fetal growth restriction; and maternal pregnancy information. Of the 244 newborns delivered in Constanta, RC, 17 were HIV-positive, while in Craiova, RC, of the 164 newborns, 9 were HIV-positive. All HIV-positive women were on combined antiretroviral therapy (cART) during pregnancy, similar to all HIV-positive newborns who received ARTs for the first six weeks. We search for the influence of anthropometrical parameters (i.e., HC, BL, and BW), as well as clinical parameters (i.e., newborn sex and Apgar score) for both HIV-negative and HIV-positive newborns, along with the survival rate of HIV-positive newborns. Results: There were no differences in the sex of the newborns within either group, with more than 50% being boys. Similarly, the Apgar score did not show any statistically significant values between the two groups (i.e., p = 0.544 for HIV-positive newborns vs. p = 0.108 for HIV-negative newborns). Interestingly, our results showed that in Craiova, RC, there was a chance of 2.16 to find an HIV-negative newborn with an HC < 10th percentile and a 2.54 chance to find an HIV-negative newborn with a BL < 10th percentile compared to Constanta, RC, without any significant differences. On the contrary, Constanta, RC, represented a higher risk of death (i.e., 3.049 times, p = 0.0470) for HIV-positive newborns compared to Craiova, RC. Conclusions: Our results support the idea that follow-up of fetal growth restriction should be part of postnatal care in this high-risk population to improve adverse birth-related outcomes.

Safety and efficacy outcomes of the Pioneer Plus catheter in endovascular revascularization of lower extremity chronic total occlusions.

OBJECTIVE: Our aim was to evaluate the efficacy and safety outcomes of the Pioneer Plus catheter (Philips, San Diego, Calif) and report the in-hospital and 30-day outcomes of lower extremity chronic total occlusion (CTO) interventions assisted by the Pioneer Plus catheter. In addition, we explored the factors associated with procedural success. METHODS: We conducted a retrospective review of 135 consecutive procedures in 116 patients from July 2011 to September 2018 performed by eight operators with various levels of experience at a high-volume center where the Pioneer Plus catheter was used for lower extremity CTO. The patient demographics, preprocedural symptoms, preprocedural testing results, procedural setting, and angiography findings were abstracted. The outcomes were divided into device-related and procedure-related outcomes. Device-related efficacy outcome included procedural success. Device-related safety outcomes included device-related complications. Procedure-related outcomes included procedure-related complications, 30-day major adverse cardiovascular events, and 30-day major adverse limb events. We conducted univariate comparisons of the provider, patient, and procedural characteristics stratified by procedural success. RESULTS: Procedural success was observed in 118 procedures overall (87.4%), and success rates ≤95.8% were observed for operators with an experience level of >25 devices deployed. No device-related complications, such as pseudoaneurysm formation, vessel perforation, or arteriovenous fistula formation, were observed. The Pioneer Plus catheter was mostly often used for CTO in the superficial femoral and popliteal arteries. Overall, the procedure-related complications included access site hematoma (5.2%), major bleeding (0.7%), pseudoaneurysm formation (0.7%), distal embolization (1.5%), and acute arterial thrombosis (1.5%). The 30-day major adverse limb events included index limb unplanned amputation (0.7%), index limb reintervention (4.4%), and index limb acute limb ischemia (0.7%) and occurred in 5.9% of the procedures. The only factor associated with procedural success was operator experience (P < .0001). CONCLUSIONS: The results from the present study have shown that Pioneer Plus catheter use is safe and effective when used to cross lower extremity CTO. However, further investigation is needed to identify patient- and provider-level factors to optimize patient outcomes.

Systematic review and meta-analysis of outcomes of lower extremity peripheral arterial interventions in patients with and without chronic kidney disease or end-stage renal disease.

