bluuebunny/crossref_metadata_2025 huggingface dataset:
Main results of the first Brazilian Registry of Heart Failure (BREATHE)
Authors: Albuquerque D C , Barros E Silva P G , Lopes R D , Hoffmann C , Nogueira P R , Reis H , Nishijuka F A , De Figueiredo Neto J A , De Souza Neto J D , Rohde L E P , Simoes M V , Rocha R M , Moura L Z , Marcondes-Braga F G , Mesquita E T
Published: October 2022

Background

Heart failure represents a common cause of hospitalization associated with poor short-term clinical outcomes. Little is known about the long-term prognosis of these patients in Latin America.

Methods

The rationale and design of the study were previously published (1). Briefly, BREATHE was the first nation-wide prospective observational study that included patients hospitalized due to acute heart failure in Brazil. In-hospital management as well as 12-month clinical outcomes were assessed. Patients were included during two time periods: from February 2011 to December 2012 (BREATHE I) and from June 2016 to July 2018 (BREATHE Extension). Adherence to evidence-based therapies was also evaluated.

Results

A total of 3,013 patients were included in 71 centers in Brazil. The median follow-up was 346 days. The BREATHE population included 39.3% of women, had a mean age of 65.2 (± 15.6) with a mean ejection fraction of 39.7% (± 17.5). Among the comorbidities, systemic arterial hypertension was the most common, present in almost 75% of the sample. At hospital admission, 83.8% of patients had clear signs of pulmonary congestion and the main cause of decompensation was poor adherence to heart failure medications, representing 27.8% of cases. Among patients with reduced ejection fraction, the concomitant use of renin-angiotensin-aldosterone inhibitors, beta-blocker and spironolactone at hospital discharge was 44.5% and decreased to 35.2% after 3 months (p<0.01). Mortality rate at 12 months was 28.9 for every 100 patient years with 26.2% readmission at 90 days and 46.4% at 365 days. The most common etiology of heart failure was ischemic disease (Figure 1) but the worst prognosis was associated with Chagas disease (Figure 2) including an analysis of a composite outcome encompassing death, myocardial infarction, stroke or cardiac arrest after discharge.

Conclusions

In this large national prospective registry of patients hospitalized with acute heart failure, mortality and readmission were higher than what have been reported globally. Poor adherence to evidence-based therapies was a common both at hospital discharge and 1-year of follow-up.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Brazilian Society of Cardiology
Midodrine in treatment of post coronary revascularization vasoplagia; pilot, open label, assessor blinded randomized clinical trial
Authors: Sheikhy A , Ziaoddini M , Navid H , Ahmadi-Tafti H , Hosseini K
Published: October 2022

Purpose

Post cardiac surgery hypotension and inotrope dependence are among major causes of prolonged intensive care unit (ICU) stay. Besides routine managements, catecholamine inotrope-vasopressors are the traditional treatment. However, there is an increasing interest to catecholamine-sparing agents, such as Midodrine, oral alfa1 agonist, in patients with vasoplegia. Up to now there are no randomized study with midodrine on post cardiac surgery patients.

Material and method

In this pilot, open label, assessor blind, randomized clinical trial from June 2020 to December 2021, 65 patients with refractory (more than 24 hours inotropes) hypotension after coronary revascularization were included. Patients were randomly assigned to receive Midodrine add-on therapy (10 mg stat and 5 mg po every 12 hours) or placebo add-on routine treatment. The primary outcome was liberation time from IV inotrope-support. Secondary outcomes were ICU admission time and total vasopressor dosage after randomization.

Results

32 patients enrolled in Midodrine group, with a mean age of 60.72, and 33 patients received placebo with mean age of 63.27. Median liberation time from inotrope was 27 hours in Midodrine group and 49 hours in placebo group (p=0.022). ICU admission time for Midodrine and placebo groups were 115 and 121 hours, respectively (p=0.990). Total vasopressor dosage after randomization were similar in two studied groups, 4352 μg in Midodrine group and 5637 μg in placebo group (p=0.405). No adverse event was observed in Midodrine group.

