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For patients with end-stage hereditary transthyretin (TTR) cardiac amyloidosis, heart or heart-liver transplant can be considered. Due to advances in treatment, liver transplant may no longer be necessary, even if concomitant polyneuropathy is present as there are novel therapies that may halt, and in some cases reverse the burden of disease. We present a case of mixed phenotype TTR amyloidosis (cardiac involvement and polyneuropathy) successfully treated with orthotopic heart transplant (OHT) and patisiran therapy. A 73-year-old previously healthy African American male was referred for evaluation due to new-onset dyspnea. Electrocardiogram revealed atrial flutter with a controlled ventricular response. Echocardiogram was notable for severe biventricular hypertrophy, severe biatrial enlargement, severely depressed ejection fraction, and a pericardial effusion. An endomyocardial biopsy confirmed amyloid deposits. Mass spectrometry and genetic testing confirmed the presence of a pathogenic mutation in the TTR gene. During that same time period, the patient reported neuropathy. Nerve conduction studies revealed decrement in conduction consistent with an amyloid polyneuropathy. Despite initiation of tafamidis, the patient's clinical picture deteriorated, and he eventually required initiation of inotropes as a bridge to OHT. He successfully underwent OHT and was discharged home soon after. His immediate and long-term post-operative course was uneventful up until 10 months post-transplant, when the patient began to report worsening symptoms of neuropathy. Neurologic evaluation confirmed the clinical presence of an amyloid polyneuropathy, previously supported by nerve conduction studies. The patient was initiated on patisiran, an anti-transthyretin RNA interference agent, approximately one-year following transplant. At 18 months, the patient reports stability of his polyneuropathy symptoms and has not had any complications from patisiran infusions. In patients undergoing OHT for hereditary TTR cardiac amyloidosis with concomitant polyneuropathy, post-transplant treatment with patisiran can be considered to halt progression of polyneuropathy. Effects on other organs including the transplanted heart may also be favorable, although this area is absent supporting data. [ABSTRACT FROM AUTHOR]

Malnutrition has been associated with poor clinical outcomes in patients with coronary artery disease who undergo percutaneous coronary intervention and in patients with heart failure. This study aims to assess the impact of the geriatric nutritional risk index (GNRI) on clinical outcomes in patients undergoing orthotopic heart transplantation (OHT). Consecutive patients undergoing OHT were included from 2018 to present after the change in UNOS listing criteria. Patients 60 years-old or greater were included in this study and those that survived to discharge were included. Fifty-seven patients were identified. Geriatric nutritional risk index (GNRI) was calculated using pre-procedure body mass index (BMI) and serum albumin for each patient. Patients were stratified into two groups: GNRI < 98 (low GNRI) and >98 (normal GNRI). Primary outcomes were mortality, stroke, heart failure readmissions, and all-cause readmissions at one year. The mean age of study subjects was 66.0 years. Seventy-seven percent of patients were male. Fifteen patients were included in the low GNRI group. Patients with normal GNRI were more likely to be readmitted (p = 0.114), transplant related readmissions (p = 0.131), and significantly more infection related readmissions (p = 0.026). Normal nutritional status as designated by a GNRI of >98 was not predictive of fitness. However, was related with higher rates of readmission as compared to those with low GNRI—a paradox as compared to prior literature. Although, GNRI is well established in percutaneous coronary intervention, heart failure, and aortic stenosis it appears that this does not hold true in patients undergoing OHT. [ABSTRACT FROM AUTHOR]