OBJECTIVE: Patients with chronic kidney disease (CKD) have a greater risk of peripheral arterial disease (PAD). Although individual studies have documented an association between CKD and/or end-stage renal disease (ESRD) and adverse outcomes in patients undergoing PAD interventions in an era of technological advances in peripheral revascularization, the magnitude of the effect size is unknown. Therefore, we performed a meta-analysis to compare the outcomes of PAD interventions for patients with CKD/ESRD with those patients with normal renal function, stratified by intervention type (endovascular vs surgical), reflecting contemporary practice. METHODS: Five databases were analyzed from January 2000 to June 2019 for studies that had compared the outcomes of lower extremity PAD interventions for patients with CKD/ESRD vs normal renal function. We included both endovascular and open interventions, with an indication of either claudication or critical limb ischemia. We analyzed the pooled odds ratios (ORs) across studies with 95% confidence intervals (CIs) using a random effects model. Funnel plot and exclusion sensitivity analyses were used for bias assessment. RESULTS: Seventeen observational studies with 13,140 patients were included. All included studies, except for two, had accounted for unmeasured confounding using either multivariable regression analysis or case-control matching. The maximum follow-up period was 114 months (range, 0.5-114 months). The incidence of target lesion revascularization (TLR) was greater in those with CKD/ESRD than in those with normal renal function (OR, 1.68; 95% CI, 1.25-2.27; P = .001). The incidence of major amputations (OR, 1.97; 95% CI, 1.37-2.83; P < .001) and long-term mortality (OR, 2.28; 95% CI, 1.45-3.58; P < .001) was greater in those with CKD/ESRD. The greater TLR rates with CKD/ESRD vs normal renal function were only seen with endovascular interventions, with no differences for surgical interventions. The differences in rates of major amputations and long-term mortality between the CKD/ESRD and normal renal function groups were statistically significant, regardless of the intervention type. CONCLUSIONS: Patients with CKD/ESRD who have undergone lower extremity PAD interventions had worse outcomes than those of patients with normal renal function. When stratifying our results by intervention (endovascular vs open surgery), greater rates of TLR for CKD/ESRD were only seen with endovascular and not with open surgical approaches. Major amputations and all-cause mortality were greater in the CKD/ESRD group, irrespective of the indication. Evidence-based strategies to manage this at-risk population who require PAD interventions are essential.

Drug-coated balloon versus plain old balloon angioplasty in femoropopliteal disease: An updated meta-analysis of randomized controlled trials.

BACKGROUND: Drug-coated balloon (DCB) angioplasty has emerged as a mainstay of therapy for the treatment of peripheral arterial disease (PAD) involving the superficial femoral and popliteal arteries. We performed a meta-analysis including all available randomized controlled trials (RCTs) to date which compare DCB to plain balloon angioplasty (POBA) in femoropopliteal disease (FPD). METHODS: Five databases were analyzed including EMBASE, PubMed, Cochrane, Scopus, and Web-of-Science from January 2000 to September 2018 for RCTs comparing DCB to POBA in patients with FPD. Heterogeneity was determined using Cochrane's Q-statistics. Random effects model was used. RESULTS: Twenty-two RCTs, including five trials of in-stent restenosis (ISR) intervention, with 3,217 patients were included in the analysis. Mean follow-up was approximately 21.6 ± 14.4 months. Overall, DCB use was associated with a 51% reduction in target vessel revascularization (TLR) when compared to POBA at follow-up (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.40-0.61, P < 0.0001). Rates of TLR were 45% lower in the DCB group when compared to POBA in patients with ISR (RR: 0.55, 95% CI: 0.37-0.81, P = 0.002). DCB was associated with lower rates of binary stenosis, late lumen loss and higher primary safety endpoints. Major amputation and mortality were not different between DCB and POBA. CONCLUSIONS: Use of DCBs is associated with improved vessel patency and a lower risk of TLR when compared to POBA in patients with FPD, especially in the setting of ISR. There was no difference in mortality between DCB and POBA in our meta-analysis. Extended follow-up of the available RCT data will be essential to analyze long-term device-related mortality.

Prospective chest pain evaluation in the emergency department with use of high-sensitivity C-reactive protein (PROCEED-CRP study).

We evaluated the clinical value of a single measurement of high-sensitivity C-reactive protein (hs- CRP) in patients presenting to the emergency department with chest pain. We screened 408 consecutive patients of whom 292 comprised the final cohort for this study. Hs-CRP measured in the emergency department (ED) in patients presenting with chest pain and admitted for evaluation of acute myocardial infarction was neither sensitive nor specific in predicting acute myocardial infarction, myocardial ischemia on SPECT imaging, need for coronary revascularization, or cardiovascular or all-cause rehospitalization at 30 days. In addition, use of a specific CRP cut off >1 was not associated with an increase in all-cause rehospitalization at 30 days.

