Citations

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>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<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>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 Transcatheter mitral edge-to-edge repair (TEER) with MitraClip offers a less invasive alternative for patients with severe, symptomatic mitral regurgitation (MR) who are considered high risk for surgery. However, patient selection for TEER remains challenging given the variability in underlying MR pathology and current discordance among studies regarding predictors of procedural efficacy and clinical outcomes. Purpose This study aimed to assess acute procedural changes and long-term outcomes in patients who underwent TEER according to the proportionality of MR, defined as the ratio of the effective regurgitant orifice area (EROA) and left ventricular end-diastolic volume (LVEDV). Methods We analyzed patients who underwent TEER at our institution between 2014 and 2020 with available biplane left ventricular volume measurement. Relevant clinical comorbidities, demographics, and anthropometrics, along with pertinent pre- and post-procedural echocardiogram measurements, were obtained by review of the electronic medical record. The EROA to LVEDV index was calculated for all patients who were then stratified by quartiles. Patients with an EROA/LVEDV index in the lowest quartile were defined as having the most proportionate MR and those with an index in the highest quartile were defined as the most disproportionate MR. Baseline and post-TEER parameters were used to assess acute procedural and longitudinal outcomes. Results Baseline clinical and echocardiographic parameters of the 230 subjects according to quartile are shown in the table. Following TEER, there was a larger reduction in the left ventricular end-diastolic diameter and increased MR reduction with increasingly disproportionate MR (p=0.03 and p=0.05, respectively). The change in ejection fraction pre- versus post-TEER did not significantly differ across groups (p=0.64). Median follow up time was 1.7 (0.7–3.5) years; mortality occurred in 77 patients (33.5%) and heart failure hospitalizations occurred in 20 patients (8.7%) during follow up. No significant difference in all-cause mortality or post-procedural heart failure hospitalizations was identified across groups. Conclusions In our series, patients with proportionate MR were similarly symptomatic to those with disproportionate MR but had less severe MR with increased comorbidities. Post-TEER MR grade was similar between groups. Longer-term follow up in larger groups of patients is needed to determine the clinical implications. 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 >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<0.0001), along with other clinical and echo predictors (Table). In multivariate analysis, adjusting for age, sex, comorbidities, advanced NYHA class III–IV, creatinine >1.5 mg/dL, medication use, severity of AS, reduced LVEF <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<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.

Abstract Background Obesity, defined by the World Health Organization (WHO) as a BMI greater than 30k g/m2, has reached epidemic proportions worldwide, related to approximately 2.8 million deaths/year as of June 2021. WHO sub-classifies obesity based on BMI in Class 1: 30–34.9 kg/m2, Class 2: 35–39.9 kg/m2, and Class 3: ≥40 kg/m2. This state of increased body weight is associated with an increased risk of cardiovascular disease. Cardiac remodeling can be affected by obesity and/or other cardiovascular risk factors (CVRF) as an adaptive physiological response. The remodeling patterns, Normal Geometry (NG), Concentric Remodeling (CR), Concentric Hypertrophy (CH), and Eccentric Hypertrophy, are classified by changes in Relative