Programmatic approach to patients with advanced ischemic cardiomyopathy: Integrating microaxial support into strategies for the modern era.

Patients with advanced ischemic cardiomyopathy manifesting as left ventricular dysfunction exist along a spectrum of severity and risk, and thus decision-making surrounding optimal management is challenging. Treatment pathways can include medical therapy as well as revascularization through percutaneous coronary intervention or coronary artery bypass grafting. Additionally, temporary and durable mechanical circulatory support, as well as heart transplantation, may be optimal for select patients. Given this spectrum of risk and the complexity of treatment pathways, patients may not receive appropriate therapy given their perceived risk, which can lead to sub-satisfactory outcomes. In this review, we discuss the identification of high-risk ischemic cardiomyopathy patients, along with our programmatic approach to patient evaluation and perioperative optimization. We also discuss our strategies for therapeutic decision-making designed to optimize both short- and long-term patient outcomes.

Derivation and Validation of Clinical Phenotypes of the Cardiopulmonary Bypass-Induced Inflammatory Response.

BACKGROUND: Precision medicine aims to change treatment from a "one-size-fits-all" approach to customized therapies based on the individual patient. Applying a precision medicine approach to a heterogeneous condition, such as the cardiopulmonary bypass (CPB)-induced inflammatory response, first requires identification of homogeneous subgroups that correlate with biological markers and postoperative outcomes. As a first step, we derived clinical phenotypes of the CPB-induced inflammatory response by identifying patterns in perioperative clinical variables using machine learning and simulation tools. We then evaluated whether these phenotypes were associated with biological response variables and clinical outcomes. METHODS: This single-center, retrospective cohort study used Cleveland Clinic registry data from patients undergoing cardiac surgery with CPB from January 2010 to March 2020. Biomarker data from a subgroup of patients enrolled in a clinical trial were also included. Patients undergoing emergent surgery, off-pump surgery, transplantation, descending thoracoabdominal aortic surgery, and planned ventricular assist device placement were excluded. Preoperative and intraoperative variables of patient baseline characteristics (demographics, comorbidities, and laboratory data) and perioperative data (procedural data, CPB duration, and hemodynamics) were analyzed to derive clinical phenotypes using K-means-based consensus clustering analysis. Proportion of ambiguously clustered was used to assess cluster size and optimal cluster numbers. After clusters were formed, we summarized perioperative profiles, inflammatory biomarkers (eg, interleukin [IL]-6 and IL-8), kidney biomarkers (eg, urine neutrophil gelatinase-associated lipocalin [NGAL] and IL-18), and clinical outcomes (eg, mortality and hospital length of stay). Pairwise standardized difference was reported for all summarized variables. RESULTS: Of 36,865 eligible cardiac surgery cases, 25,613 met inclusion criteria. Cluster analysis derived 3 clinical phenotypes: α, ß, and γ. Phenotype α (n = 6157 [24%]) included older patients with more comorbidities, including heart and kidney failure. Phenotype ß (n = 10,572 [41%]) patients were younger and mostly male. Phenotype γ (n = 8884 [35%]) patients were 58% female and had lower body mass index (BMI). Phenotype α patients had worse outcomes, including longer hospital length of stay (mean = 9 days for α versus 6 for both ß [absolute standardized difference {ASD} = 1.15] and γ [ASD = 1.08]), more kidney failure, and higher mortality. Inflammatory biomarkers (IL-6 and IL-8) and kidney injury biomarkers (urine NGAL and IL-18) were higher with the α phenotype compared to ß and γ immediately after surgery. CONCLUSIONS: Deriving clinical phenotypes that correlate with response biomarkers and outcomes represents an initial step toward a precision medicine approach for the management of CPB-induced inflammatory response and lays the groundwork for future investigation, including an evaluation of the heterogeneity of treatment effect.

Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial.

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, and PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

Outcomes of heart transplant recipients with prior left ventricular assist device associated stroke.