Left ventricular noncompaction and aneurysm revealed by left ventriculography.

Left ventriculography (LVG) is sometimes not performed during cardiac catheterization when results of prior noninvasive tests are available. We present a rare case of left ventricular noncompaction coexisting with left ventricular aneurysm diagnosed during cardiac catheterization. LVG could provide additional information in patients with nonobstructive coronary artery disease and decreased ejection fraction on noninvasive tests.

Axial and para-axial loading response evaluation on human cadaver-harvested lumbar vertebral blocks: In vitro experiment with possible clinical implications for clinical practice.

The aim of the present study conducted on the lumbar spine was to confirm that the pronounced decrease in resistance in the system is a phenomenon that can be eminently affected by the adaptive changes that occur at the level of the intervertebral disc at axial mechanical stresses. The biomechanical trial was carried out on 11 lumbar segments L1-L5, gathered from adult human cadavers. The dissection considered the complete keeping of all bone, disc, articulated and ligamentous components in their anatomical position. All 11 samples were frozen 24 h prior to the performance of the biomechanical measurement. The specimens were placed in the testing device, their placement being conditioned by the estimated dimensional values. Thus, to calculate the load and axial resistance, the models were placed vertically, central between the test machine ferries. The testing was carried out by applying variable forces and displacement supervision. The displacement interval was represented by a segment of 0-10 mm with surveillance every 2 mm. Mobility in the sagittal plane (flexion earlier in our case) was much higher than that in the frontal plane, obviously limiting mobility via the intervertebral disc and articular complex through the presence of arches. Statistical analysis demonstrated the lack of any correlation values between the two types of movements (R2=0.005507), underlining the absence of any prediction elements. A noteworthy aspect is that the correlations appeared low, statistically insignificant, even within the same movement in the sagittal plane between the two levels, L1-L3 and L3-L5 (R2=0.610427), which may lead to the possibility of the emergence of significant differences in mobility between respective levels. The behavior type of the monitored specimens and the results obtained allowed the mapping of objective parallelism between the values obtained and the behavior in vivo of the lumbar vertebral segment.

Long-term outcome of Tako-tsubo cardiomyopathy.

BACKGROUND: Current data suggest an excellent outcome for patients with Tako-tsubo cardiomyopathy (TC). The objectives of this study were to evaluate the long-term outcome and the prognostic implication of thrombolysis in myocardial infarction myocardial perfusion grade (TMPG) in patients with TC. METHODS: Retrospective analysis of all patients diagnosed with TC at our hospital between 2003 and 2008. RESULTS: During the five-year period, we identified 27 patients with TC out of 1374 cases of emergent left heart catheterisation (2%). Mean follow-up was 27 ± 16 months. The majority were Caucasian (81%) female (96%), postmenopausal (96%), with a mean age of 68 ± 14 years. A precipitating stressor event was found in 74% of the patients, 30% being gastrointestinal triggers. Fourteen patients (52%) reached a combined end point of all cause death, cardiogenic shock, sudden cardiac death and rehospitalisation for cardiac reasons. TMPG was abnormal in 37% cases with no correlation with the outcome. CONCLUSIONS: The long-term outcome of patients with TC is worse than previously reported. TMPG does not correlate with the outcome in TC.

A rare cause of systolic murmur: unruptured right sinus of Valsalva aneurysm with right ventricular outflow tract obstruction and supracristal ventricular septal defect.

Dyspnea and heart murmur are common reasons for referrals in cardiology and both are associated with a broad differential diagnosis. Sinus of Valsalva aneurysms are rare abnormalities of the aortic root that should be considered in the differential diagnosis in young and middle aged patients. Sinus of Valsalva aneurysms are often associated with supracristal ventricular septal defects and can be identified on transthoracic echocardiography. Diagnosis of a SVA should trigger a careful search for ventricular septal defect, which may necessitate transesophageal echocardiography.

Utility of Intravascular Ultrasound in Peripheral Vascular Interventions: Systematic Review and Meta-Analysis.

