Impact of cannabidiol on myocardial recovery in patients with acute myocarditis: Rationale & design of the ARCHER trial.

AIMS: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). METHODS AND RESULTS: We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. CONCLUSIONS: The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.

Factors associated with Acute Limb Ischemia in Cardiogenic Shock and downstream Clinical Outcomes: Insights from the Cardiogenic Shock Working Group.

BACKGROUND: There are limited data depicting the prevalence and ramifications of acute limb ischemia (ALI) among cardiogenic shock (CS) patients. METHODS: We employed data from the Cardiogenic Shock Working Group (CSWG), a consortium including 33 sites. We constructed a multi-variable logistic regression to examine the association between clinical factors and ALI, we generated another logistic regression model to ascertain the association of ALI with mortality. RESULTS: There were 7,070 patients with CS and 399 (5.6%) developed ALI. Patients with ALI were more likely to be female (40.4% versus 29.4%) and have peripheral arterial disease (13.8% versus 8.3%). Stratified by maximum SCAI shock stage, the rates of ALI were stage B 0.0%, stage C 1.8%, stage D 4.1%, and stage E 10.3%. Factors associated with higher risk for ALI included: peripheral vascular disease OR 2.24 (95% CI: 1.53 - 3.23; p < 0.01) and ≥ 2 mechanical circulatory support (MCS) devices OR 1.66 (95% CI: 1.24 - 2.21, p < 0.01). ALI was highest for VA-ECMO patients (11.6%) or VA-ECMO + IABP/Impella CP (16.6%) yet use of distal perfusion catheters was less than 50%. Mortality was 38.0% for CS patients without ALI but 57.4% for CS patients with ALI. ALI was significantly associated with mortality, adjusted OR 1.40 (95% CI 1.01 - 1.95, p < 0.01). CONCLUSIONS: The rate of ALI was 6% among CS patients. Factors most associated with ALI include peripheral vascular disease and multiple MCS devices. The downstream ramifications of ALI were dire with a considerably higher risk of mortality.

Houston Methodist cardiovascular learning health system (CVD-LHS) registry: Methods for development and implementation of an automated electronic medical record-based registry using an informatics framework approach.

Objectives: To investigate the potential value and feasibility of creating a listing system-wide registry of patients with at-risk and established Atherosclerotic Cardiovascular Disease (ASCVD) within a large healthcare system using automated data extraction methods to systematically identify burden, determinants, and the spectrum of at-risk patients to inform population health management. Additionally, the Houston Methodist Cardiovascular Disease Learning Health System (HM CVD-LHS) registry intends to create high-quality data-driven analytical insights to assess, track, and promote cardiovascular research and care. Methods: We conducted a retrospective multi-center, cohort analysis of adult patients who were seen in the outpatient settings of a large healthcare system between June 2016 - December 2022 to create an EMR-based registry. A common framework was developed to automatically extract clinical data from the EMR and then integrate it with the social determinants of health information retrieved from external sources. Microsoft's SQL Server Management Studio was used for creating multiple Extract-Transform-Load scripts and stored procedures for collecting, cleaning, storing, monitoring, reviewing, auto-updating, validating, and reporting the data based on the registry goals. Results: A real-time, programmatically deidentified, auto-updated EMR-based HM CVD-LHS registry was developed with ∼450 variables stored in multiple tables each containing information related to patient's demographics, encounters, diagnoses, vitals, labs, medication use, and comorbidities. Out of 1,171,768 adult individuals in the registry, 113,022 (9.6%) ASCVD patients were identified between June 2016 and December 2022 (mean age was 69.2 ± 12.2 years, with 55% Men and 15% Black individuals). Further, multi-level groupings of patients with laboratory test results and medication use have been analyzed for evaluating the outcomes of interest. Conclusions: HM CVD-LHS registry database was developed successfully providing the listing registry of patients with established ASCVD and those at risk. This approach empowers knowledge inference and provides support for efforts to move away from manual patient chart abstraction by suggesting that a common registry framework with a concurrent design of data collection tools and reporting rapidly extracting useful structured clinical data from EMRs for creating patient or specialty population registries.

Body Mass Index and Mortality in Cardiogenic Shock.

