Reduced Morbidity and Mortality Associated With Minimally Invasive Single-vessel Coronary Artery Bypass Compared With Conventional Sternotomy.

OBJECTIVE: We aimed to describe the safety and clinical benefits of minimally invasive, nonsternotomy coronary artery bypass grafting (MICABG) using data from The Society of Thoracic Surgeons (STS) National Database. BACKGROUND: MICABG has gained popularity, owing to expected lower perioperative morbidity and shorter recovery. Despite this, concerns remain regarding anastomotic quality and the validity of proposed perioperative benefits. METHODS: We queried the STS National Database for all patients who underwent single-vessel coronary artery bypass grafting (CABG) from January 2014 to December 2016 to compare outcomes of MICABG with conventional CABG. Patients who underwent concomitant or emergent procedures were excluded. Propensity-weighted cohorts were compared by operative approach with adjustment for variability across institutions. RESULTS: Of 12,406 eligible patients, 2688 (21.7%) underwent MICABG, and 9818 (78.3%) underwent conventional CABG. Propensity weighting produced excellent balance in patient characteristics, including completeness of revascularization, body mass index, and STS predictive risk scores. MICABG was associated with significant reduction of in-hospital mortality [odds ratio (OR)=0.32, absolute reduction (AR)=0.91%, P <0.0001]; 30-day mortality (OR=0.51, AR=0.88%, P =0.001), duration of ventilation (8.62 vs 12.6 hours, P <0.0001), prolonged hospitalization (OR=0.77, AR=1.6, P =0.043), deep wound infection (OR=0.33, AR=0.68, P <0.004), postoperative transfusions (OR=0.52, AR=7.7%, P <0.0001), and STS composite morbidity (OR=0.72, AR=1.19%, P =0.008). Subgroup analysis of only off-pump left internal mammary artery-left anterior descending CABG showed similar findings. Major adverse cardiac events and graft occlusion did not differ between groups. CONCLUSIONS: MICABG is associated with lower mortality and perioperative morbidity compared with conventional sternotomy CABG. MICABG may have a role in treating single-vessel disease.

Distinct hypertrophic cardiomyopathy genotypes result in convergent sarcomeric proteoform profiles revealed by top-down proteomics.

Hypertrophic cardiomyopathy (HCM) is the most common heritable heart disease. Although the genetic cause of HCM has been linked to mutations in genes encoding sarcomeric proteins, the ability to predict clinical outcomes based on specific mutations in HCM patients is limited. Moreover, how mutations in different sarcomeric proteins can result in highly similar clinical phenotypes remains unknown. Posttranslational modifications (PTMs) and alternative splicing regulate the function of sarcomeric proteins; hence, it is critical to study HCM at the level of proteoforms to gain insights into the mechanisms underlying HCM. Herein, we employed high-resolution mass spectrometry-based top-down proteomics to comprehensively characterize sarcomeric proteoforms in septal myectomy tissues from HCM patients exhibiting severe outflow track obstruction (n = 16) compared to nonfailing donor hearts (n = 16). We observed a complex landscape of sarcomeric proteoforms arising from combinatorial PTMs, alternative splicing, and genetic variation in HCM. A coordinated decrease of phosphorylation in important myofilament and Z-disk proteins with a linear correlation suggests PTM cross-talk in the sarcomere and dysregulation of protein kinase A pathways in HCM. Strikingly, we discovered that the sarcomeric proteoform alterations in the myocardium of HCM patients undergoing septal myectomy were remarkably consistent, regardless of the underlying HCM-causing mutations. This study suggests that the manifestation of severe HCM coalesces at the proteoform level despite distinct genotype, which underscores the importance of molecular characterization of HCM phenotype and presents an opportunity to identify broad-spectrum treatments to mitigate the most severe manifestations of this genetically heterogenous disease.

Solid organ donor-recipient race-matching: analysis of the United Network for Organ Sharing database.

