bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal trend in hospitalization among patients with congenital heart disease in Denmark: a nationwide study
Authors: Lim C W , Hoejsgaard Joergensen T , Joens C , Schophuus Jensen A , Steen Baekke P , Margit Martsein C , Rahbek Schmidt M , Soendergaard L
Published: November 2023

Background

The survival rate of patients with congenital heart disease (CHD) had increased over the last decades due to improved management. However, the increased survival rate may potentially impact the number of occurrences of late cardiac complications as well as non-cardiovascular diseases requiring hospitalization, and hence warrants further study on this area.

Purpose

To delineate the temporal trend in hospitalization rate and length of stay (LOS) among patients with major and minor CHD in Denmark from 1977 to 2018 and to investigate the causes of hospitalization.

Methods

A Danish nationwide, population-based registry study including patients with CHD diagnosis from 1977 to 2018. Patients were categorized as either major or minor CHD, and by age groups (<1, 1-4, 5-17, 18-39, 40-64, ≥65 years). Hospitalization rate was reported as incidence per 100 person-years.

Results

In this study, 23,386 patients were included with 121,653 hospital admissions. From 1977-1981 to 2012-2018, the overall all-cause hospitalization rate decreased for both major (51.7 [CI: 48.0 -55.7] to 32.8 [CI: 31.0 - 34.7]) and minor CHD patients (28.4 [CI: 26.0 - 31.0] to 22.6 [CI: 21.1 - 24.1]). Median LOS for major CHD decreased from 5 days (IQR: 2 – 11) to 2 days (IQR: 1 – 6), and for minor CHD from 4 days (IQR: 2 – 8) to 2 days (IQR: 1 – 5). However, the trends when looking at specific age groups were different from the trend of overall all-cause hospitalization rate. Figure 1 shows that hospitalization rate had increased significantly for <1-year-olds for major CHD, whereas an increased trend was observed for <1, 40-64 and ≥65 years-olds for minor CHD. In addition, the trends for specific age groups when looking at the most common causes were also different from the trend of all-cause hospitalization rate. For both major and minor CHD, Table 1 shows that the hospitalization rate for <1-year-olds due to respiratory diseases had increased over time, while the hospitalization rate for 40-64-year-olds due to arrythmia had also increased over time. For ≥65-year-olds, significant increase in hospitalization rate for arrythmia was only observed for minor CHD.

Conclusion

Lower hospitalization rate for major and minor CHD after 1 year old suggests that early intervention of CHD has improved their morbidity during childhood and early adulthood. However, the increased hospitalization rates among <1 year-olds and the elderly suggest that more focus are needed in preventing non-cardiovascular diseases and late cardiac complications for the respective age groups.Figure 1Table 1
Epidemiology and prognostic relevance of morphofunctional classification of secondary mitral regurgitation
Authors: Provencio A , Diz J , Pozo Osinalde E , Mahia Casado P , Marcos Alberca P , Gomez De Diego J J , Islas F , Perez De Isla L , Perez Villacastin J
Published: November 2023

Background

Mitral regurgitation has traditionally been divided into organic and functional (FMR) due to its different etiology and prognosis. However, FMR is not a homogeneous entity, and may be secondary to annular dilation, ventricular dilation and dysfunction, or posterior leaflet restriction.

Purpose

Our aim is to assess the epidemiology of these FMR subtypes and their prognostic impact.

Methods

Patients with FMR from our center who underwent three-dimensional transesophageal echocardiography (3D-TEE) between 2016 and 2020 were retrospectively evaluated. Patients with at least moderate FMR, effective regurgitant orifice (ERO) by 3D-TEE >0.2 cm2 were selected. They were classified according to the predominant mechanism: type 1 or ventricular dysfunction, type 2 or posterior leaflet restriction, and type 3 or annular dilation. 3D-TEE and the closest transthoracic study variables, as well as baseline demographic and clinical characteristics and evolution events, were obtained and statistical analysis was performed according to FMR types.

Results

112 patients were included (66.1% male, mean age 72.3 years). 54.5% had previous hospitalization for heart failure and 53.6% had a history of ischemic heart disease. The most frequently identified FMR mechanism was type 1 (61.6%), followed by type 3 (23.2%) and type 2 (15.2%). There were significant differences in epidemiological factors and echocardiographic parameters (Table) between groups.

During follow-up, 43.8% died, received a heart transplant or LVAD and 44.6% had any hospitalization for heart failure. There were no significant differences between FMR types in relation to total mortality (p=0.28), mortality due to heart failure (p=0.13), total hospitalizations (p=0.73), or hospitalization for heart failure (p=0.12). Valvular intervention was performed in 54 patients (48.2%), 33 of them percutaneously with a clip, with no differences in FMR subtypes.

Conclusions

FMR is a heterogeneous entity and different morphotypes with different epidemiology and etiology can be identified. Despite the different mechanism, all subgroups presented a similar unfavorable prognosis and similar intervention rates.
Chronic kidney disease and survival of patients with tricuspid regurgitation
Authors: Loutati R , Copeland V , Ben-Zekry S , Fefer P , Mazor E , Klempfner R , Barbash I M , Guetta V , Segev A , Kuperstein R , Maor E
Published: November 2023

Introduction

Chronic kidney disease (CKD) patients are under-represented in clinical trials examining transcatheter interventions for tricuspid regurgitation (TR). The purpose of the current analysis was to investigate how CKD modifies the association of severe TR with overall survival.

Methods

Consecutive echocardiographic reports linked to clinical data from the largest medical center in Israel (2007-2022) were reviewed. Patients were dichotomized into four mutually exclusive TR groups (none/trivial, mild, moderate and severe), following by stratification according to CKD stage classification. The primary outcome was all-cause mortality. Kaplan Meier, Multivariate Cox regression and interaction analysis models were applied.