Wall Thickness (RWT), ≤ or >0.42, and/or Left Ventricular Mass Index (LVMI g/m2), ≤ or >88 for women and ≤ or >102 for men. Left Ventricular Ejection Fraction (LVEF) can remain within normal limits in patients with obesity with multiple CVRF and cardiac remodeling. Left Ventricular Global Longitudinal Strain (LV-GLS) and Right ventricular free wall strain (RV-FWS) can be useful to detect subclinical myocardial dysfunction. The aim of this study was to evaluate if these strain variables are affected in patients with obesity associated to other CVRF in relation to cardiac remodeling type when compared to controls. Methods 2859 patients with BMI ≥30 kg/m2 and 2616 normal-weight controls (BMI between 18.5 and 24.9 kg/m2), with normal and abnormal cardiac geometry, and normal ejection fraction by echocardiography performed between 01/01/2008 and 12/31/2018, were compared. Obesity was classified based on the World Health Organization. CVRF included were Hypertension (HTN), Diabetes Mellitus (DM), Dyslipidemia, history of Vascular Event (myocardial infarction and/or stroke), and Obstructive sleep apnea (OSA). Results BMI, cardiac geometry, CVRF, and the number of comorbidities independently affected GLS and RV-FWS (Figure 1 and Figure 2). LV-GLS and RV-FWS values [mean (SD)] in obesity classes 1, 2, and 3 were −19 (2.9), −18.9 (2.9), −18.7 (2.9) & −24.2 (5.2), −23.8 (6.2), −24.5 (5.9), respectively. In the control group LV-GLS and RV-FWS values [mean (SD)] were −20.1 (3.0) & −27 (5.6), respectively. CH was associated with the greatest decrease in LV-GLS and RV-FWS in males and females, regardless of BMI (Figure 2). LV-GLS values [mean (SD)] associated to CH for obesity class 1, 2, and 3, and controls in females were −18.4 (3.4), −18 (3.1) −17.6 (3.6), and −17.8 (4), respectively, and for obesity class 1, 2, and 3, and controls in males were −16.1 (3.5), 16.5 (3.2), −14.4 (2.7), and −16.6 (4.7), respectively (Figure 1). Conclusion Obesity associated to CVRF and CH have the lowest values of GLS in patients with normal ejection fraction. These values were exceedingly below average compared to other groups. These parameters should be used as reference values for this population. Funding Acknowledgement Type of funding sources: None.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Background The aim of this study was to establish prognostic hemodynamic parameters in patients with mitral stenosis secondary to mitral annular calcification. Methods and Results A retrospective cohort of 105 patients undergoing transseptal catheterization for hemodynamic evaluation of mitral annular calcification–related mitral stenosis between 2004 and 2020 was studied. Mitral valve gradient (MVG) and mitral valve area (MVA; calculated by the Gorlin formula) were measured using direct left atrial and left ventricular pressures. The median age of the patients was 70.3 years (58.4–76.7 years), and 53.3% were women. The median MVA was 1.7 cm 2 (1.3–2.3 cm 2 ) and MVG was 7.3 mm Hg (5.3–10.3 mm Hg); left ventricular end‐diastolic pressure was 17.6±28.3 mm Hg. During a median of 2.1 years (0.7–4.5 years), there were 63 deaths; 1‐ and 5‐year survival were 76% and 40%, respectively. There was no association between left ventricular end‐diastolic pressure and survival. After adjusting for age and comorbidities, both MVA (hazard ratio [HR], 0.50 per cm 2 ; 95% CI, 0.34–0.73) and MVG (HR, 1.1 per mm Hg; 95% CI, 1.05–1.20) were independent predictors of death. Atrial fibrillation was also independently associated with mortality. When added to a combined model, MVA remained associated with death (HR, 0.51 per cm 2 ; 95% CI, 0.33–0.79) while MVG was not. Conclusions In patients with mitral annular calcification–related mitral stenosis, survival was poor. MVA and MVG were independently associated with death, but MVA was a better predictor of outcomes.

