Non-fatal Major Adverse Cardiac Events Research Articles

Three year post heart transplant outcomes of desensitized durable mechanical circulatory support patients

The risks and benefits of desensitization therapy (DST) in highly sensitized mechanical circulatory support (MCS) patients are not well known. We investigated 3 year post-transplant outcomes of desensitized durable MCS patients. Among 689 consecutively enrolled heart transplantation recipients between 2010 and 2016, we categorized them into Group A (desensitized MCS patients, n=21), Group B (desensitized non-MCS patients, n=28) and Group C (all nondesensitized patients, n=640). Post-transplant outcomes included the incidence of primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, antibody mediated rejection (AMR) and infectious complications. The types of DST in Groups A and B were similar and included combinations of rituximab/intravenous immunoglobulin and plasmapheresis/bortezomib. Group A, compared with Group B, showed significantly higher pre-DST panel reactive antibody (PRA) (92.2±9.8 vs. 83.3±15.6, P=0.007) and higher PRA reduction after DST (-22.2±26.9 vs. -6.3±7.5, P=0.015). Groups A and C showed comparable primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, and AMR. Although statistically not significant, Group A showed numerically higher 3-year freedom from AMR than Group B. Infectious complications were similar in both Groups A and B. DST for MCS patients showed significant PRA reduction, resulting in an expansion of the donor pool. The post-transplant outcome of desensitized MCS patients showed comparable clinical outcomes to non-desensitized control patients in the same study period, revealing the safety and efficacy of DST.

Characteristics and outcomes of heart transplant recipients with a pretransplant history of malignancy

We aimed to investigate the characteristics and outcomes of HTx recipients with a history of pretransplant malignancy (PTM). Among 1062 HTx recipients between 1997 and 2013, 73 (7.1%) patients had PTMs (77 cancer cases). We analyzed post-HTx outcome, recurrence of PTM, and development of de novo malignancies. Post-HTx outcome included overall survival, 10-year survival, 10-year freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Four most common PTMs were lymphoproliferative disorders (18.2%), prostate cancers (18.2%), non-melanoma skin cancers (18.2%), and breast cancers (13.0%). Median time from PTM and HTx was 9.0 years. During a median follow-up of 8.6 years after HTx, patients with PTM, compared to those without, showed significantly higher incidence of posttransplant malignancies (43.8% vs. 20.8%, p < .001) including 9.6% (n=7) of PTM recurrences. However, patients with PTM, compared to those without, showed comparable overall survival, 10-year survival, 10-year freedom from CAV, NF-MACE, ATR, ACR, and AMR. Therefore, a history of PTM should not disqualify patients from HTx listing, while further research is necessary for early detection of posttransplant malignancies in these patients.

Change in First-year Intravascular Ultrasound Results Predicts Adverse Events in Heart Transplant Recipients: Implications for Clinical Trial Endpoints.

Heart transplantation (HTx) is an established therapeutic option for patients with advanced heart failure who are refractory to conventional guideline-directed treatments. This study aimed to reassess whether intravascular ultrasound variables could predict adverse events after HTx in the modern era. One hundred primary HTx recipients with available serial intravascular ultrasound examination results of the left anterior descending artery 4-8 wk and 1 y after HTx were enrolled, with an average follow-up duration of 5.7 y. The primary endpoint was a composite of all-cause death, nonfatal major adverse cardiac events, and angiographic cardiac allograft vasculopathy. Forty-three patients developed primary endpoints. The baseline maximal intimal thickness was independently associated with the primary endpoint (hazard ratio, 8.24; 95% confidential interval [CI], 3.21-21.21; P < 0.001), and the optimal cutoff value was 0.64 mm. A change in the plaque atheroma volume in a proximal 20-mm segment from the left anterior descending artery bifurcation >1.05 mm 3 /mm (hazard ratio, 2.75; 95% CI, 1.28-5.89; P = 0.009) and a change in the first-year maximal intimal thickness >0.27 mm (hazard ratio, 2.63; 95% CI, 1.05-6.56; P = 0.04) were independent predictors of the primary endpoint 1 y after intravascular ultrasonography. The aforementioned important clinical implications of intravascular ultrasound parameters are useful predictors of outcomes, which may be considered endpoints in modern clinical HTx trials.