Results

Final study population included 78,147 patients with a median age of 67 (IQR: 55-78 years), 2,989 (4%) of whom had severe TR. There were 19,910 (25%) patients with estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2, 14,359 (18%) with eGFR between 30-60 and 5,551 (7%) with eGFR <30. During a median follow-up period of 4 years (IQR: 1-7 years), 28,112 patients (36%) died. Kaplan-Meier survival analysis demonstrated an increased risk of death with both increasing severity of TR and/or CKD grade (log-rank p<.001 for both). Multivariate Cox analysis with adjustment for age, sex, left heart disease and pulmonary pressures demonstrated that compared to the none/trivial group, patients with severe TR were 38% more likely to die during follow up (95% CI 1.30-1.47, p<.001). The association of tricuspid regurgitation with poor survival was CKD-dependent, such that in the eGFR>60 group severe TR was associated with 19% increased risk of death, whereas among patients with eGFR<60 the risk was significantly higher and reached 34% in the same multivariate model (p for interaction <.001). Interestingly, the modification effect of CKD was mediated by RV function, such that the interaction analysis was no longer significant when RV function was incorporated into the multivariate model. Sub analysis limited to patients with isolated TR yielded consisted results.

Conclusions

While the association of severe TR with poor survival is consistent across all CKD groups, it is more pronounced among patients with advanced CKD. This association may be modulated through right ventricular function. When examining data and outcome of tricuspid clinical trials , special emphasis should be given to CKD status.Consort like figureHR modification by CKD
Soluble ST2 in acute pulmonary embolism
Authors: Uyanik M , Cinar A , Gedikli Ö , Tuna T , Coksevim M , Avci B
Published: November 2023

Purpose

ST2 is a member of the IL-1 superfamily. It consists of two components, ST2L, which is the membrane form, and sST2, which is soluble in blood. Soluble ST2 (sST2) is a cardiovascular injury–related biomarker. sST2 is also secreted in response to myocyte and fibroblast mechanical tension and has prognostic value for heart failure. Moreover, biopsy studies have shown that the alveoli are the main source of serum sST2. The extent to which sST2 is elevated in Acute Pulmonary embolism and whether sST2 can discriminate between high-risk and low-risk patients are unknown.

Methods

Patients whose diagnosis was confirmed by Pulmonary CT Angiography were included in the study. Except for pulmonary embolism, other diseases causing sST2 elevation were excluded. Echocardiographic pulmonary artery pressure, CBC, creatinine, CRP, sST2, and d-dimer tests were performed on the patients and the control group at the time of admission.

Results

After pre-assessment, 66 patients were included and 62 in the control group, met the study criteria. sST2 levels were positively correlated with the Pulmonary Embolism Severity Index (PESI). sST2 level was associated with increased mortality and prolonged hospitalization (P<0.05). Moreover, sST2 is a sensitive biomarker as D-dimer and a better prognostic predictor than D-dimer.

Conclusions

Among patients with diagnosed acute pulmonary embolism sST2 showed the superior overall prognostic performance to D-dimer. sST2 might be a useful marker in predicting high-risk patients for Acute PE in the emergency department.
Survival and predictors of outcome in moderate mixed aortic valve disease
Authors: Patel K , Thornton G , Vandermolen S , Mckenna M , Awad W , Baumbach A , Mathur A , Treibel T , Lloyd G , Mullen M , Bhattacharyya S
Published: November 2023

Background

Coexisting moderate aortic stenosis and regurgitation (MAVD) is common. The haemodynamic effect of MAVD is poorly understood with sparse data to guide risk stratification.

Purpose

This study aims to compare all-cause mortality in moderate MAVD with matched controls and identify markers associated with prognosis.

Methods

Patients with both moderate aortic stenosis (aortic valve area [AVA] 1.0-1.5cm2) and regurgitation (vena contracta [VC] 0.3-0.6cm) were identified from a multicentre registry. All-cause mortality was compared to an age and sex matched UK population. The association between echocardiographic and clinical metrics with all-cause mortality was evaluated.

Results

207 patients were included, age 78 [66-84] years and moderate MAVD (AVA 1.2 [1.1- 1.4]cm2 and VC 0.4 [0.4-0.5]cm). Over a median follow up of 3.2 years, 75/207 (36.2%) patients died. Patients with moderate MAVD had a significantly higher mortality compared to age and sex matched controls (36% versus 14.3%), p<0.001. Peak aortic jet velocity (Vmax) was the only haemodynamic metric independently associated with mortality [hazard ratio (HR): 0.61, 95% confidence interval (CI): 0.39-0.93; p=0.02] in a multivariate model along with age, creatinine and previous cerebrovascular accident. Compared to patients with Vmax >3m/sec, those with Vmax ≤3.0m/s had lower LVEF and stroke volume and a higher mortality (HR: 1.76, 95% CI: 1.10-2.80; p=0.017).

Conclusions

Moderate MAVD is associated with reduced survival compared to age and sex matched controls. Patients with discordant low Vmax ≤3 m/sec, have disproportionately worse outcome and may represent a high risk ‘low flow’ phenotype.Figure 1
Effects of SGLT2 inhibition on cardiac remodeling and heart failure development in rats with aortic stenosis
Authors: Urbano Pagan L , Gomes M J , Damatto F C , Oliveira J P G , Gatto M , Souza L M , Santos A C C , Borim P A , Rodrigues E A , Mota G A F , Campos D H S , Murata G M , Polegato B F , Okoshi M P , Okoshi K
Published: November 2023

Introduction

Aortic stenosis prevalence has been increasing as population ages. Currently, no medical therapies influence the natural history of aortic stenosis. Sodium glucose co-transporter 2 inhibitors (SGLT2i) have reduced heart failure hospitalization and cardiovascular mortality in heart failure patients with both reduced and preserved ejection fraction. The aim of this study was to evaluate the effects of SGLT2 inhibitor empagliflozin (EMPA) on cardiac remodeling and heart failure development in aortic stenosis rats.

