Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Exception-Status Listing: A Critical Pathway to Heart Transplantation for Adults With Congenital Heart Diseases.

Adults with congenital heart diseases may not be candidates for conventional therapies to control ventricular systolic dysfunction, including mechanical circulatory support, which moves potential heart-transplantation recipients to a listing status of higher priority. This results in longer waitlist times and greater mortality rates. Exception-status listing allows a pathway for this complex and anatomically heterogenous group of patients to be listed for heart transplantation at appropriately high listing status. Our study queried the United Network for Organ Sharing registry to evaluate trends in the use of exception-status listing among adults with congenital heart diseases awaiting heart transplantation. Uptrend in the use of exception-status listing precedes the new allocation system, but it has been greatest since changes were made in the allocation system. It continues to remain a vital pathway for adults with congenital heart disease (whose waitlist mortality rates are often not characterized adequately by using the waitlist-status criteria) timely access to heart transplantation.

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

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

Prioritizing heart transplantation during the COVID-19 pandemic.

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

Functional mitral regurgitation: therapeutic strategies for a ventricular disease.

Functional mitral regurgitation is a highly prevalent condition among patients with ischemic and dilated cardiomyopathies. Arising from remodeling of both the mitral valve annulus and the left ventricle, it is associated with high mortality and morbidity. In selected patients, cardiac resynchronization therapy helps to reduce functional mitral regurgitation, but surgical intervention remains the mainstay of therapy when medical therapy for left ventricular dysfunction has been inadequate. It is, however, associated with significant perioperative risks and does not alter long-term mortality. Percutaneous devices, and more recently the Mitraclip in particular, represent a promising alternative that can improve symptoms and ventricular remodeling with significantly lower periprocedural risk.

Implications of Extra-cardiac Disease in Patient Selection for Heart Transplantation: Considerations in Cardiac Amyloidosis.

Disease-modifying therapies in both light chain and transthyretin amyloidosis have improved patient functional status and survival. Conceivably, as heart failure may progress despite amyloid therapies, more patients may be considered for heart transplantation. In earlier eras, extra-cardiac amyloid deposits significantly reduced post-heart transplant patient survival and functional status compared to the non-amyloid population. In the modern era, transplant centres have reported improved outcomes in amyloidosis as patient selection has grown more stringent. Importantly, systematic candidate evaluation should assess the degree of extra-cardiac involvement, the effectiveness of disease-modifying therapies and downstream effects on patients' nutrition and frailty. This review outlines such an overall approach while also considering that organ-specific selection criteria may vary between individual transplant centres. A methodical approach to patient evaluation will promote better understanding of the prevalence and severity of extra-cardiac disease in amyloidosis patients referred for heart transplantation and of any disparities in decision outcomes in this population.

Cardio-Obstetrics and Heart Failure: JACC: Heart Failure State-of-the-Art Review.

Heart failure and cardiomyopathy are significant contributors to pregnancy-related deaths, as maternal morbidity and mortality have been increasing over time. In this setting, the role of the multidisciplinary cardio-obstetrics team is crucial to optimizing maternal, obstetrical and fetal outcomes. Although peripartum cardiomyopathy is the most common cardiomyopathy experienced by pregnant individuals, the hemodynamic changes of pregnancy may unmask a pre-existing cardiomyopathy leading to clinical decompensation. Additionally, there are unique management considerations for women with pre-existing cardiomyopathy as well as for those women with advanced heart failure who may be on left ventricular assist device support or have undergone heart transplantation. The purpose of this review is to discuss: 1) preconception counseling; 2) risk stratification and management strategies for pregnant women extending to the postpartum "fourth trimester" with pre-existing heart failure or "pre-heart failure;" 3) the safety of heart failure medications during pregnancy and lactation; and 4) management of pregnancy for women on left ventricular assist device support or after heart transplantation.

Reproductive health after thoracic transplantation: An ISHLT expert consensus statement.

Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.

Outcomes of Heart Transplant Donation After Circulatory Death.

BACKGROUND: Heart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. OBJECTIVES: We sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. METHODS: We conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. RESULTS: During the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. CONCLUSIONS: In the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Early Blood Pressure Variables Associated With Improved Outcomes in VA-ECLS: The ELSO Registry Analysis.

