Publications by authors named "Mark R Helmers"

26 Publications

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Do-it-yourself simulators and building a culture of practice in the virtual era.

JTCVS Tech 2021 Aug 19;8:100-111. Epub 2021 May 19.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.

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http://dx.doi.org/10.1016/j.xjtc.2021.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350878PMC
August 2021

The modified US heart allocation system improves transplant rates and decreases status upgrade utilization for patients with hypertrophic cardiomyopathy.

J Heart Lung Transplant 2021 Oct 10;40(10):1181-1190. Epub 2021 Jul 10.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: On October 18, 2018, the US heart allocation policy was restructured to improve transplant waitlist outcomes. Previously, hypertrophic cardiomyopathy (HCM) patients experienced significant waitlist mortality and functional decline, often requiring status exemptions to be transplanted. This study aims to examine changes in waitlist mortality and transplant rates of HCM patients in the new system.

Methods: Retrospective analysis was performed of the United Network for Organ Sharing Transplant Database for all isolated adult single-organ first-time heart transplant patients with HCM listed between October 17, 2013 and September 4, 2020. Patients were divided by listing date into eras based on allocation system. Era 1 spanned October 17, 2013 to October 17th, 2018 and Era 2 spanned October 18th, 2018 to September 4, 2020.

Results: During the study period, 436 and 212 HCM patients were listed in Eras 1 and 2, respectively. Across eras, no differences in gender, ethnicity, BMI or functional status were noted (p>0.05). LVAD utilization remained low (Era 1: 3.7% vs Era 2: 3.3%, p = 0.297). Status upgrades decreased from 49.1% to 31.6% across eras (p = 0.001). There was no statistically significant difference in waitlist mortality across eras (p = 0.332). Transplant rates were improved in Era 2 (p = 0.005). Waitlist time among transplanted patients decreased in Era 2 from 97.1 to 63.9 days (p<0.001). There was no difference in one-year survival post-transplant (p = 0.602).

Conclusions: The new allocation system has significantly increased transplant rates, shortened waitlist times, and decreased status upgrade utilization for HCM patients. Moreover, waitlist mortality remained unchanged in the new system.
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http://dx.doi.org/10.1016/j.healun.2021.06.018DOI Listing
October 2021

HCV-Positive Allograft Use in Heart Transplantation Is Associated With Increased Access to Overdose Donors and Reduced Waitlist Mortality Without Compromising Outcomes.

J Card Fail 2021 Jul 24. Epub 2021 Jul 24.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Because of ongoing shortages of donors for heart transplantation, the use of donor candidates whose availabilities are the result of drug overdoses (ODs) has become increasingly prevalent, even though these donors carry a high preponderance of the now curable hepatitis C virus (HCV). This study investigated temporal trends and regional variabilities in HVC-positive (HCV+) allograft use in heart transplantation and assessed the relationship between the use of HCV+ graft donors and the use of OD donors as well as assessing waitlist and post-transplant outcomes.

Methods And Results: A retrospective review of the United Network for Organ Sharing database assessed adults listed for heart transplantation. Patients were stratified both temporally into pre-HCV and HCV eras related to HCV+ graft use trends and regionally by degree of HCV+ allograft use. Regions of high HCV+ donor use were associated with an increase in OD donor access by 7.8% across eras compared to 0.4% in low HCV+ donor-use regions. One-year waitlist mortality decreased from 4.7% to 2.5% across eras in high HCV+ donor-use regions (P= 0.001) and remained roughly the same as before in low HCV+ donor-use regions (3.0% vs 2.4%; P= 0.244.). Post-transplant survival at 1 year remained similar across eras.

Conclusions: HCV+ donor allograft use can help to optimize donor use, decreasing waitlist mortality without compromising early survival. Ongoing assessment is essential to ensure long-term safety and efficacy of using HCV+ donors.
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http://dx.doi.org/10.1016/j.cardfail.2021.07.007DOI Listing
July 2021

How Should ECMO Be Used Under Conditions of Severe Scarcity? A Population Study of Public Perception.

