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The donor shortage in heart transplantation (HTx) has led to programs accepting older donors. Coronary calcification is common in older people and is known to correlate with underlying coronary artery disease. It is not known whether these donors with coronary calcification impart an increased risk for the recipient to develop cardiac allograft vasculopathy. Between 2010 and 2017, we assessed 31 heart transplant patients who were found to have coronary calcification within the first 3 months after heart transplantation, either by coronary angiography or chest CT scans. These patients were compared to a contemporary cohort of 192 patients (transplanted with donors >30 years old) without coronary calcification for the following outcomes: 3-year survival, 3-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), 3-year non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Those patients with donor coronary calcification compared to those without had a significantly lower 3-year freedom from CAV (64.5% vs 85.9%, P=0.001). There was no significant difference in 3-year survival, freedom from NF-MACE, and 1-year rejection episodes. The severity of CAV observed in the donor coronary calcification group included: CAV1 = 13, CAV2 = 1, CAV3 = 0. Donor coronary artery calcification appears to be a marker for greater risk for developing CAV after heart transplantation. Caution must be taken to accept these organs and if accepted, early modification of immunosuppression with a proliferation signal inhibitor may be indicated. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a major cause of late graft dysfunction and mortality after heart transplantation. The pathophysiology of CAV consists of a complex interplay between donor risk factors, recipient comorbidities, and immune-mediated processes. Despite many studies showing a correlation between donor-specific antibodies (DSA) and CAV, the effects of different DSA types on the severity of CAV remains elusive. This study investigates the characteristics of DSA amongst different CAV severity groups. We evaluated 526 adult heart transplant recipients at a single tertiary medical center between January 2010 and August 2015. Subjects were screened for DSA at the time of transplant, 1 month, 3 months, 6 months, 1 year, and then annually thereafter. CAV screening was performed with annual angiography. Subjects were divided into those with DSA (n= 143) and those without DSA (control group, n =383). Subjects with DSA were further categorized into those with persistent DSA (n=34), transient DSA (n=106), 1:8 dilution positive DSA (n=45), complement-binding (C1q) DSA (n=36), Class I DSA (n=36), and Class II DSA (n=106). The mean duration of follow up was 3.6 years. The outcomes are the incidence of CAV based on the ISHLT grading scale. Subjects with persistent DSA were found to have higher incidence of moderate-to-severe CAV (CAV2/3) compared the control group (p = <0.001). On the contrary, there was no difference in the incidence of CAV2/3 between subjects with transient DSA and the control group (p =0.873). Subjects with 1:8 dilution positive DSA and C1q positive DSA also had a higher incidence of CAV2/3 when compared those without DSA (p =0.001, p =<0.001). Between subjects with Class I and Class II DSA, only subjects with Class II DSA had higher incidence of CAV 2/3 compared to the control group (p =0.042). DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. Given CAV2/3 is linked with higher mortality post-transplantation, these DSA characteristics may serve as prognostic markers of disease and may warrant consideration for treatment. [ABSTRACT FROM AUTHOR]

Hyperlipidemia has been associated with the development of atherosclerotic cardiovascular disease in non-transplant patients. More recently, first-year LDL cholesterol was found to be a significant risk factor for the development of cardiac allograft vasculopathy (CAV) in a paper by Loupy and colleagues. Previous randomized clinical trials have demonstrated that statins can lower LDL cholesterol as well as decrease the development of CAV. Thus, most heart transplant patients are on statin therapy. In the current era with newer immunosuppressive agents, we sought to confirm that first-year lipid levels have an impact on outcome. Between 2010 and 2017 we assessed 260 HTx patients who survived to 1-year, where we assessed first-year lipid levels (where available) to include high vs low levels of total cholesterol (>200 vs <100mg/dl), LDL-cholesterol (>135 vs <70mg/dl), HDL-cholesterol (>60 vs <40mg/dl) and triglycerides levels (>200 vs <150mg/dl). The percent of patients on statin therapy for each group was included. The outcomes included 5-year survival and 5-year freedom from cardiac allograft vasculopathy (CAV: new stenosis ≥30%). High first-year HDL cholesterol levels compared to low levels had significantly greater 5-year survival although there was no significant difference in 5-year freedom from CAV. There was a trend for low LDL-cholesterol levels compared to high levels to have greater freedom from 5-year CAV. There were no significant differences in outcome in high vs low total cholesterol or high vs low triglyceride levels. There were less patients on statins in the high LDL vs low LDL-cholesterol groups. (See Table) HTx patients with high HDL may have survival benefit but CAV remains same. Further studies into the reason for this finding are being pursued. Low LDL levels appear to have benefit in 5-year outcome. [ABSTRACT FROM AUTHOR]

