Citations

Introduction: In the randomized VALOR-HCM study of symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM), mavacamten reduced the need for septal reduction therapy at 16 weeks. Because mavacamten is a cardiac myosin inhibitor that may improve ventricular compliance, this sub-study hypothesized that mavacamten would favorably impact diastolic function. Methods: Symptomatic patients on maximally-tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. Echocardiographic assessment was performed by an independent, blinded core laboratory. Diastolic grade was determined according to ASE guidelines. Between-group comparisons were made from baseline to week 16. Results: Among 112 enrolled patients, baseline left atrial volume index (LAVi) was similar (Table). At 16 weeks, mavacamten treatment resulted in a significant reduction in LAVi (-5.2 vs -0.5 with placebo, p = .003). Similarly, although lateral E/e’ and septal E/e’ were comparable at baseline, patients treated with mavacamten demonstrated a significant reduction at week 16 (lateral E/e’: -3.5 vs 0.7, p <0.001; septal E/e’: -3.3 vs 0.7, p < 0.001)(Table). Patients treated with mavacamten were also more likely to improve their diastolic dysfunction grade (31.4% vs 12.8%, p = 0.032) (Figure). Conclusions: After only 16 weeks of therapy, in a highly symptomatic oHCM population with echocardiographic-guided drug titration, mavacamten improved measures of diastolic function.

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.

Introduction: Repeated 6MWT in clinic are inconvenient for patients and disruptive to usual clinic throughput. Digital measures may be a means to overcome these challenges and reliably measure functional capacity. Methods: As part of an observational clinical trial (NCT04191356), during an 8-week observation period, patients with heart failure (HF) utilize arm-band biosensors (Biofourmis Everion®) for at least 15 hours daily while carrying out daily activities and complete an in-clinic investigator-guided 6MWT on the first and last days of participation. Interim data (N=30, age 56.17 ± 11.26; 24 males; 3 NYHA I, 25 NYHA II, 2 NYHA III) are used for validation, where the distance of baseline 6MWT is used as reference standard. Results: Passive 6MWT, which is the maximum 6-minute step count derived from daily accelerometer data (Fig 1), is strongly correlated with the reference standard (R=0.7501, P<0.0001, N=30) (Fig 2). Further analysis (Fig 2) reveals that regardless of the duration of the step count, the digital measures consistently have strong correlations with the reference standard, with the highest correlation obtained by Passive 10MWT (R=0.7746, P<0.0001, N=30). Conclusions: Early data highlights that accelerometer data collected during daily activities appears to indicate functional capacity of HF patients. Continued data will validate digital measures against various patient outcomes. Fig 1 Aggregation of Passive 6MWT from step count recorded during daily activities Fig 2 Correlation between accelerometer-derived passive step count digital measures and distance manually measured during baseline investigator-guided 6MWT as reference standard (N=30)

Introduction: The prevalence of metabolic syndrome (MS), and diabetes mellitus (DM) is increasing, and the use of biomarkers to identify subjects at risk of developing MS or DM may be useful for disease prevention. Natriuretic peptides (NPs) are well known for their role as biomarkers in heart failure (HF), but are increasingly being recognized for their favorable metabolic actions and potential role as risk modifiers for the development of DM and MS. To date, however, this risk relationship has not been well defined in the general population. Hypothesis: Adults in the general population with lower NP levels are at higher risk for developing DM or MS. Methods: A retrospective review of the Olmsted County Heart Function Study cohort, a population-based random sample of 2042 Olmsted County, MN residents aged ≥ 45 years. A subgroup of community-dwelling subjects without MS or DM at Visit 1 was identified and subjects returned for followup after 4 years (Visit 2). We compared the characteristics of subjects that developed MS or DM after 4 years to those that did not. Results: Of the 911 subjects who did not have MS or DM at visit 1, 93 (10.2%) developed either MS or DM at visit 2. Subjects who developed MS or DM at visit 2 were more likely to have higher baseline BMI (p <0.001), lower HDL (p<0.001), higher triglycerides (p < 0.001), higher insulin (p< 0.001), higher aldosterone (p < 0.001) levels, lower NT-proANP (p<0.001) and lower NT-proBNP levels (p < 0.01) compared to those that did not develop MS or DM. Those that developed MS or DM were also at higher risk for development of HF when controlling for age and sex (HR 2.73 CI 1.25-5.96). On univariate analysis, higher baseline levels of NT-proANP and NT pro-BNP had a significant negative association with developing new MS or DM (ORs per 1 SD increase: 0.64, CI 0.51-0.79 p < 0.0001 and 0.76, CI 0.62-0.95 p=0.016, respectively). Conclusions: Among adults aged ≥ 45 years in the community, low levels of NT- ANP and NT-proBNP are associated with increased risk of development of DM and MS. Further studies are warranted to determine if potentiating the natriuretic peptide system would delay the development of DM or MS.