BACKGROUND: Left ventricular assist devices (LVADs) improve survival in patients with end-stage heart failure but are associated with ischemic stroke and intracranial hemorrhage (ICH). The impact of LVAD-associated stroke on transplant candidacy and outcomes has not been characterized. METHODS: Adult patients undergoing LVAD implantation at Cleveland Clinic between 2004 to 2021 were reviewed and patients who developed ischemic stroke or ICH were identified. Post-transplant survival analysis was performed between patients with LVAD-associated stroke vs. without. RESULTS: 917 patients had an LVAD implantation of whom 244 (median age 57, 79% male) underwent subsequent transplant including 25 with prior LVAD-associated stroke. The 1- and 2-year survival after transplant in patients with LVAD-associated stroke were 100% and 95% respectively, compared with 92% and 90% in patients without stroke (p=0.156; p=0.323) Similarly, there was no difference in stroke incidence at 1- and 2 years after transplant between patients with LVAD-associated stroke (4% and 5%) and those without prior stroke (5% and 6%, p = 0.884; p=0.744). CONCLUSIONS: In this single-center retrospective study, patients with LVAD-associated stroke were significantly less likely to undergo heart transplant, but those who underwent heart transplant had similar post-transplant outcomes as patients without history of LVAD-associated stroke. Given the similar outcomes seen in this population, history of LVAD-associated stroke should not be viewed as an absolute contraindication to subsequent heart transplant.

Procedure-Specific Relationships Between Postoperative Troponin T and a Composite of Mortality and Low Cardiac Output Syndrome: A Retrospective Cohort Analysis.

BACKGROUND: Myocardial injury after coronary artery bypass grafting (CABG) is defined as troponin concentrations >10 times 99th percentile upper reference limit (URL) according to the Fourth Universal Definition. However, troponin concentrations after non-CABG cardiac surgery which indicate greater-than-expected myocardial injury and increased risk for complications remain unclear. Our goal was to assess procedure-specific relationships between troponin T and a composite outcome of low cardiac output syndrome and in-hospital mortality in cardiac surgical patients. METHODS: Patients having cardiac surgery between January 2010 and December 2017 were categorized into 4 groups by procedure: (1) CABG; (2) mitral valve repair; (3) aortic valve repair/replacement (AVR); (4) mitral valve replacement (MVR) or CABG + valve surgeries. Exclusion criteria were elevated preoperative troponin T, preoperative kidney failure, circulatory arrest, or preoperative/planned mechanical circulatory support. Logistic regression was used to assess the association between troponin T and composite outcome, both overall and by procedure, including assessment of the interaction between procedure and troponin T on outcome. RESULTS: Among 10,253 patients, 37 (0.4%) died and 393 (3.8%) developed the primary outcome. Troponin T concentrations differed by procedure (P < .001). Compared to CABG, AVR had 0.53 (99.2% confidence interval [CI], 0.50-0.56; unadjusted P < .001) times lower troponin T concentrations, while MVR/CABG + valve were 1.54 (99.2% CI, 1.45-1.62, unadjusted P < .001) times higher. There were linear relationships between log2 troponin T concentration and log odds mortality/low cardiac output syndrome. The (unadjusted) relationships were parallel for various types of surgery (interaction P = .59), but at different levels of the outcome. CONCLUSIONS: The relative increase in odds for mortality/low cardiac output syndrome per a similar increase in troponin T concentrations did not differ among cardiac surgical procedures, but the absolute troponin T concentrations did. Troponin concentrations should thus be interpreted in context of surgical procedure.

Predictive Accuracy of a Perioperative Laboratory Test-Based Prediction Model for Moderate to Severe Acute Kidney Injury After Cardiac Surgery.