Diversity in the United States is a point of keen interest within the communities. In the heart transplant selection committees, most programs believe they have no bias in accepting patients for heart transplantation. However, there may be some inherent biases that are not due to the program's decisions, but rather institutional decisions or limitations. Such limitations may include lack of medical insurance, gender, age or geography that may be present without foreknowledge. Therefore, we assessed our heart transplant selection committee decisions to assess whether there is any inherent, institutional or voluntary bias within committee decisions. Between 2016 and 2020 we assessed 296 heart transplant candidates that were presented to the heart transplant selection committee. We assessed for various factors that may be associated with patients declined for transplant for age, gender, race, social support (SIPAT score), health insurance (Medicaid), and state of residence. The standard for comparison included a Caucasian with non-Medicaid health insurance, social support, and ability to travel. The declined patients compared to the accepted patients were significantly older (64.4 vs 54.6 years) and had a higher SIPAT score (13.7 vs 11.2). There was no difference between groups in % female, % non-Caucasian, % w/non-Medicaid health insurance and % from outside California. (see table) Inherent bias within a selection committee is difficult to interpret as older patients are held to a higher standard as older age is a risk factor for lower post-transplant survival. Higher SIPAT scores are also known to be a risk for lower survival due to higher psychosocial risk. It is comforting to appreciate that there does not appear to be inherent bias in gender, race, type of health insurance and region. Larger studies are needed. [ABSTRACT FROM AUTHOR]

Chronic kidney disease after heart transplantation is not uncommon due to the nephrotoxicity of calcineurin inhibitors (CNIs). It is well established that kidney dysfunction does impact post-transplant survival. What is not known is whether early or later development of kidney dysfunction has greater impact on outcomes. Between 2010 and 2017, we assessed 130 heart transplant patients and followed their course over the first 5 years. Patients were categorized as having kidney dysfunction detected with creatinine > 1.5 mg/dL at 1-year, 3-years, and 5-years after heart transplant. These patients were subsequently followed for 5 years to assess for subsequent 5-year survival, subsequent 5-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), subsequent 5-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30%), and 5-year freedom from left ventricular dysfunction (LVEF ≤ 40%). Patients who developed kidney dysfunction at 1-year post-heart transplant appear to have similar subsequent 5-year survival compared to those with kidney dysfunction at 3 and 5 years after heart transplant. However, significantly more patients with kidney dysfunction at 1-year required subsequent kidney dialysis. (See table) Early development of kidney dysfunction appears to lead to more patients needing kidney dialysis compared to those patients that develop kidney dysfunction later post-heart transplant. Renal sparing protocols or CNI minimization should be aggressively approached in these early patients to prevent worsening of kidney dysfunction. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is seen in approximately 50% of heart transplant (HTx) recipients within 8 to 10 years. CAV may be focal and amenable to percutaneous cardiac intervention (PCI) with stent placement though the re-stenosis rate is not well established. We reviewed our experience with CAV post PCI. We assessed 40 HTx recipients transplanted 2010-2017 who underwent PCI. The impact of statin and mTOR inhibitors on in-stent re-stenosis (≥50% stenosis) after 1 and 5 years was assessed. Other outcomes post PCI included survival and development of non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, coronary intervention, defibrillator/pacemaker, stroke). In the 40 patients who underwent PCI, in-stent re-stenosis at 1- and 5-years post-PCI was 0% and 7.5% (n=3). There was no difference in restenosis based on statin use, mTOR use, or both. There was also no difference in 1- and 5-year survival or 5-year freedom from NF-MACE between groups. (Table) The occurrence of in-stent re-stenosis is very low in heart transplant patients in the current era. Whether they are on statins, statins and mTOR inhibitors, or neither does not appear to affect in-stent re-stenosis, survival and freedom from NF-MACE in this small sample. A larger set of data and further follow up will be important to confirm these findings. [ABSTRACT FROM AUTHOR]

Patients who undergo heart transplantation may be in need of a second heart transplant if they develop severe graft dysfunction. Due to the long periods of time that these patients have been on calcineurin inhibitors, chronic kidney disease may ensue. These patients who need a second heart transplant may also need a combined kidney transplant. It has not been established in these redo heart transplant patients as to what GFR places them at risk for chronic dialysis post redo heart transplant. Between 2010 and 2021, we assessed 41 heart transplant patients who underwent redo heart transplant alone. These patients were divided into GFR quintiles (<42, 42 to <52, 53 to <61, 61 to <80 and ≥80 cc/minutes) to assess subsequent need for chronic kidney dialysis post-redo heart transplant. A group of 22 combined heart-kidney transplant patients were also included for comparison. Other endpoints included post-transplant 1-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from acute cellular rejection (ACR) and freedom from antibody mediated rejection (AMR). Redo heart transplant patients undergoing a heart transplant alone in the lowest quintile had a trend toward increased need for chronic hemodialysis post-transplant. At 1-year post-transplant, GFR remained low for those redo heart patients with baseline GFR <52cc/minute. Among the GFR quintile groups, there was no significant difference in post-transplant 1-year survival, freedom from CAV, freedom from ACR and freedom from AMR. In comparison, the redo heart transplant with combined kidney transplant patients appeared to have good outcome. (see table) Redo heart transplant patients with GFR < 42 cc/min appear to be at high risk for chronic hemodialysis post redo heart transplant. These patients might be considered for a combined redo heart transplant with kidney transplantation. Larger number of patients are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

