Novel Left Ventricular Unloading Strategies in Patients on Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients requiring VA-ECMO support for any indication, who underwent novel LV unloading strategies with either direct left atrial venoarterial (LAVA) cannulation or pulmonary artery venoarterial (PAVA) venting, in comparison to Impella and intra-aortic balloon pump (IABP). The primary outcome was successful bridge to transplant, LV assist device, or myocardial recovery. Forty-six patients (63% male, mean age 52.8 ± 17.6 years) were included. Fourteen patients (30%) underwent novel unloading with either LAVA or PAVA, 11 patients (24%) underwent IABP placement, and 21 patients (46%) underwent Impella insertion. In the novel LV unloading cohort, 10 patients (71%) survived to hospital discharge. Four patients (29%) were weaned from ECMO and eight patients (57%) underwent cardiac transplantation. Although a trend favoring cannula-based unloading for the primary outcome was noted, the cohort was too small for statistical significance (79% LAVA/PAVA, 57% Impella, 45% IABP; p = 0.21). However, probability of survival was greater in the LAVA/PAVA cohort compared to Impella and IABP ( p < 0.05). Thus, we demonstrate the efficacy of LA and PA cannulation as an alternative LV unloading strategy for patients supported with peripheral VA-ECMO.

Heart-Lung Transplantation From Donation After Circulatory Death Using Mobile Normothermic Regional Perfusion.

Combined heart-lung transplant (HTLx) is the most durable treatment available for end-stage heart and lung failure. Many patients are unable to receive combined organs due to organ availability and allocation policies prioritizing separate heart or lung transplantation. While an average of 45 HTLxs have been performed per year in the United States half the listed patients do not receive organs. Recently, donation after circulatory death (DCD) utilizing normothermic regional perfusion (NRP) has been utilized for heart allografts with excellent results, and here, we present a case utilizing mobile NRP to procure a heart and lung block from a circulatory death donor and successful implantation for a recipient in a separate center.

Inhibition of angiogenesis in the management of refractory gastrointestinal bleeding in patients with LVAD support.

BACKGROUND: Gastrointestinal bleeding (GIB) in patients with continuous flow left ventricular assist devices (CF-LVADs) is often related to GI angiodysplasia (GIAD). We previously reported data on VEGF inhibition with IV bevacizumab in the treatment of LVAD-associated GIAD bleeding, and now present follow-up data on patients treated with IV bevacizumab and/or low-dose oral pazopanib. METHODS: All consecutive adult patients with LVAD-associated GIB from GIAD treated with bevacizumab or pazopanib, from July 20, 2017 to June 22, 2022, were included in the analysis. Data on hospitalizations, GI endoscopic procedures, and blood transfusions were obtained from first admission for GIB up to a median of 35.7 months following treatment initiation (range 1.3-59.8 months). RESULTS: Eleven patients (91% male, mean 69.5 ± 8.9 years) were included. Eight patients (73%) received IV bevacizumab, two patients (18%) received oral pazopanib, and one patient (9%) received bevacizumab followed by pazopanib therapy. We observed a significantly decreased number of annualized hospitalizations for GIB (median difference - 2.87, p = 0.002), blood transfusions (median difference - 20.9, p = 0.01), and endoscopies (median difference - 6.95, p = 0.007) in patients pre- and post-anti-angiogenic therapy (bevacizumab and/or pazopanib). Similarly, a significant improvement in these clinical outcomes was noted in the bevacizumab group with decreased annualized hospitalizations (median difference - 2.75, p = 0.014), blood transfusions (median difference - 24.5, p = 0.047), and number of endoscopies (median differences -6.88, p = 0.006). CONCLUSION: Anti-angiogenic therapy with IV bevacizumab and/or low-dose oral pazopanib appears to provide benefits in patients with LVAD-associated GIB with reduced hospitalizations, blood transfusions, and need for GI endoscopic procedures.

Expanded extracorporeal membrane oxygenation bridge to heart and lung transplant candidate selection does not impact outcomes compared to traditional candidate selection criteria.

