Five-year outcomes of transcatheter mitral valve implantation and redo surgery for mitral prosthesis degeneration.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) has emerged as a feasible alternative to redo surgical mitral valve replacement (SMVR) in patients with degenerated mitral prostheses, with limited comparative data. METHODS: We compared mid-term outcomes in patients with degenerated mitral valve prostheses treated with TMVR or redo SMVR. The primary endpoint was survival at 5 years of follow-up. RESULTS: From 2014 to 2020, 215 patients presented with degenerated mitral valve prostheses. Of whom 86 (40%) were treated with TMVR (75[87%] valve-in-valve and 11[13%] valve-in-ring), while 129 patients (60%) underwent SMVR. The TMVR cohort was older (p < 0.0001), more symptomatic (p = 0.0003) and had more chronic lung disease (p = 0.02), worse renal function (p = 0.02) and higher right ventricular systolic pressures (p < 0.0001). Thirty-day mortality was lower with TMVR versus SMVR (2.4% vs. 10.2%, OR4.69 [95% CI 1.25-30.5], p = 0.04) with probability of mortality at 1, 2, and 5 years being 14.7% versus 17.5%, 24.5% versus 20.7%, and 49.9% versus 34.0%, respectively. Mode of prosthesis degeneration, baseline hemodynamics, and valve selection did not appreciably impact outcomes. CONCLUSIONS: TMVR for degenerated mitral prostheses is associated with better early survival compared to SMVR despite a greater burden of comorbidities. In contrast, 5 year survival rates appear more favorable with SMVR, which may reflect the lower baseline risk of this population. Clinical, hemodynamic, and echocardiographic follow-up support the mid-term durability of TMVR for degenerated mitral prostheses. Further dedicated studies, however, are required to optimize outcomes in this challenging patient cohort and to navigate the choice of approach for each individual patient.

Atrial mitral regurgitation: Characteristics and outcomes of transcatheter mitral valve edge-to-edge repair.

BACKGROUND: Mitral transcatheter edge-to-edge repair (MTEER) is an established therapeutic approach for mitral regurgitation (MR). Functional mitral regurgitation originating from atrial myopathy (A-FMR) has been described. OBJECTIVES: We sought to assess the clinical, echocardiographic and hemodynamic considerations in A-FMR patients undergoing MTEER. METHODS: From 2014 to 2020, patients undergoing MTEER for degenerative MR (DMR), functional MR (FMR), and mixed MR were assessed. A-FMR was defined by the presence of MR > moderate in severity; left ventricular (LV) ejection fraction (LVEF) ≥ 50%; and severe left atrial (LA) enlargement in the absence of LV dysfunction, leaflet pathology, or LV tethering. The diagnosis of A-FMR (vs. ventricular-FMR [V-FMR]) was confirmed by three independent echocardiographers. Baseline characteristics, procedural outcomes as well as clinical and echocardiographic follow-up are reported. Device success was defined as final MR grade ≤ moderate; MR reduction ≥1 grade; and final transmitral gradient <5 mmHg. RESULTS: 306 patients underwent MTEER, including DMR (62%), FMR (19%), and mixed MR (19%). FMR cases included 37 (63.8%) V-FMR and 21 (36.2%) A-FMR. Tricuspid regurgitation (≥ moderate) was higher in A-FMR (80.1%) compared to V-FMR (54%) and DMR (42%). Device success did not significantly differ between A-FMR and V-FMR (57% vs. 73%, p = 0.34) or DMR (57% vs. 64%, p = 1.0). The A-FMR cohort was less likely to achieve ≥3 grades of MR reduction compared to V-FMR (19% vs. 54%, p = 0.01) and DMR (19% vs. 49.7%, p = 0.01). Patients with V-FMR and DMR demonstrated significant reductions in mean left atrial pressure (LAP) and peak LA V-wave, though A-FMR did not (LAP -0.24 ± 4.9, p = 0.83; peak V-wave -1.76 ± 9.1, p = 0.39). In follow-up, echocardiographic and clinical outcomes were similar. CONCLUSIONS: In patients undergoing MTEER, A-FMR represents one-third of FMR cases. A-FMR demonstrates similar procedural success but blunted acute hemodynamic responses compared with DMR and V-FMR following MTEER. Dedicated studies specifically considering A-FMR are needed to discern the optimal therapeutic approaches.