: The new donor heart allocation policy change occurred in October 2018. At that time, the waiting list statuses changed from 3 statuses to 6 statuses. In the old donor heart policy, Redo heart transplants (HTx) were listed as stable patients waiting at home, which were usually status 2 (old policy). After 2018, redo heart transplants are now status 4 which is a higher listing status compared to the old policy. Redo HTx patients may have higher mortality due to the fact that many have sudden death due to pulseless electrical activity arrest. It has not been established whether waitlist mortality for redo HTx as status 4 patients on the waitlist is greater than other status 4 patients. We wish to establish this waitlist mortality rate in terms of perhaps higher priority listing for these patients. : Between October 18, 2018, and December 31, 2021, we assessed 33 redo HTx patients who were accepted onto the HTx waiting list in our program. These redo HTx patients were compared to 89 non-redo HTx patients listed as Status 4 at our institution. All patients were assessed for 1-year survival on the waitlist and the percentage of patients upgraded to a higher status due to worsening heart failure. : Redo heart transplant patients listed at Status 4 compared to non-redo heart transplant patients had no significant difference for time on the waitlist, time to transplant, percent transplanted and 1-year waitlist survival. The percent of patients switched to a higher status was similar between groups (72.7% vs 68.5%). For this subgroup of patient, there was no difference for the same waitlist outcomes as above. (see table) : Waitlist status 4 for redo heart transplant patients on the heart transplant waitlist appears appropriate. More urgent listing is not indicated for these patients. [ABSTRACT FROM AUTHOR]

Monotherapy with tacrolimus alone (TAC-A) was found to be safe and effective in the TICTAC Trial. However, in that trial, tacrolimus levels were maintained at 10-12 ng/mL over the first year which resulted in a higher serum creatinine level compared to those left in combination. We have been using TAC-A at lower doses in patients who have developed leukopenia or thrombocytopenia due to immunosuppression or a natural state. The presence of cytomegalovirus infections and other viruses excluded those patients from being administered monotherapy. It has not been established whether low dose TAC-A is safe and effective. Between 2010 and 2017 we assessed 151 heart transplant patients who are maintained on monotherapy with TAC-A. Patients were maintained on a low level of TAC-A between 4-7 ng/ml. These patients were assessed for subsequent 1-year rejection, subsequent 3-year survival, 3-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), cardiac allograft vasculopathy (CAV, epicardial disease with angiographic stenosis>30%), and cardiac dysfunction (LVEF ≤ 40%). Furthermore, periodic testing was done with the T-cell immune function test to assess whether these patients were adequately immunosuppressed. Patients who were maintained on TAC-A had comparable outcomes compared to patients left in combination immunosuppression (see table). The T-cell immune function test showed that these patients had adequate immunosuppression (average was 276 ng/mL with a range of 56-794 ng/mL and standard deviation of 137.1 ng/mL) with the therapeutic range being 200-550ng/ml. Patients had an average of 11 Tacrolimus lab tests (range: 4-46). Low dose TAC-A appears safe and effective in select patients after heart transplantation guided by T cell immune function testing. Further studies with larger number of patients will be needed to confirm these findings. [ABSTRACT FROM AUTHOR]

One of the most concerning issues immediately post-heart transplant (HTx) is the development of primary graft dysfunction (PGD) and/or vasoplegia. It has been suggested that patients on angiotensin-converting enzyme inhibitors (ACEi) are at risk for the development of PGD and vasoplegia due to activation of the kallikrein pathways which can activate bradykinin (vasodilator). It is not known whether ACEi with low systolic blood pressure (SBP) prior to HTx is associated with the development of PGD and vasoplegia. We sought to answer this question in our large, single center patient population. Between 2017 and 2020, we assessed 189 patients awaiting HTx treated with ACEi (n=19) who had SBP less than 100 mmHg at the time of HTx and those patients without ACEi (n=170) but also with SBP less than 100 mmHg. Endpoints included the development of PGD (ISHLT grading scale) and vasoplegia (defined as requiring more than 2 vasoconstricting drugs with SBP still < 90 mmHg). A control group (n=176) of patients with SBP > 100mmHg was included for comparison. Patients treated with ACEi and with low SBP at the time of HTx appear to have significantly increased risk of PGD and vasoplegia development post-HTx. However, their 30-day and 1-year survival was no different compared to those patients not on ACEi (with low SBP) and those with normal blood pressure. (See table.) ACEi and lower SBP at the time of heart transplantation may be a significant risk factor for the development of PGD and vasoplegia. Stopping ACEi prior to heart transplant may be warranted but requires further study. [ABSTRACT FROM AUTHOR]

