Rahul P Sharma, MBBS, FRACP

All Publications

• Transcatheter Valve Replacement in Severe Tricuspid Regurgitation. The New England journal of medicine Hahn, R. T., Makkar, R., Thourani, V. H., Makar, M., Sharma, R. P., Haeffele, C., Davidson, C. J., Narang, A., O'Neill, B., Lee, J., Yadav, P., Zahr, F., Chadderdon, S., Eleid, M., Pislaru, S., Smith, R., Szerlip, M., Whisenant, B., Sekaran, N. K., Garcia, S., Stewart-Dehner, T., Thiele, H., Kipperman, R., Koulogiannis, K., Lim, D. S., Fowler, D., Kapadia, S., Harb, S. C., Grayburn, P. A., Sannino, A., Mack, M. J., Leon, M. B., Lurz, P., Kodali, S. K. 2024

  Abstract

  Severe tricuspid regurgitation is associated with disabling symptoms and an increased risk of death. Data regarding outcomes after percutaneous transcatheter tricuspid-valve replacement are needed.In this international, multicenter trial, we randomly assigned 400 patients with severe symptomatic tricuspid regurgitation in a 2:1 ratio to undergo either transcatheter tricuspid-valve replacement and medical therapy (valve-replacement group) or medical therapy alone (control group). The hierarchical composite primary outcome was death from any cause, implantation of a right ventricular assist device or heart transplantation, postindex tricuspid-valve intervention, hospitalization for heart failure, an improvement of at least 10 points in the score on the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS), an improvement of at least one New York Heart Association (NYHA) functional class, and an improvement of at least 30 m on the 6-minute walk distance. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy.A total of 267 patients were assigned to the valve-replacement group and 133 to the control group. At 1 year, the win ratio favoring valve replacement was 2.02 (95% confidence interval [CI], 1.56 to 2.62; P<0.001). In comparisons of patient pairs, those in the valve-replacement group had more wins than the control group with respect to death from any cause (14.8% vs. 12.5%), postindex tricuspid-valve intervention (3.2% vs. 0.6%), and improvement in the KCCQ-OS score (23.1% vs. 6.0%), NYHA class (10.2% vs. 0.8%), and 6-minute walk distance (1.1% vs. 0.9%). The valve-replacement group had fewer wins than the control group with respect to the annualized rate of hospitalization for heart failure (9.7% vs. 10.0%). Severe bleeding occurred in 15.4% of the valve-replacement group and in 5.3% of the control group (P = 0.003); new permanent pacemakers were implanted in 17.4% and 2.3%, respectively (P<0.001).For patients with severe tricuspid regurgitation, transcatheter tricuspid-valve replacement was superior to medical therapy alone for the primary composite outcome, driven primarily by improvements in symptoms and quality of life. (Funded by Edwards Lifesciences; TRISCEND II ClinicalTrials.gov number, NCT04482062.).

  View details for DOI 10.1056/NEJMoa2401918

  View details for PubMedID 39475399

• Quality of Life After Transcatheter Tricuspid Valve Replacement: 1-Year Results From TRISCEND II Pivotal Trial. Journal of the American College of Cardiology Arnold, S. V., Hahn, R. T., Thourani, V. H., Makkar, R., Makar, M., Sharma, R. P., Haeffele, C., Davidson, C. J., Narang, A., O'Neill, B., Lee, J., Yadav, P., Zahr, F., Chadderdon, S., Eleid, M., Pislaru, S., Smith, R., Szerlip, M., Whisenant, B., Sekaran, N., Garcia, S., Stewart-Dehner, T., Grayburn, P. A., Sannino, A., Snyder, C., Zhang, Y., Mack, M. J., Leon, M. B., Lurz, P., Kodali, S., Cohen, D. J. 2024

  Abstract

  Severe tricuspid regurgitation (TR) often causes substantial impairment in patient-reported health status (ie, symptoms, physical and social function, and quality of life), which may improve with transcatheter tricuspid valve replacement (TTVR).We performed an in-depth analysis of health status of patients enrolled in the TRISCEND (Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy using a Novel Device) II pivotal trial to help quantify the benefit of intervention to patients.The TRISCEND II pivotal trial randomized 400 patients with symptomatic and severe or greater TR 2:1 to TTVR with the EVOQUE tricuspid valve replacement system plus optimal medical therapy (OMT) or OMT alone. Health status was assessed with the Kansas City Cardiomyopathy Questionnaire and the 36-Item Short Form Health Survey. Changes in health status over 1 year were compared between treatment groups using mixed-effects repeated-measures models.The analysis cohort included 392 patients, of whom 259 underwent attempted TTVR and 133 received OMT alone (mean age 79.2 ± 7.6 years, 75.5% women, 56.1% with massive or torrential TR). Patients had substantially impaired health status at baseline (mean Kansas City Cardiomyopathy Questionnaire Overall Summary Score [KCCQ-OS] 52.1 ± 22.8; mean 36-Item Short Form Health Survey physical component summary score 35.2 ± 8.4). TTVR+OMT patients reported significantly greater improvement in both disease-specific and generic health status at each follow-up time point. Mean between-group differences in the KCCQ-OS favored TTVR+OMT at each time point: 11.8 points (95% CI: 7.4-16.3 points) at 30 days, 20.8 points (95% CI: 16.1-25.5 points) at 6 months, and 17.8 points (95% CI: 13.0-22.5 points) at 1 year. In subgroup analyses, TTVR+OMT improved health status to a greater extent among patients with torrential or massive TR vs severe TR (treatment effect 23.3 vs 22.6 vs 11.3; interaction P = 0.049). At 1 year, 64.6% of TTVR+OMT patients were alive and well (KCCQ-OS ≥60 points and no decline of ≥10 points from baseline) compared with 31.0% with OMT alone.Compared with OMT alone, treatment of patients with symptomatic and severe or greater TR with TTVR+OMT resulted in substantial improvement in patients' symptoms, function, and quality of life. These benefits were evident 30 days after TTVR, continued to increase through 6 months, and remained durable through 1 year. (TRISCEND II Pivotal Trial [Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy using a Novel Device]; NCT04482062).

  View details for DOI 10.1016/j.jacc.2024.10.067

  View details for PubMedID 39480380

• Mortality Burden for Patients With Untreated Aortic Regurgitation. JACC. Advances Généreux, P., Amoroso, N. S., Thourani, V. H., Rodriguez, E., Sharma, R. P., Pinto, D. S., Kwon, M., Dobbles, M., Pellikka, P. A., Gillam, L. D. 2024; 3 (10): 101228

  Abstract

  Aortic valve replacement (AVR) is indicated in patients with severe aortic regurgitation (AR); however, certain clinical factors may identify patients with less-than-severe AR at high mortality risk if untreated.The authors sought to characterize key associations with mortality across the spectrum of AR in patients not treated with AVR from a large, contemporary database.We analyzed patients >18 years of age with documented AR assessment in a deidentified real-world data set from 27 U.S. institutions with appropriate permissions (egnite Database, egnite, Inc). Diagnosed AR severity was extracted from echocardiographic reports using a natural language processing-based algorithm. Cox multivariable analysis modeled the impact of key factors on untreated mortality according to AR severity.In total, 81,378 patients were included for analysis. Hazard ratios for mortality were 1.26 (95% CI: 1.18-1.35) and 2.37 (95% CI: 1.96-2.87) for moderate and severe AR, respectively. Other significant associations included left ventricular (LV) ejection fraction ≤55% (1.09 [95% CI: 1.02-1.15]), LV dilation (1.34 [95% CI: 1.21-1.48]), left atrial dilation (1.09 [95% CI: 1.03-1.16]), atrial fibrillation (1.11 [1.04-1.17]), and elevated B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide (1.71 [95% CI: 1.60-1.84]). Modeled mortality risk increased with the presence of these key factors both alone and in combination.In patients with untreated AR, LV remodeling, left atrial remodeling, and other markers of cardiac damage are associated with substantial mortality risk, both for severe and moderate AR. Further study is needed to determine whether AVR is warranted in patients with less-than-severe AR with at-risk factors.

  View details for DOI 10.1016/j.jacadv.2024.101228

  View details for PubMedID 39296816

  View details for PubMedCentralID PMC11408366

• Benchtop Flow Stasis Quantification: In Vitro Methods and In Vivo Possibilities. Cardiovascular engineering and technology Sadri, V., Midha, P. A., Madukauwa-David, I. D., Kamioka, N., Trusty, P. M., Nair, P. J., Cohen, S., Raghav, V., Sharma, R., Babaliaros, V., Yoganathan, A. P. 2024

  Abstract

  PURPOSE: Neo-sinus flow stasis has ben correlated with transcatheter heart valve (THV) thrombosis severity and occurrence. Standard benchtop flow field quantification techniques require optical access or modified prosthesis models that may not reflect the true nature of the original valve. En face and fluoroscopic videodensitometry enable visualization of washout in regions otherwise unviewable.METHODS: This study compares two in vitro methods of assessing flow stasis in scenarios with insufficient optical access for traditional techniques such as particle image velocimetry (PIV). A series of seven paired experiments were conducted using a previously described laser-enhanced video densitometry (LEVD) and fluoroscopic video densitometry (FVD). Both sets of experiments were analyzed to calculate washout time as a measure of flow stasis. A novel flow stasis measure termed contrast attenuation ratio (CAR) is proposed as a viable single measure of flow stasis obtainable from only a small number of cardiac cycles of in vitro or in vivo fluoroscopic data. Retrospective fluoroscopic datasets (n=72) were analyzed to assess the feasibility of obtaining this metric from routine clinical practice and its ability to stratify results.RESULTS: Neo-sinus flow stasis calculated from in vitro fluoroscopy was well correlated with LEVD (r2=0.77, p=0.009). The newly proposed CAR metric showed good agreement with the commonly used "washout time" measure of flow stasis (r2=0.91, p<0.001) while allowing for assessment with incomplete or truncated data. As a proof of concept, CAR was measured in 72 consecutive retrospective fluoroscopic datasets. CAR averaged 10.6±4.6% with a range of 1.5-20.3% in these patients.CONCLUSIONS: This study demonstrates two in vitro methods that can be used to assess relative flow stasis in otherwise optically inaccessible regions surrounding cardiac or vascular implants. In addition, the fluoroscopic benchtop technique was used to validate a metric that allows for extension to routine clinical fluoroscopy. This contrast attenuation ratio (CAR) metric was found to be both accurate and clinically obtainable, and potentially offers a new method for valve thrombosis risk stratification.

