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

BackgroundTraditional 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).AimsTo investigate a new classification system for severe AS using phenomapping.MethodsConsecutive 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.ResultsIn 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).ConclusionsArtificial 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.     

Outcomes of surgical bioprosthetic aortic valve replacement for aortic insufficiency

BackgroundResults and durability of aortic valve replacement in aortic stenosis are well known, but no study has focused on the results of aortic valve replacement in aortic insufficiency.AimThe aim of this retrospective study was to describe our mid-term outcomes after aortic valve replacement for aortic insufficiency.MethodsAll consecutive adult patients who underwent bioprosthetic aortic valve replacement for aortic insufficiency at two European centres (in France and Germany) between May 2005 and December 2020 were analysed.ResultsDuring the study period, 289 patients were included. Mean age was 56.9 ± 12.5 years. Overall operative mortality was 1.5%, and the 10-year survival estimate rate was 75.0%, which was significantly lower than in the age- and sex-matched general population, with a standardized mortality ratio of 2.88 (95% confidence interval 1.96–4.08; P < 0001). Freedom from aortic valve-related death was 87.6%, and from aortic valve-related reoperation was 87.4%. No patient aged > 60 years was reoperated on during follow-up. Freedom from severe structural valve deterioration at 10 years was 73.3%, and freedom from moderate structural valve deterioration at 10 years was 50.3%. Freedom from major adverse valve-related events at 10 years was 69.7%.ConclusionsAlthough bioprosthetic aortic valve replacement for aortic insufficiency shows good early results, 10-year mortality and major adverse valve-related event rates in young patients may be a concern, with a reduction in life expectancy compared with the general population.     

Transcatheter aortic valve implantation using the SAPIEN 3 valve to treat aortic regurgitation: The French multicentre S3AR study

BackgroundTranscatheter aortic valve implantation now has a major role in the treatment of patients with severe aortic stenosis. However, evidence is scarce on its feasibility and safety to treat patients with pure aortic regurgitation.AimsWe sought to evaluate the results of transcatheter aortic valve implantation using the balloon-expandable SAPIEN 3 transcatheter heart valve (Edwards Lifesciences, Irvine, CA, USA) in patients with pure aortic regurgitation on native non-calcified valves.MethodsWe conducted a retrospective and prospective French multicentre observational study. We included all patients with symptomatic severe pure aortic regurgitation on native non-calcified valves, contraindicated to or at high risk for surgical valve replacement, who underwent transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve.ResultsA total of 37 patients (male sex, 73%) with a median age of 81 years (interquartile range 69–85 years) were screened using transthoracic echocardiography and computed tomography and were included at eight French centres. At baseline, 83.8% of patients (n = 31) had dyspnoea New York Heart Association class ≥ III. The device success rate was 94.6% (n = 35). At 30 days, the all-cause mortality rate was 8.1% (n = 3) and valve migration occurred in 10.8% of cases (n = 4). Dyspnoea New York Heart Association class ≤ II was seen in 86.5% of patients (n = 32), and all survivors had aortic regurgitation grade ≤ 1. At 1-year follow-up, all-cause mortality was 16.2% (n = 6), 89.7% (n = 26/29) of survivors were in New York Heart Association class ≤ II and all had aortic regurgitation grade ≤ 2.ConclusionTranscatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve seems promising to treat selected high-risk patients with pure aortic regurgitation on non-calcified native valves, contraindicated to surgical aortic valve replacement.     

Durability of transcatheter aortic valve implantation: A translational review

Central illustration. Transcatheter aortic valve implantation: deterioration biomarkers, pathophysiology and data durability. BVT: bioprosthetic valve thrombosis; ¹⁸FDG: ¹⁸F-fluorodeoxyglucose; HOMA index: homeostatic model assessment of insulin resistance; Lp(a): lipoprotein(a); MDCT: multidetector computed tomography; PCSK9: proprotein convertase subtilisin/kexin type 9; PET-CT: positron emission tomography; computed tomography; SVD: structural valve deterioration; TAVI: transcatheter aortic valve implantation; TTE: transthoracic echocardiography; y: years.

     

The difficult balance between thrombosis and bleeding after transcatheter aortic valve replacement: A translational review

The difficult balance between thrombosis and bleeding after transcatheter aortic valve replacement. TAVR: transcatheter aortic valve replacement.

