Network Meta-Analysis Comparing Transcatheter, Minimally Invasive, and Conventional Surgical Aortic Valve Replacement.

The landscape of aortic valve replacement (AVR) has evolved dramatically over the years, but time-varying outcomes have yet to be comprehensively explored. This study aimed to compare the all-cause mortality among 3 AVR techniques: transcatheter (TAVI), minimally invasive (MIAVR), and conventional AVR (CAVR). An electronic literature search was performed for randomized controlled trials (RCTs) comparing TAVI with CAVR and RCTs or propensity score-matched (PSM) studies comparing MIAVR with CAVR or MIAVR to TAVI. Individual patient data for all-cause mortality were derived from graphical reconstruction of Kaplan-Meier curves. Pairwise comparisons and network meta-analysis were conducted. Sensitivity analyses were performed in the TAVI arm for high risk and low/intermediate risk, as well as patients who underwent transfemoral (TF) TAVI. A total of 27 studies with 16,554 patients were included. In the pairwise comparisons, TAVI showed superior mortality to CAVR until 37.5 months, beyond which there was no significant difference. When restricted to TF TAVI versus CAVR, a consistent mortality benefit favoring TF TAVI was seen (shared frailty hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.76 to 0.98, p = 0.024). In the network meta-analysis involving majority PSM data, MIAVR demonstrated significantly lower mortality than TAVI (HR = 0.70, 95% CI = 0.59 to 0.82) and CAVR (HR = 0.69, 95% CI = 0.59 to 0.80); this association remained compared with TF TAVI but with a lower extent of benefit (HR = 0.80, 95% CI = 0.65 to 0.99). In conclusion, the initial short- to medium-term mortality benefit for TAVI over CAVR was attenuated over the longer term. In the subset of patients who underwent TF TAVI, a consistent benefit was found. Among majority PSM data, MIAVR showed improved mortality compared with TAVI and CAVR but less than the TF TAVI subset, which requires validation by robust RCTs.

Impact of aortic annular size and valve type on haemodynamics and clinical outcomes after transcatheter aortic valve implantation.

INTRODUCTION: Data on patients with small aortic annuli (SAA) undergoing transcatheter aortic valve implantation (TAVI) are limited. We aim to describe the impact of aortic annular size, particularly SAA and TAVI valve type on valve haemodynamics, durability and clinical outcomes. METHOD: All patients in National Heart Centre Singapore who underwent transfemoral TAVI for severe symptomatic native aortic stenosis from July 2012 to December 2019 were included. Outcome measures include valve haemodynamics, prosthesis-patient mismatch (PPM), structural valve degeneration (SVD) and mortality. RESULTS: A total of 244 patients were included. The mean Society of Thoracic Surgeons score was 6.22±6.08, with 52.5% patients with small aortic annulus (<23mm), 33.2% patients with medium aortic annulus (23-26mm) and 14.3% patients with large aortic annulus (>26mm). There were more patients with self-expanding valve (SEV) (65.2%) versus balloon-expandable valve (BEV) (34.8%). There were no significant differences in indexed aortic valve area (iAVA), mean pressure gradient (MPG), PPM, SVD or mortality across all aortic annular sizes. However, specific to the SAA group, patients with SEV had larger iAVA (SEV 1.19±0.35cm2/m2 vs BEV 0.88±0.15cm2/m2, P<0.01) and lower MPG (SEV 9.25±4.88 mmHg vs BEV 14.17±4.75 mmHg, P<0.01) at 1 year, without differences in PPM or mortality. Aortic annular size, TAVI valve type and PPM did not predict overall mortality up to 7 years. There was no significant difference in SVD between aortic annular sizes up to 5 years. CONCLUSION: Valve haemodynamics and durability were similar across the different aortic annular sizes. In the SAA group, SEV had better haemodynamics than BEV at 1 year, but no differences in PPM or mortality. There were no significant differences in mortality between aortic annular sizes, TAVI valve types or PPM.

Factors Affecting Rate of Progression of Aortic Stenosis and Its Impact on Outcomes.

