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.

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.

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.

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.

Characteristics and outcomes of patients with COVID-19 supported by extracorporeal membrane oxygenation: A retrospective multicenter study.

OBJECTIVE: To determine characteristics, outcomes, and clinical factors associated with death in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support. METHODS: A multicenter, retrospective cohort study was conducted. The cohort consisted of adult patients (18 years of age and older) requiring ECMO in the period from March 1, 2020, to September 30, 2020. The primary outcome was in-hospital mortality after ECMO initiation assessed with a time to event analysis at 90 days. Multivariable Cox proportional regression was used to determine factors associated with in-hospital mortality. RESULTS: Overall, 292 patients from 17 centers comprised the study cohort. Patients were 49 (interquartile range, 39-57) years old and 81 (28%) were female. At the end of the follow-up period, 19 (6%) patients were still receiving ECMO, 25 (9%) were discontinued from ECMO but remained hospitalized, 135 (46%) were discharged or transferred alive, and 113 (39%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%). Factors associated with in-hospital mortality were age (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.06-1.61 per 10 years), renal dysfunction measured according to serum creatinine level (aHR, 1.21; 95% CI, 1.01-1.45), and cardiopulmonary resuscitation before ECMO placement (aHR, 1.87; 95% CI, 1.01-3.46). CONCLUSIONS: In patients with severe COVID-19 necessitating ECMO support, in-hospital mortality occurred in fewer than half of the cases. ECMO might serve as a viable modality for terminally ill patients with refractory COVID-19.

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.

Long-term outcomes of patients with primary graft dysfunction after cardiac transplantation.

OBJECTIVES: The International Society of Heart and Lung Transplantation (ISHLT) criteria for primary graft dysfunction (PGD) after cardiac transplantation have been shown to stratify patient outcomes up to 1 year after transplantation, but scarce data are available regarding outcomes beyond the 1st year. We sought to characterize survival of patients with PGD following cardiac transplantation beyond the 1st year. METHODS: A retrospective review of consecutive patients undergoing isolated cardiac transplantation at a single centre between 2012 and 2015 was performed. Patients were diagnosed with none, mild, moderate or severe PGD by the ISHLT criteria. Survival was ascertained from the United Network for Organ Sharing database and chart review. Kaplan-Meier curves were plotted to compare survival. The hazard ratio for mortality associated with PGD severity was estimated using Cox-proportional hazards modelling, with a pre-specified conditional survival analysis at 90 days. RESULTS: A total of 257 consecutive patients underwent cardiac transplantation during the study period, of whom 73 (28%) met ISHLT criteria for PGD: 43 (17%) mild, 12 (5%) moderate and 18 (7%) severe. Patients with moderate or severe PGD had decreased survival up to 5 years after transplantation (log-rank P < 0.001). Landmark analyses demonstrated that patients with moderate or severe PGD were at increased risk of mortality during the first 90-days after transplantation as compared to those with none or mild PGD [hazard ratio (95% confidence interval) 18.9 (7.1-50.5); P < 0.001], but this hazard did not persist beyond 90-days in survivors (P = 0.64). CONCLUSIONS: A diagnosis of moderate or severe PGD is associated with increased mortality up to 5 years after cardiac transplantation. However, patients with moderate or severe PGD who survive to post-transplantation day 90 are no longer at increased risk for mortality as compared to those with none or mild PGD.

Unexpected Twists: A 61-Year-Old Male with Repeated HeartMate II Complications andSubsequent Replacement with HeartMate III.

An outflow graft twist of a left ventricular assist device (LVAD) remains a challenging clinical diagnosis and may even be misdiagnosed for other outflow obstructions. We present a case of a patient with two LVAD exchanges due to suspected outflow graft twisting in both clinical scenarios. As new LVADs continue to be designed and upgraded, clinicians must have a high index of suspicion for this rare complication.

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.

Modern Treatment Trends and Outcomes of Pulmonary Embolism With and Without Hemodynamic Significance.

BACKGROUND: Pulmonary embolism is common, but the benefit of surgical embolectomy remains unclear. National trends in embolectomy have been described to 2008. Recent data are lacking. We characterized the national trends in incidence, management, and outcomes of pulmonary embolisms, along with the population-level outcomes. METHODS: The National Inpatient Sample was queried by International Classification of Diseases-9th Revision codes for pulmonary embolisms from 2011 to 2014. Saddle embolisms, shock, and interventions, including systemic thrombolysis, catheter-directed therapy, extracorporeal membrane oxygenation, and pulmonary embolectomy, were identified. Predictors of in-hospital death were identified by logistic regression. RESULTS: We identified 1,283,063 embolism records, including 34,040 (2.6%) with saddle embolism, 31,057 (2.4%) with shock, and 1768 (0.14%) had saddle embolism with shock. Embolectomy and catheter-directed therapies were associated with reduced death in saddle embolism with shock (n = 1768; embolectomy: odds ratio [OR], 0.30; 95% confidence interval [CI], 0.19-0.48; catheter-directed therapies: OR, 0.68; 95% CI, 0.49-0.96). Systemic thrombolytics were not associated with a in-hospital death difference (OR, 1.10; 95% CI, 60.87-1.38). Extracorporeal membrane oxygenation was associated with increased death (OR, 2.07; 95% CI, 1.09-3.92). The number needed to treat for in-hospital death of saddle embolisms with shock was 4.7 (95% CI, 3.9-6.9). CONCLUSIONS: In this contemporary nationally representative sample, surgical embolectomy and catheter-directed therapies were associated reduced in-hospital death for saddle pulmonary embolism with shock, and systemic thrombolytics were not associated with in-hospital death.

