Imaging of Cardiac Sarcoidosis: An Update and Future Aspects.

Cardiac sarcoidosis (CS), an increasingly recognized disease of unknown etiology, is associated with significant morbidity and mortality. Given the limited diagnostic yield of traditional endomyocardial biopsy (EMB), there is increasing reliance on multimodality cardiovascular imaging in the diagnosis and management of CS, with EMB being largely supplanted by the use of 18F-fluorodeoxyglucose (FDG-PET) and cardiac magnetic resonance imaging (CMR). This article aims to provide a comprehensive review of imaging modalities currently utilized in the screening, diagnosis, and monitoring of CS, while highlighting the latest developments in each area.

Inhibition of angiogenesis in the management of refractory gastrointestinal bleeding in patients with LVAD support.

BACKGROUND: Gastrointestinal bleeding (GIB) in patients with continuous flow left ventricular assist devices (CF-LVADs) is often related to GI angiodysplasia (GIAD). We previously reported data on VEGF inhibition with IV bevacizumab in the treatment of LVAD-associated GIAD bleeding, and now present follow-up data on patients treated with IV bevacizumab and/or low-dose oral pazopanib. METHODS: All consecutive adult patients with LVAD-associated GIB from GIAD treated with bevacizumab or pazopanib, from July 20, 2017 to June 22, 2022, were included in the analysis. Data on hospitalizations, GI endoscopic procedures, and blood transfusions were obtained from first admission for GIB up to a median of 35.7 months following treatment initiation (range 1.3-59.8 months). RESULTS: Eleven patients (91% male, mean 69.5 ± 8.9 years) were included. Eight patients (73%) received IV bevacizumab, two patients (18%) received oral pazopanib, and one patient (9%) received bevacizumab followed by pazopanib therapy. We observed a significantly decreased number of annualized hospitalizations for GIB (median difference - 2.87, p = 0.002), blood transfusions (median difference - 20.9, p = 0.01), and endoscopies (median difference - 6.95, p = 0.007) in patients pre- and post-anti-angiogenic therapy (bevacizumab and/or pazopanib). Similarly, a significant improvement in these clinical outcomes was noted in the bevacizumab group with decreased annualized hospitalizations (median difference - 2.75, p = 0.014), blood transfusions (median difference - 24.5, p = 0.047), and number of endoscopies (median differences -6.88, p = 0.006). CONCLUSION: Anti-angiogenic therapy with IV bevacizumab and/or low-dose oral pazopanib appears to provide benefits in patients with LVAD-associated GIB with reduced hospitalizations, blood transfusions, and need for GI endoscopic procedures.

Case Series: Recurrence of Cardiac Sarcoidosis After Orthotopic Heart Transplantation.

Orthotopic heart transplantation for cardiac sarcoidosis (CS) is becoming increasingly common. Historically, there have been concerns regarding disease recurrence within the allograft. Although rarely reported in the literature, cases of recurrent CS tend to be observed in patients after dose reduction of immunosuppressive therapy and cessation of corticosteroids. Here, we present 2 cases of recurrent CS after orthotopic heart transplantation, confirmed on endomyocardial biopsy. Case 1 reports a 50-year-old man with a fulminant course of giant cell myocarditis who developed allograft recurrence with granulomas 5 years after transplantation despite maintenance corticosteroid therapy. Case 2 reports a 47-year-old man with CS who developed recurrence with the presence of giant cells 2 years after transplantation, with a benign clinical course. With these cases, we demonstrate the clinical overlap between CS and giant cell myocarditis and highlight the spectrum of the disease process. We also demonstrate that CS can recur despite corticosteroid maintenance therapy.