J Cardiothorac Vasc Anesth 2021 Jul 2. Epub 2021 Jul 2.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA; Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA. Electronic address:

Objective: To assess societal preferences regarding allocation of extracorporeal membrane oxygenation (ECMO) as a rescue option for select patients with coronavirus disease 2019 (COVID-19).

Design: Cross-sectional survey of a nationally representative sample.

Setting: Amazon Mechanical Turk platform.

Participants: In total, responses from 1,041 members of Amazon Mechanical Turk crowd-sourcing platform were included. Participants were 37.9 ± 12.6 years old, generally white (65%), and college-educated (66.1%). Many reported working in a healthcare setting (22.5%) and having a friend or family member who was admitted to the hospital (43.8%) or died from COVID-19 (29.9%).

Measurements And Main Results: Although most reported an unwillingness to stay on ECMO for >one week without signs of recovery, participants were highly supportive of ECMO utilization as a life-preserving technique on a policy level. The majority (96.7%) advocated for continued use of ECMO to treat COVID patients during periods of resource scarcity but would prioritize those with highest likelihood of recovery (50%) followed by those who were sickest regardless of survival chances (31.7%). Patients >40 years old were more likely to prefer distributing ECMO on a first-come first-served basis (21.5% v 13.3%, p < 0.05).

Conclusion: Even though participants expressed hesitation regarding ECMO in personal circumstances, they were uniformly in support of using ECMO to treat COVID patients at a policy level for others who might need it, even in the setting of severe scarcity.
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http://dx.doi.org/10.1053/j.jvca.2021.05.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249692PMC
July 2021

Repair of Isolated Native Mitral Valve Endocarditis: A Propensity Matched Study.

Semin Thorac Cardiovasc Surg 2021 Jun 29. Epub 2021 Jun 29.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.. Electronic address:

In the setting of chronic primary mitral regurgitation, the benefit of mitral valve repair over replacement is well established. However, data comparing outcomes for mitral valve surgery for endocarditis is limited. We sought to determine whether mitral valve repair offers traditional advantages over replacement in the endocarditis population. Retrospective review of our institutional mitral valve database (N = 8,181) was performed between 1998 and 2019 for all adult patients undergoing isolated mitral valve surgery for endocarditis. Patients were stratified by mitral valve repair or replacement and propensity score matching was performed to adjust for differences in baseline characteristics and degree of valve damage. Overall, 267 surgeries (124 repair, 153 replacement) met inclusion criteria during the study period. Following propensity matching, the repair cohort was associated with shorter initial ventilator times (5.6 vs 7.9 hours, p = 0.05), shorter ICU (28 vs 52 hours, p = 0.03), and hospital lengths of stays (7 vs 11 days, p < 0.01). Thirty-day mortality (0% vs 2.1%, p = 0.01) and 10-year survival (88% vs 86%, p = 0.55) were similar between cohorts. Patients in the repair cohort were less likely to require repeat mitral valve intervention at our institution for recurrent endocarditis than those in the replacement cohort (0% vs 10.6%, p = 0.03). Mitral valve repair is safe, when feasible, in the setting of isolated native valve endocarditis and may provide patients faster recovery. Experienced mitral surgeons should approach this patient population with a "repair if feasible" methodology.
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http://dx.doi.org/10.1053/j.semtcvs.2021.05.025DOI Listing
June 2021

Superoxide Dismutase-Loaded Nanoparticles Attenuate Myocardial Ischemia-Reperfusion Injury and Protect Against Chronic Adverse Ventricular Remodeling.

Adv Ther (Weinh) 2021 Jun 23;4(6). Epub 2021 Apr 23.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.