We explored the association of body mass index (BMI) with mortality in cardiogenic shock (CS). Using the Cardiogenic Shock Working Group registry, we assessed the impact of BMI on mortality using restricted cubic splines in a multivariable logistic regression model adjusting for age, gender, and race. We also assessed mortality, device use, and complications in BMI categories, defined as underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obese (30-39.9 kg/m2), and severely obese (>40 kg/m2) using univariable logistic regression models. Our cohort had 3,492 patients with CS (mean age = 62.1 ± 14 years, 69% male), 58.0% HF-related CS (HF-CS), and 27.8% acute myocardial infarction (AMI) related CS. Body mass index was a significant predictor of mortality in multivariable regression using restricted cubic splines (p < 0.0001, p = 0.194 for nonlinearity). When stratified by categories, patients with healthy weight had lower mortality (29.0%) than obese (35.1%, p = 0.003) or severely obese (36.7%, p = 0.01). In HF-CS cohort, the healthy weight patients had the lowest mortality (21.7%), whereas it was higher in the underweight (37.5%, p = 0.012), obese (29.2%, p = 0.003), and severely obese (29.9%, p = 0.019). There was no difference in mortality among BMI categories in AMI-CS.

Effectiveness of combined plasma cell therapy and costimulation blockade based desensitization regimen in heart transplant candidates.

BACKGROUND: Desensitization is one of the strategies to reduce antibodies and facilitate heart transplantation in highly sensitized patients. We describe our center's desensitization experience with combination of plasma cell (PC) depletion therapy (with proteasome inhibitor or daratumumab) and costimulation blockade (with belatacept). METHODS: We reviewed five highly sensitized patients who underwent desensitization therapy with plasma cell depletion and costimulation blockade. We evaluated the response to therapy by measuring the changes in cPRA, average MFI, and number of positive beads > 5000MFI. RESULTS: Five patients, mean age of 56 (37-66) years with average cPRA of 98% at 5000 MFI underwent desensitization therapy. After desensitization, mean cPRA decreased from 98% to 70% (p = .09), average number of beads > 5000 MFI decreased from 59 to 37 (p = .15), and average MFI of beads > 5000 MFI decreased from 16713 to 13074 (p = .26). CONCLUSION: Combined PC depletion and CoB could be a reasonable strategy for sustained reduction in antibodies in highly sensitized patients being listed for heart transplantation.

Repeat left ventricular-assisted device exchange and upgrade from second- to third-generation devices in a high-volume single center.

BACKGROUND: Pump exchange is an established strategy to treat LVAD-related complications such as thrombosis, infection, and driveline failure. Pump upgrades with an exchange to newer generation devices are being performed to the advantage of the patient on long-term support. The safety and efficacy of a repeat LVAD exchange with a concomitant upgrade to a third-generation pump have not been reported. METHODS: We performed a retrospective analysis of all consecutive patients who underwent a repeat LVAD device exchange and upgrade to HeartMate III (HMIII) at Houston Methodist Hospital between December 2018 and December 2020. RESULTS: Five patients underwent exchange and upgrade to HMIII within the specified timeframe. Four patients had already had two prior exchanges (all HMII to HMII), and one patient had one prior exchange (HVAD to HVAD). In all cases, implantation was performed as destination therapy. The surgical exchange was performed via redo median sternotomy on full cardiopulmonary bypass. No unplanned redo surgery of the device component was required. In-hospital mortality was 20% in this very high-risk population. At 1-, 3-, and 6-month follow-up, all discharged patients were on HMIII support, with no major LVAD-related adverse events reported. CONCLUSION: We report the feasibility and safety of a repeat pump exchange with an upgrade to HMIII in a high-volume center. The decision for medical therapy versus surgical exchange has to be tailored to individual cases based on risk factors and clinical stability but in expert hands, even a re-redo surgical approach grants options for good medium-term outcomes.

Patients' and physicians' beliefs and attitudes towards integrating personalized risk estimates into patient education about left ventricular assist device therapy.

