Restricted Cusp Motion in Newly Implanted Tricuspid Bioprostheses: Incidence, Predictors, and Impact on Survival.

OBJECTIVE: This study aimed to investigate the occurrence of restricted cusp motion (RCM) at the time of bioprosthetic tricuspid valve replacement (TVR) and analyzed associated risk factors and outcomes. METHODS: This study involved adult patients who underwent TVR with a bioprosthesis at our institution between 2012 and 2022. Bioprosthetic cusp motion was analyzed de-novo through a detailed review of intraoperative transesophageal echocardiograms (TEE). Two models of porcine valves were implanted, the Hancock II bioprosthesis (Medtronic, Inc, Minneapolis, Minnesota) and the St. Jude Epic bioprosthesis (St. Jude Medical, St. Paul, Minnesota). RESULTS: Among the 476 patients who met the inclusion criteria, RCM was identified on the immediate post-bypass TEE in 150 (31.5%); there was complete immobility of the cusp in 63 patients (13.2%) and limited movement of a cusp in 87 patients (18.3%). In a multivariable logistic regression analysis, the Hancock II model (OR 6.15, p<0.001), a larger orifice area (per IQR increase, OR 1.58, p=0.017), a smaller body surface area (per IQR increase, OR 0.68, p=0.040), and a lower ejection fraction (per IQR increase, OR 0.60, p=0.033) were independently associated with having RCM. Cox regression adjusting for 15 covariates revealed that RCM at time of TVR was independently associated with an increased risk of mortality (HR 1.35, p=0.049). CONCLUSIONS: This study revealed a high incidence of restricted cusp motion in bioprosthetic valves in the tricuspid position detected shortly post-implantation, which was associated with increased late mortality. To reduce the probability of restricted cusp motion, it is important to select the appropriate prosthesis model and size, particularly in small patients.

Prognostic Value of Aortic Valve Calcification in Nonsevere Aortic Stenosis with Preserved Ejection Fraction.

BACKGROUND: Aortic valve calcification(AVC) is prognostic in patients with aortic stenosis(AS). We assessed the AVC prognostic value in nonsevere AS patients. METHODS AND RESULTS: We conducted a retrospective study of 395 patients with nonsevere AS, LV ejection fraction ≥50%. The Agatston method was used for computed tomography AVC assessment. The log-rank test determined the best AVC cutoffs for survival under medical surveillance: 1185 AU in men and 850 in women, lower than the established-cutoffs for severe AS(2064AU in men and 1274 in women). Patients were divided into three AVC groups based on these cutoffs: low(<1185 AU men and <850 women), sub-severe(1185-2064AU men and 850-1274 women) and severe(>2064AU men and >1274 women). Of 395 patients(mean age 73 ± 12 years, 60.5% men, aortic valve area 1.23 ± 0.30cm2, mean pressure gradient 28 ± 8 mmHg), 218 underwent aortic valve intervention(AVI) and 158 deaths occurred during follow-up, 82 before AVI. Median survival time under medical surveillance was 2.1[0.7-4.9]years. Compared to the low AVC group, both sub-severe and severe AVC groups had higher risk for all-cause death under medical surveillance after comprehensive adjustment including echocardiographic AS severity and coronary artery calcium score(all p ≤ 0.006); while mortality risk was similar between sub-severe and severe AVC groups(all p ≥ 0.2). This mortality risk pattern persisted in the overall survival analysis after adjustment for AVI. AVI was protective of all-cause death in the sub-severe and severe AVC(all p ≤ 0.01), but not in the low AVC groups. CONCLUSIONS: Sub-severe AVC is a robust risk-stratification parameter in patients with nonsevere AS and may inform AVI timing.

The prognostic value of artificial intelligence to predict cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Aims: Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results: In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01-1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01-1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13-2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion: Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.

Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

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.

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.

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.

Aortic Valve Calcium Score by Computed Tomography as an Adjunct to Echocardiographic Assessment-A Review of Clinical Utility and Applications.

Aortic valve stenosis (AS) is increasing in prevalence due to the aging population, and severe AS is associated with significant morbidity and mortality. Echocardiography remains the mainstay for the initial detection and diagnosis of AS, as well as for grading of severity. However, there are important subgroups of patients, for example, patients with low-flow low-gradient or paradoxical low-gradient AS, where quantification of severity of AS is challenging by echocardiography and underestimation of severity may delay appropriate management and impart a worse prognosis. Aortic valve calcium score by computed tomography has emerged as a useful clinical diagnostic test that is complimentary to echocardiography, particularly in cases where there may be conflicting data or clinical uncertainty about the degree of AS. In these situations, aortic valve calcium scoring may help re-stratify grading of severity and, therefore, further direct clinical management. This review presents the evolution of aortic valve calcium score by computed tomography, its diagnostic and prognostic value, as well as its utility in clinical care.

Bicuspid aortic valve: long-term morbidity and mortality.