Donor ethnicity is a prognosticator in organ transplant. However, the impact of donor/recipient race-matching is unclear. We hypothesized that there would be increased survival in donor-recipient race-matched organ recipients because of genetic and physiologic similarities. The UNOS database from 1999 to 2018 was queried for all solid organ transplantations including heart, lung, liver, kidney, and pancreas transplants. Data were sorted by donor and recipient race into matched and unmatched categories for Caucasian, African American, and Hispanic transplant recipients. After controlling for potential confounders via inverse propensity of treatment weighting, post-transplant patient and graft survival were compared between race-matched and -unmatched donor groups for each organ. Race-matched Caucasian recipients experienced 1-3% improvement in mortality across most time points in lung, liver, and pancreas transplants, while Hispanics did not benefit. Matched African American recipients experienced 4-6% improvement in patient and graft survival in liver transplant but had 7-9% worse survival rates at 5 years in lung and pancreas transplants. Race-matching does not influence patient outcomes enough to factor into organ transplant offers. African American liver transplant recipients benefited the most. Matching was detrimental to African American lung and pancreas transplant recipients indicating there may be other factors influencing the outcomes of these transplants.

Amiodarone Use Prior to Cardiac Transplant Impacts Early Post-Transplant Survival.

PURPOSE: It remains unclear if use of amiodarone pre-cardiac transplantation impacts early post-transplant survival. METHODS: We selected all patients undergoing heart transplant from 2004 to 2006 with available information using the United Network for Organ Sharing database (n = 4057). Multivariable Cox models compared the risk of death within 30 days post-transplant in patients who were taking amiodarone at the time of transplant listing (n = 1227) to those who were not (n = 2830). RESULTS: Mean age was 52 (± 12) years, and 23% were women. Patients who died within 30 days (n = 168) were older; had higher panel reactive antibody levels, higher bilirubin levels, and higher prevalence of prior cardiac surgery; were often at status 1B; and had higher use of amiodarone at listing compared to those who survived (5.3% versus 3.6%; p = 0.02). Cause of death was unknown in 49% and was reported as graft failure in 43% of cases. In multivariable Cox models, patients on amiodarone at the time of listing had 1.56-fold higher risk of post-transplant death within 30 days (95% confidence intervals 1.08-2.27) compared to patients who were not on amiodarone at listing (C-statistic 0.70). CONCLUSION: In conclusion, patients who reported taking amiodarone at the time of listing for transplant had a higher risk of death within 30 days post-transplant.

Temporary mechanical circulatory support prevents the occurrence of a low-output state in high-risk coronary artery bypass grafting: A case series.

BACKGROUND: Coronary artery bypass grafting (CABG) is a durable treatment for coronary artery disease. Left ventricular dysfunction (LVD) (a division of cardiothoracic surgery) (ejection fraction < 35%) significantly elevates perioperative risk for patients pursuing surgical revascularization. Periprocedural support with temporary mechanical circulatory support (tMCS) has shown benefit in this patient population. METHODS: Four patients with ischemic cardiomyopathy and LVD underwent CABG at our institution between 2017 and 2018. Each patient received perioperative ventricular support using a microaxial tMCS device (Impella 5.0®). The occurrence of a postoperative low-output state (LOS) was assessed for as well as postoperative morbidity and mortality, device-specific complications, and tMCS support duration. RESULTS: All patients survived to device explant without device-related complications. Two patients required reoperation for nondevice-related bleeding. All patients were without an LOS at 24 h postoperatively with cardiac indices of 2.9-3.6 L/min/m2 , normalized serum lactate, and vasoactive-inotrope scores of 0-12.0. There was a notably high incidence of acute renal failure (50%), which was observed in patients with preoperative cardiogenic shock. One patient died 10 days after the device explant. Of the three patients that survived to discharge, two were alive at the most recent follow-up. Postoperative device support varied widely (0-500 h). CONCLUSION: Perioperative tMCS may be a viable strategy for preventing postoperative LOS in high-risk CABG patients with a low complication rate and acceptable morbidity. The application of microaxial tMCS devices in CABG is an area that warrants further investigation to delineate its impact on perioperative outcomes and potentially expand the indications for such devices.