Importance: Effective treatment of acute kidney injury (AKI) is predicated on timely diagnosis; however, the lag in the increase in serum creatinine levels after kidney injury may delay therapy initiation. Objective: To determine the derivation and validation of predictive models for AKI after cardiac surgery. Design, Setting, and Participants: Multivariable prediction models were derived based on a retrospective observational cohort of adult patients undergoing cardiac surgery between January 2000 and December 2019 from a US academic medical center (n = 58 526) and subsequently validated on an external cohort from 3 US community hospitals (n = 4734). The date of final follow-up was January 15, 2020. Exposures: Perioperative change in serum creatinine and postoperative blood urea nitrogen, serum sodium, potassium, bicarbonate, and albumin from the first metabolic panel after cardiac surgery. Main Outcomes and Measures: Area under the receiver-operating characteristic curve (AUC) and calibration measures for moderate to severe AKI, per Kidney Disease: Improving Global Outcomes (KDIGO), and AKI requiring dialysis prediction models within 72 hours and 14 days following surgery. Results: In a derivation cohort of 58 526 patients (median [IQR] age, 66 [56-74] years; 39 173 [67%] men; 51 503 [91%] White participants), the rates of moderate to severe AKI and AKIrequiring dialysis were 2674 (4.6%) and 868 (1.48%) within 72 hours and 3156 (5.4%) and 1018 (1.74%) within 14 days after surgery. The median (IQR) interval to first metabolic panel from conclusion of the surgical procedure was 10 (7-12) hours. In the derivation cohort, the metabolic panel-based models had excellent predictive discrimination for moderate to severe AKI within 72 hours (AUC, 0.876 [95% CI, 0.869-0.883]) and 14 days (AUC, 0.854 [95% CI, 0.850-0.861]) after the surgical procedure and for AKI requiring dialysis within 72 hours (AUC, 0.916 [95% CI, 0.907-0.926]) and 14 days (AUC, 0.900 [95% CI, 0.889-0.909]) after the surgical procedure. In the validation cohort of 4734 patients (median [IQR] age, 67 (60-74) years; 3361 [71%] men; 3977 [87%] White participants), the models for moderate to severe AKI after the surgical procedure showed AUCs of 0.860 (95% CI, 0.838-0.882) within 72 hours and 0.842 (95% CI, 0.820-0.865) within 14 days and the models for AKI requiring dialysis and 14 days had an AUC of 0.879 (95% CI, 0.840-0.918) within 72 hours and 0.873 (95% CI, 0.836-0.910) within 14 days after the surgical procedure. Calibration assessed by Spiegelhalter z test showed P >.05 indicating adequate calibration for both validation and derivation models. Conclusions and Relevance: Among patients undergoing cardiac surgery, a prediction model based on perioperative basic metabolic panel laboratory values demonstrated good predictive accuracy for moderate to severe acute kidney injury within 72 hours and 14 days after the surgical procedure. Further research is needed to determine whether use of the risk prediction tool improves clinical outcomes.

Incremental Value of Global Longitudinal Strain to Michigan Risk Score and Pulmonary Artery Pulsatility Index in Predicting Right Ventricular Failure Following Left Ventricular Assist Devices.

BACKGROUND: The incremental utility of right ventricular (RV) strain on predicting right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation, beyond clinical and haemodynamic indices, is not clear. METHODS: Two hundred and forty-six (246) patients undergoing LVAD implantation, who had transthoracic echocardiograms pre and post LVAD, pulmonary artery pulsatility index (PAPI) measurements and Michigan risk score, were included. We analysed RV global longitudinal strain (GLS) using speckle tracking echocardiography. RVF following LVAD implantation was defined as the need for medical support for >14 days, or unplanned RV assist device insertion after LVAD implantation. RESULTS: Mean preoperative RV-GLS was -7.8±2.8%. Among all, 27% developed postoperative RVF. A classification and regression tree analysis identified preoperative Michigan risk score, PAPI and RV-GLS as important parameters in predicting postoperative RVF. Eighty per cent (80%) of patients with PAPI <2.1 developed postoperative RVF, while only 4% of patients with PAPI >6.8 developed RVF. For patients with a PAPI of 2.1-3.2, having baseline Michigan risk score >2 points conferred an 81% probability of subsequent RVF. For patients with a PAPI of 3.3-6.8, having baseline RV-GLS of -4.9% or better conferred an 86% probability of no subsequent RVF. The sensitivity and specificity of this algorithm for predicting postoperative RVF were 67% and 93%, respectively, with an area under the curve of 0.87. CONCLUSION: RV-GLS has an incremental role in predicting the development of RVF post-LVAD implantation, even after controlling for clinical and haemodynamic parameters.