The number of risk factors not at target is associated with cardiovascular risk in a type 2 diabetic population with albuminuria in primary cardiovascular prevention. Post-hoc analysis of the NID-2 trial

BackgroundNephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes.MethodsIntervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0–1 risk factor (absent/low); 2–3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase.ResultsAbsent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04–3.52, P = 0.038 and 1.96, 95%CI 1.02–3.8, P = 0,045, respectively, vs absent/low risk group).ConclusionsThis post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk.Clinical Trial RegistrationClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925

Heart Transplantation With Older Donors: Should There Be an Age Cutoff?

Heart transplantation remains limited by donor availability. Currently, only some programs accept older donors, and their use remains contentious. We compared outcomes of heart transplant recipients who received donor hearts ≥55 years with those who received donor hearts <55 years. Records of first-time adult heart transplant recipients between 2010 and 2019 were reviewed. Endpoints included 30-day and 1-, 3-, and 5-year survival; freedom from cardiac allograft vasculopathy; freedom from nonfatal major adverse cardiac events; and freedom from any rejections. The effect of donor age ≥55 years was analyzed with Cox proportional hazards modeling, 1:2 propensity score matching, and Kaplan-Meier survival analysis. Sixty-six patients received donor hearts ≥55 years and 766 received donor hearts <55 years. In the unmatched cohort, there was no significant difference in survival between the 2 groups at 30 days (93.9% vs 97.3%, P=.127), 1 year (87.9% vs 91.6%, P=.325), 3 years (86.4% vs 86.5%, P=.888), or 5 years (78.8% vs 83.8%, P=.497). The ≥55 years group had a significantly lower freedom from cardiac allograft vasculopathy and fatal major adverse cardiac events. In propensity-matched patients, recipients of donors ≥55 years had similar survival and freedom from cardiac allograft vasculopathy but significantly lower 1-year (76.7% vs 88.3%, P=.026), 3-year (68.3% vs 84.2%, P=.010), and 5-year (63.3% vs 83.3%, P=.002) freedom from nonfatal major adverse cardiac events when compared to recipients of younger donors. Carefully selected older donors can be considered for a carefully selected group of recipients with acceptable outcomes.

A Novel Biomarker Scoring System Alone or in Combination with the GRACE Score for the Prognostic Assessment in Non-ST-Elevation Myocardial Infarction

PurposeThe Global Registry of Acute Coronary Events (GRACE) score has proven value in predicting short-term prognosis in non-ST-elevation myocardial infarction (NSTEMI), but it has only moderate discrimination for long-term outcomes. The purpose of this study is to develop and test a multi-biomarker score for better risk stratification and indication of 2-year risk in patients with NSTEMI.Patients and MethodsA total of 6076 consecutive patients with NSTEMI (66 [59–73] years, 73.1% males) admitted at Zhongshan Hospital, Fudan University were collected in this observational, prospective study between 2012 and 2018 with a 24-month follow-up. The primary endpoint was all-cause death and non-fatal major adverse cardiac events (MACE). A biomarker score ranged from 0 to 12 was constructed. The predictive power of the biomarker score was evaluated alone or combined with the GRACE score by C-statistic, net reclassification index (NRI) and integrated discrimination index (IDI).ResultsDuring a 2-year follow-up, all-cause death occurred in 159 patients (2.6%), and non-fatal MACEs were presented in 709 patients (11.7%). When added to the GRACE score, the biomarker score demonstrated better prognostic accuracy, patient reclassification and risk discrimination for both mortality and non-fatal MACEs at 2 years by improving the C-statistic from 0.714 (0.671–0.756) and 0.623 (0.600–0.646) to 0.851 (0.820–0.882) and 0.721 (0.702–0.741) with NRI >25% (P<0.001) and IDI >0.30 (P<0.001).ConclusionThe single use of biomarker score could markedly enhance the prognostic value of concurrent risk stratification tools for 2-year mortality and non-fatal MACEs in NSTEMI. The GRACE score with incorporation of the biomarker score led to more accurate risk reclassification and warrants more consideration in further NSTEMI management.

Heart transplant recipient 1-year outcomes during the COVID-19 pandemic.