Methods

Eighteen weeks after supra-aortic banding surgery, male Wistar rats were divided in four groups: Sham (n=15); sham + EMPA (Sham-EMPA, n=16); aortic stenosis (AS, n=27); and aortic stenosis + EMPA (AS-EMPA, n=27). Empagliflozin (10 mg/kg/day) was added to rat chow for 8 weeks. Echocardiogram was performed to evaluate cardiac structure and function. Myocardial collagen content was quantified by histology; activity of antioxidant enzymes and enzymes involved in energy metabolism was assessed by spectrophotometry. Protein expression was quantified by Western blot, and matrix metalloproteinase (MMP) activity by zymography. Statistical analysis: ANOVA and Bonferroni or Kruskal-Wallis and Dunn (p<0.05).

Results

AS-EMPA group had a lower frequency of anatomopathological heart failure features, a lower left ventricular (LV) dilatation (LV diastolic diameter: Sham 8.39±0.57; Sham-EMPA 8.25±0.38; AS 9.80±0.53; AS-EMPA 9.08±0.87 mm; LV systolic diameter: Sham 4.24±0.68; Sham-EMPA 4.19±0.57; AS 5.72±0.74; AS-EMPA 5.09±1.08 mm) and LV mass (Sham 0.85±0.11; Sham-EMPA 0.82±0.07; AS 2.19±0.27; AS-EMPA 1.76±0.34 g), and better diastolic function (isovolumetric relaxation time: Sham 28.6±2.28; Sham-EMPA 29.8±3.04; AS 18.9±2.59; AS-EMPA 22.9±5.02 ms) than AS. Systolic function was impaired in both AS and AS-EMPA compared to their respective controls and did not differ between AS-EMPA and AS. AS and AS-EMPA had larger myocyte diameter, higher interleukin-6 protein expression and lower catalase activity than Sham and Sham-EMPA, respectively. AS and AS-EMPA groups had lower enzyme activity from energy metabolism than their respective controls. AS presented higher lipid hydroperoxide concentration, collagen III and p65 NF-kB protein expression, and lower glutathione peroxidase activity than Sham. AS-EMPA had higher collagen I expression and inactive MMP-2 than Sham-EMPA. AS-EMPA presented higher glutathione peroxidase and intermediary active MMP-2, and lower interstitial collagen fraction (Sham 2.68±0.59; Sham-EMPA 3.16±0.33; AS 5.68±0.97; AS-EMPA 3.55±0.70 %) than AS.

Conclusion

Empagliflozin improves cardiac remodeling, diastolic function and myocardial oxidative stress, and reduces heart failure feature frequency and interstitial collagen fraction in aortic stenosis rats.
Efficacy of aortic valve replacement on Heyde syndrome-related acquired von Willebrand syndrome and gastrointestinal bleeding: a systematic review and meta-analysis
Authors: Rooijakkers M J P , Goltstein L C M J , Hoeks M , Li W W L , Van Wely M H , Rodwell L , Van Royen N , Drenth J P H , Van Geenen E M
Published: November 2023

Background

Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been shown to resolve all three associated disorders.

Purpose

To assess the efficacy of aortic valve replacement (both surgical aortic valve replacement and transcatheter aortic valve implantation) on acquired von Willebrand syndrome recovery and gastrointestinal bleeding cessation.

Methods

A systematic review and meta-analysis using MEDLINE, Embase, and the Cochrane Library was performed to identify articles on Heyde syndrome and aortic valve replacement. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 hours (T1), 24 to 72 hours (T2), 3 to 21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement, and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios (RR) were calculated using random-effects models.

Results

We identified 33 studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1,054), and 11 observational studies on gastrointestinal bleeding (n = 300). One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79-91%) at T1, 90% (74-96%) at T2, 92% (84-96%) at T3, and 87% (67-96%) at T4. The pooled proportion of Heyde patients with cessation of gastrointestinal bleeding was 73% (62-81%). Residual aortic valve disease was associated with lower recovery rates of both acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; p = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; p = 0.002).

Conclusion

Aortic valve replacement is associated with a rapid recovery of the bleeding diathesis in Heyde syndrome and cessation of gastrointestinal bleeding. Residual aortic valve disease negatively impacts clinical benefits of aortic valve replacement.Graphical Abstract
Prognostic impact of geriatric frailty profile after transcatheter aortic valve replacement (TAVR): a registry study of a tertiary referral hospital
Authors: Geers J , Van Den Bussche K , Vandeloo B , Van Loo I , Michiels V , Plein D , Beckers S , Muylle T , Lieten S , Cosyns B , Compte N , Argacha J F
Published: November 2023

Background

Assessment of frailty in patients screened for transcatheter aortic valve replacement (TAVR) can improve outcome prediction after TAVR. However, previous studies evaluating frailty indicators in this population provided heterogenic results because of the wide variety of tests and cut-off values used to assess frailty1,2. Recently, the comprehensive geriatric assessment frailty index (CGA-FI) was introduced to ensure a standardized evaluation of patient frailty3.

