bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating transforming growth factor-beta1 and progression of the mitral valve prolapse: fifteen-year follow-up
Authors: Malev E , Reeva S , Timofeev E , Zemtsovsky E
Published: October 2021

Introduction

Transforming growth factor-β1 (TGF-β1) is a crucial regulatory cytokine that contributes to the development of the mitral valve and regulates extracellular matrix protein synthesis in syndromic and non-syndromic mitral valve prolapse (MVP). Our aim was to evaluate the effect of elevated circulating TGF-β level on the progression of the valve myxomatosis and leaflets billowing at long-term follow-up.

Methods

78 asymptomatic young subjects (mean age 19.7±1.6, 72% male) with MVP were consecutively enrolled in our observational, prospective, single-center study. MVP was diagnosed by billowing one or both mitral leaflets >2 mm above the mitral annulus in the long-axis parasternal view. Concentration of TGF-β1 in serum was determined by enzyme-linked immunosorbent assay using a test system Human Platinum ELISA.

Results

During 1170 person-years of follow-up (median 14.5 years), no deaths or MVP-related events occurred. Posterior leaflet's thickening (from 3.9±1.4 mm to 4.4±1.7 mm (D=+0.5 mm), p<0.01) and increase of the billowing (progression in maximal prolapse depth from 3.5±2.4 mm to 4.8±2.8 mm (D=+1.3 mm), p<0.001) leads to the mitral regurgitation (MR) progression (vena contracta: 2.3±0.4 mm vs. 3.5±0.4 mm (D=+1.2 mm), p<0.0001) over 15 years of follow-up.

TGF-β1 serum level was increased (15.2±12.3 ng/ml) and strongly correlated with the thickening of the posterior leaflet (r=0.72; p≤0.0001). In multivariate Cox analysis the TGF-β1 level was the independent predictor of the posterior leaflet's thickening (2.07; 95% CI: 1.34 – 3.29; p=0.001) and progression of the billowing (2.89; 95% CI: 1.61 – 4.37; p=0.0001).

TGF-β1 >7.0 ng/ml was a strong predictor (area under ROC curve = 0.84 (95% CI, 0.7–0.9); sensitivity 82%, specificity 95%) for progression of MVP (maximal prolapse depth increase: D +1.9±1.2 mm (TGF-β1 >7.0 ng/ml) vs. 0.7±0.6 mm (TGF-β1 <7.0 ng/ml), p<0.0001) and MR (vena contracta increase: D +1.1±0.5 mm (TGF-β1 >7.0 ng/ml) vs. 0.5±0.4 mm (TGF-β1 <7.0 ng/ml), p<0.0001).

Conclusions

Despite the overall benign prognosis, we found the obvious echocardiographic progression of the valve myxomatosis and leaflets billowing at long-term follow-up in young person. Elevated above 7.0 ng/ml TGF-β1 serum level might serve as a prognostic biomarker and identifies patients with increased risk of the mitral valve prolapse progression.

Funding Acknowledgement

Type of funding sources: None.
Head-to-head comparison of NT-proBNP and soluble ST2 for long-term prognosis of patients with hypertrophic cardiomyopathy
Authors: Cediel Calderon G , Resta H , Codina P , Santiago-Vacas E , Domingo M , Spitaleri G , Lupon J , Bayes-Genis A
Published: October 2021

Background

N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure (HF) in hypertrophic cardiomyopathy (HCM), however, evidence regarding soluble interleukin-1 receptor-like 1 (ST2) in this population is lacking.

Purpose

To assess the ST2 and NT-proBNP significance for risk stratification of patients with HCM during long-term follow-up.

Methods

We prospectively enrolled a cohort of consecutive patients with HCM admitted to an ambulatory HF Unit in a Tertiary University Hospital. All patients had clinical and echocardiographic evaluation and measurement of NT-proBNP and ST2 at inclusion. The primary endpoint was the composite of all-cause death or HF-related hospitalization.

Results

103 patients were enrolled, 68% (n=70) males with a median (IQR) age of 60 (50–71) years. The median (IQR) of ST2 was 31.5 (IQR: 24.5 – 40.7) pg/mL. During a median follow-up of 2.5 years, 17 patients had the primary endpoint. Both, NT-proBNP and ST2 (both log-transformed) were associated with the primary endpoint in the univariable analyses (p<0.01). However, after adjustment by age, sex, NYHA functional class and left ventricular ejection fraction (LVEF), this association remained statistically significant only for ST2 (HR: 4.62, 95% CI 1.80–11.87, p=0.001 vs HR: 1.57, 95% CI 0.97–2.54, p=0.068 for NT-proBNP). The addition of ST2 to a clinical model (age, sex, NYHA functional class and LVEF) increased the Harrel's C statistic from 0.70 to 0.76, while the addition of NT-proBNP increase this C-statistic only to 0.73.

Conclusions

ST2 appears to be a valuable biomarker for the prediction of death and heart failure related hospitalization in patients with HCM, outperforming the prognostic value of NT-proBNP. Future research should delve into this association.

Funding Acknowledgement

Type of funding sources: None.
All-cause mortality and cardiovascular death in 52091 patients with hypertrophic cardiomyopathy. A nationwide cohort study
Authors: Fauchier L , Bisson A , Bodin A , Herbert J , Spiesser P H , Pierre B , Clementy N , Babuty D , Bernard A , Lip G Y H
Published: October 2021

Background

Patients with hypertrophic cardiomyopathy (HCM) have high risk of death related to cardiovascular (CV) death. Improvements in risk stratification are needed to help identify those HCM patients at higher risk of all-cause death and cardiovascular death.