Effect of eliminating pre-discharge transthoracic echocardiogram on outcomes after TAVR.

OBJECTIVES: The aim of this study was to determine the safety of eliminating the pre-discharge transthoracic echocardiogram (TTE) on 30-day outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: TTE is utilized before, during, and after TAVR. Post-procedural, pre-discharge TTE assists in assessment of prosthesis function and detection of clinically significant paravalvular leak (PVL) after TAVR. METHODS: Patients who underwent TAVR at Mayo Clinic from July 2018 to July 2019 were included in a prospective institutional registry. Patients undergoing TAVR prior to February 2019 received a pre-discharge TTE, while those undergoing TAVR after February 2019 did not. Both cohorts were evaluated with TTE at 30 days post-TAVR. RESULTS: A total of 330 consecutive patients were included. Of these, 160 patients (age 81.1 ± 7.6) had routine pre-discharge TTE, while 170 patients (age 78.9 ± 7.5) were dismissed without routine pre-discharge TTE. Mortality at 30 days was similar between the two groups (0% and 1.2%, respectively). One episode of PVL requiring intervention (0.6%) occurred in the pre-discharge TTE group and none in the group without pre-discharge TTE at 30-day follow-up. There was a similar incidence of total composite primary and secondary adverse events between the cohort receiving a pre-discharge TTE and those without (28.1% vs. 25.3%, P = 0.56) at 30 days. The most common event was need for permanent pacemaker or ICD implantation in both groups (13.1% vs. 11.8%, P = 0.71). CONCLUSIONS: Elimination of the pre-discharge TTE is safe and associated with comparable 30-day outcomes to routine pre-discharge TTE. These findings have implication for TAVR practice cost-efficiency and health care utilization.

Immobile Leaflets at Time of Bioprosthetic Valve Implantation: A Novel Risk Factor for Early Bioprosthetic Failure: A Novel Risk Factor for Early Bioprosthetic Failure.

OBJECTIVES: The clinical implications of finding immobile leaflet(s) at the time of bioprosthetic valve implantation but with acceptable prosthetic haemodynamics are uncertain. We sought to determine the characteristics of such patients and their impact on outcome. METHODS: Patients with immobile leaflet at the time of surgical bioprosthetic valve implantation were identified retrospectively by a systematic search of an institutional echocardiography database (2010-2020). Intraoperative echocardiograms were reviewed de-novo to confirm immobile leaflet(s) at the time of implantation. Cases were matched 1:2 to controls with normal bioprosthetic leaflets motion for age, sex, prosthesis position, prosthesis model, size, year of implantation, and pre-implantation left ventricular ejection fraction. Proportional hazards method was used to analyse the composite endpoint of stroke, valve thrombosis or re-intervention. RESULTS: Immobile leaflet at the time of bioprosthetic valve implantation were found in 26 patients (median age 71 ys 39% males) following tricuspid (n=13), mitral (n=11) and aortic (n=2) valve replacements; 96% received porcine prostheses; prosthesis size was 27 mm or larger in 92%. Immobile leaflet were recorded on intraoperative reports in 16 (62%) cases. It resulted in elevated gradient or mild-moderate prosthetic regurgitation in three (12%), but none led to immediate corrective action intraoperatively. At median follow-up of 21 (4-50) months, presence of immobile leaflet was associated with composite clinical endpoint of stroke, valve thrombosis or re-intervention (hazard ratio 6.8, 95% CI 1.8-25.2, p<0.01) compared to controls. CONCLUSION: Immobile leaflet immediately post-bioprosthetic valve implantation is frequently under-recognised intraoperatively and appears to be associated with early bioprosthetic dysfunction and worse clinical outcome.

Clinical predictors and impact of postoperative mean gradient on outcome after transcatheter edge-to-edge mitral valve repair.