Early revascularization is critical to reduce morbidity after myocardial infarction, although reperfusion incites additional oxidative injury. Superoxide dismutase (SOD) is an antioxidant that scavenges reactive oxygen species (ROS) but has low endogenous expression and rapid myocardial washout when administered exogenously. This study utilizes a novel nanoparticle carrier to improve exogeneous SOD retention while preserving enzyme function. Its role is assessed in preserving cardiac function after myocardial ischemia-reperfusion (I/R) injury. Here, nanoparticle-encapsulated SOD (NP-SOD) exhibits similar enzyme activity as free SOD, measured by ferricytochrome-c assay. In an I/R model, free and NP-SOD reduce active ROS, preserve mitochondrial integrity and improve cell viability compared to controls. In a rat I/R injury model, NP-encapsulation of fluorescent-tagged SOD improves intramyocardial retention after direct injection. Intramyocardial NP-SOD administration improves left ventricular contractility at 3-hours post-reperfusion by echocardiography and 4-weeks by echocardiography and invasive pressure-volume catheter analysis. These findings suggest that NP-SOD mitigates ROS damage in cardiac I/R injury and maximizes retention . NP-SOD further attenuates acute injury and protects against myocyte loss and chronic adverse ventricular remodeling, demonstrating potential for translating NP-SOD as a therapy to mitigate myocardial I/R injury.
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http://dx.doi.org/10.1002/adtp.202100036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225225PMC
June 2021

COVID-19 and cardiothoracic surgery: Effects on training and workforce utilization in a global pandemic.

J Card Surg 2021 Sep 25;36(9):3296-3305. Epub 2021 Jun 25.

Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: The COVID-19 pandemic has disrupted all aspects of healthcare, including cardiothoracic surgery (CTS). We sought to determine the pandemic's impact on CTS trainees' educational experiences.

Methods: A survey was developed and distributed to members of the Thoracic Surgery Residents Association and other international CTS trainees. Trainees were asked to evaluate their cumulative experiences and share their overall perceptions of how CTS training had been impacted during the earliest months of the COVID-19 pandemic (i.e., since March 01, 2020). Surveys were distributed and responses were recorded June 25-August 05, 2020. In total, 748 surveys were distributed and 166 responses were received (overall response rate 22.2%). Of these, 126 of 166 responses (75.9%) met inclusion criteria for final analysis.

Results: Final responses analyzed included 45 of 126 (35.7%) United States (US) and 81 of 126 (64.3%) international trainees, including 101 of 126 (80.2%) senior and 25 of 126 (19.8%) junior trainees. Most respondents (76/126, 43.2%) lost over 1 week in the hospital due to the pandemic. Juniors (12/25, 48.0%) were more likely than seniors (20/101, 19.8%) to be reassigned to COVID-19-specific units (p < .01). Half of trainees (63/126) reported their case volumes were reduced by over 50%. US trainees (42/45, 93.3%) were more likely than international trainees (58/81, 71.6%) to report reduced operative case volumes (p < .01). Most trainees (104/126, 83%) believed their overall clinical acumen was not adversely impacted by the pandemic.

Conclusions: CTS trainees in the United States and abroad have been significantly impacted by the COVID-19 pandemic, with time lost in the hospital, decreased operative experiences, less time on CTS services, and frequent reassignment to COVID-19-specific care settings.
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http://dx.doi.org/10.1111/jocs.15773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447436PMC
September 2021

Assessing predicted heart mass size matching in obese heart transplant recipients.

J Heart Lung Transplant 2021 Aug 12;40(8):805-813. Epub 2021 May 12.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Predicted heart mass (PHM) is currently the most reliable metric for donor-recipient size matching in heart transplantation. Undersizing PHM donor-recipient match more than 20% independently predicts reduced survival. However, it is unclear if this is the case in obese recipients, in whom size matching can be challenging. We examined the use of PHM undersized hearts in obese recipients and assessed its impact on survival.

Methods: The United Network for Organ Sharing database was queried for adult patients undergoing heart transplantation from 1995 to 2020. Obese recipients (BMI ≥ 30) were categorized based on donor-recipient PHM match ≤-20% (undersized) or >-20% (size-matched). Nearest-neighbor propensity score matching was performed to adjust for baseline differences between cohorts. Temporal outcomes were compared by Kaplan-Meier survival analysis.

Results: A total of 13,668 obese recipients met inclusion criteria, with 9.6% receiving undersized and 90.4% receiving size-matched hearts. The proportion of undersized donor hearts in obese recipients significantly decreased over the study period (16.2% [1995] to 7.4% [2019], NP-trend < 0.001). Propensity-score matching resulted in 984 well-matched pairs of undersized and size-matched obese recipients. Recipients of undersized hearts saw similar 30-day mortality (5.5% vs 6.0%, p= 0.11) and re-transplantation rates (1.2% vs 1.2%, p = 1.00) as size-matched recipients. Survival at 1 year (88.4% vs 87.9%, p = 0.14), and 15 years (35.1% vs 31.0%, p = 0.12) was similar across cohorts.

