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Background: Sleep disordered breathing (SDB) is frequently observed in patients with cardiovascular disease, and is associated with intermittent hypoxia, sympathetic activation, oxidative stress, and endothelial dysfunction, all of which may facilitate the development and progression of cardiovascular disease. Objectives: We sought to determine the prevalence, subtypes, and clinical implications of comorbid SDB in patients with hypertrophic cardiomyopathy (HCM). Methods: In this prospective observational study, patients with HCM without prior diagnosis of SDB were recruited to undergo inpatient polysomnography between May 1 st 2018 and October 31 st 2022. Electrocardiographic and echocardiographic parameters, cardiac biomarkers, and symptoms were comparatively assessed in patients with and without comorbid SDB. Patients were assessed for the development of major adverse cardiovascular events (MACE) during follow-up (median 29, range 3-57 months). Results Among 154 participants, 91 (59.1%) were diagnosed with SDB of whom 38 (41.8%) had mild, 22 (24.2%) moderate, 18 (19.8%) severe obstructive sleep apnea, and 13 (14.3%) had central sleep apnea. SDB was associated with greater left ventricular mass (median [IQR]) (128 [107, 161] vs. 109 [96, 134] g/m 2 , p =0.034) and E/e’ ratio (12.5 [10, 15] vs. 10.0 [8.3, 14.5], p =0.039). Patients with HCM over the age of 50 years, with body mass index ≥ 30kg/m 2 , who described their sleep as “poor” were at particularly high risk of having comorbid SDB, as were those who were diabetic, hypertensive, or described greater exertional limitation (NYHA Class ≥II 53% vs. 27%, p =0.005). Importantly, subjects with SDB had elevated baseline Troponin T levels (14 ng/L vs 11 ng/L, p =0.030), and further substantial overnight troponin increases following untreated apneic sleep (2.1ng/L vs 0.2ng/L, p =0.009). Finally, patients with comorbid SDB experienced a significantly higher proportion of incident adverse cardiovascular events (MACE hazard ratio 5.3, 95% CI, 1.6, 17.2, p =0.006) than those without SDB. Conclusions: We report a particularly high burden of previously undiagnosed SDB in patients with HCM, particularly in older, heavier, male patients. Undiagnosed SDB in HCM is not benign and is associated with symptom progression, comorbidity, and a poorer prognosis, particularly in the case of central sleep apnea. These important new findings provide rationale for heightened vigilance and routine screening for SDB in patients with HCM.

Background: Disease-causative variants in LMNA -encoded lamin A/C cause a genetic cardiomyopathy characterized by atrioventricular (AV) block, atrial fibrillation (AF) and ventricular arrhythmias (VA). Whether domain/variant-specific late gadolinium enhancement (LGE) patterns exist and carry prognostic significance is unclear. Objective: To determine if specific LGE patterns correlate with LMNA variant type/missense variant localization and clinical outcomes in a large cohort of cardiac laminopathy patients. Methods: Retrospectively, 621 genotype-positive arrhythmogenic/dilated cardiomyopathy patients were analyzed to identify those with a disease-causative variant in LMNA -encoded lamin A/C. After exclusion of patients without cardiac magnetic resonance data, pertinent demographic/clinical data was extracted from the electronic medical record. LGE distribution (subepicardial, midmyocardial, subendocardial, transmural) and location (septal, free wall, apical) patterns were analyzed by variant type (missense vs truncating) and missense variant localization (central rod domain vs tail domain) and correlated with advanced heart failure (AHF), MVA, AV block, AF and thromboembolic (TE) events. Results: 70 out of 116 (60%) LMNA variant-positive (mean age 39±12, 43% male and 94% Caucasian) were included. Missense variants localizing to the C-terminal tail region showed a higher prevalence of transmural and apical LGE (Table). Amongst the 5 (7%) patients with this distinct apical pseudo-infarct LGE pattern, p.Arg471His-LMNA was identified in all cases. Among the 48/70 (69%) of patients with clinically manifest disease, p.Arg471His-LMNA-positive patients (n=6) were noted to have an increased prevalence of TE events [3 (50%) vs 5 (12%), 0=0.050] despite a reduced prevalence of AF [2 (33%) vs 32 (76%), p= 0.031]. No difference in AHF or MVA were observed, but AV block was less prevalent [1 (20%) vs 29 (74%), p= 0.029]. Conclusion: p.Arg471His-LMNA causes a distinct apical pseudo-infarct LGE pattern associated with an increased risk of TE events and a decreased prevalence of AV block and AF. Future studies are needed to better refine the role of domain/variant-specific risk-stratification/anticoagulation in cardiac laminopathy.

