Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index (r = -0.225; ß = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; ß = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O2/s/106 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts.

BACKGROUND: Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery. METHODS: The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization. CONCLUSIONS: The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.

Oral anticoagulant use in patients with atrial fibrillation and mitral valve repair.

BACKGROUND: Patients with atrial fibrillation (AF) who have undergone mitral valve repair are at risk for thromboembolic strokes. Prior to 2019, only vitamin K antagonists were recommended for patients with AF who had undergone mitral valve repair despite the introduction of direct oral anticoagulants (DOAC) in 2010. OBJECTIVE: To characterize the use of anticoagulants in patients with AF who underwent surgical mitral valve repair (sMVR) or transcatheter mitral valve repair (tMVR). METHODS: We performed a retrospective cohort analysis of patients with AF undergoing sMVR or tMVR between 04/2014 and 12/2018 using Optum's de-identified Clinformatics® Data Mart Database. We identified anticoagulants prescribed within 90 days of discharge from hospitalization. RESULTS: Overall, 1997 patients with AF underwent valve repair: 1560 underwent sMVR, and 437 underwent tMVR. The mean CHA2DS2-VASc score among all patients was 4.1 (SD 1.9). The overall use of anticoagulation was unchanged between 2014 (72.2%) and 2018 (70.0%) (P = .49). Among patients who underwent sMVR or tMVR between April 2014 and December 2018, the use of VKA therapy decreased from 62.9% to 32.1% (P < .01 for trend) and the use of DOACs increased from 12.4% to 37.3% (P < .01 for trend). CONCLUSIONS: Among patients with AF who underwent sMVR or tMVR between 2014 and 2018, roughly 30% of patients were not treated with any anticoagulant within 90 days of discharge, despite an elevated stroke risk in the cohort. The rate of DOAC use increased steadily over the study period but did not significantly increase the rate of overall anticoagulant use in this high-risk cohort.

Coronary Artery Bypass Grafting in Cardiogenic Shock: Decision-Making, Management Options, and Outcomes.

Coronary artery bypass grafting is a highly efficacious mode of myocardial revascularization that reduces mortality from ischemic heart disease. The patient presenting after acute myocardial infarction in cardiogenic shock presents a unique challenge. Early revascularization is proven to reduce mortality, but many questions remain, including the optimal mode and extent of revascularization, the role of mechanical circulatory support, and which patients are candidates for surgical intervention. Unprecedented attention to the outcomes of cardiac surgery means decisions about the management of the acute myocardial infarction in cardiogenic shock patients are influenced by risk aversion. The authors here review this topic to arm the reader with a comprehensive understanding of the literature to better guide surgical decision-making and perioperative management.

Severe Impairment of Microcirculatory Perfused Vessel Density Is Associated With Postoperative Lactate and Acute Organ Injury After Cardiac Surgery.

OBJECTIVE: Resuscitation after cardiac surgery needs to address multiple pathophysiological processes that are associated with significant morbidity and mortality. Functional microcirculatory derangements despite normal systemic hemodynamics have been previously described but must be tied to clinical outcomes. The authors hypothesized that microcirculatory dysfunction after cardiac surgery would include impaired capillary blood flow and impaired diffusive capacity and that subjects with the lowest quartile of perfused vessel density would have an increased postoperative lactate level and acute organ injury scores. DESIGN: Prospective, observational study. SETTING: A single, tertiary university cardiovascular surgical intensive care unit. PARTICIPANTS: 25 adults undergoing elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTION: Sublingual microcirculation was imaged using incident dark field microscopy before and 2 to 4 hours after surgery in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Compared with baseline measurements, postoperative vessel-by-vessel microvascular flow index (2.9 [2.8-2.9] v 2.5 [2.4-2.7], p < 0.0001) and perfused vessel density were significantly impaired (20.7 [19.3-22.9] v 16.3 [12.8-17.9], p < 0.0001). The lowest quartile of perfused vessel density (<12.8 mm/mm2) was associated with a significantly increased postoperative lactate level (6.0 ± 2.9 v 1.8 ± 1.2, p < 0.05), peak lactate level (7.6 ± 2.8 v 2.8 ± 1.5, p = 0.03), and sequential organ failure assessment (SOFA) score at 24 and 48 hours. CONCLUSION: In patients undergoing cardiac surgery, there was a significant decrease in postoperative microcirculatory convective blood flow and diffusive capacity during early postoperative resuscitation. Severely impaired perfused vessel density, represented by the lowest quartile of distribution, is significantly related to hyperlactatemia and early organ injury.