Conclusions: A decreasing proportion of PHM undersized hearts are being utilized in obese recipients. However, utilizing PHM undersized hearts in obese recipients was not associated with a detriment in survival.
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http://dx.doi.org/10.1016/j.healun.2021.04.020DOI Listing
August 2021

Organ allocation and procurement in cardiac transplantation.

Curr Opin Organ Transplant 2021 06;26(3):282-289

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Purpose Of Review: There is a critical shortage of organs in cardiac transplantation. Recent advancements in both organ allocation and donor utilization have intended to address this shortage and optimally allocate allografts. This review evaluates several important aspects of recipient and donor management. For recipients, the focus is placed on the evolving mechanical circulatory support population and its bidirectional impact on organ allocation. From the donor standpoint, organ utilization is assessed with respect to increasing access to previously unused allografts.

Recent Findings: Implementation of the new heart allocation system in the United States has better stratified waitlist candidates by illness acuity. Compared to the prior system, those requiring venoarterial extracorporeal membrane oxygenation support are less likely to die on the waitlist, although conflicting data exists whether this has improved their posttransplant survival. The use of pretransplant intra-aortic balloon pumps has markedly increased, whereas transplantation of patients with dischargeable left ventricular assist devices has decreased. Although some studies have reported inferior short- to mid-term posttransplant survival in the new system compared to its predecessor, others report similar outcomes.Several recent advancements in donor utilization have also been noted. Coinciding with the global increase in drug overdose deaths, efforts have been made to increase use of these donors who are frequently considered 'increased risk' and are hepatitis C-positive. Grafts from these donors appear safe to use. These, alongside donation after circulatory death donors, represent potentially underutilized populations that may effectively expand the donor pool.

Summary: Recent changes in organ allocation, alongside efforts to expand the donor pool, have attempted to improve cardiac allograft utilization and reduce the imbalance between organ supply and demand. Ongoing monitoring and continuous re-evaluation of these efforts will help guide future practice.
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http://dx.doi.org/10.1097/MOT.0000000000000872DOI Listing
June 2021

Wisdom From Past Presidents of The Society of Thoracic Surgeons.

Ann Thorac Surg 2021 10 24;112(4):1372-1377. Epub 2021 Apr 24.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

The Society of Thoracic Surgeons is a highly impactful professional organization in cardiothoracic surgery and an important network of mentors for trainees. Annually, presidents of The Society of Thoracic Surgeons deliver an address encapsulating their professional experiences, lessons learned, and future vision for the field. We sought to summarize these lessons into salient points for trainees. Transcriptions from 1964 to 2018 were reviewed by residents and expounded into categories of importance for readers. Six overarching themes were identified: (1) leadership, (2) education, (3) clinical excellence and innovation, (4) humanism and professionalism, (5) diversity and inclusion, and (6) the future of cardiothoracic surgery.
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.031DOI Listing
October 2021

Therapeutic Efficacy of Cryopreserved, Allogeneic Extracellular Vesicles for Treatment of Acute Myocardial Infarction.

Int Heart J 2021 Mar 17;62(2):381-389. Epub 2021 Mar 17.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania.