Methods

This French longitudinal cohort study from the database covering hospital care from 2010 to 2019 analyzed adultshospitalized with isolated HCM. The overall sample of 52,091 patients was randomly partitioned into derivation (n=26,067) and validation (n=26,024) populations. A logistic regression model was used to construct HCM death and CV-death scores in the derivation sample, which were compared to the Charlson index, Frailty index and CHA2DS2VASc scores using c-indexes and calibration analysis.

Results

In 52,091 patients with isolated HCM, 12,676 (24.0%) died during follow-up of 3.0±2.8 years (median 2.3, interquartile range 0.4–5.0). Rate of all-cause death was 8.10%/year (7.96–8.24) and was 2.76%/year (2.68–2.84) for CV death.Independent predictors of CV death in HCM were older age, diabetes mellitus, heart failure, history of pulmonary edema, atrial fibrillation, ventricular tachycardia or fibrillation, ischemic stroke, while smoking and poor nutrition were associated with better survival (all p<0.05). In addition to these, male sex, vascular disease, alcohol related diagnoses, kidney disease, lung disease, liver disease anemia and cancer were independent predictors of all-cause death. In the derivation cohort, c-indexes for the HCM death score were 0.720 (0.713–0.727) for all-cause death and 0.695 (0.685–0.705) for CV death. For the HCM CV-death score, c-indexes were 0.679 (0.671–0.686) for all-cause death and 0.723 (0.712–0.733) for CV death. Performances were very similar in the validation cohort. Both scores had good calibrations. Charlson and Frailty indexes however had a better clinical usefulness than the HCM death score and HCM CV-death scores for predicting all-cause death. Decision curve analysis for CV death demonstrated that the HCM CV-death score had the best clinical usefulness of all the tested risk scores.

Conclusion

HCM patients have a high risk of all-cause and CV mortality. Independent predictors of CV-mortality in HCM were used to derive and validate a simple risk prediction model (French HCM CV-mortality score) which performed better than clinical scores, Charlson Index and Frailty Index; showing the best clinical usefulness, with good calibration.

Funding Acknowledgement

Type of funding sources: None.
Glucocorticoids in myocarditis therapy after COVID-19
Authors: Kovalenko V , Nesukay E , Cherniuk S , Kirichenko R , Kozliuk A , Titova N , Titov E , Giresh J
Published: October 2021

The aim of the study - to evaluate the efficacy of glucocorticoids (GC) in patients with acute myocarditis (AM) after COVID-19 infection.

Material and methods

We included 60 pts with severe AM and heart failure (HF) with reduced (<40%) left ventricular (LV) ejection fraction (EF) who had COVID-19 infection 1–2 months before the enrollment. According to the results of cardiac magnetic resonance (CMR) included pts had ≥2 Lake Louise criteria for myocarditis. All pts on the background of HF therapy (β-blockers, ACE-inhibitors, MRA antagonists, diuretics) were prescribed GC: 0.25 mg/kg per day methylprednisolone for 3 months, followed by a gradual dose reduction of 1–2 mg per week until complete discontinuation after 6 months. Evaluation before the start of GC therapy and after 6 months included CMR, 2D- and speckle-tracking echocardiography.

Results

After 6 months according to the results of CMR the number of LV segments with inflammatory lesions decreased to (3,58±0,42) from (6,32±0,77) segments in average (p=0,001). This was followed by improvement of LV systolic function: increase of LV EF in average to (43,5±2,6) from (32,2±2,4) % (p=0,003), longitudinal global systolic strain (LGSS) absolute value to (11,3±1,1) from (7,9±0,5) % (p=0,012) and circumferential global systolic strain (CGSS) to (12,1±1,0) from (8,9±0,6) % (p=0,023). Also we observed LV volume reduction: decrease of LV end-diastolic (from 118,9±8,6 to 95,3±7,2 ml/m2, p=0,033) and LV end-systolic (from 80,1±5,1 to 59,1±4,4 ml/m2, p=0,027) volume indexes. Wherein in 24 of 60 pts (41,6%) on the background of significant decrease in the number of LV segments with inflammatory lesions (to 1,34±0,21 from 6,12±0,73 segments, p=0,0001) after 6 months we observed the recovery of LV EF ≥50%, followed by an improvement of LGSS and CGSS on 42,1 and 39,4% respectively (p=0,001). According to multivariate regression analysis, predictors of LV EF recovery (≥50%) after 6 months of GC treatment were established: presence of inflammatory lesions in ≤5,0 LV segments, values of LGSS and CGSS ≥9.0% and ≥9.5% respectively before the start of GC.

Conclusions

The use of GC in pts with severe AM after COVID-19 was followed by the decrease of LV segments number affected by inflammation, improvement of LV systolic function and reduction of LV volume indexes. In 41,6% of pts GC therapy was associated with LV EF recovery after 6 months and predictors of its effectiveness were found: presence of inflammatory lesions in ≤5,0 LV segments, values of LGSS and CGSS ≥9.0% and ≥9.5% respectively before the start of GC.

Funding Acknowledgement

Type of funding sources: None.
Predictive factors for requiring heart transplantation in patients with hypertrophic cardiomyopathy: data from a referral center
Authors: Brufau-Cochs M , Ramos-Jovani M , Lopez Sainz A , Farrero M , Castel M A , Sole-Gonzalez E , Quintana E , Sandoval E , Pereda D , Rodriguez Arias J J , Fernandez Valledor A , Castella M , Perez-Villa F , Sitges M , Garcia-Alvarez A
Published: October 2021

Background

Heart transplant (HT) remains the last treatment option for patients with non-obstructive hypertrophic cardiomyopathy (HCM) who develop end-stage heart failure (HF). Early identification of patients who may require a HT in the future is crucial in order to advise them, establish the appropriate follow-up and determine the appropriate time to include them in the waiting list.