The impact of increased pulmonary arterial pressure on outcomes after transcatheter aortic valve replacement.

OBJECTIVE: To evaluate the impact of increased pulmonary artery systolic pressure (PASP) on outcomes after transcatheter aortic valve replacement (TAVR). METHODS: A total of 242 patients who underwent TAVR were retrospectively reviewed. Transthoracic echocardiography estimated PASP. The cohorts were divided into three groups according to the numerical change of PASP; Increased (post-TAVR PASP at 1 month minus pre-TAVR PASP, ≥ + 5 mmHg; n = 52), No change (-5 to +5 mmHg; n = 86) and Decreased (≤ -5 mmHg; n = 104). Patient demographics and clinical outcomes until 1 year were evaluated. Logistic regression model was used for multivariate risk analysis. RESULTS: At 1 year, the Increased group showed higher mortality (21 ± 6%) than the No change group (5 ± 2%) (hazard ratio [HR]: 4.8, 95% confidence interval [CI]: 1.7-13.5; p < .01) and the Decreased group (8 ± 3%) (HR: 2.8, 95% CI: 1.1-6.7; p = .02). Rehospitalization rate for valve-related or heart failure was also higher in the Increased group (21 ± 6%) than the No change group (10 ± 3%) (HR: 2.4, 95% CI: 1.1-6.0; p = .04). Predictors of PASP deterioration were hypertension (odds ratio [OR]: 3.9, 95% CI: 1.1-13.8; p = .04) and left ventricular end-diastolic diameter >50 mm (OR: 2.2, 95% CI: 1.1-4.6; p = .04), and the increased PASP remained an independent predictor of 1-year all-cause mortality (HR; 2.7, 95% CI: 1.0-6.8; p = .04). CONCLUSIONS: Regardless of the baseline PASP, patients with increased PASP at 1 month after successful TAVR were at higher risk of mortality and rehospitalization within 1 year. Strict medical management should be considered for patients who showed dilated left ventricle preoperatively.

Temperature-sensitive sarcomeric protein post-translational modifications revealed by top-down proteomics.

Despite advancements in symptom management for heart failure (HF), this devastating clinical syndrome remains the leading cause of death in the developed world. Studies using animal models have greatly advanced our understanding of the molecular mechanisms underlying HF; however, differences in cardiac physiology and the manifestation of HF between animals, particularly rodents, and humans necessitates the direct interrogation of human heart tissue samples. Nevertheless, an ever-present concern when examining human heart tissue samples is the potential for artefactual changes related to temperature changes during tissue shipment or sample processing. Herein, we examined the effects of temperature on the post-translational modifications (PTMs) of sarcomeric proteins, the proteins responsible for muscle contraction, under conditions mimicking those that might occur during tissue shipment or sample processing. Using a powerful top-down proteomics method, we found that sarcomeric protein PTMs were differentially affected by temperature. Specifically, cardiac troponin I and enigma homolog isoform 2 showed robust increases in phosphorylation when tissue was incubated at either 4 °C or 22 °C. The observed increase is likely due to increased cyclic AMP levels and activation of protein kinase A in the tissue. On the contrary, cardiac troponin T and myosin regulatory light chain phosphorylation decreased when tissue was incubated at 4 °C or 22 °C. Furthermore, significant protein degradation was also observed after incubation at 4 °C or 22 °C. Overall, these results indicate that temperature exerts various effects on sarcomeric protein PTMs and careful tissue handling is critical for studies involving human heart samples. Moreover, these findings highlight the power of top-down proteomics for examining the integrity of cardiac tissue samples.

Distinct sequences and post-translational modifications in cardiac atrial and ventricular myosin light chains revealed by top-down mass spectrometry.