  View details for DOI 10.1007/s13239-024-00750-1

  View details for PubMedID 39285066

• Impact of Tricuspid Regurgitation on Outcomes of Transcatheter Aortic Valve Replacement With Balloon-Expandable Valves. JACC. Cardiovascular interventions Zahr, F., Elmariah, S., Vemulapalli, S., Kodali, S. K., Hahn, R. T., Anderson, A. S., Eleid, M. F., Davidson, C. J., Sharma, R. P., O'Neill, W. W., Bethea, B., Thourani, V. H., Chakravarty, T., Gupta, A., Makkar, R. R. 2024; 17 (16): 1916-1931

  Abstract

  Tricuspid regurgitation (TR) is highly prevalent in the transcatheter aortic valve replacement (TAVR) population, but clear management guidelines are lacking.The aims of this study were to elucidate the prevalence and consequences of severe TR in patients with aortic stenosis undergoing TAVR and to examine the change in TR post-TAVR, including predictors of improvement and its impact on longer term mortality.Using Centers for Medicare and Medicaid Services-linked TVT (Transcatheter Valve Therapy) Registry data, a propensity-matched analysis was performed among patients undergoing TAVR with baseline mild, moderate, or severe TR. Kaplan-Meier estimates were used to assess the impact of TR on 3-year mortality. Multivariable analysis identified predictors of 30-day TR improvement.Of the 312,320 included patients, 84% had mild, 13% moderate, and 3% severe TR. In a propensity-matched cohort, severe baseline TR was associated with higher in-hospital mortality (2.5% vs 2.1% for moderate TR and 1.8% for mild TR; P = 0.009), higher 1-year mortality (24% vs 19.6% for moderate TR and 16.6% for mild TR; P < 0.0001), and 3-year mortality (54.2% vs 48.5% for moderate TR and 43.3% for mild TR; P < 0.0001). Among the patients with severe TR at baseline, 76.4% improved to moderate or less TR 30 days after TAVR. Baseline mitral regurgitation moderate or greater, preserved ejection fraction, higher aortic valve gradient, and better kidney function predicted TR improvement after TAVR. However, severe 30-day residual TR was associated with higher 1-year mortality (27.4% vs 18.7% for moderate TR and 16.8% for mild TR; P < 0.0001).Severe baseline and 30-day residual TR after TAVR are associated with increased mortality up to 3 years. This analysis identifies a higher risk group that could be evaluated for the recently approved tricuspid interventions.

  View details for DOI 10.1016/j.jcin.2024.07.005

  View details for PubMedID 39197990

• Paravalvular Leak Closure After Self-Expanding Transcatheter Aortic Valve Replacement Using a Steerable Sheath. Journal of the Society for Cardiovascular Angiography & Interventions Dawson, L. P., Kim, I., Haeffele, C., Sharma, R. 2024; 3 (8): 102020

  Abstract

  We present the case of an 82-year-old woman with persistent fatigue, exertional dyspnea, and dizziness related to a paravalvular leak following a self-expanding transcatheter aortic valve replacement. Successful closure was performed using a steerable sheath to negotiate a vascular plug closure device through the self-expanding valve structure.

  View details for DOI 10.1016/j.jscai.2024.102020

  View details for PubMedID 39166159

• Clinical journey for patients with aortic regurgitation: A retrospective observational study from a multicenter database. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Amoroso, N. S., Sharma, R. P., Généreux, P., Pinto, D. S., Dobbles, M., Kwon, M., Thourani, V. H., Gillam, L. D. 2024

  Abstract

  Data using real-world assessments of aortic regurgitation (AR) severity to identify rates of Heart Valve Team evaluation and aortic valve replacement (AVR), as well as mortality among untreated patients, are lacking. The present study assessed these trends in care and outcomes for real-world patients with documented AR.Using a deidentified data set (January 2018-March 2023) representing 1,002,853 patients >18 years of age from 25 US institutions participating in the egnite Database (egnite, Inc.) with appropriate permissions, patients were classified by AR severity in echocardiographic reports. Rates of evaluation by the Heart Valve Team, AVR, and all-cause mortality without AVR were examined using Kaplan-Meier estimates and compared using the log-rank test.Within the data set, 845,113 patients had AR severity documented. For moderate-to-severe or severe AR, respectively, 2-year rates (95% confidence interval) of evaluation by the Heart Valve Team (43.5% [41.7%-45.3%] and 65.4% [63.3%-67.4%]) and AVR (19.4% [17.6%-21.1%] and 46.5% [44.2%-48.8%]) were low. Mortality at 2 years without AVR increased with greater AR severity, up to 20.7% for severe AR (p < 0.001). In exploratory analyses, 2-year mortality for untreated patients with left ventricular end-systolic dimension index > 25 mm/m2 was similar for moderate (34.3% [29.2%-39.1%]) and severe (37.2% [24.9%-47.5%]) AR.Moderate or greater AR is associated with poor clinical outcomes among untreated patients at 2 years. Rates of Heart Valve Team evaluation and AVR were low for those with moderate or greater AR, suggesting that earlier referral to the Heart Valve Team could be beneficial.

  View details for DOI 10.1002/ccd.31085

  View details for PubMedID 38764317

• A case report of successful primary percutaneous coronary intervention to an occluded anomalous left main coronary artery arising from the right coronary sinus. European heart journal. Case reports Wong, C. C., Pogatchnik, B. P., Clark, D. E., Sharma, R. P. 2024; 8 (4): ytae192

  Abstract

  Background: Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital abnormality that may be encountered during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).Case summary: A 65-year-old man presented with chest pain and signs of heart failure. Electrocardiogram demonstrated atrial fibrillation with ST elevation in the high lateral leads, and he was taken emergently to the cardiac catheterization laboratory for primary PCI. Coronary angiography identified the culprit to be an occluded anomalous left main coronary artery (LMCA) arising from the right coronary cusp, and primary PCI was successfully performed in the LMCA and the left anterior descending artery (LAD). Computed tomography angiography confirmed a benign retroaortic course of the anomalous LMCA with no additional high-risk features, as well as a new left atrial appendage thrombus. He subsequently developed deep venous thrombosis, acute pulmonary embolism, and acute kidney injury secondary to renal artery embolism with associated infarction. Workup for patent foramen ovale and thrombophilia were negative, and he was discharged in a stable condition. At 2-month follow-up, he was asymptomatic with no evidence of myocardial ischaemia on stress cardiac magnetic resonance imaging.Discussion: We present the first reported case of an occluded anomalous LMCA arising from the right coronary sinus in a patient presenting with STEMI. Rapid recognition of this congenital anomaly and selection of an appropriate guide catheter were keys to achieving timely reperfusion and a good outcome in this case.

  View details for DOI 10.1093/ehjcr/ytae192

  View details for PubMedID 38665427

• Racial/Ethnic Disparities in Aortic Valve Replacement Among Medicare Beneficiaries in the United States, 2012-2019. The American journal of medicine Gupta, A., Mori, M., Wang, Y., Pawar, S. G., Vahl, T., Nazif, T., Onuma, O., Yong, C. M., Sharma, R., Kirtane, A. J., Forrest, J. K., George, I., Kodali, S., Chikwe, J., Geirsson, A., Makkar, R., Leon, M. B., Krumholz, H. M. 2024

  Abstract

  PURPOSE: There are concerns that transcatheter or surgical aortic valve replacement (TAVR/SAVR) procedures are preferentially available to White patients.OBJECTIVE: Our objective was to examine differences in utilization of aortic valve replacement and outcomes by race/ethnicity in the US for patients with aortic stenosis.METHODS: We performed a serial cross-sectional cohort study of 299,976 Medicare beneficiaries hospitalized with principal diagnosis of aortic stenosis between 2012 and 2019 stratified by self-reported race/ethnicity (Black, Hispanic, Asian, Native American, and White). Outcomes included aortic valve replacement rates within 6 months of index hospitalization and associated procedural outcomes, including 30-day readmission, 30-day and 1-year mortality.RESULTS: Within 6 months of an index admission for aortic stenosis, 86.8% (122,457 SAVR; 138,026 TAVR) patients underwent aortic valve replacement. Overall, compared with White people, Black [HR 0.87 (0.85-0.89)], Hispanic [0.92 (0.88 - 0.96)], and Asian [0.95 (0.91 - 0.99)] people were less likely to receive aortic valve replacement. Among patients who were admitted emergently/urgently, White patients (41.1%, 95% CI 40.7-41.4) had a significantly higher aortic valve replacement rate compared with Black (29.6%, 95% CI 28.3-30.9), Hispanic (36.6%, 95% CI 34.0-39.3), and Asian patients (35.4%, 95% CI 32.3-38.9). Aortic valve replacement rates increased annually for all race/ethnicities. There were no significant differences in 30-day or 1-year mortality by race/ethnicity.CONCLUSIONS: Aortic valve replacement rates within six months of aortic stenosis admission are lower for Black, Hispanic, and Asian people compared to White people. These race-related differences in aortic stenosis treatment reflect complex issues in diagnosis and management, warranting a comprehensive reassessment of the entire care spectrum for disadvantaged populations.

  View details for DOI 10.1016/j.amjmed.2023.12.026

  View details for PubMedID 38190959

• Mitral Transcatheter Edge-to-Edge Repair With the PASCAL Precision System: Device Knobology and Review of Advanced Steering Maneuvers. Structural heart : the journal of the Heart Team Garcia, S., Elmariah, S., Cubeddu, R. J., Zahr, F., Eleid, M. F., Kodali, S. K., Seshiah, P., Sharma, R., Lim, D. S. 2024; 8 (1): 100234

  Abstract

  In 2022, the Food and Drug Administration approved a second mitral transcatheter edge-to-edge repair device for the treatment of primary mitral regurgitation (PASCAL Precision Transcatheter Valve Repair System, Edwards Lifesciences, Irvine, CA). The PASCAL Precision system consists of a guide sheath, implant system, and accessories. The implant system consists of a steerable catheter, an implant catheter, and the implant (PASCAL or PASCAL Ace). The guide sheath and steerable catheter move and flex independently from each other and are not keyed, allowing for freedom of rotation in three dimensions. This manuscript provides an overview of the PASCAL Precision system and describes the basic and advanced steering maneuvers to facilitate effective and safe mitral transcatheter edge-to-edge repair.

  View details for DOI 10.1016/j.shj.2023.100234

  View details for PubMedID 38283574

  View details for PubMedCentralID PMC10818146

• Effect of Ascending Aortic Curvature on Flow in the Sinus and Neo-sinus Following TAVR: A Patient-Specific Study. Annals of biomedical engineering Kim, J. H., Sadri, V., Chen, H., Bhat, S., Kohli, K., Makkar, R., Babaliaros, V. C., Sharma, R. P., Yoganathan, A. P. 2023

  Abstract

  Patient-specific aortic geometry and its influence on the flow in the vicinity of Transcatheter Aortic Valve (TAV) has been highlighted in numerous studies using both in silico and in vitro experiments. However, there has not yet been a detailed Particle Image Velocimetry (PIV) experiment conducted to quantify the relationship between the geometry, flow downstream of TAV, and the flow in the sinus and the neo-sinus. We tested six different patient-specific aorta models with a 26-mm SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) in a left heart simulator with coronary flow. Velocities in all three cusps and circulation downstream of TAV were computed to evaluate the influence of the ascending aorta curvature on the flow field. The in vitro analysis showed that the patient-specific aortic curvature had positive correlation to the circulation in the ascending aorta (p = 0.036) and circulation had negative correlation to the particle washout time in the cusps (p = 0.011). These results showed that distinct vortical flow patterns in the ascending aorta as the main jet impinges on the aortic wall causes a recirculation region that facilitates the flow back into the sinus and the neo-sinus, thus reducing the risk of flow stagnation and washout time.