Objectives

Our study sought to find predictive factors related with requiring HT during follow-up in patients with HCM.

Methods

Consecutive patients with HCM referred to a HCM monographic clinic from 2018 to 2020 (HCM controls) and transplanted patients due to HCM in the same tertiary HT hospital since 2003 (cases) were included. Baseline (on the date of HCM diagnosis) and longitudinal data regarding clinical, genetic, ECG and echocardiographic variables were retrospectively evaluated. Follow-up was registered from HCM diagnosis to HT (in cases) or last medical check up (controls).

Results

A total of 157 patients (24 HCM-HT cases and 133 HCM controls) were included (45±19 yo; 57% male). At the time of MCH diagnosis (Table), cases were significantly younger than controls, were more frequently symptomatic and showed significantly higher BNP levels and more advanced diastolic dysfunction (larger left atrium, higher E/A ratio and lower e'); also, HCM-HT reported more family history and had higher proportion of pathogenic mutations (being MYH7 the most frequently involved). Left ventricular (LV) systolic function was slightly reduced in HCM-HT cases. In contrast, HCM controls were more frequently diagnosed by casual findings or family screening and had more LV outflow tract obstruction at first medical evaluation. LV maximal wall thickness (MWT) did not differ between groups. During a median follow-up since HCM diagnosis of 6.2 years (median follow-up of 8.9 and 7.1 years in cases and controls, respectively), HCM-HT cases presented a higher incidence of sustained ventricular tachycardia or ICD therapy (HR=4.0; CI95%:1.6–10.0 p=0.03) and HF admissions (HR=3.9; CI95%:1.8–8.1 p<0.001). There were no cardiovascular deaths during follow-up.

Conclusions

The presence of symptoms in a young non-obstructive HCM patient, along with family history and a pathogenic mutation, should advice clinicians a closer follow-up and early transfer to a HT referral center, especially if associated with diastolic dysfunction and high BNP values.

Funding Acknowledgement

Type of funding sources: None. Table 1
Left atrial strain in cardiac amyloidosis
Authors: Aimo A , Fabiani I , Spini V , Chubuchny V , Pasanisi E M , Petersen C , Poggianti E , Taddei C , Cameli M , Mandoli G E , Passino C , Emdin M
Published: October 2021

Background

Patients with cardiac amyloidosis (CA) display an enlarged and dysfunctional left atrium (LA), because of the effects of left ventricular (LV) diastolic and then systolic dysfunction, as well as the amyloid infiltration of LA wall. A single study reported impaired LA strain in CA, but differences among amyloid light-chain (AL) and transthyretin (ATTR) CA and the correlates of reduced LA strain have not been characterized.

Methods

We evaluated 426 consecutive patients undergoing a screening for suspected CA in 2 tertiary referral centres. Among them, 262 (61%) were diagnosed with CA (n=117 AL-CA, n=145 ATTR-CA). We measured peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) from 4- and 2-chamber (4C, 2C) views, and correlated them with maximum and minimum LA volumes, E/e' ratio, and LV global longitudinal strain (GLS).

Results

LA strain was much more severely impaired in patients with ATTR-CA than those without CA, and to a lesser extent than those with AL-CA (Figure). LA volumes were larger in patients with ATTR-CA than those without CA (maximal LA volume, p=0.042; minimal LA volume, p<0.001), and those with AL-CA (both volumes, p<0.001). LA strain values were more closely correlated with minimal than maximal LA volumes, and patients with AL-CA displayed stronger correlations than those with ATTR-CA or without CA; for example, Spearman's rho values for 4C-PALS vs. minimal LA volume were 0.595, 0.481, and 0.462, respectively (all p<0.001). Furthermore, LA strain correlated with E/e' in patients with AL-CA, but not in those with ATTR-CA: 4C-PALS vs. E/e', rho 0.406, p=0.001 (AL-CA), p=0.401 (ATTR-CA), and p=0.097 (no CA). Finally, LA strain correlated most closely with LV GLS in patients with AL-CA: 4C-PALS vs. LV GLS, rho 0.431, p<0.001 (AL-CA), rho 0.401, p<0.001 (ATTR-CA), rho 0.219, p=0.042 (no CA).

Conclusions

LA volume increase and reduced LA strain is particularly prominent in patients with ATTR-CA. Patients with AL-CA seem to display closer relationships between LA strain, size and haemodynamic load, possibly reflecting the most acute disease course, and lower time for amyloid deposition in the LA wall.

Funding Acknowledgement

Type of funding sources: None.
A machine learning-derived electrocardiographic algorithm for the detection of cardiac amyloidosis
Authors: Schrutka L , Anner P , Seirer B , Rettl R , Duca F , Dalos D , Dachs T M , Binder C , Badr-Eslam R , Kastner J , Loewe C , Hengstenberg C , Stix G , Dorffner G , Bonderman D
Published: October 2021

Background

The diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic value is limited.

Purpose

The aim of this study was to perform a comprehensive electrophysiological characterization in CA patients and to develop a robust, easy-to-use diagnostic tool.

Methods

First, we applied electrocardiographic imaging (ECGI) to generate detailed electroanatomical maps in CA patients and controls. Then, a machine learning approach was used to generate a surface ECG-based diagnostic algorithm from the complex dataset.

Results

Areas of low voltage were localized in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualized in the right ventricle. Potential maps showed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1 to V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in inferior leads II, III, aVF. Ten blinded cardiologists were then asked to identify CA patients by analyzing 12-lead ECGs before and after training for the defined ECG patterns. Training resulted in significant improvements in the detection rate of CA with an AUC of 0.69 before and 0.97 after training (Figure).

