Right ventricle assessment before tricuspid valve interventions.

In the latest ESC/EACTS Guidelines for the Management of Valvular Heart Disease, right ventricular dilatation and dysfunction, severe pulmonary hypertension and tricuspid annulus dilatation were reported to be the most important parameters to consider in patient selection for tricuspid valve interventions. Indeed, comprehensive right ventricular assessment is crucial in patients with severe tricuspid regurgitation who may benefit from transcatheter or surgical procedures. However, the only guideline parameter considered for intervention has been tricuspid annular dilatation in the presence of at least mild to moderate tricuspid regurgitation, with no other right ventricular markers used in the decision-making process for invasive treatment. Notably, challenges in the assessment of right ventricular function may limit establishing thresholds for defining right ventricular dysfunction. The aim of this review is to summarize current evidence on the prognostic significance of right ventricular function in patients with tricuspid regurgitation undergoing percutaneous or surgical interventions.

Benchmarking Outcomes of Surgical Aortic Valve Replacement in Patients With Bicuspid Aortic Valves.

BACKGROUND: The relative roles for transcatheter and surgical aortic valve replacement (SAVR) for bicuspid aortic valve (AV) stenosis are debated. This study analyzes the 5-year longitudinal outcomes of isolated SAVR in bicuspid vs tricuspid AV patients, particularly in low-risk patients. METHODS: All patients undergoing isolated index SAVR at 1146 United States hospitals in The Society of Thoracic Surgeons (STS) Adult Cardiac database between July 1, 2011, and December 31, 2018, with linkage to Medicare claims, were analyzed. RESULTS: A total of 65,687 patients were analyzed, including of 9131 bicuspid patients (13.9%). Compared with tricuspid patients, bicuspid patients were significantly younger (median 70 vs 74 years, P < .001) with lower Society of Thoracic Surgeons predicted risk of mortality scores (mean 1.6% vs 2.3%, P < .001) and lower risk profile. Risk-adjusted 30-day mortality and major morbidity were similar, but risk-adjusted 5-year mortality was significantly lower in the bicuspid patients (adjusted hazard ratio, 0.72; 95% CI, 0.66-0.77), specifically in low-risk patients (adjusted hazard ratio, 0.69; 95% CI, 0.64-0.76). Additionally, the bicuspid cohort had a lower 5-year readmission risk of heart failure, stroke, bleeding, or other cardiovascular causes (all P < .05). CONCLUSIONS: In this nationally representative study, 30-day mortality was similar, but risk-adjusted 5-year mortality was significantly lower in bicuspid patients undergoing isolated SAVR compared with tricuspid patients, specifically low-risk and normal left ventricular ejection fraction patients. This analysis provides a much-needed 5-year longitudinal national-level benchmark to better inform the discussion of transcatheter vs SAVR in bicuspid patients.

Estimating the Potential Economic Impact of Tissue Valve Replacement for Heart Valve Disease in China: Patient-Level and Population-Level Cost-Benefit Simulation Analyses.

OBJECTIVES: This study seeks to estimate the potential societal economic impact of treating patients with heart valve disease (HVD) in China with surgical tissue valve replacement versus mechanical valves. METHODS: This societal economic cost-benefit evaluation is based on an individual simulation model for subgroups of patients with HVD that is also aggregated to a macrosocietal model. The individual simulation model was developed to estimate the likely economic impact of surgical aortic valve replacement (SAVR) with tissue versus mechanical valves for different subgroups among all eligible patients with HVD over their remaining lifetimes. Clinical inputs were informed by health claims database analysis, expert clinical opinion, and published literature. Epidemiological inputs and demographic inputs were sourced from the published literature and the China Statistical Yearbook 2020. Health gains were valued at 3 times the average national income. RESULTS: Projected total lifetime economic gains were greater for patients receiving tissue valves. Costs were reported in 2021 US dollars. The average lifetime net economic gain for tissue valve patients was $51 736 (20.0% more than for mechanical valve patients). Increasing the use of tissue valves to 50% among all eligible patients with HVD would provide aggregate long-term economic gains of $167 billion during their remaining lifetimes. The economic gains from greater tissue valve use were due to avoiding anticoagulation monitoring costs, improved quality of life, and greater post-SAVR labor force participation. CONCLUSION: Increased use of tissue valves versus mechanical values in SAVR procedures in China would be likely to generate a substantial societal economic gain.

Characteristics of Clinical Trial Sites for Novel Transcatheter Mitral and Tricuspid Valvular Therapies.

Importance: Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials. Objective: To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies. Design, Setting, and Participants: This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022. Exposures: Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals. Main Outcome and Measures: The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies. Results: A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code-based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, -2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials. Conclusions and Relevance: In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.