BACKGROUND: The predictors and clinical significance of increased Doppler-derived mean diastolic gradient (MG) following transcatheter edge-to-edge mitral valve repair (MVTEER) remain controversial. OBJECTIVE: We sought to examine baseline correlates of Doppler-derived increased MG post-MVTEER and its impact on intermediate-term outcomes. METHODS: Patients undergoing MVTEER were analyzed retrospectively. Post-MVTEER increased MG was defined as >5 mmHg or aborted clip implantation due to increased MG intraprocedurally. Baseline MG and 3D-guided mitral valve area (MVA) by planimetry were retrospectively available in 233 and 109 patients. RESULTS: 243 patients were included; 62 (26%) had MG > 5 mmHg post-MVTEER or aborted clip insertion, including 7 (11%) that had aborted clip implantation. Mortality occurred in 63 (26%) during a median follow up of 516 days (IQR 211, 1021). Increased post-MVTEER MG occurred more frequently in females (44% vs. 16%, p < 0.001), those with baseline MVA <4.0 cm2 (71% vs. 16%), baseline MG ≥4 mmHg (61% vs. 20%), or multiple clips implanted (33% vs. 21%, p = 0.04). Increased post-MVTEER MG was associated with increased subsequent mortality compared to those with normal gradient (HR 1.91 95% CI 1.15-3.18 p = 0.016) as was aborted clip insertion compared to all others (HR 5.23 95% CI 2.06-13.28 p < 0.001). CONCLUSIONS: Smaller baseline MVA and increased baseline MG are associated with increased MG post-MVTEER and patients with a Doppler-derived post-MVTEER MG >5 mmHg suffered excess subsequent mortality. In high risk patients considered for MVTEER, identification of those at risk of iatrogenic mitral stenosis with MVTEER is important as they may be optimally treated with alternate surgical or transcatheter therapies.

Effect of a fourth-generation transcatheter valve enhanced skirt on paravalvular leak.

OBJECTIVES: The aim of this study was to assess the 30 day incidence of paravalvular leak (PVL) and need for aortic valve reintervention of a fourth generation balloon expandable transcatheter valve with enhanced skirt (4G-BEV) (SAPIEN 3 Ultra) compared with a third generation balloon expandable transcatheter valve (3G-BEV) (SAPIEN 3). BACKGROUND: The incidence of PVL has steadily declined with iterative improvements in transcatheter aortic valve replacement (TAVR) technology and implantation strategies. METHODS: Patients who underwent TAVR at Mayo Clinic from 7/2018 to 7/2019 were included in a prospective institutional registry. 4G-BEV has been utilized since 2/2019, and, after this date, 3G-BEV and 4G-BEV were simultaneously used. 4G-BEV had three sizes (20, 23, and 26 mm) while 3G-BEV included four sizes (20, 23, 26, and 29 mm). Both cohorts were evaluated at 30 days post-TAVR with a transthoracic echocardiogram to assess for PVL. RESULTS: A total of 260 consecutive patients were included. Of these, 101 patients received a 4G-BEV and 159 patients received a 3G-BEV. There were more females (p = .0005) and a lower aortic valve calcium score (p = .02) in the 4G-BEV cohort at baseline. Age, STS risk score, NYHA Class, and aortic valve mean gradient did not differ between groups. 4G-BEV was associated with a lower incidence of mild PVL (10.8 vs. 36.5%; p < .0001) and moderate PVL (0 vs. 5.8%) compared to the 3G-BEV at 30 days. There was no association between PVL and valve size in either cohort. CONCLUSIONS: Utilization of 4G-BEV is associated with reduced PVL at 30 days post-TAVR compared with 3G-BEV.

Ventricular strain analysis in patients with no structural heart disease using a vendor-independent speckle-tracking software.

BACKGROUND: Ventricular strain measurements vary depending on cardiac chamber (left ventricle [LV] or right ventricle [RV]), type of strain (longitudinal, circumferential, or radial), ventricular level (basal, mid, or apical), myocardial layer (endocardial or epicardial), and software used for analysis, among other demographic factors such as age and gender. Here, we present an analysis of ventricular strain taking all of these variables into account in a cohort of patients with no structural heart disease using a vendor-independent speckle-tracking software. METHODS: LV and RV full-thickness strain parameters were retrospectively measured in 102 patients (mean age 39 ± 15 years; 62% female). Within this cohort, we performed further layer-specific strain analysis in 20 subjects. Data were analyzed for global and segmental systolic strain, systolic strain rate, early diastolic strain rate, and their respective time-to-peak values. RESULTS: Mean LV global longitudinal, circumferential, and radial strain values for the entire cohort were - 18.4 ± 2.0%, - 22.1 ± 4.1%, and 43.9 ± 12.1% respectively, while mean RV global and free wall longitudinal strain values were - 24.2 ± 3.9% and - 26.1 ± 5.2% respectively. Women on average demonstrated higher longitudinal and circumferential strain and strain rate than men, and longer corresponding time-to-peak values. Longitudinal strain measurements were highest at the apex compared with the mid ventricle and base, and in the endocardium compared with the epicardium. Longitudinal strain was the most reproducible measure, followed closely by circumferential strain, while radial strain showed suboptimal reproducibility. CONCLUSIONS: We present an analysis of ventricular strain in patients with no structural heart disease using a vendor-independent speckle-tracking software.