For patients awaiting heart transplantation (HTx), who have high levels of circulating antibodies (greater than 70% PRA) desensitization therapy may be indicated. This will allow expansion of the donor pool for a compatible donor. As women appear to be more highly sensitized (due to multiple pregnancies), it is not clear as to whether women compared to men can benefit from desensitization therapy. We sought to answer this question with review of our large, single center database. Between 2008 and 2020, we assessed 49 patients awaiting HTx who underwent desensitization therapy. These patients were divided into groups by sex to evaluate their response to desensitization therapy. Our desensitization protocols consist of regimens including intravenous immune globulin, anti-CD20 monoclonal antibody, plasmapheresis, proteosome inhibitors. A response to desensitization therapy was assessed by the decline of the dominant circulating antibody determined by mean fluorescence intensity (MFI). Post-HTx data was assessed for 1-year survival and freedom from rejections (acute cellular rejection [ACR], antibody-mediated rejection [AMR]). Rejection episodes were compared to a control group of non-sensitized patients transplanted during the same period (n=771). Desensitization therapy in women appeared to be comparable to men considering similar desensitization protocols. There were no significant differences in waitlist mortality, time on the waitlist, or 1-year post-transplant survival, 1-year freedom ACR or AMR, between the two groups. Compared to non-sensitized patients, freedom from AMR was significantly lower in both sensitized men and women (72.7% men and 78.9% women vs. 96.5% control group). Sensitized women awaiting HTx compared to men appear to have similar response to various desensitization regimens. Post-HTx, there was more AMR in both groups, suggesting sensitization may be responsible. [ABSTRACT FROM AUTHOR]

The COVID pandemic has affected the management of heart transplant (HTx) patients. Patients were seen virtually via telemedicine and patients self-isolated at home. We assessed the impact of telemedicine and isolation during the COVID pandemic on HTx outcomes at our center. We assessed 55 HTx patients who were transplanted March - September 2020 and followed for 6 months. Patients were self-isolating and only had every other clinic visit in-person after the first month. Outcomes included 6-month survival, re-hospitalization, non-COVID infections (defined as requiring intravenous antibiotics), any treated rejection (ATR), and maintenance of therapeutic immunosuppressive blood levels. The study patients were then compared to a control group of HTx patients evaluated during March of the previous three years. The study group (during the COVID pandemic) demonstrated a significant decrease in re-hospitalization in the first 6 months following HTx compared to the control group. There was a numerical decrease in non-COVID infectious complications. There was no difference in survival or freedom from treated rejection episodes between the two groups. Reasons for rehospitalization included infections, cardiac and renal issues, malaise, and fever. Of note, 2 patients in the study group developed COVID subsequently after HTx but were not hospitalized. The COVID pandemic demonstrated that self-isolation and virtual visits resulted in less hospitalizations, possibly due to fewer infectious complications. This implies that perhaps stricter restrictions for community exposure might benefit HTx patients in the 6 months following transplantation. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion injury after heart transplant is not uncommon. This may lead to rejection and endothelial cell dysfunction with subsequent development of cardiac allograft vasculopathy (CAV). It has been reported that the use of anti-thymocyte globulin (ATG) as induction therapy post-transplant may lessen the ischemia reperfusion injury that occurs to donor hearts. This has not been confirmed. Between 2010 and 2020, we assessed 1082 heart transplant patients and divided them into those who received induction with ATG versus those who did not. In our program, ATG is given to patients who are sensitized or have baseline serum creatinine >2.0 mg/dL to delay initiation of tacrolimus. Weekly endomyocardial biopsy samples were reviewed for the first month after heart transplantation for ischemia reperfusion injury. First year outcomes included survival and freedom from CAV (stenosis ≥30%). Patients who underwent induction therapy with ATG had significantly greater freedom from any ischemia reperfusion injury noted on weekly endomyocardial biopsies in the first month post-transplant. There was no difference between the two groups in first-year survival and freedom from CAV. ATG as induction therapy appears to provide protection against ischemia reperfusion injury in donor hearts. Longer follow-up is needed to show potential outcomes benefit. This finding should be confirmed in a randomized clinical trial. [ABSTRACT FROM AUTHOR]