Rationale and clinical applications of 4D flow cardiovascular magnetic resonance in assessment of valvular heart disease: a comprehensive review.

BACKGROUND: Accurate evaluation of valvular pathology is crucial in the timing of surgical intervention. Whilst transthoracic echocardiography is widely available and routinely used in the assessment of valvular heart disease, it is bound by several limitations. Although cardiovascular magnetic resonance (CMR) imaging can overcome many of the challenges encountered by echocardiography, it also has a number of limitations. MAIN TEXT: 4D Flow CMR is a novel technique, which allows time-resolved, 3-dimensional imaging. It enables visualisation and direct quantification of flow and peak velocities of all valves simultaneously in one simple acquisition, without any geometric assumptions. It also has the unique ability to measure advanced haemodynamic parameters such as turbulent kinetic energy, viscous energy loss rate and wall shear stress, which may add further diagnostic and prognostic information. Although 4D Flow CMR acquisition can take 5-10 min, emerging acceleration techniques can significantly reduce scan times, making 4D Flow CMR applicable in contemporary clinical practice. CONCLUSION: 4D Flow CMR is an emerging CMR technique, which has the potential to become the new reference-standard method for the evaluation of valvular lesions. In this review, we describe the clinical applications, advantages and disadvantages of 4D Flow CMR in the assessment of valvular heart disease.

Medical malpractice in aortic valve and mitral valve replacement surgery in North America.

BACKGROUND: Aortic and mitral valve replacement are commonly performed by cardiovascular surgeons, but little data quantitatively analyzes the etiology and prevalence of medical malpractice litigations involving these operations. This study aims to analyze incidence, cause, and resolution of medical malpractice lawsuits involving aortic and mitral valve replacements, alone and in combination with coronary artery bypass and/or aortic procedures. METHODS: The Westlaw legal database was utilized to compile relevant litigations across the United States from 1994-2019. Clinical data, verdict data, demographic data, and litigation attributes were compiled. Fisher's Exact Tests and Mann-Whitney tests were performed for statistical analyses. One hundred four malpractice litigations involving aortic valve replacement and 55 litigations involving mitral valve replacement were included in this analysis. The mean age of patients was 55.2 years and proportion of female patients was 32.7% in aortic valve replacements litigations, compared to a mean age of 54.1 years and female patients in 61.8% of mitral valve replacements litigations. RESULTS: Significant relationships exist between an alleged failure to monitor the patient and defendant verdicts (P=0.01), delayed treatment and defendant verdicts (P=0.04), and incidence of infective endocarditis and plaintiff verdicts (P=0.04) in aortic valve replacement litigations. Similarly, significant relationships exist between an alleged failure to diagnose and settlement verdicts (P=0.047), and stroke incidence and defendant verdicts (P=0.03) in mitral valve replacement litigations. CONCLUSIONS: In addition to excellent surgeon patient/family communication, administering surgical treatment in a timely manner, diagnosing acting on concomitant medical conditions, and close patient monitoring may diminish medical malpractice litigation involving aortic and mitral valve replacement operations.

Tricuspid valve disease prevalence and the impact of tricuspid valve surgery on cardiovascular events and hospital resource use in medicare beneficiaries.

BACKGROUND: Tricuspid valve disease (TVD) is presumed common, however, little is known about its prevalence or the impact of tricuspid valve surgery (TVS) on healthcare resource use. METHODS: To describe the prevalence of TVD and assess the impact of TVS on resource utilization, Medicare Fee-For-Service beneficiaries from 2011 -2019 were assessed for the prevalence of non-rheumatic TVD. Hospital costs and rates of all-cause, cardiovascular (CV), and heart failure (HF) hospitalizations were compared in the 3 months pre TVS to acute (0-3 months) and chronic (3 -12 months) post TVS periods. RESULTS: Among 80.3 million beneficiaries from 2011 - 2019 Q1, over 700,000 (0.9%) had non-rheumatic TVD with 1.4% undergoing TVS. Thirty-day and 1 year mortality after TVS was 5.5% to15.5%. Compared with pre-surgery, CV and HF hospitalizations decreased from 0.12 to 0.08 per patient-month (P <.001), and 0.06 to 0.04 (P <.001) acutely. All-cause hospitalizations increased from 0.18 per patient-month to 0.23 per patient-month acutely post-surgery (P <.001), before decreasing to 0.09 per patient-month chronically (P <.001). Hospital costs increased from $2,174 per patient-month to $4,171 per patient-month acutely (P < .001), before falling to $1,441 per patient-month (P < .001) chronically. Lower costs for HF and CV hospitalization in both acute (P = .028 and P < .001, respectively) and chronic (P < .001 for both) periods were observed. CONCLUSIONS: TVS is associated with reduced CV and HF hospitalizations and associated hospital costs. Future work should determine whether transcatheter tricuspid valve repair offers similar or additional benefits.