Background Emerging data suggest important prognostic value to left atrial (LA) characteristics, but the independent impact of LA function on outcome remains unsubstantiated. Thus, we aimed to define the incremental prognostic value of LA coupling index (LACI), coupling volumetric and mechanical LA characteristics and calculated as the ratio of left atrial volume index to tissue Doppler imaging a′, in a large cohort of patients with isolated floppy mitral valve. Methods and Results All consecutive 4792 patients (61±16 years, 48% women) with isolated floppy mitral valve in sinus rhythm diagnosed at Mayo Clinic from 2003 to 2011, comprehensively characterized and with prospectively measured left atrial volume index and tissue Doppler imaging a′ in routine practice, were enrolled, and their long‐term survival analyzed. Overall, LACI was 5.8±3.7 and was <5 in 2422 versus ≥5 in 2370 patients. LACI was independently higher with older age, more mitral regurgitation (no 3.8±2.3, mild 5.1±3.0, moderate 6.5±3.8, and severe 7.8±4.3), and with diastolic (higher E/e′) and systolic (higher end‐systolic dimension) left ventricular dysfunction (all P ≤0.0001). At diagnosis, higher LACI was associated with more severe presentation (more dyspnea, more severe functional tricuspid regurgitation, and elevated pulmonary artery pressure, all P ≤0.0001) independently of age, sex, comorbidity index, ventricular function, and mitral regurgitation severity. During 7.0±3.0 years follow‐up, 1146 patients underwent mitral valve surgery (94% repair, 6% replacement), and 880 died, 780 under medical management. In spline curve analysis, LACI ≥5 was identified as the threshold for excess mortality, with much reduced 10‐year survival under medical management (60±2% versus 85±1% for LACI <5, P <0.0001), even after comprehensive adjustment (adjusted hazard ratio, 1.30 [95% CI, 1.10–1.53] for LACI ≥5; P =0.002). Association of LACI ≥5 with higher mortality persisted, stratifying by mitral regurgitation severity of LA enlargement grade (all P <0.001) and after propensity‐score matching ( P =0.02). Multiple statistical methods confirmed the significant incremental predictive power of LACI over left atrial volume index (all P <0.0001). Conclusions LA functional assessment by LACI in routine practice is achievable in a large number of patients with floppy mitral valve using conventional Doppler echocardiographic measurements. Higher LACI is associated with worse clinical presentation, but irrespective of baseline characteristics, LACI is strongly, independently, and incrementally determinant of outcome, demonstrating the crucial importance of LA functional response to mitral valve disease.

Introduction: Subclinical cardiovascular involvement in COVID-19 patients has not been well described. 2D-Speckle Tracking Echocardiography derived global longitudinal strain (GLS) and systolic and early diastolic strain rate (SRs, SRe) measurements are more sensitive than standard echocardiographic parameters to diagnose subclinical mechanical dysfunction in patients with normal Left Ventricle Ejection Fraction (LVEF). Hypothesis: Evaluate subclinical myocardial mechanical function and reserve in active COVID-19 systemic disease patients with normal LVEF vs controls and between survivors and non survivors of COVID-19 in the longitudinal domain of contractility. Methods & Results: 166 adult patients with active COVID 19 having normal LVEF were included and compared to 89 healthy volunteers. Baseline parameters were recorded. Peak GLS, SRs and SRe, were measured offline. Mean age was 62.53 ± 18.96 years and 87 (52%) were males and Mean LVEF was 62±5%. COVID-19 patients had higher GLS compared to controls (-20.93%±0.30 vs. -18.48%±0.40; p value <0.0001), SRs was similar (-0.97 s -1 ±0.10 vs. -0.98 s -1 ±0.02, p value 0.2528) and SRe was lower (0.85 s -1 ±0.0 vs. 1.05 s -1 ±0.02; p value <0.0001) respectively. After adjusting for age and sex, GLS, SRs and SRe was significant (p<0.001). GLS, SRs and SRe were similar in survivors vs. non survivors (p NS), both groups had elevated biomarkers (cardiac troponin, NT-pro BNP, CRP), but non survivors had higher levels (3.22±0.18 vs 3.62±0.28, p = 0.2371, 5.86±0.19 vs 7.15±0.27, p = 0.0004, 3.75±0.14 vs 4.31±0.21, p = 0.0422, 7.64±0.17 vs 8.26±0.25, p=0.0487 respectively) (Table 1). Conclusions: In our cohort, COVID-19 patients had better systolic reserve and abnormal relaxation compared to controls. There was no significant difference in strain (GLS) and strain rate (SRs & SRe) amongst survivors and non survivors in the longitudinal domain of contractility despite of higher inflammatory biomarkers in non-survivors.