Purpose

The aim of our study was to evaluate the potential value of frailty assessment by the CGA-FI for outcome prediction in TAVR patients. The prognostic effect of the geriatric profile including nutrition, cognition, mobility and depression was also examined.

Methods

A total of 102 patients treated by TAVR between 2015 and 2020 were included retrospectively. Demographic, medical history, hemodynamic, geriatric, procedural, hospital stay, and 2 years follow-up data were collected. The primary study endpoint was defined as 2-year all-cause mortality. The secondary endpoint was defined as lack of dyspnea improvement at 2-year follow-up.

Results

Mean patient age was 84.2 ± 4.3 years and 14% of patients were classified as frail according to CGA-FI > 0.2. The 2-year mortality rate after TAVR was 29.4% and lack of dyspnea improvement during follow-up was observed in 13.7% of patients. A CGA-FI > 0.2 did not predict all-cause mortality after TAVR (hazard ratio (HR): 1.302, 95% confidence interval (CI): 0.494-3.427, p=0.593 (Figure 1)). However, patients with a geriatric depression scale ≥ 5 had higher all-cause mortality risk after TAVR than patients with a geriatric depression scale < 5 (HR: 3.047, 95% CI: 1.330-6.977, p=0.008 (Figure 1)). Similarly, malnutrition status was associated with higher all-cause mortality and shorter survival time after TAVR (HR: 2.340, 95% CI: 1.008-5.432, p=0.048 (Figure 1)). In contrast, no association of CGA-FI and geriatric profile with 2-year lack of dyspnea improvement was observed.

Conclusions

A CGA-FI > 0.2 was not associated with 2 years patient mortality after TAVR. However, a geriatric depression scale ≥ 5 and malnutrition may be of prognostic value by predicting all-cause mortality after TAVR.
Impact of pre-procedural bioprosthetic leaflet calcification on hemodynamic and hlinical outcomes after aortic valve-in-valve procedure
Authors: Carter-Storch R , Poulin A , Dumont E , De Larochelliere R , Kalavrouziotis D , Rodes-Cabau J , Mohammadi S , Paradis J M , Salaun E , Clavel M A
Published: November 2023

Background

Transcatheter aortic valve replacement (TAVR) is a recognized option to treat patients with aortic bioprosthetic failure, but preprocedural factors associated with poor hemodynamic and clinical outcomes after valve-in-valve (ViV) TAVR remain unclear. In TAVR performed in native aortic valve, higher degrees of aortic valve calcification (AVC) have been associated with poorer outcome, but the association of bioprosthetic AVC and outcomes after ViV TAVR remains unknown. We hypothesize that a high amount of pre-procedural bioprosthetic AVC may result in a higher risk of patient-prosthesis mismatch (PPM) or post-procedural intervalvular regurgitation, and increased mid-term mortality.

Purpose

To assess the association of pre-procedural surgical bioprosthetic AVC and short- and mid-term hemodynamic and clinical outcomes after aortic ViV procedure.

Methods

All consecutive patients who underwent aortic ViV procedure for surgical aortic bioprosthetic failure at our institution between 2009-2022 with available pre-procedural CT were included, patients with TAVR-in-TAVR were excluded. We measured AVC with non-contrast CT, and this amount was divided by LVOT area (measured on echocardiography) to obtain AVC density (AVCD). Pre and post-procedural transthoracic echocardiograms were analyzed for aortic valve hemodynamics. Multivariate Cox-regression was performed to assess the determinants of mid-term all-cause mortality.

Results

A total of 186 patients were included. An AVCD score above the median was associated with younger age, diabetes, lower indexed aortic valve area and higher preprocedural mean gradient (figure 1). Preprocedural AVCD was not significantly different in patients with: 1) postprocedural severe PPM (n=81, 45%) vs no-moderate PPM (n=100, 55%) (207 [68-335] vs 209 [54-352] Agatston units (AU)/cm2, p=0.80); 2) ≥moderate intervalvular regurgitation (n=10, 5%) vs no-mild regurgitation (n=174, 90%) (198 [57-350] vs 251 [210-352] AU/cm2, p=0.22). Higher AVCD was not associated with 30-day mortality, stroke, or implantation of a new pacemaker (all p>0.05). During 38 [21-65] months of follow-up, multivariate factors associated with all-cause mortality were older age, diabetes, and chronic obstructive pulmonary disease, while AVCD was associated with a lower mortality (HR 0.77 (0.63-0.94) per 100 AU/cm2 increase, p=0.01).

Conclusion

High pre-procedural bioprosthetic ACVD is not associated with a poorer hemodynamic and clinical after Aortic ViV procedure for surgical bioprosthetic failure.Baseline tableSurvival curve
Left ventricular twist in patients with severe aortic stenosis: meaning and evolution after surgery
Authors: Bello A , Abecasis J , Maltes S , Santos R , Lima R , Reis C , Oliveira L , Guerreiro S , Freitas P , Ferreira A , Neves J P , Mendes M
Published: November 2023

Background

Structural and functional left ventricular (LV) remodeling is the result of myocardial adaptation to chronic pressure overload in patients with severe aortic stenosis (AS). Changes in LV rotational dynamics are supposed to occur due to increased afterload in order to maintain LV ejection fraction (EF) in this setting. However, data regarding rotational dynamics with AS severity and their evolution after aortic valve replacement (AVR) are scarce.

Goal

To describe LV twist in patients with severe AS according to LV remodeling and assess its evolution after surgical AVR.

Methodology

Single center prospective cohort study of patients with classical isolated severe AS referred to surgical AVR. Complete transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were performed before surgery for both valvular and LV remodeling assessment. TTE was performed at the 3rd to 6th post-operative month. LV twist was defined as the peak difference in systolic rotations of LV apex and base as viewed from the apex and calculated at bidimensional strain in short axis views. LV remodeling was categorized by CMR according to Figure 1. Correlation analysis was performed for indexes of AS severity and LV function.

