bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitral annular calcification in patients with severe aortic stenosis underwent transcatheter aortic valve implantation: prevalence and association with stenosis severity
Authors: Wicheantawatchai A , Theerasuwipakorn N , Chattranukulchai P , Tumkosit M , Srimahachota S , Buddhari W , Boonyaratavej S
Published: November 2023

Background

Patients with calcific aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) usually have calcification in other cardiac structures, especially mitral annulus. Severity of mitral annular calcification (MAC) and degree of mitral stenosis (MS) may be associated with hemodynamic effects and outcomes.

Purpose

We sought to investigate the prevalence of MAC in patients with severe calcific AS using mitral annular calcium score with Agatston method from cardiac computerized tomography (CT). We also aim to assess the severity grading of MAC and its association with the severity of MS evaluated by transthoracic echocardiography.

Methods

We conducted a retrospective cohort analysis of the TAVI registry at King Chulalongkorn Memorial Hospital between May 2013 and December 2021. Clinical information was extracted from medical records. The pre-TAVI echocardiography and cardiac CT were reviewed, as well as the mitral annular calcium score. The severity of MAC (no, mild, moderate, severe) was classified using cardiac CT per the modified Cleveland clinic classification system. The MS grading was based on the 2009 American society of echocardiography guidelines. MAC prevalence was studied. Analysis of the association between MAC and MS was conducted.

Results

Our cohort included a total of 188 patients (mean age of 81±8 years). 134 patients (71.3%) demonstrated evidence of MAC. 47 patients (25%) had severe MAC evaluated by cardiac CT. Among patients with severe MAC, mean age was 83±8 years, 29 patients (63%) were female, 14 patients (30%) had diabetes, and 11 (23%) of them were associated with moderate or severe MS. Patients with MAC were significantly associated with hemodynamically significant MS (moderate or severe) when compared with patients without MAC (p <0.001).

Conclusions

One-fourth of patients with severe calcific AS underwent TAVI had severe MAC. The hemodynamically significant MS was more prevalent as the severity of MAC increased. The association between MAC and long-term adverse clinical outcomes needs to be further investigated.Figure 1Figure 2
Safety and incremental prognostic value of stress CMR in patients with known chronic kidney disease
Authors: Pezel T , Unterseeh T , Hovasse T , Sanguineti F , Garot P , Champagne S , Toupin S , Ah-Sing T , Faradji A , Nicol M , Hamzi L , Dillinger J G , Henry P , Bousson V , Garot J
Published: November 2023

Background

Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established.

We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD.

Methods

Between 2008 and 2021, we conducted a bi-center longitudinal study with all consecutive symptomatic patients with known CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR <30 ml/min/1.73 m² (n=62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regressions were used to determine the prognostic value of stress CMR parameters.

Results

Of 825 patients with known CKD (71.4±8.8 years, 70% men), 769 (93%) completed the CMR protocol, and among those 702 (91%) completed the follow-up (median follow-up 6.4 (4.0–8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or nephrogenic systemic fibrosis case. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI]: 7.50–20.8; p<0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI: 7.72 to 30.9; and HR:4.67 [95%CI: 2.83-7.68]; respectively, both p<0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI=0.477; IDI=0.049).

Conclusions

In patients with known CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.Cumulative rates of MACECompeting risk analysis
Myocardial injury after transcatheter aortic valve replacement according to VARC-3 criteria
Authors: Real C , Avvedimento M , Nuche J , Franzone A , Farjat-Pasos J , Trinh K H , Delarochelliere R , Paradis J M , Poulin A , Dumont E , Kalavrouziotis D , Mohammadi S , Mengi S , Esposito G , Rodes-Cabau J
Published: November 2023

Background

Periprocedural myocardial injury (PPMI) is frequent in patients undergoing transcatheter aortic valve replacement (TAVR). PPMI after TAVR as defined by Valve Academic Research Consortium-2 (VARC-2) criteria occurs in >50% of the patients and had inconsistent results regarding prognostic significance. However, recent VARC-3 definition is more specific, having increased the troponin threshold from 15-times to 70-times the upper reference limit (URL) to define PPMI. This recent definition of PPMI following TAVR lacks the clinical validation.

Objective

To determine the incidence, predictors and clinical impact of PPMI following TAVR as defined by recent VARC-3 criteria.

Methods

We included 1,394 consecutive patients who underwent TAVR with a new generation transcatheter heart valve in two tertiary centers in Canada and Italy, from 2015 to 2022. Patients undergoing a trans-aortic or a trans-apical approach were excluded. High-sensitivity troponin levels were assessed at baseline and within 24 hours after the procedure. PPMI was defined according to VARC-3 criteria as an increase ≥70 times in troponin levels (vs. ≥15 times according to VARC-2 definition). Baseline, procedural and follow-up data were prospectively collected in a dedicated database.

Results

PPMI was diagnosed in 193 patients (14%) according to the VARC-3 criteria. Female sex and peripheral artery disease were found independent predictors of PPMI in the multivariable analysis (p<0.01 for both). PPMI was associated with a higher risk of mortality at 30-day (HR: 2.76, 95% CI: 1.54-4.95, p=0.001 for all-cause mortality; HR: 9.54, 95%CI: 2.69 to 33.80, p<0.001 for cardiovascular mortality) and 1-year-follow-up (HR: 1.52, 95%CI: 1.02-2.27, p=0.037 for all-cause mortality; HR: 3.04, 95%CI: 1.68-5.50, p<0.001 for cardiovascular mortality). PPMI according to VARC-2 criteria had no impact on mortality (Figure 1). According to restricted cubic splines analysis, the minimal threshold at which high-sensitivity troponin elevation is significantly associated with 1-year all-cause mortality is an 82-fold increase above URL (Figure 2).

