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.

Interest of TAPSE/sPAP ratio for noninvasive pulmonary arterial hypertension risk assessment.

BACKGROUND: Although ventriculoarterial coupling is associated with better survival in pulmonary arterial hypertension (PAH), existing PAH risk assessment method has not considered echocardiographic criteria of right ventricular to pulmonary artery coupling. We aimed to test the prognostic value of the echocardiographic tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio for noninvasive PAH risk assessment. METHODS: We retrospectively studied a cohort of 659 incident PAH patients from 4 independent French PH centers (training cohort: n = 306, validation cohort n = 353) who underwent follow-up TAPSE/sPAP measurement in addition to previously validated noninvasive risk stratification variables. The primary composite outcome was 3-year all-cause mortality or lung transplantation from re-evaluation. RESULTS: Mean age was 55 ± 17 years-old with a majority of female (66%). The three main PAH causes were connective tissue disease (26%), idiopathic (24%) and porto-pulmonary (19%). The primary composite outcome occurred in 71 (23%) patients. Multivariable Cox regression analysis retained 3 noninvasive low-risk criteria as associated with the primary composite outcome: NYHA I-II (p = 0.001), NTproBNP <300 ng/L or BNP <50 ng/L (p = 0.004), and TAPSE/sPAP >0.33 mm/mmHg (p = 0.004). The more the low-risk criteria achieved at follow-up, the better the event-free survival both in the training and validation cohort (log-rank p < 0.001). In the training cohort, the c-index for these 3 criteria, for COMPERA 2.0 and for the noninvasive French Pulmonary Hypertension Network method were 0.75, 95%CI(0.70-0.82), 0.72 95%CI(0.66-0.75), 0.71 95%CI(0.62-0.73), respectively. CONCLUSION: The 3 following dichotomized low-risk criteria: TAPSE/sPAP >0.33 mm/mmHg, NYHA I-II and NTproBNP <300 ng/L or BNP <50 ng/L allow to identify low-risk PAH patients at follow-up.

Left atrial unloading with an 8 mm septal cutting balloon to treat postcapillary pulmonary hypertension: a case report.

We report the case of a 58-year-old female with severe postcapillary pulmonary hypertension (averaged mean pulmonary arterial pressure was 49 mmHg, pulmonary arterial wedge pressure 29 mmHg, and right atrial pressure 8 mmHg) due to heart failure with preserved ejection fraction. A left-to-right atrial shunt was created using an 8 mm cutting balloon, under transesophageal echocardiography guidance. Both pulmonary arterial and wedge pressure dramatically decreased after the procedure. Symptoms immediately improved and benefits were sustained at 6 months of follow-up. This case suggests that iatrogenic septal defect using a cutting balloon could be an option to treat symptomatic postcapillary pulmonary hypertension.

Are routine cryoballoon procedural characteristics predictive of atrial arrhythmia recurrence in the long term?

BACKGROUND: Cryoballoon ablation is an effective procedure to treat atrial fibrillation (AF). However, AF recurrence rate at 1-year follow-up is approximately 20% despite improvements in ablation technique. AIM: To find factors predictive of AF recurrence following a first pulmonary vein isolation procedure using a second-generation cryoballoon (PVI-2CB). METHODS: This was an observational, retrospective, single-centre study. From June 2012 to April 2017, all patients who had a PVI-2CB procedure and a scheduled follow-up at Rouen University Hospital were included. The primary endpoint was atrial arrhythmia (AA) recurrence (e.g. AF, flutter or tachycardia), considering a blanking period of 2 months following the procedure. Secondary endpoints were procedural variables for each pulmonary vein (successful isolation, time to disconnection, total cryoballoon application time, number of cryoballoon applications, level of occlusion during cryoballoon application leading to successful disconnection and lowest temperature reached during successful cryoballoon application), occurrence of redo procedures, use of antiarrhythmic drugs and adverse events. RESULTS: The initial population consisted of 239 patients; six were excluded for lack of procedural variable data, giving an analysed population of 233 patients. The AA recurrence rate was 36.9% (mean follow-up 25±14 months). Mean time to AA recurrence was 10±12 months. No procedural variable was found to be predictive of AA recurrence. Only major left atrial enlargement (defined as diameter>50mm or left atrial area>30cm2 or left atrial volume>50mL/m2) was predictive (odds ratio 2.70, 95% confidence interval 1.54-4.72; P=0.001). Forty-one patients had redo procedures (17.6% of analysed population); in this subgroup, 75.6% had at least one pulmonary vein reconnected, mainly the right inferior pulmonary vein. CONCLUSIONS: At long-term follow-up, up to one-third of patients had AA recurrence after PVI-2CB. Important atrial remodelling was the only factor predictive of AA recurrence, whereas no procedural variable was found to be predictive.