Dissecting myocardial mechanics in patients with severe aortic stenosis: 2-dimensional vs 3-dimensional-speckle tracking echocardiography.

BACKGROUND: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. Identifying early subclinical markers of LV dysfunction in patients with significant AS is critical as this could provide support for earlier intervention, which may result in improved long-term outcomes. We therefore examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. METHODS: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72 ± 12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. RESULTS: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P = 0.003 for 3D twist, P < 0.001 for all others). Agreement between 2D- and 3D-GLS by concordance correlation coefficient was 0.49 (95% confidence interval: 0.39-0.57). GLS was correlated with valvulo-arterial impedance, a measure of LV afterload (r = 0.34, p < 0.001 and r = 0.23, p = 0.003, respectively). CONCLUSION: Patients with severe AS demonstrated lower-than-normal GLS and GRS but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. GLS showed a modest correlation with valvulo-arterial impedance.

Echocardiographic mimicker of thrombus on a mechanical aortic valve prosthesis due to cavitation: A paradoxical phenomenon of pressure recovery.

We describe a case of a mass-like echocardiographic density on a mechanical prosthetic aortic valve. We initially suspected a thrombus vs vegetation on transthoracic echocardiography, but after transesophageal echocardiography, the density was subsequently determined to be cavitation by reviewing the initial images in slow motion.

Sex-related differences in calcific aortic stenosis: correlating clinical and echocardiographic characteristics and computed tomography aortic valve calcium score to excised aortic valve weight.

AIMS: Calcific aortic valve stenosis (AS) is purportedly associated with less calcium burden in women than in men. We sought to examine sex-related differences and correlates of surgically excised aortic valve weight (AVW) in pure AS. METHODS AND RESULTS: Clinical and echocardiographic characteristics of 888 consecutive patients who underwent aortic valve replacement for severe AS were correlated to AVW, and in 126 patients, AVW was also correlated to computed tomography aortic valve calcium (AVC) score. Women and men had similar indexed valve area (0.42 ± 0.09 vs. 0.42 ± 0.07 cm (2)/m(2), P = 0.95) and mean systolic gradient (53 ± 15 vs. 52 ± 13 mmHg, P = 0.11), but women had higher New York Heart Association class (2.63 ± 0.70 vs. 2.50 ± 0.70, P = 0.01) and less prevalent coronary artery disease (38 vs. 52%, P < 0.0001). Aortic valve weight was lower in women (1.94 ± 0.88 vs. 3.08 ± 1.32 g, P < 0.0001) even when indexed to body surface area (1.09 ± 0.48 vs. 1.48 ± 0.62 g/m(2), P < 0.0001) or left ventricular outflow tract (LVOT) area (0.54 ± 0.23 vs. 0.71 ± 0.29 g/cm(2), P < 0.0001). Using multivariate analysis, male sex (P < 0.0001), bicuspid valve (P < 0.0001), and larger LVOT area (P < 0.0001) were the major determinants of increased AVW, along with current cigarette smoking (P = 0.007). Diabetes (P = 0.004) and hypertension (P = 0.03) were independently associated with lower AVW. Aortic valve calcium correlated well with AVW (r = 0.81, P < 0.0001) and was lower in women than in men (2520 ± 1199 vs. 3606 ± 1632 arbitrary units, P < 0.0001). CONCLUSIONS: Despite the same degree of AS severity, women have less AVC and lower AVW compared with men, irrespective of valve morphology. Aortic valve calcium is correlated to excised AVW. Hypertension, diabetes, and current cigarette smoking were independently associated with AVW.

Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients.

