HTx Patients Research Articles

Long-term paracorporeal pulsatile mechanical circulatory support in adolescent and adult patients.

OBJECTIVESOur goal was to analyse adverse events in adolescent and adult patients with the Berlin Heart EXCOR and to assess the outcome of a subsequent heart transplant (HTX).METHODSFrom 2006 to 2020, a total of 58 patients (12–64 years old) received a biventricular assist device (BIVAD) at our institution and were included in this study.RESULTSThe causes of biventricular heart failure were nonischaemic cardiomyopathy (62.1%), ischaemic cardiomyopathy (22.4%) and myocarditis (15.5%). The median INTERMACS score was I (I—III). The median age was 49 years (interquartile range, 34–55 years), and 82.8% were male. Causes of death were multiorgan failure (25.0%), septic shock (17.9%), cerebral haemorrhage (14.3%), bleeding (14.3%) and embolic events (14.3%). Major bleeding was more frequent in the patients who died while on BIVADs (60.7 vs 6.7%, P < 0.001). Wound infections were more prevalent in HTX recipients (n = 21, 70.0%). After BIVAD thrombosis, 104 chamber exchanges were performed in 28 patients (48.3%). HTXs were performed in 52.6% of the patients after a BIVAD support time of 316 ± 240 days. The mean time to follow-up of 30 HTX recipients was 1722 ± 1368 days. One-, 6- and 12-month survival after an HTX were 96.7%, 90.0% and 76.7%, respectively. Long-term survival after 5 and 10 years was 69.7%.CONCLUSIONSPump thrombosis, infections and bleeding after receiving a BIVAD did not preclude a successful HTX. Although only 50% of patients with BIVADs were successfully given a transplant, long-term survival after an HTX in patients with BIVAD was noninferior compared to that of other recipients.

Left Heart Chamber Volumetric Assessment by Automated Three-Dimensional Echocardiography in Heart Transplant Recipients.

BackgroundRecently, a new automated software (Heart Model) was developed to obtain three-dimensional (3D) left heart chamber volumes. The aim of this study was to verify the feasibility and accuracy of the automated 3D echocardiographic algorithm in heart transplant (HTx) patients. Conventional manual 3D transthoracic echocardiographic (TTE) tracings and cardiac magnetic resonance (CMR) images were used as a reference for comparison.MethodsThis study enrolled 103 healthy HTx patients prospectively. In protocol 1, left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), left atrial max volume (LAVmax), LA minimum volume (LAVmin) and LV ejection fraction (LVEF) were obtained using the automated 3D echocardiography (3DE) and compared with corresponding values obtained through the manual 3DE. In protocol 2, 28 patients’ automated 3DE measurements were compared with CMR reference values. The impacts of contour edit and surgical technique were also tested.ResultsHeart Model was feasible in 97.1% of the data sets. In protocol 1, there was strong correlation between 3DE and manual 3DE for all the parameters (r = 0.77 to 0.96, p<0.01). Compared to values obtained through manual measurements, LV volumes and LVEF were overestimated by the automated algorithm and LA volumes were underestimated. All the biases were small except for that of LAVmin. After contour adjustment, the biases reduced and all the limits of agreement were clinically acceptable. In protocol 2, the correlations for LV and LA volumes were strong between automated 3DE with contour edit and CMR (r = 0.74 to 0.93, p<0.01) but correlation for LVEF remained moderate (r = 0.65, p < 0.01). Automated 3DE overestimated LV volumes but underestimated LVEF and LA volumes compared with CMR. The limits of agreement were clinically acceptable only for LVEDV and LAVmax.ConclusionSimultaneous quantification of left heart volumes and LVEF with the automated Heart Model program is rapid, feasible and to a great degree it is accurate in HTx recipients. Nevertheless, only LVEDV and LAVmax measured by automated 3DE with contour edit seem applicable for clinical practice when compared with CMR. Automated 3DE for HTx recipients is a worthy attempt, though further verification and optimization are needed.

