Pollak, Peter

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.

Introduction: Mitral paravalvular leak (PVL) occurs in 7-17% of patients after mitral valve surgery. The percutaneous closure of these defects has become a novel treatment to prevent repeat operations. Hypothesis: We hypothesize flow dynamics correlate with clinical outcomes of patients undergoing percutaneous mitral PVL closure. Methods: We retrospectively studied 148 patients who underwent percutaneous PVL closure between 2004 and 2014 at Mayo Clinic. We measured the continuous wave (CW) Doppler time velocity integral (TVI), E velocity (as a surrogate for V wave) across the mitral valve and left ventricular ejection fraction (LVEF) by transthoracic echocardiogram within 7 days before and after PVL closure. We identified patients as non-responders if there was moderate to severe residual mitral regurgitation. t-Test was used for continuous variables and Fisher exact test was used mortality. Results: Overall, the mean CW TVI was markedly reduced by PVL closure (93±14 vs. 58±5cm, p<0.02). The E velocity also decreased after closure (3.1±0.4 vs. 1.9±0.1m/sec, p<0.04). LVEF, however, was reduced after PVL closure (62%±2 vs. 53%±1.5, p<0.02). Among non-responders (34/148 patients), there was no significant difference between the CW and E velocity before and after the procedure (CW TVI: 96±16 vs. 83+13cm, E velocity: 2.5±0.5 vs. 2.3±0.3m/sec, p=NS). The estimated 5-year mortality of patients with no or mild residual mitral regurgitation was markedly lower compared to non-responders, 43% vs 71%, p<0.05. Conclusions: The flow dynamics across the mitral valve immediately after PVL closure may correlate with long term clinical outcomes. Real time assessment of flow by transesophageal echocardiogram can be used to guide the extent of PVL closure required to change the long term clinical outcomes. Further validation and prospective studies are required.

Introduction: Percutaneous left atrial appendage closure is well established as an alternative to anticoagulation therapy for stroke prophylaxis among patients with non-valvular atrial fibrillation (NVAF) with relative or absolute contraindications to anticoagulation. Only the Watchman® (BSC) device has FDA approval for this indication. There are no current guidelines on the choice of short term antithrombotic therapy following placement of the Watchman® device. The landmark Watchman® clinical trials utilized warfarin and aspirin in the first 45 days to facilitate endothelialization; however these studies were started prior to direct oral anticoagulants (DOAC) becoming widely available. Our main objective was to compare bleeding outcomes with warfarin vs. DOACs following Watchman® device placement. Methods: We conducted a retrospective chart review of all patients who received a Watchman® device at all three Mayo Clinic sites (MN, FL, AZ) between January 2010 and December 2018 with follow up for outcomes at 45 days or 6 weeks following procedure. We conducted bivariate analysis using t-tests and chi-square tests as appropriate. A logistic regression model was constructed to evaluate the effect of anticoagulant choice on bleeding and thromboembolic outcomes. Clinically significant bleeding was defined as bleeding leading to interruption of anticoagulation regimen or requiring transfusion. Results: 232 patients were identified (33% female), mean age in years, CHADS2VASC score and HASBLED scores were 77, 5 and 4 respectively. Overall, 39% were initiated on non-warfarin therapies and 11% had a significant bleeding episode during follow up. There was no difference in clinically significant bleeding events (11% vs. 12%; OR 0.92, 95% CI: 0.32 – 2.65) with short term DOAC use compared to warfarin. Patients who received a Watchman® due to GI bleeding were more likely to have a bleeding event in the first 6 weeks following Watchman® (OR: 4.08, 95% CI: 1.30 – 12.75). Conclusion: This observational study demonstrates no significant difference in bleeding episodes with DOACs compared to warfarin during the first 6 weeks following Watchman® device placement in patients at high risk for bleeding. Larger prospective studies are needed.

Background: Left atrial appendage occlusion (LAAO) devices have successfully provided an alternative therapeutic option in patients with atrial fibrillation and high bleeding risk. However, patients with thrombocytopenia (TP) were underrepresented in the milestone trials, and the optimal strategy of postprocedural antithrombotic therapy in this group of patients remains unclear. Methods: Patients were identified from the National Cardiac Database Registry - LAAO database at all three Mayo Clinic sites in the period from 1/2016-10/2019. Patients were further divided into TP (platelet &lt; 150 x 10^9/L) and control (platelet &gt; 150 x 10^9 /L) groups for clinical outcome analysis. Outcome endpoints include composite of bleeding (GI bleeding, hemorrhagic stroke, and other non-intracranial hemorrhage) and composite thrombotic events (device thrombus, ischemic stroke, TIA and undetermined stroke). Results: A total of 249 consecutive patients were included in the final analysis. The mean age was 76.7 ± 7.2 years, and 169 (67.9%) were male; 242 (97.2%) were white. The mean CHA2DS2-VASc score was 5.3 ±1.5, and the HAS-BLED score was 3.0 ± 1.1. TP at baseline was present in 74 (29.7%) patients. The median follow-up time was 6.8 months. The use of post-procedural antithrombotic regimens was similar between the two groups (Table 1). When comparing the TP group to control, there was no significant difference in composite bleeding events (10.8% vs. 8.0%, P = 0.069) and thrombotic events (2.7% vs. 2.3%, P= 0.170). Conclusions: The presence of baseline TP does not significantly increase post-procedural bleeding risk in atrial fibrillation/atrial flutter patients who underwent an LAAO occlusion procedure with the Watchman device (Boston Scientific). This group of patients can be treated with the same antithrombotic regimen as patients with normal platelet levels. Future studies are still warranted to determine the optimal antithrombotic regimen.

