Chen W.-Y.,Kaohsiung Chang Gung Memorial Hospital |
Chen W.-Y.,Brigham and Women's Hospital |
Hong J.,Cardiovascular Division |
Hong J.,Brigham and Women's Hospital |
And 6 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy receptor for IL-33, blocking myocardial and vascular benefits, and is a prognostic biomarker in patients with cardiovascular diseases. Here we report that a highly local intramyocardial IL-33/ST2 conversation regulates the heart's response to pressure overload. Either endothelial-specific deletion of IL33 or cardiomyocyte-specific deletion of ST2 exacerbated cardiac hypertrophy with pressure overload. Furthermore, pressure overload induced systemic circulating IL-33 as well as systemic circulating IL-13 and TGF-beta1; this was abolished by endothelial-specific deletion of IL33 but not by cardiomyocyte-specific deletion of IL33. Our study reveals that endothelial cell secretion of IL-33 is crucial for translating myocardial pressure overload into a selective systemic inflammatory response. © 2015 PNAS.
Lindley K.J.,Cardiovascular Division |
Conner S.N.,University of Washington |
Cahill A.G.,University of Washington |
Novak E.,Cardiovascular Division |
Mann D.L.,Cardiovascular Division
Circulation: Heart Failure | Year: 2017
Background - Preeclampsia is a risk factor for the development of peripartum cardiomyopathy (PPCM), but it is unknown whether preeclampsia impacts clinical or left ventricular (LV) functional outcomes. This study sought to assess clinical and functional outcomes in women with PPCM complicated by preeclampsia. Methods and Results - This retrospective cohort study included women diagnosed with PPCM delivering at Barnes-Jewish Hospital between 2004 to 2014. The primary outcome was one-year event-free survival rate for the combined end point of death and hospital readmission. The secondary outcome was recovery of LV ejection fraction. Seventeen of 39 women (44%) with PPCM had preeclampsia. The groups had similar mean LV ejection fraction at diagnosis (29.6 with versus 27.3 without preeclampsia; P=0.5). Women with preeclampsia had smaller mean LV end-diastolic diameters (5.2 versus 6.0 cm; P=0.001), greater relative wall thickness (0.41 versus 0.35 mm Hg; P=0.009), and lower incidence of eccentric remodeling (12% versus 48%; P=0.03). Clinical follow-up was available for 32 women; 5 died of cardiovascular complications within 1 year of diagnosis (4/15 with versus 1/17 without preeclampsia; P=0.16). In time to event analysis, patients with preeclampsia had worse event-free survival during 1-year follow-up (P=0.047). Echocardiographic follow-up was available in 10 survivors with and 16 without preeclampsia. LV ejection fraction recovered in 80% of survivors with versus 25% without preeclampsia (P=0.014). Conclusions - PPCM with concomitant preeclampsia is associated with increased morbidity and mortality and different patterns of LV remodeling and recovery of LV function when compared with patients with PPCM that is not complicated by preeclampsia. © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., Heart Failure Society of America, and International Society for Heart & Lung Transplantation.
Phinikaridou A.,St Thomas Hospital |
Andia M.E.,St Thomas Hospital |
Andia M.E.,University of Santiago de Chile |
Saha P.,Cardiovascular Division |
And 4 more authors.
Circulation: Cardiovascular Imaging | Year: 2013
Background: Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Methods and Results: Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; P ANOVA<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10 -3 mm2]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10-3 mm2/s]). Conclusions: MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention. © 2013 American Heart Association, Inc.
