Publications by authors named "Irving L Kron"

319 Publications

Commentary: Planes, trains, and automobiles-Effective use of prolonged ex vivo heart preservation.

J Card Surg 2021 Mar 30. Epub 2021 Mar 30.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.

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http://dx.doi.org/10.1111/jocs.15520DOI Listing
March 2021

Secondary Burn Progression Mitigated by an Adenosine 2A Receptor Agonist.

J Burn Care Res 2021 Mar 26. Epub 2021 Mar 26.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA.

Background: Current burn therapy is largely supportive with limited therapies to curb secondary burn progression. Adenosine 2A receptor (A2AR) agonists have anti-inflammatory effects with decreased inflammatory cell infiltrate and release of pro-inflammatory mediators. Using a porcine comb burn model, we examined whether A2AR agonists could mitigate burn progression.

Study Design: Eight full-thickness comb burns (4 prongs with 3 spaces per comb) per pig were generated with the following specifications: temperature 115° C, 3 kg force, and 30 second application time. In a randomized fashion, animals (4 per group) were then treated with A2AR agonist (ATL-1223, 3 ng/kg/min, intravenous infusion over 6 hours) or vehicle control. Necrotic interspace development was the primary outcome and additional histologic assessments were conducted.

Results: Analysis of unburned interspaces (72 per group) revealed that ATL-1223 treatment decreased the rate of necrotic interspace development over the first 4 days following injury (p<0.05). Treatment significantly decreased dermal neutrophil infiltration at 48 hours following burn (14.63±4.30 vs 29.71±10.76 neutrophils/high-power field, p=0.029). Additionally, ATL-1223 treatment was associated with fewer interspaces with evidence of microvascular thrombi through post-burn day 4 (18.8% vs 56.3%, p=0.002). Two weeks following insult, the depth of injury at distinct burn sites (adjacent to interspaces) was significantly reduced by ATL-1223 treatment (2.91±0.47 vs 3.28±0.58 mm, p=0.038).

Conclusion: This work demonstrates the ability of an A2AR agonist to mitigate burn progression through dampening local inflammatory processes. Extended dosing strategies may yield additional benefit and improve cosmetic outcome in those with severe injury.
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http://dx.doi.org/10.1093/jbcr/irab053DOI Listing
March 2021

Two Hours of In Vivo Lung Perfusion Improves Lung Function in Sepsis-Induced Acute Respiratory Distress Syndrome.

Semin Thorac Cardiovasc Surg 2021 Mar 11. Epub 2021 Mar 11.

Department of Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Sepsis is the leading cause of acute respiratory distress syndrome (ARDS) in adults and carries a high mortality. Utilizing a previously validated porcine model of sepsis-induced ARDS, we sought to refine our novel therapeutic technique of in vivo lung perfusion (IVLP). We hypothesized that 2 hours of IVLP would provide non-inferior lung rehabilitation compared to 4 hours of treatment. Adult swine (n = 8) received lipopolysaccharide to develop ARDS and were placed on central venoarterial extracorporeal membrane oxygenation. Animals were randomized to 2 vs 4 hours of IVLP. The left pulmonary vessels were cannulated to IVLP using antegrade Steen solution. After IVLP treatment, the left lung was decannulated and reperfused for 4 hours. Total lung compliance and pulmonary venous gases from the right lung (control) and left lung (treatment) were sampled hourly. Biochemical analysis of tissue and bronchioalveolar lavage was performed along with tissue histologic assessment. Throughout IVLP and reperfusion, treated left lung PaO/FiO ratio was significantly higher than the right lung control in the 2-hour group (332.2 ± 58.9 vs 264.4 ± 46.5, P = 0.01). In the 4-hour group, there was no difference between treatment and control lung PaO/FiO ratio (258.5 ± 72.4 vs 253.2 ± 90.3, P = 0.58). Wet-to-dry weight ratios demonstrated reduced edema in the treated left lungs of the 2-hour group (6.23 ± 0.73 vs 7.28 ± 0.61, P = 0.03). Total lung compliance was also significantly improved in the 2-hour group. Two hours of IVLP demonstrated superior lung function in this preclinical model of sepsis-induced ARDS. Clinical translation of IVLP may shorten duration of mechanical support and improve outcomes.
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http://dx.doi.org/10.1053/j.semtcvs.2021.02.034DOI Listing
March 2021

Commentary: Predictors of postoperative adverse events after cone reconstruction for Ebstein's anomaly.

J Card Surg 2021 Mar 27;36(3):1018-1019. Epub 2021 Jan 27.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.

Prediction scores and metrics are being increasingly utilized throughout the fields of cardiothoracic and congenital cardiac surgery to identify areas for perioperative optimization or guide therapeutic intent. Here, we review a novel submission by Yang and colleagues to the Journal of Cardiac Surgery identifying preoperative factors that predict adverse postoperative outcomes from cone reconstruction for Ebstein's anomaly.
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http://dx.doi.org/10.1111/jocs.15376DOI Listing
March 2021

Commentary: Correlation of coronary and valve procedure outcomes between centers.

J Card Surg 2021 02 18;36(2):659-660. Epub 2020 Dec 18.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.

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http://dx.doi.org/10.1111/jocs.15241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855776PMC
February 2021

Effect of Cardiac Surgery on One-Year Patient-Reported Outcomes: A Prospective Cohort Study.

Ann Thorac Surg 2020 Dec 9. Epub 2020 Dec 9.