Extracellular vesicles (EV) that are derived from endothelial progenitor cells (EPC) have been determined to be a novel therapy for acute myocardial infarction, with a promise for immediate "off-the-shelf" delivery. Early experience suggests delivery of EVs from allogeneic sources is safe. Yet, clinical translation of this therapy requires assurances of both EV stability following cryopreservation and absence of an adverse immunologic response to EVs from allogeneic donors. Thus, more bioactivity studies on allogeneic EVs after cold storage are necessary to establish quality standards for its widespread clinical use. Thus, in this study, we aimed to demonstrate the safety and efficacy in delivering cryopreserved EVs in allogeneic recipients as a therapy for acute myocardial infarction.In this present study, we have analyzed the cardioprotective effects of allogeneic EPC-derived EVs after storage at -80°C for 2 months, using a shear-thinning gel (STG) as an in vivo delivery vehicle. EV size, proteome, and nucleic acid cargo were observed to remain steady through extended cryopreservation via nanoparticle tracking analysis, mass spectrometry, and nanodrop analysis, respectively. Fresh and previously frozen EVs in STG were delivered intramyocardially in a rat model of myocardial infarction (MI), with both showing improvements in contractility, angiogenesis, and scar thickness in comparison to phosphate-buffered saline (PBS) and STG controls at 4 weeks post-MI. Pathologic analyses and flow cytometry revealed minimal inflammatory and immune upregulation upon exposure of tissue to EVs pooled from allogeneic donor cells.Allogeneic EPC-EVs have been known to elicit minimal immune activity and retain therapeutic efficacy after at least 2 months of cryopreservation in a post-MI model.
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http://dx.doi.org/10.1536/ihj.20-224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103174PMC
March 2021

Permanent pacemaker implantation following mitral valve surgery: a retrospective cohort study of risk factors and long-term outcomes.

Eur J Cardiothorac Surg 2021 07;60(1):140-147

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA.

Objectives: Conduction disturbances requiring permanent pacemaker (PPM) implantation remain a complication following valvular surgery. PPMs confer the risk of infection, tricuspid valve regurgitation and pacing-induced cardiomyopathy. Literature examining PPM placement in mitral valve surgery (MVS) is limited.

Methods: Our institutional mitral valve (MV) database was retrospectively reviewed for adult patients undergoing surgery from 2011 to 2019. Patients with preoperative PPM were excluded. Patients were stratified by the receipt of PPM following their index operations. Multivariable logistic regression was performed to determine patient and operative risk factors for PPM. Subgroup analysis was performed on patients who underwent isolated MVS. Kaplan-Meier analysis and a multivariable Cox proportional hazards model were utilized to assess the association between PPM implantation and long-term survival.

Results: A total of 3391 (2991 non-PPM and 400 PPM) patients met the study criteria. Significant predictors of PPM included increased decade of age (odds ratio: 1.23; 95% confidence interval: 1.12-1.35), concomitant aortic (1.44; 1.10-1.90) and tricuspid valve procedures (2.21; 1.64-2.97) and prior history of myocardial infarction (1.48; 1.07-1.86). In the isolated MV repair population, annuloplasty with ring prosthesis was associated with PPM (3.09; 1.19-8.02). Patients in the replacement population did not have significant identifiable risk factors. There was no survival difference found, and postoperative PPM placement was not found to be an independent predictor of mortality.

Conclusions: Our primary aim was to elucidate predictors for PPM implantation in MVS and found increasing age and concomitant procedures to be risk factors. Receipt of PPM is associated with worse long-term survival but does not independently predict survival. Among patients undergoing isolated MV repair, use of an annuloplasty ring confers a higher risk of PPM compared to an annuloplasty band.
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http://dx.doi.org/10.1093/ejcts/ezab091DOI Listing
July 2021

Commentary: Surgery of hypertrophic cardiomyopathy: Focus really does matter.

J Thorac Cardiovasc Surg 2020 Sep 18. Epub 2020 Sep 18.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.09.065DOI Listing
September 2020

Characteristics and Attitudes of Aspiring Cardiothoracic Surgeons: A Survey Study.

Ann Thorac Surg 2021 Feb 4. Epub 2021 Feb 4.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Although recruiting highly qualified, diverse applicants into cardiothoracic surgery remains a national priority, their characteristics remain unknown. This study aims to describe current and future applicants in cardiothoracic surgery.

Methods: Aspiring cardiothoracic surgeons (students interested in matriculating in a North American training program) were voluntarily enrolled in the study through Twitter and email outreach. A 33-question survey evaluated their backgrounds, research experiences, attitudes, and interests within cardiothoracic surgery. Standard descriptive statistics were used.