Conclusion

Midodrine add-on inotrope therapy was a safe medication with appropriate compliance in ICU admitted patients after cardiac surgery, which seems to decrease the inotrope dependent time.

Funding Acknowledgement

Type of funding sources: None.
Early Intervention with Impedance-guided Heart Failure Management Improves Long-term Outcome: insights From the IMPEDANCE-HF Trial
Authors: Kleiner Shochat M , Fudim M , Kazatsker M , Kleiner I , Weinstein J M , Panjrath G , Kobo O , Roguin A , Meisel S
Published: October 2022

Background

Lung-impedance (LI) guided treatment of heart failure (HF) patients was shown to improve clinical outcomes.

Objectives

To perform a post-hoc analysis of the IMPEDANCE-HF extended trial in order to explore the mechanism underlying the improved outcome of the LI-guided compared with conventional therapy of HF patients.

Methods

The study included 290 HF patients with LVEF ≤45% randomized 1:1 to LI-guided or conventional therapy. The normal LI (NLI), representing the dry lung status, was calculated upon enrollment. The level of pulmonary congestion (LPC) was represented by ΔLIR= [(measured LI/NLI)-1] × 100%.

Results

There were 11473 outpatient visits in the LI-guided group and 10245 visits in the control group during follow-up, or 15.5 and 15.9 visits/patient×year, respectively (p=0.74). The LI-guided patients were on average less congested during follow-up than those in the control group (by 20%, p<0.01). Multivariate regression analysis showed that the likelihood of hospitalization for HF [hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.52–0.72, p<0.01) and of all-cause mortality (HR: 0.83, 95% CI: 0.70–0.98, p=0.03] were lower in the LI-guided group than in the control group. In the LI-guided group, diuretic up-titration was 2-fold more frequent and at an earlier timepoint and at a 21% lower LPC (p<0.01). In both groups the diuretic response was more prominent when up-titration was done at a lower LPC (p<0.01).

Conclusion

LI-guided diuretic titration prompted earlier, and more frequent diuretic dose increase when the LPC was only beginning to increase and this resulted in a greater decongestive response with better clinical outcomes.

Funding Acknowledgement

Type of funding sources: None.
Left atrial coupling index predicts heart failure and atrial fibrillation in the general population
Authors: Ravnkilde K , Skaarup K , Lassen M C H , Johansen N D , Benfari G , Nistri S , Jensen G B , Schnohr P , Moegelvang R , Biering-Soerensen T
Published: October 2022

Background

It is well known that left atrial (LA) function and size can provide significant information regarding the risk of atrial fibrillation (AF) and heart failure (HF). The ratio of LA volume index and tissue doppler imaging a' (peak myocardial velocity of the left ventricle in late diastole exposing the atrial contraction) provides the LA volumetric/mechanical coupling index (LACi). LACI is a novel echocardiographic measurement which combines information of LA size and function in one measure with limited previous investigation.

Purpose

The aim of the present study was to investigate the prognostic value of LACi in relation to incident HF and AF in the general population.

Methods

The present study included 4,003 participants from a prospective general population. All participants were examined with echocardiography. Incident HF and AF were investigated as separate outcomes. Exclusion criteria were AF and/or HF at baseline. LACi was calculated as the index of LAVI (left atrial volume index) and peak tissue velocity at late diastole measured with pulsed wave Doppler at the septal base of the left ventricle.

Results

Mean age was 56±17 years, 57% were female, and median LACi was 2.3 [IQR: 1.8, 3.0]. The median follow-up time was 5.4 [IQR: 4.5, 6.3] years. A total of 82 and 164 developed HF and AF during follow-up, respectively. Median LACi was significantly higher among participants developing HF (2.6 [IQR: 2.1, 3.8], P<0.001) and AF (2.8 [IQR: 2.1, 4.1], P<0.001) compared to those who remained event free (2.3 [IQR: 1.8, 3.0]). Multivariable Cox proportional hazard regression models were constructed and adjusted for gender, age, smoking status, hypercholesterolemia, diabetes mellitus, ischaemic heart disease at baseline, hypertension, left ventricular ejection fraction and left ventricular diastolic function (E/e'). LACi was an independent predictor of incident HF and of AF in both univariable and multivariable Cox regression models (Figure 1). LACi remained a significant predictor of both HF and AF in a sensitivity analysis with subgroups in which LAVI was normal and enlarged, respectively (Figure 1).