Sensitization in patients (pts) awaiting heart transplantation (HTx) can be refractory to conventional therapies such as plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and bortezomib, particularly for Class II antibodies. Pts refractory to these initial therapies may require more advanced therapies. Tocilizumab is an anti-interleukin-6 monoclonal antibody found to significantly reduce dominant HLA antibodies prior to kidney transplantation. We report here our experience with tocilizumab in refractory sensitized pts awaiting HTx. Between 2008 and 2020, we assessed 7 HTx pts who were initially treated with conventional desensitization therapies, including plasmapheresis, IVIG, rituximab, and bortezomib. Pts were then treated with tocilizumab at 8 mg/kg monthly for 6 months. Endpoints included change in calculated panel reactive antibodies (CPRA) determined just prior to the administration of tocilizumab, and 2 weeks after completion of the 6-month therapy. Antibodies were further classified into Class I and Class II to assess efficacy in each of these subgroups. 1 year post-HTx antibody mediated rejection (AMR) and survival was assessed and compared with pts transplanted without desensitization therapy in the same period (N=302). 6 of 7 sensitized pts treated with tocilizumab had a decrease in their immunodominant antibody with an average 31% reduction. For the CPRA level, 4 of 7 patients had a predominant decrease in Class II circulating antibodies. Post-HTx, compared to pts who did not receive desensitization therapies, 1st year AMR episodes were increased in the tocilizumab group (2.0% vs 14.3% respectively; p=0.032) but this did not affect survival at 1 year (92.1% vs 100% respectively; p=0.447). Highly sensitized pts on the heart transplant waitlist who are refractory to conventional desensitization therapy appear to be responsive to tocilizumab therapy. Although these pts have more AMR post-transplant, survival is comparable. [ABSTRACT FROM AUTHOR]

The donor heart allocation policy was changed in October 2018, allowing priority for waitlist candidates with intra-aortic balloon pump (IABP) support over those with inotropic support. The use of IABP has increased several-fold since the donor heart policy was put into effect in October 2018. We assessed the UNOS registry to determine if this increase was due to a shift in practice or due to increased patient instability. We reviewed 128 patients in UNOS on IABP awaiting HTx April 1, 2017 - April 1, 2018, and compared them to the 446 patients in UNOS on IABP awaiting HTx November 1, 2018 - November 1, 2019. The patients were further divided into groups based on concomitant use of inotropic support and compared pre- and post-allocation change. 30-day and 1-year survival post-HTx were assessed. In the post-policy era period of 2018, the placement of IABP without inotropes increased by 3.4-fold compared to 1 year prior to the policy change. For all patients with IABP placement, time from listing to transplant was significantly shorter after the policy change. There was no difference in 30-day and 1-year survival (Table 1). There appears to be a shift in practice where IABP support is used without inotropic support after the donor heart allocation policy change. This suggests that physicians are using IABP in place of intravenous inotropes to advocate for their patients for a higher urgency status and donor availability. This should be taken into account in the revision of future donor heart allocation policies. [ABSTRACT FROM AUTHOR]

Candidates for heart transplantation may be placed on durable left ventricular assist devices as bridge to transplantation. These patients are known to develop circulating antibodies mainly due to blood transfusion. It has been reported that up to 30-40% of these patients develop circulating antibodies which may limit the donor pool. It has not been established whether temporary mechanical circulatory support (tMCS) devices result in similar sensitization. Between 2016 and 2021, we assessed 16 patients waiting for heart transplantation who required temporary left ventricular support. tMCS included Impella (n=11) and IABP (n=5). Only patients who had no circulating antibodies at the time of tMCS were entered into this study. Blood samples were drawn beginning at 2 weeks following placement of the temporary device. Freedom from development of circulating antibodies was determined at 2-4 weeks following placement of tMCS. Only 1 of these 16 patients (6%) developed circulating antibodies just prior to heart transplantation while on tMCS. The mean time on tMCS devices prior to transplant was 22 days, and 10 of these 16 patients (63%) received packed red blood cells either during or after tMCS placement but prior to transplant. Patients placed on tMCS have a low likelihood of developing circulating antibodies despite receiving blood transfusions. tMCS does not appear to activate sensitization pathways. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic infected large portions of the US community and infected many heart transplant (HTx) patients but in distinct geographical patterns. HTx programs have reported mortality in the range of 23-29% (East Coast of the US) and in non-transplant patients in the range of 15-17%. The impact of hospitalized HTx patients with COVID-19 infection in a large West Coast heart transplant program has not been reported. We now report our outcomes for hospitalized patients with COVID-19. Between March 2020 and March 2021, we assessed 22 HTx patients who were admitted to the Cedars-Sinai Medical Center (CSMC) for COVID-19 infections. COVID-19 is known to affect many systems within the body, and we report the effects on lungs, heart, and kidney. Morbidity and mortality, including risk of death, were included within 90 days post-infection. Of the 22 HTx patients hospitalized at the CSMC, 7 patients died (31.8%). All patients had COVID-19 pneumonia requiring supplemental oxygen and 5 patients required ventilatory support. The mean peak FiO2 of the patients was 79.7%. 16 of these patients also were noted to have an increase in serum creatinine, with 6 patients requiring kidney dialysis. Cardiac function was maintained in all patients with COVID-19 and no myocarditis or cardiac dysfunction was observed. 9 patients received remdesivir and 19 patients received corticosteroids. 4 patients received tocilizumab anti-inflammatory therapy. COVID-19 resulted in significant morbidity and mortality in hospitalized heart transplant patients. Outcomes on the West Coast of the US were similar to the East Coast. The immunosuppressed state appears to be a risk factor for poor outcome and is higher compared to non-transplant hospitalized patients. [ABSTRACT FROM AUTHOR]