It has been suggested that patients with cardiac amyloidosis can have similar outcomes post orthotopic heart transplantation (OHT) compared to non-amyloid cardiomyopathies. Our aim is to report characteristics and outcomes after OHT in patients with cardiac amyloidosis in a large single-center quaternary university hospital. We performed a retrospective chart review of all patients with AL amyloid who underwent OHT from January 2017 to October 2021. Kaplan-Meier method was used to assess time to death compared to non-amyloid cardiomyopathies. Analytic sample was 280 patients, with a median follow up of 1.86 years. We had 16 patients with amyloid, aTTR amyloid was the more prevalent (50%), followed by AL (44%) and one case of ApoA1. Our cohort had a male predominance (75%), with a mean age of 61.7 years. Carpal tunnel was the most prevalent extracardiac involvement (56%), followed by renal (31%), peripheral neuropathy (31%), autonomic neuropathy (19%) and gastrointestinal (19%). Mean Vo2 max was of 14ml/min/kg; the median time on the waiting list was 35 days. The pathological light chain was Lambda in 86% of those with AL with a median difference in free light chains of 280 mg/dL. In patients with ATTR, wild type was the most prevalent (63%) compared to 38% with the V122I mutation. We did not observe mortality, graft failure or episode of antibody-mediated rejection. There was no statistical difference in survival at 3-years between amyloid (100%) and non-amyloid (93.4%) patients, Wilcoxon p-value = 0.32. Acute cellular rejection requiring treatment was observed in 2 patients, with a mean time to rejection of 100 days. Multifactorial progression of nephropathy was seen in 31% of patients. Progression of neuropathy was seen in 25% of patients and only one patient reported GI symptom progression. Patients with cardiac amyloid undergoing OHT with limited extracardiac involvement had comparable survival to patients with non-amyloid cardiomyopathies. [ABSTRACT FROM AUTHOR]

The optimal immunosuppressive therapy (IST) for patients with AL amyloid undergoing orthotopic heart transplantation (OHT) is not well defined. Our study aims to present the IST and outcomes after OHT in patients with cardiac amyloidosis at a large quaternary university hospital. In a retrospective chart review, we performed a case series of all patients with AL amyloid who underwent OHT from Jan 2017 to Oct 2020. We assessed their IST and outcomes of survival, infection and rejection. We identified 7 patients with AL amyloidosis who underwent OHT. Three patients (43%) had Mayo Stage 3, and 4 (57%) patients had stage 4. Autologous stem cell transplant (ASCT) was performed in 4 patients with a median time from OHT to ASCT of 429 days. In patients who had bone marrow biopsy, amyloid was present in 21% and the mean plasma cells visualized by immunohistochemistry was 4.41%. IST after OHT consisted of a calcineurin inhibitor, antimetabolite and steroids initially. Some required treatment with bortezomib/daratumumab for sub-optimal duration or hematologic response to AL amyloid therapies prior to OHT at which time antimetabolite was stopped. Median time to antimetabolite withdrawal was 317 days. Median times to introduction of daratumumab and bortezomib after OHT were 283 and 388 days, respectively. Figure 1 displays the time series of IST. Renal involvement was the more prevalent extracardiac organ (57%), followed by gastrointestinal (43%), carpal tunnel (29%), and peripheral neuropathy (29%). We did not observe any mortality, graft failure, episodes of acute cellular or antibody-mediated rejection. One patient had clostridium difficile infection who was admitted for monitoring. In those that require ongoing AL amyloid therapies following OHT, it may be safe to discontinue antimetabolite in efforts to minimize complications from over-immunosupression without compromising risk of rejection. Personalized IST in this traditionally high-risk population should be considered. [ABSTRACT FROM AUTHOR]