  View details for DOI 10.1007/s10439-023-03392-x

  View details for PubMedID 37922056

  View details for PubMedCentralID 8386968

• Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study. European heart journal Kodali, S., Hahn, R. T., Makkar, R., Makar, M., Davidson, C. J., Puthumana, J. J., Zahr, F., Chadderdon, S., Fam, N., Ong, G., Yadav, P., Thourani, V., Vannan, M. A., O'Neill, W. W., Wang, D. D., Tchétché, D., Dumonteil, N., Bonfils, L., Lepage, L., Smith, R., Grayburn, P. A., Sharma, R. P., Haeffele, C., Babaliaros, V., Gleason, P. T., Elmariah, S., Inglessis-Azuaje, I., Passeri, J., Herrmann, H. C., Silvestry, F. E., Lim, S., Fowler, D., Webb, J. G., Moss, R., Modine, T., Lafitte, S., Latib, A., Ho, E., Goldberg, Y., Shah, P., Nyman, C., Rodés-Cabau, J., Bédard, E., Brugger, N., Sannino, A., Mack, M. J., Leon, M. B., Windecker, S. 2023

  Abstract

  For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes.The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year.Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure.In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

  View details for DOI 10.1093/eurheartj/ehad667

  View details for PubMedID 37930776

• Contemporary Practice Patterns and Outcomes for Patients With Mitral Regurgitation: Results From a Large Multicenter Real-World Database Sharma, R., Cubeddu, R., Genereux, P., Eberst, K., Rodriguez, E., Gillam, L. ELSEVIER SCIENCE INC. 2023: B179-B180

  View details for Web of Science ID 001108754600434

• Patient-Reported Outcomes in Tricuspid Valve Intervention: Patient Preference Results From the TRISCEND II Trial Brener, M., Barker, C., Davidson, C., Narang, A., Sharma, R., Haeffele, C., Yadav, P., Thourani, V., Kodali, S., Hahn, R., Makkar, R., Makar, M., Hausleiter, J., Nabauer, M., O'Neill, W., Wang, D., Lindman, B., Zahr, F., Chadderdon, S., Eleid, M., Pislaru, S., Mancilla, M., Kemp, L., Mollenkopf, S., Ryan, M., Cohen, D. ELSEVIER SCIENCE INC. 2023: B289-B290

  View details for Web of Science ID 001108754600701

• The Mortality Burden of Untreated Aortic Stenosis. Journal of the American College of Cardiology Généreux, P., Sharma, R. P., Cubeddu, R. J., Aaron, L., Abdelfattah, O. M., Koulogiannis, K. P., Marcoff, L., Naguib, M., Kapadia, S. R., Makkar, R. R., Thourani, V. H., van Boxtel, B. S., Cohen, D. J., Dobbles, M., Barnhart, G. R., Kwon, M., Pibarot, P., Leon, M. B., Gillam, L. D. 2023

  Abstract

  The American College of Cardiology/American Heart Association guidelines recommend the assessment and grading of severity of aortic stenosis (AS) as mild, moderate, or severe, per echocardiogram, and recommend aortic valve replacement (AVR) when the AS is severe.The authors sought to describe mortality rates across the entire spectrum of untreated AS from a contemporary, large, real-world database.We analyzed a deidentified real-world data set including 1,669,536 echocardiographic reports (1,085,850 patients) from 24 U.S. hospitals (egnite Database, egnite). Patients >18 years of age were classified by diagnosed AS severity. Untreated mortality and treatment rates were examined with Kaplan-Meier (KM) estimates, with results compared using the log-rank test. Multivariate hazards analysis was performed to assess associations with all-cause mortality.Among 595,120 patients with available AS severity assessment, the KM-estimated 4-year unadjusted, untreated, all-cause mortality associated with AS diagnosis of none, mild, mild-to-moderate, moderate, moderate-to-severe, or severe was 13.5% (95% CI: 13.3%-13.7%), 25.0% (95% CI: 23.8%-26.1%), 29.7% (95% CI: 26.8%-32.5%), 33.5% (95% CI: 31.0%-35.8%), 45.7% (95% CI: 37.4%-52.8%), and 44.9% (95% CI: 39.9%-49.6%), respectively. Results were similar when adjusted for informative censoring caused by treatment. KM-estimated 4-year observed treatment rates were 0.2% (95% CI: 0.2%-0.2%), 1.0% (95% CI: 0.7%-1.3%), 4.2% (95% CI: 2.0%-6.3%), 11.4% (95% CI: 9.5%-13.3%), 36.7% (95% CI: 31.8%-41.2%), and 60.7% (95% CI: 58.0%-63.3%), respectively. After adjustment, all degrees of AS severity were associated with increased mortality.Patients with AS have high mortality risk across all levels of untreated AS severity. Aortic valve replacement rates remain low for patients with severe AS, suggesting that more research is needed to understand barriers to diagnosis and appropriate approach and timing for aortic valve replacement.

  View details for DOI 10.1016/j.jacc.2023.09.796

  View details for PubMedID 37877909

• Response to Letter to the Editor: Can we use an algorithm as an "Ariadne's thread" to escape the maze of mitral regurgitation phenotype? Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Asch, F. M., Sharma, R. P., Cubeddu, R. J., Généreux, P., Dobbles, M., Verhoef, K., Kwon, M., Rodriguez, E., Thomas, J. D., Gillam, L. D. 2023

  View details for DOI 10.1016/j.echo.2023.10.005

  View details for PubMedID 37839617

• Emergency Transcatheter Repair for Anterior Leaflet Tear Following Percutaneous Balloon Mitral Valvuloplasty. JACC. Case reports Dowling, C., Haeffele, C., Yeung, A. C., Sharma, R. P. 2023; 23: 101980

  Abstract

  We present the case of a 66-year-old woman who developed severe mitral regurgitation from rupture of the anterior mitral valve leaflet following percutaneous balloon mitral valvuloplasty. Emergency transcatheter mitral valve repair was used to reduce the severity of mitral regurgitation and facilitate definitive surgical treatment. (Level of Difficulty: Advanced.).

  View details for DOI 10.1016/j.jaccas.2023.101980

  View details for PubMedID 37954949

  View details for PubMedCentralID PMC10635879

• Gaps in Contemporary Echocardiographic Reporting Quality for Mechanisms of Mitral Regurgitation: A Call to Action. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Asch, F. M., Sharma, R. P., Cubeddu, R. J., Généreux, P., Dobbles, M., Verhoef, K., Kwon, M., Rodriguez, E., Thomas, J. D., Gillam, L. D. 2023

  View details for DOI 10.1016/j.echo.2023.08.021

  View details for PubMedID 37666349

• Percutaneous Treatment of an Aorto-Right Ventricular Fistula FollowingBalloon-Expandable Transcatheter Aortic Valve Replacement. JACC. Case reports Dowling, C., Haeffele, C., Pogatchnik, B. P., Sharma, R. P. 2023; 18: 101906

  Abstract

  We present the case of a 71-year-old man who experienced congestive cardiac failure after transcatheter aortic valve replacement with a balloon-expandable transcatheter heart valve. Echocardiography and cardiac computed tomography demonstrated an aorto-right ventricular fistula, and successful percutaneous closure was performed with a vascular plug. (Level of Difficulty: Advanced.).

  View details for DOI 10.1016/j.jaccas.2023.101906

  View details for PubMedID 37545680

• Strategies for Transcatheter Aortic Valve Replacement in Patients With a Right Aortic Arch STRUCTURAL HEART-THE JOURNAL OF THE HEART TEAM Wang, H., Akanbi, O., MacArthur, J. W., Sharma, R. P. 2023; 7 (2)

  View details for DOI 10.1016/j.shj.2022.100099

  View details for Web of Science ID 000958525700001

• Percutaneous Bailout Technique for Trapping an Embolized Valve During Valve-in-Valve TAVR. The Journal of invasive cardiology Stathogiannis, K. E., MacArthur, J. W., Lee, J. T., Sharma, R. P. 2023; 35 (3): E160

  Abstract

  A complex 15-year treatment history of a 75-year-old man with New York Heart Association class III symptoms is presented via images and video. His treatment history was noteworthy of bicuspid aortic valve (AV) and a ventricular septal defect (VSD), for which he had an AV replacement and VSD closure in 2005. In 2015, he underwent redo AV replacement and root reconstruction. Echocardiography demonstrated severe bioprosthetic AV stenosis and moderate AV regurgitation. Valve-in-valve transcatheter aortic valve replacement with a Sentinel cerebral protection device was recommended. Pre-operative computed tomography scan showed dilated aortic root and descending aorta with evidence of pseudocoarcta- tion. This case highlights the need for multidisciplinary team approach and the in-depth knowledge of various devices and techniques available.

  View details for PubMedID 36884365

• Percutaneous Bailout Technique for Trapping an Embolized Valve During Valve-in-Valve TAVR JOURNAL OF INVASIVE CARDIOLOGY Stathogiannis, K. E., MacArthur, J. W., Lee, J. T., Sharma, R. P. 2023; 35 (3): E160

  View details for Web of Science ID 001033680000012

• Ongoing experience with patient-specific computer simulation of transcatheter aortic valve replacement in bicuspid aortic valve. Cardiovascular revascularization medicine : including molecular interventions Dowling, C., Gooley, R., McCormick, L., Sharma, R. P., Yeung, A. C., Fearon, W. F., Dargan, J., Khan, F., Firoozi, S., Brecker, S. J. 2023

  Abstract

  Transcatheter aortic valve replacement (TAVR) is increasingly being used to treat younger, lower-risk patients with bicuspid aortic valve (BAV). Patient-specific computer simulation may identify patients at risk for developing paravalvular regurgitation (PVR) and major conduction disturbance. Only limited prospective experience of this technology exist. We wished to describe our ongoing experience with patient-specific computer simulation.Patients who were referred for consideration of TAVR with a self-expanding transcatheter heart valve (THV) and had BAV identified on pre-procedural cardiac computed tomography imaging underwent patient-specific computer simulation. The computer simulations were reviewed by the Heart Team and used to guide surgical or transcatheter treatment approaches and to aid in THV sizing and positioning. Clinical outcomes were recorded.Between May 2019 and May 2021, 16 patients with BAV were referred for consideration of TAVR with a self-expanding THV. Sievers Type 1 morphology was present in 15 patients and Type 0 in the remaining patient. Two patients were predicted to develop moderate-to-severe PVR with a TAVR procedure and these patients underwent successful surgical aortic valve replacement. In the remaining 14 patients, computer simulation was used to optimize THV sizing and positioning to minimise PVR and conduction disturbance. One patient with a low valve implantation depth developed moderate PVR and this complication was correctly predicted by the computer simulations. No patient required insertion of a new permanent pacemaker.Patient-specific computer simulation may be used to guide the most appropriate treatment modality for patients with BAV. The usage of computer simulation to guide THV sizing and positioning was associated with favourable clinical outcomes.