The Surgeon's Role in Cardiogenic Shock.

PURPOSE OF REVIEW: Cardiogenic shock represents a very challenging patient population due to the undifferentiated pathologies presenting as cardiogenic shock, difficult decision-making, prognostication, and ever-expanding support options. The role of cardiac surgeons on this team is evolving. RECENT FINDINGS: The implementation of a shock team is associated with improved outcomes in patients with cardiogenic shock. Early deployment of mechanical circulatory support devices may allow an opportunity to rescue these patients. Cardiothoracic surgeons are a critical component of the shock team who can deploy timely mechanical support and surgical intervention in selected patients for optimal outcomes.

Relationship of intraoperative perfusion parameters to the need for immediate extracorporeal support following heart transplantation.

PURPOSE: We sought to assess the relationship of intraoperative perfusion parameters while on cardiopulmonary bypass, including oxygen delivery (DO2), to the need for ECMO following orthotopic heart transplantation (OHT). METHODS: We included all adult (>18 years old) OHTs performed at our institution since implementation of an electronic perfusion record (March 2019-February 2020). Multi-organ transplants were excluded. The primary outcome was the need for immediate venoarterial ECMO in the OR following OHT. Univariable statistics were computed across demographic, clinical, operative, and perfusion variables, including oxygen delivery (DO2) measured each minute. RESULTS: Fifty-three OHT were included with a median age of 54 years (interquartile range, 45-61). The primary outcome occurred in eight patients (15.1%). A significantly greater proportion of patients requiring ECMO had ischemic cardiomyopathy (50.0% (4/8) vs. 15.6% (7/45), p = 0.02) and had preoperative ventricular assist devices (37.5% (3/8) vs. 8.9% (4/45), p = 0.03). Median bypass times were longer in the ECMO group (217 vs. 147 minutes, p = 0.001). Phenylephrine doses were nonsignificantly higher in ECMO patients (4.1 vs. 1.9 mg, p = 0.10). No significant differences were observed in single-point median DO2 (275 vs. 294 mL O2/min/m2 BSA, p = 0.17) and nadir DO2 (226 vs. 222, p = 0.94), but increasing time and depth of DO2 below a threshold of 300 mL O2/min/m2 BSA (i.e. area over the DO2 curve (AOC) but below threshold) was significantly associated with the need for postoperative ECMO (p = 0.04). CONCLUSION: This is the first study to examine the relationship of perfusion parameters, including oxygen delivery, to outcomes following heart transplantation. We note that DO2 < 300-AOC was significantly associated with the need for postoperative ECMO following heart transplant. Further study will clarify whether potential DO2 differences in patients who require post-OHT ECMO reflect vasoplegia, or a more causative relationship which might be leveraged to improve outcomes.

Transplant Volume Is Associated With Graft Acceptance Threshold and Center Resource Availability.

BACKGROUND: Heart transplant volume varies significantly among centers. We hypothesized that centers where the transplant team routinely accepts organs previously declined by other centers and where operating room availability is unrestricted have higher transplant volumes. METHODS AND RESULTS: We used the potential transplant recipient sequence number in the United Network for Organ Sharing database as a surrogate for graft acceptance threshold and the number of transplantations occurring on weekends and 8 major holidays as a marker of center resource availability. Centers were classified as low-, medium-, or high-volume if the average annual number of transplants were, respectively, <10, 10-30, or >30 over a 10-year period. From July 12, 2006, to December 31, 2015, 19,054 transplants were performed by 142 centers. There were 59 low-volume centers, 69 medium-volume centers, and 14 high-volume centers with median potential transplant recipient sequence numbers for transplanted candidates of 7 (interquartile range 3-11), 7 (5-10), and 15 (7-40), respectively (P = .002). The median proportion of off-hours transplantations performed by medium-volume centers was 28% (25%-31%) compared with 32% (29%-33%) by high-volume centers (P = .009). Five-year survival was equivalent among all centers (P = .053). CONCLUSIONS: Transplants for candidates with high sequence numbers and unrestricted operating room availability are associated with increased center volume without sacrificing post-transplantation survival.