BACKGROUND: Personalized risk (PR) estimates may enhance clinical decision making and risk communication by providing individualized estimates of patient outcomes. We explored stakeholder attitudes toward the utility, acceptability, usefulness and best-practices for integrating PR estimates into patient education and decision making about Left Ventricular Assist Device (LVAD). METHODS AND RESULTS: As part of a 5-year multi-institutional AHRQ project, we conducted 40 interviews with stakeholders (physicians, nurse coordinators, patients, and caregivers), analyzed using Thematic Content Analysis. All stakeholder groups voiced positive views towards integrating PR in decision making. Patients, caregivers and coordinators emphasized that PR can help to better understand a patient's condition and risks, prepare mentally and logistically for likely outcomes, and meaningfully engage in decision making. Physicians felt it can improve their decision making by enhancing insight into outcomes, enhance tailored pre-emptive care, increase confidence in decisions, and reduce bias and subjectivity. All stakeholder groups also raised concerns about accuracy, representativeness and relevance of algorithms; predictive uncertainty; utility in relation to physician's expertise; potential negative reactions among patients; and overreliance. CONCLUSION: Stakeholders are optimistic about integrating PR into clinical decision making, but acceptability depends on prospectively demonstrating accuracy, relevance and evidence that benefits of PR outweigh potential negative impacts on decision making quality.

Bloodstream infections in prolonged use of axillary-placed, intra-aortic balloon-pump support: A single-center study.

Infections from prolonged use of axillary intra-aortic balloon pumps (IABPs) have not been well studied. Bloodstream infection (BSI) occurred in 13% of our patients; however, no difference in outcome was noted between those with BSI and those without. Further studies regarding protocol developments that minimize BSI risk are needed.

Procedural Insights and Clinical Outcomes of a Novel Superior Vena Cava Occlusion Device for Acute Heart Failure: A Single-Center Experience.

The preCARDIA system is a device combining a balloon-mounted catheter and an extracorporeal system designed for intermittent occlusion of the superior vena cava. Studies have established safety and efficacy in acute decompensated heart failure. We present a single-center experience detailing 90 days outcomes and procedural insights. A 24 hours therapy session demonstrated reduced pulmonary wedge pressures and increased urine output, with cardiac output remaining unchanged. There was one readmission and no heart failure-related readmissions at 90 days. The preCARDIA device appears to be a safe mechanical diuretic strategy to manage patients with acute decompensated heart failure beyond current therapeutic strategies.

Multicenter registry and test bed for extended outpatient hemodynamic monitoring: the hemodynamic frontiers in heart failure (HF2) initiative.

Background: Hemodynamic Frontiers in Heart Failure (HF2) is a multicenter academic research consortium comprised of 14 US institutions with mature remote monitoring programs for ambulatory patients with heart failure (HF). The consortium developed a retrospective and prospective registry of patients implanted with a wireless pulmonary artery pressure (PAP) sensor. Goals/aims: HF2 registry collects demographic, clinical, laboratory, echocardiographic (ECHO), and hemodynamic data from patients with PAP sensors. The aims of HF2 are to advance understanding of HF and to accelerate development of novel diagnostic and therapeutic innovations. Methods: HF2 includes adult patients implanted with a PAP sensor as per FDA indications (New York Heart Association (NYHA) Class III HF functional class with a prior hospitalization, or patients with NYHA Class II or brain natriuretic peptide (BNP) elevation without hospitalization) at a HF2 member site between 1/1/19 to present. HF2 registry is maintained at University of Kansas Medical Center (KUMC). The registry was approved by the institutional review board (IRB) at all participating institutions with required data use agreements. Institutions report data into the electronic registry database using REDCap, housed at KUMC. Results: This initial data set includes 254 patients implanted from the start of 2019 until May 2023. At time of device implant, the cohort average age is 73 years old, 59.8% are male, 72% have NYHA Class III HF, 40% have left ventricular ejection fraction (LVEF) < 40%, 35% have LVEF > 50%, mean BNP is 560 pg/ml, mean N-Terminal pro-BNP (NTproBNP) is 5,490 pg/ml, mean creatinine is 1.65 mg/dl. Average baseline hemodynamics at device implant are right atrial pressure (RAP) of 11 mmHg, pulmonary artery systolic pressure (PASP) of 47 mmHg, pulmonary artery diastolic pressure (PADP) 21 mmHg, mean pulmonary artery pressure (mPAP) of 20 mmHg, pulmonary capillary wedge pressure (PCWP) of 19 mmHg, cardiac output (CO) of 5.3 L/min, and cardiac index (CI) of 2.5 L/min/m2. Conclusion: A real-world registry of patients implanted with a PAP sensor enables long-term evaluation of hemodynamic and clinic outcomes in highly-phenotyped ambulatory HF patients, and creates a unique opportunity to validate and test novel diagnostic and therapeutic approaches to HF.

