Elwazir, Mohamed Y.

Background A multidisciplinary approach improves guideline‐directed medical therapy in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis is unreported. Methods and Results In a retrospective cohort study, we reviewed 848 patients from our institutional cardiac sarcoidosis clinics, identifying those with a cardiac sarcoidosis diagnosis, HF (left ventricular ejection fraction <50%) at index evaluation, and echocardiograms within 90 days and 11 to 36 months. Patients were stratified by participation in a pharmacist‐led medication therapy management (MTM) program for guideline‐directed medical therapy optimization (MTM versus non‐MTM [NMTM]) without randomization. Demographics, left ventricular ejection fraction, guideline‐directed medical therapy (quantified by Kansas City Medical Optimization score), and immunosuppressive therapy were assessed. Primary outcomes included changes in Kansas City Medical Optimization score, left ventricular ejection fraction, and cardiovascular event–free survival (unplanned HF hospitalization, left ventricular assist device /heart transplant, or death). The final cohort included 111 patients (median age, 57 years; 34% women; 64% New York Heart Association class I–II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean Kansas City Medical Optimization score was similar at index evaluation (MTM, 23.2; NMTM, 29.6; P =0.83). At follow‐up (median, 16 months), the Kansas City Medical Optimization score increased significantly in both groups (MTM, 23.2 to 74.8; P <0.001; NMTM, 29.6 to 58.7; P <0.001) but was higher in MTM ( P =0.001). Mean left ventricular ejection fraction trended toward higher values in MTM (44.4% versus 40.0%, P =0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (hazard ratio, 11.97 [95% CI, 1.58–90.54]; P =0.002). Conclusions In this retrospective cohort study, a pharmacist‐led MTM program was associated with favorable guideline‐directed medical therapy optimization and lower risk of adverse cardiovascular outcomes in patients with cardiac sarcoidosis with HF.

Introduction: Cardiac sarcoidosis (CS) often results in systolic heart failure (HF) and responds favorably to guideline directed medical therapy (GDMT). A multidisciplinary team approach to HF care is recommended but few published examples exist in CS patients. Methods: We queried an institutional registry of 599 CS patients (2000-2023) for patients with index LVEF < 50% (within 90 d of index CS evaluation) and follow-up TTE within 11-36 months. In our CS medication therapy management (MTM) program (started 1/8/2019), pharmacists conduct independent visits with CS patients (in person or remote), discuss GDMT tolerance and symptoms, review monitoring laboratory studies, and adjust GDMT (ACEi/ARB/ARNi, beta-blocker, MRA, and/or SGLT2i) via collaborative practice agreement with the CS cardiologists. Patients were classified as MTM (≥1 MTM encounter) or NMTM patients (0 encounters). We compared (1) GDMT, (2) cardiac remodeling, and (3) clinical outcomes (event free survival to first heart failure hospitalization, LVAD, heart transplant, or death). Results: Nineteen percent (113/599) CS patients met inclusion criteria (34% female, 92% white, median age 57 y, 19% definite CS, 58% probable CS, 31% presumed CS), with 44 MTM (median 11.5 encounters, IQR 11) and 69 NMTM patients. Both MTM and NMTM patients were on a median 2 GDMT agents at index evaluation (p=0.21). At follow-up (median 19 mo MTM, 15 mo NMTM, p=0.05), MTM patients were on more GDMT agents than NMTM (median 3.0 vs 2.0, p<0.001), with higher % target dose of ACEi/ARB/ARNi (98% vs 71%, p=0.009), beta-blocker (87% vs 57%, p=0.004), and SGLT2i use (30% vs 9%, p=0.004), but similar MRA use (48% vs 32%, p=0.09). Immunosuppressive therapy was used in 88% patients (89% MTM vs 87% NMTM, p=0.79). Index LVEF was similar (MTM 36%, NMTM 32%, p=0.07). Mean change in LVEF (excluding LVAD/transplant patients) demonstrated a non-significant trend towards improved remodeling in MTM (+8.6%) vs NMTM patients (+5.5%; p=0.39). MTM patients exhibited lower risk of the clinical outcome (1/44 MTM vs 16/69 MTM patients; univariable HR 0.08 [95%CI 0.01 - 0.63], log-rank p=0.016). Conclusions: A pharmacist MTM program for CS patients with HF is associated with improved GDMT uptitration and clinical outcomes, emphasizing the value of collaborative multidisciplinary CS care.