OBJECTIVES: We sought to compare outcomes between intravascular ultrasound- (IVUS) versus angiography (AO)-guided peripheral vascular interventions (PVIs). Introduction: Intravascular ultrasound facilitates plaque visualization and angioplasty during PVIs for peripheral arterial disease. It is unclear whether IVUS may improve the durability of PVIs and lead to improved clinical outcomes. METHODS: This is a study-level meta-analysis of observational studies. The primary end points of this study were rates of primary patency and reintervention. Secondary end points included rates of vascular complications, periprocedural adverse events, amputations, technical success, all-cause mortality, and myocardial infarction. RESULTS: Eight observational studies were included in this analysis with 93 551 patients. Mean follow-up was 24.2 ± 15 months. Intravascular ultrasound-guided PVIs had similar patency rates when compared with AO-guided PVIs (relative risk [RR]: 1.30, 95% confidence interval [CI]: 0.99-1.71, P = .062). There was no difference in rates of reintervention in IVUS-guided PVIs when compared to non-IVUS-guided PVIs (RR: 0.41, 95% CI: 0.15-1.13, P = .085). There is a lower risk of periprocedural adverse events (RR: 0.81, 95% CI: 0.70-0.94, P = .006) and vascular complications (RR: 0.81, 95% CI: 0.68-0.96, P = .013) in the IVUS group. All-cause mortality (RR: 0.76, 95% CI: 0.56-1.04, P = .084), amputation rates (RR 0.83, 95% CI: 0.32-2.15, P = .705), myocardial infarctions (RR: 1.19, 95% CI: 0.58-2.41, P = .637), and technical success (RR: 1.01, 95% CI: 0.86-1.19, P = .886) were similar between the groups. Conclusions: Intravascular ultrasound-guided PVIs had similar primary patency and reintervention when compared with AO-guided PVIs with significantly lower rates of periprocedural adverse events and vascular complications in the IVUS-guided group.

ECG findings in acute left main coronary artery thrombosis: a case report and review of the literature.

Acute coronary syndrome due to left main coronary artery (LMCA) thrombosis is a catastrophic event associated with poor prognosis and high in-hospital mortality. Early recognition and emergent revascularization is vital for survival. Unfortunately, the electrocardiographic manifestations of LMCA thrombosis are nonspecific. This report describes the electrocardiogram (ECG) findings in a patient with LMCA thrombosis. A new right bundle branch block (RBBB) pattern, especially when associated with ST elevation in aVR and V1, should raise suspicion of this diagnosis.

Cardiac assessment of patients with Becker's muscular dystrophy.

Becker's muscular dystrophy (BMD) is one of the most common muscular dystrophy syndromes. The heart is always affected by myocardial fibrosis with early involvement of the right side. Traditionally, ECG, echocardiography and stress testing have been used to evaluate these patients. Cardiac MRI, offering superior assessment of the right side and visualization of the myocardial fibrosis could become the preferred imaging modality for evaluating patients with BMD.

Antiplatelet therapy for tibial balloon angioplasty: A clinical perspective.

Percutaneous transluminal tibial balloon angioplasty has an important role in the therapeutic approach of critical limb ischaemia. Despite a growing number of patients with critical limb ischaemia, there are no trials to guide the pharmacologic approach post intervention. Guidelines pertaining to the antiplatelet therapy post percutaneous transluminal tibial balloon angioplasty have not been developed. In addition, critical limb ischaemia patients have multiple comorbidities and a higher risk of bleeding. To examine the shortest duration of antiplatelet therapy post percutaneous transluminal tibial balloon angioplasty, we reviewed the preclinical data used to develop the standards for the current angioplasty technique.

Review of the Current Basic Science Strategies to Treat Critical Limb Ischemia.

Critical limb ischemia (CLI) is a highly morbid disease with many patients considered poor surgical candidates. The lack of treatment options for CLI has driven interest in developing molecular therapies within recent years. Through these translational medicine studies in CLI, much has been learned about the pathophysiology of the disease. Here, we present an overview of the macrovascular and microvascular changes that lead to the development of CLI, including impairment of angiogenesis, vasculogenesis, and arteriogenesis. We summarize the randomized clinical controlled trials that have used molecular therapies in CLI, and discuss the novel imaging modalities being developed to assess the efficacy of these therapies.

Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients.