Introduction and Aims of The Study: The relief of outflow obstruction after transcatheter aortic valve replacement (TAVR) is expected to improve cardiac output, LV systolic and diastolic function and to regress left ventricular (LV) mass. The impact of these changes on left atrial (LA) reservoir, conduit and contractile function remains unknown. Our aims were to compare LA functions in patients with transfemoral (TF) vs transapical (TA) TAVR and test whether they have an impact on patient outcomes. Methods: Retrospective analysis of LA deformation by speckle tracking strain echocardiography in 54 patients with TA TAVR and 54 TF TAVR, matched for age, sex and STS score. Measurements were performed pre TAVR and 1 month and 1 year post TAVR. Follow up data was available up to 5 years. Results: At baseline, there were no significant differences between the TF and TA groups with regard to patient age (81 ± 8 vs 82 ± 8 years), male gender (44% vs. 44%) or STS score (8.3 ± 4.4 vs 9.7 ± 4.5, respectively). LV filling pressures (E/e’) at baseline and 1 month were higher in TA vs. TF group (see table). LV global longitudinal strain (GLS) were similar at baseline and improved at 1 month only in the TF group (p=0.0001), while in the TA group it showed an improvement only at 1 year. LA reservoir, conduit and contractile functions improved within 1 month post TAVR in the TF group. In contrast, despite similar baseline LA functions in both groups, no improvement was observed in the TA group (see Table). At Cox proportional hazard analysis, lower LA reservoir function predicted major adverse events (death, cardiac rehospitalization or stroke) even after adjusting for age, gender and group allocation (p=0.034; risk ratio per unit decrease in LA function 1.04). Conclusion: These findings suggest that patients with TA TAVR have poor (if any) recovery of LA functions post TAVR. Presence of a stiff LA, best reflected by a persistently reduced LA reservoir strain, may contribute to the excess morbidity seen in TA patients.

Background: Cardiac amyloidosis (CA) results from extracellular deposition of insoluble amyloid fibrils in the myocardium, leading to myocardial stiffening, restrictive cardiomyopathy and poor prognosis. Thus, measurements of myocardial stiffness might help with identification of patients with cardiac amyloid deposition. The speed of wave transmission of myocardial stretch (Vm) is a novel measure of myocardial elasticity. Our aim was to investigate the behavior of Vm in the left ventricular (LV) myocardium of patients with CA. We hypothesized this wave speed will be increased in these patients and will partly explain the reduction in systolic myocardial function. Methods: We prospectively studied 23 consecutive patients with systemic amyloidosis, of whom 17 (age 59±13 years) had confirmed cardiac involvement (15 AL, 2 TTR), and compared to 18 control subjects (age 47±13 years) with normal LV function. Comprehensive transthoracic echocardiography was performed. Tissue Doppler cineloops (350-450 frames/s) were acquired from 6 LV walls from 3 standard apical views. Regional and global Vm were measured as the wave speed of the onset of myocardial stretch from LV base to apex (late diastole). Results: Subjects with CA (n=17) had higher Vm compared to normal subjects (2.5±0.8 vs 1.5±0.2 m/s; P<0.001, respectively). They also had lower LV ejection fraction (56±11 vs 65±4%; P=0.02), global longitudinal strain (GLS -14±5 vs -20±2%, P<0.001), and myocardial relaxation (mitral annulus septal e’ velocity 4.7±1.9 vs 9.2±2.4 cm/s; P<0.001) and higher LV mass (150±54 vs 87±18 g/m2; P<0.001), left atrial volume (44±7 vs 27±6 mL/m2; P<0.001), and estimated LV filling pressure (E/e’ 20±9 vs 8±3; P<0.001). There was a strong positive association between Vm and LV wall thickness (R=0.62; P<0.001), GLS (R=0.45; P=0.01) and septal E/e’ (R=0.42; P=0.02) and an inverse correlation between Vm and septal e’ (R=-0.39; P=0.03), but not with ejection fraction (P=0.37). Conclusion: This pilot study indicates that Vm is elevated in patients with CA compared to normal subjects, commensurate with the effects of amyloid deposition on LV structure and function. This novel measurement shows promise for noninvasive assessment of diastolic myocardial stiffness in patients with CA.