News Article | December 17, 2015
Metastasis — the spread of cancer from one part of the body to others — accounts for more than 90 percent of cancer-related deaths. Although the cells that seed metastasis and the sites they tend to travel to have been increasingly studied over the years, little has been known about how cancer migrates from a primary site, such as breast tissue, to a secondary site, such as the brain or bone marrow. A study by researchers from Harvard-affiliated Brigham and Women’s Hospital (BWH), published in Nature Communications, offers a new view of how cancer cells extend their reach, co-opting and transforming normal cells through “metastatic hijacking.” The researchers also find that in preclinical models, pharmacological intervention can stop the hijack before it starts, pointing to new therapeutic targets for preventing cancer cells from spreading. “Metastasis remains a final frontier in the search for a cure for cancer,” said Shiladitya Sengupta of BWH’s Bioengineering Division in the Department of Medicine and corresponding author of the study. “For the past five years we have studied how cancer travels to other parts of the body, and what we find is that communication is key.” “By working together, our labs have been able to gain greater insights into cell-cell communication in tumor states, which will shed new light on cancer as a disease and the promise and potential of emerging innovative therapies,” said Elazer Edelman of BWH’s Cardiovascular Division in the Department of Medicine. Sengupta, Edelman, and colleagues began with a simple experiment. In the lab, they constructed a 3-D tumor matrix, complete with endothelial cells, and added metastatic breast cancer cells. They observed that instead of adhering together to form a sphere, the metastatic breast cancer cells spread out along the model’s blood vessels. Using a scanning electron microscope, the researchers detected long, thin tubes extending outward from the cells — nanoscale bridges that connected the cancer cells to normal tissue. The researchers found that the molecular profiles of some of the normal endothelial cells had been changed, and hypothesized that microRNAs were being transferred over the bridges into the endothelial cells. Upon closer examination, they found that the transformed endothelial cells now harbored two microRNAs that previously had been implicated in metastasis. The researchers then used chemical compounds to prevent the nanoscale bridges from forming, disrupting communication between the tumor cells and endothelium. They did so in the laboratory-constructed model and also in a mouse model, finding that pharmacological agents, including docetaxel, which is used to treat metastatic breast cancer, decreased the number of nanoscale bridges the cells formed. In mice pretreated with the pharmacological agents, the researchers observed a significant decrease in metastatic tumor burden. In future studies, the researchers will look to see if ATPase inhibitors — drugs that have been studied for treating HIV-AIDS — may also be able to inhibit metastasis by preventing the bridges from forming. “Our study opens up new avenues for exploration and suggests that these nanoscale membrane bridges may represent new therapeutics in managing metastatic breast cancer,” said Sengupta, who is an assistant professor of medicine at Harvard Medical School. “We plan to continue searching for and evaluating treatments that take aim at these conduits.” Other researchers who contributed to this work include Yamicia Connor, Sarah Tekleab, Shyama Nandakumar, Cherelle Walls, Yonatan Tekleab, Amjad Husain, Or Gadish, Venkata Sabbisetti, Shelley Kaushik, Seema Sehrawat, Ashish Kulkarni, Harold Dvorak and Bruce Zetter. This work was supported by the National Institutes of Health, a Department of Defense Breast Cancer Research Program Breakthrough Award, an American Lung Association Innovator Award, and the National Institute of General Medical Sciences.
Hutchinson M.D.,Cardiovascular Division |
Hutchinson M.D.,University of Pennsylvania |
Gerstenfeld E.P.,Cardiovascular Division |
Desjardins B.,Cardiovascular Division |
And 10 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2011
Background-Patients with nonischemic left ventricular cardiomyopathy (LVCM) and ventricular tachycardia (VT) have complex 3-dimensional substrate with variable involvement of the endocardium (ENDO) and epicardium (EPI). The purpose of this study was to determine whether ENDO unipolar (UNI) mapping with a larger electric field of view could identify EPI low bipolar (BIP) voltage regions in patients with LVCM undergoing VT ablation. Methods and Results-The reference value for normal ENDO unipolar voltage was determined from 6 patients without structural heart disease. Consecutive patients undergoing VT ablation over an 8-year period with detailed (>100 points) LV ENDO and EPI mapping and normal LV ENDO BIP voltage were identified. From this cohort, we compared patients with structurally normal hearts and normal EPI BIP voltage (EPI=, group 1) with patients with LVCM and low LV EPI BIP voltage regions present (EPI<, group 2). Confluent regions of ENDO UNI and EPI BIP low voltage (>2 cm2) were measured. The normal signal amplitude was >8.27 mV for LV ENDO UNI electrograms. Detailed LV ENDO-EPI maps in 5 EPI= patients were compared with 11 EPI< patients. Confluent ENDO UNI low-voltage regions were seen in 9 of 11 (82%) of the EPI< (group 2) patients compared with none of 5 EPI= (group 1) patients (P>0.001). In all 9 patients with ENDO UNI low voltage, the ENDO UNI low-voltage regions were directly opposite to an area of EPI BIP low voltage (61% ENDO UNI-EPI BIP low-voltage area overlap). Conclusions-EPI arrhythmia substrate can be reliably identified in most patients with LVCM using ENDO UNI voltage mapping in the absence of ENDO BIP abnormalities. © 2011 American Heart Association, Inc.