Conclusions

About 1 out of 10 patients undergoing TAVR in the contemporary era had PPMI as defined by recent VARC-3 criteria and it had a negative impact on early and late survival. Baseline factors as female gender and peripheral disease increased the risk. Further studies on the prevention of PPMI post-TAVR and implementing measures to improve outcomes in PPMI patients are warranted.Kaplan-Meier estimates of mortalityRestricted cubic splines analysis
Biological versus mechanical SAVR patient's age threshold: PARTNER II study influenced real world practice in a large French cohort
Authors: Chabry Y , Baufreton C , Bouchot O , Camilleri L , Collart F , Demaria R , Frieh J P , Kindo M , Labrousse L , Leprince P , Marcheix B , Roussel J C , Verhoye J P , Vincentelli A , Caus T
Published: November 2023

Background/introduction

Published in 2016, PARTNER II study has shown TAVR to be non inferior to SAVR in intermediate risk patients. This result might influence the type of SAVR chosen in patients for whom a redo surgery would surely be a procedure at intermediate risk, based on estimated age at time for redo and taking into account ViV TAVI as a game changer for treating a degenerated biological prosthesis.

Purpose

To assess the choice of type of valve according to age in aortic position through the French National Database EPICARD before and after the publication of Parter II study.

Methods

We extracted from EPICARD all valvular patients operated on from 2007 to 2022 in 24 participating public or private centers chosen to represent a balanced representation of center sizes and geographical discrepancies. Patients with associated pathology of the aorta (aneurysm or dissection) and requiring a vascular aortic prosthesis were excluded.

Results

From the obtained representative study population of 101,070 valvular patients, we studied 72,375 SAVR (mean age 71.4 +/- 12.2). We observed a mechanical versus biological prosthesis ratio (MBPR) of 0.14 for the overall aortic SAVR population. Before 50 y-o, MBPR was >1.3 (p<0.001) while patients above 60 y-o received principally biological SAVR (p<0.0001). Concerning patients between 50-60 y-o patients, MBPR was 1.04 (p=0.03). Patients 50-60 y-o from the first and second quartile (before August 2015) received preferentially mechanical SAVR (p<0.001). We observed a shift towards more biological SAVR (p<0.001) for patients from the third and fourth quartile to reach a MBPR at 0.43 during the last years of the series. Incidentally, the choice of type of SAVR was influenced by associated procedures. Simultaneous mitral valve replacement were more common in case of mechanical SAVR (p<0.0001), while associated CABGs were more frequent in case of biological SAVR (p<0.0001).

Conclusion

In a large contemporary French patient population, real world practice showed that publication of the PARTNER II study was followed by a shift towards a lower threshold for biological SAVR as compared to ESC Guidelines.
Improvement of microcirculatory vessel density in the early post-operative period of heart valve surgery: an observational study
Authors: Tibirica E , Lorenzo A , Fernandes M V
Published: November 2023

Introduction

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with microcirculatory perfusion disturbances that persist after the surgery and that can cause multiple organ dysfunction. Little is known about the effects of heart surgery on the microcirculation of patients in the postoperative period of heart valve surgery.

Purpose

The purpose of the study is to identify the alterations that occur in the sublingual microcirculation of patients submitted to heart valve surgery using cardiopulmonary bypass. Such findings may guide future implementation of routine microcirculation assessment in the postoperative period of cardiac surgery.

Methods

This was a single-center cross-sectional observational study that included thirty patients aged 52 ± 14 years and enrolled during a period of four months, scheduled for heart valve surgery with CPB at a quaternary public hospital. Sublingual microcirculatory density and perfusion were assessed using a handheld camera based on incident dark-field (IDF) imaging. Each recruited patient was evaluated in two stages: 1) during hospitalization, in the preoperative period of cardiac surgery to be performed within the next 48 hours; 2) in the early postoperative phase of cardiac surgery, within the first four hours of the patient's arrival at the intensive care unit. At least three videos of 5 seconds each were obtained in both stages. Images were analyzed using automated software as well as visual analysis. For analysis purposes, we considered vessels as capillaries if diameter ranges between 6.04-15.9 µm and non-capillaries if diameter ranges between 16-50 µm.

Results

We observed a statistically significant increase in the total number of vessels (TVN) after surgery (1076 ± 156) compared to values obtained before surgery (943 ± 117, P=0.0004). In addition, the total number of capillaries vessels (TNCV) was also greater after surgery (998 ± 132) compared to the preoperative period (877 ± 106; P=0.0001), the same being observed in the total length of capillaries vessels (TLCV) after surgery (28.7 ± 3.3 mm) compared to before surgery (25.8 ± 3.0 mm; P=0.0005) and capillary vessel density (CVD) (16.4 ± 1.9 and 14.8 ± 1.7 mm/mm2) after and before surgery, respectively (P=0.0005). With regard to non-capillary vessels, no difference was observed in total number of non-capillary vessels (TNNCV) after [68 (49-104)] and before surgery [69 (49-78)] (P=0.21), as well as in total length of non-capillary vessels (TLNCV) after [1.6 (1.2-2.4)] mm and before [1.5 (1.1-1.8.)] mm (P=0.25) surgery. Finally, non-capillary vessel density (NCVD) was also similar after [0.89 (0.67-1.36)] mm/mm2 and before surgery [0.83 (0.66-1.06)] mm/mm2 (P=0.34).

