Bois, John P.

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.

Background: Angina with no obstructive coronary arteries (ANOCA) is clinically challenging to diagnose and manage. The agreement between Doppler-derived coronary flow reserve (CFR Doppl ) and PET-derived CFR (CFR PET ) in patients with ANOCA remains unclear. Aims: To evaluate the correlation between Doppler- and PET-derived CFR in patients with ANOCA. Methods: We conducted a single-center, retrospective study of adult patients (age ≥18 years) with ANOCA who were referred for evaluation of possible microvascular ischemia with Doppler- and PET-derived CFR at the Mayo Clinic (Rochester, MN) between January 1, 2018, and May 1, 2024. Pearson correlation was used to quantify the association between Doppler- and PET-derived CFR. Agreement between Doppler- and PET-derived CFR was assessed by Bland-Altman analysis using a 2-way mixed effects model with measures of absolute agreement. Results: A total of 66 patients were initially identified, of which 40 were included in the final analysis (66.7% female, median age 58 years [Q1-Q3: 45-66 years]). Median time between PET- and Doppler-derived CFR was 8 days (Q1-Q3: 1-31 days). Median CFR Doppl was 2.75 (IQR: 2.23-3.28) and median CFR PET was 2.50 (IQR: 2.10-3.10). Doppler-derived CFR displayed a wider range than PET-derived CFR (0.8-5.2 vs 1.2-4.0). A strong correlation was found between Doppler- and PET-derived CFR ( r= 0.81; p<0.001). The corresponding Bland-Altman plot showed an overall bias of 0.27±0.56 (intraclass coefficient=0.85; p<0.001). Conclusions: While invasive coronary angiography with CFR Doppl is the gold-standard for the diagnostic evaluation of ANOCA, PET imaging with CFR PET offers an excellent first line non-invasive modality for diagnosis of coronary microvascular dysfunction.

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: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by fibrofatty replacement of myocardial tissue, creating areas of electrical heterogeneity and increasing the risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Catheter ablation is commonly performed in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) for management of ventricular arrhythmias (VAs). Whether catheter ablation affects cardiac function post-procedurally is uncertain. Research Question: Does catheter ablation for ARVC result in acute change in cardiac function? Goals/Aims: To assess the impact of catheter ablation for VAs on cardiac function in the acute post-procedure setting. Methods: This retrospective study included patients with ARVC who underwent catheter ablation for VAs at Mayo Clinic. Cardiac function was assessed on pre- and post-procedure transthoracic echocardiograms (TTEs). Post-procedure TTEs were obtained within 4 weeks after the ablation procedure. Right ventricular (RV) enlargement and systolic dysfunction were evaluated as continuous variables (0=none, 1=mild, 2=mild-moderate, 3=moderate, 4=moderate-severe, 5=severe). Results: The study included 32 patients who underwent a total of 44 ablations. Mean age at the time of ablation was 49±16 years, and 24 (75%) were male. After a mean follow-up duration of 2.6±5.5 days, there was a significant worsening in mean RV dysfunction (1.6±1.5 to 2.0±1.4, P = 0.001). There were no significant changes in mean left ventricular ejection fraction (LVEF), left ventricular (LV) dimensions, and RV size. 6 (14%) patients had a >5% decline in LVEF, and 14 (32%) patients had worsening RV function. Transient inotropic support was required in 4 (9%) patients. Conclusion(s): This study is the first to assess the acute impact of catheter ablation for VAs on cardiac function in ARVC patients. These results underscore the importance of careful post-procedure monitoring and planning of the ablation target in these patients to avoid excessive ablation and therefore impairment in cardiac function.

Background: Differentiating between causes of non-ischemic cardiomyopathy is important for disease-directed treatment. Cardiac MRI (CMR) and the use of late gadolinium enhancement (LGE) have proven useful for enhancing diagnostic accuracy. Definitive assessment of cardiomyopathy etiology by explant pathology facilitates direct evaluation of CMR utility. Hypothesis: We hypothesized direct comparison between pre-transplant (Tx) CMR and explant pathology will improve the characterization of undifferentiated cardiomyopathy through examination of cases where pre- and post-Tx diagnoses were discordant. Aims: To evaluate discrepant cases to describe imaging patterns in relation to post-Tx diagnosis. Methods: Institutional Tx recipients between 2000 and June 2023 were queried for pre-Tx MRI (n=122). Discrepant cases were identified (n=8). Pre-Tx diagnostic modalities, including CMR, were reviewed, and CMR patterns were evaluated in association with ultimate explant diagnosis. Results: Of the eight patients with discrepant diagnoses, five carried clinical diagnosis of dilated cardiomyopathy, one hypertrophic cardiomyopathy, one peripartum cardiomyopathy, and one congenital heart disease having undergone tricuspid valve and ASD repair. Pathologic evaluation most frequently identified biventricular or left ventricular arrhythmogenic cardiomyopathy (ARVC) (n=6), where CMR disclosed a diffuse pattern of subepicardial LGE and pre-Tx diagnosis of DCM was most common. Two of these pathologic descriptions represented a different disease on genetic evaluation: one patient had Danon disease, another had a LMNA pathogenic variant. The presumed peripartum cardiomyopathy was identified as Fabry’s disease on pathology (however, genetic testing consistent with Danon disease). Both Danon disease patients had primarily subendocardial LGE on CMR. One patient with a DCM phenotype had HCM pathologically. Results summarized in Table 1. Conclusions: Cardiac MRI can be a useful modality for the evaluation of underlying cardiomyopathy and should prompt appropriate genetic testing. Diffuse subepicardial LGE frequently accompanied the diagnosis of ARVC whereas a non-subepicardial pattern reflected alternative etiologies identified only through genetic testing.

