Bois, John P.

Introduction: Cardiac sarcoidosis (CS) is a non-ischemic disease which can present with right ventricular (RV) dysfunction, but there is a paucity of research describing RV function and natural history in CS. Methods: We queried a registry of 512 CS patients for those with baseline and follow-up echocardiography (TTE). Demographics, medications, and baseline/follow-up TTE data were collected. RV-pulmonary arterial (RV-PA) coupling was approximated by ratio of tricuspid annular plane systolic excursion to estimated pulmonary artery systolic pressure (TAPSE:ePASP). Results: Our query yielded 343 CS patients with mean age 56y (σ=12y), who were predominantly male (67%) and white (90%) with a median follow-up 4y (interquartile range 4.1y). Most had pulmonary sarcoidosis (68%). Baseline TTE data showed left ventricular ejection fraction 48% (σ=14), abnormal RV function with RV systolic pressure (ePASP) 34 mmHg (σ=11), TAPSE 21mm (σ=5), RV S′ 0.14 m/s (σ=0.07), and RV-PA uncoupling (TAPSE:ePASP 0.69 mm/mm Hg, σ=0.25). Baseline RV function parameters did not differ by pulmonary involvement of sarcoidosis. 92% received immunosuppression and 65% received neurohormonal blockade. In long-term follow-up, the overall cohort demonstrated a trend towards worsening of both RV S’ and RV-PA coupling (P=.02 and P=.003 for linear trend, respectively) but stable ePASP (P=.11). Trends in both non-invasive ePASP and RV-PA coupling were similar in patients with and without pulmonary involvement (P=.48 and P=.79, respectively). Conclusions: In our large CS cohort with extensive follow-up, metrics of RV function and RV-PA coupling are often abnormal at CS diagnosis. Echocardiographic measures of PASP tend to remain stable but markers of RV dysfunction, including RV-PA coupling, tend to worsen throughout the disease course irrespective of pulmonary sarcoidosis. More granular phenotyping of pulmonary hypertension in CS is required to better understand this relationship.

AbstractIntroductionCardiac 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.ObjectiveTo determine if CRT improved cardiac remodeling in patients with CS.MethodsWe 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.ResultsOur 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.ConclusionsOur 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.

Introduction: Cardiac Sarcoidosis (CS) is a non-ischemic cardiomyopathy (NICM) characterized by infiltration of non-caseating granulomas involving in the heart with highly variable clinical manifestations. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its effectiveness in patients with CS. Hypothesis: We sought to determine if CRT improved cardiac remodeling and reduced hospitalizations in patients with CS. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at a Mayo Clinic site from 2000-2021. Baseline characteristics, echocardiographic parameters, heart failure hospitalization, 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. At baseline, 38 (69.1%) patients had isolated CS, while 17 (30.9%) had evidence of CS with extra-cardiac sarcoidosis. The overwhelming majority underwent CRT-D implantation (n=52, 94.5%) with 67.3% of implanted devices upgrades from prior pacemaker or implantable cardioverter defibrillator. At 6 months post-implantation there was no significant different in ejection fraction (34.8 ± 10.9 % vs. 37.7 ± 14.2 %, p = 0.237), left ventricular end systolic diameter (49.1 ± 9.9 mm vs. 45.7 ± 9.9 mm, p = 0.077) or left ventricular end-diastolic diameter (58.5 ± 10.2 mm vs. 57.5 ± 8.1 mm, p = 0.574). Within the first 6 months post-implantation, 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 LVAD implantation and 7 (12.7%) patients died. Conclusions: Our findings suggest a poor response to CRT in patients with CS with no significant evidence of reverse remodeling within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Background: Sarcoidosis is multi-system disease characterized by non-caseating granulomas, often presenting with pulmonary involvement. However, in the United States at least one-fourth of sarcoid patients have cardiovascular involvement. Sarcoid can also present as isolated cardiac sarcoidosis (CS), with symptoms that include heart failure (HF), advanced atrioventricular (AV) nodal block, ventricular tachycardia (VT), or sudden cardiac death. Consequently, it has been suggested that CS should be considered in patients presenting with high grade AV block, VT, or heart failure, with a non-ischemic presentation. Here, we present the CS experience at a tertiary medical center. Methods: Patients who underwent 18 F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) PET/CT to assess perfusion and inflammation for clinical suspicion of CS between 2009-2015 at a tertiary referral center were included in the study. These patients were retrospectively assessed for frequency of presenting features. Results: Inclusion criteria were met by 71 patients. VT was the most common presenting symptom seen in 40 of 71 patients (56%). High grade AV block was seen in 24 of 71 patients (34%). VT and high grade AV block was seen concomitantly in 9 (13%). An abnormal PET result was seen in 51 out of 71 patients (72%) with 30 of 51 having VT (59%) and 21 of 51 having AV block (41%). Of the patients with both VT and AV block, 8 of 9 had abnormal PET studies. In 34 of 71 (47%) patients with known extracardiac sarcoid, 18 (53%) had VT and 11 (32%) had AV block. HF symptoms (New York Heart Association class II-IV) were seen in 24 (34%). An abnormal resting ECG was seen in 64 out of 71 patients (90%). Conclusions: In our retrospective cohort VT is the most common presenting symptom in patients with suspicion of CS, and the combination of AV block with VT should raise concerns for an infiltrative process. In patients with extracardiac sarcoid and rhythm disturbance, cardiac involvement should be suspected and screened. Early identification of cardiovascular involvement is critical to ensure that appropriate management of the source of rhythm disturbance or heart failure is addressed before cardiovascular dysfunction is sustained.

AbstractObjectiveEndomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM‐Bx) in suspected cardiac sarcoidosis (CS) are scarce.MethodsSeventy‐nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM‐Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM‐Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation‐free survival were compared between patients with positive and negative EGM‐Bx for CS.ResultsA total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre‐procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation‐free survival were not significantly associated with the EGM‐Bx result (log‐rank p = .91).ConclusionIn patients with suspected CS, abnormal EGM‐Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM‐Bx yield.

Abstract Background Sarcoidosis is an infiltrative inflammatory condition affecting multiple organs, with cardiac involvement designated as cardiac sarcoidosis (CS). It has been proposed that inflammatory conditions like sarcoid increase the risk of venous thromboembolism (VTE), defined as pulmonary embolism (PE) and deep vein thrombosis (DVT) due to the hypercoagulable environment created by inflammation. Purpose Although previous studies have demonstrated an association with sarcoidosis and VTE, these studies failed to account for steroid use (crucial for sarcoid treatment) as an important confounder. Also, no major studies have been done previously assessing the risk of VTE in CS specifically. The objective of this investigation is to determine the association between CS, steroid treatment for CS, and VTE. Methods Patients referred to our institution with concern for sarcoid/CS were retrospectively assessed. Specific variables of interest including general baseline characteristics and those specific to CS were analyzed for their association with VTE development. Results Using Heart Rhythm Society guidelines, 649 patients were split into three categories: 235 with no sarcoid (NS), 91 with extra-cardiac sarcoid (ECS) only, and 323 with CS. In univariate analysis, 39 (12%) CS patients developed a PE vs 9 (4%) NS patients (OR 3.44, p=0.0003) and 44 (14%) CS patients developed DVT vs 18 (8%) NS patients (OR 1.90, p=0.02). In multivariate regression analysis however, neither CS nor ECS was an independent risk factor for VTE (p&gt;0.05) but steroid use was a strong predictor of VTE (HR 3.12, p=0.007 for PE, HR 6.17, p&lt;0.0001 for DVT). Also, steroid dose was found to be an independent predictor for both PE (p=0.001) and DVT (p=0.007) in a Cox proportionate hazards model (significance appeared at &gt;17.5 mg daily on a receiver operating characteristic curve). Conclusion Contrary to previous studies, the current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, steroid therapy for CS treatment leads to an increased prevalence of VTE, specifically at a dose above 17.5 mg daily. More research is required to clarify this relationship and assess the importance of steroid-sparing immunosuppressive therapy and potentially VTE prophylaxis in CS management. Steroid use and time to PE/DVT Funding Acknowledgement Type of funding source: None

Heart failure with reduced ejection fraction (HFrEF) is a progressive clinical syndrome commonly associated with left ventricle dilatation and characterized by reduced cardiac output, secondary pulmonary and systemic venous congestion, and inadequate peripheral oxygen delivery. It is common yet complex and requires synthesis of evidence-based guidelines along with strong clinical acumen. The following is a review of an illustrative case that highlights the important clinical considerations in diagnosis, assessment, and management of HFrEF commonly encountered in practice. Explanations provided highlight of the relevant pathophysiology of HFrEF as well as detailed explanations of interpretation of examinations and both noninvasive and invasive assessment in heart failure. The example provided would hopefully serve as a potential point of reference for trainees as well as healthcare practitioners for patients with HFrEF.