ABSTRACT
INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.
Subject(s)
Heart Transplantation , Myocardium , Humans , Myocardium/pathology , Heart Transplantation/adverse effects , Biopsy , Gene Expression Profiling , Graft Rejection/diagnosis , Graft Rejection/etiology , Graft Rejection/epidemiologyABSTRACT
Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.
Subject(s)
Amyloid Neuropathies, Familial , Amyloidosis , Cardiomyopathies , Heart Transplantation , Amyloid Neuropathies, Familial/surgery , Cardiomyopathies/etiology , Humans , Prealbumin , Prognosis , Survival RateABSTRACT
BACKGROUND: Cancer survivors (CS) comprise a particularly high-risk group for both de-novo and recurrent malignancies after solid organ transplantation. CASE PRESENTATION: We report a case of relapsed melanoma, presented as metastatic disease seven months after heart transplantation in a patient who had an early-stage melanoma resected 25 years prior. Treatment with a combination of dabrafenib, a BRAF inhibitor, and trametinib, a mitogen-activated protein kinase (MEK) inhibitor resulted in a near-complete metabolic response, without major adverse effects. CONCLUSION: This case demonstrates the increased risk of recurrence in CS with melanoma, which can persist decades after cancer diagnosis. These patients may be amenable to treatment using modern treatment modalities in oncology.
ABSTRACT
INTRODUCTION: High defibrillation threshold (DFT) is a clinical problem in 1-8% of implantable cardioverter-defibrillator implants. Some clinicians and investigators question whether the benefits of routine DFT testing outweigh the risks. Identification of the predictors of elevated DFT may allow selective application of DFT testing. However, the clinical characteristics of patients with high DFT in the modern era have not been well-defined. METHODS: All patients who underwent DFT testing in our institution during an 8-year period were reviewed for this retrospective study. High DFT was defined as less than a 10-J safety margin on initial testing. For each case, the two cases preceding and two cases following by the same implanter were selected as controls. RESULTS: Of the 2,138 patients who underwent DFT testing, 48 (2.2%) met criteria for high DFT. Compared to 192 control patients, patients with high DFT were more likely to be younger (P = 0.004), have nonischemic cardiomyopathy (P = 0.036), have a longer QRS interval (P = 0.026), and have a left ventricular ejection fraction (LVEF) ≤ 0.25 (P = 0.013). On multivariate analysis, only younger age (P = 0.016) and LVEF ≤ 0.25 (P = 0.010) remained statistically significant predictors of elevated DFT. CONCLUSIONS: High DFT was identified in 2.2% of ICD implants in our institution in recent years. Although younger age and depressed LVEF predicts this problem, elevated DFT occurred in patients of all ages and ejection fractions. Elimination of routine DFT testing appears to be premature given the prevalence and unpredictability of elevated DFT.