  View details for DOI 10.1016/j.carrev.2023.01.015

  View details for PubMedID 36740551

• Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients: The Stentrode With Thought-Controlled Digital Switch (SWITCH) Study. JAMA neurology Mitchell, P., Lee, S. C., Yoo, P. E., Morokoff, A., Sharma, R. P., Williams, D. L., MacIsaac, C., Howard, M. E., Irving, L., Vrljic, I., Williams, C., Bush, S., Balabanski, A. H., Drummond, K. J., Desmond, P., Weber, D., Denison, T., Mathers, S., O'Brien, T. J., Mocco, J., Grayden, D. B., Liebeskind, D. S., Opie, N. L., Oxley, T. J., Campbell, B. C. 2023

  Abstract

  Brain-computer interface (BCI) implants have previously required craniotomy to deliver penetrating or surface electrodes to the brain. Whether a minimally invasive endovascular technique to deliver recording electrodes through the jugular vein to superior sagittal sinus is safe and feasible is unknown.To assess the safety of an endovascular BCI and feasibility of using the system to control a computer by thought.The Stentrode With Thought-Controlled Digital Switch (SWITCH) study, a single-center, prospective, first in-human study, evaluated 5 patients with severe bilateral upper-limb paralysis, with a follow-up of 12 months. From a referred sample, 4 patients with amyotrophic lateral sclerosis and 1 with primary lateral sclerosis met inclusion criteria and were enrolled in the study. Surgical procedures and follow-up visits were performed at the Royal Melbourne Hospital, Parkville, Australia. Training sessions were performed at patients' homes and at a university clinic. The study start date was May 27, 2019, and final follow-up was completed January 9, 2022.Recording devices were delivered via catheter and connected to subcutaneous electronic units. Devices communicated wirelessly to an external device for personal computer control.The primary safety end point was device-related serious adverse events resulting in death or permanent increased disability. Secondary end points were blood vessel occlusion and device migration. Exploratory end points were signal fidelity and stability over 12 months, number of distinct commands created by neuronal activity, and use of system for digital device control.Of 4 patients included in analyses, all were male, and the mean (SD) age was 61 (17) years. Patients with preserved motor cortex activity and suitable venous anatomy were implanted. Each completed 12-month follow-up with no serious adverse events and no vessel occlusion or device migration. Mean (SD) signal bandwidth was 233 (16) Hz and was stable throughout study in all 4 patients (SD range across all sessions, 7-32 Hz). At least 5 attempted movement types were decoded offline, and each patient successfully controlled a computer with the BCI.Endovascular access to the sensorimotor cortex is an alternative to placing BCI electrodes in or on the dura by open-brain surgery. These final safety and feasibility data from the first in-human SWITCH study indicate that it is possible to record neural signals from a blood vessel. The favorable safety profile could promote wider and more rapid translation of BCI to people with paralysis.ClinicalTrials.gov Identifier: NCT03834857.

  View details for DOI 10.1001/jamaneurol.2022.4847

  View details for PubMedID 36622685

• First described mitral clip in an adult extracardiac Fontan patient: a case report. European heart journal. Case reports Haeffele, C. L., Lui, G. K., Peng, L., Chan, F., Sharma, R. P. 2023; 7 (1): ytac479

  Abstract

  The use of transcatheter edge-to-edge repair (TEER) in patients with advanced heart failure has been shown to reduce hospitalizations and increase survival. As patients with Fontan circulations grow older, a significant proportion of them will develop severe atrioventricular (AV) valve regurgitation in the systemic ventricle. Conventional surgical repair and transplant carry high mortality risk for the adult Fontan patient with progressive heart failure.A 51-year-old female extracardiac Fontan patient developed severe AV valve regurgitation and progressive functional decline. Based on her operative risk for conventional surgical intervention or transplant, TEER using the Abbott MitraClip device was performed. The degree of mitral regurgitation was decreased from severe to moderate regurgitation.This is the first known case describing the use of a successful TEER in an adult patient with an extracardiac Fontan. Given the increasing numbers of patients surviving into adulthood with a Fontan circulation, transcatheter interventions may provide an alternative treatment option to conventional surgeries and medical therapies.

  View details for DOI 10.1093/ehjcr/ytac479

  View details for PubMedID 36733686

  View details for PubMedCentralID PMC9887705

• Prognostic Impact of Cardiac Damage Across the Spectrum of Aortic Stenosis Severity: Results From a Large Real-World Database Genereux, P., Sharma, R., Cubeddu, R., Leon, M., Cohen, D., Kapadia, S., Makkar, R., Thourani, V., Dobbles, M., Barnhart, G., Gillam, L. ELSEVIER SCIENCE INC. 2022: B163-B164

  View details for Web of Science ID 000892594000377

• A randomized evaluation of the TriGuard HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial. European heart journal Lansky, A. J., Makkar, R., Nazif, T., Messe, S., Forrest, J., Sharma, R., Schofer, J., Linke, A., Brown, D., Dhoble, A., Horwitz, P., Zang, M., DeMarco, F., Rajagopal, V., Dwyer, M. G., Zivadinov, R., Stella, P., Rovin, J., Parise, H., Kodali, S., Baumbach, A., Moses, J., REFLECT I Trial Investigators 2021

  Abstract

  AIMS: The REFLECT I trial investigated the safety and effectiveness of the TriGuard HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR).METHODS AND RESULTS: This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5days or Montreal Cognitive Assessment worsening at 30days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5days. Cumulative scores were compared between treatment groups using the Finkelstein-Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P<0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: -5.3±99.8 TG vs. 11.8±96.4 control, P=0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P=0.0698) and at 5days (61.7 vs. 76.2%, P=0.054) compared with controls.CONCLUSION: REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.

  View details for DOI 10.1093/eurheartj/ehab213

  View details for PubMedID 34000004

• Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Replacement: REFLECT II. JACC. Cardiovascular interventions Nazif, T. M., Moses, J. n., Sharma, R. n., Dhoble, A. n., Rovin, J. n., Brown, D. n., Horwitz, P. n., Makkar, R. n., Stoler, R. n., Forrest, J. n., Messé, S. n., Dickerman, S. n., Brennan, J. n., Zivadinov, R. n., Dwyer, M. G., Lansky, A. J. 2021; 14 (5): 515–27

  Abstract

  The REFLECT II (Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Implantation) trial was designed to investigate the safety and efficacy of the TriGUARD 3 (TG3) cerebral embolic protection in patients undergoing transcatheter aortic valve replacement.Cerebral embolization occurs frequently following transcatheter aortic valve replacement and procedure-related ischemic stroke occurs in 2% to 6% of patients at 30 days. Whether cerebral protection with TriGuard 3 is safe and effective in reducing procedure-related cerebral injury is not known.This prospective, multicenter, single-blind, 2:1 randomized (TG3 vs. no TG3) study was designed to enroll up to 345 patients. The primary 30-day safety endpoint (Valve Academic Research Consortium-2 defined) was compared with a performance goal (PG). The primary hierarchical composite efficacy endpoint (including death or stroke at 30 days, National Institutes of Health Stroke Scale score worsening in hospital, and cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging at 2 to 5 days) was compared using the Finkelstein-Schoenfeld method.REFLECT II enrolled 220 of the planned 345 patients (63.8%), including 41 roll-in and 179 randomized patients (121 TG3 and 58 control subjects) at 18 US sites. The sponsor closed the study early after the U.S. Food and Drug Administration recommended enrollment suspension for unblinded safety data review. The trial met its primary safety endpoint compared with the PG (15.9% vs. 34.4% (p < 0.0001). The primary hierarchal efficacy endpoint at 30 days was not met (mean scores [higher is better]: -8.58 TG3 vs. 8.08 control; p = 0.857). A post hoc diffusion-weighted magnetic resonance imaging analysis of per-patient total lesion volume above incremental thresholds showed numeric reductions in total lesion volume >500 mm3 (-9.7%) and >1,000 mm3 (-44.5%) in the TG3 group, which were more pronounced among patients with full TG3 coverage: -51.1% (>500 mm3) and -82.9% (>1,000 mm3).The REFLECT II trial demonstrated that the TG3 was safe compared with a historical PG but did not meet its pre-specified primary superiority efficacy endpoint.

  View details for DOI 10.1016/j.jcin.2020.11.011

  View details for PubMedID 33663779

• Transcatheter aortic valve thrombosis: a review of potential mechanisms. Journal of the Royal Society, Interface Raghav, V., Midha, P., Sharma, R., Babaliaros, V., Yoganathan, A. 2021; 18 (184): 20210599

  Abstract

  Transcatheter aortic valve (TAV) thrombosis has been recognized as a significant problem that sometimes occurs as early as within 30 days after valve implantation, leading to increased concerns of stroke and long-term valve durability. In this article, a critical summary of the relevant literature on identifying potential mechanisms of TAV thrombosis from the perspective of the well-known Virchow's triad, which comprises blood flow, foreign materials and blood biochemistry, is presented. Blood flow mechanisms have been the primary focus thus far, with a general consensus on the flow mechanisms with respect to haemodynamic conditions, the influence of TAV placement and expansion and the influence of coronary flow. Less attention has been paid to the influence of blood biochemistry and foreign materials (and related endothelial damage), with little consensus among studies with regards to platelet and/or microparticle levels post-TAV implantation. Finally, we discuss the future outlook for research with unanswered scientific questions.

  View details for DOI 10.1098/rsif.2021.0599

  View details for PubMedID 34814733

• Randomized Trials Are Needed for Transcatheter Mitral Valve Replacement. JACC. Cardiovascular interventions Rogers, J. H., Sorajja, P., Thourani, V. H., Sharma, R. P., Chehab, B., Cowger, J., Heimansohn, D., Badhwar, V., Guerrero, M., Ailawadi, G. 2021; 14 (18): 2039-2046

  Abstract

  Transcatheter mitral valve replacement (TMVR) is a new therapy for treating symptomatic mitral regurgitation (MR) and stenosis. The proposed benefit of TMVR is the predictable, complete elimination of MR, which is less certain with transcatheter repair technologies such as TEER (transcatheter edge-to-edge repair). The potential benefit of MR elimination with TMVR needs to be rigorously evaluated against its risks which include relative procedural invasiveness, need for anticoagulation, and chronic structural valve deterioration. Randomized controlled trials (RCTs) are a powerful method for evaluating the safety and effectiveness of TMVR against current standard of care transcatheter therapies, such as TEER. RCTs not only help with the assessment of benefits and risks, but also with policies for determining operator or institutional requirements, resource utilization, and reimbursement. In this paper, the authors provide recommendations and considerations for designing pivotal RCTs for first-in-class TMVR devices.

  View details for DOI 10.1016/j.jcin.2021.06.014

  View details for PubMedID 34556279

• The role of flow stasis in transcatheter aortic valve leaflet thrombosis. The Journal of thoracic and cardiovascular surgery Trusty, P. M., Bhat, S. S., Sadri, V., Salim, M. T., Funnell, E., Kamioka, N., Sharma, R., Makkar, R., Babaliaros, V., Yoganathan, A. P. 2020

  Abstract

  OBJECTIVE: With the recent expanded indication for transcatheter aortic valve replacement to low-risk surgical patients, thrombus formation in the neosinus is of particular interest due to concerns of reduced leaflet motion and long-term transcatheter heart valve durability. Although flow stasis likely plays a role, a direct connection between neosinus flow stasis and thrombus severity is yet to be established.METHODS: Patients (n=23) were selected to minimize potential confounding factors related to thrombus formation. Patient-specific 3-dimensional reconstructed invitro models were created to replicate invivo anatomy and valve deployment using the patient-specific cardiac output and idealized coronary flows. Dye was injected into each neosinus to quantify washout time as a measure of flow stasis.RESULTS: Flow stasis (washout time) showed a significant, positive correlation with thrombus volume in the neosinus (rho=0.621, P<.0001). Neither thrombus volume nor washout time was significantly different in the left, right, and noncoronary neosinuses (P≥.54).CONCLUSIONS: This is the first patient-specific study correlating flow stasis with thrombus volume in the neosinus post-transcatheter aortic valve replacement across multiple valve types and sizes. Neosinus-specific factors create hemodynamic and thrombotic variability within individual patients. Measurement of neosinus flow stasis may guide strategies to improve outcomes in transcatheter aortic valve replacement.