The COVID‐19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post‐transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1‐year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted during the same months between 2011 and 2019 (n = 482). Endpoints included subsequent 1‐year survival, freedom from cardiac allograft vasculopathy, any‐treated rejection, acute cellular rejection, antibody‐mediated rejection, nonfatal major adverse cardiac events (NF‐MACE), and hospital and ICU length of stay. Patients transplanted during the pandemic had similar 1‐year endpoints compared to those of patients transplanted from years prior apart from 1‐year freedom from NF‐MACE which was significantly higher for patients transplanted during the pandemic. Despite necessary changes being made to outpatient management of heart transplant recipients, heart transplantation continues to be safe and effective with similar 1‐year outcomes to years prior.

What is the Meaning of Culture Negative Leukocytosis Immediately After Heart Transplantation?

<h3>Purpose</h3> Leukocytosis following heart transplantation (HTx) is common and most likely is due to high dose corticosteroid therapy immediately post-HTx. However, infection must be excluded with pan cultures. The use of anti-T lymphocyte globulin (ATG) induction may also cause leukocytosis due to an inflammatory reaction. We sought to determine whether culture negative leukocytosis in the first week after HTx has deleterious consequences. <h3>Methods</h3> Between 2010 and 2020, we assessed 114 patients who developed leukocytosis within the first week following HTx. Patients were divided into groups by the severity of leukocytosis (WBC 11-14.9 x 10⁹/L, 15-19.9 x 10⁹/L, ≥20 x 10⁹/L). Patients were asymptomatic, had negative cultures, and were not treated with antibiotics. The study population was compared to patients without leukocytosis following HTx. Development of infections in the ensuing 1-6 weeks postoperatively were assessed. Furthermore, 1-year outcomes including survival, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejection (any treated rejection [ATR], acute cellular rejection [ACR], antibody-mediated rejection [AMR]) were evaluated. <h3>Results</h3> Higher levels of asymptomatic leukocytosis (>15 x 10⁹/L) immediately after HTx appears to signal possible subsequent infection. However, it does not lead to unacceptable 1-year outcomes including survival, or freedom from CAV, NF-MACE, or rejection. Induction therapy with ATG does not contribute to the leukocytosis. (See table.) <h3>Conclusion</h3> Continued monitoring should be pursued for asymptomatic culture negative leukocytosis immediately after heart transplantation.

Treatment and Outcome of AL Amyloid After Heart Transplantation: Is It Viable?

<h3>Purpose</h3> In the past, light chain (AL) amyloid has been associated with poor outcomes after heart transplantation (HTx), mainly due to its complicated course. Many AL amyloid patients will require stem cell transplant following HTx. It is not known whether these patients have acceptable outcomes after HTx. <h3>Methods</h3> Between 2008 and 2020, we assessed all AL amyloid patients undergoing HTx. Patients were divided into those that required stem cell therapy and those that did not. Both groups were compared to age-matched control that did not have amyloid. Endpoints included 1-year survival, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejection (any treated rejection [ATR], acute cellular rejection [ACR], antibody-mediated rejection [AMR], biopsy-negative rejection [BNR]). <h3>Results</h3> There was no difference between AL amyloid patients with and without stem cell therapy in 1-year survival, or freedom from CAV, NF-MACE, or ATR. Compared to matched controls, post-transplant outcomes were similar. (See table.) <h3>Conclusion</h3> In the current era, therapies for AL amyloid post-heart transplant appear successful with acceptable outcome compared to non-amyloid patients. AL amyloid is not a contraindication for heart transplantation.

Does Overnight Heart Transplantation Lead to Worse Outcomes? Results from a High Volume Transplant Center