Assessment of sex- and age-dependency of risk factors for intimal hyperplasia in heart transplant patients using the high resolution of optical coherence tomography

BackgroundIntimal hyperplasia in cardiac allograft vasculopathy (CAVIH) is limiting survival in pediatric and adult patients after heart transplantation (HTx). Analysis of risk factors for CAVIH using the high resolution of intracoronary optical coherence tomography (OCT) is scarce, particularly in children, and recommendations for CAV prevention are largely based on data obtained in adults. Whether the predictive value of risk factors is age- or sex-dependent is unknown. Methods and resultsWe used OCT to test the age- and sex-dependency of established risk factors regarding pathological CAVIH in a cohort of 102 pediatric and adult HTx patients (35% <18 years, 69% male). Modifiable parameters such as lipid values, and the diagnoses of dyslipidemia and diabetes showed age- and sex-dependent differences. Regarding CAVIH, receiver-operating characteristic analysis showed that LDL-c was relevant only in female patients (area under the curve [AUC] 0.79, p = 0.007), and total cholesterol in female (AUC 0.81; p = 0.004) and pediatric patients (AUC 0.73, p < 0.05). The association of dyslipidemia with CAVIH was stronger in adult (odds ratio [OR] 6.33) than in pediatric patients (OR 5.00) and in women (OR 6.00) than in men (OR 4.57). Diabetes was associated with CAVIH only in women (OR 11.25). ConclusionIn our cohort, modifiable risk factors, particularly total cholesterol and dyslipidemia, had a different impact depending on age and sex. Targeting risk factors in selected patients might improve individual CAVIH prevention.

Population Pharmacokinetics of Caspofungin and Dose Simulations in Heart Transplant Recipients.

ABSTRACTThe effect of heart transplantation (HTx) on the pharmacokinetics (PK) of caspofungin is not well-characterized. The aim of this study was to investigate the population PK of caspofungin in HTx and non-HTx patients and to identify covariates that may affect the PK of caspofungin. Seven successive blood samples were collected before administration and at 1, 2, 6, 10, 16, and 24 h after the administration of caspofungin for at least 3 days. This study recruited 27 HTx recipients and 31 non-HTx patients with 414 plasma concentrations in total. A nonlinear mixed-effects model was used to describe the population PK of caspofungin. The PK of caspofungin was best described by a two-compartment model. The clearance (CL) and volume of the central compartment (Vc) of caspofungin were 0.385 liter/h and 4.27 liters, respectively. The intercompartmental clearance (Q) and the volume of the peripheral compartment (Vp) were 2.85 liters/h and 6.01 liters, respectively. In the final model, we found that albumin (ALB) affected the CL of caspofungin with an adjustment factor of −1.01, and no other covariates were identified. In this study, HTx was not found to affect the PK of caspofungin. Based on the simulations, the dose of caspofungin should be proportionately increased in patients with decreased ALB levels.

Comparison of LVAD as BTT with Direct Heart Transplantation

<h3>Purpose</h3> Left ventricular assist devices (LVAD) are often used to support end-stage heart failure and as a bridge-to-transplant therapy (BTT) to heart transplantation (HTx). We compared survival outcomes of continuous-flow LVAD (CF-LVAD) used BTT versus HTx patients. <h3>Methods</h3> Adult HTx and BTT patients were extracted from UNOS database (2005-2020) for analysis. CF-LVADs were implanted at and during the time of listing. Descriptive analysis (Chi-square and Mann-Whitney U testing) were performed using variables such as age, gender, ethnicity, blood groups, ventilator and ECMO usage, ventilator time, and length of stay (LOS). A Kaplan-Meier (K-M) curve compared the survival outcomes, which were analyzed by the log-rank test. Data were expressed as mean ± standard deviation using SPSS 25.0 inc. A p<0.05 value was considered significant. <h3>Results</h3> Out of 76,482 total HTx patients, adult BTT and HTx patients (n=33,297) were analyzed. 9,420 received CF-LVAD whereas n=23,877 underwent direct HTx. Data for both groups showed 74% male, 66% white, 21% black, 8% Hispanic, 3% Asian, and 2% other; mean age 53 ± 12 years; mean LOS 21 ± 25 days; blood groups O-39%, A-40%, B-15%, AB-6%; ECMO usage 1.2%; and ventilator usage 1.7%. 35% received ventilator at the time of transplant (Tx), 26% received ventilator within 3 months of Tx, and 39% received ventilator more than 3 months prior to Tx. When compared between groups, there were significant differences in age (p<0.001), gender (p<0.001), ethnicity (p<0.001), blood groups (p<0.001), ventilator time (p<0.001), ECMO usage (p<0.001), and LOS (p<0.001) and no statistical significance in ventilator usage (p=0.08). K-M graph showed 90% overall survival at 1-year (p=0.150), 86% survival at 3-years (p=0.221), 82% survival at 5-years (p=0.084), and 76% survival at 10-years (p=0.380). <h3>Conclusion</h3> The 10-year analysis period showed no statistical significance in survival differences between HTx patients with and without LVAD. All other variables except ventilator usage had significant differences in the two groups.