Conclusion

LACi is an independent predictor of HF and AF in the general population.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The Danish Heart Foundation and The Metropolitan Region of Denmark.
Prognostic value of rest B-lines with the simplified 4-site scan for predicting survival: incremental value over transthoracic echocardiography
Authors: Merli E , Ciampi Q , Arbucci R , Cortigiani L , Zagatina A , Wierzbowska-Drabik K , Djordjevic-Dikic A , Amor M , Boshchenko A , Rodriguez-Zanella H , Barbieri A , Haberka M , Gaibazzi N , Simova I , Picano E
Published: October 2022

Background

Lung ultrasound (LUS) detects pulmonary congestion as B-lines at rest.

Methods

After preliminary exclusion of 154 patients lost to follow-up, we analyzed transthoracic echocardiography (TTE) plus LUS (4-site simplified scan) data in 5165 subjects (age 64±11 years) referred to 19 certified centers of 9 countries for known or suspected coronary artery disease (n=3891, 75%), dyspnea (n=591, 12%), or screening in asymptomatic patients with risk factors (n=667, 13%). We analyzed the anterior and lateral hemi-thoraces, scanning from mid-axillary to mid-clavicular lines on the third intercostal space. B-lines score ranged from 0 (normal) to 40 (severely abnormal). By selection, follow-up information was available in all. All-cause death was the predetermined end-point.

Results

Feasibility of B-lines was 100% in all subjects. B-lines (median) were 0.1 [0–1]. Rest B-lines (≥2) were present in 863 patients (16.7%). Ejection fraction was 61±10%. After a median follow-up of 690 (Interquartile range 420–1065) days, 96 all-cause deaths occurred. Two-year mortality was 3.6% in patients with and 1.5% in patients without B-lines (p<0.001) and increased progressively with the increasing number of B-lines, from 2.4% in mild (2–4, n=630), 5.0% in moderate (5–9, n=160) and 8.2% in patients with severe (≥10, n=73) B-lines (see figure). At multivariable analysis, rest B lines (HR 1.812, 95% CI: 1.165–2.916, p=0.008) and ejection fraction (HR 0.987, 95% CI: 0.976–0.998, p=0.020) were independent predictors of all-cause death, in addition to age (HR 1.045, 95% CI: 1.023–01.067, p<0.001) and diabetes (HR 1.643, 95% CI: 1.079–2.503, p=0.021).

Conclusion

In all-comers referred for TTE, resting B-lines assessed by focused LUS with the simplified 4-site scan are detected in 1 out of 4 patients with symptos or coronary risk factors and are associated with worse survival. The severity of pulmonary congestion predicts the severity of outcomes. The prognostic value of resting B-lines is independent and additive over standard clinical and TTE predictors such as diabetes and ejection fraction. Focused LUS for pulmonary congestion can easily be incorporated in standard TTE examination.

Funding Acknowledgement

Type of funding sources: None.
Prognostic impact of plasma level of NT-pro BNP in patients with microvascular angina – a report from the international cohort study by COVADIS
Authors: Shimokawa H , Suda A , Takahashi J , Ong P , Ang D , Berry C , Camici P , Crea F , Kaski J , Pepine C , Rimoldi O , Sechtem U , Yasuda S , Beltrame J , Merz C
Published: October 2022

Aims

Although the importance of microvascular angina (MVA) has been emerging, prognostic biomarkers for MVA remain to be developed. We thus aimed to examine whether plasma level of N-terminal prohormone of brain natriuretic peptide (NT-pro BNP) could predict the prognosis of MVA patients.

