Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Preemptive Pharmacogenetic-Guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery: The Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery Pilot Trial.

OBJECTIVES: To test the hypothesis that implementation of a cytochrome P-450 2D6 (CYP2D6) genotype-guided perioperative metoprolol administration will reduce the risk of postoperative atrial fibrillation (AF), the authors conducted the Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery pilot study. DESIGN: Clinical pilot trial. SETTING: Single academic center. PARTICIPANTS: Seventy-three cardiac surgery patients. MEASUREMENTS AND MAIN RESULTS: Patients were classified as normal, intermediate, poor, or ultrarapid metabolizers after testing for their CYP2D6 genotype. A clinical decision support tool in the electronic health record advised providers on CYP2D6 genotype-guided metoprolol dosing. Using historical data, the Bayesian method was used to compare the incidence of postoperative AF in patients with altered metabolizer status to the reference incidence. A logistic regression analysis was performed to study the association between the metabolizer status and postoperative AF while controlling for the Multicenter Study of Perioperative Ischemia AF Risk Index. Of the 73 patients, 30% (n = 22) developed postoperative AF; 89% (n = 65) were normal metabolizers; 11% (n = 8) were poor/intermediate metabolizers; and there were no ultrarapid metabolizer patients identified. The estimated rate of postoperative AF in patients with altered metabolizer status was 30% (95% CI 8%-60%), compared with the historical reference incidence (27%). In the risk-adjusted analysis, there was insufficient evidence to conclude that modifying metoprolol dosing based on poor/intermediate metabolizer status was associated significantly with the odds of postoperative AF (odds ratio 0.82, 95% CI 0.15-4.55, p = 0.82). CONCLUSIONS: A CYP2D6 genotype-guided metoprolol management was not associated with a reduction of postoperative AF after cardiac surgery.

Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) impacts TGF-ß1 responses: insights into cardiac fibrosis and function following myocardial infarction.

Extracellular purine nucleotides and nucleosides released from activated or injured cells influence multiple aspects of cardiac physiology and pathophysiology. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1; CD39) hydrolyzes released nucleotides and thereby regulates the magnitude and duration of purinergic signaling. However, the impact of CD39 activity on post-myocardial infarction (MI) remodeling is incompletely understood. We measured the levels and activity of ectonucleotidases in human left ventricular samples from control and ischemic cardiomyopathy (ICM) hearts and examined the impact of ablation of Cd39 expression on post-myocardial infarction remodeling in mice. We found that human CD39 levels and activity are significantly decreased in ICM hearts (n = 5) compared with control hearts (n = 5). In mice null for Cd39, cardiac function and remodeling are significantly compromised in Cd39-/- mice following myocardial infarction. Fibrotic markers including plasminogen activator inhibitor-1 (PAI-1) expression, fibrin deposition, α-smooth muscle actin (αSMA), and collagen expression are increased in Cd39-/- hearts. Importantly, we found that transforming growth factor ß1 (TGF-ß1) stimulates ATP release and induces Cd39 expression and activity on cardiac fibroblasts, constituting an autocrine regulatory pathway not previously appreciated. Absence of CD39 activity on cardiac fibroblasts exacerbates TGF-ß1 profibrotic responses. Treatment with exogenous ectonucleotidase rescues this profibrotic response in Cd39-/- fibroblasts. Together, these data demonstrate that CD39 has important interactions with TGF-ß1-stimulated autocrine purinergic signaling in cardiac fibroblasts and dictates outcomes of cardiac remodeling following myocardial infarction. Our results reveal that ENTPD1 (CD39) regulates TGF-ß1-mediated fibroblast activation and limits adverse cardiac remodeling following myocardial infarction.NEW & NOTEWORTHY We show that CD39 is a critical modulator of TGF-ß1-mediated fibroblast activation and cardiac remodeling following myocardial infarction via modulation of nucleotide signaling. TGF-ß1-induced CD39 expression generates a negative feedback loop that attenuates cardiac fibroblast activation. In the absence of CD39 activity, collagen deposition is increased, elastin expression is decreased, and diastolic dysfunction is worsened. Treatment with ecto-apyrase attenuates the TGF-ß1-induced profibrotic cardiac fibroblast phenotype, revealing a novel approach to combat post-myocardial infarction cardiac fibrosis.