Results

A total of 80 patients with classical high flow, high gradient, preserved LV EF (46% male; mean age 71 ± 8 years old; mean aortic valve [AV] gradient 61±17.6mmHg, mean AV area 0.73±0.18cm2 , mean LVEF: 58 ± 9%) were included. LV twist before surgery was 24.5 +/- 9.7% and this was modestly correlated with both LV flow (r = 0.315, p= 0.001) and AV gradients (r = 0.315, p = 0.013). Rotational indexes were no different across distinct types of LV remodeling. After AVR there was a significant decrease in LV twist (24.5 +/- 9.7% vs. 16.5 +/- 8.3%, p<0.001), despite significant improvement in global longitudinal strain (-14.7 ± 3.9% vs -16.1 ± 3.1%, p < 0.001) and maintenance of preserved LVEF (58 ± 9% vs 60 +/- 8%, p = 0.07).

Conclusion

As LV twist has an inverse relation to GLS after AVR, this may represent a compensatory mechanism for LVEF preservation in patients with severe AS. Rotational mechanics seems to be independent from structural LV remodeling in this setting.
Patient characteristics and long-term outcomes in patients undergoing transcatheter aortic valve implantation in a failed surgical prosthesis versus in a native valve
Authors: Begun X , Butt J H , Kristensen S L , Weeke P E , Backer O D , Strange J E , Schou M , Kober L , Fosboel E L
Published: November 2023

Background

Valve-in-valve transcatheter aortic valve implantation (TAVI) is an increasingly used treatment for failed surgical aortic prosthesis, but data from clinical practice are limited.

Purpose

We examined patient characteristics and outcomes of patients undergoing TAVI in a surgical valve compared with patients undergoing TAVI in a native valve.

Methods

Patients undergoing TAVI from January 1, 2008, to December 31, 2020, were identified using Danish nationwide registries.

Results

In total, 6070 patients undergoing TAVI were identified; 247 (4%) patients had a history of SAVR (The valve-in-valve cohort). Patients with valve-in-valve-TAVI were younger but had a greater burden of cardiovascular comorbidities compared with patients with native-valve-TAVI. The cumulative 30-day risk of death was 2.4% (95% CI: 1.0% to 5.0%) in patients with valve-in-valve-TAVI and 2.7% (95% CI: 2.3% to 3.1%) in patients with native-valve-TAVI (Figure 1A). Correspondingly, the cumulative 5-year risk of death was 42.5% (95% CI: 34.2% to 50.6%) and 44.8% (95% CI: 43.2% to 46.4%), respectively. Within 30 days post-procedure, 11 (0.2%) patients with valve-in-valve-TAVI and 748 (13.8%) patients with native-valve-TAVI, had a pacemaker implantation. In multivariable Cox proportional hazard analysis, patients with valve-in-valve TAVI did not have a significantly different risk of rehospitalization from any cause compared to patients with native valve TAVI at 30 days (HR 0.80 [95% CI 0.58-1.10]) and at 5 years (HR 0.85 [95% CI 0.73-1.00]) (Figure 1B). Furthermore, in adjusted analysis, valve-in-valve-TAVI was not associated with significantly different risk of death at 30 days (Hazard ratio (HR)= 0.98, 95% CI 0.43-2.22) and 5 years (HR=0.81, 95% CI 0.64-1.03) compared with native-valve-TAVI.

Conclusions

TAVI in a failed surgical aortic prosthesis as compared to TAVI in a native valve, was not associated with significantly different short- and long-term mortality. Although these findings to some extent reflect thorough patient selection, valve-in-valve-TAVI appears to be a safe procedure.
The impact of resting heart rate on adverse outcomes and haemodynamic progression of aortic stenosis
Authors: Courtney W , Budgeon C , Giudicatti L , Strange G , Playford D , Ihdayhid A , Schultz C , Hillis G S
Published: November 2023

Introduction

A high resting heart rate (RHR) is an established risk factor for cardiovascular disease, adverse cardiac events, accelerated calcification in coronary artery disease and carotid stenosis, and increased aortic valve calcification in patients with and without a confirmed diagnosis of aortic stenosis (AS). Aortic valve calcification is the most common precursor to AS and is associated with significantly faster disease progression.

There are few studies exploring the effects of RHR on the progression of AS, the development of severe stenosis, and the risk of complications and death.

Purpose

We hypothesised that an elevated RHR would be associated with poorer outcomes and more rapid haemodynamic disease progression in patients with AS and tested this in a large cohort of patients without severe disease.

Methods

Using the National Echocardiography Database of Australia (NEDA) we undertook a retrospective observational study on patients without severe AS, a bicuspid aortic valve or prior aortic valve replacement. The association between baseline RHR and time to the composite primary endpoint of severe AS, aortic valve replacement or cardiovascular death was tested using Cox proportional hazards regression. In addition, the relationship between baseline RHR and the components of this composite was investigated.

Subsequently, the relationship between annualised AS progression rate, defined as change in standard indices of AS severity (maximal jet velocity [Vmax], mean pressure gradient [MPG], and aortic valve area [AVA]), and RHR were analysed using general linear models.