We present a case of end-stage lung disease secondary to mixed connective tissue disease (MCTD) with concomitant myocarditis. The patient is a 37-year-old male initially diagnosed with interstitial lung disease due to MCTD at age 30. He was started on hydroxychloroquine (HCQ) at age 32 and later switched to mycophenolate mofetil (MMF). At that time, his left ventricular ejection fraction (LVEF) was 30%. His LVEF improved to 47% while on MMF and carvedilol but his pulmonary status worsened, and eventually he was placed on the lung transplant list. He was returned to HCQ due to progression while on MMF. A follow-up echocardiogram performed one year later for clinical decline revealed a LVEF of 15%. HCQ was discontinued for concern of cardiac toxicity and MMF was resumed. Repeat echocardiograms revealed improved LVEF although prohibitive for lung transplant alone. He was approved for heart and lung transplant, and soon thereafter, underwent successful transplant. Explant of lungs revealed extensive interstitial fibrosis with moderate chronic inflammation. Explant of heart revealed patchy lymphocytic myocarditis with myocyte damage and areas of fibrosis with myocyte hypertrophy. MCTD is an autoimmune process that has a variety of end-organ manifestations, variably affecting the cardiovascular system and subsequently portending a poorer prognosis. Albeit rare, myocarditis is a known complication of MCTD. Because symptoms are insidious, we emphasize the importance of high clinical suspicion for myocarditis in patients with known MCTD. Diagnosis of myocarditis is made by biopsy, although imaging may be suggestive. The use of fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging may be of value due to its ability to localize inflammation in the form of increased myocardial FDG uptake. In patients presenting with unexplained systolic dysfunction in the setting of MCTD, FDG-PET may be a screening tool and if myocardial inflammation is noted, there may be a role for increased immunosuppression. While this strategy was not employed in our patient, his improvement in LVEF while on MMF compared to HCQ and explant histology suggest a process that may have responded to escalation of immunosuppression. This has further implications as decision regarding single versus multi-organ transplant may be affected by medical therapy response. [ABSTRACT FROM AUTHOR]

Heart transplantation for patients with end-stage congenital heart disease (CHD) is considered high risk due to increased peri-operative mortality at index hospitalization. However, survivors have comparable conditional 1-year survival and a superior 15-year survival when compared to non-CHD recipients. Outcomes from a multidisciplinary CHD team caring for this complex population are presented. We conducted a retrospective review, at a large volume transplant center from 2017-2021 to identify consecutive patients who underwent single or dual-solid organ transplantation for the indication of end-stage CHD. Overall post-transplant survival at 6 and 12 months for this CHD cohort were compared to the other heart, heart-lung, and heart-liver transplants during the same period. There were 21 consecutive patients with end-stage CHD who were transplanted during the study period. A total of 12 recipients (57%) had single ventricle physiology with the most common defects being tricuspid atresia and hypoplastic left heart syndrome. Most were male (71%) with a mean age of 29 years (Table 1). There was a high proportion of dual-organ transplants (43%) with the most common being heart-liver (Table 1). Post-transplant survival at 6 and 12 months were 95% and 94%, respectively compared to 97% and 96%, respectively for similar transplant recipients for non-CHD indications. The single mortality in the CHD cohort occurred in a dual-organ transplant recipient (listed status 1A) with single ventricle and died 72 hours post-operatively due to severe, nonspecific graft dysfunction requiring extracorporeal membrane oxygenation support. This study demonstrates an excellent post-transplant survival (94% at 12 months) for CHD patients can be achieved when a collaborative approach between pediatric and adult transplantation teams with congenital disease expert is employed in the pre-, peri- and post-transplantation period. [ABSTRACT FROM AUTHOR]

The LMNA cardiomyopathies are caused by mutations in the Lamin A/C gene that can cause varying phenotypes. The purpose of this study was to characterize differences in outcomes between dilated and non-dilated patients with LMNA cardiomyopathy. We performed a retrospective analysis of patients who received a genetic cardiomyopathy panel from 2017-2021 and were found to have a LMNA mutation. Dilated phenotype was defined as left ventricular end diastolic diameter >5.8cm in males and >5.2cm in females. Kaplan Meier analysis using birth as the reference point was used to compare age of advanced therapies between the groups. A total of 20 patients were found to have LMNA mutations, 6 dilated, 14 nondilated. Age of diagnosis was younger in the dilated phenotype. There were no other differences in demographics or comorbid conditions between the groups. LVEF was lower in the dilated group. While was no difference in AICD placement between groups, incidence of advanced therapies, defined as either LVAD or heart transplant, was higher in the dilated group (Table 1). Patients with the dilated phenotype required advanced therapies at an earlier age. (Figure 1). There was 1 death at the age of 67 in the non-dilated group. There was no difference in mutation significance between groups, with 25% of all LMNA mutations in this group being a variant of unknown significance. All except 1 of the mutations were substitutions. Although incidence of comorbid conditions and arrhythmias are similar between groups, the dilated phenotype has a more severe disease course, presenting and requiring advanced therapies at a younger age compared to the non-dilated phenotype. [ABSTRACT FROM AUTHOR]