Department of Surgery, Washington University School of Medicine, St. Louis, MO. Electronic address:

Background: Current cardiac surgery risk algorithms and quality measures focus on perioperative outcomes. However, delivering high-value, patient-centered cardiac care will require a better understanding of long-term patient-reported quality of life after surgery. Our objective was to prospectively assess the effect of cardiac surgery on long-term patient-reported outcomes.

Methods: Patients undergoing cardiac surgery at an academic medical center (2016-2017) were eligible for enrollment. Patient-reported outcomes were measured using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) preoperatively and one year postoperatively across five domains: mental health, physical health, physical functioning, social satisfaction, and applied cognition. Baseline data and perioperative outcomes were obtained from the Society of Thoracic Surgeons database. The effect of cardiac surgery on long-term patient-reported quality of life was assessed.

Results: Ninety-eight patients were enrolled and underwent cardiac surgery, with 92.9% (91/98) successful follow-up. The most common operation was CABG (63.3% [62/98]), with 60.2% (59/98) undergoing an elective operation. One-year all-cause mortality was 5.1% (5/98). Rate of major morbidity was 11.2% (11/98). Cardiac surgery significantly improved patient-reported outcomes at one year across four domains: mental health (Preop: 47.3±7.7 vs. Postop: 51.1±8.9, p=0.0004), physical health (41.2±8.2 vs. 46.3±9.3, p=0.0003), physical functioning (39.8±8.6 vs. 44.8±8.5, p<0.0001), and social satisfaction (46.8±10.9 vs. 50.7±10.8, p=0.023). Hospital discharge to a facility did not impact one-year patient-reported outcomes.

Conclusions: Cardiac surgery improves long-term patient-reported quality of life. Mental, physical, and social well-being scores were significantly higher one year postoperatively. Data collection with NIH PROMIS provides meaningful, quantifiable results that may improve delivery of patient-centered care.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.061DOI Listing
December 2020

Commentary: The over and under on ischemic mitral regurgitation repair.

J Thorac Cardiovasc Surg 2020 Oct 20. Epub 2020 Oct 20.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Va. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.10.025DOI Listing
October 2020

Commentary: Litigation risk in congenital cardiac surgery.

J Card Surg 2021 Jan 12;36(1):143-144. Epub 2020 Oct 12.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.

The risk of malpractice litigation is substantial for congenital cardiac surgeons. It is important for providers to be equipped with strategies to minimize this risk without compromising patient care. Below, we provide a commentary on a recent article from the Journal of Cardiac Surgery discussing litigation risk in this field. To minimize liability and provide optimal care, it is critical that congenital cardiac surgeons focus on both tangible objectives, such as decreasing procedural errors, and less tangible objectives, such as improving surgeon empathy and emotional intelligence.
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http://dx.doi.org/10.1111/jocs.15110DOI Listing
January 2021

Isolated Lung Perfusion in the Management of Acute Respiratory Distress Syndrome.

Int J Mol Sci 2020 Sep 17;21(18). Epub 2020 Sep 17.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22902, USA.

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource utilization. While our understanding of this disease has improved, the majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. There is a dramatic need for the development and breakthrough of new methods for the treatment of ARDS. Isolated machine lung perfusion is a promising surgical platform that has been associated with the rehabilitation of injured lungs and the induction of molecular and cellular changes in the lung, including upregulation of anti-inflammatory and regenerative pathways. Initially implemented in an ex vivo fashion to evaluate marginal donor lungs prior to transplantation, recent investigations of isolated lung perfusion have shifted in vivo and are focused on the management of ARDS. This review presents current tenants of ARDS management and isolated lung perfusion, with a focus on how ex vivo lung perfusion (EVLP) has paved the way for current investigations utilizing in vivo lung perfusion (IVLP) in the treatment of severe ARDS.
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http://dx.doi.org/10.3390/ijms21186820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555278PMC
September 2020

REPLY: CONCOMITANT AORTIC REPLACEMENT: HOW PROACTIVE SHOULD WE BE?

J Thorac Cardiovasc Surg 2021 02 27;161(2):e152-e153. Epub 2020 Aug 27.

Department of Surgery, University of Arizona-Tucson, Tucson, Ariz.

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http://dx.doi.org/10.1016/j.jtcvs.2020.07.108DOI Listing
February 2021

A 30-year analysis of National Institutes of Health-funded cardiac transplantation research: Surgeons lead the way.

J Thorac Cardiovasc Surg 2020 Jul 5. Epub 2020 Jul 5.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Va. Electronic address:

Objectives: Obtaining National Institutes of Health funding for heart transplant research is becoming increasingly difficult, especially for surgeons. We sought to determine the impact of National Institutes of Health-funded cardiac transplantation research over the past 30 years.

Methods: National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results was queried for R01s using 10 heart transplant-related terms. Principal Investigator, total grant funding amount, number of publications, and citations of manuscripts were collected. A citation-based Grant Impact Metric was assigned to each grant: sum of citations for each manuscript normalized by the funding of the respective grant (per $100K). The department and background degree(s) (MD, PhD, MD/PhD) for each funded Principal Investigator were identified from institutional faculty profiles.

Results: A total of 321 cardiac transplantation R01s totaling $723 million and resulting in 6513 publications were analyzed. Surgery departments received more grants and more funding dollars to study cardiac transplantation than any other department (n = 115, $249 million; Medicine: n = 93, $208 million; Pathology: 26, $55 million). Surgeons performed equally well compared with all other Principal Investigators with respect to Grant Impact Metric (15.1 vs 20.6; P = .19) and publications per $1 million (7.5 vs 6.8; P = .75). Finally, all physician-scientists (MDs) have a significantly higher Grant Impact Metric compared with nonclinician researchers (non-MDs) (22.3 vs 16.3; P = .028).