BACKGROUND: Aging is a complex physiological phenomenon, intricately associated with cardiovascular pathologies, where platelets play a central pathophysiological role. Although antiplatelets are commonly employed to prevent and treat major adverse cardiovascular events, aging associated intraplatelet changes remain largely unexplored. METHODS: Platelets were studied in high cardiovascular risk patients (aged 40-100 years) comparing them to younger healthy subjects. This was followed by cross sectional and longitudinal mice studies. Flow cytometry, biochemical and molecular assays were used to study platelets comprehensively. FINDINGS: CVD Patients were categorized in the age groups 40-59, 60-79, and 80-100 years. Progressive decline in platelet health was observed in the 40-79 years age cohort, marked by increase in oxidative stress, hyperactivation and apoptotic markers. Paradoxically, this was reversed in patients aged above 79 years and the improved platelet phenotype was associated with lower oxidative damage. The platelets from the very old (80-100 year) group were found to be preloaded with increased antioxidants, which also contributed to higher resistance against induced redox insults. Cross sectional mouse studies excluded the effect of comorbidities and medications. Longitudinal mouse studies implicate an adaptive increase in antioxidant levels as the mechanism. INTERPRETATION: We report a novel age associated, non-linear redox regulation in platelets in both humans and mice. In advanced age, there occurs an adaptive increase in platelet antioxidants, reducing the intracellular ROS and leading to a healthier platelet phenotype. Clinically, our results advocate the use of less aggressive antiplatelet therapies for CVD in the elderly population. FUND: Study funded by NIH-NHLBI, RO1-HL122815 and RO1-HL115247.

Mitochondrial MsrB2 serves as a switch and transducer for mitophagy.

Mitophagy can selectively remove damaged toxic mitochondria, protecting a cell from apoptosis. The molecular spatial-temporal mechanisms governing autophagosomal selection of reactive oxygen species (ROS)-damaged mitochondria, particularly in a platelet (no genomic DNA for transcriptional regulation), remain unclear. We now report that the mitochondrial matrix protein MsrB2 plays an important role in switching on mitophagy by reducing Parkin methionine oxidation (MetO), and transducing mitophagy through ubiquitination by Parkin and interacting with LC3. This biochemical signaling only occurs at damaged mitochondria where MsrB2 is released from the mitochondrial matrix. MsrB2 platelet-specific knockout and in vivo peptide inhibition of the MsrB2/LC3 interaction lead to reduced mitophagy and increased platelet apoptosis. Pathophysiological importance is highlighted in human subjects, where increased MsrB2 expression in diabetes mellitus leads to increased platelet mitophagy, and in platelets from Parkinson's disease patients, where reduced MsrB2 expression is associated with reduced mitophagy. Moreover, Parkin mutations at Met192 are associated with Parkinson's disease, highlighting the structural sensitivity at the Met192 position. Release of the enzyme MsrB2 from damaged mitochondria, initiating autophagosome formation, represents a novel regulatory mechanism for oxidative stress-induced mitophagy.

Comorbidities frequency in Takotsubo syndrome: an international collaborative systematic review including 1109 patients.

BACKGROUND: To identify predisposing factors that can result in the onset of takotsubo syndrome, we performed an international, collaborative systematic review focusing on clinical characteristics and comorbidities of patients with takotsubo syndrome. METHODS: We searched and reviewed cited references up to August 2013 to identify relevant studies. Corresponding authors of selected studies were contacted and asked to provide additional quantitative details. Data from each study were extracted by 2 independent reviewers. The cumulative prevalence of presenting features and comorbidities was assessed. Nineteen studies whose authors sent the requested information were included in the systematic review, with a total of 1109 patients (951 women; mean age, 59-76 years). Evaluation of risk factors showed that obesity was present in 17% of patients (range, 2%-48%), hypertension in 54% (range, 27%-83%), dyslipidemia in 32% (range, 7%-59%), diabetes in 17% (range, 4%-34%), and smoking in 22% (range, 6%-49%). Emotional stressors preceded takotsubo syndrome in 39% of patients and physical stressors in 35%. The most common comorbidities were psychological disorders (24%; range, 0-49%), pulmonary diseases (15%; range, 0-22%), and malignancies (10%; range, 4%-29%). Other common associated disorders were neurologic diseases (7%; range, 0-22%), chronic kidney disease (7%; range, 2%-27%), and thyroid diseases (6%; range, 0-37%). CONCLUSIONS: Patients with takotsubo syndrome have a relevant prevalence of cardiovascular risk factors and associated comorbidities. Such of associations needs to be evaluated in further studies.