Background: Immunocompromised (IC) patients are at greater risk from cardiac surgery. Transcatheter aortic valve replacement (TAVR) may be more preferable for treating severe aortic stenosis (AS), though data regarding outcomes of IC patients are limited. Methods: We reviewed TAVR procedures performed at our institution from 1/2015-12/2019.We defined IC as either active malignancy receiving oncologic treatment or post organ transplant on immunosuppression, HIV, chronic steroid use (>5mg/day), or autoimmune disorder. Survival probability was estimated using the Kaplan-Meier (KM) method. Cox regression was used to evaluate the association of IC with survival. Results: Of 173 patients who underwent TAVR, 56 (32%) were IC: 30 (54%) had active malignancy undergoing active treatment, 19 (34%) were IC without malignancy, and 7 (13%) had both. Among the 19 IC patients without malignancy, 4 were post organ transplant, 3 were taking chronic steroids, 2 had autoimmune disorder, 1 had HIV, and 10 had ≥2 combination of the above. IC patients, as compared to non-IC patients, had similar baseline demographics and STS risk score (median 4.3 vs. 4.4), respectively. There were 37 deaths (16 IC and 21 non-IC) over a median follow up of 1.4 years (IQR 1.0-2.0 years). 1-year survival after TAVR was 84.5% for IC patients and 89.0% for non-IC patients (log rank p = 0.51). After adjusting for age and sex, an association between IC and survival was observed but not found to be statistically significant (adjusted HR, 1.55; 95% CI, 0.80-3.00). Conclusions: IC patients undergoing TAVR have similar baseline characteristics as non-IC patients with a trend towards worse survival. Longer term follow-up may help clarify the impact of IC status on survival after TAVR.

AbstractBackgroundChange in left atrial pressure (LAP) has been shown to be associated with symptom improvement post‐MitraClip; however, the association between acute procedural changes in transmitral diastolic mean gradient (MG) compared to LAP and symptom improvement is not well established.Methods164 consecutive patients undergoing MitraClip at Mayo Clinic between June 2014 and May 2018 were included. Preclip and postclip MG and LAP were recorded. Baseline demographics, clinical, and echocardiographic outcomes, including 30‐day New York Heart Association (NYHA) functional status were obtained from patient charts.ResultsMedian age was 81.5 years (IQR: 76.3, 87), 34% were female and 94.5% had NYHA class III and IV functional status at baseline. At baseline, median MG was 4 mmHg (IQR: 3, 5) and LAP was 19 mmHg (IQR: 16, 23.5). Following MitraClip deployment, the median MG was 4 mmHg (IQR: 3, 6) and the median LAP was 17 mmHg (IQR: 14, 21), 69.5% of patients had less than moderate MR. There was no statistically significant association between change in MG and NYHA functional class at 30 days (OR = 0.95, 95% CI: 0.76–1.20). However, a reduction in LAP following MitraClip deployment was significantly associated with improvement in NYHA functional status at 30 days following adjustments for age and sex (aOR 3.36, 95% CI: 1.34–8.65). There was no significant correlation between change in mean LAP and change in MG (p = .98).ConclusionUnlike change in left atrial pressure, change in MG post‐MitraClip was not associated with patient reported outcomes at 30 days and did not correlate with change in left atrial pressure. Long‐term follow up is needed to evaluate the impact of LA pressure on symptoms.