Conclusion

In patients undergoing heart valve surgery, there was a significant increase in postoperative microvessel number, mainly due to the increase in the density of capillaries vessels.
Left atrial pump strain predicts long-term mortality in patients undergoing transcatheter aortic valve implantation
Authors: Winkler N E , Anwer S , Rumpf P M , Tsiourantani G , Donati T G , Michel J , Kasel A M , Tanner F C
Published: November 2023

Introduction

Speckle-tracking echocardiography is an increasingly important tool for assessing aortic stenosis (AS). Left atrial reservoir (LARS) and pump strain (LAPS) were studied for their association with long-term mortality in AS patients undergoing transcatheter aortic valve implantation (TAVI).

Purpose

To investigate left atrial function assessed by LARS and LAPS and its association with all-cause mortality during long-term follow-up after TAVI.

Methods

From our prospective AS cohort study, 198 patients with severe AS were identified who underwent TAVI and had a comprehensive preinterventional echocardiographic examination allowing full target analysis. Five-year all-cause mortality was defined as the endpoint.

Results

Left atrial volume index (LAVI) was increased (mean (SD): 46.9 ml/m2 (±16.5)) and left atrial deformation impaired (LARS (21.7% (±6.9); LAPS (-9.5% (±4.5)), while left ventricular ejection fraction (LVEF) (56.7% (±11.5)) was preserved in the study population. Over a follow-up time of five years, 49 patients (24.7%) died. LARS and LAPS were more impaired in non-survivors (20.0% (±6.5) and -8.1% (±4.0), respectively; Figure) than in survivors (22.3% (±6.9); P=0.042 and -9.9% (±4.5), respectively; P=0.014; Figure), while LAVI did not differ (P=0.248). Univariable Cox regression models demonstrated that LAPS was associated with mortality (P=0.014), while LARS was not (P=0.066) (Table A). In bivariable and multivariable models, the association of LAPS with mortality was independent of LVEF and LAVI, and inclusion of LAPS improved the fitness (≤2) of these models (Table B). Furthermore, the improvement in ≤2 was significant for all models (ANOVA P=0.012, P=0.013, and P=0.015, respectively).

Conclusion

LAPS was associated with long-term mortality after TAVI, while LARS and LAVI were not. The association of LAPS was independent of LVEF and LAVI and showed potential incremental value for assessment of outcome association. Hence, LAPS may be useful for predicting long-term outcome after TAVI.
An artificial intelligence algorithm for detection of severe aortic stenosis: a clinical cohort study
Authors: Strom J , Playford D , Stewart S , Strange G
Published: November 2023

Background/Introduction

Despite guideline based indications, nearly 1/3 of patients with symptomatic severe aortic stenosis (AS) are not referred for intervention. Artificial Intelligence Decision-Support Algorithms (AI-DSAs) may be helpful to identify individuals with AS at risk for premature mortality but few have been validated for use.

Purpose

To evaluate an AI-DSA based on echocardiogram report data to augment the detection of severe AS within a well-resourced health care setting.

Methods

Blinded to clinical information, an AI-DSA trained to identify an aortic valve area (AVA) <1cm2 using minimal input data was applied to routine transthoracic echocardiogram reports from 31,141 US Medicare beneficiaries (≥ 65 years old) at a large US academic medical center (2003-2017) (Figure).

Results

Performance of the AI-DSA to detect an AVA <1cm2 was excellent (sensitivity 95.2%, specificity 94.8%, negative predictive value 99.8%). The AI-DSA identified 1,549 (5.0%) individuals with guideline-defined severe AS plus 463 (1.5%), 979 (3.1%), and 28,150 (90.4%) individuals with a severe AS (not meeting guidelines), moderate AS, and low-probability AS phenotypes. Five-year mortality was 73.9%, 77.1%, 71.2%, and 43.6% respectively (adjusted HR compared to low-probability AS, HR 1.40, 95% CI 1.31-1.50 [guideline severe], HR 1.31, 1.17-1.46 [non-guideline severe], HR 1.21, 1.12-1.23 [moderate], p < 0.001 for all). Overall, rates of aortic valve replacement (AVR) remained low, even in those with an AVA <1cm2 (21.9%), despite it being associated with improved survival. Findings remained consistent among outpatients, those investigated in the past decade and those with left ventricular systolic dysfunction.

Conclusions

Without relying on left ventricular outflow tract measurements, an AI-DSA used echocardiographic reports to reliably identify those with severe AS. These results suggest possible utility for this AI-DSA to enhance detection of individuals with the phenotype of severe AS, at risk for adverse outcomes.Figure:Graphical Abstract
Syncope at rest in severe aortic stenosis may persist after intervention and is associated with poor outcomes
Authors: Garcia M , Ybarra Falcon C , Martin Paniagua S , Lozano Ibanez A , Alanon Hernandez A , Cabezon G , Ramos N , Amat Santos I J , Sevilla T , Revilla A , Carrasco M , Lopez J , Rollan M J , Vilacosta I , San Roman J A
Published: November 2023

Background

syncope in patients with severe aortic stenosis (AS) is an indication for intervention (AVR). The evolution of syncope after AVR and its association to outcomes remain unknown.

Purpose

we aimed to describe the evolution of syncope in patients with symptomatic severe AS undergoing AVR, whether its trigger has an impact on outcomes, and its prognostic significance.

Methods

data from patients with severe AS who underwent AVR were collected. Total death and cardiovascular death were considered events.