Methods

In the international prospective cohort study of MVA patients by the Coronary Vasomotor Disorders International Study (COVADIS) group, we evaluated the association between plasma level of NT-pro BNP and the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina.

Results

We examined a total of 226 MVA patients (M/F 66/160, 61.9±10.2 [SD] years) with both plasma NT-pro BNP levels and echocardiographic data in the COVADIS study. Plasma NT-pro BNP level was elevated (median 94 pg/ml, IQR 45–190) while mean LVEF (69.2±10.9%) and E/e' (10.7±5.2) were almost normal. During follow-up period of a median of 365 days (IQR 365–482), 29 MACEs occurred. ROC curve analysis identified plasma NT-pro BNP level of 78 pg/ml as the optimal cut-off value. Multivariable logistic regression analysis revealed that plasma NT-pro BNP level ≥78 pg/ml significantly correlated with the incidence of MACE (odds ratio (OR) [95% confidence interval (CI)] 3.11 [1.14–8.49], P=0.03). When divided into 2 groups by NT-pro BNP 78 pg/ml, the Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with NT-pro BNP ≥78 (log lank, P=0.03) (Figure).

Conclusions

These results indicate that plasma NT-pro BNP level is a novel prognostic biomarker for MVA patients.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Japan Heart Foundation
Immuno-inflammatory response in patients after myocardial infarction and involvement in fibrosis in vitro
Authors: Miquelestorena-Standley E , Vinhais Da Silva A V , Monnier M , Chadet S , Lemoine R , Ivanes F , Angoulvant D
Published: October 2022

Background

Pathophysiology of acute myocardial infarction (AMI) has been described in mice and is based on a three-stage model involving temporal modifications of immune cells and fibroblasts. The acute inflammatory phase is followed by a reparative phase and fibrous scar maturation phase. Purinergic signaling, particularly P2Y11 receptor, has been reported to be involved in the regulation of inflammation after ischemia and could be an actor of resolution of inflammation after AMI.

Purpose

The aims of our study were: (1) to characterize the immune and P2Y11R profiles of AMI patients and (2) to analyze interactions between patients' immune cells and cardiac fibroblasts in vitro.

Methods

We collected peripheral blood mononuclear cells (PBMC) of 182 patients at various times (H0, H4, H24, H48, D3, M1, M6, M12) after reperfused ST-segment elevation AMI, and of 30 healthy donors. Expression level of genes involved in tolerogenicity profile of dendritic cells (HMOX1, STAT3, IDO1), in T cell polarization (CD4, FOXP3, TBX21/GATA3) as well as P2RY11 were evaluated by RT-PCR. P2Y11R expression was analyzed using flow cytometry. PBMC and human cardiac fibroblasts (HCF) were co-cultured during one day (5PBMC/1 HCF) and gene level expression (ACTA2/VIM, COL1A1), phenotype (α-SMA/vimentin) and secretory (soluble collagen) profiles were analyzed by RT-PCR, flow cytometry and Sircol assay.

Results

In the first 48 hours after AMI, the expression level of HMOX1 (fold-change = 8.478 at H48, p<0.0001), STAT3 (2.856 at H0, p=0.0027) and CD4 increased (2.451 at H48, p=0.0052); IDO1 (0.2055 at H24, p<0.0001) and TBX21/GATA3 ratio decreased (0.4498 at H48, p=0.0026); FOXP3 did not vary significantly. In the same time, the expression level of P2RY11 increased (2.124 at H0, p=0.0015) as well as protein expression in T cells (median MFI = 845.5 at H0 vs 229.5 for healthy donors, p=0.0375). In vitro, we observed a non-significant increase of ACTA2/VIM ratio in HCF co-cultured with H24, M1, M6 PBMC; of α-SMA/vimentin with H48, M12 PBMC; of COL1A1 with H24, H48, M12 PBMC; and of soluble collagen in coculture supernatant with M1 PBMC.