     

Early pacemaker insertion after aortic valve replacement with an Edwards Intuity sutureless valve

BackgroundPostoperative conduction disorders are serious adverse events in patients undergoing aortic valve replacement, and may prolong the duration of hospitalization and require pacemaker insertion.AimOur aim was to evaluate the rate of pacemaker insertion after implantation of an Edwards Intuity sutureless aortic valve (Edwards Lifesciences, Irvine, CA, USA) compared with a standard surgical bioprosthesis.MethodsThis retrospective single-centre study included patients who underwent aortic valve replacement with an Intuity sutureless aortic valve or a standard bioprosthetic valve between 4 June 2014 and 27 June 2016. The main outcome criterion was the rate of postoperative pacemaker insertion. Secondary outcome criteria included the rate of new conduction disorders, the rate of atrial arrhythmia or paroxysmal conduction disorders, mortality and duration of hospital stay.ResultsNinety-three patients received an Intuity sutureless aortic valve (median age 76 years, interquartile range 71–80 years), and 176 were implanted with a standard biological aortic valve (median age 73 years, interquartile range 68–79 years; P = 0.007). The rate of postoperative pacemaker insertion, after adjustment, was 22.44% in the Intuity group and 5.66% in the standard aortic valve group (P = 0.030). The main indications for postoperative pacemaker insertion were complete atrioventricular block and left bundle branch block with prolongation of the H-V interval. The rate of new postoperative left bundle branch block conduction disorders was significantly higher in patients implanted with an Intuity valve (odds ratio 5.28, 95% confidence interval 1.59 to 23.05; P = 0.012).ConclusionHigher rates of pacemaker insertion and new conduction disorders were observed in patients implanted with an Intuity sutureless bioprosthesis compared with those who received a standard surgical aortic valve.     

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation

BackgroundThe optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) − the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume − is a volumetric measure of LV myocardial shortening independent of size or geometry.AimTo assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice.MethodsClinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied.ResultsDuring an estimated median follow-up of 49 (22–77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21 ± 5% for patients with MCF <30% and 40 ± 6% for those with ≥30% (P < 0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51−3.58; P < 0.001). Moreover, MCF < 30% improved the predictive performance of models, with better global fit, reclassification and discrimination.ConclusionsMCF < 30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.     

Watchful waiting care or early intervention in asymptomatic severe aortic stenosis: Where we are

Central illustration. Patient-centred benefit versus risk analysis of early aortic valve replacement (AVR) for asymptomatic severe aortic stenosis. AKI: acute kidney injury; PM: pacemaker; PPM: patient prosthesis mismatch.

     

Impact of left atrial and diastolic ventricular dysfunction on mortality in patients with aortic stenosis

BackgroundDiastolic dysfunction (DD) is common in severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF ≥ 50%).AimTo determine the impact of American Society of Echocardiography/European Association of Cardiovascular Imaging-recommended DD grading and left atrial strain on mortality in a cohort of patients with severe AS and preserved LVEF.MethodsWe studied patients with severe AS (aortic valve area indexed < 0.6 cm²/m² and/or aortic valve area < 1 cm²), LVEF ≥ 50% and no or mild AS-related symptoms. The endpoint was all-cause mortality.ResultsA total of 387 patients (median age 76 years; 53% women) were studied. During a median follow-up of 57 (interquartile range 37; 83) months, 158 patients died. After adjustment for prognostic factors, patients with grade II or III DD had an increased mortality risk versus patients with grade I DD (adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.11–2.38; P = 0.013; aHR 4.73, 95% CI 2.49–8.99; P < 0.001; respectively). Adding peak atrial longitudinal strain (PALS) ≤ 14% to a multivariable model including DD grade improved predictive performance, with better global model fit, reclassification and discrimination. Patients with grade III DD or grade II DD + PALS ≤ 14% displayed an increased mortality risk versus patients with grade I DD + PALS > 14% (aHR 4.17, 95% CI 2.46–7.06; P < 0.0001). Those with grade I DD + PALS ≤ 14% or grade II DD + PALS > 14% were at intermediate risk (aHR 1.63, 95% CI 1.07–2.49; P = 0.024).ConclusionsOur results demonstrate the strong relationship between DD and mortality in patients with severe AS and preserved LVEF. Patients with grade III or grade II DD and impaired PALS are at very high risk. These data demonstrate the importance of a comprehensive assessment of diastolic function in patients with severe AS.