Multiorgan procurement is associated with a survival benefit after heart transplantation.

We assessed the impact of donor multiorgan procurement on survival following orthotopic heart transplantation (OHT). From the UNOS STAR database, we included all adult (≥18 Y) heart transplants (OHT) performed since 2000 and used donor IDs to determine how many other organs were procured from the same donor as the recipient's heart allograft (regardless of recipient). The Kaplan-Meier survival functions and risk-adjusted Cox proportional hazards regression models were computed to assess the association of multiorgan procurement with post-heart transplantation mortality. We included 40 336 OHT patients. Including the heart, the median number of donor organs procured was 3 (IQR, 3-4). Heart donors underwent liver procurement in 89.7%; kidney(s) in 98.1% (single 95%, bilateral 5%); lung(s) in 38.0% (single 28%, bilateral 72%); pancreas in 10.4%; and intestine in 1.6%. Following risk adjustment across 16 recipient- and donor-specific variables, an increasing number of organs procured were independently associated with reduced post-OHT mortality (HR 0.98, 95% CI 0.96-0.99, P = .025). Though no significant associations were found examining specific organ types, double lung procurement trended toward a protective effect (HR 0.96, 0.92-1.01, P = .086), with counts of non-lung organs procured still bordering on significance (HR 0.97, 95% CI 0.95-1.00, P = .067). These results likely reflect improved multiorgan donor quality.

Left Ventricular Assist Devices.

Ventricular assist device has rapidly emerged as a durable and safe therapy for end-stage heart failure patients with >22 000 implantations to date. Though originally conceived for bridge-to-transplant indication, significant advancements in medical management as well as technology with arrivals of newer generation devices have improved patient outcomes, leading to increasing use as destination therapy. Despite such improvement, however, the burden of adverse events remains significant and defines the most pressing issue in the current state of ventricular assist device therapy. Eventual use of ventricular assist device technology as a comparable alternative to heart transplantation will ultimately rely on our ability to mitigate these risks. Therefore, this review article provides the narrative surrounding the rapid integration of this technology into the heart failure paradigm, specifically in the context of the most recent data on its outcomes and adverse event profiles. It describes ongoing investigations and general trends that may have significant implications for future improvements in device-related outcomes, as the field continues to grow as the epitome of synergy between advancements in engineering and clinical medicine.

Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation.

BACKGROUND: In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial. METHODS: We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed. RESULTS: Among surviving patients, the mean (±SD) 2-year LVESVI was 52.6±27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6±39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07). CONCLUSIONS: In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.).

Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation.

BACKGROUND: In a trial comparing coronary-artery bypass grafting (CABG) alone with CABG plus mitral-valve repair in patients with moderate ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI) or survival after 1 year. Concomitant mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation, but patients had more adverse events. We now report 2-year outcomes. METHODS: We randomly assigned 301 patients to undergo either CABG alone or the combined procedure. Patients were followed for 2 years for clinical and echocardiographic outcomes. RESULTS: At 2 years, the mean (±SD) LVESVI was 41.2±20.0 ml per square meter of body-surface area in the CABG-alone group and 43.2±20.6 ml per square meter in the combined-procedure group (mean improvement over baseline, -14.1 ml per square meter and -14.6 ml per square meter, respectively). The rate of death was 10.6% in the CABG-alone group and 10.0% in the combined-procedure group (hazard ratio in the combined-procedure group, 0.90; 95% confidence interval, 0.45 to 1.83; P=0.78). There was no significant between-group difference in the rank-based assessment of the LVESVI (including death) at 2 years (z score, 0.38; P=0.71). The 2-year rate of moderate or severe residual mitral regurgitation was higher in the CABG-alone group than in the combined-procedure group (32.3% vs. 11.2%, P<0.001). Overall rates of hospital readmission and serious adverse events were similar in the two groups, but neurologic events and supraventricular arrhythmias remained more frequent in the combined-procedure group. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation undergoing CABG, the addition of mitral-valve repair did not lead to significant differences in left ventricular reverse remodeling at 2 years. Mitral-valve repair provided a more durable correction of mitral regurgitation but did not significantly improve survival or reduce overall adverse events or readmissions and was associated with an early hazard of increased neurologic events and supraventricular arrhythmias. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).

Continuous-Flow LVAD Support Causes a Distinct Form of Intestinal Angiodysplasia.