BACKGROUND: Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. METHODS: We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. RESULTS: Over a mean follow-up of 3.3 ± 3.4 years, patients with E/e' ≥15 with exercise (n = 1,323; 9.2%) had lower exercise capacity (7.3 ± 2.1 vs 9.1 ± 2.4 metabolic equivalents, P < .0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P < .0001). Approximately 6% (n = 837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P < .0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR] = 0.58 [0.48-0.69]; P < .0001), had higher risk than if E/e' ≤8 (HR = 1.56 [1.37-1.78], P < .0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P < .0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR = 8.99 [4.7-17.3], P < .0001). CONCLUSION: Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.

Pulmonary Vein Flow Morphology After Transcatheter Mitral Valve Edge-to-Edge Repair as Predictor of Survival.

BACKGROUND: Data on the prognostic factors after mitral valve (MV) transcatheter edge-to-edge repair (TEER; MV-TEER) are limited. Pulsed-wave Doppler interrogation of pulmonary vein flow (PVF) is a convenient method to assess the hemodynamic burden of residual mitral regurgitation (MR), which could be of utility as a predictor of outcomes. METHODS: Patients that underwent MV-TEER between May 2014 and December 2021 at our institution were evaluated. Pulmonary vein flow patterns post-MV-TEER were reviewed on the procedural transesophageal echocardiogram and classified as normal (systolic dominant or codominant) or abnormal (systolic blunting or reversal). The PVF pattern was correlated with all-cause mortality at follow-up. RESULTS: Two-hundred sixty-five patients had diagnostic PVF post-MV-TEER, with 73 (27.5%) categorized as normal and 192 (72.5%) categorized as abnormal. Patients with abnormal PVF morphology were more likely to have atrial fibrillation (70% vs 42%, P < .001) and greater than moderate residual MR (16% vs 3%, P = .01) and had higher mean left atrial pressure (18.1 ± 5.0 vs 15.9 ± 4.2 mm Hg, P = .002) and left atrial V wave (26.6 ± 8.5 vs 21.4 ± 7.3 mm Hg, P < .001) postprocedure. In multivariable analysis, abnormal PVF morphology post-MV-TEER was independently associated with mortality at follow-up (hazard ratio = 1.70; 95% CI, 1.06-2.74; P = .03) after correction for end-stage renal disease, atrial fibrillation, and residual MR. Results were similar in subgroups of patients with moderate or less and those with mild or less residual MR. CONCLUSIONS: Pulmonary vein flow morphology is a simple and objective tool to assess MR severity immediately post-MV-TEER and offers important prognostic information to optimize procedural results. Additional studies are needed to determine whether patients with abnormal PVF pattern post-MV-TEER would benefit from more intensive goal-directed medical therapy postprocedure.

Staging Extramitral Cardiac Damage in Mitral Annular Calcification With Mitral Valve Dysfunction.

BACKGROUND: Mitral annular calcification (MAC) is a progressive degenerative process associated with comorbidities and increased mortality. A staging system that considers extramitral cardiac damage in MAC may help improve patient selection for mitral valve interventions. OBJECTIVES: This study sought to develop a transthoracic echocardiogram (TTE)-based cardiac staging system in patients with MAC and significant mitral valve dysfunction and assess its prognostic utility. METHODS: We retrospectively evaluated all adults who underwent TTE over 1 year at Mayo Clinic with MAC and significant mitral valve dysfunction defined as mitral stenosis and/or at least moderate mitral regurgitation. Patients were categorized into 5 stages according to extramitral cardiac damage by TTE. All-cause mortality and heart failure hospitalization were assessed. RESULTS: For the 953 included patients, the mean age was 76.2 ± 10.7 years, and 54.0% were women. Twenty-eight (2.9%) patients were classified in stages 0 to 1, 499 (52.4%) in stage 2, 115 (12.1%) in stage 3, and 311 (32.6%) in stage 4. At the 3.8-year follow-up, mortality was significantly higher in patients in stages 2 to 4 compared to stages 0 to 1 and increased with each stage. Survival differences were maintained after adjustment for age, diabetes mellitus, and glomerular filtration rate. The rate of heart failure hospitalization was significantly higher in stages 3 and 4 compared to stages 0 to 1. Similar results were observed in subgroup analysis in patients with moderate or severe MAC, predominant mitral stenosis, or predominant mitral regurgitation. CONCLUSIONS: Using the proposed extramitral cardiac damage staging system in patients with MAC and significant mitral valve dysfunction, more advanced stages are associated with higher mortality.