Myosin is the principal component of the thick filaments that, through interactions with the actin thin filaments, mediates force production during muscle contraction. Myosin is a hexamer, consisting of two heavy chains, each associated with an essential (ELC) and a regulatory (RLC) light chain, which bind the lever-arm of the heavy chain and play important modulatory roles in striated muscle contraction. Nevertheless, a comprehensive assessment of the sequences of the ELC and RLC isoforms, as well as their post-translational modifications, in the heart remains lacking. Herein, utilizing top-down high-resolution mass spectrometry (MS), we have comprehensively characterized the sequences and N-terminal modifications of the atrial and ventricular isoforms of the myosin light chains from human and swine hearts, as well as the sites of phosphorylation in the swine proteins. In addition to the correction of disparities in the database sequences of the swine proteins, we show for the first time that, whereas the ventricular isoforms of the ELC and RLC are methylated at their N-termini, which is consistent with previous studies, the atrial isoforms of the ELC and RLC from both human and swine are Nα-methylated and Nα-acetylated, respectively. Furthermore, top-down MS with electron capture dissociation enabled localization of the sites of phosphorylation in swine RLC isoforms from the ventricles and atria to Ser14 and Ser22, respectively. Collectively, these results provide new insights into the sequences and modifications of myosin light chain isoforms in the human and swine hearts, which will pave the way for a better understanding of their functional roles in cardiac physiology and pathophysiology.

Complete Characterization of Cardiac Myosin Heavy Chain (223 kDa) Enabled by Size-Exclusion Chromatography and Middle-Down Mass Spectrometry.

Myosin heavy chain (MHC), the major component of the myosin motor molecule, plays an essential role in force production during muscle contraction. However, a comprehensive analysis of MHC proteoforms arising from sequence variations and post-translational modifications (PTMs) remains challenging due to the difficulties in purifying MHC (∼223 kDa) and achieving complete sequence coverage. Herein, we have established a strategy to effectively purify and comprehensively characterize MHC from heart tissue by combining size-exclusion chromatography (SEC) and middle-down mass spectrometry (MS). First, we have developed a MS-compatible SEC method for purifying MHC from heart tissue with high efficiency. Next, we have optimized the Glu-C, Asp-N, and trypsin limited digestion conditions for middle-down MS. Subsequently, we have applied this strategy with optimized conditions to comprehensively characterize human MHC and identified ß-MHC as the predominant isoform in human left ventricular tissue. Full sequence coverage based on highly accurate mass measurements has been achieved using middle-down MS combining 1 Glu-C, 1 Asp-N, and 1 trypsin digestion. Three different PTMs: acetylation, methylation, and trimethylation were identified in human ß-MHC and the corresponding sites were localized to the N-terminal Gly, Lys34, and Lys129, respectively, by electron capture dissociation (ECD). Taken together, we have demonstrated this strategy is highly efficient for purification and characterization of MHC, which can be further applied to studies of the role of MHC proteoforms in muscle-related diseases. We also envision that this integrated SEC/middle-down MS strategy can be extended for the characterization of other large proteins over 200 kDa.

Top-Down Proteomics of Large Proteins up to 223 kDa Enabled by Serial Size Exclusion Chromatography Strategy.

Mass spectrometry (MS)-based top-down proteomics is a powerful method for the comprehensive analysis of proteoforms that arise from genetic variations and post-translational modifications (PTMs). However, top-down MS analysis of high molecular weight (MW) proteins remains challenging mainly due to the exponential decay of signal-to-noise ratio with increasing MW. Size exclusion chromatography (SEC) is a favored method for size-based separation of biomacromolecules but typically suffers from low resolution. Herein, we developed a serial size exclusion chromatography (sSEC) strategy to enable high-resolution size-based fractionation of intact proteins (10-223 kDa) from complex protein mixtures. The sSEC fractions could be further separated by reverse phase chromatography (RPC) coupled online with high-resolution MS. We have shown that two-dimensional (2D) sSEC-RPC allowed for the identification of 4044 more unique proteoforms and a 15-fold increase in the detection of proteins above 60 kDa, compared to one-dimensional (1D) RPC. Notably, effective sSEC-RPC separation of proteins significantly enhanced the detection of high MW proteins up to 223 kDa and also revealed low abundance proteoforms that are post-translationally modified. This sSEC method is MS-friendly, robust, and reproducible and, thus, can be applied to both high-efficiency protein purification and large-scale proteomics analysis of cell or tissue lysate for enhanced proteome coverage, particularly for low abundance and high MW proteoforms.