RATIONALE: The objective of this autopsy study was to determine whether gastrointestinal angiodysplasia develops during continuous-flow left ventricular assist device (LVAD) support. OBJECTIVE: LVAD support causes pathologic degradation of von Willebrand factor (vWF) and bleeding from gastrointestinal angiodysplasia at an alarming rate. It has been speculated that LVAD support itself may cause angiodysplasia. The relationship to abnormal vWF metabolism is unknown. We tested the hypothesis that abnormal gastrointestinal vascularity develops during continuous-flow LVAD support. METHODS AND RESULTS: Small bowel was obtained from deceased humans, cows, and sheep supported with a continuous-flow LVAD (n=9 LVAD, n=11 control). Transmural sections of jejunum were stained with fluorescein isothiocyanate-conjugated isolectin-B4 for endothelium to demarcate vascular structures and quantify intestinal vascularity. Paired plasma samples were obtained from humans before LVAD implantation and during LVAD support (n=41). vWF multimers and degradation fragments were quantified with agarose and polyacrylamide gel electrophoresis and immunoblotting. Abnormal vascular architecture was observed in the submucosa of the jejunum of human patients, cows, and sheep supported with a continuous-flow LVAD. Intestinal vascularity was significantly higher after LVAD support versus controls (5.2±1.0% versus 2.1±0.4%, P=0.004). LVAD support caused significant degradation of high-molecular-weight vWF multimers (-9±1%, P<0.0001) and accumulation of low-molecular-weight vWF multimers (+40±5%, P<0.0001) and vWF degradation fragments (+53±6%, P<0.0001). CONCLUSIONS: Abnormal intestinal vascular architecture and LVAD-associated vWF degradation were consistent findings in multiple species supported with a continuous-flow LVAD. These are the first direct evidence that LVAD support causes gastrointestinal angiodysplasia. Pathologic vWF metabolism may be a mechanistic link between LVAD support, abnormal angiogenesis, gastrointestinal angiodysplasia, and bleeding.

Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.

Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

Surgical ablation of atrial fibrillation during mitral-valve surgery.

BACKGROUND: Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. METHODS: We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). RESULTS: More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P=0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. CONCLUSIONS: The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).

Long-term outcome of surgical cryoablation for refractory ventricular tachycardia in patients with non-ischemic cardiomyopathy.

Aims: Limited data exist on the long-term outcome of patients (pts) with non-ischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) refractory to conventional therapies undergoing surgical ablation (SA). We aimed to investigate the long-term survival and VT recurrence in NICM pts with VT refractory to radiofrequency catheter ablation (RFCA) who underwent SA. Methods and results: Consecutive pts with NICM and VT refractory to RFCA who underwent SA were included. VT substrate was characterized in the electrophysiology lab and targeted by RFCA. During SA, previous RFCA lesions/scars were identified and targeted with cryoablation (CA; 3 min/lesion; target -150 °C). Follow-up comprised office visits, ICD interrogations and the social security death index. Twenty consecutive patients with NICM who underwent SA (age 53 ± 16 years, 18 males, LVEF 41 ± 20%; dilated CM = 9, arrhythmogenic right ventricular CM = 3, hypertrophic CM = 2, valvular CM = 4, and mixed CM = 2) were studied. Percutaneous mapping/ablation in the electrophysiology lab was performed in 18 and 2 pts had primary SA. During surgery, 4.9 ± 4.0 CA lesions/pt were delivered to the endocardium (2) and epicardium (11) or both (7). VT-free survival was 72.5% at 1 year and over 43 ± 31 months (mos) (range 1-83mos), there was only one arrhythmia-related death. There was a significant reduction in ICD shocks in the 3-mos preceding SA vs. the entire follow-up period (6.6 ± 4.9 vs. 2.3 ± 4.3 shocks/pt, P = 0.001). Conclusion: In select pts with NICM and VT refractory to RFCA, SA guided by pre-operative electrophysiological mapping and ablation may be a therapeutic option.

Redo mitral valve surgery following prior mitral valve repair.

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.

Unexpected abrupt increase in left ventricular assist device thrombosis.

BACKGROUND: We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS: We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS: A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS: The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Surgical treatment of moderate ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS: We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS: At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P=0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P=0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P=0.002), and more neurologic events (P=0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS: In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00806988.).