Seizures may occur following heart transplantation (HTx), especially since tacrolimus can lower a seizure threshold. HTx recipients are also at high stroke risk given many patients have existing cerebrovascular disease. The purpose of the study was to assess the prevalence and risk factors for seizures in HTx recipients at our center. We assessed 560 patients who underwent HTx between 2015-2020 for the development of seizures within the first month post HTx. We assessed impact of putative risk factors on early post transplant seizures, including prior stroke, atherosclerotic vascular disease, prior seizures, diabetes, prior smoking, and male sex. 40 of 560 HTx patients (7.3%) developed seizures in the first post-transplant month. The seizure group was compared to the control group (n=520) for risk factors for seizures (see table). Univariate analysis found that hypertension, history of atherosclerosis, and history of previous seizures were significant risk factors to develop seizures in the first postoperative month. Multivariate analysis found that only hypertension and history of previous seizures were significantly associated with early seizures post-HTx. All patients with seizures were placed on anti-seizure medications and had tacrolimus switched to cyclosporine. Seizures in the first post-transplant month occur in a significant minority of patients. Patients undergoing heart transplant with both history of hypertension and seizures are at risk to develop seizures in the early postoperative period. These patients might be considered for prophylactic anti-seizure therapy in the first 30 days following HTx surgery. [ABSTRACT FROM AUTHOR]

The calcineurin inhibitors (CNIs), including tacrolimus and cyclosporine, have revolutionized heart transplantation (HTx) in terms of maintaining low rejection rates. However, CNIs have significant side effects, such as nephropathy, hypertension, malignancy, and hypomagnesemia. It is this hypomagnesemia that has not been addressed as to whether this has an impact on outcome after HTx. Hypomagnesemia has been involved in muscle cramping and cardiac arrhythmias. Therefore, we reviewed our HTx patients and their magensium (Mg) levels to assess outcome in the first 6 months after HTx. Between 2010 and 2020, we assessed 956 HTx patients and recorded their Mg levels in the first 6 months after HTx. Patients with low Mg levels less than or equal to 1.8 mg/dL were assessed for complications including muscle cramping, cardiac arrhythmias, rehospitalization, and rejection episodes. Patients with low Mg levels were grouped into mildly low Mg levels (1.7-1.8 mg/dL) and moderately low Mg levels (1.4-1.7 mg/dL). Patients were compared to control patients who had normal Mg levels (>1.8 mg/dL) during this period of time. Patients with mildly or moderately low Mg levels compared to patients with normal Mg levels had no difference in muscle cramping, rejection episodes, cardiac arrhythmias, or use of antihypertensive medications. Kidney function was clinically similar in all groups. There were more arrhythmias in the normal Mg group. Patients had an average of 32 blood draws to assess Mg levels. Mildly to moderately low hypomagnesemia did not have significant adverse effects in heart transplant patients. Aggressive Mg replacement may not be essential. [ABSTRACT FROM AUTHOR]

Approximately 30% of patients (pts) awaiting heart transplantation (HT) develop anti-HLA antibodies (Abs) due to sensitizing events. Highly sensitized pts have peak Panel Reactive Antibody (PRA) levels≥80%. We assessed the efficacy of desensitization therapy (DTx) on these pts awaiting HT. Between 2010-19, we assessed 78 pts awaiting HT with peak PRA≥80% (mean peak PRA 91.6%, range 80-100%). These pts received DTx with intravenous immunoglobulin (IVIG) alone (n=18), rituximab-based therapy (n=5), plasma exchange (PE) alone (n=15), bortezomib-based therapy (BTZ)(n=30), and finally combination therapy with rituximab/BTZ (n=-10). Peak PRAs (mean fluorescent intensity, MFI) were obtained before and after treatment. All pts received ATG induction and IVIG with eculizumab given to pts crossing high level donor-specific Ab (DSA). 3-year outcomes including survival, freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30%), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new onset heart failure, percutaneous coronary intervention, cardioverter defibrillator/pacemaker implant, stroke), and 1-year freedom from rejection [acute cellular rejection (ACR), Ab-mediated rejection (AMR)] were obtained. A group of non-sensitized pts without pre-HT anti-HLA Abs was used as control. With each DTx, peak PRA was reduced (table). Post-HT, there was lower freedom from 1-year AMR in the highly sensitized pt groups compared to the control group. 3-year survival, freedom from CAV and NF-MACE were similar among all groups. 26 highly sensitized pts received eculizumab perioperatively for crossing high level DSA. Although there is variability in how highly sensitized pts respond, pre-HT DTx appears beneficial and enables pts to undergo successful HT. Further studies and longer follow-up are needed to identify the optimal therapy for each highly sensitized individual. [ABSTRACT FROM AUTHOR]