Results: There were 111 participants, 40 of whom were female (36.0%) and 27 of whom identified as an underrepresented minority (24.3%). Of the total, 63 belonged to an institution with a cardiothoracic surgery training program (56.8%). A total of 91 students envisioned having a mostly operative career (82.0%) and 75 envisioned pursuing educational roles (67.6%). The most popular surgical specialties were heart transplantation (50.5%) and aortic surgery (47.8%). Participants selected having a high-intensity operative environment (81.2%) and an innovative academic environment (58.8%) as the most attractive qualities. Perceived lack of work-life balance (46%) and toxic training or work environment (28%) were the greatest deterrents. Finances during the application process were perceived as a potential barrier by 41 students (36.9%). Approximately 75% of students (83 of 111) had faculty as mentors; 46.8% (56 of 111) thought that cardiothoracic surgery faculty were approachable but had limited time for mentorship.

Conclusions: This survey study characterized a nationally selected pool of aspiring cardiothoracic surgeons using social media. Future studies involving larger and more diverse cohorts are warranted to find areas for improvement in recruitment, retention, and diversity.
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http://dx.doi.org/10.1016/j.athoracsur.2021.01.040DOI Listing
February 2021

Relationship of Cardiopulmonary Bypass Times and Outcomes in Minimally Invasive Mitral Valve Surgery.

Ann Thorac Surg 2021 09 23;112(3):1032-1033. Epub 2021 Jan 23.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, 3400 Spruce St, 6 Silverstein Pavilion, Philadelphia, PA 19104. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2021.01.019DOI Listing
September 2021

Mitral Valve Surgery in Pulmonary Hypertension Patients: Is Minimally Invasive Surgery Safe?

Ann Thorac Surg 2021 06 28;111(6):2012-2019. Epub 2020 Sep 28.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Compared with conventional full sternotomy (FS) approaches, minimally invasive mitral valve surgery (MIMVS) offers improved cosmesis, decreased pain and bleeding, and faster recovery without compromising repair or survival rates. However, little is known about outcomes in patients with pulmonary hypertension (PH), an independent risk factor for morbidity and mortality.

Methods: Retrospective review was performed between 2002 and 2019 for all adult patients undergoing isolated mitral valve surgery. Patients with PH (mean pulmonary artery pressure ≥25 mm Hg) were stratified by FS or MIMVS, and nearest-neighbor propensity score matching was performed to adjust for differences in baseline characteristics.

Results: Overall, 591 operations (317 MIMVS, 274 FS) met inclusion criteria during the study period. Nearest-neighbor propensity matching generated 112 well-matched pairs. Cardiopulmonary bypass (137 vs 89.5 minutes, P < .001), cross-clamp (102 vs 63 minutes, P < .001), and total operative times (241 vs 178.5 minutes, P < .001) were longer for the MIMVS group. Postoperatively, MIMVS was associated with shorter initial ventilator times (6 vs 9.6 hours, P < .001) and hospital lengths of stay (7 vs 8 days, P = .049), as well as blood product usage rates (26.8% vs 41.1%, P = .03). Survival at 30 days (0.0% vs 2.7%, P = .12) and 10 years (log-rank, P = .661) were similar between groups.

Conclusions: MIMVS is safe in patients with PH and provides traditional benefits of minimally invasive surgery, including shorter initial ventilator times and hospital length of stay, without compromising on long-term survival.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.147DOI Listing
June 2021

Association Among Surgeon Experience, Patient Risk, and Outcomes in Coronary Artery Bypass Grafting.

Ann Thorac Surg 2021 01 13;111(1):86-93. Epub 2020 Jun 13.

Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: There is an association between surgeon experience and outcomes after cardiac surgery. However, this association is not well studied in the context of patient risk. The purpose of this single-center, retrospective, observational study was to describe how surgeon experience relates to patient risk in isolated coronary artery bypass grafting (CABG) surgery and how this impacts patient outcomes.

Methods: Surgeon experience was defined as time between the surgeon finishing fellowship and date of the patient's surgery. Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) was used to define patient risk. The Kaplan-Meier method was used to calculate long-term survival, and multivariable Cox proportional hazards regression was used to determine the effect of surgeon experience on survival.