Conclusion

Our results suggest that P2Y11R could be involved in evolution of immune response after AMI, and that, in the first 2 days, circulating immune cells have a reparative profile and could participate in the transformation of fibroblast into myofibroblasts.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Fondation pour la recherche médicale
Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals of the general population with and without diabetes mellitus
Authors: Haller P M , Gossling A , Brenner H , Iacoviello L , Kee F , Linneberg A , Thorand B , Salomaa V , Soederberg S , Voelzke H , Sans S , Palmieri L , Veronesi G , Blankenberg S , Westermann D
Published: October 2022

Introduction

Cardiovascular biomarkers may reflect different aspects of cardiovascular disease, including myocardial tissue damage (high-sensitive cardiac troponin [hs-cTn]), hemodynamic stress (N-terminal prohormone of brain natriuretic peptide [NT-proBNP)), or inflammation (high-sensitivity C-reactive protein [hs-CRP]).

Purpose

To determine the risk for fatal and non-fatal cardiovascular events in patients with diabetes mellitus (DM), a high-risk group for cardiovascular complications, after accounting for these biomarkers and to determine the risk associated with these biomarkers.

Methods

Harmonized data of population-based studies from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomaCaRE) and MOnica Risk, Genetics, Archiving and Monograph (MORGAM) consortia were used to calculate hazard ratios (HRs, 95% confidence intervals [CI] per standard deviation) for these biomarkers adjusted for diabetes, patient characteristics and biomarkers for their association with the primary endpoint of fatal and non-fatal cardiovascular events during a median follow-up of 9.6 years (maximum 28 years). Additionally, a years-of-life-lost analysis was conducted stratified by prevalent diabetes and specific biomarker cut-offs known to be associated with increased risk for events (hs-cTnI >5 ng/L, NTproBNP >125 ng/L, hs-CRP >5mg/L).

Results

We included 95,302 individuals, of whom 6,501 had DM (6.8%). Cox-regression analysis revealed DM to be independently associated with the primary endpoint (2.1 [95% CI 1.9, 2.3], p<0.001) despite adjustment for clinical characteristics and biomarkers. Also, all three biomarkers were independent predictors themselves: log-transformed NT-proBNP 1.3 [95% CI 1.3, 1.4] p<0.001; log-transformed hs-CRP 1.2 [95% CI 1.1, 1.2] p<0.001; third-root-transformed hs-cTnI 1.1 [95% CI 1.0, 1.1] p=0.0038). The sex-, age- and cohort-adjusted HR for the primary endpoint according to absolute biomarker concentrations derived by cox-regression models using cubic splines is provided for the three biomarkers in Figure 1. Upon dichotomization of biomarkers, individuals with diabetes and at least one elevated biomarker lost a median of 15.5 healthy years because of the primary endpoint (Kaplan-Meier plot in Figure 2, with age on the x-axis).

Conclusion

Our findings confirm that diabetes confers a residual cardiovascular risk beyond adjustment for clinical characteristics and cardiovascular biomarker. Furthermore, biomarkers may aid in the identification of patients at highest risk, which should be considered in future models of risk prediction.

Funding Acknowledgement

Type of funding sources: None.
Prediction of all-cause mortality in cardiovascular patients by using machine learning models
Authors: Tsarapatsani K , Pezoulas V , Sakellarios A , Tsakanikas V , Marz W , Kleber M , Michalis L , Fotiadis D
Published: October 2022

Background

Cardiovascular disease (CVD) is the leading cause of death worldwide. The prediction of all-cause death in patients with chronic cardiovascular risk will enable improved preventive strategies.

Purpose

This study aims to predict death of patients, who suffering from cardiovascular disease, within a follow-up period of 20 years. For this purpose was utilized the Ludwigshafen Risk and Cardiovascular Health (LURIC) study was utilized and employed machine learning models.

Methods

The Ludwigshafen Risk and Cardiovascular Health (LURIC) study was used in this analysis, which includes 3,316 patients (mean age 61.98 years, 69.2% male, 1722 deceased patients and 1594 alive or censored patients). After performing feature selection, 23 clinical and laboratory markers were included in our analysis. Pre-processing techniques such as SelectKbest and KNNImputer, were applied to the dataset and then it was splitted into a train and test (30%) set. The prediction of 20-year-risk of death was accomplished using the following machine learning algorithms: Logistic Regression (LR), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGB) and Adaptive Boosting (AdaB). 10-fold cross validation was applied to verify the results of the models.