BACKGROUND AND AIMS: Bicuspid aortic valve (BAV) is the most common congenital heart anomaly. Lifetime morbidity and whether long-term survival varies according to BAV patient-sub-groups are unknown. This study aimed to assess lifetime morbidity and long-term survival in BAV patients in the community. METHODS: The authors retrospectively identified all Olmsted County (Minnesota) residents with an echocardiographic diagnosis of BAV from 1 January 1980 to 31 December 2009, including patients with typical valvulo-aortopathy (BAV without accelerated valvulo-aortopathy or associated disorders), and those with complex valvulo-aortopathy (BAV with accelerated valvulo-aortopathy or associated disorders). RESULTS: 652 consecutive diagnosed BAV patients [median (IQR) age 37 (22-53) years; 525 (81%) adult and 127 (19%) paediatric] were followed for a median (IQR) of 19.1 (12.9-25.8) years. The total cumulative lifetime morbidity burden (from birth to age 90) was 86% (95% CI 82.5-89.7); cumulative lifetime progression to ≥ moderate aortic stenosis or regurgitation, aortic valve surgery, aortic aneurysm ≥45 mm or z-score ≥3, aorta surgery, infective endocarditis and aortic dissection was 80.3%, 68.5%, 75.4%, 27%, 6% and 1.6%, respectively. Survival of patients with typical valvulo-aortopathy [562 (86%), age 40 (28-55) years, 86% adults] was similar to age-sex-matched Minnesota population (P = .12). Conversely, survival of patients with complex valvulo-aortopathy [90 (14%), age 14 (3-26) years, 57% paediatric] was lower than expected, with a relative excess mortality risk of 2.25 (95% CI 1.21-4.19) (P = .01). CONCLUSION: The BAV condition exhibits a high lifetime morbidity burden where valvulo-aortopathy is close to unavoidable by age 90. The lifetime incidence of infective endocarditis is higher than that of aortic dissection. The most common BAV clinical presentation is the typical valvulo-aortopathy with preserved expected long-term survival, while the complex valvulo-aortopathy presentation incurs higher mortality.

Right heart catheterization predictors of symptomatic improvement in patients undergoing transcatheter tricuspid valve edge-to-edge repair.

BACKGROUND: Transcatheter tricuspid valve edge-to-edge repair (TTEER) is associated with improvement in outcomes for symptomatic patients with severe tricuspid regurgitation (TR). However, reliable predictors for clinical success are not yet fully defined. This study aims to describe right heart catheterization (RHC) findings in patients referred for TTEER and identify hemodynamic characteristics of patients who experience immediate symptomatic improvement following successful TR intervention. METHODS: Patients who underwent TTEER and had a separate RHC within the preceding 6 months were included. Hemodynamic tracings from the RHC and TTEER procedures were reviewed and recorded. Clinical success was defined as a successful device implant with at least 1-grade of TR reduction and improvement in NYHA class by 1 or more grades on 30-day echocardiogram and clinical follow-up. RESULTS: Thirteen patients underwent an RHC within 6 months of TTEER procedure (median age 76 years [IQR: 73-80]). All patients were on a stable dose of loop diuretics. Baseline right atrial pressure was severely elevated (mean 19 mmHg [IQR: 9-24 mmHg]) with prominent CV waves. Median pulmonary capillary wedge pressure (PCWP) was 20 mmHg (IQR: 14-22) and 70% of patients had a mean PCWP > 15 mmHg at rest. Median PCWP CV-wave was 34 mmHg (IQR: 23-42). Higher PCWP CV-wave height (40 mmHg [IQR 33-43] versus 18 mmHg [IQR 17-31]) was associated with lower likelihood of clinical success (OR 0.83, 95% CI: 0.35-0.97, p = 0.04). CONCLUSIONS: Inclusion of invasive hemodynamics as part of pre-TTEER evaluation may allow for improved TR phenotyping and patient selection. Patients with a large left atrial CV wave on resting RHC were less likely to experience immediate symptomatic improvement despite procedural success with TTEER.

Pulmonary artery pulsatility index in patients with tricuspid valve regurgitation: a simple non-invasive tool for risk stratification.

AIMS: Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle in patients with TR and to investigate their association with outcomes. The pulmonary artery pulsatility index (PAPi) has emerged as a haemodynamic risk predictor in left heart disease and pulmonary hypertension (PH). Whether PAPi discriminates risk in unselected patients with greater than or equal to moderate TR is unknown. METHODS AND RESULTS: In 5079 patients with greater than or equal to moderate TR (regardless of aetiology) and PA systolic and diastolic pressures measured on their first echocardiogram, we compared all-cause mortality at 5 years based on the presence or absence of PH and PAPi levels. A total of 2741 (54%) patients had PH. The median PAPi was 3.0 (IQR 1.9, 4.4). Both the presence of PH and decreasing levels of PAPi were associated with larger right ventricles, worse right ventricular systolic function, higher NT-pro BNP levels, greater degrees of right heart failure, and worse survival. In a subset of patients who had an echo and right heart catheterization within 24 h, the correlation of non-invasive to invasive PA pressures and PAPi levels was very good (r = 0.76). CONCLUSION: In patients with greater than or equal to moderate TR with and without PH, lower PAPi is associated with right ventricular dysfunction, right heart failure, and worse survival. Incorporating PA pressure and PAPi may help stratify disease severity in patients with greater than or equal to moderate TR regardless of aetiology.

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.

Prevalence and Natural History of Mitral Annulus Calcification and Related Valve Dysfunction.

OBJECTIVE: To evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography. METHODS: A retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD. RESULTS: Of 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD-, 86% in MAC-/MVD+, and 92% in MAC-/MVD-. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10). CONCLUSION: In a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.