Understanding the Aortic Root Using Computed Tomographic Assessment: A Potential Pathway to Improved Customized Surgical Repair.

There is continued interest in surgical repair of both the congenitally malformed aortic valve, and the valve with acquired dysfunction. Aortic valvar repair based on a geometric approach has demonstrated improved durability and outcomes. Such an approach requires a thorough comprehension of the complex 3-dimensional anatomy of both the normal and congenitally malformed aortic root. In this review, we provide an understanding of this anatomy based on the features that can accurately be revealed by contrast-enhanced computed tomographic imaging. We highlight the complimentary role that such imaging, with multiplanar reformatting and 3-dimensional reconstructions, can play in selection of patients, and subsequent presurgical planning for valvar repair. The technique compliments other established techniques for perioperative imaging, with echocardiography maintaining its central role in assessment, and enhances direct surgical evaluation. This additive morphological and functional information holds the potential for improving selection of patients, surgical planning, subsequent surgical repair, and hopefully the subsequent outcomes.

Cost-utility analysis of heart surgeries for young adults with severe rheumatic mitral valve disease in India.

BACKGROUND: Rheumatic mitral valve disease (RMVD) is a major cause of acquired valvular disease in India. We compared the cost-effectiveness of surgical treatment strategies for young adults with severe RMVD from an Indian public payer perspective. METHODS: We developed a Markov model to reflect the burden of RMVD among a hypothetical cohort of 20-year-olds in India and to estimate quality-adjusted life years (QALYs) and lifetime costs associated with three strategies: (1) Repair; (2) Mechanical valve replacement (MVR-M); and (3) Bioprosthetic valve replacement (MVR-B), compared to a baseline strategy involving a mix of surgeries approximating the standard of care in India (32% Repair, 33% MVR-M, 35% MVR-B). Data on disease burden, intervention effects, and direct medical costs (2018 US$) were obtained from the literature. Deterministic and probabilistic sensitivity analyses were conducted to assess model uncertainty. RESULTS: Repair ($2530, 9.7 QALYs) was less costly and more effective than the standard of care ($2990, 8.7 QALYs) and MVR-M ($3220, 6.2 QALYs). The incremental cost-effective ratio for MVR-B ($3190, 10.1 QALYs) compared to Repair was $1590 per QALY, which may be cost-effective at a threshold of India's per-capita gross domestic product (GDP: $2005). The optimal choice between Repair or MVR-B was sensitive to variations in surgery costs, background mortality, and risks for reoperation. CONCLUSIONS: Our model-based analysis suggests that Repair is the optimal strategy and MVR-M should not be recommended for this subpopulation. MVR-B may be cost-effective in contexts where quality of Repair is not assured, newer generation bioprostheses are used, or the costs of the bioprosthetic valve decrease.

Bicuspid aortic valve annulus: assessment of geometry and size changes during the cardiac cycle as measured with a standardized method to define the annular plane.

PURPOSE: Bicuspid aortic valve (BAV) is a complex malformation affecting not merely the aortic valve. However, little is known regarding the dynamic physiology of the aortic annulus in these patients and whether it is similar to tricuspid aortic valves (TAV). Determining the BAV annular plane is more challenging than for TAV. Our aim was to present a standardized methodology to determine BAV annulus and investigate its changes in shape and dimensions during the cardiac cycle. METHODS: BAV patients were prospectively included and underwent an ECG-gated cardiac CTA. The annulus plane was manually identified on reconstructions at 5% intervals of the cardiac cycle with a new standardized method for different BAV types. Based on semi-automatically defined contours, maximum and minimum diameter, area, area-derived diameter, perimeter, asymmetry ratio (AR), and relative area were calculated. Differences of dynamic annular parameters were assessed also per BAV type. RESULTS: Of the 55 patients included (38.4 ± 13.3 years; 58% males), 38 had BAV Sievers type 1, 10 type 0, and 7 type 2. The minimum diameter, perimeter, area, and area-derived diameter were significantly higher in systole than in diastole with a relative change of 13.7%, 4.8%, 13.7%, and 7.2% respectively (all p < 0.001). The AR was ≥ 1.1 in all phases, indicating an elliptic shape, with more pronounced flattening in diastole (p < 0.001). Different BAV types showed comparable dynamic changes. CONCLUSIONS: BAV annulus undergo significant changes in shape during the cardiac cycle with a wider area in systole and a more elliptic conformation in diastole regardless of valve type. KEY POINTS: • A refined method for the identification of the annulus plane on CT scans of patients with bicuspid aortic valves, tailored for the specific anatomy of each valve type, is proposed. • The annulus of patients with bicuspid aortic valves undergoes significant changes during the cardiac cycle with a wider area and more circular shape in systole regardless of valve type. • As compared to previously published data, the bicuspid aortic valve annulus has physiological dynamics similar to that encountered in tricuspid valves but with overall larger dimensions.