Impact of Female Sex on Cardiogenic Shock Outcomes: A Cardiogenic Shock Working Group Report.

BACKGROUND: Studies reporting cardiogenic shock (CS) outcomes in women are scarce. OBJECTIVES: The authors compared survival at discharge among women vs men with CS complicating acute myocardial infarction (AMI-CS) and heart failure (HF-CS). METHODS: The authors analyzed 5,083 CS patients in the Cardiogenic Shock Working Group. Propensity score matching (PSM) was performed with the use of baseline characteristics. Logistic regression was performed for log odds of survival. RESULTS: Among 5,083 patients, 1,522 were women (30%), whose mean age was 61.8 ± 15.8 years. There were 30% women and 29.1% men with AMI-CS (P = 0.03). More women presented with de novo HF-CS compared with men (26.2% vs 19.3%; P < 0.001). Before PSM, differences in baseline characteristics and sex-specific outcomes were seen in the HF-CS cohort, with worse survival at discharge (69.9% vs 74.4%; P = 0.009) and a higher rate of maximum Society for Cardiac Angiography and Interventions stage E (26% vs 21%; P = 0.04) in women than in men. Women were less likely to receive pulmonary artery catheterization (52.9% vs 54.6%; P < 0.001), heart transplantation (6.5% vs 10.3%; P < 0.001), or left ventricular assist device implantation (7.8% vs 10%; P = 0.01). Regardless of CS etiology, women had more vascular complications (8.8% vs 5.7%; P < 0.001), bleeding (7.1% vs 5.2%; P = 0.01), and limb ischemia (6.8% vs 4.5%; P = 0.001). More vascular complications persisted in women after PSM (10.4% women vs 7.4% men; P = 0.06). CONCLUSIONS: Women with HF-CS had worse outcomes and more vascular complications than men with HF-CS. More studies are needed to identify barriers to advanced therapies, decrease complications, and improve outcomes of women with CS.

Cardiac Tamponade With a Transaortic Percutaneous Left Ventricular Assist Device: When Alarms Caused No Alarm.

A 57-year-old man with end-stage heart failure presented with incessant ventricular tachycardia in the setting of cardiogenic shock, requiring support with a percutaneous left ventricular assist device. He underwent ablation of the ventricular tachycardia. Hours later the console alarm was evident, and the patient experienced worsening shock and elevated central venous pressure, leading to a diagnosis of cardiac tamponade. (Level of Difficulty: Advanced.).

Imaging for implementation of heart failure guidelines.

The classification of heart failure with implications for pharmacological therapeutic interventions rests on defining ejection fraction (EF) which is an imaging parameter. Imaging can provide diagnostic clues as to aetiology of heart failure; it can also guide and help assess response to treatment. Echocardiography, CMR, cardiac computed tomography, positron emission tomography, and Tc 99 m pyrophosphate scanning provide information about the aetiology of heart failure. Further, echocardiography plays the primary role in the evaluation of LV diastolic function and the estimation of left ventricular (LV) filling pressures both at rest and with exercise during diastolic stress testing. Heart failure guidelines recognize four stages (A, B, C, and D) for heart failure. Cardiac imaging along with risk factors and clinical status is needed for identifying these stages. There are joint societal echocardiographic guidelines by American Society of Echocardiography (ASE) of Echocardiography and European Association of Cardiovascular Imaging that are applicable to the imaging of heart failure patients. There are also separate guidelines for the evaluation of patients being considered for LV assist device implantation and for multimodality imaging of patients with heart failure and preserved EF. Cardiac catheterization is needed in patients whose haemodynamic status is uncertain after clinical and echocardiographic evaluation and to evaluate for coronary artery disease. Myocardial biopsy can identify the presence of myocarditis or specific infiltrative diseases when the findings by non-invasive imaging are not conclusive.

Translating Pressure Into Practice: Operational Characteristics of Ambulatory Hemodynamic Monitoring Program in the United States.