  View details for DOI 10.1016/j.jtcvs.2020.10.139

  View details for PubMedID 33342573

• A Review of the Partner Trials. Interventional cardiology clinics Markham, R., Sharma, R. 2020; 9 (4): 461–67

  Abstract

  Aortic stenosis (AS) of moderate or greater severity has an estimated prevalence of 5% in people older than 65 years. Survival is poor after onset of symptoms, and surgical aortic valve replacement was the gold-standard treatment for decades. However, more than one-third of patients with symptomatic AS were untreated due to high surgical risk, exposing a clinical need for a less invasive therapy for aortic valve stenosis. The PARTNER trials were pivotal in presenting robust evidence for the safety, feasibility, and efficacy of transcatheter aortic valve replacement in the management of AS and paved the way for clinical use worldwide.

  View details for DOI 10.1016/j.iccl.2020.07.002

  View details for PubMedID 32921370

• Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial. Lancet (London, England) Makkar, R. R., Cheng, W., Waksman, R., Satler, L. F., Chakravarty, T., Groh, M., Abernethy, W., Russo, M. J., Heimansohn, D., Hermiller, J., Worthley, S., Chehab, B., Cunningham, M., Matthews, R., Ramana, R. K., Yong, G., Ruiz, C. E., Chen, C., Asch, F. M., Nakamura, M., Jilaihawi, H., Sharma, R., Yoon, S., Pichard, A. D., Kapadia, S., Reardon, M. J., Bhatt, D. L., Fontana, G. P. 2020

  Abstract

  BACKGROUND: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs.METHODS: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing.FINDINGS: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups.INTERPRETATION: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves.FUNDING: Abbott.

  View details for DOI 10.1016/S0140-6736(20)31358-1

  View details for PubMedID 32593323

• Comparison of Valve Performance of the Intra-Annular Self-Expanding Portico (TM) Transcatheter Aortic Valve With Contemporary Supra-Annular Self-Expanding and Intra-Annular Balloon-Expandable Valves: Insights From the PORTICO IDE Trial Makkar, R. R., Waksman, R., Groh, M., Russo, M. J., Hermiller, J., Worthley, S., Chehab, B., Asch, F. M., Sharma, R. P., Jilaihawi, H., Pichard, A. D., Reardon, M. J., Fontana, G. P. ELSEVIER SCIENCE INC. 2020: S46

  View details for Web of Science ID 000513916500116

• Percutaneous Pulmonary Vein Stenting to Treat Severe Pulmonary Vein Stenosis After Surgical Reconstruction. Innovations (Philadelphia, Pa.) Dalal, A. R., Markham, R. n., Haeffele, C. n., Sharma, R. n., Watkins, A. C. 2020: 1556984520933962

  Abstract

  A 36-year-old female underwent left lower lobectomy with left atrial and left upper pulmonary vein (LUPV) reconstruction with a bovine pericardial patch for an intrathoracic pheochromocytoma. Postoperatively, she developed shortness of breath and transesophageal echocardiography demonstrated LUPV stenosis with increased velocities. Computed tomography angiogram of the chest revealed LUPV stenosis at the left atrium ostium with an area of 39 mm2. Under angiographic and echocardiographic guidance, a 10 × 19 mm Omnilink Elite uncovered stent was deployed in the LUPV ostia. While reported following left atrial ablation, pulmonary vein stenting can be successful in a pulmonary vein surgically reconstructed with bovine pericardium.

  View details for DOI 10.1177/1556984520933962

  View details for PubMedID 32639846

• Endovascular Neuromodulation: Safety Profile and Future Directions. Frontiers in neurology Raza, S. A., Opie, N. L., Morokoff, A., Sharma, R. P., Mitchell, P. J., Oxley, T. J. 2020; 11: 351

  Abstract

  Endovascular neuromodulation is an emerging technology that represents a synthesis between interventional neurology and neural engineering. The prototypical endovascular neural interface is the StentrodeTM, a stent-electrode array which can be implanted into the superior sagittal sinus via percutaneous catheter venography, and transmits signals through a transvenous lead to a receiver located subcutaneously in the chest. Whilst the StentrodeTM has been conceptually validated in ovine models, questions remain about the long term viability and safety of this device in human recipients. Although technical precedence for venous sinus stenting already exists in the setting of idiopathic intracranial hypertension, long term implantation of a lead within the intracranial veins has never been previously achieved. Contrastingly, transvenous leads have been successfully employed for decades in the setting of implantable cardiac pacemakers and defibrillators. In the current absence of human data on the StentrodeTM, the literature on these structurally comparable devices provides valuable lessons that can be translated to the setting of endovascular neuromodulation. This review will explore this literature in order to understand the potential risks of the StentrodeTM and define avenues where further research and development are necessary in order to optimize this device for human application.

  View details for DOI 10.3389/fneur.2020.00351

  View details for PubMedID 32390937

• Timing and Outcomes of Percutaneous Coronary Intervention in Patients Who Underwent Transcatheter Aortic Valve Implantation. The American journal of cardiology Ochiai, T. n., Yoon, S. H., Flint, N. n., Sharma, R. n., Chakravarty, T. n., Kaewkes, D. n., Patel, V. n., Nakamura, M. n., Cheng, W. n., Makkar, R. n. 2020

  Abstract

  Limited data exist regarding the timing of percutaneous coronary intervention (PCI) in patients with coronary artery disease who underwent transcatheter aortic valve implantation (TAVI). We aimed to investigate clinical outcomes of patients who underwent TAVI and planned PCI according to the timing of PCI in relation to the TAVI. Consecutive patients with severe aortic stenosis who underwent TAVI with planned PCI between January 2013 and November 2017 were included. Patients were divided according to the timing of PCI. The primary end point was major adverse cardiac and cerebrovascular events, defined as a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke. Among 1,756 patients who underwent TAVI, 258 patients underwent planned PCI either before TAVI (n = 143, 55.4%), concomitantly with TAVI (n = 77, 29.8%), or after TAVI (n = 38, 14.7%). All patients in the post-TAVI PCI group were treated using balloon-expandable valves, and neither hemodynamic instability during TAVI nor PCI-related complications were observed. In a multivariable analysis, the timing of PCI was not associated with 2-year major adverse cardiac and cerebrovascular events rate (concomitant vs pre-TAVI, hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.52 to 1.66; p = 0.79; post- vs pre-TAVI, HR: 0.45; 95% CI: 0.18 to 1.16; p = 0.10). In conclusion, there were no significant differences in terms of mid-term outcomes among pre-TAVI, concomitant, and post-TAVI PCI groups when the timing of PCI was carefully selected by heart team.

  View details for DOI 10.1016/j.amjcard.2020.01.043

  View details for PubMedID 32106928

• Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: first in-human experience. Journal of neurointerventional surgery Oxley, T. J., Yoo, P. E., Rind, G. S., Ronayne, S. M., Lee, C. M., Bird, C. n., Hampshire, V. n., Sharma, R. P., Morokoff, A. n., Williams, D. L., MacIsaac, C. n., Howard, M. E., Irving, L. n., Vrljic, I. n., Williams, C. n., John, S. E., Weissenborn, F. n., Dazenko, M. n., Balabanski, A. H., Friedenberg, D. n., Burkitt, A. N., Wong, Y. T., Drummond, K. J., Desmond, P. n., Weber, D. n., Denison, T. n., Hochberg, L. R., Mathers, S. n., O'Brien, T. J., May, C. N., Mocco, J. n., Grayden, D. B., Campbell, B. C., Mitchell, P. n., Opie, N. L. 2020

  Abstract

  Implantable brain-computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation.Two participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks.Unsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%-100.00%) (trial mean (median, Q1-Q3)) at a rate of 13.81 (13.44, 10.96-16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%-100.00%) at 20.10 (17.73, 12.27-26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants.We describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.

  View details for DOI 10.1136/neurintsurg-2020-016862

  View details for PubMedID 33115813

• Variation in the Timing of Percutaneous Coronary Intervention and Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement Ochiai, T., Yoon, S., Flint, N., Sharma, R., Patel, V., Chakravarty, T., Nakamura, M., Cheng, W., Makkar, R. ELSEVIER SCIENCE INC. 2019: B670

  View details for Web of Science ID 000487306300671

• Patching residual leaks following a MitraClip procedure EUROINTERVENTION Kar, S., Sharma, R. 2019; 15 (6): E482–E483

  View details for DOI 10.4244/EIJV15I6A87

  View details for Web of Science ID 000490324300003

  View details for PubMedID 31395574

• Computed tomography characteristics of the aortic valve and the geometry of SAPIEN 3 transcatheter heart valve in patients with bicuspid aortic valve disease EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING Kawamori, H., Yoon, S., Chakravarty, T., Maeno, Y., Kashif, M., Israr, S., Abramowitz, Y., Mangat, G., Miyasaka, M., Rami, T., Kazuno, Y., Takahashi, N., Jilaihawi, H., Nakamura, M., Cheng, W., Friedman, J., Berman, D., Sharma, R., Makkar, R. R. 2018; 19 (12): 1408–18

  Abstract

  We assessed the geometry of transcatheter heart valve (THV) and valve function associated with SAPIEN 3 implantation in patients with bicuspid aortic valve (BAV) stenosis.We included 280 consecutive patients who had a contrast computed tomography (CT) before and after transcatheter aortic valve implantation (TAVI) in our institution. Each THV was assessed by CT at five cross-sectional levels: inflow, annulus, mid, sinus, and outflow. The geometry of THV was assessed for eccentricity (1 - minimum diameter/maximum diameter) and expansion (CT derived external valve area/nominal external valve area). CT measurements and transthoracic echocardiogram data were compared between BAV and tricuspid aortic valve (TAV). Among 280 patients, 41 patients were diagnosed as BAV. Compared to TAV, BAV was associated with lower expansion at mid-level, sinus-level, and outflow-level (mid 94.1 ± 6.8% vs. 98.1 ± 7.8%; P = 0.002, sinus 95.9 ± 7.2% vs. 101.6 ± 8.5%; P < 0.001, outflow 107.6 ± 6.2% vs. 109.9 ± 6.6%; P = 0.043), and higher eccentricity at all levels [inflow 3.5% (1.9-5.3) vs. 6.0% (3.2-7.5); P < 0.001, annulus 3.1% (1.6-5.2) vs. 5.4% (3.1-7.8); P = 0.002, mid 3.0% (1.4-4.9) vs. 6.0% (3.3-10.4); P < 0.001, sinus 3.0% (1.7-5.1) vs. 7.6% (4.0-11.4); P < 0.001, and outflow 2.5% (1.3-4.3) vs. 4.9% (2.2-7.5); P < 0.001]. There were no differences in frequency of paravalvular leak ≥ moderate and mean post-procedural gradient between BAV and TAV.BAV patients have greater THV eccentricity at all levels and lower THV expansion at mid, sinus, and outflow levels than the TAV patients. There were no differences in parameters of valve function between BAV and TAV patients. Despite the observed geometrical differences, TAVI with SAPIEN 3 in BAV patients allows for feasible valve function.