Results

320 consecutive patients with severe AS, without other valve disease and/or coronary artery disease, who survived AVR were evaluated. The work focuses on the 53 patients who reported syncope (29 on effort, 21 at rest, 3 unknown). Clinical and echocardiographic variables were similar in patients with syncope and without syncope. After a median follow-up of 69 months (IQR: 55-88), no patient with syncope on effort before intervention had syncope after intervention. By contrast, 8 of the 21 patients with syncope at rest presented syncope during the follow-up (38%; p<0.001); all 8 syncopes appeared at rest: 3 needed a pacemaker, 3 were diagnosed as neuromediated or of hypotensive origin and 2 were arrhythmic. Only syncope after intervention was associated with cardiovascular death (HR 5.74; 95%CI [2.17-15.17]; p<0,001]).

Conclusions

syncope on effort in patients with severe AS disappears after AVR but syncope at rest remains in a high proportion of patients. Syncope after AVR is associated with poor prognosis. Our results suggest that, in patients with severe AS and syncope at rest, other causes of syncope must be ruled out before proceeding to AVR.Adjusted Kaplan Meier survival curves
Randomized study for the optimal treatment of symptomatic patients with low gradient severe aortic valve stenosis and preserved left ventricular ejection fraction (ROTAS trial)
Authors: Galli E , Coisne A , Le Ven F , Sportouch C , Lairez O , Bernard A , Oger E , Le Pabic E , Donal E
Published: November 2023

Background

the best management of symptomatic patients with low gradient (LG) severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) has not been established in randomized controlled trials.

The ROTAS trial aimed to assess the superiority of aortic valve replacement (AVR) versus optimized medical therapy (OMT) in symptomatic patients with LG severe AS and preserved LVEF.

Methods and Results

Fifty-two patients (age 79±7 years; males 46%, mean aortic gradient: 31±5 mmHg; aortic surface: 0.8±0.1 cm², LVEF 61±8%) were randomized 1:1 to AVR or OMT.

The stroke volume index (SVi, cut-off 35 ml/m²) was considered for randomisation so that the same percentage of patients with reduced SVi was present in the two groups. The follow-up lasted 14±7 months.

An early interruption of the study occurred in 2021 because of the extremely low inclusion rate during the COVID-2019 pandemic and the large tendency to already implant TAVI in patients with severe LG AS with preserved LVEF.

In all patients, a multimodality approach, including dobutamine stress echocardiography and/or aortic calcium score was applied to confirm AS severity.

The primary end-point (a composite of overall death and heart failure hospitalisation) occurred in 13 (25%) patients.

Patients receiving OMT did not experience worse survival compared to patients receiving AVR (HR=1.57, 95% CI:0.51-4.83, p=0.4275). Kaplan-Meier curves showed similar event-free survival (log-rank p=0.4236) among the 2 groups (Figure 1).

Conclusions

In the randomized ROTAS trial, AVR was not associated with a better prognosis in symptomatic patients with LG severe AS and preserved LVEF.Figure 1
Is there an outcome penalty linked to guideline-based class-I indications for valvular surgery? long-term analysis of patients with high gradient severe aortic stenosis
Authors: De Azevedo D , Boute M , Hanet V , Tribouilloy C , Marechaux S , Altes A , Bohbot Y , Rusimaru D , Thellier N , Pouleur A C , Pasquet A , Gerber B L , Vanoverschelde J L , Vancraeynest D
Published: November 2023

Background

Current ACC/AHA guidelines recommend aortic valve replacement (AVR) as class-I triggers in patients with high-gradient severe aortic stenosis (HGSAS) in presence of symptoms and/or left ventricular dysfunction (LVEF<50%). Whether waiting for these triggers could be associated with long-term outcome penalty after AVR remains poorly studied.

Objective

To examine the impact of guideline-based class-I triggers on long-term post-operative survival in patients with HGSAS.

Methods

We used an international registry including consecutive patients operated on for HGSAS between 2000 and 2017. 2030 Patients were included in the analysis and retrospectively classified according to the guideline-based indication: no Class-I trigger (no symptoms and LVEF>50%, n=853), Symptoms with LVEF>50% (n=965), or LVEF<50% (regardless of symptoms, n=212). Survival was compared in a multivariate Cox-model and after inverse probability weighting-[IPW] for relevant variables. Finally, we explored the most sensitive left ventricular ejection fraction threshold for predicting mortality risk.

Results

10-years survival was better among patients without any class-I trigger than with symptoms or LVEF<50% (67±3 vs 56±3 vs 53±7% respectively, p<0.001). After adjustment for covariates, risk of death increased significantly when patients were operated on with symptoms (HR: 1.48, [95%CI: 1.17-1.86]) or with LVEF<50% (HR: 1.47, [95%CI: 1.05-2.06]) compared to patients with no class-I trigger. Furthermore, LVEF<55% emerged as a more sensitive threshold for the prediction of post-operative mortality in comparison with LVEF<50% (see table), allowing a better separation of survival curves and indicating that patients with LVEF 50-55% are already at risk with long term consequences even after AVR. Interestingly, among asymptomatic patients with LVEF >55%, performing AVR restituted a normal life expectancy (comparable to the Belgian population of same age, see figure). Finally, the outcome penalty after AVR when waiting for symptoms or LVEF<55% was confirmed in IPW analysis (HR: 1.43, [95%CI: 1.13-1.82] and HR: 1.63, [95%CI: 1.19-2.23], respectively).