The Mechanism and Natural History of Mitral Regurgitation in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an infl/ammatory cardiomyopathy that can present with mitral regurgitation (MR), but few studies describe the mechanisms and natural history of MR in CS. We queried an institutional registry of 512 patients with CS for moderate or greater MR at diagnosis. Baseline demographic and echocardiography (TTE) data were collected. MR was classified by Carpentier type. Positron emission tomography was analyzed for 2-deoxy-2-[fluorine-18] fluoro-d-glucose (FDG) avidity of anterolateral and posteromedial papillary muscles. Follow-up TTE and positron emission tomography imaging of patients treated with immunosuppression was analyzed for MR severity and FDG avidity changes. Fifty-four patients were identified. Mean left ventricular ejection fraction was 39.3%, effective regurgitant orifice 0.34 cm2, and MR regurgitant volume 46.3 ml. Carpentier type I was the most common MR mechanism (46.3%). Forty-one patients had follow-up TTE (median follow-up 1.7 years, interquartile range 2.6 years). Evaluating preprocedural follow-up TTE only, MR severity was significantly reduced, with 37% of patients showing reduction by at least 1 severity grade (p = 0.04). With postprocedural TTE included, 61% of patients showed alleviation of MR severity with mean decrease in grade - 0.98 (p <0.001). Sixty-eight percent of patients had anterolateral/posteromedial FDG avidity. Papillary muscle FDG avidity resolved in 80% of patients (n = 20, median follow-up 1.6 years, interquartile range 2.5 years). In conclusion, Carpentier type I functional MR is the most common MR mechanism in CS. MR severity and papillary muscle FDG avidity decrease after treatment, and MR resolution is further strengthened by procedural intervention in a minority of patients, suggesting an overall favorable natural history of MR in CS.

18F-FDG/13N-ammonia cardiac PET findings in ATTR cardiac amyloidosis.

18F-flurodeoxyglycose (FDG)/13N-ammonia positron emission tomography/computed tomography (PET/CT) is frequently utilized to evaluate cardiac sarcoidosis (CS) but findings can reflect other forms of myocardial inflammation or altered myocardial metabolic activity. Herein, we present five cases where cardiac PET findings suggested CS, but right ventricular endomyocardial biopsy samples revealed ATTR-type cardiac amyloidosis.

Cardiac resynchronization therapy response in cardiac sarcoidosis.

INTRODUCTION: Cardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS. OBJECTIVE: To determine if CRT improved cardiac remodeling in patients with CS. METHODS: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, and major adverse cardiac events (MACE) were assessed. RESULTS: Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT-D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT-P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end-diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p < .0001). Within the first 6 months postimplantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow-up of 4.1± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent left ventricular assist device implantation and 7 (12.7%) patients died. CONCLUSIONS: Our findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

First Report of Proton Beam Therapy in a Patient With a Left Ventricular Assist Device.

A 77 year old man previously implanted with a HeartMate II left ventricular assist device (LVAD) as destination therapy and an implantable cardioverter defibrillator presented with a left upper lobe squamous cell lung cancer. Oncology determined that proton beam therapy was indicated for treatment, and a multidisciplinary team of radiation physicists, radiation oncologists, and LVAD providers developed a protocol to proceed safely. He was successfully treated with combined proton beam radiation therapy and reduced dose chemotherapy. This case demonstrates feasibility and considerations of proton beam therapy for malignancy relevant to patients with implantable cardiac devices including LVADs.

Artificial Intelligence-Enabled Electrocardiography to Screen Patients with Dilated Cardiomyopathy.

Undiagnosed dilated cardiomyopathy (DC) can be asymptomatic or present as sudden cardiac death, therefore pre-emptively identifying and treating patients may be beneficial. Screening for DC with echocardiography is expensive and labor intensive and standard electrocardiography (ECG) is insensitive and non-specific. The performance and applicability of artificial intelligence-enabled electrocardiography (AI-ECG) for detection of DC is unknown. Diagnostic performance of an AI algorithm in determining reduced left ventricular ejection fraction (LVEF) was evaluated in a cohort that comprised of DC and normal LVEF control patients. DC patients and controls with 12-lead ECGs and a reference LVEF measured by echocardiography performed within 30 and 180 days of the ECG respectively were enrolled. The model was tested for its sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) based on the prevalence of DC at 1% and 5%. The cohort consisted of 421 DC cases (60% males, 57±15 years, LVEF 28±11%) and 16,025 controls (49% males, age 69 ±16 years, LVEF 62±5%). For detection of LVEF≤45%, the area under the curve (AUC) was 0.955 with a sensitivity of 98.8% and specificity 44.8%. The NPV and PPV were 100% and 1.8% at a DC prevalence of 1% and 99.9% and 8.6% at a prevalence of 5%, respectively. In conclusion AI-ECG demonstrated high sensitivity and negative predictive value for detection of DC and could be used as a simple and cost-effective screening tool with implications for screening first degree relatives of DC patients.