<h3>Purpose</h3> Prior studies showed an association between nighttime surgery and worse outcomes after kidney and liver transplants. We evaluated if outcomes are inferior after nighttime heart transplants. <h3>Methods</h3> An institutional registry identified 1087 adult heart transplants between 2010 and 2020. Overnight transplants (incision time 7pm-5am, n=541) were compared to daytime transplants (incision time 5am-7pm, n=546). Outcomes included in-hospital complications, 5-year survival, 5-year incidence of non-fatal major adverse cardiac events (NF-MACE) (myocardial infarction, new congestive heart failure, percutaneous coronary intervention, pacemaker implant, stroke) and treated rejections, with death as a competing risk <h3>Results</h3> Nighttime transplants had similar recipient/donor profile to daytime transplants, except for more pre-transplant blood transfusions (41.2% vs. 33.9%, p=0.01) and geographically closer donors (63, IQR 24-299 vs. 98, IQR 35-348 miles, p=0.02). They had longer aortic cross clamp time (90, IQR 73-111 vs. 86, IQR 70-106 mins, p=0.02) but similar rates of primary graft dysfunction (14.3% vs. 16.5%, p=0.3) and reoperation for bleeding (3.1% vs. 4.2%, p=0.35) compared to daytime transplants. There was no difference in 5-year survival (Figure), NF-MACE (28%, 95% CI 23.4-32.9 vs. 31.4%, 95% CI 26.7-36.3, p=0.33) and rejections (22.9%, 95% CI 19.1-26.9 vs. 19.6%, 95% CI 20.4-28.0, p=0.65) between nighttime and daytime surgery. In multivariate analysis, nighttime surgery was not associated with increased mortality, after adjusting for baseline peripheral vascular disease, multiorgan transplant, urgent status, pre-transplant MCS/inotrope, MELD score, and ischemic time (HR 0.92, 95% CI 0.59-1.42, p=0.69) <h3>Conclusion</h3> Overnight transplants had outcomes comparable to daytime transplants in a high-volume transplant center. We attribute this to system-based practices to improve patient safety.

Intra-Aortic Balloon Pump or Impella 5.0/5.5 as a Bridge to Heart Transplantation?

<h3>Purpose</h3> Impella 5.0/5.5 provide superior hemodynamic support and left ventricle unloading compared to intra-aortic balloon pump (IABP) but may be associated with more device-related complications. Limited comparative data exists on their use in patients with advanced heart failure awaiting transplantation. We evaluated patients bridged to transplant (BTT) with IABP versus Impella 5.0 or 5.5 <h3>Methods</h3> A prospective institutional registry identified 142 patients undergoing either IABP (n=77) or Impella 5.0/5.5 (n=65) implantation as BTT between 1/1/2017 and 12/31/2020. Analysis included only patients who were transplanted. Outcomes included 6-months survival, 6-months freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, pacemaker implant, stroke) and treated rejections <h3>Results</h3> The percentage of transplanted patients who were bridged with either Impella 5.0/5.5 or IABP increased from 19% (19/100) in 2017 to 28.6% (30/105) in 2020. Successful transplantation occurred in 75% (49/65) patients bridged with Impella and 68.9% (53/77) bridged with IABP (p=0.39). Among transplanted patients, several baseline characteristics differed between the Impella and IABP groups, including longer device duration, more pre-transplant packed red blood cell (PRBC) transfusions, and more multi-organ transplants in Impella patients (all p<0.05). At 6 months, post-transplant survival and stroke rates were similar (both p>0.5). In patients bridged with IABP, rates of rejections trended lower, while rates of CAV and NF-MACE were numerically higher, primarily driven by higher rates of pacemaker implant (Table) <h3>Conclusion</h3> The use of IABP and Impella 5.0/5.5 as BTT is increasing, with excellent 6-month survival. Registry analysis may help quantify the impact of increased blood product and induction therapy requirement associated with Impella 5.0/5.5 use

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.

Is Sacubitril/Valsartan a Risk Factor for Vasoplegia/Primary Graft Dysfunction After Heart Transplantation?

<h3>Purpose</h3> Primary graft dysfunction (PGD) is seen in 7-29% of heart transplant (HTx) patients. Many of these patients with PGD also develop significant vasoplegia which requires high doses of intravenous vasoconstrictors. Outcomes of these patients with severe PGD is compromised within 30 days after HTx. Risk factors for the development of severe PGD have included angiotensin-converting enzyme inhibitors (ACEi). There may be a connection between ACEi and the kallikrein-kinin system whereby bradykinin is increased, thus resulting in more vasoplegia and PGD. It is not known whether the new drug, sacubitril/valsartan (S/V), is also a risk factor for the development of vasoplegia/severe PGD as bradykinin is also increased with sacubitril. Therefore, we reviewed our large HTx program to see if there is a correlation with S/V as a risk factor for this complication. <h3>Methods</h3> Between 2015 and 2020, we assessed 65 HTx patients who were on S/V at the time of transplantation. Vasoplegia was defined as requiring more than 2 vasoconstricting drugs with systolic blood pressure still <90 mmHg. PGD was defined as per the ISHLT classification scheme (within 24 hours post-transplant). These patients on S/V were compared to patients on ACEi/ARB (1:1 control for age, sex, transplant year). Outcomes included survival, freedom from cardiac dysfunction, and freedom from non-fatal major adverse cardiac events in the first year after HTx. <h3>Results</h3> Compared to ACEi/ARB, S/V had similar risk for the development of vasoplegia or severe PGD. Furthermore, 1-year survival, freedom from cardiac dysfunction, and freedom from NF-MACE were not significantly different between groups. (see table) <h3>Conclusion</h3> Patients undergoing HTx on S/V do not appear to be at risk for vasoplegia or severe PGD.

