Greason, Kevin L.

Abstract Background Staging classification for severe aortic stenosis (AS) based on the extent of cardiac damage has been correlated with outcomes in the general population. This is categorized based on the following echocardiographic findings: stage 1 (increase in the left ventricular mass index; E/e’>14; and left ventricular ejection fraction <50%); stage 2 (left atrial volume index >34ml/m2; moderate to severe mitral regurgitation and atrial fibrillation), stage 3 (systolic pulmonary hypertension> 60mmHg and moderate to severe tricuspid regurgitation) and stage 4 (moderate to severe right ventricular dysfunction); its applicability in a cancer population exposed to chemo+/- radiotherapy and its correlation with MACE has not been explored. Purpose To evaluate if this staging system predicts MACE (cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure) at 18 months after TAVR in cancer patients who were previously exposed to cardiotoxic therapies. Methods We retrieved data of patients that underwent TAVR from 2013 to 2021. 544 patients were included in this study and divided in 3 groups: 187 patients with prior chest Radiotherapy and Chemotherapy (RT/CT), 155 with CT only, and 202 cancer patients not exposed to CT or RT control group. This was further subdivided in two groups based on the staging system in: stage ≤ 2 and ≥3. Fisher's exact test or chi-square was used to compare categorical variables and clinical outcomes among groups and ANOVA for continuous variables. Echocardiographic findings and correlation with the outcome were evaluated by a multivariable Cox model analysis and assessed by a proportional hazards model for time to event. Kaplan–Meier curves were performed to determine the event-free survival rate. Significance was considered as a p<0.05. Results RT/CT had a higher prevalence of moderate to severe mitral regurgitation (11.8%) p <0.001 and tricuspid regurgitation (13.9%) p=0.02. Stage ≥3 was (24.1%) in the RT/CT, (9.4%) in CT, and (16.1%) in controls p= 0.004. Additionally, stage ≥3 was a predictor of MACE at 18 months: RT/CT group HR 6.43 (3.06 – 13.1) p<0.001, CT HR 4.49 CI (2.27 – 8.89) p<0.001 and control HR 2.20 CI (1.13 – 4.26) p=0.02 (Table 1). MACE at 18 months for stage ≥3 was higher for all groups vs. stage ≤ 2. MACE at 18 months after TAVR was significantly higher in stage >3 for RT/CT (57.4%) and CT only (61.2%) vs. CL (27.2%) p<0.001 (Figure 1B). Conclusions In addition to predicting aortic stenosis risk in cancer patients before TAVR, cardiac damage staging is a strong predictor of MACE at 18 months in patients post-RT/CT and CT and suggests that these patients may benefit from earlier stratification for TAVR prior to reaching stage 3. Future studies with longer follow-up should be explored to evaluate its usefulness in this complex population.

Introduction: Bioprosthetic valve thrombosis is a recognized cause of bioprosthetic valve dysfunction. It was found to be associated with accelerated bioprosthetic degeneration and higher rates of valve re-replacement. Hypothesis: Warfarin for 3 months after transcatheter aortic valve replacement (TAVR) protects against accelerated valve degeneration and is therefore associated with better outcomes compared to dual antiplatelet (DAPT) and single antiplatelet therapies (SAPT). Methods: Adult patients who underwent TAVR (2012-2019) were identified retrospectively (n=1,501). Patients with atrial fibrillation were excluded (n=657). Patients were classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen. Structural valve degeneration (SVD) was considered when patients developed new ≥ moderate trans-prosthetic regurgitation, increase in mean gradients ≥10 mmHg from baseline, or when gradients exceeded 20 mmHg. Discharge date was considered time zero. Results: Overall, 844 patients [mean age 80 (±9), 43% females, mean Society of Thoracic Surgeons risk score 6.7 (±5.0)] were included. Warfarin was used in 633 (75%) patients, DAPT in 164 (19%), and SAPT in 47 (6%). Median follow-up time was 2.5 (IQR 1.2-3.9) years. There was no difference in outcomes of ischemic stroke, death, valve re-intervention, SVD, their composite endpoint, or hemorrhagic stroke and hemorrhagic stroke/RBC transfusion events (Figures 1 & 2), even after adjustment for confounders. Conclusion: Warfarin after TAVR was not associated with better clinical or hemodynamic outcomes or with worse adverse events compared to DAPT and SAPT.