Characteristics and Outcome of COVID-19 Infection in Heart Transplantation Recipients in the Netherlands

PurposeImmunocompromised patients are at high-risk for complicated COVID-19 infection. The aim of this study is to describe the characteristics and outcome of heart transplantation (HTx) recipients infected with COVID-19 in the Netherlands.MethodsAll HTx patients with a COVID-19 infection between February 2020 and June 2021, proven by positive polymerase chain reaction-test or positive serology in one of the three heart transplant centers in the Netherlands were retrospectively included. The primary endpoint of this study is all-cause mortality.ResultsCOVID-19 was diagnosed in 54/665 (8%) HTx patients, mean time from HTx was 11±8 years, mean age 53±14 years and 39% were female. Immunosuppressive therapy was reduced in 37%, 21 (39%) patients required hospitalization and all-cause mortality was 6%. Severe COVID-19 disease (hospitalized with ICU admission or mortality) was seen in 7 (13%) patients. Compared to patients with mild (not hospitalized) or moderate (hospitalized, no ICU admission) COVID-19 infection, patients with severe COVID-19 infection were generally older (p=0.007) and had a history of ischemic heart failure (p=0.004) more frequently. Compared to patients with moderate COVID-19 infection, severe COVID-19 patients were transplanted earlier and had a significantly higher body mass index (30±3 vs 26±3; p=0.01). Myocardial infarction, cellular rejection and pulmonary embolism were observed once in three different HTx patients. Physical complaints post-infection persisted with a median of 30 days (IQR 30-83 days) in 16 (39%) cases.ConclusionHTx patients are at increased risk for complicated COVID-19 infection with frequent hospitalization, but mortality is substantially lower than previously described.

Bedside Ultrasound of Internal Jugular Vein for Right Ventricular Function Assessment

<h3>Purpose</h3> Assessing right ventricular (RV) function is important in critically ill heart failure patients and candidacy for mechanical circulatory support options. In addition, diastolic heart failure and fluid overload are the earliest manifestations of rejection and coronary vasculopathy in heart transplant (HTx) recipients. Echocardiographic measurements can be difficult to obtain due to body habitus and poor ultrasound windows. Using ultrasound (POCUS) to assess dynamic changes in internal jugular vein (IJV) dimension could be a quick and reproducible method for bedside RV function assessment. <h3>Methods</h3> Patients scheduled to undergo right heart catheterization (RHC) as their standard of care were prospectively enrolled. While supine, the IJV was imaged at the apex of the sternocleidomastoid. Using M-mode on a portable ultrasound machine, maximum (Dmax) and minimum (Dmin) anteroposterior diameters were measured during normal breathing. Respiratory variation in diameter (RVD) was then calculated using the following equation [(Dmax - Dmin)/Dmax] and expressed as a percentage. RHC was then performed within one hour. <h3>Results</h3> A total of 92 heart failure patients were enrolled with mean age 58 and mean BMI 30.3. IJV dimensions could be assessed in all patients irrespective of BMI. Poor right ventricular (RV) function (right ventricular stroke work index -RVSWI) of <5 g/m/beat/m² was associated with low RVD (16% vs 34%, p = 0.001). An IJV RVD of < 15% had 82% specificity for RVSWI < 5 (ROC AUC 0.774). When using pulmonary artery pulsatility pressure (PAPi), an RVD of <15% had 79% specificity for a PAPi ≤ 2. When combined with a Dmin of 1cm, the specificity increased to 87% (Odds ratio 3.75, p=0.016). 21 of these assessments were in HTx patients, showing similar correlation. A Dmax >1.1cm or RVD <20% individually had specificity of 80% for RAP >=10 mmHg (both with ROC AUC > 0.800). Again, RVSWI <5 was associated with low RVD (19% vs 41%, p = 0.02). In the 14 biopsies performed in HTx patients, 4 were noted with >= 2R acute cellular rejection and all 4 of these had an RAP >=8mmHg, Dmax >1cm and RVD <20% (p<0.01). <h3>Conclusion</h3> Less dynamic IJV diameter variation on POCUS correlates with poor RV function and may be an early indicator of rejection in HTx patients. This assessment can be easily done at bedside regardless of body habitus, with great specificity and can be helpful in the diagnostic management of these patients.