Results

The initial study cohort comprised 55 585 individuals: 54% male, mean age 63 years and median baseline RHR 70 bpm. The composite primary endpoint, reached by 7 434 patients, was independently associated with RHR (hazard ratio [per 10bpm increase], 1.04; 95% CI, 1.02-1.05; p < 0.001). RHR was also independently associated with time to developing severe AS (hazard ratio [per 10bpm increase], 1.06; 95% CI, 1.01-1.12; p = 0.017) and cardiovascular death (hazard ratio [per 10bpm increase], 1.04; 95% CI, 1.02-1.06; p < 0.001). The event rate was significantly higher in patients with a RHR of at least 70 bpm (the median RHR) compared to those with an RHR less than 70 bpm.

In addition, RHR was independently associated with rate of change of each individual measurement index of AS severity including Vmax (β = 0.65 cm/s/year [per 10 bpm increase]; p < 0.001), MPG (β = 0.05 mmHg/ year [per 10 bpm increase]; p<0.001), and AVA (β = -0.01 cm2/year [per 10 bpm increase]; p < 0.001).

Conclusions

RHR is independently associated with adverse clinical outcomes and haemodynamic progression of AS in patients without severe disease. Future randomised controlled trials should investigate the effect of lowering RHR on clinical endpoints and progression of AS.
LGE in CMR and outcomes in cardiac sarcoidosis
Authors: Dhaliwal S , Al-Sadawi M , Aslam F , Kim P , Gier C , Henriques M , Singh A , Almasry I , Rashba E , Fan R
Published: November 2023

Background

Late-gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a predictor of adverse events in patients with cardiac sarcoidosis (CS). This meta-analysis evaluated the correlation between LGE and mortality, ventricular arrhythmias (VA), sudden cardiac death (SCD), and heart failure (HF) outcomes.

Methods

A literature search was conducted for studies reporting the association between LGE in CS and the study endpoints. The endpoints are: mortality, VA and SCD, and HF hospitalization. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum follow-up duration was one year.

Results

A total of 17 studies and 1,915 CS patients (595 with LGE vs 1,320 without LGE) were included; mean follow-up was 3.3 years (ranging between 17 to 84 months). LGE was associated with increased all-cause mortality (OR 6.05, 95% CI 3.16-11.58; P<0.01), cardiovascular mortality (OR 5.83, 95% CI 2.89-11.77; P<0.01) and VA and SCD (OR 16.48, 95% CI 8.29-32.73; P<0.01). The presence of LGE in the right ventricle is associated with higher risk of VT (OR 6.11, 95% CI 1.14-32.68; P 0.035). LGE was associated with an increased risk of HF hospitalization (OR 17.47, 95% CI 5.54-55.03; P<0.01).

Conclusion

LGE in CS patients is associated with increased mortality, VA and SCD, and HF hospitalization during long-term follow up. The presence of LGE in the right ventricle is associated with higher risk of VT.
Clinical outcomes after transcatheter aortic valve implantation in patients older than 90 years of age
Authors: Ehara N E , Taniguchi T T , Kim K K , Toyota T T , Okada T O , Kinoshita M K , Kobori A K , Sasaki Y S , Murai R M , Furukawa Y F
Published: November 2023

Background

The prevalence of severe aortic valve stenosis is increasing due to the prolonged life expectancy. Transcatheter aortic valve implantation (TAVI) is a minimally invasive treatment for severe aortic stenosis that is particularly attractive for elderly patients. However, there are limited data evaluating clinical outcomes in patients older than 90 years of age undergoing TAVI.

Purpose

The aim of this study was to compare in-hospital clinical outcomes between nonagenarians undergoing TAVI versus patients younger than 90 years of age and to evaluate 2-year clinical outcomes of all-cause death, stroke, and hospitalization for heart failure among nonagenarians.

Methods and results

A total of 57 nonagenarians (12%) and 418 patients younger than 90 years of age (mean 82.5 years of age) undergoing TAVI from February 2014 to February 2023 in our institution were included. Among nonagenarians, 83.7% had hypertension, 8.9% had diabetes mellitus, 17.9% had atrial fibrillation, and 10.5% had malignant diseases. Self-expanding valves were more often implanted in nonagenarians (43.9% vs. 29.0%, p=0.02) and nonagenarians were likely to undergo transfemoral TAVI (89.5% vs. 84.0%, p=0.28) Mean hospitalization days after TAVI was almost similar between nonagenarians and patients younger than 90 years of age (12.5 days vs. 12.8 days, p=0.90). Rates of in-hospital disabling stroke (3.6% vs. 1.8%, p = 0.38) and need for permanent pacemaker implantation (8.8% vs. 5.7%, p = 0.37) tended to be higher in nonagenarians. The rate of major vascular complication was almost similar between two groups (3.5% vs. 4.8%, p=0.66). The 2-year survival rates of all-cause death, stroke and hospitalization for heart failure, composites of all-cause death and stroke and composites of all-cause death, stroke and hospitalization for heart failure among nonagenarians were 86.3%, 87.5%, 88.9%, 80.6% and 74.0%, respectively. During an average 1.6-year follow-up period, nine deaths occurred among nonagenarians. Of those, seven patients died from non-cardiovascular causes.

Conclusion

In this single center analysis, clinical outcomes in nonagenarians undergoing TAVI were acceptable compared with patients younger than 90 years of age.
The prevalence and prognostic impact of aortic valve diseases in heart failure with mildly reduced ejection fraction
Authors: Schupp T , Abel N A , Reinhardt M R , Schmitt A S , Pumpe K P , Weidner K W , Akin I A , Behnes M B
Published: November 2023

Objective

This study aims to investigate the prevalence and prognostic value of aortic valve diseases in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF).

Background

Limited data regarding the prognostic impact of aortic valve diseases in patients with HFmrEF is available.