Introduction: Unexplained high-grade AV block (AVB) in patients age <65 years is among the salient features of cardiac sarcoidosis (CS). Guidelines recommend that CS patients with high-grade AVB should receive an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) rather than a permanent pacemaker (PPM). However, in clinical practice, CS may be recognized after PPM implantation for high-grade AVB. Aims: To evaluate the characteristics and outcomes of patients diagnosed with CS after PPM implantation for high-grade AVB and assess the decision-making and rationale for upgrade to ICD/CRT-D. Methods: Retrospective review of the Mayo Clinic Sarcoid Registry (n=848) was performed to identify all patients for which a PPM was implanted for high-grade AVB prior to the diagnosis of CS. Baseline clinical and imaging characteristics were collected during index evaluation at our institution. Decision-making for ICD upgrade, lead management strategy, immunosuppression initiation, and outcomes were assessed. Results: Overall, 29 of 848 (3.4%) of CS patients (62% probable/definite CS; 77% male; median (IQR) age 56 (48-61) years; and median (IQR) LVEF 58% (50-62) received a PPM for high-grade AVB prior to a CS diagnosis. Median (IQR) interval between PPM implant and index evaluation was 10 (3-23) months. Eight of 29 patients underwent upgrade to ICD (n=4) or CRT-D (n=4). Among them, the pacing lead was extracted in 4. All patients were upgraded for primary prevention of sudden cardiac death (SCD), with 3 of them also having LVEF<50% requiring upgrade to CRT-D. Twenty-two (79%) patients in the total cohort were treated with immunosuppression. During median (IQR) follow-up 37 months (11-74), 1 patient in the upgrade group had sustained VT appropriately treated with anti-tachycardia pacing. No events were documented among patients in the non-upgrade group. At last follow-up, 6 (75%) patients in the upgrade group and 12 (57%) in the non-upgrade group were pacemaker dependent. Median LVEF change was 0% in patients who underwent upgrade to CRT-D and –0.2% in those who underwent upgrade to ICD or no upgrade. Conclusions: In this cohort of patients diagnosed with CS several months after a PPM had been implanted for high-grade AVB, incident VT/VF was infrequent with contemporary CS management. In the absence of other SCD risk factors, CS patients who received a PPM for high-grade AVB prior to their CS diagnosis may not require ICD upgrade.

Introduction: The prevalence and prognostic significance of PVC and NSVT in cardiac sarcoidosis (CS), especially in patients with normal or mildly decreased LV function, are not well known and were investigated in the current study. Methods: We included 192 patients with definite and probable CS with LVEF>35%, no prior history of VT/VF or sudden cardiac death, who underwent up to 48 hours of Holter monitoring. They were followed retrospectively for the composite endpoint of sustained VT/VF, advanced heart failure therapy, and all-cause mortality. We performed multivariable analysis for the association of PVC burden and NSVT with the composite endpoint. Covariates were considered if they were present in at least 95% of the study sample and were significantly associated with the composite endpoint in univariable analysis. Results: The median PVC burden in the overall population was 0.3% (IQR 0.02-2.5%) and 36 (18.8%) patients had a PVC burden ≥5%. Sixty-two (32.3%) patients had NSVT detected during monitoring. The PVC burden and prevalence of NSVT in patient subgroups are shown in Figures 1 and 2. A total of 33 (17.2%) patients experienced one of the composite endpoints at a median follow-up of 3 years. In the multivariable analysis (Figure 3), PVC burden ≥5% versus <5% (HR 3.96 [1.19, 5.97], p-value <0.01) and presence of NSVT (HR 4.55 [2.09, 9.94], p-value <0.01) were associated with the composite outcome. Conclusion: Our results suggest that a high PVC burden and the presence of NSVT carry isolated prognostic value in CS. In addition, ventricular ectopy does not appear to be an indicator of disease activity based on abnormal uptake on PET scan.

Abstract We report a case of severe hypertriglyceridemia (HTG) complicated by hyperviscosity syndrome as a possible adverse reaction to risankizumab-rzaa in a 49-year-old male with a history of longstanding uncontrolled type 2 diabetes, obesity, and coronary artery disease with prior ST-elevation myocardial infarction. On admission, the patient presented with xanthomatous plaques, chest and epigastric discomfort, and headache. Subsequent blood testing revealed severely elevated triglyceride (TG) levels at 7670 mg/dL (86.59 mmol/L) [reference range: &lt;150 mg/dL; 1.69 mmol/L] and total cholesterol at 934 mg/dL (24.14 mmol/L) [reference range: &lt;200 mg/dL; 5.17 mmol/L]. Triglyceride levels decreased and symptoms resolved with dietary restrictions and plasmapheresis. At follow-up, his TG remained elevated but improved, and he was advised to continue lipid-lowering medications as well as cessation of risankizumab. While the patient presented with high risk factors, we posit that the subacute presentation of severe HTG is a possible result of his recent course of risankizumab-rzaa therapy for management of psoriasis. This is noteworthy as pharmaceutical surveys and clinical trials do not list severe HTG as an adverse effect. Postmarketing surveillance studies are essential to confirm this potential association and monitor drug safety. In summary, this case highlights a possible link between risankizumab and severe HTG, emphasizing the importance of ongoing pharmacovigilance to identify and manage unexpected adverse effects associated with new medications.

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.