The Outcome of West Nile Virus Infection After Heart Transplantation

<h3>Purpose</h3> West Nile Virus after heart transplant (HTx) is rare. However, it has occurred in our large, single-center heart transplant program. West Nile Virus is reportedly spread by mosquitoes and has been seen in various areas within the United States. We now report on our experience. <h3>Methods</h3> Between 2013 and 2017, we assessed 5 HTx patients found to have acquired West Nile Virus after HTx. The outcomes of these patients are now assessed. Endpoints included 1-year subsequent survival, neurologic status, rejections, cardiac function, cardiac allograft vasculopathy (CAV, stenosis ≥30%), and non-fatal major adverse cardiac events (NF-MACE). <h3>Results</h3> Mortality in this population is 100%. Patients were severely neurologically compromised and completely dependent on 24/7 care. One patient was alert and ambulatory but aspirated on soup, thought to possibly be due to suppressed gag/cough reflex. The patient subsequently died. The other four patients were severely neurologically comprised—all with flaccid paralysis/quadriplegia, although able to communicate by moving eyes, facial gestures, and/or head and lip movement. All patients were able to communicate but were dependent on external feeding. <h3>Conclusion</h3> West Nile Virus is devastating post-HTx with high mortality and significant morbidity which has left these patients in almost a comatose state.

Are Markedly Oversized Donor Hearts Associated with Poor Outcome After Heart Transplantation?

<h3>Purpose</h3> In heart transplantation, donor-to-recipient (D-R) size matching has been done by height and weight. Recently, predicted heart mass (PHM) has been found to be more clinically useful to predict outcome. Using PHM, under-sizing a donor heart for a larger recipient with high pulmonary artery pressures leads to increased mortality. It has recently been noted in the ISHLT registry that there may be increased risk in placing an oversized donor heart using weight into a smaller recipient. This clinical outcome has not been established using PHM. We sought to address this question in our large, single center experience using PHM. <h3>Methods</h3> Between January 2010 and June 2020, we assessed 588 D-R heart matches. We used PHM to assess outcome differences when the donor hearts were oversized. We divided the D-R ratio by PHM into two categories: Normal (N: 90-110%, n=524), and markedly oversized (MO: greater than 140%, n=64). Outcomes included 1-year survival, freedom from 1-year rejection (acute cellular rejection [ACR], antibody-mediated rejection [AMR]), freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), freedom from cardiac dysfunction (LVEF ≤40%), and freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). <h3>Results</h3> MO (n=64) compared to N (n=524) using PHM showed no difference in 1-year survival, freedom from ACR, freedom from CAV, freedom from NF-MACE, and freedom from cardiac dysfunction. There was a significantly lower freedom from 1-year AMR in the MO group due to more female recipients (sensitized due to previous pregnancies) in this group (71% MO group vs 20% N group). <h3>Conclusion</h3> Markedly oversized donor to recipient matching using PHM does not result in poor outcomes after heart transplantation. This has potential to expand the donor pool, particularly for smaller patients.

Do Women Truly Have Less Than Optimal Outcome Post-Heart Transplantation Compared to Men

<h3>Purpose</h3> It has been reported from the ISHLT registry that women have less optimal outcome after heart transplantation (HTx) compared to men. It is not known whether this difference is due to rejection, NF-MACE, or decreased survival. <h3>Methods</h3> Between 2010 and 2020, we assessed 1071 HTx patients and divided them by male and female sex. 309 females and 762 males were included in the study. Post-transplant outcomes included 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), 1-year freedom from rejection (acute cellular rejection [ACR], antibody-mediated rejection [AMR]), and 1-year freedom from de novo DSA production. Women were divided into two groups, sensitized (PRA >10%) or non-sensitized. <h3>Results</h3> When comparing women to men, women had similar survival, freedom from CAV, and freedom from NF-MACE, but significantly lower freedom from ATR, AMR, and de novo DSA production. Women who were sensitized had similar survival but lower freedom from rejection and DSA production compared to non-sensitized women. 26% of our female patients were sensitized. <h3>Conclusion</h3> Major post-transplant outcomes are similar for women and men. However, sensitization may be the reason for more AMR in women but it does not affect short-term major outcomes. Longer follow-up and impact of these outcomes need to be assessed.