News Article | December 6, 2016
INGELHEIM, Germany & INDIANAPOLIS--(BUSINESS WIRE)--The U.S. Food and Drug Administration (FDA) approved a new indication for Jardiance® (empagliflozin) tablets to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. Jardiance® is the first type 2 diabetes treatment approved with this additional indication and the only oral type 2 diabetes medicine shown in a clinical trial to provide a life-saving cardiovascular benefit. Jardiance® is marketed by Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY). “As the only diabetes treatment approved by the FDA to reduce the risk of cardiovascular death, Jardiance® represents a tremendous step forward in our efforts to reduce the impact of heart disease among adults with type 2 diabetes and cardiovascular disease,” said Dr Georg van Husen, Corporate Senior Vice President, Head of the Therapeutic Area CardioMetabolism, Boehringer Ingelheim. “This approval is another example of our commitment to the discovery and development of treatment options for adults with type 2 diabetes. We believe that Jardiance® is an important treatment option for this patient population.” Jardiance® is not for people with type 1 diabetes or people with diabetic ketoacidosis (increased ketones in the blood or urine). The approval is based on breakthrough evidence from the landmark EMPA-REG OUTCOME® trial, which investigated the effects of Jardiance® compared with placebo when added to standard of care type 2 diabetes and cardiovascular medicines in adults with type 2 diabetes and established cardiovascular disease. In the trial, Jardiance® significantly reduced the risk of the combined primary endpoint of cardiovascular death, non-fatal heart attack or non-fatal stroke by 14 percent versus placebo (HR 0.86, 95% CI: 0.74-0.99); absolute risk reduction was 1.6 percent for Jardiance® versus placebo. This primary finding was driven by a significant 38 percent reduction in the risk of cardiovascular death (HR 0.62, 95% CI: 0.49-0.77); absolute risk reduction was 2.2 percent for patients taking Jardiance® versus placebo. There was no change in the risk of non-fatal heart attack (HR 0.87, 95% CI: 0.70-1.09) or non-fatal stroke (HR 1.24, 95% CI: 0.92-1.67). The cardiovascular benefits of Jardiance® were consistent among patient subgroups. Adults with type 2 diabetes should not take Jardiance® if they have severe kidney problems or are on dialysis, or if they are allergic to empagliflozin or any ingredient in Jardiance®. Jardiance® can cause dehydration and low blood pressure. Jardiance® can also cause increased ketones in the blood (ketoacidosis), serious urinary tract infection, acute kidney injury and impairment in renal function, low blood glucose when used with insulin or insulin secretagogues (e.g., sulfonylurea, a medication used to treat type 2 diabetes), vaginal yeast infections and yeast infections of the penis, and increased cholesterol. “People with diabetes are two to four times more likely to develop cardiovascular disease than people without diabetes. The new indication for empagliflozin enables physicians for the first time to provide adults with type 2 diabetes with a diabetes medication that can reduce their risk of dying from cardiovascular disease,” said Professor Christopher P. Cannon, M.D., Cardiovascular Division, Brigham and Women's Hospital and professor of medicine, Harvard Medical School. “It also gives physicians an opportunity to speak with and educate people with type 2 diabetes about their increased risk for cardiovascular disease and to help them understand this serious complication of their condition.” “Despite significant medical advances, approximately two out of three people with type 2 diabetes in the US still die from cardiovascular disease. The Boehringer Ingelheim and Lilly Diabetes Alliance is proud to bring a groundbreaking innovation to millions of adults with type 2 diabetes and established cardiovascular disease,” said Enrique Conterno, Senior Vice President and President, Lilly Diabetes. “As part of our ongoing