Effective top-down LC/MS+ method for assessing actin isoforms as a potential cardiac disease marker.

Actin is the major component of the cytoskeleton, playing an essential role in the structure and motility of both muscle and nonmuscle cells. It is highly conserved and encoded by a multigene family. α-Cardiac actin (αCAA) and α-skeletal actin (αSKA), encoded by two different genes, are the primary actin isoforms expressed in striated muscles. The relative expression levels of αSKA and αCAA have been shown to vary between species and under pathological conditions. In particular, an increased αSKA expression is believed to be a programmed response of a diseased heart. Therefore, it is essential to quantify the relative expression of αSKA and αCAA, which remains challenging due to the high degree of sequence similarity between these isoforms (98.9%). Herein, we developed a top-down liquid chromatography/mass spectrometry-based ("LC/MS+") method for the rapid purification and comprehensive analysis of α-actin extracted from muscle tissues. We thoroughly investigated all of the actin isoforms in healthy human cardiac and skeletal muscles. We found that αSKA is the only isoform expressed in skeletal muscle, whereas αCAA and αSKA are coexpressed in cardiac muscle. We then applied our method to quantify the α-actin isoforms in human healthy hearts and failing hearts with dilated cardiomyopathy (DCM). We found that αSKA is augmented in DCM compared with healthy controls, 43.1 ± 0.9% versus 23.7 ± 1.7%, respectively. As demonstrated, top-down LC/MS+ provides an effective and comprehensive method for the purification, quantification, and characterization of α-actin isoforms, enabling assessment of their clinical potential as cardiac disease markers.

Effects of the HeartMate II left ventricular assist device as observed by serial echocardiography.

BACKGROUND: The HeartMate II is the most frequently used left ventricular assist device (LVAD) in patients with end-stage heart failure. There is a paucity of data regarding its longitudinal cardiac effects, particularly that on diastole. METHODS: This retrospective study was an evaluation of echocardiograms preoperatively and at 3, 6, and 12 months postoperatively in patients with a HeartMate II. Measurements included left ventricle (LV) dimensions, ejection fraction (EF), right ventricle (RV) size and function, parameters of diastolic function, and an analysis of mitral regurgitation (MR), tricuspid regurgitation (TR), aortic insufficiency (AI), and aortic valve thickening. RESULTS: Forty-seven patients were evaluated. LV dimensions decreased but EF, RV size, and RV function were unchanged. Right ventricular systolic pressure (RVSP) and diastolic parameters including mitral inflow E/A, deceleration time (DT), pulmonary vein inflow, left atrial size, and overall diastolic grade improved. LV relaxation measured by tissue Doppler (e') was unchanged and the E/e' ratio was also unchanged. Regarding valve function, MR decreased, TR was unchanged, and the aortic valve became increasingly thickened with increased AI severity. CONCLUSIONS: The HeartMate II unloads the LV as shown by decreased LV size, decreased MR, reduced RVSP, and improved patterns of mitral inflow. However, neither systolic function nor diastolic relaxation improves in this cohort. RV size and function also remain unchanged. The aortic valve shows increased thickening and AI likely from valve leaflet fusion. These results provide detailed functional and hemodynamic information regarding the longitudinal effects of the HeartMate II.

Supporting the right ventricle in postcardiotomy renal dysfunction: A case series.

Postcardiotomy RV dysfunction is an under-recognized cause of acute kidney injury (AKI). Insertion of a percutaneous right ventricular assist device (RVAD) reduces central venous hypertension and congestive nephropathy by augmenting cardiac output. In selected patients, percutaneous RVAD insertion may improve renal function and obviate the need for long-term dialysis.

Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells.

We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

Thoracoabdominal Normothermic Regional Perfusion for Cardiac Procurement.