Results: Between 2002 and 2018, 7652 patients underwent isolated CABG. STS PROM was 1.35% (interquartile range [IQR], 0.70%-2.80%), 1.55% (IQR, 0.79%-3.34%), 1.78% (IQR, 0.84%-3.84%), and 1.19% (IQR, 0.62%-2.41%) in surgeon experience quartiles 1 (0.01-6.05 years), 2 (6.05-11.5 years), 3 (11.5-16.6 years), and 4 (16.6-32.1 years), respectively (P < .001). For patients in the lowest PROM quartile, Kaplan-Meier survival was similar across surgeon experience groups (P = .66). For patients in the highest PROM quartile, increasing surgeon experience was associated with better survival (P < .001). Cox regression identified surgeon experience as a protective factor (hazard ratio, 0.99, P = .027). In the least experienced surgeon group, increased ejection fraction was a protective factor for long-term survival (hazard ratio, 0.97; 95% confidence interval, 0.95-0.99).

Conclusions: Increasing surgeon experience is associated with higher-risk patients, but the most experienced surgeons take on lower-risk patients. Greater experience correlates with improved outcomes, especially with higher-risk cases.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.122DOI Listing
January 2021

Commentary: Calpains: Another piece of the cardiac fibrosis puzzle.

J Thorac Cardiovasc Surg 2020 Feb 21. Epub 2020 Feb 21.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.01.012DOI Listing
February 2020

Commentary: One and done: The case for single-dose del Nido cardioplegia.

J Thorac Cardiovasc Surg 2020 11 21;160(5):1203-1204. Epub 2019 Sep 21.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2019.09.020DOI Listing
November 2020

Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome.

J Clin Invest 2020 02;130(2):686-698

Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene, which encodes the pro-α 1 chain of collagen III. Loss of structural integrity of the extracellular matrix is believed to drive the signs and symptoms of this condition, including spontaneous arterial dissection and/or rupture, the major cause of mortality. We created 2 mouse models of vEDS that carry heterozygous mutations in Col3a1 that encode glycine substitutions analogous to those found in patients, and we showed that signaling abnormalities in the PLC/IP3/PKC/ERK pathway (phospholipase C/inositol 1,4,5-triphosphate/protein kinase C/extracellular signal-regulated kinase) are major mediators of vascular pathology. Treatment with pharmacologic inhibitors of ERK1/2 or PKCβ prevented death due to spontaneous aortic rupture. Additionally, we found that pregnancy- and puberty-associated accentuation of vascular risk, also seen in vEDS patients, was rescued by attenuation of oxytocin and androgen signaling, respectively. Taken together, our results provide evidence that targetable signaling abnormalities contribute to the pathogenesis of vEDS, highlighting unanticipated therapeutic opportunities.
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http://dx.doi.org/10.1172/JCI130730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994142PMC
February 2020

Redo mitral valve surgery following prior mitral valve repair.

J Card Surg 2018 Dec 12;33(12):772-777. Epub 2018 Dec 12.

Division of Cardiovascular Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: The optimal treatment strategy following a failed mitral valve repair remains unclear. This study evaluated early and long-term outcomes of redo mitral valve repair (MVr) and replacement (MVR) after prior mitral valve repair.

Methods: Patients undergoing redo mitral valve surgery after prior mitral valve repair at a single institution between 2002 and 2014 were reviewed. Primary outcomes included operative mortality (30-day or in-hospital mortality) and long-term freedom from mitral valve reoperation and death. Secondary outcomes included postoperative complications.

Results: 305 patients underwent redo MVr (n = 48) or MVR (n = 257) after prior mitral valve repair. Concomitant procedures included tricuspid valve repair or replacement (23%), aortic valve replacement (6%), and coronary artery bypass grafting (4%), with no differences between cohorts. 18% were performed via right mini-thoracotomy (24% MVr vs 18% MVR, P = 0.31). Unadjusted and risk-adjusted operative mortality were lower with MVr (0% vs 8%, P = 0.04). Rates of postoperative complications were similar except for blood product transfusion (35% MVr vs 59% MVR, P = 0.003) and prolonged mechanical ventilation (8% MVr vs 29% MVR, P = 0.003). Long-term freedom from mortality was comparable: 96% MVr versus 86% MVR at 1 year and 78% MVr versus 68% MVR at 5 years (P = 0.29).

