Unsupervised clustering of patients with severe aortic stenosis: A myocardial continuum.

BACKGROUND: Traditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS). AIMS: To investigate a new classification system for severe AS using phenomapping. METHODS: Consecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm2 were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable. RESULTS: In total, 613 patients were initially recruited, with a mean±standard deviation AVA of 0.72±0.17 cm2. Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n=1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46-3.26; P<0.001). CONCLUSIONS: Artificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease.

Impact of Right Ventricular Systolic Dysfunction on Outcome in Aortic Stenosis.

BACKGROUND: Pulmonary hypertension is an established outcome predictor in patients with aortic stenosis (AS), but the prognostic impact of right ventricular dysfunction has not been well studied. METHODS: We included 2181 patients (50.4% men; mean age, 77 years) with aortic valve area <1.3 cm2 and analyzed the occurrence of all-cause death during follow-up according to tricuspid annular plane systolic excursion (TAPSE) quartiles. RESULTS: Patients in the lowest quartile (TAPSE <17 mm) were at a high risk of death, whereas survival was comparable for the 3 other quartiles. Five-year survival was 55±2% for TAPSE <17 mm, 72±2% for TAPSE of 17 to 20 mm, 71±2% for TAPSE of 20 to 24 mm, and 73±2% for TAPSE >24 mm (overall P<0.001). TAPSE <17 mm was associated with increased mortality after adjustment for established prognostic factors (adjusted hazard ratio [HR], 1.55 [95% CI, 1.21-1.97]) and after further adjustment for aortic valve replacement (AVR; adjusted HR, 1.47 [95% CI, 1.15-1.87]). The excess mortality risk associated with TAPSE <17 mm was noticed in both patients managed initially conservatively (adjusted HR, 1.46 [95% CI, 1.20-1.76]) and patients who underwent early (within 3 months after diagnosis) AVR (adjusted HR, 1.61 [95% CI, 1.03-2.52]). In asymptomatic patients with severe AS and preserved ejection fraction, TAPSE <17 mm was independently predictive of mortality (adjusted HR, 2.14 [95% CI, 1.31-3.51]). Early AVR was associated with similar survival benefit in TAPSE <17 and ≥17 mm (adjusted HR, 0.23 [95% CI, 0.16-0.34] for TAPSE <17 mm, adjusted HR, 0.26 [95% CI, 0.19-0.35] for TAPSE ≥17 mm; P for interaction, 0.97). CONCLUSIONS: Right ventricular dysfunction is an important and independent predictor of mortality in AS. TAPSE <17 mm at the time of AS diagnosis is a marker of poor survival under conservative management and after AVR even in asymptomatic patients with severe AS. AVR was associated with a pronounced reduction in mortality independent of TAPSE suggesting that AVR should be discussed before right ventricular dysfunction occurs in severe AS.

The dangerous and contradictory prognostic significance of PVR<3WU when TAPSE<16mm in postcapillary pulmonary hypertension.

AIMS: In 2019, pulmonary vascular resistance (PVR) < 3WU was adopted to stratify patients at low risk in pulmonary hypertension due to left heart disease (PH-LHD) as well those with isolated PH-LHD. We sought to evaluate whether supervised machine learning with decision tree analysis, which provides more information than Cox Proportional analysis by forming a hierarchy of multiple covariates, confirms this risk stratification. METHODS AND RESULTS: Two hundred two consecutive patients (mean age: 69 ± 11 years, female: 42%) with mean pulmonary artery pressure ≥ 20 mmHg and wedge pressure > 15 mmHg were recruited. Transpulmonary pressure gradient ⩾̸ 12 mmHg, PVR ⩾̸ 3WU, diastolic pressure gradient ⩾̸ 7 mmHg, pulmonary arterial capacitance < 1.1 mL/mmHg, tricuspid annular plane systolic excursion (TAPSE) < 16 mm, peak systolic tissue Doppler velocity < 10 cm/s, right ventricular end-diastolic area ⩾̸ 25 cm2 were the seven categorical values entered into the model due to their prognostic significance in PH. We used the chi-squared automatic interaction detection method to predict mortality. Each node and branch were compared using survival analysis at 6-year follow-up. Mean pulmonary artery pressure, wedge pressure, cardiac index, and PVR were 40.3 ± 10.0 mmHg, 22.3 ± 7.1 mmHg, 2.9 ± 0.8 L/min/m2 , and 3.6 ± 2.1WU, respectively. Among the seven dichotomous, TAPSE was first selected following by PVR. Compared with patients with PVR < 3WU and TAPSE ⩾̸ 16 mm, patients with PVR ⩾̸ 3WU and TAPSE ⩾̸ 16 mm, or patients with PVR ⩾̸ 3WU and TAPSE<16 mm had significantly increased mortality, HR = 3.0, 95% CI = [1.4-6.4], P = 0.006 and HR = 3.3, 95% CI = [1.6-6.9], P = 0.002, respectively, while patients with PVR < 3WU and TAPSE < 16 mm exhibited the worst prognosis, HR = 7.2, 95% CI = [3.3-15.9], P = 0.0001. CONCLUSIONS: Used for solving regression and classification problems, decision tree analysis confirms that PVR and TAPSE have to be analysed together in PH-LHD and revealed the dangerous and contradictory prognostic significance of PVR < 3WU when TAPSE<16 mm.