Conclusion

Using a machine learning approach, a robust ECG-based tool was developed to detect CA from detailed electroanatomical mapping of CA patients. The developed tool proved to be a simple and reliable diagnostic tool to suspect CA without the aid of advanced imaging modalities.

Funding Acknowledgement

Type of funding sources: None.
Impact of COVID-19 in adult patients with congenital heart disease
Authors: Cardoso I , Branco T B , Constante A , Martins J , Sousa L , Viegas J , Rito T , Ferreira R C
Published: October 2021

Background

COVID-19 is responsible for a worldwide pandemic, causing more than 13 000 deaths to date in Portugal. Data already exists regarding the increased risk of adverse events in patients with cardiovascular diseases, however the impact of SARS-CoV-2 infection in patients (P) with congenital heart disease (CHD) is still under investigation.

Aims

To evaluate the impact of COVID-19 in adult patients with congenital heart disease in our tertiary centre

Methods

Adult patients seen at the CHD outpatient's clinic at a tertiary centre, who became infected with SARS-CoV-2 infection up to February 2021 were included. Assessment of patients' symptoms, need for hospitalization and admission in an intensive care unit was assessed based on medical records.

Results

We identified 36 patients (pts) with COVID-19 infection. Symptoms were present in 31 (86%). The median age was 39 (32–49) years, 58% were females. Seven P (19%) had complex cyanotic disease; three (8%) Tetralogy of Fallot; three (8%) transposition of great arteries (one after Senning procedure and 2 after arterial switch); six (14%) right ventricle obstacle; two (8%) atrioventricular canal defect; four (11%) atrial septal defect; five (14%) ventricular septal defect; five (14%) aortic coarctation; two aortopathies (one submitted do David procedure); one subaortic stenosis; two (6%) had Eisenmenger syndrome. The majority (61%) of P had previous surgery and 58% were at New York Heart Association class of I. Mild symptoms were reported by 24 P (67%). Seven adults experienced moderate symptoms (dyspnea and hypoxia) that led to hospitalization for oxygen therapy, although none required mechanical ventilation. One death was reported. There was a significant association between the gravity of CHD and hospitalizations (p=0.012).

Conclusion

Our pts had mainly mild to moderate symptoms and did not appear to have a disproportionately negative outcome; the need for hospitalization was more frequent in patients with higher CHD gravity. These findings are in line with the emerging data regarding COVID-19 in CHD P, and may be in part explained by the patient's young age and functional status.

Funding Acknowledgement

Type of funding sources: None.
Pulmonary valve replacement in women with repaired tetralogy of Fallot. Contrasting indications compared with men
Authors: Ladron R , Walls A J , Cejudo P , Rodriguez-Puras M J , Manso B , Fernandez-Vivancos C , Camacho R , Gallego P
Published: October 2021

Background

Recent data suggest that in pulmonary regurgitation (PR) after repair of Tetralogy of Fallot (rToF) sex may influence right ventricular (RV) size, mass and function. We hypothesized that women with rToF and PR constitute a patient population with different preoperative clinical characteristics and different postoperative outcomes compared with men.

Methods

We collected retrospectively demographic data, clinical variables, imaging and functional variables in a cohort of 166 rToF patients (50% males; median age 35; IQR 26–41 years) with at least moderate PR. A transannular patch was used in 73 and 79% of men and women, respectively. The most recent data preceding death and pulmonary valve replacement (PVR) were requested. Variables were compared between men and women.

Results

Over follow-up, none of the patients died but 35 (42.7%) men and 23 (27.4%) women underwent PVR (p=0.05) at a median age of 32.5 (IQR 23.7–42.7 years). Women are more likely to undergo surgery after developing symptoms, while the criterion for surgery in men was ventricular size. At surgery, women were nearly twice as likely to have class III or IV symptoms preoperatively as men. Although PR fraction was similar between the two groups, indexed ventricular volumes were substantially higher and RV function was lower in males, compared to females. 20% of women had a RVEDVi ≥160ml and a RVESVi ≥80ml, compared with 35 and 32% of men, respectively (p=0.06), and only 6% of woman had an RVEDVi >180ml, compared with 18% of men (p=0.01). Fibrosis detected on late gadolinium was observed in 100% of men but only in 20% of women (p=0.009).

Conclusions

Under comparable loading conditions, a striking difference was noted in the condition leading to the surgical indication. These results suggest that the generalization of the RV dimension surgical criteria results in criteria almost never reached by women. Recommendations need more focus on sex differences.

Funding Acknowledgement

Type of funding sources: None.
Cardiac MRI risk factors predict atrial arrhythmia development in repaired tetralogy of Fallot patients
Authors: Pinsker B L , Serfas J D , Awerbach J D , Dizon S , Campbell M J , Krasuski R A
Published: October 2021

Background/Introduction

Tetralogy of Fallot (TOF) patients with atrial arrhythmias (AA) experience greater morbidity and mortality than do their arrhythmia-free counterparts. Cardiac MRI (cMRI) has proven useful in elucidating risk factors for arrhythmia development in this population, but more work needs to be done to assess the efficacy of predicting AA onset.

Purpose

To evaluate demographic and clinical metrics, including those routinely assessed on cMRI, that predict AA onset in repaired TOF.

Methods

175 repaired TOF patients ≥18 years of age and without prior AA undergoing initial cMRI between 2003 and 2020 were identified from a tertiary U.S. hospital database. Subsequent development of AA (specifically atrial fibrillation, atrial flutter, and atrial tachycardia) was evaluated by chart review and device checks (if present). Kaplan-Meier analysis was used to assess arrhythmia-free survival based on cMRI characteristics, and log-rank test used to compare differences in survival curves. Cutoff values for Kaplan-Meier analysis were the mean value (for the respective variable being measured) of our cohort at the time of their initial cMRI.

