Rayfield, Corbin

Summary: Background: Peripheral arterial disease (PAD) increases cardiovascular (CV) morbidity and mortality, but remains underdiagnosed and undertreated. Several trials support low-dose direct oral anticoagulant (DOAC) use in PAD treatment, although this has yet to be widely adopted in clinical practice. Patients and methods: We conducted a retrospective study of patients who underwent ankle-brachial index testing (ABI) from 1996 – 2020 at Mayo Clinic. We included patients with PAD defined by abnormal ABI (<1.0 or >/=1.4). Primary outcomes evaluated were myocardial infarcts (MI), ischemic strokes (IS), critical limb ischemia (CLI)/amputation, bleeding events and all-cause mortality. DOAC and warfarin use were each compared to no anticoagulant use for the outcomes using univariate analysis and multivariate analysis. Results: 22,162 patients had abnormal ABI readings; 1,266 were on warfarin and 269 were on DOAC for any indication. Both the DOAC and warfarin groups showed significant a decrease in all-cause mortality. The DOAC group showed superior mortality outcomes with HR 0.50 [95% CI 0.40–0.63], p-value <0.001 compared to warfarin with HR 0.88 [95% CI 0.81–0.96], p-value <0.004. There appeared to be a similar trend for MI and CLI/amputation however this was not statistically significant. IS was similar with only warfarin being statistically significant. The DOAC group had improved bleeding outcomes compared to the warfarin group, HR 0.53 (95% CI 0.24–0.85), p-value 0.007. Notably, the addition of ASA for both AC groups resulted in significant HR >1. Conclusions: Our study shows that anticoagulation use, particularly DOACs, is associated with decreased all-cause mortality in patients with PAD. There appears to be a favorable trend for DOACs in MI, IS and CLI/amputation. Lastly, DOACs were found to have superior outcomes with bleeding events.

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Idiopathic ventricular fibrillation (IVF) is responsible for 5-7% of sudden cardiac arrests in the absence of substrate for ventricular arrhythmia, structural diseases, or primary arrhythmic syndromes. The characteristics, management, and prognosis of these patients are unclear. Purpose To investigate the clinical features, management, and prognosis of IVF in our hospital healthcare system Methods Mayo Database Explorer software was used to identify IVF patients from our hospital electronic medical records between 1990 to 2022 in 5 states. The medical records were manually reviewed. Results A total of 132 patients were initially diagnosed with IVF. During the 9.2±6.8 years mean follow-up, 36 [27.3%] patients were later diagnosed with structural diseases or primary arrhythmic syndromes (dilated cardiomyopathy [41.7%], Long QT syndrome [27.8%], catecholaminergic polymorphic ventricular tachycardia [8.3%], Brugada syndrome [5.6%], mitral valve-related arrhythmia [5.6%], and short QT syndrome [2.8%]). Among the rest of the 96 patients with true IVF (mean age 38.4±15.7 years, male 59.4%, Caucasian 80.2%, hypertension 28.1%, diabetes 8.3%), 91 (94.8%) patients presented with out-of-hospital cardiac arrest and 88 (91.7%) patients had a history of syncope. Early repolarization and fragmented QRS were noted in 32 (33.3%) and 28 (29.1%) patients, respectively. Defibrillators were implanted in 92 (95.8%) patients. Genetic testing was performed in 35 (36.5%) patients, and possible associated mutations were found in 13 (37.1%) patients. An Electrophysiology study was conducted in 55 (57.3%) patients, and ventricular fibrillation was induced in 17 (30.9%) patients. The medical management with antiarrhythmic drugs was selected in 60 (62.5%) patients, and the catheter ablation ± anti-arrhythmic drugs was selected in 36 (37.5%) patients. The recurrence of ventricular fibrillation during 9.2±6.8 years of mean follow-up was significantly higher in the ablation strategy group (p=0.0003) (Figure 1). Conclusions We reported the largest cohort of IVF patients from a single healthcare system. Early repolarization and fragmented QRS were common in IVF. The possible associated mutations were found in one-third of IVF who underwent genetic testing. The ventricular fibrillation recurrences were significantly higher in the catheter ablation strategy group.