Results

The efficiency of each machine learning algorithm has been evaluated. XGB outperformed the others, achieving the highest accuracy (76.00%) and Area under (AUC) the Receiver Operating Characteristic Curve (ROC curve) value (0.776). The AUC value of the LR, SVM and AdaB are 0.761, 0.746 and 0.751, respectively. Figure 1 presents the ROC curve and AUC values for all models. Furthermore, the accuracy (ACC), precision, specificity, recall, F1-score and standard deviation were estimated for each classifier (Table 1).

Conclusion

We predicted all-cause mortality in patients with 20 years cardiovascular risk, using machine learning models and data of 3,316 patients. The most accurate predictive model was achieved by the eXtreme Gradient Boosting, with an accuracy equal to 76.00% and an AUC value of 0.776.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): HORIZON2020
Effect of an early invasive strategy based on time of symptom onset in patients with non-ST elevation myocardial infarction
Authors: Bae S A , Cha J J , Kim S W , Lim S , Kim J H , Joo H J , Park J H , Park S M , Hong S J , Yu C W , Lim D S , Jeong M H , Ahn T H
Published: October 2022

Background

A limitation of the current guidelines of the timing of invasive coronary angiography (ICA) for patients with non-ST-segment elevation (NSTE) acute coronary syndrome is based on randomization time. So far, no study has reported the clinical outcomes of invasive strategy timing based on the time of symptom onset. Herein, we aimed to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with NSTE myocardial infarction (MI).

Methods and results

Among 13,104 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health, we evaluated 5,856 patients with NSTEMI. The patients were categorized according to symptom-to-catheter (StC) time (<48 h and ≥48 h). The primary outcome was 3-year all-cause mortality, and the secondary outcome was a 3-year composite of all-cause mortality, recurrent MI, and hospitalization for heart failure. Overall, 3,919 (66.9%) patients were classified into the StC time <48 h group. This group had lower all-cause mortality than the StC time ≥48 h group (7.3% vs. 13.4%, p<0.001). The continuous association of StC time and risk of primary and secondary endpoints showed shorter StC time (reference: 48 h), and lower adjusted hazard ratio reduction was observed. In multivariable analysis, independent predictors of delayed ICA were older age, non-specific symptoms, no use of emergency medical services, no ST-segment deviation, chronic kidney disease, and Global Registry of Acute Coronary Events score >140.

Conclusion

Early invasive strategy based on the StC time improves all-cause mortality in patients with NSTEMI.

Funding Acknowledgement

Type of funding sources: None.
Value of exercise echocardiography in paradoxical low gradient severe aortic stenosis
Authors: Peteiro Vazquez J C , Bouzas-Mosquera A , Vazquez-Rodriguez J M
Published: October 2022

Low-flow and/or low-gradient paradoxical severe aortic stenosis (AS) is a controversial entity from a diagnostic and prognostic point of view. We aimed to assess the role of exercise echocardiography (ExE) in asymptomatic or equivocal symptoms patients with this condition.

Methods

Fifty patients (mean age 74±11 years, 70% women) with severe AS (aortic valve area [AVA] <1 cm2) and low-flow low-gradient (stroke volumen <35 ml/m2; mean gradient <40 mmHg), or only low gradient (n=27) AS, and preserved LV ejection fraction (LVEF >50%) were studied by treadmill ExE. AVA, gradients, LVEF and wall motion score index (WMSI) were assessed.