Conclusions: Surgeon-scientists are equally productive and impactful compared with nonsurgeons despite decreasing funding rates at the National Institutes of Health and greater pressure from administrators to increase clinical productivity.
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http://dx.doi.org/10.1016/j.jtcvs.2020.06.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782209PMC
July 2020

Variability and Utilization of Concomitant Atrial Fibrillation Ablation During Mitral Valve Surgery.

Ann Thorac Surg 2021 01 18;111(1):29-34. Epub 2020 Jul 18.

Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Virginia.

Background: Concomitant surgical ablation for atrial fibrillation (AF) at the time of mitral valve surgery is a Society of Thoracic Surgeons Class IA recommendation with evidence from randomized trial data. We hypothesized that concomitant AF ablation rates have increased over time with implementation of this evidence-based practice.

Methods: All patients (N = 7261) undergoing mitral valve operations (2011-2018) were queried from a regional Society of Thoracic Surgeons database. Patients with preoperative AF were stratified by concomitant AF ablation. Trends in concomitant ablation were evaluated over time as well as by center and surgeon mitral surgical volume. The associations between patient and center factors on implementation of concomitant ablation were assessed with multivariate regression.

Results: A total of 1675 patients with preoperative AF underwent isolated mitral valve operations, with 1044 (64.6%) undergoing concomitant ablation. The utilization of concomitant ablation decreased over the study period (-2.82%/year), and was strongly associated with surgeon mitral valve volume (high 78.2% vs medium 62.5% vs low 59.0%; P < .001). Multivariate regression demonstrated age and comorbidities were strong predictors, but high volume mitral surgeons (odds ratio [OR], 2.2; P < .001) were twice as likely to perform concomitant AF ablation. Finally, patients with preoperative AF undergoing ablation were significantly less likely to be in AF at discharge (10.1% vs 53.8%; P < .001).

Conclusions: Despite increasing evidence and societal recommendations, we demonstrate a persistent underutilization of concomitant AF ablation during isolated mitral surgery across a large number of low-volume and high-volume centers. These data suggest significant variability and may represent an opportunity for improvement.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.125DOI Listing
January 2021

Gastrointestinal Complications After Cardiac Surgery: Highly Morbid but Improving Over Time.

J Surg Res 2020 10 5;254:306-313. Epub 2020 Jun 5.

Division of Thoracic & Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Background: Gastrointestinal complications after cardiac surgery are associated with high morbidity and mortality. We sought to determine the granular impact of individual gastrointestinal complications after cardiac surgery and assess contemporary outcomes.

Materials And Methods: Patients undergoing cardiac surgery from 2010 to 2017 (6070 patients) were identified from an institutional Society of Thoracic Surgeons database. Records were paired with institutional data assessing gastrointestinal complications and cost. Patients were stratified by early (2010-2013) and current (2014-2017) eras.

Results: A total of 280 (4.6%) patients experienced gastrointestinal complications including Clostridiumdifficile infection (94, 33.6%), gastrointestinal bleed (86, 30.7%), hepatic failure (66, 23.6%), prolonged ileus (59, 21.1%), mesenteric ischemia (47, 16.8%), acute cholecystitis (17, 6.0%), and pancreatitis (14, 5.0%). Gastrointestinal complications were associated with higher rates of early postoperative major morbidity [206 (73.6%) versus 773 (13.4%), P < 0.0001], mortality [78 (27.9%) versus 161 (2.8%), P < 0.0001], length of stay (23 versus 6 d, P < 0.0001), and discharge to a facility [115 (41.1%) versus 1395 (24.1%), P < 0.0001]. Patients suffering gastrointestinal complications had worse risk-adjusted long-term survival (hazard ratio: 3.0, P < 0.0001) and higher adjusted cost ($9,173, P = 0.05). Between eras, there was no difference in incidence of gastrointestinal complications [139 (4.4%) versus 141 (4.8%), P = 0.51] or rate of specific complications (all P > 0.05). However, long-term survival increased in modern era (P < 0.0001).

Conclusions: Although incidence of gastrointestinal complications after cardiac surgery has not changed over time, long-term survival has improved. Gastrointestinal complications remain associated with high resource utilization and major morbidity, but patients are now more likely to recover, highlighting the benefit of quality improvement efforts.
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http://dx.doi.org/10.1016/j.jss.2020.02.019DOI Listing
October 2020

Adenosine A2A receptor agonist (regadenoson) in human lung transplantation.

J Heart Lung Transplant 2020 06 13;39(6):563-570. Epub 2020 Feb 13.

Division of Developmental Immunology, La Jolla Institute for Immunology and Department of Pharmacology, University of California, San Diego, California.

Background: Currently, there are no clinically approved treatments for ischemia-reperfusion injury after lung transplantation. Pre-clinical animal models have demonstrated a promising efficacy of adenosine receptor (AR) agonists as a treatment option for reducing ischemia-reperfusion injury. The purpose of this human study, is to conduct a Phase I clinical trial for evaluating the safety of continuous infusion of an AR agonist in lung transplant recipients.

Methods: An adaptive, two-stage continual reassessment trial was designed to evaluate the safety of regadenoson (AR agonist) in the setting of lung transplantation. Continuous infusion of regadenoson was administered to lung transplant recipients that was started at the time of skin incision. Adverse events and dose-limiting toxicities, as pre-determined by a study team and assessed by a clinical team and an independent safety monitor, were the primary end-points for safety in this trial.