A 68 year old female with hyperlipidemia and tobacco use presented with acute, substernal, chest pressure that occurred during yard work. She had no prior history of coronary artery disease or stable angina. Electrocardiograms (ECG) did not have ischemic changes but high sensitivity troponin was elevated at 285 ng/L and peaked at 1308 ng/L. Therapy was started for acute coronary syndrome and nitroglycerin drip for continued discomfort. Echocardiogram showed ejection fraction of 61% and akinesis of the infero-septum at the mid-ventricle. Coronary angiogram showed diffuse narrowing of the large first septal branch artery (S1) concerning for coronary intramural hematoma. No other significant coronary artery disease was present. Cardiac magnetic resonance (CMR) confirmed hypokinesis of the septum and subendocardial delayed enhancement in the interventricular septum at the mid ventricle suggestive of an isolated septal perforator infarct. She was conservatively managed and discharged 48 hours later. Four days later she had recurrent chest pressure and was re-admitted. Her ECG showed J-point elevation in the anteroseptal leads. Repeat coronary angiogram showed unchanged type 2 spontaneous coronary artery dissection of S1 and a small coronary cameral fistula between the distal septal branch and the right ventricle. The diagnosis of spontaneous coronary artery dissection of the first septal branch is rare and may be missed on angiogram. CMR in addition to invasive coronary angiography aides in the evaluation of this rare cause of acute myocardial infarction and changes clinical management decisions including observation time and evaluation for fibromuscular dysplasia.

Case Presentation: 49-year-old male without known cardiovascular history presented with three days of atypical chest discomfort. 12-lead EKG revealed ST-segment elevations in II-III-aVF and depression in V1 suggestive of an acute infero-posterior MI (A), Troponin T at 6.85 ng/mL. Following administration of DAPT and heparinization, emergent coronary angiography proved a dominant RCA with proximal 60% and middle 100% occlusion (B), 80% focal stenosis at mid-LAD and 70% focal stenosis at prox-LCx (C). PCI with intra-aortic balloon pump support was performed, with two DES deployed in the RCA, use of a trans-venous pacemaker was required for complete AV block, and two defibrillations required for ventricular fibrillation. Following further hemodynamic compromise unexplained by his hemodynamic parameters, TEE was performed, demonstrating a large mid/distal infero-septum ventricular septal defect with left to right shunt (D, E and F), as well as a basal/mid infero-septum large pseudo-aneurysm (PSA) cavity (contained rupture) (G: low velocity Doppler flow from LV to PSA cavity, H and I show intact septum). The patient continued to decompensate requiring escalation to temporary mechanical circulatory support with VA-ECMO. Heart transplantation was initially considered, family decided to withdraw care due to multi-organ failure and poor prognosis Discussion: Due to widespread availability of primary percutaneous coronary intervention with early reperfusion, mechanical complications post MI are less common in current days. Following transmural MI, persistent hypotension and cardiogenic shock should alert for complications such as VSD or PSA. While VSD may be amenable to percutaneous or surgical closure, PSA is associated with very high mortality even if surgery is attempted. Given the presence of both a VSD and PSA, mechanical support with VA-ECMO allowed us to support the patient for several days as a bridge to decision regarding heart transplantation