Extracorporeal membrane oxygenation is used as a bridge to transplant (ECMO-BTT) in selected patients. The objective of this study was to determine whether 1-year post-transplant and post-ECMO survival are impacted by traditional compared to expanded selection criteria. We performed a retrospective study of patients >17 years who received ECMO as bridge to transplant (BTT) or bridge to transplant decision for lung or combined heart and lung transplantation at the Mayo Clinic Florida and Rochester. Institutional protocol excludes patients >55 years, maintained on steroids, unable to participate in physical therapy, with body mass index >30 or <18.5 kg/m2, non-pulmonary end-organ dysfunction, or unmanageable infections from ECMO-BTT. For this study, adherence to this protocol was considered traditional whereas exceptions to the protocol were considered expanded selection criteria. A total of 45 patients received ECMO as bridge therapy. Out of those 29 patients (64%) received ECMO as bridge to transplant and 16 patients (36%) as bridge to transplant decision. The traditional criteria cohort consisted of 15 (33%) patients and expanded criteria cohort consisted of 30 (67%) patients. In the traditional cohort, 9 (60%) of 15 patients were successfully transplanted compared to 16 (53%) of 30 patients in the expanded criteria cohort. No difference in being delisted or dying on the waitlist (OR: 0.58, CI: 0.13-2.58), surviving to 1-year post-transplant (OR: 0.53, CI: 0.03-9.71) or 1-year post-ECMO (OR: 0.77, CI: 0.0.23-2.56) was observed between the traditional criteria and expanded criteria cohorts. At our institution, we did not see differences in odds of 1-year post-transplant and post-ECMO survival between those who met traditional criteria compared to those who did not. Multicenter, prospective studies are needed to evaluate the impact of ECMO-BTT selection criteria.

Infections in Patients With Left Ventricular Assist Devices: Current State and Future Perspectives.

Mechanical circulatory support is increasingly being used as bridge-to-transplant and destination therapy in patients with advanced heart failure. Technologic improvements have led to increased patient survival and quality of life, but infection remains one of the leading adverse events following ventricular assist device (VAD) implantation. Infections can be classified as VAD-specific, VAD-related, and non-VAD infections. Risk of VAD-specific infections, such as driveline, pump pocket, and pump infections, remains for the duration of implantation. While adverse events are typically most common early (within 90 days of implantation), device-specific infection (primarily driveline) is a notable exception. No diminishment over time is seen, with event rates of 0.16 events per patient-year in both the early and late periods postimplantation. Management of VAD-specific infections requires aggressive treatment and chronic suppressive antimicrobial therapy is indicated when there is concern for seeding of the device. While surgical intervention/hardware removal is often necessary in prosthesis-related infections, this is not so easily accomplished with VADs. This review outlines the current state of infections in patients supported with VAD therapy and discusses future directions, including possibilities with fully implantable devices and novel approaches to treatment.

Heart Transplantation from COVID-19-Positive Donors: A Word of Caution.

BACKGROUND: During the COVID-19 pandemic, efforts to maintain solid-organ transplantation have continued, including the use of SARS-CoV-2-positive heart donors. METHODS: We present our institution's initial experience with SARS-CoV-2-positive heart donors. All donors met our institution's Transplant Center criteria, including a negative bronchoalveolar lavage polymerase chain reaction result. All but 1 patient received postexposure prophylaxis with anti-spike monoclonal antibody therapy, remdesivir, or both. RESULTS: A total of 6 patients received a heart transplant from a SARS-CoV-2-positive donor. One heart transplant was complicated by catastrophic secondary graft dysfunction requiring venoarterial extracorporeal membrane oxygenation and retransplant. The remaining 5 patients did well postoperatively and were discharged from the hospital. None of the patients had evidence of COVID-19 infection after surgery. CONCLUSION: Heart transplants from SARS-CoV-2 polymerase chain reaction-positive donors are feasible and safe with adequate screening and postexposure prophylaxis.

Interventricular-Septal Output While Supported on Left Ventricular Assist Device Therapy.

The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized in vivo. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data were collected pre-operatively and up to 2 years after implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)×heart rate. A total of 110 patients were included. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS') and TAPSE were observed after implant ( p < 0.0001). However, ISO gradually decreased over time ( p < 0.0001). While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI, 1.4-16.5; p = 0.012) even after adjusting for relevant clinical variables ( p ≤ 0.01 for each model). RV function is known to be influenced by mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation.