Results

Over a median follow-up of 3.3 years, 30 patients (17%) developed AA, including 16 with atrial fibrillation (53%), 20 with atrial flutter (67%), and 2 with atrial tachycardia (7%). Age at cMRI (p<0.01), history of hypertension (p=0.01), and time from birth to complete TOF repair (p<0.05) predicted AA. cMRI predictors included indexed right ventricular (RV) end diastolic and systolic volumes (both p<0.01), as well as indexed right atrial (RA) volume (p<0.05) and pulmonic regurgitation (PR) fraction (p<0.05). Indexed RV and RA volumes but not left sided chamber volumes predicted the development of atrial fibrillation. All Kaplan-Meier survival distributions were significantly different with the exception of those for right atrial volumes.

Conclusions

Our study suggests that RA and RV volumes may play a valuable role in predicting atrial arrhythmia onset in the repaired TOF population. Disease progression in a predominantly right-sided heart disease may play a role in predicting the onset of both “right sided” arrhythmias such as atrial flutter, as well as “left sided” arrhythmias such as atrial fibrillation. Additionally, the increased AA burden in patients with mild RV dilation seen in our study may suggest a potential benefit to early pulmonic valve replacement in this patient group.

Funding Acknowledgement

Type of funding sources: None. Clinical and cMRI CharacteristicsKaplan-Meier Survival Analysis
Short-term prognostic value of heart failure diagnosis in a contemporary cohort of patients with ACHD
Authors: Maessen L , De Meester P , Santens B , Troost E , Budts W , Moons P , Van De Bruaene A
Published: October 2021

Background

Heart failure (HF) is one of the primary causes of premature death in patients with adult congenital heart disease (ACHD), yet population-specific data remains scarce. This study aims at assessing the short-term value of prognostic value of a heart failure diagnosis in patients with adult congenital heart disease, and its relation to ACHD classification systems such as the Bethesda disease complexity classification and the physiological severity classification.

Methods

This study included 3995 patients under active follow-up at our institution. We used a standardized definition of ACHD-HF. Predictors of the composite primary outcome: death, transplant or ventricular assist device (VAD) were identified using uni- and multivariable Cox proportional hazard models.

Results

Mean age was 35.7±13.3 years. According to the Bethesda disease complexity classification 33.5% of patients had simple defects, 55.6% moderate defects, and 10.9% severe defects. Based on the physiological severity classification, 18.0% of patients were in physiological stage A, 35.6% in physiological stage B, 42.2% in physiological stage C, and 4.2% in physiological stage D. The overall prevalence of ACHD-HF was 6.4%. During a median follow up of 1.8 (IQR 1.3–2.9) years, patients with ACHD-HF had a worse outcome with 27.3% reaching the composite primary endpoint of death, heart transplant or VAD implantation, compared to 1.4% of ACHD patients without HF. Event-free survival was 91.1%, 72.0% and 46.1% at 2, 4 and 6 years in patients with ACHD-HF, compared to 99.5%, 98.7% and 95.1% in ACHD patients without HF. In multivariable analysis the presence of heart failure (HR 4.6; 95% CI 2.9–7.2; p<0.001) and the physiological severity classification (HR 3.1; 95% CI 2.3–4.1; p<0.001) were independently associated with the composite primary outcome, whereas the Bethesda disease complexity classification was not (HR 0.9; 95% CI 0.7–1.3; p=0.701).

Conclusion

The risk of mortality, transplant and VAD is substantially increased in ACHD-HF patients. Our data provides insight into the short term prognostic value of a HF diagnosis in ACHD patients, helping physicians to gauge the prognosis in ACHD-HF and thereby guide management decisions. In addition to the physiological severity classification, the presence of HF proves to be a valuable prognostic marker in patients with ACHD.

Funding Acknowledgement

Type of funding sources: None. Kaplan–Meier analysesUni- and multivariable Cox regression
Comparison of D-dimer level measured on the third day of hospitalization with D-dimer level in predicting in-hospital mortality in COVID-19 patients
Authors: Selcuk M , Cinar T , Gunay N , Keskin M , Cicek V , Kilic S , Asal S , Orhan A L
Published: October 2021

Objective

The present study aimed to compare the value of D-dimer measured on the 3rd day of hospitalization with admission D-dimer level in predicting in-hospital mortality in coronavirus disease 2019 (COVID-19) cases.

Method

In total, 231 patients with COVID-19 disease were included in the study. D-dimer levels were estimated using immunoturbidimetric assay with normal range of 0–500 μg/mL. In the current research, the primary outcome was the in-hospital mortality.

Results

In the present research, 39 (16.8%) COVID-19 cases died during the index hospitalization. In a multivariable analysis; age, D-dimer (3rd day) (OR: 1.00, 95% CI: 1.00–1.00, p<0.001), WBC count, and creatinine were independent predictors of the in-hospital death for COVID-19 cases. The ideal value of D-dimer level on the 3rd day of hospitalization was 774 μq/mL (area under curve (AUC): 0.903, 95% CI: 0.836–0.968; p<0.01) with sensitivity of 83.2% and specificity of 83.6%. It was noted that D-dimer level on the 3rd day of hospitalization had a higher sensitivity (83.2% vs 67.6%, respectively) and AUC value than that of D-dimer level on admission (0.903 vs 0.799, respectively).

Conclusion

The main finding in this investigation was that D-dimer elevation on the 3rd of hospitalization is more sensitive predictor of in-hospital mortality than D-dimer elevation on admission in COVID-19 patients. Even though further investigations are needed to forecast precise prognosis in patients with COVID-19 disease in terms of D-dimer levels, we believe that D-dimer levels on the 3rd day of hospitalization have an enhanced potential to be used as a prognostic marker in routine clinical practice.