The rate of aortic stenosis (AS) progression in patients with moderate AS is unclear. This study examined the risk factors of progression from moderate to severe AS and its impact on clinical outcomes. A total of 954 patients with moderate AS (valve area >1.0 and ≤1.5 cm²) and follow-up echocardiograms were included. AS progressed to severe (valve area <1.0 cm1) in 589 patients (61.7%) over a median follow-up of 2.46 (interquartile range [IQR] 1.29 to 3.91) years. Of those who progressed to severe AS, patients were subdivided into Slow (n = 294, over 3.91 [IQR 3.11 to 5.10] years) versus Fast (n = 295, over 1.29 [IQR 0.85 to 1.85] years) Progressors, according to the median time between the 2 echocardiograms. The correlates of fast AS progression and its impact on cumulative survival and freedom from valve intervention were evaluated. On multivariate analysis, age, thickened left ventricle posterior wall, severe renal impairment, and aortic valve area were significantly associated with fast AS progression. Over a median follow-up of 6.34 (IQR 4.05 to 9.55) years, 228 patients (38.7%) died. Despite similar aortic valve intervention rates, Fast Progressors had worse 5-year survival (61.2% vs 81.9%, log-rank p <0.001) and event-free (valve intervention and all-cause mortality) survival rates (16.2% vs 55.9%, log-rank p <0.001). On multivariable Cox analysis, shorter progression to severe AS (in years) was independently associated with increased risk of all-cause mortality (hazard ratio 1.26, 95% confidence interval 1.16 to 1.37, p <0.001), or combined aortic valve intervention and death (hazard ratio 1.46, 95% confidence interval 1.38 to 1.55, p <0.001). In conclusion, fast progression from moderate to severe AS is associated with worse outcomes.

Predicting premature termination of exercise during Bruce protocol stress echocardiography.

AIMS: Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be "steep", and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool. METHODS AND RESULTS: We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration < 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e' > 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all < 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p < 0.001). CONCLUSION: These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep.

Prognostic Implications of Associated Cardiac Abnormalities Detected on Echocardiography in Patients With Moderate Aortic Stenosis.

OBJECTIVES: This study aimed to evaluate the prevalence and prognostic value of the extent of extra-aortic valvular cardiac abnormalities in a large multicenter registry of patients with moderate AS. BACKGROUND: The prognostic significance of a new classification system that incorporates the extent of cardiac injury (beyond the aortic valve) has been proposed in patients with severe aortic stenosis (AS). Whether this can be applied to patients with moderate AS is unclear. METHODS: Based on the echocardiographic findings at the time of diagnosis of moderate AS (aortic valve area between 1.0 and 1.5 cm2 and dimensionless velocity index ratio of ≥0.25), a total of 1,245 patients were included and analyzed retrospectively. They were recategorized into 5 groups according to the extent of extra-aortic valvular cardiac abnormalities: none (Group 0), involving the left ventricle (Group 1), the left atrial or mitral valve (Group 2), the pulmonary artery vasculature or tricuspid valve (Group 3), or the right ventricle (Group 4). Patients were followed for all-cause mortality and combined endpoint (all-cause mortality, stroke, heart failure, or myocardial infarction). RESULTS: The distribution of patients according to the proposed classification was 13.1%, 26.8%, 42.6%, 10.6%, and 6.9% in Groups 0, 1, 2, 3, and 4, respectively. During a median follow-up of 4.3 (2.4 to 6.9) years, 564 (45.3%) patients died. There was a significant higher mortality rates with increasing extent of extra-aortic valvular cardiac abnormalities (log-rank p < 0.001). On multivariable analysis, the presence of extra-aortic valvular cardiac abnormalities remained independently associated with all-cause mortality and combined outcome, adjusted for aortic valve replacement as a time-dependent covariable. In particular, Group 2 and above were independently associated with all-cause mortality. CONCLUSIONS: In patients with moderate AS, the presence of extra-aortic valvular cardiac abnormalities is associated with poor outcome.

Impact of Chronic Kidney Disease on Outcomes in Transcatheter Aortic Valve Implantation.

INTRODUCTION: Chronic kidney disease (CKD) is a significant comorbidity in aortic stenosis (AS) patients. We examined the impact of baseline CKD, postoperative acute kidney injury (AKI) and CKD progression on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI). MATERIALS AND METHODS: Consecutive patients with severe AS who underwent TAVI were classified into CKD stages 1-2 (≥60 mL/min/1.72m2), 3 (30-59 mL/min/1.73m2) and 4-5 (<30 mL/min/1.73m2 or dialysis) based on estimated glomerular filtration rate (eGFR). Primary outcome was mortality and secondary outcomes included 1-year echocardiographic data on aortic valve area (AVA), mean pressure gradient (MPG) and aortic regurgitation (AR). RESULTS: A total of 216 patients were included. Higher eGFR was associated with lower overall mortality (adjusted hazards ratio [AHR] 0.981, 95% confidence interval [CI] 0.968-0.993, P = 0.002). CKD 4-5 were associated with significantly higher mortality from non-cardiovascular causes (P <0.05). Patients with CKD 3-5 had higher incidence of moderate AR than those with CKD 1-2 (P = 0.010); no difference in AVA and MPG was seen. AKI patients had higher mortality (P = 0.008), but the effect was attenuated on multivariate analysis (AHR 1.823, 95% CI 0.977-3.403, P = 0.059). Patients with CKD progression also had significantly higher mortality (AHR 2.969, 95% CI 1.373-6.420, P = 0.006). CONCLUSION: CKD in severe AS patients undergoing TAVI portends significantly higher mortality and morbidity. Renal disease progression impacts negatively on outcomes and identifies a challenging subgroup of patients for optimal management.