Cost Analysis of Minimally Invasive Mitral Valve Surgery in the UK National Health Service.

BACKGROUND: In the UK National Health Service, finite resources make the adoption of minimally invasive (MI) mitral valve surgery challenging unless greater operative costs (vs sternotomy [ST]) are balanced by postoperative savings. This study examined whether the cost analysis now became unfavorable. METHODS: All patients (n = 380) undergoing isolated mitral valve surgery with or without a maze procedure over a 3-year period by either MI or ST approaches were included. Propensity matching (2 cohorts, 1:1 matched;, n = 75 per group) and multivariable regression were used to assess for the effect on cost. Cost data were prospectively collected from Service Line Reporting and reported in Sterling (£) as median (interquartile range [IQR]). RESULTS: Matched data revealed that total hospital costs were equivalent (MI vs ST, £16,672 [IQR, £15,044, £20,611] vs £15,875 [IQR, £12,281, £20,687]; P .33). Three of 15 costing pools were significantly different: operative costs were higher for the MI group (MI vs ST, £7458 [IQR, £6738, £8286] vs £5596 iIQR, £4204, £6992]; P < .001), whereas ward costs (boarding, nursing) (MI vs ST, £1464 [IQR, £1146, £1864] vs £1733 [IQR, £1403, £2445] P = .006) and pharmacy services (MI vs ST, £187 [IQR, £140, £239] vs £244 [IQR, £179, £375] P < .001) were lower for the MI group. Hospital stay was shorter in the MI group (MI vs ST, 6 days [IQR, 5, 8 days] vs 8 days [IQR, 6, 11 days]; P < .001). Multivariable regression produced similar findings. CONCLUSIONS: There was no difference in overall hospital cost between MI and ST mitral valve surgery: higher operative costs of MI surgery were offset by lower postoperative costs, with a 2-day shorter hospital stay.

Paravalvular Leak Assessment: Challenges in Assessing Severity and Interventional Approaches.

PURPOSE OF REVIEW: With increasing use of prosthetic valves to treat degenerative valvular heart disease (VHD) in an aging population, the incidence and adverse consequences of paravalvular leaks (PVL) are better recognized. The present work aims to provide a cohesive review of the available literature in order to better guide the evaluation and management of PVL. RECENT FINDINGS: Despite gains in operator experience and design innovation, significant PVL remains a significant complication that may present with congestive heart failure and/or hemolytic anemia. To date, clear consensus or guidelines on the evaluation and management of PVL remain lacking. Although the evolution of transcatheter valve therapies has had a tremendous impact on the management of patients with VHD, the limitations and complications of such techniques, including PVL, present further challenges. Incidence of PVL, graded as moderate or greater, ranges from 4 to 7.4% in surgical and transcatheter valve replacements, respectively. Improved imaging modalities and the advent of novel surgical and percutaneous therapies have undoubtedly yielded a better understanding of PVL including its anatomical location, mechanism, severity, and treatment options. Echocardiography, used in conjunction with cardiac computed tomography and cardiac magnetic resonance, provides essential details for diagnosis and management of PVL. Transcatheter intervention has become a favored approach in lieu of surgical intervention in select patients after previous surgical or percutaneous valve replacement. PVL treatment with vascular plugs, balloon post-dilation, and the valve-in-valve methods have shown technical success with promising clinical outcomes in appropriately selected patients.

Early vs late cardiac surgery in patients with native valve endocarditis-United States Nationwide Inpatient database.