Prognostic importance of Kidney, Heart and Interstitial lung diseases (KHI triad) in PH: A machine learning study.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous, severe and progressive disease with an impact on quality of life and life-expectancy despite specific therapies. AIMS: (i) to compare prognosis significance of each PH subgroup in a cohort from a referral center, (ii) to identify phenotypically distinct high-risk PH patient using machine learning. METHODS: Patients with PH were included from 2002 to 2019 and routinely followed-up. We collected clinical, laboratory, imaging and hemodynamic variables. Four-year survival rate of each subgroups was then compared. Next, phenotypic domains were imputed with 5 eigenvectors for missing values and filtered if the Pearson correlation coefficient was>0.6. Thereafter, agglomerative hierarchical clustering was used for grouping phenotypic variables and patients: a heat map was generated and participants were separated using Penalized Model-Based Clustering. P<0.05 was considered significant. RESULTS: 328 patients were prospectively included (mean age 63±18 yo, 46% male). PH secondary to left heart disease (PH-LHD) and lung disease (PH-LD) had a significantly increased mortality compared to pulmonary arterial hypertension (PAH) patients: HR=2.43, 95%CI=(1.24-4.73) and 2.95, 95%CI=(1.43-6.07) respectively. 25 phenotypic domains were pinpointed and 3 phenogroups identified. Phenogroup 3 had a significantly increased mortality (log-rank P=0.046) compared to the others and was remarkable for predominant pulmonary disease in older male, accumulating cardiovascular risk factors, and simultaneous three major comorbidities: coronary artery disease, chronic kidney disease and interstitial lung disease. CONCLUSION: PH-LHD and PH-LD has 2-fold and 3-fold increase in mortality, respectively compared with PAH. PH patients with simultaneous kidney-cardiac-pulmonary comorbidities were identified as having high-risk of mortality. Specific targeted therapy in this phenogroup should be prospectively evaluated.

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.

Direct measurement of cardiac stiffness using echocardiographic shearwave imaging during open-chest surgery: A pilot study in human.

PURPOSE: Cardiac stiffness is a marker of diastolic function with a strong prognostic significance in many heart diseases that is not measurable in clinical practice. This study investigates whether elastometry, a surrogate for organ stiffness, is measurable in the heart using ShearWave Imaging. METHODS: In 33 anesthetized patients scheduled for cardiac surgery, ShearWave imaging was acquired epicardially using a dedicated ultrasound machine on the left ventricle parallel to the left anterior descending coronary artery in a loaded heart following the last cardiac beat. Cardiac elastometry was measured offline using the Young modulus with customized software. RESULTS: Overall, the ejection fraction was 61 ± 10%. E/A and E/e' ratios were 1.0 ± 0.5 and 10.5 ± 4.1, respectively. Cardiac elastometry averaged 15.3 ± 5.3 kPa with a median of 18 kPa. Patients with high elastometry >18 kPa were older (P = .04), had thicker (P = .02) but smaller LV (P = .004), had larger left atria (P = .05) and a higher BNP level (P = .04). We distinguished three different transmural elastometry patterns: higher epicardial, higher endocardial, or uniformly distributed elastometry. CONCLUSION: Elastometry measurement was feasible for the human heart. This surrogate for cardiac stiffness dichotomized patients with low and high elastometry, and provided three different phenotypes of transmural elastometry with link to diastolic function.