Methods

A large retrospective study was used including all consecutive hospitalized patients with HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41 – 49%) from 2016 to 2022 according to current European guidelines. The prognostic impact of moderate to severe aortic valve stenosis (AS) and aortic valve insufficiency (AI) was compared to patients without (i.e., non-AS and non-AI, respectively). The primary endpoint was the first heart-failure related re-hospitalization at 3 years. Secondary endpoints comprised amongst others in-hospital mortality. Kaplan-Meier, uni- and multivariable Cox regression analyses were applied for statistics.

Results

800 consecutive patients with HFmrEF were included. The prevalence of AS was 10% (moderate 6% and severe 4%) and AI 8% (moderate 7% and severe 1%). The risk of first heart-failure related hospitalization was not significantly affected by the presence of AS (14% vs. 8%; log rank p=0.092; HR= 1.727; 95% CI 0.908 - 3.284; p=0.096), however, HFmrEF patients with moderate to severe AI were associated with an increased risk of heart-failure related re-hospitalization compared to patients without (18% vs. 8%; log rank p=0.010; HR= 2.270; 95% CI 1.193 - 4.317; p=0.012). Even after multivariable adjustment, the risk of heart failure related re-hospitalization was still significantly higher in patients with moderate to severe AI (HR= 2.022; 95% CI 1.030 - 3.969; p=0.041). Finally, patients with moderate or severe AS and patients with moderate or severe AI revealed no significant difference of in-hospital mortality (4% vs. 3%; p=0.807 and 3% vs. 3%; p=0.946).

Conclusions

In patients hospitalized with HFmrEF between 2016 and 2022, patients with moderate to severe AI – but not AS – had a higher risk of heart failure related re-hospitalization at 3 years.
Association of late-gadolinium enhancement on cardiac magnetic resonance with cardiovascular outcomes and mortality in patients with aortic stenosis
Authors: Tao M , Moussa S , Sheng S , Dhaliwal S , Tam E , Goldschmidt M , Mann N
Published: November 2023

Background

Late-gadolinium enhancement (LGE) on cardiac magnetic resonance has been associated with increased risk of adverse events in various clinical settings. This association in patients with aortic stenosis is not well established.

Purpose

This meta-analysis assessed the association between LGE on CMR with all-cause moratlity, cardiovascular (CV) mortality, and major adverse cardiovascular events (MACE) in patients with aortic stenosis.

Methods

A literature search was conducted for studies reporting the association between LGE in aortic stenosis and the primary endpoint of all-cause mortality. Secondary endpoints included CV mortality and MACE. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum duration of follow-up was 12 months.

Results

A total of 11 studies and 2527 patients (1279 with LGE vs 1248 without LGE) were included; mean follow up was 30 months (ranging between 12 to 52 months). LGE is associated with increased risk of all-cause mortality on long-term follow-up (odds ratio 2.87, 95% confidence interval 2.03-4.04; P<0.01). Heterogeneity was low-moderate: Chi2= 12.28, df8, I2 =35%. Subgroup analysis of only patients who underwent aortic valve replacement demonstrated that LGE is associated with increased risk of all-cause mortality on long-term follow-up (OR 2.49, 95% CI 1.94-3.20; P<0.01).

For secondary endpoints, LGE was not associated with a statistically significant increase in risk of CV mortality or MACE, however there is a trend toward increased risk (OR 2.43, 95% CI 0.95-6.23; P = 0.06; OR 2.33, 95% CI 0.86-6.28; P=0.09).

Conclusions

Our results suggest that LGE is associated with increased risk of all-cause mortality in patients with aortic stenosis regardless of whether aortic valve replacement is performed. LGE was not associated with a statistically significant increased risk of CV mortality or MACE, however additional high quality prospective studies are needed to further evaluate these endpoints.
The serum haemoglobin to creatinine ratio predicts 1-year adverse outcomes in patients undergoing transcatheter aortic valve implantation
Authors: Ikuta A , Oka T , Matushita S , Kadota K , Komiya T , Fuku Y
Published: November 2023

Background

The baseline serum haemoglobin and renal function are both important predictors of adverse outcomes in patients with severe aortic valve stenosis (AS) after transcatheter aortic valve implantation (TAVI), there are no reports that has examined the correlation between those combined data and adverse outcomes, however.

Purpose

In this study, we examined whether the combined index of anaemia and renal failure is predictive of 1-year prognosis in patients undergoing TAVI.

Methods and Results

This study is a retrospective, single-centre, and observational study. Between January 2015 and June 2021, 469 consecutive patients with severe AS underwent TAVI in our hospital. After excluding dialysis patients, 458 patients were analysed in this study. Patients were categorized into three groups (tertiles) according to their value of haemoglobin to creatinine (Hgb/Cr) raio. The Hgb/Cr ratio was calculated from the serum haemoglobin and creatinine on the day before TAVI. The primary and secondary clinical outcomes measure was defines as all-cause mortality and heart failure hospitalization at 1-year after TAVI.

Results

The mean age was 85.5 ± 4.8 years, and the mean the Society of Thoracic Surgeons score (STS) was 7.0 ± 4.7, the mean serum creatinine, eGFR and haemoglobin were 0.97 ± 0.47 mg/dL, 49.1 ± 21.3 mL/min/1.73 m2 and 13.8 ± 5.9 g/dL, respectively. The procedural success rate and length of admission day after TAVI were equivalent for tertile 1, tertile 2, and tertile 3 groups. In-hospital mortality was higher in tertile 1, tertile 2, and tertile 3 groups, in that order (8.7% vs. 2.6% vs. 0%; p<0.01). Cumulative incidences all-cause mortality and heart failure hospitalization rate were significantly better in tertile 1, tertile 2, and tertile 3 groups, in that order, respectively (16.9% vs. 7.2% vs. 2.0%; p<0.01, 10.7% vs. 3.4% vs. 0.7%; p<0.01, respectively). The index of the area under curve of Hgb/Cr ratio for all-cause mortality and heart failure hospitalization at 1-year after TAVI were 0.73 and 0.73, respectively. The cut-off values were 10.1 for all-cause mortality (odds ratio: 4.78; 95% confidence interval; 2.43-9.74; p<0.01) and 10.4 for heart failure hospitalization (odds ratio: 5.3; 95% confidence interval; 2.21-14.1; p<0.01).