Results: Between January 2018 and March 2019, 14 recipients were enrolled in the trial. Of these, 10 received the maximum infused dose of 1.44 µg/kg/min for 12 hours. No dose-limiting toxicities were observed. The steady-state plasma regadenoson levels sampled before the reperfusion of the first lung were 0.98 ± 0.46 ng/ml. There were no mortalities within 30 days.

Conclusions: Regadenoson, an AR agonist, can be safely infused in the setting of lung transplantation with no dose-limiting toxicities or drug-related mortality. Although not powered for the evaluation of secondary end-points, the results of this trial and the outcome of pre-clinical studies warrant further investigation with a Phase II randomized controlled trial.
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http://dx.doi.org/10.1016/j.healun.2020.02.003DOI Listing
June 2020

Mortality After Repeat Revascularization Following PCI or CABG for Left Main Disease: The EXCEL Trial.

JACC Cardiovasc Interv 2020 02 15;13(3):375-387. Epub 2020 Jan 15.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York. Electronic address:

Objectives: The aim of this study was to investigate the incidence and impact on mortality of repeat revascularization after index percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD).

Background: The impact on mortality of the need of repeat revascularization following PCI or CABG in patients with unprotected LMCAD is unknown.

Methods: All patients with LMCAD and site-assessed low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores randomized to PCI (n = 948) or CABG (n = 957) in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial were included. Repeat revascularization events were adjudicated by an independent clinical events committee. The effect of repeat revascularization on mortality through 3-year follow-up was examined in time-varying Cox regression models.

Results: During 3-year follow-up, there were 346 repeat revascularization procedures among 185 patients. PCI was associated with higher rates of any repeat revascularization (12.9% vs. 7.6%; hazard ratio: 1.73; 95% confidence interval: 1.28 to 2.33; p = 0.0003). Need for repeat revascularization was independently associated with increased risk for 3-year all-cause mortality (adjusted hazard ratio: 2.05; 95% confidence interval: 1.13 to 3.70; p = 0.02) and cardiovascular mortality (adjusted hazard ratio: 4.22; 95% confidence interval: 2.10 to 8.48; p < 0.0001) consistently after both PCI and CABG (p = 0.85 for both endpoints). Although target vessel revascularization and target lesion revascularization were both associated with an increased risk for mortality, target vessel non-target lesion revascularization and non-target vessel revascularization were not.

Conclusions: In the EXCEL trial, repeat revascularization during follow-up was performed less frequently after CABG than PCI and was associated with increased mortality after both procedures. Reducing the need for repeat revascularization may further improve long-term survival after percutaneous or surgical treatment of LMCAD. (EXCEL Clinical Trial; NCT01205776).
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http://dx.doi.org/10.1016/j.jcin.2019.09.019DOI Listing
February 2020

Pulsed ultrasound attenuates the hyperglycemic exacerbation of myocardial ischemia-reperfusion injury.

J Thorac Cardiovasc Surg 2021 04 2;161(4):e297-e306. Epub 2019 Nov 2.

Department of Surgery, University of Virginia, Charlottesville, Va. Electronic address:

Objective: Acute hyperglycemia during myocardial infarction worsens outcomes in part by inflammatory mechanisms. Pulsed ultrasound has anti-inflammatory potential in bone healing and neuromodulation. We hypothesized that pulsed ultrasound would attenuate the hyperglycemic exacerbation of myocardial ischemia-reperfusion injury via the cholinergic anti-inflammatory pathway.

Methods: Acute hyperglycemia was induced in wild-type C57BL6 or acetylcholine-receptor knockout (α7nAChR) mice by intraperitoneal injection of glucose. Pulsed ultrasound (frequency 7 MHz, bursting mechanical index 1.2, duration 1 second, repeated every 6 seconds for 2 minutes, 20-second total exposure) was performed at the spleen or neck after glucose injection. Separate mice underwent vagotomy before treatment. The left coronary artery was occluded for 20 minutes, followed by 60 minutes of reperfusion. The primary end point was infarct size in explanted hearts.

Results: Splenic pulsed ultrasound significantly decreased infarct size in wild-type C57BL6 mice exposed to acute hyperglycemia and myocardial ischemia-reperfusion injury (5.2% ± 4.4% vs 16.9% ± 12.5% of risk region, P = .013). Knockout of α7nAChR abrogated the beneficial effect of splenic pulsed ultrasound (22.2% ± 12.1%, P = .79 vs control). Neck pulsed ultrasound attenuated the hyperglycemic exacerbation of myocardial infarct size (3.5% ± 4.8%, P = .004 vs control); however, the cardioprotective effect disappeared in mice that underwent vagotomy. Plasma acetylcholine, β2 adrenergic receptor, and phosphorylated Akt levels were increased after splenic pulsed ultrasound treatment.

Conclusions: Pulsed ultrasound treatment of the spleen or neck attenuated the hyperglycemic exacerbation of myocardial ischemia-reperfusion injury leading to a 3-fold decrease in infarct size. Pulsed ultrasound may provide cardioprotection via the cholinergic anti-inflammatory pathway and could be a promising new nonpharmacologic, noninvasive therapy to reduce infarct size during acute myocardial infarction and improve patient outcomes.
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http://dx.doi.org/10.1016/j.jtcvs.2019.10.096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195241PMC
April 2021

SPECT imaging of lung ischemia-reperfusion injury using [Tc]cFLFLF for molecular targeting of formyl peptide receptor 1.

Am J Physiol Lung Cell Mol Physiol 2020 02 4;318(2):L304-L313. Epub 2019 Dec 4.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia.