Variances in Humoral Responses to Different Spike Protein Domains After SARS-CoV-2 Vaccination in Lung and Heart Transplant Recipients

PurposeSolid organ transplant recipients are lacking an adequate immune response to SARS-CoV-2 vaccination. Therefore, these patients are still at risk and potentially in need of booster vaccinations. Furthermore, it is important to differentiate between the recipients of distinct organs. The efficacy of SARS-CoV-2 vaccination is usually examined via antibodies specific for the spike protein with assays containing the S1 and receptor-binding-domains (RBD) and rather rarely the S2 domain. To gain information about the humoral response in Tx recipients, it is feasible to compare the immunogenicity of these three domains. To address this, we compared the IgG antibody levels specific for the three spike protein domains in heart (HTx) vs lung (LTx) transplant recipients.MethodsBlood plasma 4-6 weeks after the second dose of SARS-CoV-2 vaccination (85% mRNA) of n=100 LTx and n=40 HTx patients was analysed for S1, S2 and RBD-specific IgG antibodies by Luminex-based multiplex assays. The threshold for positive antibody responses was set separately for each spike domain based on the median MFI + 2σ in an unexposed pre-pandemic control group.ResultsFor all three spike protein domains, HTx patients showed a significantly higher rate of positive IgG responses than the LTx patients (73% vs 43%). The comparison of MFI values for S1-, S2- and RBD-specific IgG further underlines the superior antibody response by HTx patients with higher MFI values for S1 (p = 0.0001, S2 p = 0.008, RBD p < 0.0001). In the LTx cohort, MFI values for S2- (p < 0.0001) as well as for RBD-specific IgG (p < 0.0001) were higher than for S1. The same applies for S2 vs S1 (p < 0.0001) and RBD vs S1 (p = 0.0018) in the HTx cohort. Comparing the MFI of S2 vs RBD, the levels of domain-specific IgG were higher for S2 than RBD in both LTx (p < 0.0001) and HTx patients (p = 0.0914).ConclusionHTx patients exhibit a moderately good IgG response to vaccination while LTx recipients show lower antibody responses. Based on the more efficient antibody production against S2 as opposed to the RBD and especially S1-domain, the S2-specific IgG response should be taken into consideration when evaluating the general immune response and the resulting protection after SARS-CoV-2 vaccination in transplant recipients. Both groups of patients might benefit from booster vaccinations.

Metabolic Syndrome in Heart Transplantation: An Underestimated Risk Factor?

<h3>Purpose</h3> Metabolic Syndrome (MS) is a multifactorial condition that increases the risk of cardio-vascular events, it's frequent in Heart transplant (HTx) candidates and worsens with immunosuppressive therapy. Aim of the study was to analyse the impact of MS on long-term outcome of HTx patients. <h3>Methods</h3> MS was defined through the presence of at least 3 of the following factors: • -Triglyceride ≥150mg/dl or drug treatment for hypertriglyceridemia • -HDL <40mg/dl for men and <50mg/dl for women • -Blood glucose ≥100mg/dl or diabetes mellitus • -Arterial pressure ≥130/80 or hypertensive drug treatment • -BMI>30 In 349 HTx patients since 2007, mortality and morbidity predictors were evaluated. <h3>Results</h3> MS was present in 35% of patients pre-HTx and 47% within the first year of follow-up. Five-year survival in patients with pre-HTx MS was worst (65% vs 78%, p<0.01), as well as in those with MS in the first year of follow-up (78% vs 89%, p<0.01). At the univariate analysis, risk factors for mortality were recipient age (HR 1.07, 1.04-1.09, p<0.01), pre-HTx MS (HR 1.86, 1.29-2.69, p<0.01), pre-HTx hypertension (HR 2.46, 1.70-3.55, p<0.01), pre-HTx hypertriglyceridemia (HR 1.50, 1.04-2.18, p=0.03), chronic renal failure (HR 2.95, 2.03-4.27, p<0.01), MS and diabetes at 1-year follow-up (HR 2.00, 1.25-3.19, p<0.01; HR 2.02, 1.27-3.23, p<0.01, respectively). The last two resulted also risk factors for CAV (HR 1.86, 1.16-2.99, p=0.01; HR 1.67, 1.03-2.69, p=0.04, respectively). MS at 1-year follow-up determined a significant higher risk to develop CAV at 5- and 10-year follow-up (25% vs 14% and 44% vs 25%, p<0.01). <h3>Conclusion</h3> MS is an important risk factor for both mortality and morbidity post-HTx, suggesting the need for a strict monitoring of metabolic disorders with a careful nutritional follow-up in HTx patients.