In donation after circulatory death donors, warm ischemia time is a significant threat to successful cardiac transplantation. The ability to perfuse these organs during the minutes after death, until cardiac evaluation is completed to satisfaction, is crucial in limiting total warm ischemic time. Thoracoabdominal normothermic regional perfusion (TANRP) has emerged as a promising strategy for recovering and monitoring these hearts. We propose a series of clinical practice pearls that we follow for all donation after circulatory death procurements to streamline the process of setting up a TANRP circuit and ensuring all team members present at time procurement are familiar with the procedure. Bicaval cannulation is achieved via the abdomen for aortic cannulation, and via the chest for right atrial cannulation, avoiding deairing maneuvers and providing the shortest possible duration from incision to initiation of cardiopulmonary bypass. Here, we describe a series of practice techniques which we have utilized in our early experience with TANRP.

Top-down quantitative proteomics identified phosphorylation of cardiac troponin I as a candidate biomarker for chronic heart failure.

The rapid increase in the prevalence of chronic heart failure (CHF) worldwide underscores an urgent need to identify biomarkers for the early detection of CHF. Post-translational modifications (PTMs) are associated with many critical signaling events during disease progression and thus offer a plethora of candidate biomarkers. We have employed a top-down quantitative proteomics methodology for comprehensive assessment of PTMs in whole proteins extracted from normal and diseased tissues. We systematically analyzed 36 clinical human heart tissue samples and identified phosphorylation of cardiac troponin I (cTnI) as a candidate biomarker for CHF. The relative percentages of the total phosphorylated cTnI forms over the entire cTnI populations (%P(total)) were 56.4 ± 3.5%, 36.9 ± 1.6%, 6.1 ± 2.4%, and 1.0 ± 0.6% for postmortem hearts with normal cardiac function (n = 7), early stage of mild hypertrophy (n = 5), severe hypertrophy/dilation (n = 4), and end-stage CHF (n = 6), respectively. In fresh transplant samples, the %P(total) of cTnI from nonfailing donor (n = 4), and end-stage failing hearts (n = 10) were 49.5 ± 5.9% and 18.8 ± 2.9%, respectively. Top-down MS with electron capture dissociation unequivocally localized the altered phosphorylation sites to Ser22/23 and determined the order of phosphorylation/dephosphorylation. This study represents the first clinical application of top-down MS-based quantitative proteomics for biomarker discovery from tissues, highlighting the potential of PTMs as disease biomarkers.

Mesenchymal stromal cells are present in the heart and promote growth of adult stem cells in vitro.

BACKGROUND AIMS: For many years the human heart has been considered a terminally differentiated organ with no regenerative potential after injury. Recent studies, however, have cast doubt on this long-standing dogma. The objective of this study was to investigate the presence of and characterize mesenchymal stromal cells (MSC) in the adult mouse heart. The impact of MSC on growth and differentiation of adult cardiac stem cells (CSC) was also analyzed. METHODS: A combination of lineage-negative/c-kit-negative (Lin(-)/c-kit(-)) immunoselection with a plastic-adhesion technique was used to isolate cardiac-derived MSC. The differentiation capacity and expression of surface markers were analyzed. To investigate the impact of MSC on growth and differentiation of adult CSC, Green Fluorescent Protein (GFP(+)) adult CSC were co-cultured with GFP(-) cardiac-derived MSC. RESULTS: MSC were present in the adult mouse heart and they met the criteria established to define mouse MSC. They expressed surface markers and were able to differentiate, in a controlled manner, into multiple lineages. In addition, cardiac-derived MSC promoted the survival and expansion of adult CSC in vitro. CONCLUSIONS: MSC can be isolated from the mouse heart and they promote growth and differentiation of adult CSC. The findings from this study could have a significant beneficial impact on future heart failure treatment. Co-culture and co-implantation of cardiac-derived MSC with adult CSC could provide extensive cardiac regeneration and maintenance of the CSC population after implanted into the heart.

Cardiac computed tomography and quadricuspid aortic valve: a case report.