Conclusions: When technically feasible, mitral valve re-repair can be safely performed with outcomes comparable to MVR.
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http://dx.doi.org/10.1111/jocs.13944DOI Listing
December 2018

Capping off ventricular assist.

J Thorac Cardiovasc Surg 2019 02 1;157(2):e39-e40. Epub 2018 Sep 1.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2018.08.046DOI Listing
February 2019

Response to: Total arch replacement for repair of porcelain aorta.

J Thorac Cardiovasc Surg 2018 02;155(2):530

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.

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http://dx.doi.org/10.1016/j.jtcvs.2017.10.033DOI Listing
February 2018

Robotic versus laparoscopic radical nephrectomy: comparative analysis and cost considerations.

Can J Urol 2016 Oct;23(5):8435-8440

The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Introduction: Robotic-assisted laparoscopic radical nephrectomy (RRN) is an increasing utilized alternative to laparoscopic radical nephrectomy (LRN); however, there is a little data on comparative effectiveness and cost of these procedures. We analyzed perioperative outcomes and hospital charge difference among patients undergoing laparoscopic radical nephrectomy (LRN) and robotic radical nephrectomy (RRN).

Materials And Methods: Our institutional renal mass registry was queried for patients who underwent either LRN or RRN from 2010 to 2014. Demographic, perioperative outcomes and hospital charge data were compared between surgical approaches.

Results: Overall, 319 minimally invasive radical nephrectomies were performed during the study period. Of these, 243 were LRN and 76 were RRN. Patient demographic and tumor characteristics were similar between groups. Among operative characteristics, operative time (136 min versus 139 min, p = 0.531), intraoperative complications (2.8% versus 2.0%, p = 0.650), and length of stay (2 days versus 2 days, p = 0.745) were similar for LRN and RRN, respectively. Estimated blood loss (50 mL versus 100 mL, p = 0.041) and rate of conversion to an alternative surgical approach (1.0% versus 11.1%, p < 0.001) were higher in RRN. RRN cases were also more likely to include lymph node dissection (12.6% versus 24.2%, p = 0.031). Total charges trended higher for RRN but did not meet traditional levels of significance ($14,913 versus $16,265, p = 0.171).

Conclusions: RRN appears to be a clinically equivalent alternative to LRN with similar perioperative outcomes, albeit at greater hospital charges.
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October 2016

Mapping the BH3 Binding Interface of Bcl-xL, Bcl-2, and Mcl-1 Using Split-Luciferase Reassembly.

Biochemistry 2015 Apr 13;54(16):2632-43. Epub 2015 Apr 13.

Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States.

The recognition of helical BH3 domains by Bcl-2 homology (BH) receptors plays a central role in apoptosis. The residues that determine specificity or promiscuity in this interactome are difficult to predict from structural and computational data. Using a cell free split-luciferase system, we have generated a 276 pairwise interaction map for 12 alanine mutations at the binding interface for three receptors, Bcl-xL, Bcl-2, and Mcl-1, and interrogated them against BH3 helices derived from Bad, Bak, Bid, Bik, Bim, Bmf, Hrk, and Puma. This panel, in conjunction with previous structural and functional studies, starts to provide a more comprehensive portrait of this interactome, explains promiscuity, and uncovers surprising details; for example, the Bcl-xL R139A mutation disrupts binding to all helices but the Bad-BH3 peptide, and Mcl-1 binding is particularly perturbed by only four mutations of the 12 tested (V220A, N260A, R263A, and F319A), while Bcl-xL and Bcl-2 have a more diverse set of important residues depending on the bound helix.
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http://dx.doi.org/10.1021/bi501505yDOI Listing
April 2015

Profiling small molecule inhibitors against helix-receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2.

Chem Commun (Camb) 2010 Nov 20;46(42):8020-2. Epub 2010 Sep 20.

Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Blvd, Tucson, AZ 85721, USA.

We validate a practical methodology for the rapid profiling of small molecule inhibitors of protein-protein interactions. We find that a well known BH3 family inhibitor can potently inhibit the p53/hDM2 interaction.
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http://dx.doi.org/10.1039/c0cc02969fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576826PMC
November 2010
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