Outcomes of COVID-19 in an Advanced Heart Failure Practice: A Single Center Study

PurposePatients with heart failure (HF) carry an increased risk of mortality and morbidity with COVID-19. The objective of this study is to compare the outcomes of HF (stage C or D), Left Ventricular Assist Device (LVAD) or Heart Transplant (HTx) patients who were diagnosed with COVID-19.MethodsOut of 2635 patients followed in our program (HF=2234, LVAD=167, HTx=234), 96 patients diagnosed with COVID-19 infection between March 2020 to January 2021 were included in this study. Hospital length of stay (LOS), requirement for mechanical ventilation, and mortality rate were compared. Kaplan-Meier analysis was used to compare survival.ResultsThe distribution of COVID among the 96 patients was: HTx = 15.8%, LVAD = 9.6% and HF = 1.9%. Table 1 outlines the clinical characteristics and outcomes of the 3 cohorts. A total of 49 patients were hospitalized: 18 (41.9%) HF, 8 (50%) LVAD, and 23 (62.2%) HTx. Of the hospitalized patients, 5 (27.8%) required ICU care in the HF, 2 (25%) LVAD, and 6 (26.1%) HTx groups. The median ICU LOS was significantly higher in HTx (24 days, p=0.04) when compared to HF (10 days) group. HTx patients had the highest 180-day mortality, followed by LVAD, and then HF patients (18.9%, 12.5% and 11.6%, respectively). All deaths occurred within 50 days from diagnosis. Among LVAD patients, COPD was the highest predictor of mortality (69% prevalence).ConclusionThis report is among the first to describe the impact of COVID-19 on a comprehensive advanced heart failure (HF) practice. Our data highlights the risks of morbidity and mortality faced by HF and immunocompromised patients with COVID-19 infection. A mortality rate of 19% with HTx patients acquiring COVID is ominous (even if better than reported rates of 25%). Likewise, though not as high, mortality rates for COVID infected advanced HF and LVAD patients of 12% each represent substantial risk. Protecting these patients with all possible preventative and therapeutic options is an essential imperative.

Heart Transplantation in Systemic Diseases: How Far Can We Go?