Pulsatile Pressure Delivery of Continuous-Flow Left Ventricular Assist Devices Is Markedly Reduced Relative to Heart Failure Patients.

Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD-supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002-0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06-0.17) or HOHF population at 0.25 (IQR, 0.13-0.37; p < 0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; pint < 0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy.

Extracorporeal membrane oxygenation in COVID-19 compared to other etiologies of acute respiratory failure: A single-center experience.

BACKGROUND: The COVID-19 pandemic has led to a boom in the use of V-V ECMO for ARDS secondary to COVID. Comparisons of outcomes of ECMO for COVID to ECMO for influenza have emerged. Very few comparisons of ECMO for COVID to ECMO for ARDS of all etiologies are available. OBJECTIVES: To compare clinically important outcome measures in recipients of ECMO for COVID to those observed in recipients of ECMO for ARDS of other etiologies. METHODS: V-V ECMO recipients between March 2020 and March 2022 consisted exclusively of COVID patients and formed the COVID ECMO group. All patients who underwent V-V ECMO for ARDS between January 2014 and March 2020 were eligible for analysis as the non-COVID ECMO comparator group. The primary outcome was survival to hospital discharge. Secondary outcomes included ECMO decannulation, ECMO duration >30 days, and serious complications. RESULTS: Thirty-six patients comprised the COVID ECMO group and were compared to 18 non-COVID ECMO patients. Survival to hospital discharge was not significantly different between the two groups (33% in COVID vs. 50% in non-COVID; p = 0.255) nor was there a significant difference in the rate of non-palliative ECMO decannulation. The proportion of patients connected to ECMO for >30 days was significantly higher in the COVID ECMO group: 69% vs. 17%; p = 0.001. There was no significant difference in serious complications. CONCLUSION: This study could not identify a statistically significant difference in hospital survival and rate of successful ECMO decannulation between COVID ECMO and non-COVID ECMO patients. Prolonged ECMO may be more common in COVID. Complications were not significantly different.

Early national trends of lung allograft use during donation after circulatory death heart procurement in the United States.

Objective: Innovative technology such as normothermic regional perfusion and the Organ Care System has expanded donation after circulatory death heart transplantation. We wanted to investigate the impact of donation after circulatory death heart procurement in concurrent lung donation and implantation at a national level. Methods: We reviewed the United Network for Organ Sharing database for heart donation between December 2019 and March 2022. Donation after circulatory death donors were separated from donation after brain death donors and further categorized based on concomitant organ procurement of lung and heart, or heart only. Results: A total of 8802 heart procurements consisted of 332 donation after circulatory death donors and 8470 donation after brain death donors. Concomitant lung procurement was lower among donation after circulatory death donors (19.3%) than in donation after brain death donors (38.0%, P < .001). The transplant rate of lungs in the setting of concomitant procurement is 13.6% in donation after circulatory death, whereas it is 38% in donation after brain death (P < .001). Of the 121 lungs from 64 donation after circulatory death donors, 22 lungs were retrieved but discarded (32.2%). Normothermic regional perfusion was performed in 37.3% of donation after circulatory death donors, and there was no difference in lung use between normothermic regional perfusion versus direct procurement and perfusion (20.2% and 18.8%). There was also no difference in 1-year survival between normothermic regional perfusion and direct procurement and perfusion. Conclusions: Although national use of donation after circulatory death hearts has increased, donation after circulatory death lungs has remained at a steady state. The implantation of lungs after concurrent procurement with the heart remains low, whereas transplantation of donation after circulatory death hearts is greater than 90%. The use of normothermic regional perfusion lungs has been controversial, and we report comparable 1-year outcomes to standard donation after circulatory death lungs. Further studies are warranted to investigate the underlying mechanisms of normothermic regional perfusion on lung function.

Cardiovascular mechanism of donor brain death and heart recipient survival.