Conclusions

Guideline-based Class-I triggers for AVR in patients with HGSAS is associated with profound outcome consequences on long-term postoperative mortality. Our data argue that patients with HGSAS should be operated on before the onset of these triggers. Finally, our data suggest that a threshold of LVEF<55% is a stronger predictor of outcome than LVEF<50%.
Use of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis
Authors: Bahlmann E , Gerdts E , Einersen E , Midtbo H , Pedersen E , Rossebo A , Willems S , Cramariuc D
Published: November 2023

Objective

Assessment of flow is important in grading of aortic valve stenosis (AS). Sex-specific thresholds for low flow were recently proposed (stroke volume index <40 ml/m² in men and <32 ml/m² in women, respectively). We tested the prognostic association of these cut-offs in AS patients with concordantly and discordantly graded AS based on pressure recovery adjusted aortic valve area.

Methods

Data from 1353 patients (38.6% women) with asymptomatic mild-moderate AS and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. Discordantly graded AS (DGASEL) was defined as combined pressure recovery adjusted aortic valve area (energy loss) <1.0 cm² and mean aortic gradient <40 mmHg and concordantly graded mild-moderate AS as combined EL ≥1.0 cm² and mean aortic gradient <40mmHg. Patients were further grouped into normal and low flow. Outcome was assessed using both Kaplan-Meier curves and Cox regression analyses with concordantly graded AS with normal flow as comparator.

Results

In the total study population, mild-moderate AS with normal flow was present in 915 patients, mild-moderate AS with low flow in 253 patients, DGASEL with normal flow in 57 patients and DGASEL with low flow in 126 patients.

During a median of 4.3 years follow-up, survival free of death and/or hospitalization for heart failure was significantly lower in patients with DGASEL irrespective of flow compared to those with mild-moderate AS with normal flow (both P<0.05, Figure). In Cox regression analysis, after adjustment for hypertension, age, sex, heart rate, randomized study treatment, aortic valve replacement and degree of aortic valve calcification, DGASEL with normal or low flow were both associated with increased risk of combined death and hospitalization for heart failure (P<0.05) (Table). However, no prognostic difference was found between groups with normal vs. low flow within groups of discordantly or concordantly graded AS.

Conclusions

Identification of low flow by the proposed sex-specific thresholds of stroke volume index <40 ml/m² in men and <32 ml/m² in women needs more validation before inclusion in clinical guidelines.

Figure. Kaplan-Meier plot of event-free survival from combined death and heart failure hospitalization in groups of patients with mild-moderate AS normal flow, mild-moderate AS low flow, DGASEL with normal flow and DGASEL with low flow.

Table. Association of combined death and hospitalization for heart failure in groups of concordantly and discordantly graded AS with normal and low flow. Multivariable Cox analysis.
Long term impact of measured and predicted prosthesis patient mismatch following transcatheter aortic valve replacement
Authors: Tomii D , Okuno T , Heg D , Nakase M , Lanz J , Praz F , Stortecky S , Reineke D , Windecker S , Pilgrim T
Published: November 2023

Objectives

To investigate the long-term clinical impact of prosthesis-patient mismatch (PPM) in patients undergoing transcatheter aortic valve implantation(TAVI).

Background

Both measured and predicted effective orifice area indexed to the body surface area (EOAi) have been suggested to define PPM in patients undergoing TAVI. The impact of PPM on clinical outcomes may accumulate with extended follow-up and vary according to the definition used.

Methods

Patients included in a prospective TAVI registry were stratified by the presence of moderate (0.65-0.85 cm2/m2 or 0.55-0.70 cm2/m2 if obese) or severe (≤0.65 cm2/m2 or ≤0.55 cm2/m2 if obese) PPM according to echocardiographically measured EOAi (measured PPM) prior to discharge, predicted EOAi based on published EOA reference values for each valve model and size (predicted PPMTHV), or predicted EOAi based on EOA reference derived from computed tomography measurements of aortic annulus dimension (predicted PPMCT).

Results

In an analysis of 2,463 patients, the incidence of measured PPM (moderate: 27.0%; severe: 8.7%) was higher than the incidence of predicted PPMTHV (moderate: 11.3%; severe: 1.2%) or predicted PPMCT (moderate: 12.0%; severe: 0.1%). During a median time to death of 843 days, mortality rates at 10 years were comparable in patients with versus without measured PPM or predicted PPMCT. In contrast, patients with moderate predicted PPMTHV had a lower risk of 10-year all-cause mortality compared with those without PPM (HR: 0.69; 95% CI: 0.52-0.90).

Conclusions

The use of predicted as compared to measured EOAi results in a lower estimate of PPM severity in TAVI ptients. We observed no increased risk of death in patients with PPM throughout 10-year of follow-up.Incidence of PPM after TAVIImpact of Measured an Predicted PPM
Perioperative risk reassessment of non-cardiac surgery during last 10 years in patients with asymptomatic significant aortic stenosis
Authors: Park S , Bak M J , Lee S H , Park J C , Kim D , Kim J H , Kim E K , Chang S A , Lee S C , Park S W
Published: November 2023

Background

Aortic valve stenosis (AS) is a common geriatric disease and the number of patients with significant AS in need of non-cardiac surgery is expected to increase. Significant AS is considered a major risk factor for non-cardiac surgery.

Method

There were 113078 patients who underwent non-cardiac surgery with intermediate-to high risk in general anesthesia from 2011 to 2019 at our Medical Center. There were 221 patients with asymptomatic significant AS among this population.

First, to investigate the effect of significant AS on adverse events after surgery, Major adverse cardiovascular events (MACE) and Perioperative adverse cardiovascular events (PACE) occurrences were compared in the control group and asymptomatic significant AS group. Second, in order find out the factors affecting the occurrence of MACE and PACE in patients with asymptomatic significant AS, patients with and without MACE and PACE were compared and multivariable analysis was performed in patients with asymptomatic significant AS.