2-Year Clinical and Echocardiography Follow-Up of Transcatheter Mitral Valve Replacement With the Transapical Intrepid System.

BACKGROUND: Thirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. OBJECTIVES: The authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. METHODS: Patient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. RESULTS: The cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, >50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. CONCLUSIONS: This analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years.

Incidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice.

OBJECTIVES: Prior data indicate a very rare risk of serious adverse drug reaction (ADR) to ultrasound enhancement agents (UEAs). We sought to evaluate the frequency of ADR to UEA administration in contemporary practice. METHODS: We retrospectively reviewed 4 US health systems to characterize the frequency and severity of ADR to UEA. Adverse drug reactions were considered severe when cardiopulmonary involvement was present and critical when there was loss of consciousness, loss of pulse, or ST-segment elevation. Rates of isolated back pain and headache were derived from the Mayo Clinic Rochester stress echocardiography database where systematic prospective reporting of ADR was performed. RESULTS: Among 26,539 Definity and 11,579 Lumason administrations in the Mayo Clinic Rochester stress echocardiography database, isolated back pain or headache was more frequent with Definity (0.49% vs 0.04%, P < .0001) but less common with Definity infusion versus bolus (0.08% vs 0.53%, P = .007). Among all sites there were 201,834 Definity and 84,943 Lumason administrations. Severe and critical ADR were more frequent with Lumason than with Definity (0.0848% vs 0.0114% and 0.0330% vs 0.0010%, respectively; P < .001 for each). Among the 3 health systems with >2,000 Lumason administrations, the frequency of severe ADR with Lumason ranged from 0.0755% to 0.1093% and the frequency of critical ADR ranged from 0.0293% to 0.0525%. Severe ADR rates with Definity were stable over time but increased in more recent years with Lumason (P = .02). Patients with an ADR to Lumason since the beginning of 2021 were more likely to have received a COVID-19 vaccination compared with matched controls (88% vs 75%; P = .05) and more likely to have received Moderna than Pfizer-Biotech (71% vs 26%, P < .001). CONCLUSION: Severe and critical ADR, while rare, were more frequent with Lumason, and the frequency has increased in more recent years. Additional work is needed to better understand factors, including associations with recently developed mRNA vaccines, which may be contributing to the increased rates of ADR to UEA since 2021.

Impact of Atrial Fibrillation on Outcomes in Very Severe Aortic Valve Stenosis.

The prevalence and impact of atrial fibrillation (AF) versus sinus rhythm (SR) on outcomes in very severe aortic stenosis (vsAS) of the native valve is unknown. The aim of the study was to determine the prognostic significance of AF in vsAS. A total of 563 patients with vsAS (transaortic valve peak velocity ≥5 m/s) and left ventricular ejection fraction ≥50% were identified retrospectively. Patients were divided by rhythm at the time of index transthoracic echocardiogram (AF: n = 50 [9%] vs SR: n = 513 [91%]). Patients with AF were older (83.1 ± 7.5 vs 72.5 ± 12.2 y, p <0.001) and had no difference in gender distribution (p = 0.49) but had a higher Charlson co-morbidity index (2 [1,3] vs 1 [0,2], p = 0.01). There was no difference in transaortic peak velocity (5.3 ± 0.3 m/s vs 5.4 ± 0.4 m/s, p = 0.13) and left ventricular ejection fraction was comparable (63 ± 7 vs 66 ± 7%, p = 0.01). Age-, gender-, Charlson co-morbidity index-, and time-dependent aortic valve replacement (AVR)-adjusted overall mortality at 5 years was significantly higher in patients with AF than patients with SR (hazard ratio [HR] 1.88 [1.23 to 2.85], p = 0.003). AVR was associated with improved survival (HR = 0.30 [0.22 to 0.42], p <0.001), with no statistically significant interaction of AVR and rhythm (p = 0.36). Outcomes were also compared in the 2 SR:1 AF propensity-matched analyses (100 SR: 50 AF), with matching done according to age, gender, clinical co-morbidities, and year of echocardiogram. In the propensity-matched analysis, age-, gender-, and time-dependent AVR-adjusted all-cause mortality was higher in AF (HR 2.32 [1.41 to 3.82], p <0.001). In conclusion, AF was not uncommon in vsAS and identified a subset of patients at a much higher risk of mortality without AVR.