  View details for DOI 10.1093/ehjci/jex333

  View details for Web of Science ID 000455360200016

  View details for PubMedID 29315371

• Transcatheter aortic valve replacement in bicuspid aortic valve stenosis: where do we stand? JOURNAL OF CARDIOVASCULAR SURGERY Yoon, S., Sharma, R., Chakravarty, T., Miyasaka, M., Ochiai, T., Nomura, T., Gellada, N., Nemanpour, S., Nakamura, M., Chen, W., Makkar, R. 2018; 59 (3): 381–91

  Abstract

  Bicuspid aortic valve is the most common congenital cardiac defect in adults, and symptom typically develops in adulthood. In the majority of cases, bicuspid aortic valve disease progress with ages and surgical aortic valve replacement is performed with excellent operative outcomes. However, with the relatively slow progression of disease, surgical aortic valve replacement is required in elderly patients but the surgical risk often deemed extremely high due to old age and multiple comorbidities. Transcatheter aortic valve replacement (TAVR) has evolved from a novel technology to an established therapy for intermediate- and high-risk patients with symptomatic severe aortic valve stenosis (AS). Numerous studies have demonstrated the safety and efficacy of TAVR, and more than 250,000 patients have been treated with this technology. Although randomized trials have established TAVR as the standard treatment, these trials excluded congenital bicuspid AS due to its unique morphological features. Nevertheless, the growing experience, accumulated knowledge, and advancements of new technology lead to the expand use of TAVR to other pathologies or other populations such as bicuspid AS. With integration of imaging multimodalities (computed tomography and echocardiography), the diagnosis and classification of bicuspid aortic valve has been changing. Due to unfavorable anatomic features of bicuspid AS, the outcomes of TAVR in bicuspid AS was suboptimal, particularly when using the first-generation transcatheter valves. However, the newer-generation transcatheter valves significantly improved the outcomes of TAVR in bicuspid AS. Nonetheless, several issues still remain to be resolved. Given longer life expectancy in patients with bicuspid AS undergoing TAVR, durability of transcatheter valves is concerned. In addition, patients with bicuspid aortic valves often have concomitant dilatation of proximal part of ascending aorta (aortopathy), but limited data exist about the clinical prognosis of bicuspid aortic valve with concomitant aortopathy in elderly patients. Considering the expanding indication of TAVR to lower surgical risk and younger population, these issues should be evaluated in future studies.

  View details for DOI 10.23736/S0021-9509.18.10350-8

  View details for Web of Science ID 000445207000014

  View details for PubMedID 29332374

• Response by Sharma et al to Letter Regarding Article, "The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus". Circulation Sharma, R., Midha, P. A., Babaliaros, V., Makkar, R. R., Yoganathan, A. P. 2018; 137 (19): 2094-2095

  View details for DOI 10.1161/CIRCULATIONAHA.118.033769

  View details for PubMedID 29735601

• Recurrent severe aortic stenosis after transfemoral transcatheter valve-in-valve-in-valve replacement JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Ochiai, T., Yoon, S., Sharma, R., Chakravarty, T., Nakamura, M., Cheng, W., Makkar, R. 2018; 155 (5): E141–E144

  View details for DOI 10.1016/j.jtcvs.2017.12.120

  View details for Web of Science ID 000430195900001

  View details for PubMedID 29422220

• Too little, too much or just right? Goldilocks revisited…. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Sharma, R., Henry, T. D. 2018; 91 (5): 840-841

  Abstract

  This study highlights the low rates of UCA in OHCA patients in a real-world setting Presentation with ST elevation, shockable rhythm and history of CAD were more likely to result in UCA for OHCA patients Further studies are required to help create a systematic and standardized approach to UCA in OHCA patients.

  View details for DOI 10.1002/ccd.27613

  View details for PubMedID 29634858

• Relation Between Left Ventricular Outflow Tract Calcium and Mortality Following Transcatheter Aortic Valve Implantation AMERICAN JOURNAL OF CARDIOLOGY Maeno, Y., Abramowitz, Y., Yoon, S., Israr, S., Jilaihawi, H., Watanabe, Y., Sharma, R., Kawamori, H., Miyasaka, M., Kazuno, Y., Takahashi, N., Hariri, B., Mangat, G., Kashif, M., Chakravarty, T., Nakamura, M., Cheng, W., Makkar, R. R. 2017; 120 (11): 2017–24

  Abstract

  Left ventricular outflow tract (LVOT) calcium is known to be associated with adverse procedural outcomes after transcatheter aortic valve implantation (TAVI), yet its effect on midterm outcomes has not been previously investigated. The aim of this study was to determine the influence of LVOT calcium on 2-year mortality after TAVI. A total of 537 consecutive patients underwent TAVI and 2 groups were established, stratified based on the severity of the LVOT calcium. The primary outcome was 2-year overall survival rate. The ≥moderate LVOT calcium group included 107 patients (19.9%) and the remaining 430 patients (80.1%) were included in the ≤mild LVOT calcium group. After a median follow-up of 717 days (interquartile range 484 to 828), the Kaplan-Meier analysis revealed that the 2-year overall survival probability was significantly lower in the ≥moderate LVOT calcium group than in the ≤mild LVOT calcium group (log-rank p = 0.001). On a Cox hazard model, ≥moderate LVOT calcium was associated with increased all-cause mortality after TAVI (hazard ratio 1.74, p = 0.009). In the subgroup analysis, based on valve designs, SAPIEN 3-TAVI done in the setting of ≥moderate LVOT calcium had a relatively similar survival probability as those of ≤mild LVOT calcium (log-rank p = 0.18), which is in contrast with older generation valves (log-rank p = 0.001). In conclusion, patients with ≥moderate LVOT calcium were shown to have a lower survival probability in the midterm follow-up after TAVI, compared with those with ≤mild LVOT calcium. Patients with high-grade LVOT calcium should be monitored with longer-term follow-ups after TAVI.

  View details for DOI 10.1016/j.amjcard.2017.08.018

  View details for Web of Science ID 000417889000018

  View details for PubMedID 28941599

• The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus CIRCULATION Midha, P. A., Raghav, V., Sharma, R., Condado, J. F., Okafor, I. U., Rami, T., Kumar, G., Thourani, V. H., Jilaihawi, H., Babaliaros, V., Makkar, R. R., Yoganathan, A. P. 2017; 136 (17): 1598-+

  Abstract

  Transcatheter heart valve (THV) thrombosis has been increasingly reported. In these studies, thrombus quantification has been based on a 2-dimensional assessment of a 3-dimensional phenomenon.Postprocedural, 4-dimensional, volume-rendered CT data of patients with CoreValve, Evolut R, and SAPIEN 3 transcatheter aortic valve replacement enrolled in the RESOLVE study (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Dysfunction With Multimodality Imaging and Its Treatment with Anticoagulation) were included in this analysis. Patients on anticoagulation were excluded. SAPIEN 3 and CoreValve/Evolut R patients with and without hypoattenuated leaflet thickening were included to study differences between groups. Patients were classified as having THV thrombosis if there was any evidence of hypoattenuated leaflet thickening. Anatomic and THV deployment geometries were analyzed, and thrombus volumes were computed through manual 3-dimensional reconstruction. We aimed to identify and evaluate risk factors that contribute to THV thrombosis through the combination of retrospective clinical data analysis and in vitro imaging in the space between the native and THV leaflets (neosinus).SAPIEN 3 valves with leaflet thrombosis were on average 10% further expanded (by diameter) than those without (95.5±5.2% versus 85.4±3.9%; P<0.001). However, this relationship was not evident with the CoreValve/Evolut R. In CoreValve/Evolut Rs with thrombosis, the thrombus volume increased linearly with implant depth (R2=0.7, P<0.001). This finding was not seen in the SAPIEN 3. The in vitro analysis showed that a supraannular THV deployment resulted in a nearly 7-fold decrease in stagnation zone size (velocities <0.1 m/s) when compared with an intraannular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased.Although transcatheter aortic valve replacement thrombosis is a multifactorial process involving foreign materials, patient-specific blood chemistry, and complex flow patterns, our study indicates that deployed THV geometry may have implications on the occurrence of thrombosis. In addition, a supraannular neosinus may reduce thrombosis risk because of reduced flow stasis. Although additional prospective studies are needed to further develop strategies for minimizing thrombus burden, these results may help identify patients at higher thrombosis risk and aid in the development of next-generation devices with reduced thrombosis risk.

  View details for DOI 10.1161/CIRCULATIONAHA.117.029479

  View details for Web of Science ID 000413496200006

  View details for PubMedID 28724752

• Effect of ascending aortic dimension on acute procedural success following self-expanding transcatheter aortic valve replacement A multicenter retrospective analysis INTERNATIONAL JOURNAL OF CARDIOLOGY Maeno, Y., Yoon, S., Abramowitz, Y., Watanabe, Y., Jilaihawi, H., Lin, M., Chan, J., Sharma, R., Kawashima, H., Israr, S., Kawamori, H., Miyasaka, M., Rami, T., Kazuno, Y., Mangat, G., Kashif, M., Chakravarty, T., Kao, H., Lee, M., Nakamura, M., Kozuma, K., Cheng, W., Makkar, R. R. 2017; 244: 100–105

  Abstract

  Self-expanding (SE) valves are characterized with long stent frame design and the radial force of the device exists both in the inflow and outflow level. Therefore, we hypothesized that device success of SE-valves may be influenced by ascending aortic dimensions (AAD). The aim of this study was to determine the influence of AAD on acute device success rates following SE transcatheter aortic valve replacement (TAVR).In 4 centers in the United States and Asia, 214 consecutive patients underwent SE-TAVR. Outcomes were assessed in line with Valve Academic Research Consortium criteria. AAD was defined as the sum of the short and long axis aortic diameter divided by 2. Overall, device success rate was 85.0%. Multivariate analysis revealed that increased AAD (Odds ratio 1.27) and % oversizing (Odds ratio 0.88) were found to be independent predictors of unsuccessful device implantation. The c-statistic of the model for device success was area under the curve 0.79, sensitivity 81.3% and specificity 44.0%. Co-existence of several risk factors was associated with an exponential fall to 64.2% in device success rate. For a large AAD, however, optimally oversized SE-valves (threshold 16.2%) resulted with high device success rates compared to suboptimal oversizing (88.6% vs. 64.2%, p=0.005).Larger AAD and smaller degrees of oversizing were confirmed to be the most relevant predictors of unsuccessful device implantation following SE-valve implantations. Optimal oversizing of great significance was noted, particularly that with a large AAD.

