Thoraco-abdominal normothermic regional perfusion for thoracic transplantation in the United States: current state and future directions.

PURPOSE OF REVIEW: To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery. RECENT FINDINGS: taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels. SUMMARY: taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.

Urinary Cell-Cycle Arrest Biomarkers as Early Predictors of Acute Kidney Injury After Ventricular Assist Device Implantation or Cardiac Transplantation.

OBJECTIVES: Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS: This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors' center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. MEASUREMENTS AND MAIN RESULTS: The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. CONCLUSION: Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).

COVID-19 in recent heart transplant recipients: Clinicopathologic features and early outcomes.

BACKGROUND: The impact of COVID-19 on heart transplant (HTx) recipients remains unclear, particularly in the early post-transplant period. METHODS: We share novel insights from our experience in five HTx patients with COVID-19 (three within 2 months post-transplant) from our institution at the epicenter of the pandemic. RESULTS: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID-19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C-reactive protein, procalcitonin, and ferritin. All had bilateral ground-glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged. CONCLUSIONS: COVID-19 appears to negatively impact outcomes early after heart transplantation.

Extracorporeal membrane oxygenation as a salvage therapy for patients with severe primary graft dysfunction after heart transplant.

BACKGROUND: Severe primary graft dysfunction (PGD) is the leading cause of early death after heart transplant. AIM: To examine the outcomes of heart transplant recipients who received venoarterial extracorporeal membrane oxygenation (VA-ECMO) for severe PGD. METHODS: We reviewed electronic health records of adult patients who underwent heart transplant from November 2005 through June 2015. We defined severe PGD according to International Society for Heart and Lung Transplantation consensus statements. RESULTS: Of 1030 heart transplant patients, 31 (3%) had severe PGD and required VA-ECMO. The mean (range) age was 59 (43-69) years. Fifteen patients (48%) underwent prior sternotomy and 10 (32%) received a left ventricular assist device as a bridge to transplant. Severe PGD manifested as failure to wean from cardiopulmonary bypass in 20 patients (65%) and as severe hemodynamic instability in the immediate postoperative period in 10 (32%), including cardiac arrest in 3 (10%). Twenty-five patients (81%) were successfully weaned from VA-ECMO, and 19 (61%) were discharged; the other 12 (39%) died. CONCLUSIONS: Although VA-ECMO is a common method for providing mechanical circulatory support to patients with PGD, multicenter studies are needed to assess factors associated with successful outcomes and improved survival of these patients.

Durable left ventricular assist device implantation in extremely obese heart failure patients.

Left ventricular assist devices (LVADs) have improved clinical outcomes and quality of life for those with end-stage heart failure. However, the costs and risks associated with these devices necessitate appropriate patient selection. LVAD candidates are becoming increasingly more obese and there are conflicting reports regarding obesity's effect on outcomes. Hence, we sought to evaluate the impact of extreme obesity on clinical outcomes after LVAD placement. Consecutive LVAD implantation patients at our center from June 2008 to May 2016 were studied retrospectively. We compared patients with a body mass index (BMI) ≥40 kg/m2 (extremely obese) to those with BMI < 40 kg/m2 with respect to patient characteristics and surgical outcomes, including survival. 252 patients were included in this analysis, 30 (11.9%) of whom met the definition of extreme obesity. We found that patients with extreme obesity were significantly younger (47[33, 57] vs. 60[52, 67] years, P < 0.001) with fewer prior sternotomies (16.7% vs. 36.0%, P = 0.04). They had higher rates of pump thrombosis (30% vs. 9.0%, P = 0.003) and stage 2/3 acute kidney injury (46.7% vs. 27.0%, P = 0.003), but there were no differences in 30-day or 1-year survival, even after adjusting for age and clinical factors. Extreme obesity does not appear to place LVAD implantation patients at a higher risk for mortality compared to those who are not extremely obese; however, extreme obesity was associated with an increased risk of pump thrombosis, suggesting that these patients may require additional care to reduce the need for urgent device exchange.