Anticytomegalovirus CD4+ T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

[Figure: see text].

Intraoperative venous congestion and acute kidney injury in cardiac surgery: an observational cohort study.

BACKGROUND: Increased intravascular volume has been associated with protection from acute kidney injury (AKI), but in patients with congestive heart failure, venous congestion is associated with increased AKI. We tested the hypothesis that intraoperative venous congestion is associated with AKI after cardiac surgery. METHODS: In patients enrolled in the Statin AKI Cardiac Surgery trial, venous congestion was quantified as the area under the curve (AUC) of central venous pressure (CVP) >12, 16, or 20 mm Hg during surgery (mm Hg min). AKI was defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria and urine concentrations of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 ([TIMP-2]⋅[IGFBP7]), a marker of renal stress. We measured associations between venous congestion, AKI and [TIMP-2]⋅[IGFBP7], adjusted for potential confounders. Values are reported as median (25th-75th percentile). RESULTS: Based on KDIGO criteria, 104 of 425 (24.5%) patients developed AKI. The venous congestion AUCs were 273 mm Hg min (81-567) for CVP >12 mm Hg, 66 mm Hg min (12-221) for CVP >16 mm Hg, and 11 mm Hg min (1-54) for CVP >20 mm Hg. A 60 mm Hg min increase above the median venous congestion AUC above each threshold was independently associated with increased AKI (odds ratio=1.06; 95% confidence interval [CI], 1.02-1.10; P=0.008; odds ratio=1.12; 95% CI, 1.02-1.23; P=0.013; and odds ratio=1.30; 95% CI, 1.06-1.59; P=0.012 for CVP>12, >16, and >20 mm Hg, respectively). Venous congestion before cardiopulmonary bypass was also associated with increased [TIMP-2]⋅[IGFBP7] measured during cardiopulmonary bypass and after surgery, but neither venous congestion after cardiopulmonary bypass nor venous congestion throughout surgery was associated with postoperative [TIMP-2]⋅[IGFBP7]. CONCLUSION: Intraoperative venous congestion was independently associated with increased AKI after cardiac surgery.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Prioritizing heart transplantation during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation-wide reduction in operative volume. The impact of COVID-19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID-19 on a single, large-volume heart transplant program. METHODS: A retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30-day survival. RESULTS: From March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30-day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029). CONCLUSION: We demonstrate that a single, large-volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID-19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program.

Mean platelet volume and cardiac-surgery-associated acute kidney injury: a retrospective study.

PURPOSE: Increased mean platelet volume (MPV) may indicate platelet activation, platelet aggregation, and a resulting prothrombotic state. Such changes in the postoperative period have been associated with organ injury and adverse outcomes. We hypothesized that changes in MPV after cardiac surgery are associated with both a higher risk of acute kidney injury (AKI) and mortality. METHODS: In this retrospective study, we evaluated consecutive patients undergoing adult cardiac surgery patients between 12 December 2011 and 5 June 2018. The change in MPV was derived by calculating the difference between the baseline MPV before surgery and the average postoperative MPV just prior to the occurrence of AKI. We defined postoperative AKI according to Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury as either a ≥ 50% increase in serum creatinine in the first ten postoperative days, or an increase of ≥ 0.3 mg·dL-1 during any 48-hr window across the ten-day postoperative period. Multivariable logistic regression analysis was used to examine the association between MPV change and postoperative AKI and mortality. RESULTS: Of the 4,204 patients studied, 1,373 (32.7%) developed postoperative AKI, including 83 (2.0%) and 38 (0.9%) who developed stages II and III AKI, respectively. Compared with patients who had an increase in median postoperative MPV of 0.2 femtolitre (fL), those with an increase of 0.8 fL had an 80% increase in the odds of developing AKI (adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI],1.36 to 2.38; P < 0.001) and were almost twice as likely to progress to a higher severity AKI (aOR, 1.66; 95% CI, 1.28 to 2.16; P < 0.001). Change in MPV was not associated with mortality (aOR,1.32; 95% CI, 0.92 to 1.89; P = 0.14). CONCLUSION: Increased MPV change in the postoperative period was associated with both increased risk and severity of AKI, but not mortality.