Background: Prior studies have reported conflicting results of persistent iatrogenic atrial septal defect (iASD) and its impact following a transcatheter edge-to-edge repair (TEER) procedure. This study aims to evaluate the incidence of iASD and its clinical and hemodynamic impact after a TEER. Methods: Consecutive patients who underwent a TEER procedure from June 2014 to September 2020 at the Mayo Clinic were identified. The presence of iASD was retrospectively identified on post-procedure transthoracic echocardiography (TTE) to group patients into an iASD+ group and an iASD− group for comparison of prognosis and cardiac function. Results: A total of 316 patients were included; the mean age was 79.1 ± 9.1 years, and 67.7% were male. Persistent iASD was diagnosed in 108 (34.2%) patients. There was no difference concerning all-cause mortality, heart failure hospitalization, and stroke/TIA between groups at follow-up (median follow-up of 9 months). Post-procedure TTE demonstrated no differences regarding right ventricle (RV) and left ventricle (LV) dimensions and function, including TAPSE (15.2 ± 4.6 vs. 15.4 ± 5.5 mm, p = 0.875), and LV ejection fraction (51.1 ± 14.0% vs. 51.3 ± 13.9%, p = 0.933). However, patients with iASD had higher RV systolic pressure (48.7 ± 14.4 vs. 45.5 ± 14.5 mmHg, p = 0.042) compared with patients without iASD. Conclusion: Notwithstanding higher RV pressures, patients with persistent iASD had no hemodynamic compromise and an equal prognosis compared with those without a residual atrial defect after a TEER procedure. These findings support the mid-term safety of procedures in which an interatrial defect needs to be created and would argue against the need for interventional closure.

Introduction: Multiple supervised machine learning (ML) models have been used to assess the outcomes in patients who underwent transcatheter aortic valve replacement (TAVR) procedure, however, supervised ML requires significant expert time for annotation and labeling. Unsupervised ML can provide insight into the dataset without this process. Hypothesis: We hypothesized that unsupervised k-means ML can identify distinct phenogroups in TAVR patients that can predict prognosis without a priori knowledge. Methods: A retrospective study of patients who underwent TAVR (Jan 2012-Dec 2017) at Mayo Clinic sites was performed. Baseline demographics, EKG, cardiac computed tomography, and echocardiographic data were abstracted. Variables with ≥ 20% missing data were excluded. Prior to the k-means clustering algorithm, principal component analysis was used for dimensionality reduction. Input variables were analyzed according to k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 1071 consecutive patients were included in the final analysis. A total of 141 unique variables were used. The mean age was 80.7±8.6 years, 58.2% were male. Patients were divided into 2 distinct phenogroups. In the two phenogroups, cluster 0 (n=639) has significantly better survival than cluster 1 (n= 432) (log-rank p=0.0002) (Figure 1). Cluster 1 has features of low flow-low gradient (LFLG) hemodynamic profile, including lower systolic blood pressure, mean aortic valve gradient, peak aortic valve velocity, and worse LV ejection fraction. Conclusions: Unsupervised ML can identify distinct phenotype features with prognostic significance in TAVR patients. Our results suggest that patients with LFLG hemodynamic features are intrinsically different from other TAVR patients and require more attention to avoid adverse outcomes.

Introduction: Peripheral arterial disease (PAD) increases cardiovascular (CV) morbidity and mortality, but remains underdiagnosed and undertreated. Several trials support low-dose rivaroxaban in PAD treatment, although this has yet to be widely adopted in clinical practice. The effect of warfarin and direct oral anticoagulants (DOACs) on comprehensive PAD outcomes warrants further study. Hypothesis: Anticoagulant therapy, particularly DOACs, improves CV outcomes in PAD. Methods: We conducted a retrospective study of patients who underwent ankle-brachial index testing (ABI) from 1996 – 2020 at Mayo Clinic. We included patients with PAD defined by abnormal ABI (<1.0 or >/=1.4). Prolonged (>6 months) DOAC or warfarin use was compared to no anticoagulant therapy. Multivariable (MV) regression, controlling for baseline CV risk factors, was used. Results: 21,891 patients had abnormal ABI readings; 3,093 were on warfarin and 267 were on DOAC for any indication. Anticoagulation improved mortality, with DOACs superior to warfarin. DOACs improved critical limb ischemia (CLI)/amputation in univariate analysis, although this was not significant in MV. Patients with poorly compressible vessels (ABI >/=1.4) had increased limb outcomes compared to reduced ABI (<1.0). Ischemic stroke and myocardial infarction occurred more frequently in those on anticoagulation, but the risk was less for DOACs vs. warfarin. Notably, both anticoagulant groups had greater baseline comorbidity than the non-anticoagulant group; the DOAC and warfarin groups were similar. Major bleeding (6.7%) was increased in both anticoagulant groups, but less so with DOACs and this was similar to the bleeding risk seen with aspirin (HR 1.20). Conclusion: Anticoagulant therapy improved mortality in a large cohort of PAD patients. The risk of limb events appears improved in those on DOACs. DOACs showed improved risk profiles compared to warfarin regarding CV and bleeding outcomes.