  View details for DOI 10.1016/j.ijcard.2017.05.120

  View details for Web of Science ID 000406943600018

  View details for PubMedID 28622944

• Clinical outcomes and prognostic factors of transcatheter aortic valve implantation in bicuspid aortic valve patients ANNALS OF CARDIOTHORACIC SURGERY Yoon, S., Sharma, R., Chakravarty, T., Kawamori, H., Maeno, Y., Miyasaka, M., Nomura, T., Ochiai, T., Israr, S., Rami, T., Nakamura, M., Chen, W., Makkar, R. R. 2017; 6 (5): 463–72

  Abstract

  The purpose of this study was to evaluate the outcomes of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (AS).From April 2012 and December 2016, 108 patients with bicuspid AS underwent TAVR using the Sapien XT (34 patients) and Sapien 3 (74 patients) valves. Procedural and clinical outcomes were assessed according to VARC-2 criteria and compared between the two devices.In the overall cohort, the majority of patients were male (71.3%) with an intermediate surgical risk and a mean Society of Thoracic Surgeons (STS) score of 5.2%. Compared to the Sapien XT group, the Sapien 3 group had a significantly lower STS score (3.3%±2.0% vs. 6.7%±3.6%; P=0.001). Compared to the Sapien XT group, the Sapien 3 group had a significantly lower rate of moderate or severe paravalvular leak (2.7% vs. 14.7%; P=0.03) and higher device success (97.3% vs. 82.4%; P=0.006). There were no significant differences between the two groups in terms of 30-day all-cause mortality, stroke, life-threatening bleeding, major vascular complication and acute kidney injury (stage 2 or 3). Cumulative all-cause mortality at 1-year follow-up was 6.9%. There were no significant differences in cumulative event rates for all-cause mortality at 1-year follow-up between the two groups (9.4% vs. 4.6%; log-rank P=0.47). By univariate analysis, major vascular complication was significantly associated with overall all-cause mortality [hazard ratios (HR): 7.57; 95% confidence interval (CI): 1.51-37.86; P=0.014].TAVR using the balloon-expandable valves provided acceptable procedural and clinical outcomes in patients with bicuspid AS. The new-generation Sapien 3 valves showed improved procedural outcomes compared to the early-generation Sapien XT valves.

  View details for DOI 10.21037/acs.2017.09.03

  View details for Web of Science ID 000418471200006

  View details for PubMedID 29062741

  View details for PubMedCentralID PMC5639233

• Advanced Imaging of Intracranial Atherosclerosis: Lessons from Interventional Cardiology FRONTIERS IN NEUROLOGY Pavlin-Premrl, D., Sharma, R., Campbell, B. V., Mocco, J., Opie, N. L., Oxley, T. J. 2017; 8: 387

  Abstract

  Intracranial atherosclerosis is a major cause of ischemic stroke. Patients with a high degree of stenosis have a significant rate of stroke despite medical therapy. Two randomized trials of stenting have failed to show benefit. Improving periprocedural complication rates and patient selection may improve stenting outcomes. Fractional flow reserve (FFR), intravascular ultrasound (IVUS), and optical coherence tomography (OCT) are intravascular imaging techniques employed to improve patient selection and stent placement in interventional cardiology. FFR has been shown to improve cardiovascular outcomes when used in patient selection for intervention. Studies of FFR in intracranial atherosclerosis show that the measure may predict which plaques lead to stroke. IVUS is used in cardiology to quantify stenosis and assist with stent placement. Comparisons with histology show that it can reliably characterize plaques. Several case reports of IVUS in intracranial arteries show the technique to be feasible and indicate it may improve stent placement. Plaque characteristics on IVUS may help identify vulnerable plaques. In interventional cardiology, OCT provides excellent visualization of vessel geometry and is useful periprocedurally. Images reliably identify thin-capped fibroatheromas and other plaque features. Case reports indicate that OCT is safe for use in intracranial arteries. OCT can be used to identify perforator vessels and so may be useful in avoiding perforator strokes, a common complication of stenting. Plaque characteristics on OCT may be useful in patient selection.

  View details for DOI 10.3389/fneur.2017.00387

  View details for Web of Science ID 000407590300001

  View details for PubMedID 28855886

  View details for PubMedCentralID PMC5557768

• Outcomes in Transcatheter Aortic Valve Replacement for Bicuspid Versus Tricuspid Aortic Valve Stenosis JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Yoon, S., Bleiziffer, S., De Backer, O., Delgado, V., Arai, T., Ziegelmueller, J., Barbanti, M., Sharma, R., Perlman, G. Y., Khalique, O. K., Holy, E. W., Saraf, S., Deuschl, F., Fujita, B., Ruile, P., Neumann, F., Pache, G., Takahashi, M., Kaneko, H., Schmidt, T., Ohno, Y., Schofer, N., Kong, W. F., Tay, E., Sugiyama, D., Kawamori, H., Maeno, Y., Abramowitz, Y., Chakravarty, T., Nakamura, M., Kuwata, S., Yong, G., Kao, H., Lee, M., Kim, H., Modine, T., Wong, S., Bedgoni, F., Testa, L., Teiger, E., Butter, C., Ensminger, S. M., Schaefer, U., Dvir, D., Blanke, P., Leipsic, J., Nietlispach, F., Abdel-Wahab, M., Chevalier, B., Tamburino, C., Hildick-Smith, D., Whisenant, B. K., Park, S., Colombo, A., Latib, A., Kodali, S. K., Bax, J. J., Sondergaard, L., Webb, J. G., Lefevre, T., Leon, M. B., Makkar, R. 2017; 69 (21): 2579–89

  Abstract

  Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with bicuspid aortic valve stenosis (AS).This study sought to compare the procedural and clinical outcomes in patients with bicuspid versus tricuspid AS from the Bicuspid AS TAVR multicenter registry.Outcomes of 561 patients with bicuspid AS and 4,546 patients with tricuspid AS were compared after propensity score matching, assembling 546 pairs of patients with similar baseline characteristics. Procedural and clinical outcomes were recorded according to Valve Academic Research Consortium-2 criteria.Compared with patients with tricuspid AS, patients with bicuspid AS had more frequent conversion to surgery (2.0% vs. 0.2%; p = 0.006) and a significantly lower device success rate (85.3% vs. 91.4%; p = 0.002). Early-generation devices were implanted in 320 patients with bicuspid and 321 patients with tricuspid AS, whereas new-generation devices were implanted in 226 and 225 patients with bicuspid and tricuspid AS, respectively. Within the group receiving early-generation devices, bicuspid AS had more frequent aortic root injury (4.5% vs. 0.0%; p = 0.015) when receiving the balloon-expanding device, and moderate-to-severe paravalvular leak (19.4% vs. 10.5%; p = 0.02) when receiving the self-expanding device. Among patients with new-generation devices, however, procedural results were comparable across different prostheses. The cumulative all-cause mortality rates at 2 years were comparable between bicuspid and tricuspid AS (17.2% vs. 19.4%; p = 0.28).Compared with tricuspid AS, TAVR in bicuspid AS was associated with a similar prognosis, but lower device success rate. Procedural differences were observed in patients treated with the early-generation devices, whereas no differences were observed with the new-generation devices.

  View details for DOI 10.1016/j.jacc.2017.03.017

  View details for Web of Science ID 000401695900001

  View details for PubMedID 28330793

• Optimal sizing for SAPIEN 3 transcatheter aortic valve replacement in patients with or without left ventricular outflow tract calcification EUROINTERVENTION Maeno, Y., Abramowitz, Y., Jilaihawi, H., Israr, S., Yoon, S., Sharma, R. P., Kazuno, Y., Kawamori, H., Miyasaka, M., Rami, T., Mangat, G., Takahashi, N., Okuyama, K., Kashif, M., Chakravarty, T., Nakamura, M., Cheng, W., Makkar, R. R. 2017; 12 (18): E2177–E2185

  Abstract

  The impact of left ventricular outflow tract calcification (LVOT-CA) on SAPIEN 3 transcatheter aortic valve replacement (S3-TAVR) is not well understood. The aims of the present study were to determine optimal device sizing for S3-TAVR in patients with or without LVOT-CA and to evaluate the influence of residual paravalvular leak (PVL) on survival after S3-TAVR in these patients.This study analysed 280 patients (LVOT-CA=144, no LVOT-CA=136) undergoing S3-TAVR. Optimal annular area sizing was defined as % annular area sizing related to lower rates of ≥mild PVL. Annular area sizing was determined as follows: (prosthesis area/CT annulus area-1)×100. Overall, ≥mild PVL was present in 25.7%. Receiver operating characteristic curve analysis for prediction of ≥mild PVL in patients with LVOT-CA showed that 7.2% annular area sizing was identified as the optimal threshold (area under the curve [AUC] 0.71). Conversely, annular area sizing for no LVOT-CA appeared unrelated to PVL (AUC 0.58). Aortic annular injury was seen in four patients (average 15.5% annular area oversizing), three of whom had LVOT-CA. Although there was no difference in one-year survival between patients with ≥mild PVL and without PVL (log-rank p=0.91), subgroup analysis demonstrated that patients with ≥moderate LVOT-CA who had ≥mild PVL had lower survival compared to patients with ≥mild PVL and none or mild LVOT-CA (log-rank p=0.010).In the setting of LVOT-CA, an optimally sized S3 valve is required to reduce PVL and to increase survival following TAVR.

  View details for Web of Science ID 000400782100005

  View details for PubMedID 28117281

• Transcatheter Mitral Valve Replacement for Degenerated Bioprosthetic Valves and Failed Annuloplasty Rings. Journal of the American College of Cardiology Yoon, S. H., Whisenant, B. K., Bleiziffer, S. n., Delgado, V. n., Schofer, N. n., Eschenbach, L. n., Fujita, B. n., Sharma, R. n., Ancona, M. n., Yzeiraj, E. n., Cannata, S. n., Barker, C. n., Davies, J. E., Frangieh, A. H., Deuschl, F. n., Podlesnikar, T. n., Asami, M. n., Dhoble, A. n., Chyou, A. n., Masson, J. B., Wijeysundera, H. C., Blackman, D. J., Rampat, R. n., Taramasso, M. n., Gutierrez-Ibanes, E. n., Chakravarty, T. n., Attizzani, G. F., Kaneko, T. n., Wong, S. C., Sievert, H. n., Nietlispach, F. n., Hildick-Smith, D. n., Nombela-Franco, L. n., Conradi, L. n., Hengstenberg, C. n., Reardon, M. J., Kasel, A. M., Redwood, S. n., Colombo, A. n., Kar, S. n., Maisano, F. n., Windecker, S. n., Pilgrim, T. n., Ensminger, S. M., Prendergast, B. D., Schofer, J. n., Schaefer, U. n., Bax, J. J., Latib, A. n., Makkar, R. R. 2017; 70 (9): 1121–31

  Abstract

  Limited data exist regarding transcatheter mitral valve replacement (TMVR) for patients with failed mitral valve replacement and repair.This study sought to evaluate the outcomes of TMVR in patients with failed mitral bioprosthetic valves (valve-in-valve [ViV]) and annuloplasty rings (valve-in-ring [ViR]).From the TMVR multicenter registry, procedural and clinical outcomes of mitral ViV and ViR were compared according to Mitral Valve Academic Research Consortium criteria.A total of 248 patients with mean Society of Thoracic Surgeons score of 8.9 ± 6.8% underwent TMVR. Transseptal access and the balloon-expandable valve were used in 33.1% and 89.9%, respectively. Compared with 176 patients undergoing ViV, 72 patients undergoing ViR had lower left ventricular ejection fraction (45.6 ± 17.4% vs. 55.3 ± 11.1%; p < 0.001). Overall technical and device success rates were acceptable, at 92.3% and 85.5%, respectively. However, compared with the ViV group, the ViR group had lower technical success (83.3% vs. 96.0%; p = 0.001) due to more frequent second valve implantation (11.1% vs. 2.8%; p = 0.008), and lower device success (76.4% vs. 89.2%; p = 0.009) due to more frequent reintervention (16.7% vs. 7.4%; p = 0.03). Mean mitral valve gradients were similar between groups (6.4 ± 2.3 mm Hg vs. 5.8 ± 2.7 mm Hg; p = 0.17), whereas the ViR group had more frequent post-procedural mitral regurgitation moderate or higher (19.4% vs. 6.8%; p = 0.003). Furthermore, the ViR group had more frequent life-threatening bleeding (8.3% vs. 2.3%; p = 0.03), acute kidney injury (11.1% vs. 4.0%; p = 0.03), and subsequent lower procedural success (58.3% vs. 79.5%; p = 0.001). The 1-year all-cause mortality rate was significantly higher in the ViR group compared with the ViV group (28.7% vs. 12.6%; log-rank test, p = 0.01). On multivariable analysis, failed annuloplasty ring was independently associated with all-cause mortality (hazard ratio: 2.70; 95% confidence interval: 1.34 to 5.43; p = 0.005).The TMVR procedure provided acceptable outcomes in high-risk patients with degenerated bioprostheses or failed annuloplasty rings, but mitral ViR was associated with higher rates of procedural complications and mid-term mortality compared with mitral ViV.