POS-250 A RANDOMIZED TRIAL OF EFFECT OF CHOLECALCIFEROL SUPPLEMENTATION ON CARDIOVASCULAR DISEASE, INFLAMMATION, AND BONE METABOLISM MARKERS IN CKD: BASELINE CHARACTERISTICS OF FEASIBILITY PHASE

Studies have linked lower vitamin D levels with cardiovascular disease (CVD) and mortality in general population and chronic kidney disease (CKD). The preliminary evidence of vitamin D supplementation is encouraging but there is a huge void with respect to good quality long term data supporting the use of this promising intervention for translation into better outcomes for CVD in CKD. This study is exploring the effect of cholecalciferol supplementation on cardiovascular disease, markers of inflammation and bone metabolism in CKD. We present the baseline characteristics of feasibility phase of the trial. The study is a multicentric, prospective, randomized, placebo controlled, double blind trial in two parallel groups and feasibility phase is being done at Postgraduate Institute of Medical Education and Research, Chandigarh, India. The trial is registered at Clinical Trials Registry of India (CTRI/2019/05/019211). After a run-in period of 2 weeks, the enrolled subjects are randomized in 1:1 to receive either 60,000 IU/2 weeks of cholecalciferol or matching placebo. The subjects will be then followed up every three month till 3 years. The primary outcome of the study is a composite of major adverse cardiac events (MACE). Secondary outcome measures include all-cause mortality, need of RRT, change in hsCRP, IL-6, iPTH, FGF-23, bone specific alkaline phosphatase, and CTX-1. A total of 720 subjects have been screened till date. Out of 119 enrolled, 86 subjects have been randomized over 24 months period. 76% subjects have completed annual follow up at 12 months, 66% subjects - 15thmonths follow up, 40%- 18 months follow up, 26% subjects - 21 months follow up, 6% subjects – 24 months follow up. Baseline characteristics and serum biomarkers levels has been analysed in 80 subjects. Mean age of the subjects were 51.3 ± 12.2 years and 58.8 % were males. Serum haemoglobin levels were 11.6 ±1.7 g/dl. Mean eGFR was 26.3 (17.4, 35.1) ml/min/1.73m2. Outcome events were; MACE: 1 (due to CVD), death other than due to MACE: 1 (due to COVID 19), subjects with composite of all-cause death and non-fatal MACE: 2, subject with need of RRT:1 and subjects with composite of 50% decline in GFR or need of RRT: 3. 2 serious adverse events unrelated to study drug were reported during the course of study. Table: Baseline levels of various serum biomarkers Tabled 1CharacteristicsTotal (N = 80)Serum creatinine (mg/dL)2.7 ± 1.1Serum calcium (mg/dL)9.2 (8.8, 9.4)Serum inorganic phosphorous (mg/dL)3.8 (3.2, 4.2)Serum intact parathyroid hormone (pg/mL)172.0 (94.6, 327.9)Serum 25-hydroxyvitamin D3 (ng/mL)28.5 (22.6, 38.2)Bone alkaline phosphatase (U/L)29.7 (22.1, 43.7)Fibroblast growth factor-23 (pg/mL)131.0 (37.9, 139.7)C-reactive protein (ng/mL)4.4 (1.9, 7.6)Interleukin-6 (pg/mL)4.0 (2.1, 2.3)Carboxy terminal telopeptide (ng/mL)1.2 (0.2, 2.3) Open table in a new tab Despite COVID 19 related restrictions being in place for most of the last 18 months, the study has been able to screen and enrol participants. The follow ups have been ensured either through physical or remote (mobile/telephonic) means. Once in the multi-centric phase, the study will be able to test a relatively inexpensive intervention in the form of vitamin D supplementation for CVD in CKD.