Primary graft dysfunction after lung transplantation, a consequence of ischemia-reperfusion injury (IRI), is a major cause of morbidity and mortality. IRI involves acute inflammation and innate immune cell activation, leading to rapid infiltration of neutrophils. Formyl peptide receptor 1 (FPR1) expressed by phagocytic leukocytes plays an important role in neutrophil function. The cell surface expression of FPR1 is rapidly and robustly upregulated on neutrophils in response to inflammatory stimuli. Thus, we hypothesized that use of [Tc]cFLFLF, a selective FPR1 peptide ligand, would permit in vivo neutrophil labeling and noninvasive imaging of IRI using single-photon emission computed tomography (SPECT). A murine model of left lung IRI was utilized. Lung function, neutrophil infiltration, and SPECT imaging were assessed after 1 h of ischemia and 2, 12, or 24 h of reperfusion. [Tc]cFLFLF was injected 2 h before SPECT. Signal intensity by SPECT and total probe uptake by gamma counts were 3.9- and 2.3-fold higher, respectively, in left lungs after ischemia and 2 h of reperfusion versus sham. These values significantly decreased with longer reperfusion times, correlating with resolution of IRI as shown by improved lung function and decreased neutrophil infiltration. SPECT results were confirmed using Cy7-cFLFLF-based fluorescence imaging of lungs. Immunofluorescence microscopy confirmed cFLFLF binding primarily to activated neutrophils. These results demonstrate that [Tc]cFLFLF SPECT enables noninvasive detection of lung IRI and permits monitoring of resolution of injury over time. Clinical application of [Tc]cFLFLF SPECT may permit diagnosis of lung IRI for timely intervention to improve outcomes after transplantation.
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http://dx.doi.org/10.1152/ajplung.00220.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052676PMC
February 2020

Reduced-flow ex vivo lung perfusion to rehabilitate lungs donated after circulatory death.

J Heart Lung Transplant 2020 01 18;39(1):74-82. Epub 2019 Sep 18.

Departments of Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Background: Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs.

Methods: A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion.

Results: After transplant, left lung-specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 ± 87.7 mm Hg vs. 252.7 ± 166.0 mm Hg, p = 0.017; 4-hour: 429.7 ± 93.6 mm Hg vs. 231.5 ± 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 ± 9.4 ml/cm HO vs. 10.2 ± 3.5 ml/cm HO, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 ± 0.7 vs. 8.8 ± 1.1, p = 0.040) and interleukin-1β expression (927 ± 300 pg/ng protein vs. 2,070 ± 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group.

Conclusions: EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.
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http://dx.doi.org/10.1016/j.healun.2019.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001159PMC
January 2020

Comprehensive National Institutes of Health funding analysis of academic cardiac surgeons.

J Thorac Cardiovasc Surg 2020 06 9;159(6):2326-2335.e3. Epub 2019 Sep 9.

Division of Cardiac Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Va. Electronic address:

Objective: To determine trends in National Institutes of Health (NIH) funding for cardiac surgeons, hypothesizing they are at a disadvantage in obtaining funding owing to intensive clinical demands.

Methods: Cardiac surgeons (adult/congenital) currently at the top 141 NIH-funded institutions were identified using institutional websites. The NIH funding history for each cardiac surgeon was queried using the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER). Total grant funding, publications, and type was collected. Academic rank, secondary degrees, and fellowship information was collected from faculty pages. Grant productivity was calculated using a validated grant impact metric.

Results: A total of 818 academic cardiac surgeons were identified, of whom 144 obtained 293 NIH grants totaling $458 million and resulting in 6694 publications. We identified strong associations between an institution's overall NIH funding rank and the number of cardiac surgeons, NIH grants to cardiac surgeons, and amount of NIH funding to cardiac surgeons (P < .0001 for all). The majority of NIH funding to cardiac surgeons is concentrated in the top quartile of institutions. Cardiac surgeons had a high conversion rates from K awards (mentored development awards) to R01s (6 of 14; 42.9%). Finally, we demonstrate that the rate of all NIH grants awarded to cardiac surgeons has increased, driven primarily by P and U (collaborative project) grants.

Conclusions: NIH-funded cardiac surgical research has had a significant impact over the last 3 decades. Aspiring cardiac surgeon-scientists may be more successful at top quartile institutions owing to better infrastructure and mentorship.
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http://dx.doi.org/10.1016/j.jtcvs.2019.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546359PMC
June 2020

Risk Aversion in Cardiac Surgery: 15-Year Trends in a Statewide Analysis.

Ann Thorac Surg 2020 05 23;109(5):1401-1407. Epub 2019 Sep 23.

Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Background: With a rising emphasis on public reporting, we hypothesized that select hospitals are becoming increasingly risk-averse by avoiding high-risk operations. Further, we evaluated the association between risk-averse practices, outcomes, and publicly reported quality measures.

Methods: Clinical data from 78,417 patients undergoing cardiac surgery (2002-2016) from a regional consortium was paired with publicly available reimbursement and quality data. High-risk surgery was defined as predicted risk of mortality ≥5%. Hospital risk aversion was defined as a significant decrease in both high-risk volume and proportion, with cases stratified by hospital risk aversion status for univariate analysis.