RéSUMé: OBJECTIF: Un volume plaquettaire moyen (VPM) augmenté peut être indicatif d'une activation plaquettaire, d'une agrégation plaquettaire, et de l'état prothrombotique qui en résulte. De tels changements en période postopératoire ont été associés à des lésions aux organes et à des devenirs défavorables. Nous avons émis l'hypothèse que des changements du VPM après une chirurgie cardiaque seraient associés à un risque plus élevé d'insuffisance rénale aiguë et de mortalité. MéTHODE: Dans cette étude rétrospective, nous avons évalué des patients adultes consécutifs subissant une chirurgie cardiaque entre le 12 décembre 2011 et le 5 juin 2018. Le changement de VPM a été dérivé en calculant la différence entre le VPM de base avant la chirurgie et le VPM postopératoire moyen juste avant la survenue de l'IRA. Nous avons défini une IRA postopératoire sur la base des Directives Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury (Les maladies rénales: Guide d'exercice clinique pour améliorer les devenirs globaux pour l'insuffisance rénale aiguë) en tant qu'une augmentation ≥ 50 % de la créatine sérique au cours des dix premiers jours postopératoires, ou une augmentation de ≥ 0,3 mg·dL−1 pendant toute fenêtre de 48 h au cours des dix premiers jours postopératoires. Une analyse multivariée de régression logistique a été utilisée pour examiner l'association entre le changement de VPM et l'IRA postopératoire et la mortalité. RéSULTATS: Parmi les 4204 patients à l'étude, 1373 (32,7 %) ont souffert d'IRA postopératoire, y compris 83 (2,0 %) et 38 (0,9 %) qui ont développé des IRA de stade II et III, respectivement. Par rapport aux patients ayant manifesté une augmentation du VPM postopératoire médian de 0,2 femtolitre (fL), ceux affichant une augmentation de 0,8 fL ont démontré une augmentation de 80 % de la probabilité d'IRA (rapport de cotes ajusté [RCA], 1,80; intervalle de confiance [IC] 95 %, 1,36 à 2,38; P < 0,001) et couraient un risque pratiquement deux fois plus élevé de voir leur IRA progresser à un stade plus grave (RCA, 1,66; IC 95 %, 1,28 à 2,16; P < 0,001). Les changements de VPM n'étaient pas associés à la mortalité (RCA, 1,32; IC 95 %, 0,92 à 1,89; P = 0,14). CONCLUSION: Une augmentation accrue du VPM en période postopératoire a été associée à un risque et une gravité accrus d'IRA, mais pas à la mortalité.

CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study.

OBJECTIVES: The Preemptive Pharmacogenetic-guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) pilot trial aims to use existing institutional resources to develop a process for integrating CYP2D6 pharmacogenetic test results into the patient electronic health record, to develop an evidence-based clinical decision support tool to facilitate CYP2D6 genotype-guided metoprolol administration in the cardiac surgery setting, and to determine the impact of implementing this CYP2D6 genotype-guided integrated approach on the incidence of postoperative atrial fibrillation (AF), provider, and cost outcomes. DESIGN: One-arm Bayesian adaptive design clinical trial. SETTING: Single center, university hospital. PARTICIPANTS: The authors will screen (including CYP2D6 genotype) up to 600 (264 ± 144 expected under the adaptive design) cardiac surgery patients, and enroll up to 200 (88 ± 48 expected) poor, intermediate, and ultrarapid CYP2D6 metabolizers over a period of 2 years at a tertiary academic center. INTERVENTIONS: All consented and enrolled patients will receive the intervention of CYP2D6 genotype-guided metoprolol management based on CYP2D6 phenotype classified as a poor, intermediate, extensive (normal), or ultrarapid metabolizer. MEASUREMENTS AND MAIN RESULTS: The primary outcome will be the incidence of postoperative AF. Secondary outcomes relating to rates of CYP2D6 genotype-guided prescription changes, costs, lengths of stay, and implementation metrics also will be investigated. CONCLUSIONS: The PREEMPTIVE pilot study is the first perioperative pilot trial to provide essential information for the design of a future, large-scale trial comparing CYP2D6 genotype-guided metoprolol management with a nontailored strategy in terms of managing AF. In addition, secondary outcomes regarding implementation, clinical benefit, safety, and cost-effectiveness in patients undergoing cardiac surgery will be examined.