Utilization of high donor sequence number grafts in cardiac transplantation.

Donor sequence number (DSN) represents the number of candidates to whom a graft was offered and declined prior to acceptance for transplantation. We sought to investigate the outcomes of patients receiving high DSN grafts. Consecutive isolated adult cardiac transplantations performed at a single-center were reviewed. Recipients were grouped into standard (≤75th percentile) DSN and high (>75th percentile) DSN. A previously validated donor risk index was used to quantify the risk associated with donor grafts, and recipient outcomes were assessed. Overall, 254 patients were included: 194 standard DSN (range 1-79) and 60 high DSN (range 82-1723). High DSN grafts were harvested at greater distance (P < .001) with increased ischemia time (P < .001), resulting in a modest increase in donor risk index (1 point median difference, P = .014). High DSN recipients were less frequently listed as UNOS status 1A (P < .001). Despite a nonsignificant trend toward increased in-hospital/30-day mortality in high DSN recipients, there were no differences in primary graft dysfunction or 1-year survival (high DSN 89% vs standard DSN 88%, P = .82). After adjustment for risk factors, high DSN was not associated with increased 1-year mortality (hazard ratio 1.18, 95%-CI 0.54-2.58, P = .68).

Rational Heart Transplant From a Hepatitis C Donor: New Antiviral Weapons Conquer the Trojan Horse.

BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely used for orthotopic heart transplantation (HT) owing to post-transplantation risks. New highly effective HCV antivirals may alter the landscape. METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. On daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir (400 mg)-velpatasvir (100 mg) (Epclusa; Gilead) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy). RESULTS: We report the kinetics of acute hepatitis C viremia and therapeutic response to treatment with a new pangenotypic antiviral agent after donor-derived acute HCV infection transmitted incidentally with successful cardiac transplantation to an HCV-negative recipient. Prompt resolution of viremia was noted by the 1st week of a 12 week course of antiviral therapy. Sustained virologic remission continued beyond 12 weeks after completion of HCV therapy (SVR-12). CONCLUSIONS: The availability of effective pangenotypic therapy for HCV may expand donor availability. The feasibility of early versus late treatment of HCV remains to be determined through formalized protocols. We hypothesize pharmacoeconomics to be the greatest limitation to widespread availability of this promising tool.

HeartMate II Left Ventricular Assist Device Pump Exchange: A Single-Institution Experience.

Background Left ventricular assist devices (LVADs) have revolutionized the treatment of patients with end-stage heart failure. These devices are replaced when pump complications arise if heart transplant is not possible. We present our experience with HeartMate II (HMII (Thoratec, Plesanton, California, United States)) LVAD pump exchange. Materials and Methods We retrospectively reviewed all cases that required pump exchange due to LVAD complication from November 2011 until June 2016 at a single high-volume institution. The indications, demographics, and outcome were extracted and analyzed. Results Of 250 total patients with implanted HMII LVADs, 16 (6%) required pump exchange during the study period. The initial indications for LVAD placement in these patients were bridge to transplantation (n = 6 [37.5%]) or destination therapy (n = 10 [62.5%]). Fifteen patients (93.8%) required pump exchange due to pump thrombosis and 1 (6.2%) due to refractory driveline infection. Nine patients (56.2%) underwent repeat median sternotomy while a left subcostal approach was used in the remaining seven patients. Fifteen patients (93.7%) survived until hospital discharge. During the follow-up period (median, 155 days), 11 patients remained alive and 4 of these underwent successful cardiac transplantation. Conclusion HMII LVAD pump exchange can be safely performed for driveline infection or pump thrombosis when heart transplantation is not an option.

How to Do It: The Commando Operation for Reconstruction of the Fibrous Skeleton with Double Valve Replacement.

Infiltrative processes that extend into the intervalvular fibrosa, such as infection or calcification, often mandate a complex reconstructive procedure known as the Commando operation. First described less than 20 years ago, this operation is not widely implemented, with experience limited to a few select centers. This report provides a detailed summary of our approach to this intricate procedure.