Introduction: In seniors, the prevalence of abdominal aortic aneurysms (AAA) is high (9-10%). We aim to characterize AAA growth rates (slow vs. rapid) to help inform management strategies, including individualized imaging surveillance frequency. Hypothesis: Modeling thrombosis may improve the characterization of AAAs' growth status. Methods: 3D geometrical AAA models with and without thrombosis (vessel lumen only) were generated for 70 human subjects using available contrast-enhanced CTA data. AAA growth rates were categorized as slow (< 5 mm/year) or rapid (≥ 5 mm/year) based on serial imaging. Python scripts were used to calculate geometrical parameters (83) with and without thrombosis. Patient-specific relevant health information was retrieved through a review of medical records. Support vector machine (SVM), a well-established machine learning method, was run with 10-fold cross-validation (100 iterations) to assess the predictive accuracy. Results: Among 70 AAAs studied, the ratio between rapidly-growing and slowly-growing was nearly 1:2. The combination of antihypertensive medication, coronary artery disease, juxta-aneurysm aortic size, and five geometrical parameters quantifying the extent of thrombosis provided the best accuracy for AAA's growth status. The area under receiving operating curve (AUROC) was 0.85, and total accuracy was 0.81, with 57% and 93% of rapidly- and slowly-growing AAAs correctly identified, respectively. Excluding patients with aneurysm thrombus, the AUROC and accuracy in predicting rapidly-growing AAAs decreased to 0.82 and 48%, respectively. Conclusions: machine-learning-based predictive modeling appears feasible for characterizing AAA's growth rate status. Manual aortic image segmentation, required for data analytics, is labor-intensive (on average, 1 hour). Leveraging artificial intelligence-based segmentation methodology may provide an automated solution to improve workflow and feasibility.

Background: Highly caffeinated energy drinks (HCEDs) can trigger life-threatening cardiac arrhythmias in individuals with and without an underlying genetic predisposition. Though the mechanism(s) responsible for these events remain unclear, it has been postulated that high caffeine may alter heart rate, blood pressure, cardiac contractility, and cardiac repolarization in a manner that is pro-arrhythmic. Objective: To describe our experience regarding sudden cardiac arrest (SCA) events occurring in proximity to HCED consumption in patients with underling genetic heart diseases. Methods: All SCA survivors referred to the Mayo Clinic Windland Smith Rice Genetic Heart Rhythm Clinic for clinical and/or molecular evaluation were reviewed to identify those with a history of HCED consumption prior to their event. Patient demographics, clinical characteristics, documented HCED consumption, and temporal relationship of HCED consumption to SCA were extracted from the electronic medical record. Results: Among 144 SCA survivors with a structurally normal heart, 8 (6 females; mean age at event 28 ± 8 years) experienced an unexplained SCA associated temporally with HCED consumption. Of these, 5 (63%) had either long QT syndrome (n=3) or catecholaminergic polymorphic ventricular tachycardia (n=2). The remaining 3 were diagnosed with unexplained SCA/idiopathic ventricular fibrillation after a comprehensive evaluation. Three patients (37%) were habitual HCED consumers while 5 (63%) imbibed for the first time with consumption ranging from several hours to a few minutes before the SCA. Seven patients (88%) required a rescue shock (average 2 ± 2 shocks/patient) while 1 was manually resuscitated. Upon follow-up, 6 (75%) were dismissed with an implantable cardioverter defibrillator, 1 (13%) on pharmacologic therapy, and 1 (13%) underwent denervation surgery. All SCA survivors have quit drinking HCEDs and have been event-free since. Conclusion: Overall, 8/144 (5.6%) of SCA survivors evaluated in our program experienced a SCA in proximity to consuming a HCED. Although larger cohort studies are needed to elucidate the precise mechanism for HCED-triggered/associated SCA and quantify its precise pro-arrhythmic risk, it seems prudent to sound an early warning.