Conclusions

The Hgb/Cr ratio was associated with all-cause mortality and heart failure hospitalization in patients who underwent TAVI. Calculation of Hgb/Cr ratio on the day before TAVI could be useful for predicting adverse outcomes at 1-year in patients undergoing TAVI.
Comorbidity is the driver of adverse outcomes in patients with moderate aortic stenosis
Authors: Sen J , Wahi S , Marwick T
Published: November 2023

Background

Recent studies showed moderate aortic stenosis (AS) was associated with adverse cardiovascular outcomes. Ongoing studies are addressing whether moderate AS may benefit from early transcatheter aortic valvular replacement (TAVR). However, a high comorbidity burden is common, and may be the main driver of poor outcomes.

Purpose

We aimed to identify clusters of patients with moderate AS based on comorbidity and echocardiographic profiles.

Methods

Unsupervised clustering algorithms (including K means, partition around medoids (PAM), hierarchical clustering, Density-Based Spatial Clustering of Applications with Noise (DBSCAN), and Hierarchical Density-Based SCAN (HDBSCAN)) of comorbidities, demographics and echocardiographic parameters were conducted in patients diagnosed with moderate AS [aortic valvular area (AVA) 1-1.5 cm2 or peak velocity (Vmax) 3-4 m/s or dimensionless severity index (DSI) 0.25-0.5]. Cumulative hazard plots and Cox proportional hazards regression models were used to assess the difference in time to cardiac death, heart failure hospitalization or aortic valvular intervention between the clusters.

Results

Four distinct clusters were identified AS patients (n=2,409) using PAM algorithm. The highest risk of cardiovascular outcomes was found among patients in Cluster 4 (Comorbid cluster), followed by Cluster 3 (Risk factors cluster), and Cluster 2 (Valve morphology cluster) (Table 1, Figure 1). Comparing cardiac death outcomes between patients treated with TAVR vs. no TAVR in each cluster revealed that TAVR was of most benefit in Cluster 2 (HR = 0.05, 95% CI: 0.01-0.34, p=0.002).

Conclusions

Multiple comorbidities are the key driver of worse outcomes in patients with moderate AS, which can affect treatment outcomes from TAVR. Thus, careful attention to the comorbidities is imperative in the management of patients with moderate AS.Table 1.Characteristics of 4 clustersFig 1.Cumulative Hazard Plot
Association of aortic valve size with the degree of aortic valve calcification in patients with severe aortic stenosis
Authors: Mousavi R A , Lamm G , Will M , Hoebart P , Kammerlander A A , Schwarz K , Vock P , Hoppe U , Mascherbauer J
Published: November 2023

Background

The development and progression of aortic valve calcification (AVC) is a major contributor to the severity of aortic stenosis (AS). Currently, the 2021 ESC/EACTS Guidelines recommend the use of the Agatston AVC score to predict the likelihood of severe AS in patients with unclear echocardiographic AS severity. It has been shown that AS in women is associated with less AVC, thus lower AVC thresholds for the diagnosis of severe AS in women are recommended. It has furthermore been demonstrated that women generally have smaller hearts. However, whether small aortic valve (AV) size, independent from sex, is associated with less AVC in patients with severe AS has not been explored.

Purpose

The aim of this study was to assess the association of AV dimension and the degree of AVC in severe AS.

Methods

AVC was assessed on computed tomography using the Agatston score in consecutive patients with severe AS. AV diameter and indexed AV annulus area adjusted for body surface area were measured. To analyze the association with AVC, Spearman rank correlation as well as multivariate linear regression models adjusted for age, sex, left ventricular ejection fraction and cardiovascular risk factors were performed.

Results

In total 446 patients (mean age 81±6 years, 45% female) were included. Median Agatston Score was 2949 AU [2135-3986] in men and 1755 AU [1303-2571] in women. Mean AV diameter was 24±2mm and mean indexed annulus area was 248±43mm2.

We observed a significant correlation between AV Agatston score and AV diameter (r=0.6; p<0.001 Figure 1 Panel A) as well as between AV Agatston score and indexed annulus area (r=0.5; p <0.001; Figure 1 Panel B). On multivariate analysis AV diameter (β=273; p<0.001), indexed annulus area (β=13; p<0.001) and sex (β=396; p<0.001) were independently associated with AVC by the Agatston score. In addition, separate regression analyses in men and women showed a significant association of AV diameter (β(men)=265; β(women)=275; both p<0.001) and indexed annulus area (β(men)=13; β(women)=11; both p<0.001) with the AV Agatston score. Hypertension, dyslipidemia, diabetes mellitus, smoking and chronic kidney disease showed no statistically significant association with the amount of AVC.

Conclusion

Our results indicate that patients with severe AS and larger AV dimensions present with more AVC on Agatston scoring, independent from sex. From surgical data, it is known that smaller aortic bioprostheses cause higher gradients, consequently we hypothesize here, that less calcification is required in small valves to cause significant narrowing. Thus, AVC cut-offs for the diagnosis of AS should be indexed for AV size rather than sex.