commitment to people with type 2 diabetes, we are also expanding our efforts to educate the public on the link between cardiovascular disease and type 2 diabetes.” In 2014, Jardiance® was approved by the FDA as an adjunct to diet and exercise to improve glycemic control, or blood glucose levels, in adults with type 2 diabetes. EMPA-REG OUTCOME® was a long-term, multicenter, randomized, double-blind, placebo-controlled trial of more than 7,000 patients, from 42 countries, with type 2 diabetes and established cardiovascular disease. The study assessed the effect of Jardiance® (10 mg or 25 mg once daily) added to standard of care compared with placebo added to standard of care. Standard of care was comprised of glucose-lowering agents and cardiovascular drugs (including for blood pressure and cholesterol). The primary endpoint was defined as time to first occurrence of cardiovascular death, non-fatal heart attack or non-fatal stroke. Over a median of 3.1 years, Jardiance® significantly reduced the risk of cardiovascular death, non-fatal heart attack or non-fatal stroke by 14 percent versus placebo. Risk of cardiovascular death was reduced by 38 percent, with no significant difference in the risk of non-fatal heart attack or non-fatal stroke. The safety profile of Jardiance® in the EMPA-REG OUTCOME® trial was consistent with that of previous trials. The overall incidence of adverse events was similar to placebo. Approximately 29 million Americans and an estimated 415 million people worldwide have diabetes, and nearly 28 percent of Americans with diabetes—totaling 8 million people—are undiagnosed. In the U.S., approximately 12 percent of those aged 20 and older have diabetes. Type 2 diabetes is the most common type, accounting for an estimated 90 to 95 percent of all diagnosed adult diabetes cases in the U.S. Diabetes is a chronic condition that occurs when the body does not properly produce or use the hormone insulin. Due to the complications associated with diabetes, such as high blood sugar, high blood pressure and obesity, cardiovascular disease is a major complication and the leading cause of death associated with diabetes. People with diabetes are two to four times more likely to develop cardiovascular disease than people without diabetes. Approximately 50 percent of deaths in people with type 2 diabetes worldwide and 68 percent of deaths in people with type 2 diabetes in the U.S. are caused by cardiovascular disease. In the U.S., health care costs for managing cardiovascular conditions in patients with diabetes totaled more than $23 billion in 2012. Having diabetes can shorten a person’s lifespan by as much as six years compared with someone without diabetes.* And having both diabetes and a history of heart attack or stroke can shorten a person’s lifespan by as much as 12 years compared with someone without these conditions.** * Based on having a history of diabetes at age 60. ** Based on having a history of diabetes and heart attack or stroke at age 60. Jardiance® (empagliflozin) is an oral, once daily, highly selective sodium glucose co-transporter 2 (SGLT2) inhibitor approved for use in Europe, the United States and other markets around the world for the treatment of adults with type 2 diabetes. Jardiance® works by blocking the reabsorption of glucose (blood sugar) by the kidney, leading to urinary glucose excretion, and lowering blood glucose levels in people with type 2 diabetes. SGLT2 inhibition targets glucose directly and works independently of β-cell function and the insulin pathway. Jardiance® is not for people with type 1 diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine). This press release is issued from Boehringer Ingelheim Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where Boehringer Ingelheim and Eli Lilly and Company do business. Please click on the link below for ‘Notes to Editors’ and ‘References’:
Norton N.,Cardiovascular Division |
Robertson P.D.,University of Washington |
Rieder M.J.,University of Washington |
Zuchner S.,University of Miami |
And 6 more authors.