Purpose Few data are already available on the follow up of heart transplant (HTx) patients for systemic rare diseases. Aim of the study was to assess the cardiovascular, non-cardiovascular outcome and quality of life (QoL) of heart transplant patients with systemic diseases. Methods We have reviewed all the cases of HTx in rare diseases performed in our Cardiothoracic Department from 1985 to Feb 2021. QoL was assessed by SF-36 questionnaire. Results Since 1985, out of the 680 HTx performed at our Centre, 25 patients had a systemic rare disease (cardiac amyloidosis, Danon, Becker distrophy, see Fig 1) as cause of advanced heart failure (HF) needing of HTx. Mean age was 45±15 years old, mostly males (76%); 3 patients were in urgent list. The peripheral muscular involvement was present in 11 cases; however, almost all patients retained the capacity of walking. Donors mean age was 37±11 and 16 (64%) were male. Eleven (44%) were considered non-standard donors (ischemic time >4 hours in 5 (20%), cardiac arrest or LVEF<50% or coronary artery disease in 3 (12%), previous drug abuse in 2 (8%). Considering the cardiovascular outcome, the survival was 100% at 30-days, 96% and 90% at 1 and 5 years after HTx in a median follow up of 72 (range 7-318) months. Rejection >2 grade was in 6 (24%), while cardiac allograft vasculopathy in 4 (16%). Related the non-cardiovascular outcome, there was ocular and muscular worsening in 6 (24%) and 9 (36%) cases, while 3 (12%) developed severe psychosis. Lastly, the SF-36 questionnaire showed lower scores for the items related to Physical Component Summary, while similar scores compared to the general population for the Mental Component Summary. Conclusion In a median follow up of 5 years, HTx patients with systemic rare disease showed a satisfied general survival. The ocular and muscular worsening related to the systemic disease could be very frequent, conditioning the QoL. The relapse of the systemic disease is a rare event, although possible. Few data are already available on the follow up of heart transplant (HTx) patients for systemic rare diseases. Aim of the study was to assess the cardiovascular, non-cardiovascular outcome and quality of life (QoL) of heart transplant patients with systemic diseases. We have reviewed all the cases of HTx in rare diseases performed in our Cardiothoracic Department from 1985 to Feb 2021. QoL was assessed by SF-36 questionnaire. Since 1985, out of the 680 HTx performed at our Centre, 25 patients had a systemic rare disease (cardiac amyloidosis, Danon, Becker distrophy, see Fig 1) as cause of advanced heart failure (HF) needing of HTx. Mean age was 45±15 years old, mostly males (76%); 3 patients were in urgent list. The peripheral muscular involvement was present in 11 cases; however, almost all patients retained the capacity of walking. Donors mean age was 37±11 and 16 (64%) were male. Eleven (44%) were considered non-standard donors (ischemic time >4 hours in 5 (20%), cardiac arrest or LVEF<50% or coronary artery disease in 3 (12%), previous drug abuse in 2 (8%). Considering the cardiovascular outcome, the survival was 100% at 30-days, 96% and 90% at 1 and 5 years after HTx in a median follow up of 72 (range 7-318) months. Rejection >2 grade was in 6 (24%), while cardiac allograft vasculopathy in 4 (16%). Related the non-cardiovascular outcome, there was ocular and muscular worsening in 6 (24%) and 9 (36%) cases, while 3 (12%) developed severe psychosis. Lastly, the SF-36 questionnaire showed lower scores for the items related to Physical Component Summary, while similar scores compared to the general population for the Mental Component Summary. In a median follow up of 5 years, HTx patients with systemic rare disease showed a satisfied general survival. The ocular and muscular worsening related to the systemic disease could be very frequent, conditioning the QoL. The relapse of the systemic disease is a rare event, although possible.

COVID Pandemic and Social Mitigations Decrease Hospitalizations for Heart Transplant Patients

<h3>Purpose</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusion</h3> 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.

The Effects of Hypomagnesemia Post Heart Transplantation

<h3>Purpose</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusion</h3> Mildly to moderately low hypomagnesemia did not have significant adverse effects in heart transplant patients. Aggressive Mg replacement may not be essential.

Is There Heterogeneity on Outcome of Hospitalized Heart Transplant Patients with COVID-19 Infection Across the US?

PurposeThe 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.MethodsBetween 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.ResultsOf 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.ConclusionCOVID-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.

NP Telehealth Blood Pressure Management in Heart Transplant Patients - A Single Center Experience

<h3>Purpose</h3> Hypertension (HTN) is common in heart transplant (HTx) recipients due to calcineurin inhibitors, steroids and renal disease. HTN increases risk of transplant vasculopathy, left ventricular hypertrophy, and renal failure, emphasizing need for adequate control. We assessed the effectiveness of nurse practitioner (NP) telehealth visits in achieving adequate blood pressure (BP) control in HTx patients (pts). <h3>Methods</h3> A retrospective study included HTx pts scheduled for a video or telephone visit with a HTx NP for BP management between Sept 2020 and July 2021. Pts hypertensive during a clinic visit, and requiring initiation or adjustment of antihypertensives, were referred for a follow up NP telehealth visit. Target BP goal was <130/80. Pts were instructed to obtain sitting BP 1-2 times/day at home, 2 hours after taking BP medications. Data obtained: BP measurements at clinic and with each NP telehealth visit, number of days from intervention to attainment of goal BP, number of NP visits conducted, and number of antihypertensive agents required to reach goal BP. <h3>Results</h3> Of 73 pts, 60 were followed by NP until target BP reached, 13 pts were hospitalized, lost to follow up, transferred care locally, or still undergoing titration of antihypertensives by NP. Of the 60 pts, average number of days to attain goal BP was 40.7 days, 83% of pts required 1-2 NP telehealth visits to attain goal BP, 78% of pts required 1-2 antihypertensive agents to attain goal BP. <h3>Conclusion</h3> NP telehealth BP management was effective in achieving target BP efficiently in HTx pts. Further studies evaluating long term BP control and optimal frequency of visits should be conducted.