Funding Acknowledgement

Type of funding sources: None. Table 1Figure 1
Available bleeding scoring systems poorly predict major bleeding in the acute phase of pulmonary embolism
Authors: Mathonier C , Badoz M , Besutti M , Schiele F , Meneveau N , Guillon B , Chopard R
Published: October 2021

Background

Bleeding prediction scores may help to guide acute management of patients with pulmonary embolism (PE). However, existing scoring systems have not been validated for in-hospital assessment. We aimed to compare 6 available bleeding scores, in a real-life cohort for the prediction of major in-hospital bleeding.

Methods

We recorded in-hospital characteristics of 2,754 PE patients included in a prospective observational multicenter cohort study contributing 18,028 person-days of follow-up. We assessed the VTE-BLEED, RIETE, ORBIT, HEMORRA2HAGES, ATRIA, and HAS-BLED scores at baseline. ISTH-defined bleeding events were independently adjudicated. The accuracy of the scores for the prediction of in-hospital bleeding was evaluated and compared.

Results

We observed 82 first in-hospital major bleeding events (3.0% (95% CI, 2.4–3.7)). Overall, the predictive power of bleeding scores was poor, with a C index ranging from 0.57 to 0.69 (Figure 1). The RIETE score had the numerically highest model fit and best discriminatory capacity, but without reaching statistical significance versus the ORBIT, HEMORR2HAGES, and ATRIA scores. The VTE-BLEED and HAS-BLED scores had significantly lower C indices, integrated discrimination improvement, and net reclassification improvement compared to the four others.

Conclusion

Currently available scoring systems have insufficient accuracy for the prediction of in-hospital major bleeding in patients with acute PE. The development of acute-PE-specific risk scores is needed to optimally target patients that warrant bleeding-prevention strategies.

Funding Acknowledgement

Type of funding sources: None. Figure 1
TAPSE or right-to-lleft ventricle diameter ratio at echocardiography to predict death in patients with acute pulmonary embolism: a meta-analysis
Authors: Cimini L A , Maraziti G , Candeloro M , Plywaczewska M , Pruszczyk P , Di Nisio M , Agnelli G , Becattini C
Published: October 2021

Background

Right ventricle (RV) dysfunction at echocardiography is a recognized predictor of death or clinical deterioration in patients with acute pulmonary embolism (PE). However, the best predictor of death among echo parameters of RV dysfunction is unknown.

Purpose

This meta-analysis is aimed at assessing the role of individual parameter of RV dysfunction at echocardiography to predict all-cause short-term death in patients with acute PE.

Methods

OVID was searched between 1993 and January 2020 for studies i) including patients with confirmed acute PE; ii) reporting on RV assessment at echocardiography at admission; iii) reporting on short-term all-cause or PE-related death. The primary study outcome is short-term (30 days or in-hospital) all-cause mortality.

Results

We report here on the role of tricuspid annular plane excursion (TAPSE) and right-to-left ventricle diameter ratio (RV/LV) at echocardiography as predictors of short-term death in patients with acute PE. TAPSE. Abnormal TAPSE at echocardiography was associated with increased risk for short-term death in all-comers with acute PE (eight studies; 3298 patients; RR 2.78 CI 95% 0.53–14.63; Figure 1) and in hemodynamically stable patients (six studies; 3013 patients; RR 2.76 CI 95% 1.44–5.30 I2 58%). The association is confirmed for different cut-off values of TAPSE (≥15mm or any cut-off value >15mm). RV/LV. In eight studies reporting on continuous measures, the difference between mean right and left ventricle diameter at echocardiography in patients who died vs those who survived ranged from 0.02 to 0.3 mm. Abnormal RV/LV ratio at echocardiography was not associated with increased risk for short-term death in all-comers with acute PE (six studies; 2292 patients; RR 1.48 CI 95% 0.43–5.08), nor in hemodynamically stable patients (four studies; 1014 patients; RR 1.20 CI 95% 0.72–1.99, I2=0%).

Conclusion

Abnormal TAPSE is associated with short-term death in patients with acute PE. In these patients, the prognostic role of RV/LV diameter ratio as stand-alone parameter of RV dysfunction at echocardiography remains unclear.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Association between TAPSE and all-cause
Survival of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension listed for lung transplantation
Authors: Magnani I , Dardi F , Palazzini M , Zuffa E , Guarino D , Daddi N , Dolci G , Antonacci F , Solli P , Paganelli G M , De Lorenzis A , Rotunno M , Ballerini A , Manes A , Galie N
Published: October 2021

Background

Lung transplantation (LT) still remains a treatment option for patients with pulmonary arterial hypertension (PAH) and not operable chronic thromboembolic pulmonary hypertension patients (CTEPH).

Purpose

The study is intended to compare the survival of transplant recipients (TR) and the survival of not-transplanted (NT) patients since listing.

Methods

We included all patients with PAH and not-operable CTEPH listed for LT. The survival of NT, TR and of all listed patients was evaluated starting from the date of listing (patients were censored as alive at the time of LT). The survival of TR was also evaluated starting from the date of the LT.

Results

125 patients were included (112, 90% had PAH). Fifty-eight (46%) patients were transplanted, after a mean waiting time of 1.5±1.3 years. Forty-one patients (33%) died while on the list and 25 (20%) patients were alive on the list on December 2019. The survival of NT patients at 1, 3 and 5 years after listing was 74%, 42%, 33%, respectively. The survival of TR patients at 1, 3 and 5 years after listing was 90%, 70%, 63%, respectively. The survival of all patients since listing (intention to treat analysis) at 1, 3 and 5 years was 85%, 59%, 48% respectively. The survival of TR at 1, 3 and 5 years since transplantation was 63%, 61%, 59%, respectively.