Dynamic Assessment of Pulmonary Artery Pulsatility Index Provides Incremental Risk Assessment for Early Right Ventricular Failure After Left Ventricular Assist Device.

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Association between In-hospital Mortality and Low Cardiac Output Syndrome with Morning versus Afternoon Cardiac Surgery.

BACKGROUND: Recent work suggests that having aortic valve surgery in the morning increases risk for cardiac-related complications. This study therefore explored whether mortality and cardiac complications, specifically low cardiac output syndrome, differ for morning and afternoon cardiac surgeries. METHODS: The study included adults who had aortic and/or mitral valve repair/replacement and/or coronary artery bypass grafting from 2011 to 2018. The components of the in-hospital composite outcome were in-hospital mortality and low cardiac output syndrome, defined by requirement for at least two inotropic agents at 24 to 48 h postoperatively or need for mechanical circulatory support. Patients who had aortic cross-clamping between 8 and 11 am (morning surgery) versus between 2 and 5 pm (afternoon surgery) were compared on the incidence of the composite outcome. RESULTS: Among 9,734 qualifying operations, 0.4% (29 of 6,859) died after morning, and 0.7% (20 of 2,875) died after afternoon surgery. The composite of in-hospital mortality and low cardiac output syndrome occurred in 2.8% (195 of 6,859) of morning patients and 3.4% (97 of 2,875) of afternoon patients: morning versus afternoon confounder-adjusted odds ratio, 0.96 (95% CI, 0.75 to 1.24; P = 0.770). There was no evidence of interaction between morning versus afternoon and surgery type (P = 0.965), and operation time was statistically nonsignificant for surgery subgroups. CONCLUSIONS: Patients having aortic valve surgery, mitral valve surgery, and/or coronary artery bypass grafting with aortic cross-clamping in the morning and afternoon did not have significantly different outcomes. No evidence was found to suggest that morning or afternoon surgical timing alters postoperative risk.

Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. METHODS: This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. RESULTS: Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). CONCLUSIONS: Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.

Improved outcomes in CABG patients with atrial fibrillation associated with surgical left atrial appendage exclusion.

BACKGROUND: We sought to determine the impact of left atrial appendage clip exclusion (LAACE) on coronary artery bypass grafting (CABG) outcomes among patients with pre-existing atrial fibrillation (AF). METHODS: From October 1, 2015 to October 1, 2017, 4210 Medicare beneficiaries with pre-existing AF underwent isolated CABG (i.e., without ablation) with (n = 931) or without (n = 3279) LAACE. Inverse probability of treatment weighting was used to evaluate the effect of concomitant LAACE on short- and long-term outcomes after CABG. Long term risks of thromboembolism and mortality were assessed using competing-risk regression and Cox proportional hazard models. RESULTS: Operative mortality, length of stay, and 30-day readmission did not differ between groups. Thromboembolism risk was 26% lower for the CABG + LAACE group compared with isolated CABG over a 2-year time-to-event analysis (sub hazard ratio [sHR] 0.74, 95% confidence interval [CI] 0.54-1.00, p = .049). There were no differences in ischemic stroke rates. All-cause mortality risk was 45% lower for CABG + LAACE during the late follow-up period (91-730 days; HR 0.55, 95% CI 0.32-0.95, p = .031). The late period annual absolute all-cause mortality rate was 3.7% for CABG + LAACE and 6.9% for isolated CABG. There were lower readmission rates (31% vs. 43%, p < .001) and total inpatient days (4.0 days vs. 7.2 days, p < .01.) for the CABG + LAACE during follow-up. Total hospital in and out-patient treatment costs were similar between groups through one year. CONCLUSIONS: Concomitant LAA exclusion via an epicardial closure device is associated with reduced CABG mortality, thromboembolic events, and readmissions in patients with pre-existing atrial fibrillation.

Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery.

BACKGROUND: Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. METHODS: In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 µg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 µg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. RESULTS: A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. CONCLUSIONS: Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621 .).

Coronary Artery Bypass Graft Patency and Survival in Patients on Dialysis.

BACKGROUND: Little is known about graft patency after coronary artery bypass grafting (CABG) performed in patients on dialysis. Our aim was to assess patency of internal thoracic artery (ITA) grafts and saphenous vein grafts (SVGs) in these patients. METHODS: From 1/1997 to 1/2018, 500 patients on dialysis underwent primary CABG with or without concomitant procedures at Cleveland Clinic, 40 of whom had 48 postoperative angiograms for recurrent ischemic symptoms. Complete follow-up was obtained on all but 1 patient lost to follow-up 1 y after CABG. Thirty-six ITA grafts and 65 SVGs were evaluable for stenosis and occlusion. RESULTS: Two of 40 patients (5%) had emergency CABG; 3 (7.5%) with calcified aortas had a change in operative strategy to avoid ascending aortic manipulation, 2 (5%) had poor conduit quality, and 12 (30%) had severe diffuse atherosclerotic disease with calcification of the coronary targets causing technical difficulties. Thirty-three patients (82%) were bypassed with an in situ ITA and 3 (7.5%) had a free ITA graft. Three of 36 ITA grafts were occluded at 0.78, 1.8, and 9.4 y (too few to model). SVG patency was 52% and 37% at 1 and 2 y, respectively. CONCLUSIONS: Among patients on dialysis who underwent CABG, coronary angiography for ischemic symptoms in a select subset revealed that SVG patency was lower than expected from published reports in the general CABG population and may contribute to the poor prognosis of this cohort. Further work is needed to guide graft selection and improve graft patency in dialysis patients.

Neither Preoperative Pulse Pressure nor Systolic Blood Pressure Is Associated With Cardiac Complications After Coronary Artery Bypass Grafting.

BACKGROUND: Increased pulse pressure has been associated with adverse cardiovascular events, cardiac and all-cause mortality in surgical and nonsurgical patients. Whether increased pulse pressure worsens myocardial injury and dysfunction after cardiac surgery, however, has not been fully characterized. We examined whether cardiac surgical patients with elevated pulse pressure are more susceptible to myocardial injury, dysfunction, cardiac-related complications, and mortality. Secondarily, we examined whether pulse pressure was a stronger predictor of the outcomes than systolic blood pressure. METHODS: This retrospective observational study included adult cardiac surgical patients having elective isolated on-pump coronary artery bypass grafting (CABG) between 2010 and 2017 at the Cleveland Clinic. The association between elevated pulse pressure and (1) perioperative myocardial injury, measured by postoperative troponin-T concentrations, (2) perioperative myocardial dysfunction, assessed by the requirement for perioperative inotropic support using the modified inotropic score (MIS), and (3) cardiovascular complications assessed by the composite outcome of postoperative mechanical circulatory assistance or in-hospital mortality were assessed using multivariable linear regression models. Secondarily, the association between pulse pressure versus systolic blood pressure and the outcomes were compared. RESULTS: Of 2704 patients who met the inclusion/exclusion criteria, complete data were available for 2003 patients. Increased pulse pressure over 40 mm Hg was associated with elevated postoperative troponin-T level, estimated to be 1.05 (97.5% confidence interval [CI], 1.02-1.09; P < .001) times higher per 10 mm Hg increase in pulse pressure. The association between pulse pressure and myocardial dysfunction and the composite outcome of cardiovascular complications and death were not significant. There was no difference in the association with pulse pressure versus systolic blood pressure and troponin-T concentrations. CONCLUSIONS: Elevated preoperative pulse pressure was associated with a modest increase in postoperative troponin-T concentrations, but not postoperative cardiovascular complications or in-hospital mortality in patients having CABG. Pulse pressure was not a better predictor than systolic blood pressure.