Two Cases of BK Polyoma Virus Nephropathy in Patients with Isolated Heart Transplantation: Clinical Usefulness of Urinary Cytology

<h3>Introduction</h3> BK polyoma virus (BKpV) nephropathy (BKpVN) has been often reported in patients with kidney transplantation, whereas reports regarding BKpVN in patients with heart transplantation (HTx) is still sparse. <h3>Case Report</h3> We recently encountered two patients who developed BKpVN after HTx. Both patients (Case 1 and 2) coincidentally received HTx at the age of 56. A standard triple-drug regimen consisting of tacrolimus, mycophenolate mofetil (MMF), and a corticosteroid was started after surgery and the regimen was converted to everolimus (EVL) with reduced tacrolimus within 6 months after HTx because of donor transmitted atherosclerosis in both patients. Case 1 further underwent percutaneous coronary intervention 3.5 years after HTx. Despite renal-sparing immunosuppresion, values of creatinine begun to increase after HTx in both patients and they were diagnosed with BKpVN through high viral DNA copy number in the urine and blood. Regarding case 1, pathological analysis of kidney biopsy specimens disclosed interstitial infiltrate with lymphocytes associated with tubular injury which also lead to the diagnosis of BKpVN. Retrospectively, both patients were positive for decoy cell within 1 year after HTx therefore, these patients should have been recognized as high risk for BKpVN. After the diagnosis of BKpVN, immunosuppressive regimen of them was further changed to minimum dose of EVL (a trough concentration of 6-7 ng/ml) and MMF (500 mg daily) respectively under the guidance of myocardial biopsy and they have been uneventful for over a year after the diagnosis of BKpVN despite severe chronic kidney disease. <h3>Summary</h3> We presented two rare cases of BKpVN after HTx. In our institution, urinary cytology is regularly examined if there are decoy cells which we think are the sign of over immunosuppression. However, decoy cells detected by urinary cytology also suggest that there is subclinical BKpV infection. Urinary cytology, a noninvasive and cost-effective examination, should be routinely performed for the risk assessment of BKpVN even in HTx patients, since detecting decoy cell would be helpful for the early diagnosis of BKpVN.

Is Donor/Recipient Cytomegalovirus Mismatch Truly Associated with Increased Risk for Cardiac Allograft Vasculopathy in the Current Era?

<h3>Purpose</h3> Cytomegalovirus (CMV) infections have been associated with the subsequent development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). This is most prominent with patients receiving a donor with positive CMV serology when the patient is CMV serology negative. This mismatched patient cohort was subsequently reviewed for the development of CMV serology positivity, CMV syndrome, and CMV disease (specific organ involvement). <h3>Methods</h3> Between 2010 and 2016, we assessed 138 HTx patients who had CMV mismatch (donor positive/recipient negative). Patients were treated with CMV prophylaxis with Valcyte for 1 year. CMV patients were then divided (data at 1-year) into those that developed serology positive CMV on IgG, CMV syndrome (who presented with fever, chills, and sweats), CMV disease (organ specific disease, such as retinitis, peritonitis, gastroenteritis). All groups were then assessed for 5-year survival and the development of CAV by angiography. <h3>Results</h3> In CMV mismatched patients, there was no significant difference in 5-year survival or freedom from angiographic CAV in those patients with clinical CMV (asymptomatic IgG positive, CMV syndrome, CMV disease groups) compared to the asymptomatic IgG negative group. <h3>Conclusion</h3> In the current era, CMV mismatch patients (donor positive/recipient negative CMV serology) do not appear to be at increased risk for poor outcome. Valcyte prophylaxis for 1 year may be beneficial.

Experience with Eculizumab in Highly Sensitized Patients Undergoing Heart Transplantation

<h3>Purpose</h3> The use of eculizumab, which is a complement blockade inhibitor, has been demonstrated to be efficacious in highly sensitized patients undergoing heart transplantation (HTx). The hypothesis is that the complement blockade protects the heart from hyperacute rejection and from other potential adverse responses. It is postulated that the complement blockade may downregulate antibody production. We reviewed our single center study using eculizumab for highly sensitized patients to assess for post-transplant outcomes. <h3>Methods</h3> Between 2013 and 2020, we assessed 29 HTx patients who are highly sensitized, defined as calculated panel reactive antibody (cPRA) greater than 70% who underwent HTx with eculizumab therapy perioperatively. In all cases, donor-specific antibody (DSA) was crossed at the time of transplant but with a negative CDC prospective crossmatch. Eculizumab was given intraoperatively, post-op day 1, post-op day 7, and then given weekly for the first month and monthly for the second and third months post-transplant. The development of hyperacute rejection, antibody-mediated rejection, hemodynamic compromise rejection, and development of de novo DSA in the first-year post-transplant were assessed. <h3>Results</h3> Eculizumab use in highly sensitized patients resulted in 93.1% 1-year survival and no patient developing hyperacute rejection. There were 11 first-year AMR episodes noted, with one episode associated with hemodynamic compromise. All antibody levels began to wane in the first-year post-transplant. <h3>Conclusion</h3> The use of eculizumab in highly sensitized patients (crossing DSA at transplant) appears to be effective in allowing these patients to undergo safe heart transplantation.