Conclusions

Despite biases in the comparison of non-randomized groups, the data confirm a better long-term survival since listing of TR as compared with NT PAH or not-operable CTEPH patients.

Funding Acknowledgement

Type of funding sources: None.
The biventricular dysfunction evaluation in the different types of pulmonary hypertension
Authors: Sirenko Y , Zhyvilo I , Radchenko G , Torbas O , Batsak Y
Published: October 2021

Background

Right ventricular (RV) function is well-known prognostic factor in patients with pulmonary hypertension (PH). However, situation becomes critical when underfilling of left ventricle (LV) leads to systemic hypoperfusion and scenario worsening.

Objective

To evaluate the relationship of RV and LV dysfunction in patients with the different forms of PH.

Methods

We evaluated parameters of RV and LV function and their relationship during right heart catheterization (RHC) in 125 patients with different forms of pulmonary arterial hypertension (PAH) and 51 patients with chronic thromboembolic PH (CTEPH), 7 patients with PH associated with left heart disease (LHD) and 17 patients in whom PH was excluded after procedure. In all patients recommended echocardiography protocol (Echo) and NT-proBNP level evaluation were performed.

Results

In the group without PH the RV stroke work index (RVSWI) level and its ratio to the LV stroke work index (LVSWI) were lowest and in the normal range: 7,0±0,7 ml·mmHg/m2 and 0,13±0,02 respectively. In all patients with PH, we noted the significant elevation of RVSWI >20 ml·mmHg/m2. Patients with PAH and CTEPH had a smaller left atrium, LV volumes on Echo and decreased stroke volume and pulmonary artery wedge pressure. The underfilling of LV in IPAH and CTEPH groups accompanied by severe lowering of LWSWI to 35–45 ml·mmHg/m2 (p<0,05 compared with LHD group and patients without PH). In spite of the levels of cardiac index were similar in patients with LHD and without PH, the RVSWI (23,1±2,7 ml·mmHg/m2) and its RVSWI/LVSWI ratio (0,53±0,09) were significantly higher in LHD group and confirmed severe RV overload. Only in HIV infection group observed severe depression of the pumping function of both heart's sides and levels of RWSWI and LVSWI were lowest, but the ratio was elevated (0,53) and indicated RV overload. Similar data were observed when we compare pumping coefficients of RV and LV in different groups. We did not find any association between NT-proBNP level and the LV volume and function.

Conclusion

The simultaneous evaluation of parameters of RV and LV function and their ratio during RHC in patients with different types of PH allowed not just to estimate the degree of RV overload and dysfunction, but also LV underfilling and dysfunction.

Funding Acknowledgement

Type of funding sources: None.
Clinical features and survival in pulmonary Takayasu's arteritis associated pulmonary hypertension: a national registry study
Authors: Zhu Y.-J , Jiang X , Peng F.-H , Wang L , Ma W , Cao Y.-S , Pan X , Zhang G.-C , Zhang F , Fan F.-L , Wu B.-X , Huang W , Yang Z.-W , Hong C , Jing Z.-C
Published: October 2021

Background

The clinical features and long-term outcomes of patients with pulmonary Takayasu's arteritis associated pulmonary hypertension (PTA-PH) have not been well studied.

Purpose

To assess the clinical characteristics and long-term survival outcome in patients with PTA-PH.

Methods

We conducted a multi-center cohort study using the clinical, functional, and hemodynamic data from the National Rare Diseases Registry System of China. Patients with Takayasu's arteritis and pulmonary artery involvement, who fulfilled the 1990 American College of Rheumatology and/or modified Ishikawa criteria, from 13 referral centers of China, were included. The diagnosis of pulmonary hypertension (PH) was confirmed by right heart catheterization findings. The primary outcome was time from diagnosis of PTA-PH to the occurrence of all-cause death.

Results

Between Jan. 2007 and Jan. 2019, a total of 140 patients with PTA-PH were included, with a mean age of 41.4±14.3 years at diagnosis, and a female predominance (81%). The most common symptoms were exertional dyspnea (91%) and hemoptysis (36%). The majority of patients (87%) exhibited bilateral pulmonary artery involvement. Pulmonary lobar artery was the most frequently affected vessel (100%), followed by segmental artery (82%) and left/right pulmonary artery trunk (49%). Severely compromised hemodynamic profiles were identified in these patients, indicating by elevated mean pulmonary artery pressure (48, interquartile range [IQR] 38–59 mm Hg) and pulmonary vascular resistance (9.4, IQR 5.7–13.3 Wood U). The overall 1-year, 3-year, and 5-year survival rates in PTA-PH were 94.0%, 83.2%, and 77.2%, respectively (Figure). Predictors associated with increased risk of all-cause death were the presence of syncope (hazard ratio [HR]: 4.88; 95% CI: 1.62–14.74; p=0.005), N-terminal pro-B type natriuretic peptide level (HR: 1.04; 95% CI: 1.02–1.06; p<0.001), and right atrial pressure (HR: 1.07; 95% CI: 1.02–1.73; p=0.009).

Conclusions

In this national registry study, the reported clinical features and long-term prognosis of patients with PTA-PH are novel findings. These findings may provide new insights on this specific pulmonary hypertension entity.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The National Key Research and Development Program of China Kaplan-Meier plot for survival rate
Long-term outcomes in patients undergoing transcatheter aortic valve implantation: insights on clinical outcomes and prognostic markers from a large cohort of patients
Authors: Munoz-Garcia M , Munoz-Garcia E , Munoz Garcia A J , Dominguez-Franco A J , Alonso-Briales J H , Jimenez-Navarro M F , Hernandez-Garcia J M , Gomez-Doblas J J
Published: October 2021

Transcatheter Aortic valve Replacement (TAVR) has emerged as paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Clinical and performance data on long-term TAVR are still limited. The aim of this study was to determine the survival and the factors predicting mortality after TAVR with the first and second generation of prostheses.