BACKGROUND: As utilization of veno-arterial extracorporeal life support (VA-ECLS) in treatment of cardiogenic shock (CS) continues to expand, clinical variables that guide clinicians in early recognition of myocardial recovery and therefore, improved survival, after VA-ECLS are critical. There remains a paucity of literature on early postinitiation blood pressure measurements that predict improved outcomes. OBJECTIVES: The objective of this study is to help identify early blood pressure variables associated with improved outcomes in VA-ECLS. METHODS: The authors queried the ELSO (Extracorporeal Life Support Organization) registry for cardiogenic shock patients treated with VA-ECLS or venovenous arterial ECLS between 2009 and 2020. Their inclusion criteria included treatment with VA-ECLS or venovenous arterial ECLS; absence of pre-existing durable right, left, or biventricular assist devices; no pre-ECLS cardiac arrest; and no surgical or percutaneously placed left ventricular venting devices during their ECLS runs. Their primary outcome of interest was the survival to discharge during index hospitalization. RESULTS: A total of 2,400 CS patients met the authors' inclusion criteria and had complete documentation of blood pressures. Actual mortality during index hospitalization in their cohort was 49.5% and survivors were younger and more likely to be Caucasian, intubated for >30 hours pre-ECLS initiation, and had a favorable baseline SAVE (Survival After Veno-arterial ECMO) score (P < 0.05 for all). Multivariable regression analyses adjusting for SAVE score, age, ECLS flow at 4 hours, and race showed that every 10-mm Hg increase in baseline systolic blood pressure (HR: 0.92 [95% CI: 0.89-0.95]; P < 0.001), and baseline pulse pressure (HR: 0.88 [95% CI: 0.84-0.91]; P < 0.001) at 24 hours was associated with a statistically significant reduction in mortality. CONCLUSIONS: Early (within 24 hours) improvements in pulse pressure and systolic blood pressure from baseline are associated with improved survival to discharge among CS patients treated with VA-ECLS.

Heart failure with recovered ejection fraction: a distinct clinical entity.

BACKGROUND: A subset of patients with heart failure (HF) and preserved left ventricular ejection fraction (EF) previously had EF <40%. We postulated that such "recovered" EF patients would be prevalent in a referral HF population and clinically distinct from those with persistently preserved or reduced EF. METHODS AND RESULTS: We identified all subjects with a clinical diagnosis of HF seen in the advanced heart disease practice at our center from March to October 2008. Patients were classified into 1 of 3 groups based on retrospective review of the medical record: EF persistently ≥40% (HF-PEF), EF recovered to ≥40% (HF-REF) and low EF, <40% (HF-LEF). Clinical and echocardiographic characteristics were compared across groups using standard chi-square and analysis of variance tests. A total of 358 heart failure patients were identified, including 56 with HF-PEF, 121 with HF-REF, and 181 with HF-LEF. Compared with HF-PEF, HF-REF patients were younger with less atrial fibrillation, hypertension, and diabetes. Also, they tended to have lower systolic blood pressure, better renal function, and larger left ventricular diameter at end diastole. HF-REF patients were more similar to HF-LEF, but were younger and had lower rates of coronary artery disease. Of the 3 groups, HF-REF patients had the mildest reported HF symptoms and fewest previous HF hospitalizations. CONCLUSIONS: Patients with HF-REF comprise a substantial proportion of those with HF and EF ≥40% followed in an ambulatory referral practice. These patients appear to be clinically distinct from the residual HF population and should be specifically targeted for further research.

Outcomes of Older Patients in the Recent Era of Heart Kidney Transplantation.

BACKGROUND AND OBJECTIVE: Variable age thresholds are often used at transplant centers for simultaneous heart and kidney transplantation (HKT). We hypothesize that selected older recipients enjoy comparable outcome to younger recipients in the current era of HKT. METHODS: We performed a retrospective analysis of HKT outcomes in the United Network for Organ Sharing (UNOS) registry from 2006 to 2018, classifying patients by age at transplant as ≥ 65 or < 65 years. The primary outcome was patient death. Secondary outcomes included all-cause kidney graft failure and death-censored kidney allograft failure. RESULTS: Of 973 patients, 774 (80%) were younger than 65 years (mean 52 ± 10 years) and 199 (20%) were 65 years or older (mean 67 ± 2 years). The older HKT cohort had fewer blacks (22% vs 35%, P = .01) and women (12 vs 18%, P = .04). Fewer older patients received dialysis (30% vs 54%, P < .001) and mechanical support (36% vs 45%, P = .03) before HKT. Older recipients received organs from slightly older donors. The median follow-up time was shorter for patients 65 years or older than for the younger group (2.3 vs 3.3 years, P < .001). Patient survival was similar between the groups (mean 8.8 vs 9.8 years, P = .3), with the most common causes of death being cardiovascular (29%) and infectious complications (28%). There was no difference in all-cause kidney graft survival (mean 8.7 vs 9.3 years, P = .8). Most commonly, recipients died with a functional renal allograft (59.8%), and this occurred more commonly in older patients (81.4% vs 54.8%, P = .001). Cox proportional hazard modeling showed that higher donor age (hazard ratio [HR] 1.015, P = .01; HR 1.022, P = .02) and use of pre-transplant dialysis (HR 1.5, P = .004; HR 1.8, P = .006) increased the risk for both all-cause and death-censored kidney allograft failure, respectively. CONCLUSIONS: Our study showed that carefully selected older patients have outcomes similar to those of a younger cohort and argues for comprehensive evaluation of the recipients with age as part of comorbidity assessment rather than use of an arbitrary age threshold for candidacy.