Predicting Right Ventricular Failure After LVAD Implantation: Role of Tricuspid Valve Annulus Displacement.

OBJECTIVES: Right ventricular failure after left ventricular assist device implantation increases postoperative morbidity and mortality. Whether intraoperative echocardiographic and hemodynamic measurements predict right ventricular failure is unclear. Speckle-tracking-derived tricuspid annulus displacement may provide a useful, effective, and straightforward predictor of severe right ventricular failure in patients having left ventricular device implantation. The aim of this study was to determine if intraoperative tricuspid annulus displacement is a stronger discriminator compared with the global longitudinal strain and modified tricuspid annular plane systolic excursion, the Michigan risk score, and pulmonary artery pulsatility index. DESIGN: Retrospective analysis. SETTING: A tertiary-care referral center. PARTICIPANTS: Patients scheduled for left ventricular assist device implantation from January 2010 to December 2017. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: The authors examined 86 patients undergoing left ventricular assist device implantation with adequate intraoperative echocardiographic images. The analyses did not demonstrate an association between tricuspid annulus displacement and severe right ventricular failure (univariate C-statistics <0.60 for all 4 echocardiographic measures). The discrimination ability was not significantly better than strain (DeLong test p = 0.44) and modified tricuspid annular plane systolic excursion (p = 0.89). The discrimination ability of tricuspid annulus displacement measurements was not better than the Michigan risk score (p = 0.65) and pulmonary artery pulsatility index (p = 0.73). CONCLUSIONS: Intraoperative echocardiographic parameters, including tricuspid annulus displacement, modified tricuspid annular plane systolic excursion, and strain, are poor discriminators of severe right ventricular failure after left ventricular assist device implantation. The preoperative Michigan risk-scoring system and intraoperative pulmonary artery pulsatility index are equally unreliable.

Successful management of COVID-19 and associated coagulopathy in a patient with durable left ventricular assist device.

Patients with durable left ventricular assist devices pose special problems for management in the setting of COVID-19 infection. We describe the successful management of a 44-year-old man with severe COVID-19 infection and HeartMate 3 left ventricular assist device. His course was complicated by cytokine storm and COVID-19-associated coagulopathy. We describe our institutional protocol for managing COVID-19 infection in patients on mechanical circulatory support, focusing on the need for a thoughtful, multidisciplinary approach.

Primary isolated CABG restrictive blood transfusion protocol reduces transfusions and length of stay.

BACKGROUND: Cardiac surgery accounts for 10-15% of blood transfusions in the US, despite benefits and calls of limiting its use. We sought to evaluate the impact of a restrictive transfusion protocol on blood use and clinical outcomes in patients undergoing isolated primary coronary artery bypass grafting (CABG). METHODS: Blood conservation measures, instituted in 2012, include preoperative optimization, intraoperative anesthesia, and pump fluid restriction with retrograde autologous priming and vacuum-assisted drainage, use of aminocaproic acid and cell saver, intra- and postoperative permissive anemia, and administration of iron and low-dose vasopressors if needed. Medical records of patients who underwent isolated primary CABG from 2009 to 2012 (group A; n = 375) and 2013 to 2016 (group B; n = 322) were compared. RESULTS: CABG with grafting to three or four coronary arteries was performed in 262 (70%) and 222 (69%) patients and bilateral internal thoracic artery grafting in 202 (54%) and 196 (61%) patients in groups A and B, respectively. Mean preoperative and intraoperative hematocrit was 40.3% and 40.7%, 28.9% and 29.4% in groups A and B, respectively. Total blood transfusion was 24% and 6.5%, intraoperative transfusion 11% and 1.2%, and postoperative transfusion 20% and 5.6% (P < .0001 for all) in groups A and B, respectively. Median postoperative length of stay was 5.0 days in group A and 4.5 days in group B (P = .02), with no significant differences in mortality or morbidity. CONCLUSIONS: A restrictive transfusion protocol reduced blood transfusions and postoperative length of stay without adversely affecting outcomes following isolated primary CABG.

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.