Result

There was no significant difference between the three groups in the ratio of primary and secondary outcomes, MACE (p value 0.971) and PACE (p value 0.185). Outcomes such as cardiac death, arrest, myocardial infarction, and stroke were also not significantly different.

Significant factors with MACE were coronary artery disease (OR* 6.256, 95% CI** [1.258 - 31.115], p value = 0.026) and cardiac damage stage (OR 9.241, 95% CI [1.314 - 64.976], p value = 0.025). Factors significantly associated with PACE were dialysis (OR 13.486, 95% CI [1.742 - 104.371], p value 0.013), arrhythmia (OR 11.219, 95% CI [3.474 - 36.231], p value <0.001), LVEF (OR 0.928, 95% CI [0.882 - 0.977], p value 0.004), and cardiac damage stage (OR 2.199, 95% CI [1.055 - 4.584], p value 0.036). MACE increased at LVEF less than 62.5% and PACE increased at LVEF less than 61.7%.

Conclusion

There was no significant difference in major post-operative cardiovascular events between patients with asymptomatic significant AS and the control group. Advanced cardiac damage stage in significant aortic stenosis is an important factor in perioperative risk of non-cardiac surgery.Perioperative outcome in 30 daysRisk factor analysis for PACE
The impact of calcium and vitamin D supplement intake on survival in patients with concomitant moderate aortic and mitral valve disease
Authors: Gaballa A , Hajj Ali A , El Dahdah J , Popovic Z , Wang T K M , Reed G W , Rodriguez L , Griffin B , Roselli E E , Gillinov A M , Kapadia S , Svensson L G , Desai M
Published: November 2023

Background

Calcium and vitamin D supplement intake has increased among the elderly population, who are prone to deficiency. We sought to assess the association between calcium and vitamin D supplementation and the long-term outcomes in patients diagnosed with concomitant moderate aortic and mitral valve disease.

Methods

We included 3257 patients (aged 71.7 ± 12.9 years; 55.2% male; 83.1% white), who presented to the Cleveland Clinic between 2010 and 2018, diagnosed with concomitant moderate aortic and mitral valves disease. The patients were followed up with a mean period of 21.8 months (range 1-155.8). Patients were stratified based on the supplementation with calcium and vitamin D. Focusing on the aortic component of the concomitant valvular disease, patients were further subdivided into two groups; Aortic Stenosis (AS) with either Mitral Regurgitation (MR) or Stenosis (MS)(group 1), and Aortic Regurgitation (AR) with either MR or MS(group 2). The primary endpoints were death and heart failure hospitalization. The data was analyzed using Kaplan Meier survival analysis on SPSS.

Results

Of the total 3257 patients included in this study, 2273 (70%) were not supplemented, and 984 (30%) were supplemented with calcium and vitamin D. Supplementation with calcium and vitamin D was significantly associated with a higher risk of all-cause mortality (HR=1.114, 95% CI [1.003-1.237]; p=0.043) (Figure 1). However, no significant association with heart failure hospitalization was noted (HR=1.003, 95% CI [0.884-1.139]; p=0.958). On further sub-group analysis of the aortic component, 1045 (32%) patients in group 1 and 2212 (68%) patients in group 2 were assessed. In group 1, 701 (67%) patients were not supplemented, and 344 (33%) were supplemented. Calcium and vitamin D supplementation was associated with a significantly higher risk of all-cause mortality in patients with AS (HR=1.203, 95% CI [1.017-1.425]; p=0.031). Conversely in patients with AR (group 2), 1572 (71%) patients were not supplemented, and 640 (29%) were supplemented, and no significant association was exhibited in this group (HR=1.044, 95% CI [0.913-1.193]; p=0.531) (Figure 2).

Conclusion

In our cohort of patients with concomitant moderate aortic and mitral valve disease, the intake of calcium and vitamin D supplements was associated with higher mortality specifically in patients with aortic stenosis.Figure 1Figure 2
Aortic stenosis rapid progression is associated with premature cardiac damage independently of baseline severity
Authors: Teixeira R , Almeida M , Sousa-Nunes F , Neves I , Leite M , Lobo A , Santos D , Brandao M , Diaz S , Saraiva F , Barros A , Sampaio F , Fontes-Carvalho R
Published: November 2023

Background

Aortic stenosis (AS) is one of the major valvular heart diseases in developed countries. Degenerative fibrocalcific AS is a progressive disease of the valve and, ultimately, the myocardium. AS is a potentially fatal disease characterized not only by a narrowing of the aortic orifice but also by gradual cardiac damage (CD) that may extend beyond the left ventricle (LV). However, the presence and extent of extra-aortic cardiac damage did not reflect the baseline hemodynamic severity of AS in retrospective studies.

Purpose

This study aims to determine the rate of AS progression and its impact on cardiac damage and survival.

Methods

We retrospectively identified 914 patients (age 76 ± 8 years, 52% female, median follow-up time 6.8 years) with AS who had undergone > 1 echocardiogram. Bayesian hierarchical nonlinear models were used to predict aortic peak velocity as a function of time and estimate individual AS acceleration rates. Then, patients were clustered into rapid (RP) and slow progressors (SP) using machine learning algorithms.