Introduction: Cardiac sarcoidosis (CS) results in HFrEF, but its natural history and response to GDMT remains uncertain. Methods: We queried a registry of 631 CS patients evaluated at our institution to identify those with LVEF < 35% on TTE within 30 d of diagnosis and a follow-up TTE 12-18 months later (external CS diagnoses were excluded). Demographics, LVEF, NT-proBNP, GDMT, immunosuppression, CIED, and outcomes (hyperkalemia, LVAD/transplant, CV hospitalization, death) were recorded. Results: Overall, 25/631 (4%) of CS patients had an LVEF <35% at initial presentation (36% female, 84% white; median age of 58 y; probable/not biopsy-proven CS in 52%). Mean baseline LVEF was 27% (σ=7%), NT-proBNP 1736 pg/mL (n=11), potassium 4.3 mEq/L (n=18), and median NYHA Class II (54%). Patients were on a mean 1.7 GDMT agents at CS diagnosis (Figure). Most were treated with immunosuppression (88%) for mean 0.75 y, usually prednisone (88%, mean 16 mg daily) and fewer with mycophenolate (32%, mean 1875 mg daily), methotrexate (28%, mean 18mg weekly), or TNF-α inhibitor (4%). 64% were on trimethoprim-sulfamethoxazole prophylaxis. At follow-up (median 317 d), 3 patients (12%) required LVAD and 1 (4%) required heart transplant. Mean LVEF improved to 37% (excluding LVAD/transplant, σ=11%, p=0.001). CIED prevalence increased from 48 to 81% (p=0.03). Overall GDMT did not change (mean 2.0 agents, p=0.2) and only beta-blocker dose changed (64 to 138 mg mean daily metoprolol equivalents). Potassium did not change (p=0.4) and hyperkalemic events were infrequent (16%). No patients died, but unplanned hospitalization occurred in 36% of patients. Conclusions: CS patients with HFrEF are usually on partial GDMT at diagnosis, presumably due to earlier recognition of HFrEF, but intensification of GDMT may be limited. Despite improved LVEF which may be due to GDMT, immunosuppression, and/or CIED, over 1/3 patients were hospitalized within 18 mo, highlighting the high-risk profile of HFrEF in CS.

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.

AbstractBackgroundDuring high‐resolution anorectal manometry (HR_ARM), the raw data are converted into software‐derived summary variables (e.g., rectoanal gradient during evacuation) that capture only a snapshot of the data collected during HR_ARM and are less useful than newer indices, which are also derived from the raw data, for diagnosing defecatory disorders (DD). However, it is cumbersome and time‐consuming to extract raw data from the program and calculate such indices. This study aimed to devise a user‐friendly approach to extract anorectal pressures measured with HR_ARM.MethodsAnorectal pressures at rest, during anal squeeze, and evacuation were measured with HR_ARM in 180 women, among whom 60 each were healthy, had DD, or fecal incontinence. A reverse engineering approach extracted pressure values from color images in HR_ARM reports. The summary variables generated by the software and a reverse engineering approach were compared with Lin's concordance correlation coefficient (CCC), pairedt‐tests, and Bland–Altman's tests.ResultsAnorectal pressures summarized by the software and a reverse engineering method were highly concordant for anal resting (CCC [95% CI], 0.98 [0.97, 0.99]) and squeeze pressures (0.99 [0.99, 0.99) and the rectoanal gradient during evacuation with an empty (0.98 [0.97, 0.98]) and a filled balloon (0.99 [0.99, 0.99]). For most variables, the paired t and Bland–Altman comparisons were not significant.ConclusionsAnorectal pressures can be accurately determined from pressure topography images in HR_ARM reports. In future, this reverse engineering approach can be harnessed to compile large HR_ARM datasets across centers and to uncover newer, potentially more useful summary rectoanal pressure variables.

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

To our knowledge, natural history has not been reported for cardiac sarcoidosis (CS) diagnosed by pathologic evaluation of the apical core at left ventricular assist device (LVAD) implantation or cardiac transplantation. We retrospectively identified 232 consecutive patients meeting CS criteria. Of these patients, 54 were diagnosed by pathologic confirmation of CS, 10 after evaluation of the apical core (LVAD implant) or explanted heart (transplant). We compared clinical characteristics at initial evaluation and outcomes for these 10 patients with those of 10 patients with known CS before LVAD implant/transplant. In the study group, five patients (50%) had confirmed extracardiac sarcoidosis before LVAD implant/transplant; five had not been diagnosed with sarcoidosis. Mean (standard deviation) left ventricular ejection fraction at initial evaluation was 23% (16%), and left ventricular end-diastolic dimension was 61 (10) mm. Four patients died during follow-up; however, no survival difference was found for the 10 patients diagnosed incidentally and the group with a previous diagnosis or institutional LVAD/transplant cohorts. Patients diagnosed with CS on pathological examination of the apical core/explanted heart may have severe dilated cardiomyopathy as the initial presentation. Outcomes for patients with CS after advanced heart failure therapies may be comparable with those of non-CS patients.