Results: The rate of high-risk cases decreased from 17.9% in 2002 to 12.6% in 2016. Significant risk aversion was seen in 39% of hospitals, which had a 59% decrease in high-risk volume vs a 16% decrease at non-risk-averse hospitals. In the last 5 years, declining high-risk cases at risk-averse hospitals were driven by fewer cases from transfers (19.2% vs 28.1%, P < .001) and the emergency department (17.6% vs 19.2%, P = .001). Only non-risk-averse hospitals had mortality rates lower than expected (risk-averse: 0.97 [95% confidence interval, 0.91-1.03], P = .30; non-risk-averse: 0.88 [95% confidence interval, 0.83-0.94], P = .001). There were no differences by risk aversion status in reported ratings or financial incentives (all P > .05).

Conclusions: Over 60% of hospitals continue to operate on high-risk patients, with concentration of care driven by transfer patterns. These non-risk-averse hospitals are high-performing with better-than-expected outcomes, particularly in high-risk cases. Transparency and objectivity in reporting are essential to ensure continued access for these high-risk patients.
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http://dx.doi.org/10.1016/j.athoracsur.2019.08.027DOI Listing
May 2020

Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery.

Ann Surg 2019 May 2. Epub 2019 May 2.

Department of Surgery, Washington University School of Medicine, St. Louis, MO.

Objective: To evaluate meaningful, patient-centered outcomes including alive-at-home status and patient-reported quality of life 1 year after cardiac surgery.

Background: Long-term patient-reported quality of life after cardiac surgery is not well understood. Current operative risk models and quality metrics focus on short-term outcomes.

Methods: In this combined retrospective/prospective study, cardiac surgery patients at an academic institution (2014-2015) were followed to obtain vital status, living location, and patient-reported outcomes (PROs) at 1 year using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS). We assessed the impact of cardiac surgery, discharge location, and Society of Thoracic Surgeons perioperative predicted risk of morbidity or mortality on 1-year outcomes.

Results: A total of 782 patients were enrolled; 84.1% (658/782) were alive-at-home at 1 year. One-year PROMIS scores were global physical health (GPH) = 48.8 ± 10.2, global mental health (GMH) = 51.2 ± 9.6, and physical functioning (PF) = 45.5 ± 10.2 (general population reference = 50 ± 10). All 3 PROMIS domains at 1 year were significantly higher compared with preoperative scores (GPH: 41.7 ± 8.5, GMH: 46.9 ± 7.9, PF: 39.6 ± 9.0; all P < 0.001). Eighty-two percent of patients discharged to a facility were alive-at-home at 1 year. These patients, however, had significantly lower 1-year scores (difference: GPH = -5.1, GMH = -5.1, PF = -7.9; all P < 0.001). Higher Society of Thoracic Surgeons perioperative predicted risk was associated with significantly lower PRO at 1 year (P < 0.001).

Conclusions: Cardiac surgery results in improved PROMIS scores at 1 year, whereas discharge to a facility and increasing perioperative risk correlate with worse long-term PRO. One-year alive-at-home status and 1-year PRO are meaningful, patient-centered metrics that help define long-term quality and the benefit of cardiac surgery.
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http://dx.doi.org/10.1097/SLA.0000000000003357DOI Listing
May 2019

Travel distance and regional access to cardiac valve surgery.

J Card Surg 2019 Oct 2;34(10):1044-1048. Epub 2019 Aug 2.

Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Virginia.

Objective: Evidence in other surgical subspecialties suggests patients traveling farther to undergo surgery have worse outcomes. We sought to determine the impact of travel distance and travel beyond closest center on outcomes after valve surgery.

Methods: Patients who underwent valve surgery ±CABG with a Society of Thoracic Surgeons (STS) predicted risk and zip code were extracted from a statewide STS database (2011-016). Patients were stratified by those receiving care greater than or equal to 20 miles from the closest surgical center (Traveler) or at the closest center (Non-Traveler). Multivariate logistic regression assessed the effects of travel distance and traveler status on mortality and major morbidity adjusted for STS predicted risk, median income by zip code, and payer status.

Results: Median travel distance for all patients (n = 4765) was 19 miles and after risk-adjustment increasing distance was associated with reduced operative mortality (odds ratio [OR], 0.94 [0.89-1.00], P = .049) with no impact on major morbidity. Travelers (445 patients, 9.3%) had lower median income, higher self-pay and reoperative status, but similar urgent/emergent status and STS risk as Non-Travelers. Travelers had lower operative mortality (1.6% vs 4.3%, P = .005) which remained statistically lower after risk-adjustment (OR, 0.32 [0.14-0.75], P = .009). This mortality difference was particularly pronounced in patients with postoperative complications (3.1% vs 7.9%, P = .005).

Conclusions: Contrary to other surgical subspecialties, farther travel distance and bypassing the nearest surgical center were associated with lower rates of operative mortality and failure to rescue. Either referral patterns or financials reasons may result in Travelers ending up at high performing centers that prevent escalation of complications.
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http://dx.doi.org/10.1111/jocs.14199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776674PMC
October 2019

Impact of Complications After Cardiac Operation on One-Year Patient-Reported Outcomes.

Ann Thorac Surg 2020 01 16;109(1):43-48. Epub 2019 Jul 16.

Division of Thoracic & Cardiovascular Surgery, University of Virginia, Charlottesville, Virginia. Electronic address:

Background: Current reporting on cardiac surgical outcomes focuses on a patient's status at 30 days and lacks long-term meaningful data. The purpose of this study was to determine the impact of complications after cardiac operation on patient-reported outcomes (PROs) at 1 year after surgery.

Methods: All patients undergoing cardiac operation at an academic institution (2014-2015) were contacted 1 year after surgery to obtain vital status, location, and PROs using the validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH-PROMIS). Records were merged with Society of Thoracic Surgeons (STS) data, and multivariate linear regression evaluated the risk-adjusted effects of complications on 1-year PROs.