Epicardial fat thickness predicts atrial fibrillation recurrence after a first pulmonary vein isolation procedure using a second-generation cryoballoon.

BACKGROUND: Atrial fibrillation is the most common arrhythmia in adults. A relationship between epicardial adipose tissue and atrial fibrillation has recently been reported. AIM: To evaluate the impact of epicardial fat thickness on the outcome of patients who underwent a first pulmonary vein isolation procedure using a second-generation cryoballoon. METHODS: From February 2012 to February 2017, all patients who underwent a first pulmonary vein isolation procedure using a second-generation cryoballoon at Rouen University Hospital were included. Data were collected retrospectively. Epicardial fat thickness was assessed by cardiac magnetic resonance imaging. The primary endpoint was documented atrial fibrillation recurrence at 4 months. RESULTS: A first pulmonary vein isolation procedure using a second-generation cryoballoon was performed in 288 patients; among them, 231 patients (80.2%) underwent cardiac magnetic resonance imaging. Epicardial fat thickness could be measured accurately in 206 patients (71.5%). Recurrence of atrial fibrillation at 4 months occurred in 32/206 patients (15.5%). In the multivariable analysis, factors predictive of atrial fibrillation recurrence at 4 months were: epicardial fat thickness (hazard ratio 1.96, 95% confidence interval 1.20-3.18; P=0.007), the presence of high left atrium enlargement (hazard ratio 4.63, 95% confidence interval 1.17-18.38; P=0.03) and atrial fibrillation recurrence before hospital discharge (hazard ratio 7.55, 95% confidence interval 2.50-22.81; P<0.001). CONCLUSION: Epicardial fat thickness is a predictive factor for atrial fibrillation recurrence after a first pulmonary vein isolation procedure using a second-generation cryoballoon.

Pacemaker memory in post-TAVI patients: Who should benefit from permanent pacemaker implantation?

BACKGROUND: One of the most frequent complications of transcatheter aortic valve implantation (TAVI) is the occurrence of atrioventricular (AV) conduction disorders secondary to AV node or His bundle injury leading to permanent pacemaker implantation (PPI). The objective was to quantify the rate of ventricular pacing (VP), according to post-TAVI indication for PPI using recorded pacemaker memory. METHODS: From October 2009 to January 2017' all patients who had PPI following TAVI performed at Rouen University Hospital were included. Indications for PPI were: ≥ 1 episode of complete atrioventricular block (CAVB) or 2:1 atrioventricular block, and new-onset persistent left bundle branch block (NOP-LBBB) with either prolonged PR interval (> 200 ms) or HV interval (>70 ms). The primary endpoint was VP percentage at the first pacemaker interrogation (a VP percentage ≥ 1% was considered as significant). RESULTS: Out of 936 TAVI patients (Sapien-3' n = 379 [Edwards Lifesciences, Irvine, CA, USA]; Sapien-XT' n = 513; CoreValve' n = 44, Medtronic, Minneapolis, MN, USA), 87 (9.3%) had PPI. Eighty of these 87 patients were followed-up and analyzed. At the first pacemaker interrogation, a significant VP percentage was observed in 60/80 followed-up patients (75%), in 46/51 patients (90.2%) implanted for CAVB, and 12/23 patients (52.2%) implanted for NOP-LBBB associated with either prolonged PR or HV interval. No clinical predictive factor of significant VP percentage was found. CONCLUSION: In the post-TAVI period, our data support PPI in patients with CAVB even if paroxysmal. Our data also suggest PPI may be considered in patients with NOP-LBBB associated with either prolonged PR or HV interval.