Does the Degree of Diastolic Dysfunction in the First Year After Heart Transplant Affect Subsequent Outcomes?

<h3>Purpose</h3> Diastolic dysfunction in the first year post-heart transplantation (HTx) is not uncommon. This can be due to hypertension, rejection, or calcineurin inhibitor therapy treatments. It has not been well established whether this first-year diastolic dysfunction affects outcome post-HTx. <h3>Methods</h3> Between 2010 and 2016, we assessed HTx patients who developed diastolic dysfunction by echocardiography in the first year post-HTx. Patients with diastolic dysfunction were further divided into groups with mild, moderate, and severe diastolic dysfunction as determined by echo parameters. These patients were compared to patients who survived the first year who had no evidence of diastolic dysfunction. Subsequent 5-year survival, cardiac function (echocardiogram ejection fraction), cardiac allograft vasculopathy (CAV: stenosis ≥30% by angiography), and non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke) were assessed for the patient groups. <h3>Results</h3> Patients with diastolic dysfunction had significantly lower 5-year survival and freedom from NF-MACE compared to the control group. The development of CAV at 5 years post-HTx was not significantly different among the study groups. There was not a linear correlation of worsening diastolic dysfunction to poorer outcomes. (See table.) <h3>Conclusion</h3> Any diastolic dysfunction appears to be a risk factor for poor outcomes post-HTx and should be addressed in terms of comorbid problems.

Variability in Donor-Derived Cell-Free DNA Levels Predicts Mortality Risk in Heart Transplant Recipients

<h3>Purpose</h3> Longitudinal surveillance of heart transplant (HTx) recipients using donor-derived cell-free DNA (dd-cfDNA) allows non-invasive detection of molecular injury patterns. We hypothesized that variability in dd-cfDNA levels over time identifies patients at risk of adverse outcomes. <h3>Methods</h3> 72 adult HTx patients monitored with gene expression profiling (GEP) and dd-cfDNA (AlloMap, AlloSure; CareDx Inc., Brisbane, CA) at our center were included. Variability (ASV) was defined as standard deviation of the 3 most recent (3-value) or all (all-value) sequential dd-cfDNA results and scaled x 10 for analysis (ASV*10). We used a Cox proportional hazards model to assess the association between ASV and mortality and a survival classification and regression tree (CART) algorithm to define a threshold for increased mortality risk. <h3>Results</h3> Patients had a median of 6 (IQR 4-9) paired GEP/dd-cfDNA results spaced 40.8 (IQR 31.5 - 66.1) days apart. 48.6% of patients had dd-cfDNA below the assay limit of detection (<0.12%); the remainder had a median dd-cfDNA of 0.17% (IQR: 0.12 - 0.45%) and a mean all-value ASV of 0.24 (SD: 0.40). ASV*10 of patients who died (2.62, SD 2.66) trended higher than of those who survived (0.54, SD 1.10) over a median follow-up of 480 days (IQR 244 - 859). In a univariate Cox model, the 3-value ASV*10 was associated with an increased risk of mortality (HR 1.66, 95% CI 1.14 - 2.41, p<0.009). Only a trend was evident after multivariate adjustment <b>[Figure 1a]</b>. Using a CART algorithm, a 3-value ASV*10 of 2.97 discriminated between patients at high and low risk of mortality after HTx <b>[Figure 1b]</b>. <h3>Conclusion</h3> In this proof-of-concept study evaluating the clinical utility of longitudinal dd-cfDNA results, we found that higher variability in dd-cfDNA over time was associated with an increased risk of mortality after HTx. Additional studies utilizing larger datasets are needed to validate and expand on our findings.