E/e' in relation to outcomes in ST-elevation myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a high-risk condition especially when filling pressure is raised, and earlier reports have suggested that E/e' is associated with poor outcome. However, whether E/e' predicts risk better than LVEF, which is the current standard of practice, is not known. We investigated this question in the largest and most rigorous study of MI patients so far. METHODS AND RESULTS: We studied 660 patients with ST-elevation MI (STEMI) treated with primary percutaneous coronary intervention and related E/e' to short-term mortality (in-hospital death), as well as long-term events at 2 years comprising (a) a composite of MI, stroke, heart failure, and death, and (b) death alone. Short-term models were adjusted for age, sex, and LVEF. Long-term models were adjusted for age, sex, diabetes, revascularization procedure, history of MI, hypertension, renal function, drugs on discharge, and LVEF. Elevated E/e'> 15 indicated higher risk of short-term events (n = 19:7.0% (95% confidence interval 3.4-10.8%) vs. 1.0% (0.3 - 2.3%); adjusted odds ratio 3.7 (1.3-10.5)). While elevated E/e' was also associated with long-term outcomes (n = 103 composite events: 15.9% (11.9% - 21.4%) vs 6.8% (5.2% - 8.7%), P < .001; n = 38 death events: 6.0% (3.9% - 9.5%) vs 2.0% (1.3% - 3.2%), P = .001), E/e' was rendered nonsignificant for long-term outcomes by multivariable adjustment (p = ns for both). LVEF, on the contrary, was a highly significant predictor in the adjusted long-term model. CONCLUSION: E/e' is associated with poor outcome in STEMI, but LVEF is a stronger predictor of long-term risk.

Allometric Relationships for Cardiac Size and Longitudinal Function in Healthy Chinese Adults　- Normal Ranges and Clinical Correlates.

BACKGROUND: Cardiac size measurements require indexing to body size. Allometric indexing has been investigated in Caucasian populations but a range of different values for the so-called allometric power exponent (b) have been proposed, with uncertainty as to whether allometry offers clinical utility above body surface area (BSA)-based indexing. We derived optimal values for b in normal echocardiograms and validated them externally in cardiac patients. METHODS AND RESULTS: Values for b were derived in healthy adult Chinese males (n=1,541), with optimal b for left ventricular mass (LVM) of 1.66 (95% confidence interval 1.41-1.92). LV hypertrophy (LVH) defined as indexed LVM >75 g/m1.66 was associated with adverse outcomes in an external validation cohort (n=738) of patients with acute coronary syndrome (odds ratio for reinfarction: 2.4 (1.1-5.4)). In contrast, LVH defined by BSA-based indexing or allometry using exponent 2.7 exhibited no significant association with outcomes (P=NS for both). Cardiac longitudinal function also varied with body size: septal and RV free wall s', TAPSE and lateral e' all scaled allometrically (b=0.3-0.9). CONCLUSIONS: An optimal b of 1.66 for LVM in healthy Chinese was found to validate well, with superior clinical utility both to that of BSA-based indexing and to b=2.7. The effect of allometric indexing of cardiac function requires further study.

Impact of aortic root size on left ventricular afterload and stroke volume.

PURPOSE: The left ventricle (LV) ejects blood into the proximal aorta. Age and hypertension are associated with stiffening and dilation of the aortic root, typically viewed as indicative of adverse remodeling. Based on analytical considerations, we hypothesized that a larger aortic root should be associated with lower global afterload (effective arterial elastance, EA) and larger stroke volume (SV). Moreover, as antihypertensive drugs differ in their effect on central blood pressure, we examined the role of antihypertensive drugs for the relation between aortic root size and afterload. METHODS: We studied a large group of patients (n = 1250; 61 ± 12 years; 78 % males; 64 % hypertensives) from a single-center registry with known or suspected coronary artery disease. Aortic root size was measured by echocardiography as the diameter of the tubular portion of the ascending aorta. LV outflow tract Doppler was used to record SV. RESULTS: In the population as a whole, after adjusting for key covariates in separate regression models, aortic root size was an independent determinant of both SV and EA. This association was found to be heterogeneous and stronger in patients taking a calcium channel blocker (CCB; 10.6 % of entire population; aortic root size accounted for 8 % of the explained variance of EA). CONCLUSION: Larger aortic root size is an independent determinant of EA and SV. This association was heterogeneous and stronger in patients on CCB therapy.