Circulation: Cardiovascular Genetics | Year: 2012
Background-Human exome sequencing is a recently developed tool to aid in the discovery of novel coding variants. Now broadly applied, exome sequencing data sets provide a novel opportunity to evaluate the allele frequencies of previously published pathogenic rare variants. Methods and Results-We examined the exome data set from the National Heart, Lung and Blood Institute Exome Sequencing Project and compared this data set with a catalog of 197 previously published rare variants reported as causative of dilated cardiomyopathy (DCM) from familial and sporadic cases. Of these 197, 33 (16.8%) were also present in the Exome Sequencing Project database, raising the question of whether they were uncommon polymorphisms. Supporting functional data has been published for 14 of the 33 (42%), suggesting they are unlikely to be false-positives. The frequencies of these functional variants in the Exome Sequencing Project data set ranged from 0.02 to 1.33% (median 0.04%), which when applied as a cutoff to filter variants in a DCM pedigree identified an additional DCM candidate gene. A greater proportion of sporadic DCM cases had variants that were present in the Exome Sequencing Project data set versus novel variants (ie, not in the Exome Sequencing Project; 44% versus 21%; P=0.002), suggesting some of the variants identified as disease causing in sporadic DCM are either false-positives or low penetrance alleles in human populations. Conclusions-Rare nonsynonymous variants identified in DCM subjects also present at very low frequencies in public databases are likely relevant for DCM. Allele frequencies >0.04% are of less certain pathogenicity, especially if identified in sporadic cases, although this cutoff should be viewed as preliminary. © 2012 American Heart Association, Inc.
Alonso A.,University of Minnesota |
Bengtson L.G.S.,University of Minnesota |
Maclehose R.F.,University of Minnesota |
Lutsey P.L.,University of Minnesota |
And 2 more authors.
Stroke | Year: 2014
BACKGROUND AND PURPOSE - : In randomized trials, patients with atrial fibrillation (AF) receiving dabigatran, a direct oral anticoagulant, had lower risk of intracranial bleeding (ICB) than those on warfarin. However, concerns exist about potential worse outcomes in dabigatran users if bleeding occurs, given the lack of approved reversal agents. Thus, we examined in-hospital mortality in AF patients with ICB being treated with dabigatran versus warfarin in a real-world population in the United States. METHODS - : We analyzed healthcare utilization claims in the Truven Health Marketscan Research Databases. The study sample included patients with AF admitted to a hospital with a primary diagnosis of ICB. Information on medications, inpatient, and outpatient diagnoses was obtained from available claims. Propensity score-adjusted risk ratios and 95% confidence intervals of in-hospital mortality comparing current users of dabigatran versus warfarin were estimated using relative risk regression. RESULTS - : Among 2391 AF patients admitted with ICB (2290 on warfarin, 101 on dabigatran), 531 died during their admission. In-hospital mortality was similar in those treated with warfarin (22%) or dabigatran (20%). Compared with warfarin users, the propensity score-adjusted risk ratio (95% confidence interval) of mortality in dabigatran users was 0.93 (0.62-1.37). Associations were similar across different ICB subtypes (intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hematoma). CONCLUSIONS - : In this sample of AF patients with ICB on oral anticoagulants, dabigatran was not associated with higher in-hospital mortality compared with warfarin. Hence, reluctance to use dabigatran because of a lack of approved reversal agents is not supported by our results. © 2014 American Heart Association, Inc..
Xiong Q.,Cardiovascular Division |
Xiong Q.,Center for Magnetic Resonance Research |
Ye L.,Cardiovascular Division |
Zhang P.,Cardiovascular Division |
And 10 more authors.