Weakness and deconditioning are common findings in those with critical illness. Mobilization is associated with improved outcomes.VA-ECMO is the highest level of mechanical circulatory support (MCS) offered with bypass of the heart and lungs. Mortality is approximately 60% for those on VA-ECMO support. This retrospective study aims to present characteristics and outcomes associated with mobilization on VA-ECMO. Patients were identified at our quarternary care system. Seventy-five consecutive were cannulated with VA-ECMO support for cardiogenic shock over a three year period. Seven patients were mobilized while on VA-ECMO. Baseline characteristics, fraility, ICU Mobility scales, and standard outcomes as defined by the Extracorporeal Life Support Organization were obtained. The mobilized group was younger (39.7 ± 17.7 years vs 55.3 ± 14.6 years; p = 0.010) and were more likely to have normal body mass index (22.4 ± 5.1 kg/m2 vs 28.2 ± 6.5; p = 0.025). All patients mobilized were male (100% vs 70.5%). Mobilized patients had support cannulas placed in the femoral position with 6/7 (85.7%) having ipsilateral venous and femoral access. Five (71.4%) patients had percutaneous devices placed in the contralateral femoral artery or left axillary artery. Five (71.4%) patients were cannulated peripherally. All patients mobilized on VA-ECMO survived to discharge while 29.4% of patients not mobilized survived to discharge (p = 0.008). Vascular complications between mobilized (0%) and non-mobilized patients (7; 10.9%) were non-significant (p = 0.584). Patients mobilized on VA-ECMO are more likely to survive than those who were not mobilized. Complex patients with the presence of MCS devices can be mobilized. Thorough multidisciplinary planning must be taken to ensure that access sites are secure and patients that are appropriate for extubation are extubated in a timely manner while on VA-ECMO. Thought should be given to cannulation location and insertion depth and how this will affect a patient ability to mobilize. Patients with VA-ECMO as a bridge to transplant may introduce selection bias and may skew safety profiles. Ultimately, this study is limited in its single center, retrospective nature, but further prospective trials should be utilized to help identify appropriate candidates for mobilization while on VA-ECMO support for cardiogenic shock. [ABSTRACT FROM AUTHOR]

Protein-losing enteropathy (PLE) is a complication after the Fontan operation believed to result from lymphatic dysfunction. As a consequence of protein loss, patients can develop hypogammaglobinemia (HGG). PLE typically resolves following heart transplant, but changes in immunoglobulin levels are not well-described. HGG can increase peri-transplant infection risk and may impair the accurate assessment of pre-transplant antibodies against potential donors. In our case series, we present the changes in immunoglobulin levels among patients palliated with the Fontan procedure that later underwent heart transplant. Patients who underwent Fontan with subsequent heart or heart-liver transplant were included (n=10). Variables included are listed in Table 1. Post-transplant IgG levels were collected at a minimum of 3 months post-transplant to avoid interference from high-dose steroids and higher doses of immunomodulation used in the immediate post-transplant period. HGG was defined as IgG < 700 mg/dL pre-transplant. The mean age at transplant was 22.3 years; 90% of patients were male. Three (30%) patients had HGG. Two had complete resolution of HGG. The third was treated with subcutaneous immunoglobulin before transplant. PLE resolved post-transplant. One of the patients with HGG had a persistent de novo donor-specific antibody in the setting of immunosuppression non-adherence. In this case series, we present HGG as a consideration in patients palliated with Fontan. Due to the risk of infection, HGG may lead clinicians to reduce immunosuppression in the peri-transplant period. HGG may also impact the ability to detect the degree of sensitization as the panel of reactive antibodies relies on sufficient immunoglobulin titers against human-leukocyte antigen to identify unacceptable donors. Lastly, if HGG resolves predictably post heart-transplant, that may have further implications on early risk for rejection in this patient population. [ABSTRACT FROM AUTHOR]