OBJECTIVE: Although the standard treatment of infective endocarditis (IE) is antimicrobial therapy, surgical intervention is required in some cases. However, the optimal timing of surgery remains unclear. Hence, we conducted a population-based analysis using the National Inpatient Sample (NIS) database to assess the outcomes of early versus late surgery in patients with native valve IE. METHODS: We queried the NIS database for all hospitalized patients between 2006 and 2016 with a primary diagnosis of IE who had cardiac surgery. We stratified surgery as early ≤7 or late >7 days of admission. Multivariable logistic regression models were used to assess in-hospital mortality and postoperative complications. Length of stay (LOS) and total hospital cost (HC) were evaluated using multivariable log-normal regression models. RESULTS: A total of 13 056 patients (57.6% in the early group and 42.4% in the late group) were included. The in-hospital mortality rate in the early group was 5.0% compared to 5.4% in the late intervention group (adjusted odds ratio, 1.20, 95% confidence interval [CI] 0.79-1.81). Overall median LOS was reduced in the early group by 48.2% (95% CI, 46.5%-49.9%, 12.4 days in the early group and 25.9 days in late group), as well as HC which was reduced in the early group by 28.3% (95% CI, 26.0%-30.6%). CONCLUSION: Among patients with native valve IE who needed cardiac surgery, the time of surgical intervention did not affect the in-hospital mortality. However, early surgery was associated with significantly shorter LOS and lower HC.

Assessment of normal hemodynamic profile of mechanical pulmonary prosthesis by doppler echocardiography: a prospective cross-sectional study.

OBJECTIVES: Very few reports have described the Doppler-derived echocardiographic parameters for mechanical pulmonary valve prosthesis (MPVP). This study aims to describe the normal Doppler hemodynamic profile of MPVP using Doppler echocardiography. METHODS: The current prospective, single center observational study enrolled 108 patients who underwent pulmonary valve replacement (PVR) surgery for the first time and had a normally functioning prosthesis post-operation. The hemodynamic performance of MPVPs, considering flow dependent and flow independent parameters, was evaluated at two follow-up points, at week one and week four post-operation. All assessments were conducted by an experienced echocardiographer. RESULTS: The mean age (±SD) of the participants was 26.4 (±8.98). Tetralogy of Fallot (ToF) was the most common underlying disease leading to PVR, with a prevalence of 88%. At first week post-operation, measurement of indices reported the following values (±SD): peak pressure gradient (PPG): 18.51(±7.64) mm Hg; mean pressure gradient (MPG): 10.88(±5.62) mm Hg; peak velocity (PV): 1.97(±0.43)m/s; doppler velocity index (DVI): 0.61(±18); pulmonary velocity acceleration time (PVAT): 87.35(±15.16) ms; effective orifice area (EOA): 2.98(±1.02) cm2;and effective orifice area to body surface area ratio (EOA/ BSA): 1.81(±0.62) cm2/m2. Comparing these measurements with those obtained from the second follow-up (at week four post-op) failed to hold significant difference in all values except for PVAT, which had increased from its primary value (p = 0.038). Also, right ventricular (RV) function showed significant improvement throughout the follow up period. CONCLUSION: The findings of this study help strengthen the previously scarce data pool and better establish the normal values for Doppler hemodynamics in mechanical pulmonary prosthesis.

Prevalence of atrial fibrillation before cardiac surgery and factors associated with concomitant ablation.

OBJECTIVE: Surgical ablation for atrial fibrillation concomitant with cardiac surgery is now a Class I recommendation for selected patients. Understanding how the revised recommendations will affect appropriate use of surgical ablation is challenging because the reported prevalence of preoperative atrial fibrillation depends on the definition used. The objective was to determine the prevalence of atrial fibrillation in the 3 years before cardiac surgery and the rate of concomitant surgical ablation. METHODS: Patients with and without a diagnosis of atrial fibrillation in the 3 years before surgical coronary artery bypass, aortic valve replacement, or mitral valve replacement/repair were identified in the 2014 Medicare Standard Analytical File. RESULTS: Patients had prior atrial fibrillation in 28.4% of 79,134 cardiac surgeries. Prior atrial fibrillation was associated with risk factors for increased cardiac surgical morbidity/mortality, including recent heart failure, renal failure, and lung disease. Black patients were less likely to have prior atrial fibrillation but more likely to have had infrequent care for it. Isolated coronary artery bypass had the lowest prevalence but highest absolute number of prior atrial fibrillation cases. Concomitant surgical ablation was performed in 22.1% of patients with prior atrial fibrillation. Patients with mitral valve surgery were 3-fold more likely to receive surgical ablation. Women were less likely to have prior atrial fibrillation but less likely to have surgical ablation when they did. CONCLUSIONS: Medicare beneficiaries had a substantially higher prevalence of atrial fibrillation diagnoses in the 3 years before cardiac surgery than previously published rates of preoperative atrial fibrillation. Concomitant surgical ablation was performed in less than one-quarter of patients with atrial fibrillation undergoing cardiac surgery for other indications.

Levosimendan in patients with reduced left ventricular function undergoing isolated coronary or valve surgery.

OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS: Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.