  View details for PubMedID 28838360

• Controversies in Out of Hospital Cardiac Arrest? Interventional cardiology clinics Sharma, R. P., Stub, D. 2016; 5 (4): 551-559

  Abstract

  Cardiac arrest is a major cause of morbidity and mortality and accounts for nearly 500,000 deaths annually in the United States. In patients suffering out-of-hospital cardiac arrest, survival is less than 15%, with considerable regional variation. Although most deaths occur during the initial resuscitation, an increasing proportion occur in patients hospitalized after initially successful resuscitation. In these patients, the significant subsequent morbidity and mortality is due to "post cardiac arrest syndrome." Until recently, most single interventions have yielded little improvement in rates of survival; however, there is growing recognition that optimal treatment strategies during the postresuscitation phase may improve outcomes.

  View details for DOI 10.1016/j.iccl.2016.06.011

  View details for PubMedID 28582003

• Impact of Body Mass Index on the Outcomes Following Transcatheter Aortic Valve Implantation CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Abramowitz, Y., Chakravarty, T., Jilaihawi, H., Cox, J., Sharma, R. P., Mangat, G., Nakamura, M., Cheng, W., Makkar, R. R. 2016; 88 (1): 127–34

  Abstract

  To investigate the influence of body mass index (BMI) on short- and midterm outcomes following transcatheter aortic valve implantation (TAVI).Although obesity is a major risk factor for cardiovascular mortality, numerous studies reported a beneficial effect of obesity on survival in patients with cardiovascular disease and in patients after cardiac interventions. Moreover, all previous reports examining the relation between BMI and outcomes following TAVI have underscored the "obesity paradox" in these patients.During a 3 year period, 805 patients with severe aortic stenosis that underwent TAVI at our institute were evaluated. Based on baseline BMI, patients were classified as normal weight (18.5-24.9 kg/m(2) ), overweight (25.0-29.9 kg/m(2) ), or obese (≥30 kg/m(2) ). TAVI endpoints, device success, and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions.Obese patients were significantly younger, had higher prevalence of diabetes mellitus and chronic lung disease, and had lower prevalence of frailty. Device success was similar between the 3 groups. All-cause mortality up to 30 days was 2.9% (10/340) vs 4.5% (12/268) vs 0.5% (1/186) in patients with normal weight, overweight, and obesity, respectively (p = 0.048). In a multivariable model, overweight and obese patients had similar overall mortality compared to patients with normal weight.We found no evidence for the existence of an obesity paradox following TAVI. Correction for possible confounders such as frailty in the present cohort may explain the discrepancy between the current report and the previous reports that suggested a protective effect for increased BMI following TAVI. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.26394

  View details for Web of Science ID 000379984000028

  View details for PubMedID 26756702

• Outcomes in Patients With Transcatheter Aortic Valve Replacement and Left Main Stenting The TAVR- LM Registry JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chakravarty, T., Sharma, R., Abramowitz, Y., Kapadia, S., Latib, A., Jilaihawi, H., Poddar, K., Giustino, G., Ribeiro, H. B., Tchetche, D., Monteil, B., Testa, L., Tarantini, G., Facchin, M., Lefevre, T., Lindman, B. R., Hariri, B., Patel, J., Takahashi, N., Matar, G., Mirocha, J., Cheng, W., Tuzcu, M. E., Sievert, H., Rodes-Cabau, J., Colombo, A., Finkelstein, A., Fajadet, J., Makkar, R. R. 2016; 67 (8): 951–60

  Abstract

  A percutaneous approach with transcatheter aortic valve replacement (TAVR) and percutaneous coronary intervention (PCI) of the left main coronary artery (LM) is frequently used in high-risk patients with coexisting aortic stenosis and LM disease. Outcomes of TAVR plus LM PCI have not been previously reported.The primary objective of the TAVR-LM registry is to evaluate clinical outcomes in patients undergoing TAVR plus LM PCI.Clinical, echocardiographic, computed tomographic, and angiographic characteristics were retrospectively collected in 204 patients undergoing TAVR plus LM PCI. In total, 128 matched patient pairs were generated by performing 1:1 case-control matching between 167 patients with pre-existing LM stents undergoing TAVR and 1,188 control patients undergoing TAVR without LM revascularization.One-year mortality (9.4% vs. 10.2%, p = 0.83) was similar between the TAVR plus LM PCI cohort and matched controls. One-year mortality after TAVR plus LM PCI was not different in patients with unprotected compared with protected LMs (7.8% vs. 8.1%, p = 0.88), those undergoing LM PCI within 3 months compared with those with LM PCI greater than 3 months before TAVR (7.4% vs. 8.6%, p = 0.61), and those with ostial versus nonostial LM stents (10.3% vs. 15.6%, p = 0.20). Unplanned LM PCI performed because of TAVR-related coronary complication, compared with planned LM PCI performed for pre-existing LM disease, resulted in increased 30-day (15.8% vs. 3.4%, p = 0.013) and 1-year (21.1% vs. 8.0%, p = 0.071) mortality.Despite the anatomic proximity of the aortic annulus to the LM, TAVR plus LM PCI is safe and technically feasible, with short- and intermediate-term clinical outcomes comparable with those in patients undergoing TAVR alone. These results suggest that TAVR plus LM PCI is a reasonable option for patients who are at high risk for surgery.

  View details for DOI 10.1016/j.jacc.2015.10.103

  View details for Web of Science ID 000370490000009

  View details for PubMedID 26916485

  View details for PubMedCentralID PMC5091082

• Impact of Preprocedural B-Type Natriuretic Peptide Levels on the Outcomes After Transcatheter Aortic Valve Implantation AMERICAN JOURNAL OF CARDIOLOGY Abramowitz, Y., Chakravarty, T., Jilaihawi, H., Lee, C., Cox, J., Sharma, R. P., Mangat, G., Cheng, W., Makkar, R. R. 2015; 116 (12): 1904–9

  Abstract

  There are limited data on the effect of baseline B-type natriuretic peptide (BNP) on the outcome after transcatheter aortic valve implantation (TAVI). We investigated the influence of baseline BNP levels on the short-term and midterm clinical outcomes after TAVI. During a 3-year period, 780 patients with severe aortic stenosis underwent TAVI at our institute and had baseline BNP levels. We compared the high, mid, and low tertiles of BNP levels. TAVI end points, device success, and adverse events were considered according to the Valve Academic Research Consortium 2 definitions. Device success was significantly lower for patients with high BNP (98.1% vs 96.2% vs 91.9% for the low, mid, and high BNP tertiles, respectively; p = 0.003). All-cause mortality up to 30 days was 1.2% (3 of 260) versus 2.3% (6 of 260) versus 5% (13 of 260), respectively (p = 0.03). Six-month mortality rate was 4.1% (10 of 241) for the low BNP tertile, 5% (12 of 239) for the mid BNP tertile, and 17.1% (40 of 234) for the high BNP tertile (p <0.001). In the multivariate model, high tertile of baseline BNP was found to be significantly associated with all-cause mortality (hazard ratio 3.3, 95% confidence interval 1.64 to 6.48; p = 0.001). In conclusion, elevated BNP levels are associated with increased short-term and midterm mortality after TAVI. We recommend measurement of baseline BNP as part of risk stratification models for TAVI.

  View details for DOI 10.1016/j.amjcard.2015.09.031

  View details for Web of Science ID 000366786500019

  View details for PubMedID 26602075

• Unmasking of familial long QT syndrome type 2 with crystal methamphetamine exposure HEART RHYTHM Kumar, S., Sharma, R., Kalman, J. M. 2014; 11 (10): 1836–38

  View details for DOI 10.1016/j.hrthm.2014.05.034

  View details for Web of Science ID 000343112200031

  View details for PubMedID 24882508

• Randomized double-blind placebo-controlled crossover study to determine the effects of esomeprazole on inhibition of platelet function by clopidogrel JOURNAL OF THROMBOSIS AND HAEMOSTASIS Fernando, H., Bassler, N., Habersberger, J., Sheffield, L. J., Sharma, R., Dart, A. M., Peter, K. H., Shaw, J. A. 2011; 9 (8): 1582–89

  Abstract

  Pharmacokinetic studies suggest that clopidogrel and esomeprazole are metabolized by similar hepatic enzymes; however, previous studies have not identified a biochemical interaction.To determine whether addition of esomeprazole to patients receiving aspirin and clopidogrel reduces the antiplatelet effects of clopidogrel.Patients with a history of an acute coronary syndrome who had previously received clopidogrel were recruited. Subjects were commenced on clopidogrel and randomized to one of two treatment arms (esomeprazole or placebo) for 6 weeks. Following a 2-week washout period for study medications, patients were crossed over onto the alternative treatment arm for a further 6 weeks. Platelet function tests were undertaken at baseline, following the first treatment period, after washout and following the second treatment period.Thirty-one patients were enrolled. Significant attenuation of clopidogrel's antiplatelet effects was seen with co-administration of esomeprazole compared with placebo. Vasodilator stimulated phosphoprotein (VASP), platelet aggregometry (area under the curve (AUC)) and VerifyNow results were 54.7% ± 2.8 platelet reactivity index (PRI), 66.3 ± 2.6 AUC units and 213.1 ± 14.1 platelet reactivity units (PRU) with esomeprazole vs. 47% ± 2.7 PRI, 59.7 ± 3.7 AUC units and 181.4 ± 14.6 PRU with placebo (P < 0.01 esomeprazole vs. placebo for all measures). There was no significant difference in platelet aggregometry (maximal aggregation) between the esomeprazole group (68.9% ± 2.7 units) and placebo-treated group (64.5% ± 4.1 units; P > 0.05).Esomeprazole when co-administered with aspirin and clopidogrel results in a significant attenuation of clopidogrel's antiplatelet effects.

  View details for DOI 10.1111/j.1538-7836.2011.04414.x

  View details for Web of Science ID 000293791400019

  View details for PubMedID 21696537