Heart transplant patients develop many opportunistic infections due to chronic immunosuppression. One of the more common complications is that of Clostridium difficile (CDif) causing gastroenteritis, usually represented as diffuse diarrhea. It appears that these opportunistic infections such as CDif may have an impact on the immune system via the microbiome. It has not been demonstrated whether patients who develop CDif are at higher risk for the subsequent development of rejection or chronic rejection known as cardiac allograft vasculopathy (CAV) years after the event. Between 2010 and 2018, we assessed 69 heart transplant patients who developed CDif within the first year post-transplant. These patients were assessed for subsequent 3-year survival, 3-year freedom from CAV (stenosis ≥30% by angiography), 3-year freedom from non-fatal major adverse cardiac event (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), and 1-year freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR). These patients were compared to a group (case controlled for time from transplant, age, gender) who did not develop CDif. The average time of infection following transplant was 2.2 ± 3.0 months. The heart transplant patients who developed CDif had significantly lower subsequent 3-year survival, 3-year freedom from NF-MACE, and lower 1-year freedom from AMR compared to the control group. There was no significant difference in the development of CAV (see table). Assessment of specific immunosuppression, antibiotic prophylaxis, and specific CDif treatment did not have an impact on outcome. Heart transplant patients who developed first-year CDif appeared to have immune modulation that adversely affects subsequent outcome. Further investigation to study the microbiome is needed in order to elucidate the mechanisms that are in process. [ABSTRACT FROM AUTHOR]

Patients who are awaiting heart transplantation (HTx) have blood screened for circulating antibodies. Antibodies can sometimes come and go and not be detected at the time of HTx. However, there are instances when the patient has demonstrated donor specific antibodies (DSA) in the past but yet are not present at the time of HTx. It is not known whether these historical DSA have an impact on post-HTx outcomes. Between 2010 and 2019, we assessed 11 patients awaiting HTx who had historical DSA but none detected at the time of HTx. These patients were compared to patients with DSA at the time of HTx and also compared to a non-sensitized group of patients undergoing HTx in a contemporaneous era. Post-HTx detection of DSA was performed and assessed if there was an amnestic response to the historical DSA. DSA are routinely checked post-HTx at 1, 3, 6, 12 months post-operatively. Other endpoints included 1-year freedom from any treated rejection, acute cellular rejection, and antibody-mediated rejection. 1-year survival, 1-year freedom from non-fatal major adverse cardiac event (NF-MACE, defined as MI, new CHF, PCI, ICD/pacemaker placement, stroke) and 1-year freedom from cardiac allograft vasculopathy were also recorded. Patients with historical DSA did not have an amnestic response with an increase of that specific DSA post-HTx. The historical DSA group compared to the non-sensitized group had no significant differences in 1-year survival, freedom from DSA, CAV, NF-MACE or rejections. Specifically, the historical DSA group did not appear to have an increase in any type of rejection in the first year post-HTx compared to (crossing) DSA at transplant group or the non-sensitized group. (See table) Historical DSA does not appear to be a factor in terms of an amnestic response possibly due to the immunosuppression that is being administered. Therefore, crossing historical DSA at heart transplant does not appear to have adverse sequelae. [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is caused by the parasite T cruzi and may reactivate in immunosuppressed transplant recipients. The incidence of CD has increased in Southern California as patients with Chagas cardiomyopathy may progress to require heart transplantation. While there are prophylactic medications for CD, is it not clear whether this prophylaxis prevents CD reactivation. We reviewed 13 recipients transplanted between 1999 and 2019 who had CD prior to transplant. These patients had CD serologies checked at 1, 3, 6, 12 months post-transplant. 7 had T cruzi IgG antibodies and were given nifurtimox (n=2) or benznidazole (n=5). The other 6 did not develop antibodies and were not given antimicrobial therapy. Outcomes were compared: symptomatic CD, 1-year survival, freedom from rejection [any-treated (ATR), acute cellular (ACR) and antibody-mediated rejections (AMR)]. The patients who received antimicrobial therapy had numerically better 1-year survival. There was no difference in 1-year rejection (Table). Of the 7 patients who received antimicrobial therapy, none had CD reactivation while 3 patients in the no-prophylaxis group had CD reactivation. Heart transplant patients with a history of CD appear to have acceptable outcome when closely monitored and administered antimicrobial therapy when indicated. Administration of prophylactic antimicrobial therapy to all CD, even without IgG antibodies, may be considered. [ABSTRACT FROM AUTHOR]