Bioimpedance Spectroscopy in Heart Transplantation: Posttransplant Changes in Body Composition and Effects in Outcomes.

BACKGROUND: Bioimpedance spectroscopy yields measurements of fat-free mass, fat mass, phase angle, and other measures. Bioimpedance spectroscopy has been validated as a preoperative assessment tool in cardiac surgical studies, in which low phase angle predicted morbidity and mortality. No studies have evaluated bioimpedance spectroscopy following heart transplantation. METHODS: We evaluated body composition, nutrition status (Subjective Global Assessment, body mass index, midarm muscle circumference, and triceps skinfolds), and functional status (handgrip strength and 6-min walk test) in 60 adults. Body composition measurements via a 256-frequency bioimpedance spectroscopy device included fat and fat-free mass as well as phase angle calculated at 50 kHz. Testing was completed at baseline and 1, 3, 6, and 12 mo following heart transplantation. Mortality and hospital readmissions were analyzed. RESULTS: Phase angle and fat mass increased while fat-free mass decreased; grip strength and 6-min walk test improved after transplantation (all P < 0.001). Improvement in phase angle in the first month postoperatively was associated with reduced risk of readmission. Low perioperative and 1-mo phase angles were associated with prolonged posttransplant length of stay (median: 13 versus 10 d, P = 0.03), increased infection-related readmissions (40% versus 5%, P = 0.001), and increased 4-y mortality (30% versus 5%, P = 0.01). CONCLUSIONS: Phase angle, grip strength, and 6-min walk test distance improved after heart transplantation. Low phase angle appears to be associated with suboptimal outcomes and may be a feasible and affordable method to predict outcomes. Further research should ascertain whether preoperative phase angle can predict outcomes.

Subjective Assessment Underestimates Fraility in Patients With Heart Failure Referred for Advanced Therapies.

Assessment of frailty is key for evaluation for advanced therapies (ATs). Most programs use a subjective provider assessment (SPA) or "eye-ball" test; however, objective measures exist. The modified five-item Fried Frailty Index (mFFI) is a validated tool to assess frailty. We compared SPA to mFFI testing in patients referred for AT. We also compared levels of macrophage migration inhibitory factor (MIF), an inflammatory biomarker associated with worse outcomes in heart failure, between frail and not frail subjects. Seventy-eight patients referred for evaluation for AT underwent both SPA and mFFI testing. Three cardiac surgeons independently assessed patients for frailty (SPA). SPA significantly underestimated frailty compared with mFFI testing and correlation between SPA and mFFI was not strong (κ = 0.02-0.14). Providers were correct 84% of the time designating a subject as frail, but only 40% of the time designating as not frail. Agreement between all three providers was robust (76%), which was primarily driven by designation as not frail. There was no significant difference in plasma MIF levels between frail and not frail subjects (47.6 ± 25.2 vs . 45.2 ± 18.9 ng/ml; p = 0.6). Clinicians significantly underestimate frailty but are usually correct when designating a patient as frail.

Donor heart selection: Evidence-based guidelines for providers.

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.

S-nitrosylation in cardiovascular signaling.

Well over 2 decades have passed since the endothelium-derived relaxation factor was reported to be the gaseous molecule nitric oxide (NO). Although soluble guanylyl cyclase (which generates cyclic guanosine monophosphate, cGMP) was the first identified receptor for NO, it has become increasingly clear that NO exerts a ubiquitous influence in a cGMP-independent manner. In particular, many, if not most, effects of NO are mediated by S-nitrosylation, the covalent modification of a protein cysteine thiol by an NO group to generate an S-nitrosothiol (SNO). Moreover, within the current framework of NO biology, endothelium-derived relaxation factor activity (ie, G protein-coupled receptor-mediated, or shear-induced endothelium-derived NO bioactivity) is understood to involve a central role for SNOs, acting both as second messengers and signal effectors. Furthermore, essential roles for S-nitrosylation have been implicated in virtually all major functions of NO in the cardiovascular system. Here, we review the basic biochemistry of S-nitrosylation (and denitrosylation), discuss the role of S-nitrosylation in the vascular and cardiac functions of NO, and identify current and potential clinical applications.