Introduction: Unsupervised machine learning (ML) can provide insight into a dataset without significant expert time for annotation and labeling, but was never used to assess the heterogeneous MitraClip population. Hypothesis: We hypothesized that unsupervised k-means ML could identify prognostically-distinct phenogroups in MitraClip patients without a priori knowledge of the dataset. Methods: Patients who underwent MitraClip (June 2014-September 2020) at Mayo Clinic sites were identified from the Mayo institutional NCDR database for baseline and follow-up data. Variables with ≥ 50% missing data were excluded. A k-means algorithm was used for clustering analysis. Input variables were grouped according to 4 distinct k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 389 consecutive patients were included in the final analysis, and 95 unique variables were used. The mean age was 80.3±8.7 years; 256 (65.8%) were male. The mean STS MV Replace score was 9.1±5.7. Fifty-five (14.5%) patients died during the mean follow duration (185 days). Kaplan-Meier analysis showed significant survival differences among clusters (Figure 1). The cluster (cluster 2, n=120) with best survival performance (all-cause mortality 3.3%) had features of non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation. Cluster 3 (n=66) had the worst survival performance (all-cause mortality 27.3%) and opposite features than cluster 2. Conclusions: Unsupervised ML can identify distinct phenotype clusters with prognostic significance in MitraClip patients. Patients with non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation are intrinsically different from other MitraClip patients and should be considered the potential optimal candidates.

Background/Introduction: More than moderate tricuspid regurgitation (TR) at baseline is associated with worse outcome in MitraClip patients. The presence of iatrogenic ASD (iASD) may cause right-sided volume overload and lead to adverse events. However, the real effects of iASD are not well-investigated in these patients who are vulnerable to right-sided volume overload. Methods: Patients with more than moderate TR who underwent a successful MitraClip procedure in the period from June 2014 to September 2020 were identified from the Mayo institutional NCDR database. Follow-up transthoracic echocardiography (TTE) at about 1 year after the procedure was used to determine the presence of iASD, and speckle-tracking strain analysis was done. Patients were grouped according to the presence of iASD (iASD+ group vs. iASD- group) for statistical analysis. Results: A total of 141 consecutive patients were included for the final analysis (iASD+ group n=44 and iASD- group n=97). The mean age was 79.3 ± 8.8 years, and 72.3% were male. Follow-up echocardiography and speckle-tracking strain data did not show a significant difference in either left or right ventricular function in conventional echocardiographic parameters and strain. LA reservoir strain (13.7 ± 6.9 vs 11.5±7.5, P=0.0418) was the only parameter with significant difference among the two groups. Details are summarized in Table 1 . Conclusion: The presence of iASD can decompress the left atrium, but does not affect left or right ventricular strain function in MitraClip patients with more than moderate baseline TR.

A 68-year-old man, with a history of non-Hodgkin’s lymphoma in remission, was admitted for homonymous hemianopsia, headaches and subacute progressive cognitive decline. Imaging revealed brain infarcts and angiography suggested vasculitis. A brain biopsy, however, revealed an intravascular large B-cell lymphoma (IVLBL). Central nervous system (CNS) vasculitis and IVLBL of the brain are extremely rare diseases that can have an almost identical clinical presentation. Angiographic findings are very similar but usually are reported as compatible with vasculitis. Brain biopsy or a random skin biopsy are crucial in diagnosing IVLBL as the accuracy of angiographic findings for CNS vasculitis is low.

PurposeDespite the intra- and intertumoral heterogeneity seen in glioblastoma multiforme (GBM), there is little definitive data on the underlying cause of the differences in patient survivals. Serial imaging assessment of tumor growth allows quantification of tumor growth kinetics (TGK) measured in terms of changes in the velocity of radial expansion seen on imaging. Because a systematic study of this entire TGK phenotype—growth before treatment and during each treatment to recurrence —has never been coordinately studied in GBMs, we sought to identify whether patients cluster into discrete groups on the basis of their TGK.Patients and MethodsFrom our multi-institutional database, we identified 48 patients who underwent maximally safe resection followed by radiotherapy with imaging follow-up through the time of recurrence. The patients were then clustered into two groups through a k-means algorithm taking as input only the TGK before and during treatment.ResultsThere was a significant survival difference between the clusters ( P = .003). Paradoxically, patients among the long-lived cluster had significantly larger tumors at diagnosis ( P = .027) and faster growth before treatment ( P = .003) but demonstrated a better response to adjuvant chemotherapy ( P = .048). A predictive model was built to identify which cluster patients would likely fall into on the basis of information that would be available to clinicians immediately after radiotherapy (accuracy, 90.3%).ConclusionDichotomizing the heterogeneity of GBMs into two populations—one faster growing yet more responsive with increased survival and one slower growing yet less responsive with shorter survival—suggests that many patients who receive standard-of-care treatments may get better benefit from select alternative treatments.