Right ventricular myocardial biomarkers in human heart failure.

BACKGROUND: Right ventricular (RV) dysfunction contributes to mortality in chronic heart failure (HF). However, the molecular mechanisms of RV failure remain poorly understood, and RV myocardial biomarkers have yet to be developed. METHODS AND RESULTS: We performed RNA sequencing (RNA-seq) on 22 explanted human HF RVs and 5 unused donor human heart RVs (DON RV) and compared results to those recently reported from 16 explanted human LVs We used Bowtie-Tophat for transcript alignment and transcriptome assembly, DESeq for identification of differentially expressed genes (DEGs) and Ingenuity for exploration of gene ontologies. In the HF RV, RNA-seq identified 130,790 total RNA transcripts including 13,272 protein coding genes, 10,831 long non-coding RNA genes and 8,605 pseudogenes. There were 800-1000 DEGs between DON and HF RV comparison groups with differences concentrated in cytoskeletal, basement membrane, extracellular matrix (ECM), inflammatory mediator, hemostasis, membrane transport and transcription factor genes, lncRNAs and pseudogenes. In an unbiased approach, the top 10 DEGs SERPINA3, SERPINA5, LCN6, LCN10, STEAP4, AKR1C1, STAC2, SPARCL1, VSIG4 and F8 exhibited no overlap in read counts between DON and HF RVs, high sensitivities, specificities, predictive values and areas under the receiver operating characteristic curves. STEAP4, SPARCL1 and VSIG4 were differentially expressed between RVs and LVs, supporting their roles as RV-specific myocardial biomarkers. CONCLUSIONS: Unbiased, comprehensive profiling of the RV transcriptome by RNA-seq suggests structural changes and abnormalities in inflammatory processes and yields specific, novel HF RV vs HF LV myocardial biomarkers not previously identified by more limited transcriptome profiling approaches.

Evidence for right ventricular lipotoxicity in heritable pulmonary arterial hypertension.

RATIONALE: Shorter survival in heritable pulmonary arterial hypertension (HPAH), often due to BMPR2 mutation, has been described in association with impaired right ventricle (RV) compensation. HPAH animal models are insulin resistant, and cells with BMPR2 mutation have impaired fatty acid oxidation, but whether these findings affect the RV in HPAH is unknown. OBJECTIVES: To test the hypothesis that BMPR2 mutation impairs RV hypertrophic responses in association with lipid deposition. METHODS: RV hypertrophy was assessed in two models of mutant Bmpr2 expression, smooth muscle-specific (Sm22(R899X)) and universal expression (Rosa26(R899X)). Littermate control mice underwent the same stress using pulmonary artery banding (Low-PAB). Lipid content was assessed in rodent and human HPAH RVs and in Rosa26(R899X) mice after metformin administration. RV microarrays were performed using human HPAH and control subjects. RESULTS: RV/(left ventricle + septum) did not rise directly in proportion to RV systolic pressure in Rosa26(R899X) but did in Sm22(R899X) (P < 0.05). Rosa26(R899X) RVs demonstrated intracardiomyocyte triglyceride deposition not present in Low-PAB (P < 0.05). RV lipid deposition was identified in human HPAH RVs but not in controls. Microarray analysis demonstrated defects in fatty acid oxidation in human HPAH RVs. Metformin in Rosa26(R899X) mice resulted in reduced RV lipid deposition. CONCLUSIONS: These data demonstrate that Bmpr2 mutation affects RV stress responses in a transgenic rodent model. Impaired RV hypertrophy and triglyceride and ceramide deposition are present as a function of RV mutant Bmpr2 in mice; fatty acid oxidation impairment in human HPAH RVs may underlie this finding. Further study of how BMPR2 mediates RV lipotoxicity is warranted.

Acute cardiogenic shock secondary to blunt traumatic aortic valve injury.