A quadricuspid aortic valve is rare and often incidentally found by echocardiography, surgically, or on post mortem examination. Aortic regurgitation is common and if severe enough can lead to symptoms of dyspnea. We report a case of a quadricuspid aortic valve, which was found by cardiac multidetector computed tomography during a pre-operative assessment for severe aortic regurgitation.

Heart and kidney transplant: should they be combined or subsequent?

AIMS: End-stage heart failure patients often present with severe kidney failure and have limited treatment options. We compared the clinical characteristics and outcomes among end-stage heart and kidney failure patients who underwent combined heart and kidney transplant (HKTx) with those who underwent kidney transplant after heart transplant (KAH). METHODS AND RESULTS: All patients from 2007-2016 who underwent combined HKTx (n = 715) and those who underwent KAH (n = 130) using the United Network for Organ Sharing database were included. Kaplan-Meier curves and Cox models compared survivals and identified predictors of death. Number of combined HKTx performed annually in United States increased from 59 in 2007 to 146 in 2016 whereas KAH decreased from 34 in 2007 to 6 in 2016. Among KAH patients, average wait time for kidney transplant was 3.0 years, time to dialysis or to kidney transplant after heart transplant did not differ with varying severity of kidney disease at baseline (P for both >0.05). Upon follow-up (mean 3.5 ± 2.7 years), 151 patients died. In multivariable models, patients who underwent combined HKTx had 4.7-fold greater risk of death [95% confidence interval (CI) 2.4-9.4) than KAH patients upon follow up. A secondary analysis using calculation of survival only after kidney transplant for KAH patients still conferred higher risk for combined HKTx patients [hazard ratio (HR) 2.6 95% CI 1.33-5.15]. In subgroup analyses after excluding patients on dialysis (HR 3.99 95% CI 1.98-8.04) and analysis after propensity matching for age, gender, and glomerular filtration rate (HR 3.01 95% CI 1.40-6.43) showed similar and significantly higher risk for combined HKTx patients compared with KAH patients. Lastly, these results also remained unchanged after excluding transplant centres who performed only one type of procedure preferentially, i.e. HKTx or KAH (HR 4.70 95% CI 2.35-9.42). CONCLUSIONS: National registry data show continual increase in combined HKTx performed annually in the United States but inferior survival compared with KAH patients. Differences in patient characteristics or level of kidney dysfunction at baseline do not explain these poor outcomes among HKTx patients compared with KAH patients. Consensus guidelines are greatly needed to identify patients who may benefit more from dual organ transplants.

Association of preoperative duration of inotropy on prevalence of right ventricular failure following LVAD implantation.

AIMS: 20% to 40% of left ventricular assist device (LVAD) device implantations are complicated by right ventricular (RV) failure that results in significant morbidity and mortality. We hypothesized that the duration on milrinone infusion is an independent risk factor for RV failure following LVAD implantation. METHODS AND RESULTS: Retrospective demographic, clinical and hemodynamic data were collected on all adults with ACC/AHA stage D heart failure on intravenous milrinone who underwent LVAD implantation between 2012 and 2019. Patients (n = 104) were divided into two groups, those on milrinone <30 days (STM, n = 55) vs. ≥30 (LTM, n = 49). The primary endpoint was the prevalence of RV failure (need for inotropic support for more than 14 days or RV assist device) within 30 days post-LVAD implantation. There were no significant differences between STM and LTM patients with respect to demographic, echocardiographic, right heart catheterization data, or baseline medications. The mean age of patients was 55.6 ± 12 years (70% male patients). Mean duration on milrinone was 13.7 vs. 81.0 days in STM and LTM, respectively. Forty-five (43.3%) patients developed RV failure. LTM had higher prevalence of RV failure with odds ratio (OR) = 5.04 (95% CI 2.18-11.68, P = 0.0002). After adjusting for age, gender, and co-morbidity count, the OR was 6.33 (95% CI 2.51-15.93), P < 0.0001. CONCLUSIONS: In this retrospective study of ACC/AHA stage D HF patients, longer duration of milrinone infusion was associated with higher prevalence of RV failure after LVAD implantation.