Circulation | Year: 2013
Background-: The use of cells derived from human induced pluripotent stem cells as cellular therapy for myocardial injury has yet to be examined in a large-animal model. Methods and Results-: Immunosuppressed Yorkshire pigs were assigned to 1 of 3 groups: A myocardial infarction group (MI group; distal left anterior descending coronary artery ligation and reperfusion; n=13); a cell-treatment group (MI with 4×10 vascular cells derived from human induced pluripotent stem cells administered via a fibrin patch; n=14); and a normal group (n=15). At 4 weeks, left ventricular structural and functional abnormalities were less pronounced in hearts in the cell-treated group than in MI hearts (P<0.05), and these improvements were accompanied by declines in scar size (10.4±1.6% versus 8.3±1.1%, MI versus cell-treatment group, P<0.05). The cell-treated group displayed a significant increase in vascular density and blood flow (0.83±0.11 and 1.05±0.13 mL·min·g, MI versus cell-treatment group, P<0.05) in the periscar border zone (BZ), which was accompanied by improvements in systolic thickening fractions (infarct zone,-10±7% versus 5±5%; BZ, 7±4% versus 23±6%; P<0.05). Transplantation of vascular cells derived from human induced pluripotent stem cells stimulated c-kit cell recruitment to BZ and the rate of bromodeoxyuridine incorporation in both c-kit cells and cardiomyocytes (P<0.05). Using a magnetic resonance spectroscopic saturation transfer technique, we found that the rate of ATP hydrolysis in BZ of MI hearts was severely reduced, and the severity of this reduction was linearly related to the severity of the elevations of wall stresses (r=0.82, P<0.05). This decline in BZ ATP utilization was markedly attenuated in the cell-treatment group. Conclusions-: Transplantation of vascular cells derived from human induced pluripotent stem cells mobilized endogenous progenitor cells into the BZ, attenuated regional wall stress, stimulated neovascularization, and improved BZ perfusion, which in turn resulted in marked increases in BZ contractile function and ATP turnover rate. © 2013 American Heart Association, Inc.
Tschabrunn C.M.,Harvard University |
Roujol S.,Cardiovascular Division |
Nezafat R.,Cardiovascular Division |
Faulkner-Jones B.,Beth Israel Deaconess Medical Center |
And 3 more authors.
Heart Rhythm | Year: 2016
Background Human ventricular tachycardia (VT) after myocardial infarction usually occurs because of subendocardial reentrant circuits originating in scar tissue that borders surviving myocardial bundles. Several preclinical large animal models have been used to further study postinfarct reentrant VT, but with varied experimental methodologies and limited evaluation of the underlying substrate or induced arrhythmia mechanism. Objective We aimed to develop and characterize a swine model of scar-related reentrant VT. Methods Thirty-five Yorkshire swine underwent 180-minute occlusion of the left anterior descending coronary artery. Thirty-one animals (89%) survived the 6-8-week survival period. These animals underwent cardiac magnetic resonance imaging followed by electrophysiology study, detailed electroanatomic mapping, and histopathological analysis. Results Left ventricular (LV) ejection fraction measured using CMR imaging was 36% ± 6.6% with anteroseptal wall motion abnormality and late gadolinium enhancement across 12.5% ± 4.1% of the LV surface area. Low voltage measured using endocardial electroanatomic mapping encompassed 11.1% ± 3.5% of the LV surface area (bipolar voltage ≤1.5 mV) with anterior, anteroseptal, and anterolateral involvement. Reentrant circuits mapped were largely determined by functional rather than fix anatomical barriers, consistent with "pseudo-block" due to anisotropic conduction. Sustained monomorphic VT was induced in 28 of 31 swine (90%) (67 VTs; 2.4 ± 1.1; range 1-4) and characterized as reentry. VT circuits were subendocardial, with an arrhythmogenic substrate characterized by transmural anterior scar with varying degrees of fibrosis and myocardial fiber disarray on the septal and lateral borders. Conclusion This is a well-characterized swine model of scar-related subendocardial reentrant VT. This model can serve as the basis for further investigation in the physiology and therapeutics of humanlike postinfarction reentrant VT. © 2016 Heart Rhythm Society.