Patients more than 50 years of age routinely undergo screening colonoscopies. These patients can develop severe end-stage heart disease and may require heart transplantation. Many of these patients present in cardiogenic shock and it is unclear whether the use of colonoscopy is safe and efficacious in the screening of these patients for candidacy for heart transplantation. In our single-center program, we preform colonoscopies routinely on older patients at risk for colon cancer (family history, previous polyps or adenomas, stools heme positive) awaiting heart transplantation. We now report our experience of performing colonoscopes in these patients who are in cardiogenic shock, defined as patients who are on intravenous inotropic or left ventricular assist device (LVAD) support to maintain acceptable cardiac hemodynamics. Between 2014 and 2019, we evaluated 300 heart transplant candidates who developed cardiogenic shock, defined as the need for IV inotropes or LVAD support. 30 of these patients underwent colonoscopy while on IV inotropes (n=27) and LVAD (n=3). All patients had compensated hemodynamics and anticoagulation was held prior to the procedure. Of the 30 patients with inotropic/LVAD support who underwent colonoscopy, the average age was 61.5 years and 87% were male. The specific inotrope(s) administered are listed in the table. The following findings at colonoscopy were found: 0 adenomas and 13 benign malignancies. There was no metastatic disease demonstrated. There were no complications arising from this colonoscopy except for bleeding due to biopsies that required hemoclips but no blood transfusions. Inotropic/LVAD support was continued through these procedures. Colonoscopies for evaluation of heart transplant candidates who are in cardiogenic shock are acceptable, but caution should be taken in terms of risk for bleeding. Colonoscopies in cardiogenic shock should be limited to patients who are at risk for colon cancer. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is one of the major factors limiting long-term survival. A severe form of CAV is small vessel disease which results in restrictive cardiac physiology (RCP). This RCP causes a very stiff heart which leads to significant reduction in cardiac index and elevation of cardiac pressures. The pathophysiology behind this RCP is most likely due to small vessel CAV with scarring and fibrosis. The outcome of patients with this RCP has not been well established. Between 2010 and 2017 we assessed 23 heart transplant patients who developed RCP defined by right atrial pressure ≥ 15 mmHg, pulmonary artery diastolic pressure ≥ 15 mmHg, pulmonary capillary wedge ≥ 15 mmHg, and cardiac index ≤ 2.2 mm. Subsequent outcomes after diagnosis of RCP were 3-year survival, freedom from CAV (angiographic stenosis>30%), non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), development of donor-specific antibodies (DSA) and re-hospitalizations. 1-year freedom from acute cellular rejection (ACR) was also assessed as risk factors for the development of RCP. The study group was compared with a case-controlled group 2:1 matched by age, gender, and era. The average time from transplant to the diagnosis of RCP was 1.5 ± 1.4 years. The RCP group compared to control had significantly lower subsequent 3-year survival, 3-year freedom from CAV, NF-MACE and hospitalizations. There was also a lower freedom from 1-year cellular rejection episodes and DSA in the RCP group compared to control. (See table) Heart transplant patients who develop early RCP appear to have significantly reduced survival. ACR and DSA are associated with the development of RCP. As these patients do not appear to have a reversible cause, appropriate patients may be assessed for re-transplantation. [ABSTRACT FROM AUTHOR]

Cyclosporine (CsA) became available in the US in 1983 and improved clinical outcomes. Another calcineurin inhibitor, tacrolimus (TAC), became available in the 1990s and demonstrated benefit in further reducing rejection. In most heart transplant (HTx) programs, TAC is currently the drug of choice for immunosuppression. However, a switch to CsA does occur due to adverse effects from TAC. It is not well-established that this switch to CSA results in subsequent non-inferior outcomes. Therefore, we reviewed our single center experience to assess for real world potential outcomes. Between 2010 and 2017, we identified 58 HTx patients who were administered CsA in place of TAC mostly due to neurologic adverse effects from TAC. For comparison, a TAC group was matched based on age, sex, baseline renal function and time from transplant. The average time of this switch occurred at 6.6 ± 1.1 months post-transplant. Outcomes included subsequent 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR) and 3-year subsequent survival, freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), and freedom non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). The CsA/MMF group compared to the TAC/MMF group had significantly lower subsequent 3-year survival and worse renal function at 1-year (after the switch to CsA). There was similar subsequent 3-year freedom from CAV and NF-MACE and 1-year rejections between the two groups. (see table) In the current era in a large, single center study there are indications that a switch to CsA from TAC may be inferior in heart transplant recipients. Further investigation with larger numbers is needed to confirm these findings. [ABSTRACT FROM AUTHOR]