Results: A total of 782 eligible patients underwent cardiac operation, with PROs data available for 91% of patients alive at 1 year (648 of 716). Mean NIH-PROMIS scores were global physical health (GPH), 48.8 ± 10.2; global mental health (GMH), 51.3 ± 9.5; and physical functioning (PF), 45.5 ± 10.2 (reference score for general adult population, 50 ± 10). Occurrence of an STS Major Morbidity (prolonged ventilation, renal failure, reoperation, stroke, or deep sternal wound infection) significantly reduced 1-year PROs (GPH, 45.4 ± 8.9 [P < .001]; GMH, 48.6 ± 9.5 [P = .01]; PF, 40.9 ± 10.2 [P < .001]). After risk adjustment, incidence of a STS Major Morbidity, prolonged ventilation, or renal failure had a significant adverse effect on 1 or more PRO domains.

Conclusions: Although cardiac surgical patients have PROs scores similar to the general population, complications after cardiac operation continue to negatively influence patient quality of life 1 year after surgery. Use of NIH-PROMIS shows that prolonged ventilation and renal failure have the largest impact on 1-year patient-reported outcomes.
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http://dx.doi.org/10.1016/j.athoracsur.2019.05.067DOI Listing
January 2020

Commentary: Do not fear the ascending aorta.

J Thorac Cardiovasc Surg 2020 05 7;159(5):1681-1682. Epub 2019 Jun 7.

Department of Surgery, University of Arizona Health Sciences, Tucson, Ariz. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2019.05.055DOI Listing
May 2020

Goal-directed resuscitation following cardiac surgery reduces acute kidney injury: A quality initiative pre-post analysis.

J Thorac Cardiovasc Surg 2020 05 17;159(5):1868-1877.e1. Epub 2019 May 17.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Objective: Acute kidney injury (AKI) occurs in 20% of patients following cardiac surgery. To reduce AKI in our institution, we instituted a quality improvement (QI) initiative using a goal-directed volume resuscitation protocol. Our protocol was designed to achieve quantifiable physiologic goals (eg, cardiac index > 2.5 L/min/m, mean arterial pressure > 65 mm Hg) using fluid and vasoactive agents. The objective of this study was to evaluate AKI in the pre- and post-QI eras, hypothesizing that AKI incidence would decrease in the post-QI era.

Methods: In this observational retrospective cohort study, we identified patients who underwent cardiac operations from July 2011 to July 2015 with a risk score available. Kidney injury was determined using the lowest postoperative GFR within 7 days of surgery and standard Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (RIFLE) classification criteria. The primary outcome was the rate of AKI, as defined by glomerular filtration rate-based RIFLE classification criteria injury, in the post- versus pre-QI eras.

Results: A total of 1979 patients were included, of whom 725 were in the pre-QI cohort, and 1254 in the post-QI cohort. Overall, rates of RIFLE classification criteria risk, injury and failure were 27.5%, 5.9%, and 3.6%, respectively. RIFLE classification criteria injury saw the largest decrease in the post-QI cohort (8.1% vs 4.6%; P = .001). Multivariable analysis demonstrated a 37% reduction in the odds of AKI in the post-QI cohort (adjusted odds ratio, 0.63; 95% confidence interval, 0.43-0.90).

Conclusions: A goal-directed volume resuscitation protocol centered on patient fluid responsiveness is associated with significantly reduced risk for AKI after cardiac surgery. Protocol-driven approaches should be employed in intensive care units to improve outcomes.
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http://dx.doi.org/10.1016/j.jtcvs.2019.03.135DOI Listing
May 2020

Development and Validation of Procedure-Specific Risk Score for Predicting Postoperative Pulmonary Complication: A NSQIP Analysis.

J Am Coll Surg 2019 10 18;229(4):355-365.e3. Epub 2019 Jun 18.

Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA.

Background: Postoperative pulmonary complications (PPCs; unplanned reintubation, postoperative pneumonia, and failure to liberate from mechanical ventilation within 48 hours), contribute significantly to increased rates of morbidity and mortality. Procedure type is an important factor that contributes risk in generalized PPC prediction models. The objective of this study was to develop and validate procedure-specific risk scores for the 6 procedures with the highest rates of PPCs.

Study Design: American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use File data (2005 to 2015) for patients undergoing pancreatectomy, hepatectomy, esophagectomy, abdominal aortic aneurysm repair, open aortoiliac repair, and lung resection were used for analysis. Multivariable logistic regression was used to develop pulmonary complications risk scores (PCRS) for each procedure. Youden indices were used to identify cutoff points within each PCRS and were further validated using a random selection of the original NSQIP dataset collected.

Results: Twenty-one variables were included in the initial analysis, which yielded unique relative risk score models for each procedure. Within all the risk score models, long operative time (within the last quartile) was a strong predictor of PPCs. An increased rate of PPCs was associated with increasing PCRS values in both the training and validation samples for all procedures.

Conclusions: Important variables were identified for 6 common procedures that yield an increased risk of PPCs. These variables differed by procedure type, outlining the importance of procedure-specific risk scores. Each procedure-specific PCRS developed in this study can be used by health care professionals to better predict the risk of PPCs and to optimize patient outcomes.
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.05.028DOI Listing
October 2019

Outcomes of left main revascularization in patients with acute coronary syndromes and stable ischemic heart disease: Analysis from the EXCEL trial.

Am Heart J 2019 08 4;214:9-17. Epub 2019 May 4.