BACKGROUND: Ambulatory hemodynamic monitoring (AHM) using an implantable pulmonary artery pressure sensor (CardioMEMS) is effective in improving outcomes for patients with heart failure. The operations of AHM programs are crucial to clinical efficacy of AHM yet have not been described. METHODS AND RESULTS: An anonymous, voluntary, web-based survey was developed and emailed to clinicians at AHM centers in the United States. Survey questions were related to program volume, staffing, monitoring practices, and patient selection criteria. Fifty-four respondents (40%) completed the survey. Respondents were 44% (n = 24) advanced HF cardiologists and 30% (n = 16) advanced nurse practitioners. Most respondents practice at a center that implants left ventricular assist devices (70%) or performs heart transplantation (54%). Advanced practice providers provide day-to-day monitoring and management in most programs (78%), and use of protocol-driven care is limited (28%). Perceived patient nonadherence and inadequate insurance coverage are cited as the primary barriers to AHM. CONCLUSIONS: Despite broad US Food and Drug Administration approval for patients with symptoms and at increased risk for worsening heart failure, the adoption of pulmonary artery pressure monitoring is concentrated at advanced heart failure centers, and modest numbers of patients are implanted at most centers. Understanding and addressing the barriers to referral of eligible patients and to broader adoption in community heart failure programs is needed to maximize the clinical benefits of AHM.

Impact of exercise on pulmonary artery pressure in patients with heart failure using an ambulatory pulmonary artery pressure monitor.

Background: In this multicenter prospective study, we explored the relationship between pulmonary artery pressure (PAP) at rest and in response to a 6-min walk test (6MWT) in ambulatory patients with heart failure (HF) with an implantable PAP sensor (CardioMEMS, Abbott). Methods: Between 5/2019 and 2/2021, HF patients with a CardioMEMS sensor were recruited from seven sites. PAP was recorded in the supine and seated position at rest and in the seated position immediately post-exercise. Results: In our cohort of 66 patients, mean age was 70 ± 12 years, 67% male, left ventricular ejection fraction (LVEF) < 50% in 53%, mean 6MWT distance was 277 ± 95 meters. Resting seated PAPs were 31 ± 15 mmHg (systolic), 13 ± 8 mmHg (diastolic), and 20 ± 11 mmHg (mean). The pressures were lower in the seated rather than the supine position. After 6MWT, the pressures increased to PAP systolic 37 ± 19 mmHg (p < 0.0001), diastolic 15 ± 10 mmHg (p = 0.006), and mean 24 ± 13 mmHg (p < 0.0001). Patients with elevated PAP diastolic at rest (>15 mmHg) demonstrated a greater increase in post-exercise PAP. Conclusion: The measurement of PAP with CardioMEMS is feasible immediately post-exercise. Despite being well-managed, patients had severely limited functional capacity. We observed a significant increase in PAP with ambulation which was greater in patients with higher baseline pressures.

Outflow cannula alignment in continuous flow left ventricular devices is associated with stroke.

We sought to evaluate whether differences in left ventricular assist device (LVAD) canula alignment are associated with stroke. There is a paucity of clinical data on contribution of LVAD canulae alignment to strokes. We conducted a retrospective analysis of patients who underwent LVAD implantation at Houston Methodist hospital from 2011 to 2016 and included those who had undergone cardiac computed tomography (CT) with contrast. LVAD graft alignment using X-ray, echocardiography, and cardiac CT was evaluated. The primary outcome was stroke within 1 year of LVAD implantation. Of the 101 patients that underwent LVAD Implantation and cardiac CT scan during the study period, 78 met inclusion criteria. The primary outcome occurred in 12 (15.4%) patients with a median time to stroke of 77 days (interquartile range: 42-132 days). Of these, 10 patients had an ischemic and two had hemorrhagic strokes. The predominant device type was Heart Mate II (94.8%). Patients with LVAD outflow cannula to aortic angle lesser than 37.5° and those with outflow graft diameter of anastomosis less than 1.5 cm (assessed by cardiac CT) had significantly higher stroke risk (p < 0.001 and p = 0.01 respectively). In HMII patients, a lower LVAD speed at the time of CT scan was associated with stroke. Further studies are needed to identify optimal outflow graft configuration to mitigate stroke risk.