Predictors and impact of right heart failure severity following left ventricular assist device implantation.

BACKGROUND: Right heart failure (RHF) is a well-known consequence of left ventricular assist device (LVAD) placement, and has been linked to negative surgical outcomes. However, little is known regarding risk factors associated with RHF. This article delineates pre- and intra-operative risk factors for RHF following LVAD implantation and demonstrates the effect of RHF severity on key surgical outcomes. METHODS: We performed a retrospective analysis of consecutive LVAD patients treated at our center between 2008 and 2016. RHF was categorized using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definition of none/mild, moderate, severe, and acute-severe. We constructed a predictive model using multivariable logistic regression and performed a competing risks analysis for survival stratified by RHF severity. RESULTS: Of 202 subjects, 52 (25.7%) developed moderate or worse RHF. Cardiopulmonary bypass (CPB) time and nadir hematocrit contributed jointly to the model of RHF severity (moderate or worse vs. none/mild; area under the curve =0.77). Postoperative length of stay (LOS) was shortest in the non/mild group and longest in the acute-severe group (median 13 vs. 29.5 days; P<0.001). Stage 2/3 acute kidney injury (range, 26-57%, P=0.002), respiratory failure (13-94%, P<0.001), stroke (0-32%, P=0.02), and 1-year mortality (19-64%, P=0.002) differed by severity. Those with acute-severe RHF had 5.4 [95% confidence interval (CI), 2.5-11.8] times the risk of 1-year mortality compared to those who did not have RHF. CONCLUSIONS: RHF remains a postoperative threat and is associated with worsened surgical outcomes. Ongoing research will reveal further opportunities to mitigate RHF post-LVAD.

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.

Outcomes of Moderate-to-Severe Acute Kidney Injury following Left Ventricular Assist Device Implantation.

BACKGROUND: Although acute kidney injury (AKI) is a common complication following cardiac surgery, less is known about the occurrence and consequences of moderate/severe AKI following left ventricular assist device (LVAD) implantation. METHODS: All patients who had an LVAD implanted at our center from 2008 to 2016 were reviewed to determine the incidence of, and risk factors for, moderate/severe (stage 2/3) AKI and to compare postoperative complications and mortality rates between those with and those without moderate/severe AKI. RESULTS: Of 246 patients, 68 (28%) developed moderate/severe AKI. A multivariable logistic regression comprising body mass index and prior sternotomy had fair predictive ability (area under the curve = 0.71). A 1-unit increase in body mass index increased the risk of moderate/severe AKI by 7% (odds ratio = 1.07; 95% confidence interval: 1.03-1.11); a prior sternotomy increased the risk more than 3-fold (odds ratio = 3.4; 95% confidence interval: 1.84-6.43). The group of patients with moderate/severe AKI had higher rates of respiratory failure and death than the group of patients with mild/no AKI. Patients with moderate/severe AKI were at 3.2 (95% confidence interval: 1.2-8.2) times the risk of 30-day mortality compared to those without. Even after adjusting for age and Interagency Registry for Mechanically Assisted Circulatory Support profile, those with moderate/severe AKI had 1.75 (95% confidence interval: 1.03-3.0) times the risk of 1-year mortality compared to those without. DISCUSSION: Risk-stratifying patients prior to LVAD placement in regard to AKI development may be a step toward improving surgical outcomes.

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.

Changes in pulmonary artery pressure before and after left ventricular assist device implantation in patients utilizing remote haemodynamic monitoring.

AIMS: The time course of changes in pulmonary artery (PA) pressure due to left ventricular assist devices (LVADs) is not well understood. Here, we describe longitudinal haemodynamic trends during the peri-LVAD implantation period in patients previously implanted with a remote monitoring PA pressure sensor. METHODS AND RESULTS: We retrospectively studied PA pressure trends in patients implanted with CardioMEMS™ PA pressure sensor between October 2007 and March 2017 who subsequently had an LVAD procedure. Data are presented as mean ± standard deviation, and P-values are calculated using standard t-test with equal variance. Among 436 patients in cohort, 108 (age 58 ± 11 years, 82% male) received an LVAD and 328 (age 60 ± 13 years, 70% male) did not. The mean PA pressure at sensor implant was higher by 29% (P < 0.001) among patients who later received LVAD. Mean PA pressure 6 months prior to LVAD implant was 35.5 ± 8.5 mmHg, increasing to 39.4 ± 9.9 mmHg (P = 0.04) at 4 weeks before LVAD, and then decreasing 27% to 28.8 ± 8.4 mmHg (P < 0.001) at 3 months post-implant and stabilizing at 31.0 ± 9.4 mmHg at 1 year. CONCLUSIONS: Patients who later receive LVADs have higher PA pressures at sensor implant and show a further increase leading up to LVAD implantation. There is a significant reduction of PA pressures post-LVAD implantation that persists long term. PA pressure monitoring may aid in the clinical decision making of timing for LVAD implantation and in management of LVAD patients.