Background: The estimated prevalence of attention-deficit/hyperactivity disorder (ADHD) globally is about 5%. For patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), ADHD-directed stimulant therapy is relatively contraindicated. However, previous studies have shown that use of these treatments is safe for patients with long QT syndrome, a similar genetic heart disease. Whether this is the same for patients with CPVT remains unknown. Objective: To evaluate ADHD-directed treatment, outcome, and frequency of CPVT-triggered events in patients with CPVT and concomitant ADHD. Methods: A retrospective electronic medical record review of 216 patients with CPVT evaluated in Mayo Clinic’s Windland Smith Rice Genetic Heart Rhythm Clinic was performed to determine the prevalence of concomitant ADHD and the incidence of CPVT-triggered events in these patients. Results: Overall, 14 patients (6%) were diagnosed with CPVT and concomitant ADHD (6 female, average age 19 ± 3 years). At the time of first evaluation, ADHD-directed stimulant therapy was stopped or advised against in 8/14 patients (57%). It was (re)started in 11 patients (79%) following comprehensive evaluation and treatment initiation for CPVT with pharmacologic therapy in 14/14 patients (100%), denervation surgery in 12 (86%), and an implantable cardioverter defibrillator in 4 (29%). Prior to Mayo Clinic evaluation, 10 patients (71%) treated for CPVT had a breakthrough cardiac event, without being on stimulant therapy, while 4 patients (29%) had an event while being treated for both CPVT and ADHD for an average time on stimulant therapy of 6 ± 6 years. Following CPVT treatment optimization and ADHD stimulant (re)initiation, patients have remained event-free for a total of 82 patient years (mean follow-up 6 ± 5 years). Conclusion: Among patients with CPVT, the prevalence of ADHD was similar to that in the general population, which can be treated safely and effectively with stimulant therapy. Although the rate of adverse events was low in stimulant-treated patients, physicians should weigh the potential effects of suboptimal treatment of ADHD with the theoretical proarrhythmic risk from stimulant medications on a case-by-case basis.

Introduction: Rare cardiac complications of COVID-19 and COVID-19 mRNA vaccination include pericarditis and myocarditis. Patients with recurrent pericarditis may be at increased risk of triggered recurrence. The known efficacy of the interleukin (IL)-1 antagonist rilonacept in treating and preventing recurrence could inform COVID-19 disease and vaccination management. Methods: The Phase 3 trial RHAPSODY was a global, double-blind, placebo-controlled, randomized-withdrawal study. A long-term extension (LTE) enabled up to 24 months further open-label treatment from May 2020 until June 2022. Concomitant vaccination data and adverse events, including COVID-19, were collected. Results: No COVID-19 cases were reported during the run-in and randomized withdrawal periods (n=86). As of the 6 May 2022 data cutoff, a COVID-19 AE was reported in 19% (14/74) of LTE subjects, of whom 12 were on rilonacept: 5 of 44 fully-vaccinated (≥14 days beyond second serial dose) subjects (11.4%) and 9 of 30 unvaccinated or partially-vaccinated subjects (30.0%). Of the fully-vaccinated subjects, 1 case occurred ~11 months post primary vaccination cycle (no booster). COVID-19 severity was mild (n= 11), moderate (n=2), or severe (n=1). All cases resolved except the severe AE complicated by comorbidities; the subject discontinued. Of 12 subjects receiving rilonacept at the time of COVID-19 diagnosis, 10 maintained dosing with rilonacept, 1 interrupted rilonacept for ~4 weeks, and 1 discontinued rilonacept permanently; none experienced a pericarditis recurrence (PR) after the AE. The remaining 2 subjects had previously interrupted rilonacept for off-treatment observation: one had a PR >4.5 months after suspending rilonacept and 18 days after COVID-19 resolution; no PR in the other (>6 months). There were no PR AEs associated with COVID-19 vaccination (all subjects were receiving rilonacept). Conclusions: In patients on rilonacept in this study, although numbers are small, vaccination reduced COVID-19 events, pericarditis recurrence was not increased by vaccination or disease, and no pericarditis recurrences occurred during rilonacept treatment. One pericarditis recurrence occurred remotely after rilonacept suspension in the peri-COVID-19 period.