Right ventricular systolic strain in patients with pulmonary hypertension: clinical feasibility, reproducibility, and correlation with ejection fraction.

BACKGROUND: Right ventricular (RV) systolic function is the major determinant of prognosis in patients with pulmonary hypertension (PH) with quantitative assessment by speckle-tracking strain echocardiography emerging as a viable candidate measure. METHOD: We evaluated a prospective cohort of 231 patients with known or suspected PH referred for clinical echocardiography. All underwent measurement of RV free-wall systolic strain by sonographer staff. Digital images were recorded for blinded offline assessment by an expert echocardiographer. Reproducibility was assessed using the analysis methods of Bland-Altman and the Cohen's-Kappa coefficient. RESULTS: RV strain was feasible in 213 (92%). The average RV systolic pressure was 59 ± 22 mmHg. RV systolic strain correlated with functional class, NT-proBNP, and the degree of RV enlargement. The average free-wall systolic strain was - 20 ± 7% (range - 2 to - 37%). The RV strain measures (clinical practice versus blinded expert) had an excellent correlation with a normal distribution (R2 0.87, p < 0.0001). By Bland-Altman analysis, the mean difference in measurement was - 1.7% (95% CI - 1.4 to - 2.1) with a correlation of 0.93, p value of < 0.0001. The reproducibility of RV strain for clinically relevant thresholds was also excellent (Kappa coefficients 0.68-0.83). There was no effect on the variability of strain measures across body mass, pulmonary pressures, or rhythm. RV strain correlated with RV diastolic volumes and ejection fraction with RV free wall strain being the best echo predictor for a reduction in ejection fraction. CONCLUSION: Here RV systolic strain was found to be highly feasible and reproducible in clinical practice with excellent levels of agreement for clinically relevant thresholds.

Cerebral and Retinal Infarction in Bicuspid Aortic Valve.

Background Description of cerebral and retinal infarction in patients with bicuspid aortic valve (BAV) is limited to case reports. We aimed to characterize cerebral and retinal infarction and examine outcomes in patients with BAV. Methods and Results Consecutive patients from 1975 to 2015 with BAV (n=5401) were retrospectively identified from the institutional database; those with confirmed cerebral or retinal infarction were analyzed. Infarction occurring after aortic valve replacement was not included. Patients were grouped according to infarction pathogenesis: embolism from a degenerative calcific BAV (BAVi); non-BAV, large artery atherosclerotic or lacunar infarction (LAi); and non-BAV, non-large artery embolic infarction (nLAi). There were 83/5401 (1.5%) patients, mean age 54±12 years and 28% female, with confirmed cerebral or retinal infarction (LAi 23/83 [28%]; nLAi 30/83 [36%]; BAVi 26/83 [31%]; other 4/83 [5%]). Infarction was embolic in 72/83 (87%), and 35/72 (49%) were cardioembolic. CHA2DS2-VASc score was 1.4±1.2 in BAVi (P=0.188 versus nLAi) and 2.3±1.2 in LAi (P=0.005). Recurrent infarction occurred in 41% overall (50% BAVi, P=0.164 and 0.803 versus LAi and nLAi). BAVi was more commonly retinal (39% BAVi versus 13% LAi, P=0.044 versus 0% nLAi, P=0.002). Patients with BAVi and LAi were more likely to have moderate-to-severe aortic stenosis and undergo aortic valve replacement compared with patients with nLAi. Conclusions Cardioembolism, often from degenerative calcification of the aortic valve, is a predominant cause of cerebral and retinal infarction in patients with BAV and is frequently recurrent. Cerebral and retinal infarction should be regarded as a complication of BAV.

Underestimation of Aortic Stenosis Severity by Doppler Mean Gradient during Atrial Fibrillation: Insights from Aortic Valve Weight.