Identification of a novel presumed cardiac sarcoidosis category for patients at high risk of disease.

BACKGROUND: Histologic evidence is required for a definitive diagnosis of cardiac sarcoidosis (CS) by published guidelines; however, the sporadic nature of the disease may produce false negative biopsy results, causing CS to be underdiagnosed. We sought to establish a clinical category of CS absent histologic findings. METHODS: Patients evaluated for CS were stratified into 3 groups: probable CS and definite CS based on Heart Rhythm Society (HRS) criteria and presumed CS, ie, patients without any histologic evidence of sarcoidosis, but with unexplained high-grade atrioventricular block or ventricular arrhythmia and findings suggestive of CS on either cardiac magnetic resonance imaging or positron emission tomography. The primary end point was hospitalization-free and overall survival at 10 years. RESULTS: A total of 383 patients were included in the study: 59, definite CS; 223, probable CS; and 101, presumed CS (62, isolated CS and 39, systemic CS). Compared with patients meeting HRS criteria for CS, patients with presumed CS had lower odds of New York Heart Association class III or IV symptoms (odds ratio [OR], 0.44 [95% CI, 0.23-0.83]; P = .01) but greater odds of previous ventricular tachycardia (OR, 2.4 [95% CI, 1.4-4.0]; P = .001) or history of resuscitated sudden cardiac arrest (OR, 2.9 [95% CI, 1.0-8.6]; P = .05). Hospitalization-free and overall survival were similar among groups (P = .51 and P = .71, respectively). CONCLUSIONS: Clinical categorization of patients with presumed CS identified a high-risk cohort comparable to patients with histologic evidence of disease, although caution should be exercised in reaching this diagnosis without paying due diligence to the differential diagnosis.

Percutaneous Axillary Intra-aortic Balloon Pump Insertion Technique as Bridge to Advanced Heart Failure Therapy.

In patients with advanced heart failure (HF), temporary mechanical circulator support (TMCS) is used to improve hemodynamics, via left ventricular unloading, and end-organ function as a bridge to definitive therapy. While listed for cardiac transplantation, use of TMCS may be prolonged, preventing adequate mobility. Here, we describe the technique for placement of a percutaneous axillary intra-aortic balloon pump (IABP) using single-site arterial access to facilitate ambulation and subsequent safe removal without surgery or a closure device. Retrospective review of the experience with this approach at a single institution between September 2017 and February 2020 documented feasibility and safety. Baseline demographics, hemodynamic data, and clinical outcomes were collected. Thirty-eight patients had a total of 56 IABPs placed. There were no significant access site or cerebrovascular complications. One fifth of IABPs (21.4%) had balloon failure or migration, requiring placement of a new device, though no patients had significant complications from balloon failure. The majority (81.6%) of patients in the cohort on axillary IABP support were ambulatory and ultimately received the intended therapy (63.2% transplant, 13.2% durable left ventricular assist device, 5.3% other cardiac surgery). Percutaneous, axillary IABP is feasible and associated with an acceptable complication rate as a bridge to definitive therapy.

Heart-After-Liver Transplantation Attenuates Rejection of Cardiac Allografts in Sensitized Patients.

BACKGROUND: In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation. OBJECTIVES: The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection. METHODS: Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained. RESULTS: A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction. CONCLUSIONS: A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Risk of Liver Dysfunction After Left Ventricular Assist Device Implantation.