Background: Blunt cardiac injuries rarely result in aortic valve cusp rupture, leading to acute aortic insufficiency and cardiogenic shock. This rare clinical entity carries a high mortality rate if left undiagnosed and not managed surgically, with few patients surviving beyond 24 h. It presents a diagnostic challenge in the polytrauma patient in shock, with multiple possible and complementary etiologies. Case presentation: We present a 56-year-old male with persistent hypotension, a wide pulse pressure, and elevated serum troponin levels suggesting blunt cardiac injury after a motor vehicle accident. Transthoracic and transesophageal echocardiography revealed normal biventricular function but severe aortic insufficiency due to prolapse of the left coronary cusp.He was taken emergently to surgery, where aortic valve exploration revealed complete left coronary cusp avulsion from the aortic annulus with a mid-cusp tear, requiring aortic valve replacement with a bioprosthetic valve. Postoperative echocardiography showed normal biventricular function with a well-seated bioprosthetic aortic valve with no insufficiency. Conclusions: Traumatic aortic valve injury can lead to torn or prolapsed cusps causing acute aortic insufficiency leading to cardiogenic shock, but early recognition with appropriate and targeted diagnostic imaging is vital to prevent rapid patient deterioration and demise.

Increasing Utilization of Extended Criteria Donor Hearts for Transplantation: The OCS Heart EXPAND Trial.

BACKGROUND: Extended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. OBJECTIVES: This study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. METHODS: In this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft-related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. RESULTS: A total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft-related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. CONCLUSIONS: Use of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754).

Developmental changes in cardiac expression of KCNQ1 and SCN5A spliceoforms: Implications for sudden unexpected infant death.

BACKGROUND: Sudden unexpected infant death (SUID) occurs unpredictably and remains unexplained after scene investigation and autopsy. Approximately 1 in 7 cases of SUID can be related to a cardiac cause, and developmental regulation of cardiac ion channel genes may contribute to SUID. OBJECTIVE: The goal of this study was to investigate the developmental changes in the spliceoforms of SCN5A and KCNQ1, 2 genes implicated in SUID. METHODS: Using reverse transcription quantitative real-time polymerase chain reaction, we quantified expression of SCN5A (adult and fetal) and KCNQ1 (KCNQ1a and b) spliceoforms in 153 human cardiac tissue samples from decedents that succumbed to SUID ("unexplained") and other known causes of death ("explained noncardiac"). RESULTS: There is a stepwise increase in the adult/fetal SCN5A spliceoform ratio from <2 months (4.55 ± 0.36; n = 51) through infancy and into adulthood (17.41 ± 3.33; n = 5). For KCNQ1, there is a decrease in the ratio of KCNQ1b to KCNQ1a between the <2-month (0.37 ± 0.02; n = 46) and the 2- to 4-month (0.28 ± 0.02; n = 52) age groups. When broken down by sex, race, or cause of death, there were no differences in SCN5A or KCNQ1 spliceoform expression, except for a higher ratio of KCNQ1b to KCNQ1a at 5-12 months of age for SUID females (0.40 ± 0.04; n = 9) than for males (0.25 ± 0.03; n = 6) and at <2 months of age for SUID white (0.42 ± 0.03; n = 19) than for black (0.33 ± 0.05; n = 9) infants. CONCLUSION: This study documents the developmental changes in SCN5A and KCNQ1 spliceoforms in humans. Our data suggest that spliceoform expression ratios change significantly throughout the first year of life.

Minimally invasive mitral valve surgery expands the surgical options for high-risks patients.