Repair of disrupted mitral annuloplasty following blunt chest trauma.

Traumatic mitral valve injury is rare, and few data exist regarding the impact of trauma on a previously repaired mitral valve. The case is presented of a dehisced mitral annuloplasty caused by a motor vehicle accident. The patient underwent successful re-repair of the mitral valve repair.

Endogenous S-nitrosothiols protect against myocardial injury.

Despite substantial evidence that nitric oxide (NO) and/or endogenous S-nitrosothiols (SNOs) exert protective effects in a variety of cardiovascular diseases, the molecular details are largely unknown. Here we show that following left coronary artery ligation, mice with a targeted deletion of the S-nitrosoglutathione reductase gene (GSNOR(-/-)) have reduced myocardial infarct size, preserved ventricular systolic and diastolic function, and maintained tissue oxygenation. These profound physiological effects are associated with increases in myocardial capillary density and S-nitrosylation of the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha) under normoxic conditions. We further show that S-nitrosylated HIF-1alpha binds to the vascular endothelial growth factor (VEGF) gene, thus identifying a role for GSNO in angiogenesis and myocardial protection. These results suggest innovative approaches to modulate angiogenesis and preserve cardiac function.

Management of extensive intracardiac thombosis in a patient with polycythemia vera undergoing coronary artery bypass grafting.

Polycythemia vera (PV) is a chronic myeloproliferative disorder with a predilection for thrombotic complications in affected patients. Intracardiac thrombosis is a rare manifestation of this disease, as documented in only a few published cases. In this report, we describe a PV patient who suddenly developed extensive thrombosis within all four cardiac chambers and severe ventricular dysfunction during a coronary artery bypass procedure. We also detail the intraoperative salvage maneuvers implemented in this case, which included deep hypothermic circulatory arrest with retrocerebral perfusion and four chamber thrombectomy.

Minimally Invasive Off-Pump Technique for Temporary Left Ventricular Support.

Use of short-term mechanical circulatory support (MCS) for cardiogenic shock has rapidly increased. Most common initial MCS strategies entail institution of peripheral extracorporeal membrane oxygenation (ECMO) or temporary ventricular assist devices. For patients with anatomically small peripheral arteries or insufficient circulatory support, sternotomy and central cannulation techniques may be necessary. These invasive approaches are associated with increased risk of bleeding and other significant complications. We describe a minimally invasive, off-pump technique to provide adequate hemodynamic support and left ventricular unloading, allowing early postoperative ambulation, and ability to easily provide additional right ventricular/ECMO support if needed.

Assessment of cardiac recovery in patients supported with venoarterial extracorporeal membrane oxygenation.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used to support patients in cardiogenic shock (CS). Early determination of disposition is paramount, as longer durations of support have been associated with worse outcomes. We describe a stepwise, bedside weaning protocol to assess cardiopulmonary recovery during VA-ECMO. METHODS AND RESULTS: Over 1 year, we considered all patients on VA-ECMO for CS for the Weaning Protocol (WP) at our centre. During the WP, patients had invasive haemodynamic monitoring, echocardiography, and blood gas analysis while flow was reduced in 1 LPM decrements. Ultimately, the circuit was clamped for 30 min, and final measures were taken. Patients were described as having durable recovery (DR) if they were free of pharmacological and mechanical support at 30 days post-decannulation. Over 12 months, 34 patients had VA-ECMO for CS. Fourteen patients were eligible for the WP at 4-12 days. Ten patients tolerated full flow reduction and were successfully decannulated. Twenty-four per cent of the entire cohort demonstrated DR with no adverse events during the WP. Patients with DR had significantly higher ejection fraction, cardiac index, and smaller left ventricular size at lowest flow during the WP. CONCLUSIONS: We describe a safe, stepwise, bedside weaning protocol to assess cardiac recovery during VA-ECMO. Early identification of patients more likely to recover may improve outcomes during ECMO support.