AbstractBackgroundObesity has been associated with an increased risk of vascular complication during percutaneous coronary intervention, but there are no data on the risk of vascular complication during percutaneous transfemoral transcatheter aortic valve insertion (TAVI).ObjectivesWe hypothesized there would be a similar increased risk associated with TAVI.MethodsWe reviewed the records of 1176 patients who received percutaneous transfemoral transcatheter aortic valve insertion from September 2015 to September 2020. All patients received 1) preoperative computed tomoraphy angiography assessment of the abdomen and pelvis to delineate iliofemoral artery anatomy, 2) ultrasound‐guided percutaneous femoral arterial access, and 3) pre‐closure of the delivery sheath femoral access site. Vascular complication was recorded based on definitions set forth by Valve Academic Research Consortium 3.ResultsThe median age of patients was 81 years, and 60% were men. The median body mass index (BMI) was 29 kg/m2 (range, 11–67), and 91 (8%) patients had a value ≥40 kg/m2 (i.e., morbid obesity). Delivery sheath size was 14‐French in 859 (73%) patients, 16‐French in 311 (26%), and 18‐French in 6 (1%). Vascular complication occurred in 53 (5%) patients, including 39 (7%) among the first half of procedures and 14 (2%) among the second half (p < 0.001). When stratified by obesity status (BMI < or ≥30 kg/m2, p < 0.001), the complication rate was 4% in nonobese patients and 5% in obese patients. Multivariable analysis showed no overall association between risk of vascular complication and BMI categories (p = 0.583)BMI continuous values (p = 0.529), or sheath size (p = 0.217).ConclusionsObesity is not associated with a vascular complication during percutaneous transfemoral transcatheter aortic valve insertion. The operation should not be denied in obese patients.

Abstract OBJECTIVES Delayed sternal closure (DSC) after cardiac surgery is a temporizing measure to address coagulopathy or haemodynamic instability after cardiac surgery. We sought to study: (i) indications and temporal trends for DSC, (ii) factors associated with time to chest closure and (iii) its impact on short-term and long-term outcomes. METHODS From January 2007 to December 2017, 494 patients (median age 67 years, 66% males) required DSC after cardiac surgery. Medical records were reviewed for indications, risk factors, time to DSC and outcomes. Multivariable Cox regression via landmark analysis of 486 5-day survivors was used to investigate the impact of time to chest closure on early and late survival. RESULTS Coagulopathy and haemodynamic instability were the most common indications. Median time to chest closure was 2 days. Pre-/intraoperative extracorporeal membranous oxygenation, severe right ventricular dysfunction and diabetes mellitus were associated with longer time to chest closure. Longer time to closure was associated with increased risk of operative complications and operative mortality, but did not have a statistically significant association with late mortality. Increasing age, pulmonary hypertension and a greater number of prior sternotomies were also found to be associated with overall mortality. CONCLUSIONS While longer time to chest closure was associated with increased rates of operative complications and operative mortality, it did not reveal a statistically significant association with long-term survival.

Abstract OBJECTIVES Low forced expiratory volume in 1 s (FEV1) and elevated N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) have been individually associated with poor outcomes after transcatheter aortic valve replacement (TAVR). We hypothesized a combination of the 2 would provide prognostic indication after TAVR. METHODS We categorized 871 patients who received TAVR from 2008 to 2018 into 4 groups according to baseline FEV1 (&lt;60% or ≥60% predicted) and NT-Pro-BNP (&lt;1601 or ≥1601 pg/ml): group A (n = 312, high FEV1, low NT-Pro-BNP), group B (n = 275, high FEV1, high NT-Pro-BNP), group C (n = 123 low FEV1, low NT-Pro-BNP) and group D (n = 161, low FEV1, high NT-Pro-BNP). The primary end point was survival at 1 and 5 years. RESULTS Patients in group A had more severe aortic stenosis and achieved the best long-term survival at 1 [93% (95% CI: 90–96)] and 5 [45.3% (95% CI: 35.4–58)] years. Low FEV1 and high NT-Pro-BNP (group D) patients had more severe symptoms, higher Society of Thoracic Surgeons predicted risk of operative mortality, lower ejection fraction and aortic valve gradient at baseline. Patients in group D had the worst survival at 1 [76% (95% CI: 69–83)] and 5 years [13.1% (95% CI: 7–25)], hazard ratio compared to group A: 2.29 (95% CI: 1.6–3.2, P &lt; 0.001) with 25.7% of patients in New York Heart Association class III–IV. Patients in groups B and C had intermediate outcomes. CONCLUSIONS The combination of FEV1 and NT-Pro-BNP stratifies patients into 4 groups with distinct risk profiles and clinical outcomes. Patients with low FEV1 and high NT-Pro-BNP have increased comorbidities, poor functional outcomes and decreased long-term survival after TAVR.