BACKGROUND: Incident liver dysfunction after left ventricular assist device implantation has been previously associated with adverse outcomes, yet data on perioperative risk markers are sparse. METHODS: We retrospectively reviewed consecutive patients undergoing continuous-flow left ventricular assist device implant between 2007 and 2017 at a single institution. Perioperative variables were evaluated by univariate modeling and adjusted for false discovery rate. Variables most significantly associated with incident Interagency Registry for Mechanically Assisted Circulatory Support-defined liver dysfunction (INT-LD) were evaluated using logistic regression and optimal cutpoints were defined. One-year survival was evaluated using Kaplan-Meier analysis. RESULTS: We included 359 patients (79% male; mean age 59 ± 13 years; 46% ischemic; 64% destination therapy). Lower right ventricular stroke work index at the time of right heart catheterization, higher right atrial pressure 6 hours after right heart catheterization, higher preoperative total bilirubin, longer cardiopulmonary bypass time, and greater volume of intraoperative ultrafiltration were most strongly associated with incident INT-LD (adjusted P < .01 for each). Initial right ventricular stroke work index less than 460 mm Hg∗mL/m2 (odds ratio [OR] 4.6; 95% confidence interval [CI], 2.3 to 9.4), 6-hour right heart catheterization 14 mm Hg or greater (OR 4.3; 95% CI, 2.1 to 8.8), cardiopulmonary bypass time longer than 137 minutes (OR 3.3; 95% CI, 1.8 to 6.2; P < .01 for all), ultrafiltration more than 2.95 L (OR 3.7; 95% CI, 2 to 6.8), and total bilirubin greater than 1.4 mg/dL (OR 2.7; 95% CI, 1.4 to 5) were each strongly associated with risk of INT-LD, which was associated with decreased unadjusted 1-year survival (P < .001). CONCLUSIONS: Right ventricular stroke work index, right heart catheterization, cardiopulmonary bypass time, and ultrafiltration were each more strongly associated with elevated risk of INT-LD after left ventricular assist device implant than total bilirubin. Therefore, optimization of right ventricular hemodynamics and minimizing cardiopulmonary bypass time and ultrafiltration could potentially reduce the risk of liver dysfunction, but these observations require prospective validation.

Primary Malignant Pericardial Mesothelioma: A Clinical Case Series Illustrating the Necessity of a Multidisciplinary Approach.

Primary malignant pericardial mesothelioma is a rare cardiac neoplasm. The authors evaluated risk factors, clinical presentation, and outcomes by reviewing all biopsy-confirmed cases at one institution. The use of multimodality imaging, detailed hemodynamic assessment for the presence of an effusive-constrictive profile, and cytology evaluation can support the diagnosis. (Level of Difficulty: Advanced.).

Right Ventricular Dysfunction and Long-Term Risk of Sudden Cardiac Death in Patients With and Without Severe Left Ventricular Dysfunction.

BACKGROUND: Right ventricular systolic dysfunction (RVD) often coexists with various cardiopulmonary diseases. However, the association between RVD and risk of sudden cardiac death (SCD) has not been well studied. This study examined the risk of SCD associated with RVD in patients with heterogeneous underlying cardiac diseases. METHODS: The Mayo Clinic cardiac care unit database included 5463 consecutive patients with complete echocardiographic evaluation to assess right ventricular systolic function and RVD severity. Prospective surveillance follow-up was obtained for all patients. SCD was adjudicated when a malignant ventricular arrhythmia was documented as the primary rhythm leading to death. RESULTS: The prevalence of mild RVD and moderate-severe RVD was 14.9% and 17.1%, respectively. Patients with RVD were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and lower baseline left ventricular ejection fraction compared with those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of SCD was highest in patients with moderate-severe RVD (7.4% versus 4.4% in mild RVD versus 1.6% in normal right ventricular function; P<0.001). After adjustment for baseline characteristics, mild RVD (adjusted hazard ratio, 1.57; P=0.046) and moderate-severe RVD (adjusted hazard ratio, 1.91; P=0.006) were independently associated with an increased risk of SCD. Moderate-severe RVD remained an independent predictor of SCD for patients with left ventricular ejection fraction >35% without or with preexisting implantable cardioverter-defibrillator (adjusted hazard ratio, 4.12; P=0.003 and adjusted hazard ratio, 5.04; P<0.001, respectively). CONCLUSIONS: Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.

Outcomes After Cardiac Transplant for Wild Type Transthyretin Amyloidosis.

BACKGROUND: The true prevalence of heart failure due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced heart failure and the natural history of extracardiac ATTRwt. METHODS: We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes, were obtained. RESULTS: Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean, 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mm Hg) before HTx. Three-year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 mL·kg·min) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n = 2) and peripheral nerve involvement (n = 4) by ATTRwt developed late. CONCLUSIONS: This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation.

Association Between Early Cardiac Rehabilitation and Long-term Survival in Cardiac Transplant Recipients.