Clinical Trials Center, Cardiovascular Research Foundation, New York, NY; Center for Interventional Vascular Therapy, Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, NY. Electronic address:

Background: Prompt revascularization is often required in acute coronary syndromes (ACS), whereas stable ischemic heart disease (SIHD) may allow for more measured procedural planning. Whether the acuity of presentation preferentially affects outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with left main coronary artery disease (LMCAD) is unknown. We investigated whether the acuity of presentation discriminated patients who derived a differential benefit from PCI versus CABG in the randomized Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial.

Methods: We used multivariable Cox models to assess the interaction between the acuity of presentation, type of revascularization and outcomes in patients with low or intermediate SYNTAX scores enrolled in EXCEL.

Results: At baseline, 1151 patients (60.7%) presented with SIHD and 746 patients (39.3%) presented with an ACS. The acuity of presentation was not associated with the primary endpoint of all-cause death, MI, or stroke at 3 years (multivariable adjusted hazard ratio [HR] 0.94; 95% CI 0.70-1.26, P = .64). The primary endpoint rate was similar in patients assigned to PCI versus CABG whether they presented with SIHD (adjusted HR 1.04; 95% CI 0.73-1.48]) or with ACS (HR 0.82; 95% CI 0.54-1.26) (P = .34).

Conclusions: The acuity of presentation did not predict outcomes in patients with LMCAD undergoing revascularization, nor did it discriminate patients who derive greater event-free survival from PCI versus CABG.
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http://dx.doi.org/10.1016/j.ahj.2019.04.016DOI Listing
August 2019

Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During Extracorporeal Cardiopulmonary Resuscitation.

Ann Surg 2019 06;269(6):1176-1183

Department of Surgery, University of Virginia, Charlottesville, VA.

Objective: We tested the hypothesis that systemic administration of an A2AR agonist will reduce multiorgan IRI in a porcine model of ECPR.

Summary Background Data: Advances in ECPR have decreased mortality after cardiac arrest; however, subsequent IRI contributes to late multisystem organ failure. Attenuation of IRI has been reported with the use of an A2AR agonist.

Methods: Adult swine underwent 20 minutes of circulatory arrest, induced by ventricular fibrillation, followed by 6 hours of reperfusion with ECPR. Animals were randomized to vehicle control, low-dose A2AR agonist, or high-dose A2AR agonist. A perfusion specialist using a goal-directed resuscitation protocol managed all the animals during the reperfusion period. Hourly blood, urine, and tissue samples were collected. Biochemical and microarray analyses were performed to identify differential inflammatory markers and gene expression between groups.

Results: Both the treatment groups demonstrated significantly higher percent reduction from peak lactate after reperfusion compared with vehicle controls. Control animals required significantly more fluid, epinephrine, and higher final pump flow while having lower urine output than both the treatment groups. The treatment groups had lower urine NGAL, an early marker of kidney injury (P = 0.01), lower plasma aspartate aminotransferase, and reduced rate of troponin rise (P = 0.01). Pro-inflammatory cytokines were lower while anti-inflammatory cytokines were significantly higher in the treatment groups.

Conclusions: Using a novel and clinically relevant porcine model of circulatory arrest and ECPR, we demonstrated that a selective A2AR agonist significantly attenuated systemic IRI and warrants clinical investigation.
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http://dx.doi.org/10.1097/SLA.0000000000002685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757347PMC
June 2019

Commentary: Cervical aortic arch repair-an overarching success.

J Thorac Cardiovasc Surg 2020 06 4;159(6):2214-2215. Epub 2019 Apr 4.

Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va; Department of Surgery, University of Arizona Health Sciences, Tucson, Ariz. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2019.03.086DOI Listing
June 2020

Determining Which Prosthetic to Use During Aortic Valve Replacement in Patients Aged Younger than 70 Years: A Systematic Review of the Literature.

Heart Surg Forum 2019 02 28;22(2):E070-E081. Epub 2019 Feb 28.

Department of Surgery, University of Virginia, Charlottesville, VA., USA.

Background: The choice of bioprosthesis versus mechanical prosthesis in patients aged less than 70 years undergoing aortic valve replacement (AVR) remains controversial, with guidelines disparate in their recommendations. The objective of this study was to explore outcomes after AVR for various age ranges based on type of prosthesis.

Methods: A systematic review was undertaken according to the Preferred Reporting Instructions for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using Medline (PubMed), Cochrane, Web of Science, Embase, and Scopus databases. Rates of long-term survival (primary outcome), reoperation, major bleeding, thromboembolism, stroke, structural valve deterioration, and endocarditis were compared between subjects receiving biologic and mechanical prostheses. Findings were grouped into patients aged <60 years, aged ≤65 years, and finally aged <70 years.

Results: A total of 19 studies met inclusion criteria. Seven evaluated patients aged <60 years, 4 of which found mechanical prosthesis patients to have higher long-term survival, whereas the remaining studies found no difference. Eight additional studies included patients aged 65 years or younger, and 9 studies included patients aged <70 years. The former found no difference in survival between prosthesis groups, whereas the latter favored mechanical prostheses in 3 studies. Bleeding, thromboembolism, and stroke were more prevalent in patients with a mechanical prosthesis, whereas reoperation was more common in those receiving a bioprosthesis.

Conclusions: Published literature does not preclude the use of bioprostheses for AVR in younger patients. As new valves are developed, the use of bioprosthetic aortic valves in younger patients will likely continue to expand. Clinical trials are needed to provide surgeons with more accurate guidelines.
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http://dx.doi.org/10.1532/hsf.2131DOI Listing
February 2019