Mitral valve replacement may be indicated in delayed MitraClip (Abbott) failure. Although it would be best to preserve the chordal apparatus during surgical mitral valve replacement, this has not been reported for delayed MitraClip failure, probably because there is almost always impressive inflammation around the MitraClip, which has likely precluded previous attempts at chordal preservation. A successful surgical chordal preservation mitral valve replacement in delayed MitraClip failure is reported here.

Abstract Aims Aortic stenosis (AS) induces characteristic changes in left ventricular (LV) mechanics that can be reversed after aortic valve replacement (AVR). We aimed to comprehensively characterize LV mechanics before and after AVR in patients with severe AS and identify predictors of short-term functional recovery and long-term survival. Methods and results We prospectively performed comprehensive strain analysis by 2D speckle-tracking echocardiography in 88 patients with severe AS and LV ejection fraction ≥50% (mean age 71 ± 12 years, 42% female) prior to and within 7 days after AVR. Patients were followed for up to 5.2 years until death from any cause or last encounter. Within days after AVR, we observed an absolute increase in global longitudinal strain (GLS) (−16.0 ± 2.0% vs. −18.5 ± 2.1%, P&lt;0.0001) and a decrease in apical rotation (10.5 ± 4.0° vs. 8.3 ± 2.8°, P = 0.0002) and peak systolic twist (18.2 ± 5.0° vs. 15.5 ± 3.8°, P = 0.0008). A baseline GLS is less negative than −16.2% was 90% sensitive and 67% specific in predicting a ≥ 20% relative increase in GLS. During a median follow-up of 3.8 years, a global circumferential systolic strain rate (GCSRs) less negative than −1.9% independently predicted lower survival. Conclusion In patients with severe AS, a reversal in GLS, apical rotation, and peak systolic twist abnormalities towards normal occurs within days of AVR. Baseline GLS is the strongest predictor of GLS recovery but neither was associated with long-term survival. In contrast, abnormal baseline GCSRs are associated with worse outcomes.

Background The management of severe mitral regurgitation (MR) after transcatheter edge‐to‐edge repair (TEER) remains a clinical conundrum. Considering the growing volume of TEER, more outcomes data for mitral surgery in this cohort are needed. Methods and Results Symptomatic patients with persistent or recurrent severe MR after TEER evaluated between May 2014 and June 2021 were included. The primary outcome was all‐cause mortality in patients who were treated with surgery versus medical therapy. The Kaplan–Meier and Cox regression methods were used to report risk‐adjusted survival analyses. Among the 142 included patients, 44 (31.0%) underwent mitral surgery. Patients who underwent surgery were younger than those treated medically (74.1±8.9 versus 78.6±10.5 years, P =0.01). Major comorbidities were similar except obesity, sleep apnea, left ventricular dimensions, and ejection fraction. Society of Thoracic Surgeons Predicted Risk of Operative Mortality was 9.0±4.7 versus 7.9±4.9 in the surgical versus medical therapy groups, respectively, P =0.22. Time from TEER to detection of severe MR was similar in both groups (median [interquartile range] 97.5 [39.5–384] versus 93.5 [40–389] days in the surgical versus medical groups, respectively [ P >0.05]). In the surgical group, valve replacement was performed in all patients. Operative mortality was 4.5% (observed/expected ratio 0.55), and major complications were uncommon. After risk‐adjustment, surgery was associated with significantly lower all‐cause mortality (adjusted hazard ratio, 0.33 [95% CI, 0.12–0.92], P =0.001) compared with medial therapy. Conclusions Compared with medical therapy, mitral surgery in patients with severe persistent or recurrent MR after TEER is associated with lower mortality despite the high‐risk profile of these patients. Patients with severe MR after TEER should be considered for surgery at a referral mitral surgical center.