Methods

From April 2008 to December 2019, the auto-expandible prostheses were implanted in 765 patients with symptomatic severe aortic stenosis with deemed high risk. The first generation prostheses included CoreValve and Accutrak System and the second prostheses included Evolut R and Pro.

Results

The mean age was 79.4±6.6 years. The logistic EuroSCORE and STS score were 17.1±11% and 5.7±3.9%, respectively. The implantation success rate was 98.87%. In-hospital mortality was 3.7%, and the combined endpoint of death, vascular complications, myocardial infarction or stroke had a rate of 15.1%.

The clinical outcomes in according to prosthesis generation were, for pacemaker requirement (CoreValve vs. Accutrak system vs. Evolut R vs. and Evolut pro) 35.3% vs. 26.1% vs. 14.3% vs. 14%, p=0.001; and the paravalvular aortic regurgitation, were: none 28% vs. 44.8% vs. 43.3% vs. 58; mild 40% vs. 32.3% vs. 30.8% vs. 35.2%; moderate 32% vs. 20.3 vs. 23.9% vs. 5.7%; severe 0% vs. 2.6% vs. 0% vs. 1.1, p 0.001

The late mortality (beyond 30 days) was 35.9%. Survival at 1, 3, 5, 7 and 9 years were 88.9%, 76.1%, 61.1%, 44% and 32.6% respectively, after a mean follow-up of 42.3±27 months. The NYHA functional class improved from 3.1±0.6 to 1.77±0.7 in the follow-up.

At 5 years, 5 patients had severe prosthetic valve dysfunction (severe stenosis and moderate transvalvular regurgitation

The predictors of cumulative mortality were: Charlson index [HR 1.25 (95% CI 1.077–1.461), p=0.004], Readmision Heart Failure [HR 3.02 (95% CI 1.554–5.879), p=0.001], stroke post-TAVR [HR 3.472 (95% CI 1.115–10.53), p=0.032], residual aortic regurgitation [HR 1.45 (95% CI 1.093–1.934), p=0,010], and severe pulmonary hypertension [HR −0.983 (95% CI 0.645–0.423) p=0.032].

Conclusions

TAVR is associated with significant survival benefit throughout 3.09 years of follow-up. Survival during follow-up depends particularly among patients with associated comorbidities and cardiac markers such as aortic regurgitation or pulmonary hypertension

Funding Acknowledgement

Type of funding sources: None.
Type 2 diabetes and risk of major cardiovascular events in peripheral artery disease versus coronary artery disease patients
Authors: Saely C H , Vonbank A , Larcher B , Mader A , Maechler M , Sprenger L , Mutschlechner B , Benda M , Leiherer A , Muendlein A , Drexel H
Published: October 2021

The prevalence of type 2 diabetes (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD.

The purpose of this study was to investigate how the incidence of major cardiovascular events compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes (T2DM).

We prospectively recorded major cardiovascular events and death over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123).

When compared to the incidence of MACE in CAD+/T2DM- patients (25.1%), it was significantly higher in CAD+/T2DM+ patients (35.4%; p<0.001), in PAD+/T2DM- patients (30.2%; p=0.022) and in PAD+/T2DM+ patients (47.2%; p<0.001). Patients with both PAD and T2DM in turn were at a higher risk than CAD+/T2DM+ or PAD+/T2DM- patients (p=0.001 and p<0.001, respectively). The incidence of MACE did not differ significantly between PAD+/T2DM- and CAD+/T2DM+ patients (p=0.413). Compared to patients with CAD, Cox regression analyses after multivariate adjustment showed an adjusted hazard ratio of 1.46 [1.14–1.87], p=0.002 for the presence of PAD. Conversely, T2DM increased the risk of MACE after multivariate adjustment in CAD and PAD patients (adjusted HR 1.58 [1.27–1.98], p<0.001).

In conclusion, our data show that T2DM and the presence of PAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of MACE.

Funding Acknowledgement

Type of funding sources: None.
Pre-dilatation prior to carotid artery stenting in very severe carotid artery stenosis: beneficial or detrimental?
Authors: Ocal L , Kup A , Celik M , Cersit S , Keskin M , Havan N , Gursoy M O , Eren H , Dogan S , Ozturk B , Uyan C , Turkmen M M
Published: October 2021

Background

There are many technical variations in carotid artery stenting and there is not a clear recommendation in pre-dilatation (Pre-D) prior to stenting. In this study we investigated the role of Pre-D before carotid artery stenting in patients with very severe carotid artery stenosis (≥90%).

Methods

A total of 298 patients with a carotid stenosis equal to or more than 90% were included to our study. Patients were divided into two groups as Pre-D and No-Pre-D. In-hospital and 3-year long-term clinical outcomes were compared between the groups.

Results

During the hospitalization, major stroke was more common in Pre-D group [n=6 (5.5%) vs. n=3 (1.5%), respectively], whereas overall ipsilateral stroke rates were similar between the groups. The rates of myocardial infarction were similar between the groups. In- hospital mortality was significantly higher in the Pre-D group than non-pre-D group [n=4 (3.6%) vs. n=0 (0%), respectively]. During the 3-year follow up period, the rates of ipsilateral stroke, major stroke, transient ischemic attack, myocardial infarction, and mortality were similar between the groups.

Conclusion

According to the literature, this is the first study evaluates the role of Pre-D in very severe (>90%) carotid artery stenosis. The current study demonstrated that Pre-D might have a detrimental effect on in-hospital outcomes.

Funding Acknowledgement

Type of funding sources: None.