OBJECTIVE: To determine whether participation in early cardiac rehabilitation (CR) after heart transplant (HTx) affects long-term survival. PATIENTS AND METHODS: A retrospective review was conducted in 201 patients who underwent HTx at Mayo Clinic between June 1, 2000, and July 31, 2013. Patients were excluded with multiorgan transplant, no CR data, and follow-up less than 90 days after HTx. Demographic and exercise data at baseline before HTx were collected. Post-HTx exercise capacity, biopsy, CR data, and medications were collected at 1 through 5 and 10 years. RESULTS: Overall survival at 1, 5, and 10 years was 98%, 88%, and 82%, respectively; 29 patients died. Number of CR sessions attended in the first 90 days after HTx predicted survival in multivariate regression, controlling for baseline post-HTx 6-minute walk test (6MWT) results and rejection episodes (hazard ratio, 0.90; 95% CI, 0.82-0.97; P=.007). Additional univariate predictors of survival included pre-HTx 6MWT results, weight at HTx, and body mass index and systolic blood pressure at CR enrollment. Pre-HTx 6MWT results, body mass index, and post-HTx were associated with improvement in peak oxygen consumption. CONCLUSION: This report demonstrates, for the first time, an association between CR and long-term survival in patients after HTx. Further work should clarify the most beneficial aspects of CR.

Arrhythmias in Patients with Cardiac Implantable Electrical Devices after Implantation of a Left Ventricular Assist Device.

Utilization of continuous-flow left ventricular assist devices (CF-LVADs) for advanced heart failure is increasing, and the role of cardiac implantable electrical devices (CIED) is unclear. Prior studies of the incidence of arrhythmias and shocks are frequently limited by ascertainment. One hundred and seventy-eight patients were examined with a previous CIED who were implanted with a CF-LVAD. Medical history, medications, and CIED data from device interrogations were gathered. A cardiac surgery control group (n = 38) was obtained to control for surgical factors. Several clinically significant events increased after LVAD implantation: treated-zone ventricular arrhythmias (VA; p < 0.01), monitored-zone VA (p < 0.01), antitachycardia pacing (ATP)-terminated episodes (p < 0.01), and shocks (p = 0.01), although administered shocks later decreased (p < 0.01). Presence of a preimplant VA was associated with postoperative VA (odds ratio [OR]: 4.31; confidence interval [CI]: 1.5-12.3, p < 0.01). Relative to cardiac surgery, LVAD patients experienced more perioperative events (i.e., monitored VAs and shocks, p < 0.01 and p = 0.04). Neither implantable cardioverter defibrillator (ICD) shocks before implant nor early or late postimplant arrhythmias or shocks predicted survival (p = 0.07, p = 0.55, and p = 0.55). Our experience demonstrates time-dependent effects on clinically significant arrhythmias after LVAD implantation, including evidence that early LVAD-related arrhythmias may be caused by the unique arrhythmogenic effects of VAD implant.

Current indications, strategies, and outcomes with cardiac transplantation for cardiac amyloidosis and sarcoidosis.

PURPOSE OF REVIEW: We describe the general strategies for the management of cardiac amyloidosis with particular focus on the use of cardiac transplantation for amyloid cardiomyopathy. Within this article, we highlight recent data regarding the use of combined heart transplant-chemotherapy, use of cardiac transplant in mutant amyloid disease, and underutilization of cardiac transplantation in sarcoidosis. RECENT FINDINGS: Several center experiences have been recently published, describing management strategies in AL amyloid, with focus on timing of chemotherapy as it relates to transplant, and in mutant amyloid in particular. SUMMARY: Outcomes after heart transplantation are typically worse than in patients undergoing heart transplantation for nonamyloid disease. Staged heart transplantation followed by autologous stem cell transplant therapy appears to provide the best long-term outcome for AL amyloid in highly selected patients. Mutant transthyretin amyloidosis is a disorder related to production of abnormal transthyretin protein in the liver. Combined heart/liver transplant has been utilized to treat both the production of the abnormal transthyretin protein and manage the cardiac dysfunction in highly selected patients, with favorable outcomes. Wild-type transthyretin amyloidosis occurs predominantly in older men. Cardiac transplantation can be utilized for highly selected patients. Sarcoidosis with cardiac involvement, unresponsive to immunosuppressive therapy, may be treated successfully with cardiac transplantation.