Results

APV was best modeled by a logistic function of time. 483 patients were clustered as RP (53 %) and 431 as SP (47 %), with acceleration rate coefficients estimated at 0.14 ± 0.02 years-1 and 0.09 ± 0.02 years-1, respectively (p < 0.01). No association between progression rate and clinical variables was found. Compared with SP, RP had significantly higher 5-year incidences of LV damage, combined left atrium and mitral valve damage and combined tricuspid valve damage and pulmonary hypertension (all p ≤ 0.01). No statistically significant differences were seen for right ventricle damage between RP and SP, as the number of events was low. After multivariate adjustment for age, gender, comorbidities and baseline AS severity, RP remained an independent predictor for all extra-aortic cardiac damages except for the RV dysfunction. Importantly, baseline AS severity was not predictive of AS-related CD. RP was associated with higher mortality (HR 1.28, p = 0.02), persisting after adjustment for demographics, comorbidities, AS severity, and time-dependent aortic valve replacement (AVR) (HR = 1.36, p < 0.01).

Conclusions

RP may impair cardiac adaption to rapidly changing loading conditions, which induces premature cardiac damage that may not be reversible in the late stages of AS, when guideline-triggered interventions are currently delivered.
Long noncoding RNA H19 is elevated in aortic valve stenosis and governs antigenic response and valvular endothelial cell phenotypes through endothelial to mesenchymal transition
Authors: Hosen D R
Published: November 2023

Background

Long noncoding RNAs (lncRNAs) have emerged as important regulators of cardiovascular disease, including aortic valve stenosis (AVS). Endothelial to mesenchymal transition (EndMT) is a transdifferentiation process that is associated with the development of AVS in the elderly population. Although several recent studies have reported that lncRNAs are dysregulated and might play a crucial role in EndMT, no specific role of lncRNA was reported in AVS pathogenesis. Here, we sought to investigate the role of H19 in EndMT during the pathogenesis of AVS.

Methods and results

High-throughput lncRNA sequencing of human aortic valve tissue explanted from patients with AVS due to severe stenosis during surgical aortic valve replacement (SAVR) demonstrated that certain lncRNAs [H19, AGAP2-AS1 (PUNISHER), GAS5, MALAT1] are significantly dysregulated compared to patients without AVS. To validate the RNA-seq data, 60 patients with AVS (n=30) or without AVS (n=30) were prospectively investigated. Among these, H19 (p=0.002), AGAP2-AS1 (p=0.002), and GAS5 (0.02) were significantly upregulated in patients with AVS, compared to non-AVS patients. Aortic valvular endothelial cells (VECs) were isolated from explanted valve tissue from AVS patients or obtained commercially. In vitro EndMT-promoting stimuli (TNFα or TGFß+IL1ß) were used for VEC stimulation for 5 days. RT-qPCR was used to quantify the expression of EndMT markers (EC markers, vWF, and NOS3, and mesenchymal markers, αSMA, SM22, Vimentin, and SNAI2). Loss of H19 led to dysregulation of the EC gene network and protein expression patterns that were analyzed by qRT-PCR, immunoblotting, and immunofluorescence, respectively. Further experiments show that silencing of H19 affects migration and proliferation, and promotes EndMT in EC. Functional assays suggested that H19 is a critical regulator of angiogenic properties. The molecular signature of angiogenesis was investigated using a RT-qPCR-based angiogenesis array to identify the regulation of angiogenesis with 84-angiogenesis-related genes. Mechanistically, the angiogenesis array revealed that H19 regulates Jagged Canonical Notch Ligand 1 (JAG1) (4.43-fold vs. control EC), an important regulator of NOTCH1 signaling, and pro-angiogenic factor in EC. Accordingly, EndMT marker expressions were dysregulated upon H19 depletion. A high-throughput luciferase reporter array demonstrated STAT3 activation upon H19 knockdown. Depletion of H19 increased the phosphorylation of STAT3 at TYR705 and pharmacological inhibition of STAT3 activation abolished the effects of H19 silencing on EndMT marker expression as well as on angiogenesis. Overexpression of H19 in VEC abrogated the H19-mediated promotion of JAG1- and VEGFA gene- and protein expression.
Improved detection of echocardiographically occult left ventricular thrombi following ST-elevation myocardial infarction
Authors: Lechner I , Reindl M , Holzknecht M , Tiller C , Fink P , Oberhollenzer F , Mayr A , Bauer A , Metzler B , Reinstadler S J
Published: November 2023

Background and Aims

Patients with STEMI are at significant risk for developing left ventricular thrombi (LVT). However, this complication often (up to 65%) remains undetected by using transthoracic echocardiography (TTE), referred to as TTE-occult LVT. The aim of this study was to investigate predictors of TTE-occult LVT and to propose a clinical model for improved detection of TTE-occult LVT post ST-elevation myocardial infarction (STEMI).

Methods

In total, 870 STEMI patients underwent TTE and cardiac magnetic resonance (CMR), the reference method for LVT detection, 3 days after infarction. Clinical and echocardiographic predictors were analyzed. Primary endpoint was the presence of TTE-occult LVT identified by CMR-Imaging.

Results

From the overall cohort, 37 patients (4%) showed an LVT by CMR. Of these thrombi, 25 (68%) were not identified by TTE. TTE-occult thrombi did not significantly differ in volume (1.4 vs. 2.74cm3), diameter (19.0 vs. 23.3mm), number of fragments or shape compared with TTE-apparent LVT (all p>0.05). For predicting these TTE-occult LVT, apical wall motion score using the 16-segment model (AWMS16Seg) showed highest validity (AUC:0.91 [95%CI:0.89-0.93];p<0.001), with an association independent of ejection fraction and AWMS17Seg (OR:1.68 [95%CI:1.43-1.97];p<0.001), clinical (body mass index, peak troponin) and angiographic (culprit lesion, post-interventional TIMI flow) associates of TTE-occult LVT (all p<0.05). Dichotomization at AWMS16Seg≥8 (n=260, 30%) allowed for a detection of all TTE-occult LVT (sensitivity:100%), with a corresponding specificity of 77%.