BACKGROUND: Heart donation after donor brain death from cardiac arrest despite successful resuscitation may be associated with worse recipient outcomes due to potential graft ischemia or underlying rhythmic/structural defects. However, selected grafts from such donors often have normal cardiac function and anatomy. We investigated whether a cardiovascular mechanism of donor brain death (CV-DBD) was associated with worse recipient outcomes. METHODS: We queried the United Network for Organ Sharing (UNOS) database for first-time, single-organ, adult (age 18+) heart transplant recipients and their associated donors between January 2005 and March 2021. Recipients were stratified by donor status (CV-DBD vs. non-CV-DBD). We performed multivariable Cox proportional hazards modeling to ascertain whether receiving a CV-DBD graft was independently associated with mortality. RESULTS: Of 35,833 included recipients, 2,702 (7.5%) received CV-DBD grafts. The associated donors were significantly more likely to be female, older, and have a history of diabetes, hypertension, and substance use (all p < .001). On unadjusted Kaplan-Meier analysis, CV-DBD recipients had a significantly reduced median survival than non-CV-DBD recipients (12.0 vs. 13.1 years, log-rank p = .04). However, after adjusting for donor/recipient age, recipient comorbidities, annualized center volume, and transplantation era, CV-DBD organ status was not associated with recipient mortality (hazard ratio: 1.05, 95% confidence interval: 0.96-1.13, p = .28). CONCLUSION: In this analysis of over 35,000 heart transplants, CV-DBD status was not associated with adjusted recipient survival. Donor brain death due to cardiac arrest should not be an absolute contraindication to heart donation, although graft function should be carefully assessed before transplantation.

Lung transplantation long-term survival is worse in patients who have undergone previous cardiac surgery.

OBJECTIVES: Approximately 10% of lung transplant recipients have had previous cardiothoracic surgery. We sought to determine if previous surgery affects outcomes after lung transplant at a national level. METHODS: The United Network for Organ Sharing database was analysed from 2005 to 2019 to include adult patients who underwent lung transplant who had previous cardiac surgery and previous thoracic surgery. T-test and chi-squared analysis were used to compare perioperative outcomes. Long-term survival comparison was performed using the Kaplan-Meier method in an unadjusted and propensity-matched analysis. RESULTS: Out of 24 784 lung transplants, 691 (2.7%) had previous cardiac surgery and 1321 (6.5%) had previous thoracic surgery. Operative mortality was worse in previous cardiac surgery [42 (6.1%)] versus no previous cardiac surgery [740 (3.1%), P < 0.001] and in previous thoracic surgery [65 (4.9%)] versus no previous thoracic surgery [717 (3.1%), P < 0.001]. The previous thoracic surgery group had more primary graft failure and treated rejection during the first-year post-transplant. There was no difference in stroke, dialysis, intubation and extracorporeal membrane oxygenation at 72 h. Long-term survival was significantly worse for lung transplant patients who had undergone previous cardiac surgery (median 3.8 vs 6.3 years, P < 0.001) due to an increase in cardiovascular deaths (P = 0.008) and malignancy (P = 0.043). However, there was no difference in previous thoracic surgery (median 6.6 vs 6.1 years, P = 0.337). CONCLUSIONS: Previous cardiac surgery prior to lung transplant results in worse survival related to cardiovascular death and malignancies. Previous thoracic surgery worsens perioperative outcomes but does not affect long-term survival.

Transplanting thoracic COVID-19 positive donors: An institutional protocol and report of the first 14 cases.

We present our institution's protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances.

Reoperative Total Arch Repair Using a Trifurcated Graft and Selective Antegrade Cerebral Perfusion.

BACKGROUND: This study reviews the outcomes of our reoperative total arch repair technique using a trifurcated graft and selective antegrade cerebral perfusion. METHODS: Fifty patients underwent reoperative total arch repair from January 2005 to September 2020, with either a one-stage repair (n = 9) or two-stage repair (n = 41). The two-stage technique includes minimal dissection of the mediastinal structures, an arch-first technique using a trifurcated graft, and construction of a classical elephant trunk through a partial transverse incision distally in the old graft or in the aorta just distal to the old graft. RESULTS: The median age was 63 years. Chronic dissection was the most frequent indication (88%), and 98% had undergone a previous proximal aortic repair at a median interval of 3 years. The median cardiopulmonary bypass, myocardial ischemic, selective antegrade cerebral perfusion, and lower body circulatory arrest times were 226, 103, 97, and 98 minutes, respectively. The minimum nasopharyngeal and bladder temperature were 16.5°C and 20.0°C, respectively. Operative mortality was 2%, the incidence of stroke was 2%, and the incidence of spinal cord injury was 0%. Stage II repair was performed in 37 patients (open, 33 patients; endovascular, 4 patients), with 2 mortalities and no spinal cord injury. The median duration between stage I and II was 63 days. Survival and aortic event free rates at 3 years were 88.4% ± 4.9%, and 89.8% ± 5%, respectively. CONCLUSIONS: We report a reoperative total arch repair technique that minimizes dissection of the cardiac structures, simplifies the distal anastomosis, and protects vital organs, such as the brain, heart, and spinal cord.