BACKGROUND: A simplified minimally invasive mitral valve surgery (MIMVS) approach avoiding cross-clamping and cardioplegic myocardial arrest using a small (5 cm) right antero-lateral incision was developed. We hypothesized that, in high-risk patients and in patients with prior sternotomy, this approach would yield superior results compared to those predicted by the Society of Thoracic Surgeons (STS) algorithm for standard median sternotomy mitral valve surgery. METHODS: Five hundred and four consecutive patients (249 males/255 females), median age 65 years (range 20-92 years) underwent MIMVS between 1/06 and 8/09. Median preoperative New York Heart Association function class was 3 (range 1-4). Eighty-two (16%) patients had an ejection fraction ≤35%. Forty-seven (9%) had a STS predicted mortality ≥10%. Under cold fibrillatory arrest (median temperature 28°C) without aortic cross-clamp, mitral valve repair (224/504, 44%) or replacement (280/504, 56%) was performed. RESULTS: Thirty-day mortality for the entire cohort was 2.2% (11/504). In patients with a STS predicted mortality ≥ 10% (range 10%-67%), the observed 30-day mortality was 4% (2/47), lower than the mean STS predicted mortality of 20%. Morbidity in this high-risk group was equally low: 1 of 47 (2%) patients underwent reexploration for bleeding, 1 of 47 (2%) patients suffered a permanent neurologic deficit, none had wound infection. The median length of stay was 8 days (range 1-68 days). CONCLUSIONS: This study demonstrates that MIMVS without aortic cross-clamp is reproducible with low mortality and morbidity rates. This approach expands the surgical options for high-risk patients and yields to superior results than the conventional median sternotomy approach.

Preparing for Bundled Payments: Impact of Complications Post-Coronary Artery Bypass Grafting on Costs.

BACKGROUND: Bundled payments for coronary artery bypass grafting (CABG) provide a single reimbursement for care provided from admission through 90 days post-discharge. We aim to explore the impact of complications on total institutional costs, as well as the drivers of high costs for index hospitalization. METHODS: We linked clinical and internal cost data for patients undergoing CABG from 2014 to 2017 at a single institution. We compared unadjusted average variable direct costs, reporting excess cost from an uncomplicated baseline. We stratified by The Society of Thoracic Surgeons preoperative risk and quality outcome measures as well as value-based outcomes (readmission, post-acute care utilization). We performed multivariable linear regression to evaluate drivers of high costs, adjusting for preoperative and intraoperative characteristics and postoperative complications. RESULTS: We reviewed 1789 patients undergoing CABG with an average of 2.7 vessels (SD 0.89). A significant proportion of patients were diabetic (51.2%) and obese (mean body mass index 30.6, SD 6.1). Factors associated with increased adjusted costs were preoperative renal failure (P = .001), diabetes (P = .001) and body mass index (P = .05), and postoperative stroke (P < .001), prolonged ventilation (P < .001), rebleeding requiring reoperation (P < .001) and renal failure (P < .001) with varying magnitude. Preoperative ejection fraction and insurance status were not associated with increased adjusted costs. CONCLUSIONS: Preoperative characteristics had less of an impact on costs post-CABG than postoperative complications. Postoperative complications vary in their impact on internal costs, with reoperation, stroke, and renal failure having the greatest impact. In preparation for bundled payments, hospitals should focus on understanding and preventing drivers of high cost.

Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation and the growing interest in donation after circulatory death (DCD), our institution recently began procuring cardiac allografts from DCD donors. METHODS: Between October 2020 and March 2021, 15 patients with heart failure underwent cardiac transplantation using DCD allografts. Allografts were procured using a modified extracorporeal membrane oxygenation circuit for thoracic normothermic regional perfusion (TA-NRP) and were subsequently transported using cold static storage. Data collection and analysis were performed with institutional review board approval. RESULTS: The mean age of the DCD donors was 23 ± 7 years and average time on TA-NRP was 56 ± 8 minutes. Total ischemic time was 183 ± 31 minutes and distance from transplant center was 373 ± 203 nautical miles. Recipient age was 55 ± 14 years, with 8 (55.3%) recipients on durable left ventricular assist device support. Post-transplant, 6 (40%) recipients experienced mild left ventricle primary graft dysfunction (PGD-LV), 3 (20%) recipients experienced moderate PGD-LV, and no recipients experienced severe PGD-LV. Postoperative transthoracic echocardiogram demonstrated left ventricular ejection fraction >55% in all recipients. One recipient (6.6%) developed International Society for Heart and Lung Transplantation 2R acute cellular rejection on first biopsy. At last follow-up, all 15 recipients were alive past 30-days. CONCLUSIONS: Cardiac DCD provides an opportunity to increase the availability of donor hearts for transplantation. Utilizing TA-NRP with cold static storage, we have extended the cold ischemic time of DCD allografts to almost 3 hours, allowing for inter-hospital organ transport.