BACKGROUND: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity when obtained during atrial fibrillation (AF) compared with sinus rhythm (SR). Aortic valve weight (AVW) is a flow-independent measure of AS severity. The objective of this study was to determine whether AVW or AVW/MG ratio was increased in AF versus SR in patients with AS. METHODS: Excised native aortic valves from 495 consecutive patients (median age, 77 years; interquartile range [IQR], 71-82 years; 40% women), with left ventricular ejection fractions ≥50% who underwent surgical aortic valve replacement for native valve severe AS (aortic valve area ≤ 1 cm2 or indexed aortic valve area ≤ 0.6 cm2/m2) were weighed. Excised AVW/MG ratios were compared in AF versus SR in patients with high-gradient AS (aortic peak velocity ≥ 4 m/sec or MG ≥ 40 mm Hg) and low-gradient AS (aortic peak velocity < 4 m/sec and MG < 40 mm Hg) in sex-specific analyses. RESULTS: AF was present in 51 patients (10%; 11 of 51 [22%] had low-gradient AS) and SR in 444 (90%; 23 of 444 [5%] had low-gradient AS). There was no difference in sex distribution between AF and SR. Aortic valve area was not different, but forward stroke volume index and transaortic valve flow rate were lower in AF (P ≤ .002 for all); MG was lower in AF versus SR (median, 46 mm Hg [IQR, 37-50 mm Hg] vs 50 mm Hg [IQR, 44-61 mm Hg]; P < .0001). Overall AVW was not different (median, 2,290 mg [IQR, 1,830-3,063 mg] vs 2,140 mg [IQR, 1,530-2,958 mg]; P = .31), but overall AVW/MG ratio was higher in AF (median, 55 [IQR, 41-67] vs 42 [IQR, 30-55]; P = .001). In sex- and MG-specific analyses, the AVW/MG ratio was higher in AF compared with SR in men with high-gradient AS (median, 58 [IQR, 41-75] vs 51 [IQR, 39-61]; P = .03), but the differences were not statistically significant between AF and SR in other groups. CONCLUSIONS: AVW was discordant to Doppler MG in AF compared with SR in men with high-gradient AS. Additional studies of the relationship of MG to other measures of AS severity, such as leaflet fibrosis, are needed.

Impact of atrial fibrillation on outcomes in asymptomatic severe aortic stenosis: a propensity-matched analysis.

Background: Atrial fibrillation (AF) portends poor prognosis in patients with aortic stenosis (AS). Objectives: This study aimed to study the association of AF vs. sinus rhythm (SR) with outcomes in asymptomatic severe AS during routine clinical practice. Methods: We identified 909 asymptomatic patients from 3,208 consecutive patients with aortic valve area ≤1.0 cm2 and left ventricular ejection fraction ≥50% at a tertiary academic center. Patients were grouped by rhythm at the time of transthoracic echocardiogram [SR: 820/909 (90%) and AF: 89/909 (10%)]. Propensity-matched analyses (2 SR:1 AF) matching 174 SR to 89 AF patients by age, sex, and clinical comorbidities were used to compare outcomes. Results: In the propensity-matched cohort, median age (82 ± 8 vs. 81 ± 9 years, p = 0.31), sex distribution (male 58% vs. 52%, p = 0.30), and Charlson comorbidity index (4.0 vs. 3.0, p = 0.26) were not different in AF vs. SR. Median follow-up duration was 2.6 (IQR: 1.0-4.4) years. The 1-year rate of aortic valve replacement (AVR) was not different (AF: 32% vs. SR: 37%, p = 0.31). All-cause mortality was higher in AF [hazard ratio (HR): 1.68 (1.13-2.50), p = 0.009]. Independent predictors of mortality were age [HR: 1.92 (1.40-2.62), p < 0.001], Charlson comorbidity index [1.09 (1.03-1.15), p = 0.002], aortic valve peak velocity [HR: 1.87 (1.20-2.94), p = 0.006], stroke volume index [HR: 0.75 (0.60-0.93), p = 0.01], moderate or more mitral regurgitation [HR: 2.97 (1.43-6.19), p = 0.004], right ventricular systolic dysfunction [HR: 2.39 (1.29-4.43), p = 0.006], and time-dependent AVR [HR: 0.36 (0.19-0.65), p = 0.0008]. There was no significant interaction of AVR and rhythm (p = 0.57). Conclusions: Lower forward flow, right ventricular systolic dysfunction, and mitral regurgitation identified increased risk of subsequent mortality in asymptomatic patients with AF and AS. Additional studies of risk stratification of asymptomatic AS in AF vs. SR are needed.