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

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

Sex-specific differences in access and response to medical and device therapies in heart failure: State of the art.

Women with heart failure (HF) are more symptomatic than their male counterparts. Despite deriving similar benefits from both medical and devices therapies, women continue to be underrepresented in clinic trials. Important sex-based disparities exist in enrollment in clinical trials and access to medical and device-based therapies, in part stemming from differences in medical and psychosocial comorbidities. Disparities in access to beneficial interventions likely contribute to the greater symptom burden identified in women with HF. Improved focus on the enrollment of women in clinical trials will allow a better understanding of the underpinnings of these disparities and improve the care of women with HF.

Pregnancy outcomes in heart transplant recipients.

BACKGROUND: The population of female heart transplant recipients of reproductive age is growing, and counseling regarding reproductive decisions is important. We describe maternal and fetal outcomes of pregnancy in the Transplant Pregnancy Registry International. METHODS: Data regarding pregnancies between 1987 and 2016 were collected via questionnaires, phone interviews, and medical records review. Demographics, comorbidities, changes in immunosuppressive regimens, rejection episodes during pregnancy, data on maternal retransplants, and deaths were recorded. RESULTS: A total of 91 patients reported 157 pregnancies. Mean maternal age at conception was 27 ± 5.6 years. The most common indications for transplant were congenital heart disease (22%) and viral myocarditis (18%). Average transplant to conception interval was 7 ± 6.1 years. Immunosuppression was calcineurin inhibitor-based in almost all patients, with 20% of recipients taking mycophenolic acid (MPA) while pregnant. Complications during pregnancy included pre-eclampsia (23%) and infections (14%). Rejection was reported during 9% of pregnancies and within 3 months postpartum in 7%. Livebirths occurred in 69%, with no neonatal deaths. Miscarriages occurred in 26% of pregnancies, 49% of which had MPA exposure. Mean follow-up post pregnancy was 8.9 ± 6.5 years. At last follow-up, 30 recipients had died, an average of 9.4 ± 6.2 years after pregnancy. The most common causes included allograft vasculopathy and rejection. CONCLUSIONS: This is the largest reported series of pregnancies in heart transplant recipients and demonstrates that two thirds of pregnancies reported are successful. MPA exposure is associated with increased risk of teratogenicity and miscarriage. Pre-pregnancy counseling should include discussions of risk of MPA exposure, rejection, graft dysfunction, and maternal survival.

Trends in Renal Function Among Heart Transplant Recipients of Donor-Derived Hepatitis C Virus.

Donor-derived hepatitis C (dd-HCV) infection may increase the risk of renal impairment (RI) among heart transplantation (HT) recipients. Sofosbuvir, an integral component of HCV direct-acting antivirals (DAAs) has also been linked to RI. To date, no study has examined the trends in renal function for HT recipients of dd-HCV infection and assessed safety and efficacy of Sofosbuvir-based DAAs. Between September 2016 and June 2018, 46 HCV-naive patients and one patient with a history of HCV treated pretransplant, underwent HT from HCV-positive donors (follow-up available through October 10, 2018). Patients were treated with Ledipasvir-Sofosbuvir (genotype 1) or Sofosbuvir-Velpatasvir (genotype 3) for 12 or 24 weeks; no dose adjustments were made for renal function. Data on renal function were available for 23 patients who achieved a sustained virologic response at 12 weeks after the treatment (SVR12; cohort A) and 18 patients who completed 1 year of follow-up (cohort B). Treatment of dd-HCV infection was initiated at a median of 6 weeks post-HT. In both cohorts, a nonsignificant reduction in median estimated glomerular filtration rate (eGFR; ml/min/1.73 m) was noted (cohort A: pretransplant eGFR: 62 [interquartile range {IQR}: 1-84] to SVR12 eGFR: 49 [IQR: 37-82]; p = 0.43; cohort B: pretransplant eGFR: 65 [IQR: 54-84] to 1 year post-HT eGFR: 56 [IQR: 39-75]; p = 0.29). Pretreatment renal function had no significant impact on changes in renal function during treatment. All patients tolerated DAAs well with 100% completion rate to the assigned therapy and duration and 100% success at achieving SVR12. In this first and largest reported case series to date of HT recipients with dd-HCV infection, we observed that neither the dd-HCV infection nor its treatment with Sofosbuvir-based DAAs increased the risk of RI. Sofosbuvir-based DAAs appear safe, tolerable, and effective for HCV treatment even in presence of severe RI.

Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C.

Importance: For patients awaiting heart transplant, hepatitis C-positive donors offer an opportunity to expand the donor pool, shorten wait times, and decrease wait-list mortality. While early reported outcomes among few heart transplant recipients have been promising, knowledge of 1-year outcomes in larger cohorts of patients is critical to shared decision-making with patients about this option. Objective: To better define the association of hepatitis C-positive donors with heart transplant volumes, wait-list duration, the transmission and cure of donor-derived hepatitis C, and morbidity and mortality at 1 year. Design, Setting, and Participants: This was a prospective, single-center observational study of 80 adult (age 18 years or older) patients who underwent heart transplant using hearts from hepatitis C-positive donors between September 2016 and April 2019 at a large academic medical center. Among donors, who were considered hepatitis C-positive if results from hepatitis C antibody and/or nucleic acid testing were positive, 70 had viremia and 10 were seropositive but did not have viremia. Follow-up was available through May 15, 2019. Comparisons were drawn with patients who underwent transplant with hearts from hepatitis C-negative donors during the same period. Exposures: In addition to standard posttransplant management, transplant recipients who developed donor-derived hepatitis C infection were treated with direct-acting antivirals. Main Outcomes and Measures: The main outcomes included wait-list duration and 1-year survival in all patients, and for those who developed donor-derived hepatitis C, the response to direct-acting antiviral treatment. Results: Of 80 patients, 57 (71.3%) were men, 55 (68.7%) were white, and 17 (26.3%) were black; the median age at transplant was 54.5 years (interquartile range, 46-62 years). Following consent to accept hearts from hepatitis C-exposed donors, the median days to heart transplant was 4 (interquartile range, 1-18). No recipients of donors with negative nucleic acid testing results (10 [12.5%]) developed donor-derived hepatitis C. Of 70 patients who were recipients of donors with positive nucleic acid testing results, 67 (95.7%) developed donor-derived hepatitis C over a median follow-up of 301 days (interquartile range, 142-617). Treatment with direct-acting antivirals was well tolerated and yielded sustained virologic responses in all treated patients. Within the cohort with infection, 1-year patient survival was 90.4%, which was not significantly different compared with the cohort without infection or with patients who received transplants from hepatitis C-negative donors during the same period. Conclusions and Relevance: In the era of direct-acting antivirals, hepatitis C-positive donors are a viable option to expand the donor pool, potentially reducing wait-list duration and mortality. In heart transplant recipients with donor-derived hepatitis C, infection is well-tolerated and curable, and 1-year survival is equivalent to that in recipients of hepatitis C-negative donors.

Right ventricular assist device in end-stage pulmonary arterial hypertension: insights from a computational model of the cardiovascular system.

BACKGROUND: The high mortality rate of pulmonary arterial hypertension (PAH) mainly relates to progressive right ventricular (RV) failure. With limited efficacy of medical therapies, mechanical circulatory support for the RV has been considered. However, there is lack of understanding of the hemodynamic effects of mechanical support in this setting. METHODS: We modeled the cardiovascular system, simulated cases of PAH and RV dysfunction and assessed the theoretical effects of a continuous flow micro-pump as an RV assist device (RVAD). RVAD inflow was sourced either from the RV or RA and outflow was to the pulmonary artery. RVAD support was set at various flow rates and additional simulations were carried out in the presence of atrial septostomy (ASD) and tricuspid regurgitation (TR). RESULTS: RVAD support increased LV filling, thus improving cardiac output and arterial pressure, unloading the RA and RV, while raising pulmonary arterial and capillary pressures in an RVAD flow-dependent manner. These effects diminished with increasing disease severity. The presence of TR did not significantly impact the hemodynamic effects of RVAD support. ASD reduced the efficacy of RVAD support, since right-to-left shunting decreased and ultimately reversed with increasing RVAD support due to the progressive drop in RA pressure. CONCLUSIONS: The results of this theoretical analysis suggest that RVAD support can effectively increase cardiac output and decreases RA pressure with the consequence of increasing pulmonary artery and capillary pressures. Especially in advanced PAH, low RVAD flow rates may mitigate these potentially detrimental effects while effectively increasing systemic hemodynamics.