Long-term outcomes after heart transplantation using ex vivo allograft perfusion in standard risk donors: A single-center experience.

The Organ Care System (OCS) is an ex vivo perfusion platform for donor heart preservation. Short/mid-term post-transplant outcomes after its use are comparable to standard cold storage (CS). We evaluated long-term outcomes following its use. Between 2011 and 2013, 38 patients from a single center were randomized as a part of the PROCEED II trial to receive allografts preserved with CS (n=19) or OCS (n=19). Endpoints included 8-year survival, survival free from graft-related deaths, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejections. Eight-year survival was 57.9% in the OCS group and 73.7% in the CS group (p=.24). Freedom from CAV was 89.5% in the OCS group and 67.8% in the CS group (p=.13). Freedom from NF-MACE was 89.5% in the OCS group and 67.5% in the CS group (p=.14). Eight-year survival free from graft-related death was equivalent between the two groups (84.2%vs. 84.2%, p=.93). No differences in rejection episodes were observed (all p>.5). In select patients receiving OCS preserved allografts, late post-transplant survival trended lower than those transplanted with an allograft preserved with CS. This is based on a small single-center series, and larger numbers are needed to confirm these findings.

Efficacy and safety of drug-coated balloons according to coronary vessel size. A report from the BASKET-SMALL 2 trial.

IntroductionIn BASKET-SMALL 2, drug-coated balloons (DCB) were non-inferior to drug-eluting stents (DES) in de-novo stenosis of small coronary vessels (≤ 2.75 mm) regarding clinical endpoints up to 36 months.AimIn the present subgroup analysis, we aimed to analyze the effect of the two treatment strategies in different vessel sizes.Material and methodsPatients were analyzed according to the size of the device used (small > 2.5 mm vs. very small ≤ 2.5 mm). The primary endpoint was major adverse cardiac events (MACE), while secondary endpoints were target vessel revascularization (TVR), non-fatal myocardial infarction, cardiac death, and all-cause mortality, all at 36 months. Interactions for the different groups were assessed with Cox regression analysis.ResultsOverall, 758 patients were enrolled in this analysis, of which 437 (58%) had very small vessel disease. There were similar results in both treatment groups for the primary endpoint in both small and very small vessels (DCB vs DES, MACE at 3 years in small vessels HR = 1.31, 95% CI: 0.74–2.32, p = 0.355, and very small vessels HR = 0.82, 95% CI: 0.49–1.39, p = 0.468). Second generation paclitaxel-eluting stents showed significantly higher rates for MACE (p = 0.041), TVR (p = 0.004) and non-fatal myocardial infarction (p = 0.036) compared to DCB in very small coronary arteries at 3 years, while results were similar in small coronary arteries.ConclusionsEfficacy and safety of DCB are similar irrespective of vessel size. However, there is a beneficial effect of DCB over paclitaxel-eluting stents regarding TVR, non-fatal myocardial infarction and MACE that is most pronounced in very small coronary arteries.

Abstract 12489: Blood Type A1 Donor and Recipient Matching for Heart Transplant: Does It Matter?

Introduction: ABO antibodies bind specific carbohydrate moieties defining the A and B antigens. With blood group A, inter-individual variation in transferase specificity and efficiency results in differential antigen expression and density. These subgroups of A are termed non-A1 and have fewer A antigen epitopes per red blood cell, which is less immunogenic. Our goal was to assess the impact of transplantation of an A1 organ to a non-A1 recipient. Methods: We assessed 138 blood-type A heart transplant recipients transplanted between 2013 and 2020. Comparison groups included a "match" group (A1 donor into A1 recipient, and non-A1 donor into non-A1 recipient, n=88) and a "mismatch" group (A1 donor into non-A1 recipient, and non-A1 donor into A1 recipient, n=50). Outcomes included 1-year survival, freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, percutaneous coronary intervention, defibrillator/pacemaker implant, stroke), and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Results: The mismatch group exhibited similar subsequent 1-year survival, freedom from CAV, and freedom from NF-MACE and subsequent 1-year freedom from ATR, ACR, and AMR compared to the match group. (Table) Conclusions: The mismatch of blood type in A1 and non-A1 between donors and recipients does not adversely affect outcomes after heart transplantation. Selective matching of specific A blood typing for heart transplantation is not necessary.