Direct Axillary Artery Cannulation for Type A Dissection and Impact of Dissected Innominate Artery.

BACKGROUND: This study assessed the safety of direct axillary artery (AX) cannulation for acute type A dissection (ATAD) repair, including the impact of innominate artery dissection (IAD). METHODS: Of 281 consecutive patients who underwent ATAD repair from 2007 to 2020, preoperative computed tomography was available in 200 (IAD, n = 101; non-IAD, n = 99). IAD with compromised true lumen was defined as dissection in which the false lumen was greater than 50% of the IA diameter (n = 75 of 101). RESULTS: AX cannulation was attempted in 188 patients (94.0%), with a 1.6% vascular injury rate (3 patients), comprising bypass to the distal AX in 2 patients and local dissection in 1 patient. Deep hypothermic circulatory arrest was used for the distal repair in 89.5% of patients. Right AX cannulation was used in 80.2% of patients with IAD and in 88.9% without IAD (P = .075). Patients with IAD had more cerebral (21.8% vs 5.1%, P = .001) and arm malperfsion (11.9% vs 4.0%, P = .075). Operative death and stroke were comparable between non-IAD (8.1% vs 7.9%, P = 1.00) and IAD (4.0% vs 5.3%, P = .689) groups. The right AX was successfully used in 77.3% of IAD patients with a compromised true lumen, with comparable hospital outcomes to noncompromised IAD patients. Upper extremity malperfusion, multiorgan malperfusion, low ejection fraction, and female sex were predictors for noncannulation of the right AX. CONCLUSIONS: Routine direct AX cannulation strategy is safe in ATAD repair. Right AX cannulation can be used in most patients with IAD, even with a compromised true lumen, with low mortality, stroke, and vascular injury rates.

Failure to Rescue Contributes to Center-Level Differences in Mortality After Lung Transplantation.

BACKGROUND: The clinical response to postoperative complications after lung transplantation (LTx) may contribute to mortality differences among transplantation centers. The ability to avoid mortality after a complication-failure to rescue (FTR)-may be an effective quality metric in LTx. METHODS: The United Network for Organ Sharing database was queried for adult, first-time, lung-only transplantations from May 2005 to December 2015. Transplantation centers were stratified into equal-sized terciles on the basis of observed operative mortality rates. Several postoperative complications were identified, including stroke, acute rejection, acute kidney injury requiring hemodialysis, airway dehiscence, and extracorporeal membrane oxygenation 72 hours after surgery. Rates of FTR were calculated as the number of operative mortalities in patients who had complications divided by the number of patients who had any postoperative complications. RESULTS: Our study population included 16,411 LTx operations performed at 69 transplantation centers. LTx centers were stratified into terciles with average perioperative mortality of 4.0% for low-mortality centers, 6.9% for intermediate-mortality centers, and 12.4% for high-mortality centers. Low-mortality centers had slightly lower complication rates (low, 15.0% vs intermediate, 17.1% vs high, 19.1%; P < .001). Differences in FTR rate were significantly more pronounced (low, 14.9% vs intermediate, 23.9% vs high, 34.2%; P < .001). Multivariable logistic regression and generalized linear models demonstrated an independent association between high FTR rates and high mortality in LTx (P < .001). CONCLUSIONS: Differences in rates of FTR contribute significantly to per-center variability in mortality after LTx. FTR can serve as a quality metric to identify opportunities for improvement in management of perioperative adverse events.