Treatment Intensity for the Management of Cardiogenic Shock: Comparison Between STEMI and Non-STEMI.

Background: Cardiogenic shock is a leading cause of mortality in patients with acute myocardial infarction. Objectives: The authors sought to compare clinical characteristics, hospital trajectory, and drug and device use between patients with ST-segment elevation myocardial infarction-related cardiogenic shock (STEMI-CS) and those without (non-ST-segment elevation myocardial infarction complicated by cardiogenic shock [NSTEMI-CS]). Methods: We analyzed data from 1,110 adult admissions with cardiogenic shock complicating acute myocardial infarction (AMI-CS) across 17 centers within Cardiogenic Shock Working Group. The primary end point was in-hospital mortality. Results: Our study included 1,110 patients with AMI-CS, of which 731 (65.8%) had STEMI-CS and 379 (34.2%) had NSTEMI-CS. Most patients were male (STEMI-CS: 71.6%, NSTEMI-CS: 66.5%) and White (STEMI-CS: 53.8%, NSTEMI-CS: 64.1%). In-hospital mortality was 41% and was similar among patients with STEMI-CS and NSTEMI-CS (43% vs 39%, P = 0.23). Patients with out-of-hospital cardiac arrest had higher in-hospital mortality in patients with NSTEMI-CS (63% vs 36%, P = 0.006) as compared to patients with STEMI-CS (52% vs 41%, P = 0.16). Similar results were observed for in-hospital cardiac arrest in patients with STEMI-CS (63% vs 33%, P < 0.001) and NSTEMI-CS (60% vs 32%, P < 0.001). Only 27% of patients with STEMI-CS and 12% of NSTEMI-CS received both a drug and temporary mechanical circulatory support device during the first 24 hours, which increased to 78% and 61%, respectively, throughout the course of the hospitalization (P < 0.001 for both). Conclusions: Despite increasing use of inotropic and vasoactive support and mechanical circulatory support throughout the hospitalization, both patients with STEMI-CS and NSTEMI-CS remain at increased risk for in-hospital mortality. Randomized controls trials are needed to elucidate whether timing and sequence of escalation of support improves outcomes in patients with AMI-CS.

Combined Heart-Kidney Transplantation: Indications, Outcomes, and Controversies.

Renal dysfunction, a prevalent comorbidity in advanced heart failure, is associated with significant morbidity and mortality after heart transplantation. In the recent era, the field of combined heart-kidney transplantation has experienced great success in the treatment of both renal and cardiac dysfunction in end-stage disease states, and the number of transplants has increased dramatically. In this review, we discuss appropriate indications and selection criteria, overall and organ-specific outcomes, and future perspectives in the field of combined heart-kidney transplantation.

Tissue plasminogen activator in left ventricular assist device-related intravascular hemolysis after failed augmented anticoagulation.

OBJECTIVES: We sought to examine the efficacy and safety of adding fibrinogen-guided low-dose multi-day Alteplase™ tissue plasminogen activator (tPA) in the management of intravascular hemolysis (IVH) in patients with the HeartMate II (HM-II) continuous flow (CF) left ventricular assist device (LVAD) who failed to achieve IVH resolution with conventional augmented anticoagulation (AAC). BACKGROUND: IVH in patients with LVAD is often treated with AAC, failing which pump exchange is considered. We hypothesized that a trial of low-dose tPA after failed AAC therapy could resolve IVH and prevent pump exchange in some patients. METHODS: We performed a retrospective study of 31 HM-II CF LVAD patients admitted to our center from January 2015 to January 2020 for IVH management who received tPA following failed AAC. Primary 6-month outcomes included successful IVH resolution, unsuccessful IVH resolution requiring pump exchange, gastrointestinal bleeding, ischemic and hemorrhagic cerebrovascular accident (CVA), and death. RESULTS: Thirty-one patients with IVH were treated with tPA following failed AAC. Successful resolution of IVH occurred in 22/31 (71%) patients. Pump exchange occurred in 9/31 (29%) patients. Gastrointestinal bleeding occurred in 7/31 (22.6%) patients. Ischemic CVA occurred in 6/31 (19.4%) patients. CONCLUSIONS: Management of IVH with administration of low-dose tPA after failed AAC is feasible and may prevent pump exchange in some patients.