Abstract Background Older adults with severe aortic stenosis (AS) are at high risk of mortality unless surgical or transcatheter aortic valve replacement (AVR) is performed. Risk stratification often becomes complicated in frail elders with multi-morbidity, and time constraints limit thorough evaluation of geriatric comorbidities in the outpatient clinic setting. Purpose Utilization of an automated administratively-derived electronic health record (EHR) tool may aid in risk stratification of AS patients undergoing AVR. Methods We reviewed patients with severe AS undergoing AVR at our hospital program and cross-referenced with the Elder Risk Assessment (ERA) score. The ERA score is an administratively abstracted score derived on adults &gt;60 years old followed by general medicine clinic. It contains the following variables: marital status, age, hospitalized days in preceding 2 years, diabetes, coronary disease, heart failure, stroke, pulmonary disease, cancer, and dementia; higher scores indicate greater risk for adverse outcomes. Kaplan-Meier method was used to estimate survival by ERA score tertile. Cox regression was used to test the association of ERA with survival. Results There were 97 patients with severe AS undergoing AVR with ERA scores. Mean age was 80.6 (±6.6) years, 37% were female, average Society of Thoracic Surgery (STS) score was 3.6% (± 2.6), and 7% had transcatheter AVR. Co-morbidities were prevalent and included atrial fibrillation (41%), chronic renal failure (16%), stroke (14%), and diabetes (35%). Over a mean follow-up of 68 months (± 37.9 months), there were 62 deaths. Elevated ERA score was associated with worse long term survival (p=0.016 by log-rank) (Figure 1), with only 49% surviving at 5 years in the highest ERA tertile vs 68% in the lowest ERA tertile. Cox regression demonstrated that the relative risk of death per 6 unit increase in ERA score was 1.54 (95% CI 1.21–1.96, P&lt;0.001) in single variable analysis and 1.43 (95% CI 1.11–1.84, P=0.006) after adjusting for STS score. Conclusions Patients undergoing AVR for severe AS are often co-morbid older adults. An automated EHR derived ERA score was independently associated with survival after accounting for STS score and may streamline and improve risk assessment in these patients. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic

Abstract Funding Acknowledgements None Background Cardiac Power Index (CPI) is an integrative hemodynamic measure of cardiac pumping capability and is the product of the simultaneously measured mean arterial pressure (MAP) and cardiac output (CO). In patients with aortic stenosis (AS), MAP is not reflective of mean systolic left ventricular (LV) pressure due to the transvalvular gradient. Non-invasive assessment of mean systolic LV pressure is challenging in severe aortic stenosis. CPI assessed using systemic MAP was previously shown to predict survival post transcatheter aortic valve replacement (TAVR). Purpose We evaluated the utility of a gradient adjusted CPI in predicting survival post TAVR compared to CPI alone Methods A retrospective study was performed including patients undergoing TAVR with 1 year follow-up. Baseline demographics, clinical, and echocardiographic data were abstracted from a cohort of 1,011 patients. CPI was calculated, (CO x MAP)/ (451 x BSA) Watts/m2. Gradient adjusted CPI was calculated using an augmented MAP i) adding aortic valve mean gradient(AVMG) to systolic blood pressure (CPI1); ii) adding aortic valve maximal instantaneous gradient to systolic blood pressure (CPI2) and iii) adding AVMG to MAP (CPI3). Patient survival score was calculated using a step up technique to identify the cut off value for CPI and gradient adjusted CPI to identify, where the maximum difference in mortality occurred. Multivariate cox-regression analysis was performed to adjust for baseline covariates. Receiver operator curves(ROC) for CPI and gradient adjusted CPI were calculated to predict survival post TAVR. Results The mortality rate at 1 yr was 16%. Mean age and AVMG of survivors was 81 +/- 9 yrs and 43 +/-14 mmHg vs 80 +/-9 yrs and 42 +/- 13 mmHg in the deceased group. Proportion of female patients was similar in both groups (p = 0.7). Patients in the deceased group at baseline had a higher prevalence of chronic lung disease, atrial fibrillation, heart failure within 2-weeks of procedure, higher STS-PROM score, lower serum albumin level, higher prevalence of moderate to severe tricuspid regurgitation, higher right ventricular systolic pressure and higher prevalence of dialysis. Both CPI and gradient adjusted CPI were independently associated with survival at 1 year. The area under ROC for CP, CP1, CP2 and CP3 were 0.67 (95% confidence interval [CI] 0.62 - 0.72), 0.65 (95% CI 0.60 – 0.70), 0.66 (95% CI 0.61 – 0.71) and 0.63 (95% CI 0.58 – 0.68) respectively. Conclusion Gradient adjusted CPI did not improve accuracy of predicting post TAVR survival at 1 year compared to CPI alone. Abstract P339 Figure. Area under ROC

AbstractBackgroundMitraClip is an effective transcatheter therapy for mitral regurgitation (MR). However, MitraClip is challenging in commissural MR and the optimal therapeutic approach is unclear.MethodsWe describe a case series of six consecutive patients with severe commissural primary mitral regurgitation who underwent MitraClip insertion followed by an Amplatzer Vascular Plug (AVP) II occluder between the commissure and the MitraClip.ResultsThe procedure was successful in all patients. MR was reduced from severe to mild/trivial in 50% and moderate in 50% of cases. On 30‐day follow‐up, NYHA class had improved from III (6 patients) to I (2 patients), II (2 patients), and III (2 patients). The mean transmitral gradient was 2.5 ± 1.8 mmHg at baseline and 4.8 ± 2.6 mmHg following the procedure. One patient developed hemolysis immediately post procedure. The other five patients remained well during a median follow‐up of 20 months (range 5–50 months) with no reported device dislodgement.ConclusionsElective treatment of severe commissural MR with a laterally or medially placed MitraClip coupled with an AVP II occluder between the clip and the commissure is feasible and safe. This approach may provide a useful management alternative in selected patients.