Abstract Background Bioprosthetic valve thrombosis is currently a well-recognized cause of bioprosthetic valve dysfunction. It was found to be associated with accelerated degeneration of the bioprosthesis with higher rates of valve re-replacement, even after treatment with anticoagulation. We hypothesized that the use of warfarin for three months after transcatheter aortic valve replacement (TAVR) protects against accelerated valve degeneration and is therefore associated with better outcomes compared to dual antiplatelet therapy (DAPT). Methods Consecutive adult patients who underwent TAVR in our clinic between 2012 and 2019 were identified retrospectively. Patients with atrial fibrillation were excluded. Subsequently, patients who received DAPT were propensity matched to up to 2 patients who received three months of warfarin as part of their anti-thrombotic regimen. Matching was performed for variables that were significantly different at baseline between the two groups and included diabetes mellitus, prior myocardial infarctions, chronic lung disease, peripheral arterial disease, hemoglobin at time of TAVR, kidney function [creatinine&gt;2], use of angiotensin-converting enzyme inhibitors / angiotensin II receptor blockers, beta blockers, the Society of Thoracic Surgeons (STS) score [STS ≥8, STS 4–8, STS&lt;4], and valve size. The two groups were then compared for outcomes of ischemic stroke, death, valve re-replacement/intervention, the composite endpoint of the aforementioned three outcomes, as well as the three-month outcome of hemorrhagic strokes. Kaplan Meier was used for outcome analysis, and discharge date was considered time zero. Patients who had their anti-thrombotic therapy interrupted were censored at that time point. Results A total of 1,373 patients who underwent TAVR were identified. Of these, 576 patients with atrial fibrillation were excluded. Baseline characteristics were compared between 633 patients who received three months of warfarin and 164 patients who received DAPT after TAVR. After matching the two groups, 435 patients were included in the final analysis [warfarin in 281, DAPT in 154; median time to last follow up 2.61 years], Table 1. There was no difference in matched (Figure 1) or unmatched analysis (not shown) in outcomes of ischemic stroke, death, valve re-replacement/intervention, their composite endpoint, or hemorrhagic strokes (p&gt;0.05 for all). Conclusion Antithrombotic regimen including three months of warfarin after TAVR was not associated with better outcomes of ischemic strokes, deaths, and valve re-replacement/intervention or with increased risk of hemorrhagic strokes compared to DAPT. Funding Acknowledgement Type of funding sources: None.

Abstract Background Increased left ventricular (LV) stiffness (LVStiffn) was shown to be associated with mortality in patients with severe aortic stenosis (AS), despite aortic valve replacement (AVR), and may contribute to future heart failure (HF) symptoms. The aim was to assess whether preoperative LVStiffn is a risk factor of HF in these patients. Methods A retrospective analysis was done in patients with severe AS who underwent AVR (93% surgical). LV end-diastolic pressure-volume relations (P=aVb) were reconstructed from LV end-diastolic volumes and estimated end-diastolic pressures (from E/e'); LVStiffn at 30 mmHg (CS30) and capacitance (V30) were then derived. Primary endpoint was development of symptomatic HF at &gt;1 month post AVR. Results 1,837 patients were studied (age 76±10 years, 62% males, LVEF 61±12%; Table). Mean CS30 was 2.2±1.3 mmHg/mL and V30 64±17 mL/m2. Patients with higher CS30 ≥3 mmHg/mL were older, more frequently female, and had more comorbidities. During a median follow-up of 5.0 [3.0–7.9] years, 607 (33%) patients developed HF. A higher CS30 (≥3 mmHg/mL), but not V30 (P=0.32), was associated with higher risk of HF events (HR 1.86 [95% CI 1.52–2.27], P&lt;0.0001), along with other clinical and echo predictors (Table). In multivariate analysis, adjusting for age, sex, comorbidities, advanced NYHA class III–IV, creatinine &gt;1.5 mg/dL, medication use, severity of AS, reduced LVEF &lt;50%, diastolic dysfunction grade ≥2, right ventricular size and pulmonary hypertension, a higher CS30 ≥3 mmHg/mL remained independently associated with HF events (adjusted HR 1.61 [1.29–2.01], P&lt;0.0001; Figure). Conclusion Increased LVStiffn in patients with severe AS undergoing AVR is associated with HF at follow-up, despite the benefits brought by AVR, and can help identify patients with poorer outcomes who may need closer monitoring/more intensive treatment of comorbidities Funding Acknowledgement Type of funding sources: None.