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: Proton beam irradiation to the ventricular myocardium may enable non-invasive targeting of ventricular tachycardia. Previous work has demonstrated the feasibility of imaging ablation lesion with late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI). Hypothesis: We hypothesize that proton beam irradiation will lead to progressively increasing density of LGE corresponding to lesion formation during follow-up after treatment delivery. Aim: The aim of the current study was to determine the time course of LGE intensity in ventricular myocardium following proton beam therapy. Methods: Eleven swine were irradiated with 40 Gy proton beam in the anterior or lateral left ventricular (LV) followed by LGE cardiac MRI every 4 weeks for up to 24 weeks. After manual contouring of the endocardial and epicardial myocardium, a region of interest (ROI) in the area irradiated with 0-5 Gy was contoured (remote ROI). The mean and standard deviation (SD) of the signal intensity (SI) of the remote ROI were calculated. Light LGE was defined as voxels with SI > mean+2SD but < mean+3SD of the remote ROI, while voxels with SI > mean+3SD of the remote ROI were classified as having dense LGE. Voxels identified as bright due to image artifacts or noise were manually removed. The analysis was conducted in a fashion blinded to swine ID and time point after irradiation. Results: A total of 33 time points were analyzed (3.1 ± 1.4 MRI studies per swine). Figure 1A shows a representative time course of LGE in the same swine, progressing from diffuse light LGE at 8 weeks to dense LGE at 16-24 weeks. Figure 1B demonstrates the proportion of light versus dense LGE across timepoints in irradiated myocardial regions. At 8 weeks, light and dense LGE areas were evenly distributed. At 12 to 24 weeks, dense LGE increased to approximately 75%. The proportion of dense versus light LGE was significantly higher at 12, 16, and 24 weeks, as compared to 8 weeks. Conclusion: In ventricular myocardium, diffuse light LGE evident at 8 weeks progresses to denser LGE at 12-24 weeks following proton beam irradiation corresponding with lesion formation.

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.

PURPOSE The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. METHODS The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341 ) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. RESULTS In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. CONCLUSION The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

AbstractIntroductionLittle is known regarding the prevalence and prognostic implications of non‐sustained ventricular tachycardia (NSVT) in patients with wild‐type transthyretin cardiac amyloidosis (ATTRwt‐CA). We aimed to investigate the prevalence of NSVT in patients with ATTRwr‐CA, and the association of NSVT with sustained ventricular arrhythmias (VA) and all‐cause mortality.MethodsIn a cohort of ATTRwt‐CA patients from 2011 to 2022 without prior sustained VA, we ascertained the presence and characteristics of NSVT during clinically indicated ambulatory Holter monitoring. Patients were stratified based on the presence of NSVT at baseline. The primary and secondary endpoints of sustained VA and all‐cause mortality, respectively, were assessed during follow‐up.ResultsThe cohort included 217 patients with ATTRwt‐CA (95% males, median age 75 years; median NYHA class 2). Baseline Holter monitoring demonstrated NSVT in 116 (53%) patients. During a median follow‐up of 27 months (IQR 16–45) after the index Holter monitor, 11 (5.1%) patients reached the primary endpoint of sustained VA (incidence 1.8 per 100 person‐years, all monomorphic VT), and 46 (21%) patients died. In univariable Cox proportional hazard model, NYHA class 3 or 4 heart failure (p = .048), the presence of NSVT (p = .04), the duration of longest NSVT run (p = .029), and the percentage of ventricular ectopy (p < .001) were associated with the primary outcome. When adjusting for age and NYHA class 3 or 4 heart failure, the presence of NSVT remained associated with the primary outcome (p = .03). All‐cause mortality was not significantly different between patients with and without NSVT. A cutoff for ventricular ectopy burden of 0.5%, the median for all patients in this study, was associated with increased risk in sustained VA (log‐rank p = .004) and mortality (log‐rank p = .02).ConclusionNSVT is highly prevalent among ATTRwt‐CA patients undergoing clinically indicated Holter monitoring and may confer an increased risk of incident sustained VA.

Abstract Background Radiofrequency ablation (RFA) has been effective in managing premature ventricular contractions (PVCs). Despite improvement in ablation techniques, recurrence remains high for LV summit PVCs. Epicardial ablation here is often precluded due to fat and proximity to coronaries, thus, aggressive but safe endocardial options are needed. Purpose To evaluate the safety and effectiveness of ultra-long ablation (&gt;240 seconds) duration for refractory LV summit PVCs. Methods Patients with deep intramural LV summit PVCs were identified by lack of PVC elimination or late (&gt;60 s suppression) and recurrence post-lesion under the left aortic sinus of Valsalva. We included patients who received the longest RFA of at least 240 seconds (maximum 15 minutes). RFA power was titrated slowly from 20 to 35W, carefully ensuring that the impedance drop did not exceed 12 ohms. Acute procedure success was defined as clinical PVC suppression for ≥60 minutes after the last lesion. Short-term success was defined as symptom improvement, ejection fraction (EF) recovery, and drop in PVC burden at 3 months. Results Twenty patients (59.5 ± 16.4 years, 55% male) were included. Baseline features are shown in Table 1. All RFA were delivered endocardially. No steam pops were noted. PVC burden was significantly lower at 3-month follow-up (P&lt; 0.01), Figure 1A. Most patients had a normal ejection fraction (EF) at baseline; thus, no significant difference change in EF was observed (Figure 1B). One complication was recorded, which was tamponade likely caused by coronary sinus dissection requiring pericardiocentesis. Acute success was achieved in 95.0% of the cases, and all cases followed at 3 months (18/18) achieved short-term success. Conclusion Ultra-long duration RFA with lesions ≥ 240 seconds at 35W per lesion for LV summit PVCs appeared to be safe and effective in achieving acute and short-term success. The lack of acute suppression should not discourage operators, as there seems to be delayed suppression in some cases. Careful monitoring of biophysics is paramount when attempting this technique.