Conclusions

After acute STEMI, AWMS16Segserved as simple and very robust predictor of TTE-occult LVT. An AWMS16Seg-based algorithm to identify patients for additional CMR-imaging offers great potential to optimize detection of TTE-occult LVT following STEMI.Key IllustrationProposed Algorithm
Thirty-year follow-up of patients submitted to percutaneous balloon mitral valvuloplasty for severe rheumatic mitral stenosis
Authors: Jacinto S , Ferreira A P , Almeida Morais L , Bernardes L , Cacela D , Rodrigues I , Galrinho A , Moura Branco L , Timoteo A T , Rio P , Soares C , Fondinho C , Cruz Ferreira R
Published: November 2023

Background

Percutaneous balloon mitral valvuloplasty (PBMV) remains the mainstay of treatment for patients with severe rheumatic mitral stenosis (MS) and a favorable anatomy.

Aim

The present study aimed to assess very long-term outcomes after PBMV.

Methods

A retrospective analysis of PBMV performed at a single tertiary center between August 1991 and September 2022 was conducted. Successful PBMV was defined as a post-procedural functional mitral valve area (MVA) ≥1.5 cm2, mitral regurgitation less than moderate, and absence of in-hospital major cardiac or cerebrovascular events. The primary endpoint was composed of overall mortality and need for mitral reintervention (percutaneous and/or surgical).

Results

A total of 238 PBMV for severe rheumatic MS were conducted in our center during the specified timeframe (88.7% [n=211] female gender; mean age 48 ± 16 years; 48.6% [n=108] had atrial fibrillation [AFib]; 78.8% [n=149] had a Wilkins score ≤8). Acute success was achieved in 88% (n=198) procedures. Acute complications were present in 10.2% (n=23), mainly severe mitral regurgitation (n=10) and acute cerebrovascular events (n=5). During a mean follow-up of 15.3 ± 9.4 years, the incidence of the primary endpoint was 55% (n=131) (overall mortality 32.9% [n=77] and mitral valve reintervention 22.1% [n=54]). On bivariate analysis, higher age (p=0.042), presence of AFib (p=0.002), unsuccess of the procedure (p<0.001), acute complications (p=0.001) and larger left atrial (LA) diameter (p=0.05) were statistically significant for the occurrence of the primary endpoint. On multivariate analysis, larger LA diameter (hazard ratio [HR]: 1.03; 95% CI: 1.00-1.06; p=0.022), unsuccessful procedure (HR: 3.30; 95% CI: 1.56-7.01; p=0.002) and presence of complications (HR: 0.37; 95% CI: 0.17-0.84; p=0.017) were the only independent predictors of the primary endpoint.

Conclusion

In a large registry of patients submitted to PBMV for severe rheumatic MS, more than half met the primary endpoint for overall mortality or need for reintervention, up to 30 years after the procedure. This supports the dismal prognosis of this pathology. Prediction of late favorable results is multifactorial and appears to be determined by smaller LA diameter, absence of complications and acute success of the procedure.Event-free survival after PBMV
A new regional Rheumatic Heart Disease Registry: results of the first 2595 patients
Authors: Kotit S , Yacoub M H
Published: November 2023

Background

Rheumatic Heart Disease (RHD) remains a major cause of morbidity and mortality in low- and middle-income countries. However, specific disease characteristics and progression varies in different regions.

Purpose

We here present preliminary results of a new regional RHD registry.

Methods

A total of 2595 consecutive patients with clinical and echocardiographic RHD were registered from March 2009 and February 2023, and their baseline clinical and echo characteristics, demographics, comorbidities, the pattern and severity of valvular involvement, intervention history and treatment practices were recorded. Follow-up ranged from 1 to 168 months (47±38.8) and was complete in 90.4% of the patients.

Results

The age of the patients ranged from 3-86 years (40.18±13.83). The majority was female (n=1765, 68%). At enrolment only 26 (1%) patients were on secondary penicillin prophylaxis. Symptoms were present in 73.8% (n=1916) of the patients (NYHA III: n=984, 37.9%). 2226 (85.8%) patients had moderate-to-severe multivalvular disease complicated by pulmonary hypertension (n=877, 33.8%), atrial fibrillation (AF) (n=750, 28.9%), cerebrovascular events (n=158, 6%), infective endocarditis (n=17, 0.66%) and thrombosis of valve prosthesis (n=14, 0.54%). Previous cardiac intervention was reported by 492 patients (19%).

Regular 6 monthly follow-up at our centre for periods ranging from 1 to 168 months (47±38.8). During this period a total of 1309 (50.4%) patients underwent cardiac procedures. Balloon Mitral Valvuloplasty was performed in 289 patients (11.1%).

Cerebrovascular events (n=92, 3.5%), LA thrombus (n=22, 0.85%), infective endocarditis (n=13, 0.5%) and thrombosis of valve prosthesis (n=19, 0.73%) occurred during follow-up. Patient mortality was 12.6% (n=328) during the study period (47±38.8 months).

Penicillin prophylaxis rate was 63.3% (n=1742), however, only 15% of these patients followed the penicillin prophylaxis schedule.

Conclusions

In spite of continued cardiac care in this study, young patients with rheumatic heart disease have high morbidity and mortality. Further efforts to determine the exact causes involved and improve prognosis are warranted.