Results

Maximal achieved workload was 6.7±2.2 metabolic equivalents (METs), and LVEF (%) increased with exercise from 59±8 to 63±10. Symptoms were elicited in 14 patients (8 angina; 6 dyspnea). Five patients had wall motion abnormalities (WMAs) at rest (10%) and 18 at exercise (36%). Angiography showed CAD in 19 patients (exercise WMAs in 10) and was normal in 17 (exercise WMAs in 3). Maximum/mean transaortic gradients increased from 51±12/28±7 mmHg to 68±19/35±8 mmHg with exercise. Fourteen patients had mean gradient ≥40 mmHg with exercise (28%). There was a trend towards smaller AVA at rest and exercise in patients with exercise mean gradient ≥40 mmHg (0.78 vs 0.87 cm2, p=0.06; and 0.83 vs 0.97 cm2, p=0.07). During follow-up of 20±17 months, there were 35 events: 2 deaths, 3 admittances for cardiac failure, 2 myocardial infarctions, 26 prosthesis implantations due to worsening (with coronary intervention in 8), and 2 revascularizations. Independent predictors of events were treatment with digoxine (HR=31.3, 95% CI: 5.2–187.5, p<0.001) and exercise WMSI (HR=12.3, 95% CI: 3.6–41.8, p<0.001).

Conclusions

ExE offers supplementary information in low gradient severe AS. In 1/3 symptoms developed. Also in 1/3 there was significant increase in gradients. The presence of exercise WMAs was able to predict outcome.

Funding Acknowledgement

Type of funding sources: None.
P2Y12 inhibitors monotherapy in patients undergoing complex vs. non-complex percutaneous coronary intervention: a meta-analysis of randomized trials
Authors: Oliva A , Castiello D , Franzone A , Condorelli G , Colombo A , Esposito G , Stefanini G , Piccolo R
Published: October 2022

Background

Monotherapy with P2Y12 inhibitors (P2Y12i) is emerging as alternative strategy to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, early withdrawal of aspirin as part of P2Y12i monotherapy regimens may pose concerns in high-risk patients, such as those undergoing complex PCI.

Purpose

To evaluate the efficacy and safety of P2Y12i monotherapy after a short course of DAPT (1- to 3-month) compared with standard DAPT (≥12-month) according to PCI complexity.

Methods

We performed a meta-analysis of randomized trials using random effects models to combine hazard ratios (HRs) with 95% confidence intervals (CIs). No restrictions were applied to the type of P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) or to the definition of complex PCI. Within-trial interactions were pooled to estimate heterogeneity between complex and noncomplex PCI strata. The study protocol was registered in the PROSPERO (CRD42021291027).

Results

We screened 7,502 unique citations, of which 2,948 were screened at title and abstract level and 576 were judged potentially eligible for full-text assessment. We included in the analysis five trials (1–5) enrolling 31,627 patients, of whom 8,328 (26.3%) underwent complex PCI; characteristics of trials and patient populations are summarized in Table 1. Risk estimates for efficacy and safety outcomes associated with P2Y12i monotherapy and standard DAPT across studies included in the analysis, stratified by complex and noncomplex PCI, are reported in Figure 1. P2Y12i monotherapy compared with standard DAPT was associated with a similar risk of all-cause death, stent thrombosis, and stroke, with no evidence for interaction between complex and noncomplex PCI. We found heterogeneity in the treatment effect of P2Y12i monotherapy vs. standard DAPT with respect to myocardial infarction (P-interaction=0.027). Compared with standard DAPT, P2Y12i monotherapy decreased the risk of myocardial infarction in complex PCI (HR 0.77, 95% CI 0.60–0.99, P=0.042), but not in noncomplex PCI patients (HR 1.09, 95% CI 0.90–1.30, P=0.382). The risk of major bleeding was significantly reduced by P2Y12i monotherapy with a consistent treatment effect (P-interaction=0.699) in both complex and noncomplex PCI strata.

Conclusions

Patients undergoing complex PCI may derive more benefit and less harm from P2Y12i monotherapy after early aspirin withdrawal compared with standard DAPT, resulting in decreased risks of myocardial infarction and bleeding.

Funding Acknowledgement

Type of funding sources: None.
Real-world data from the use of ranolazine in patients with stable angina pectoris: the RANGER study
Authors: Stafylas P , Olympios C , Dermitzakis A , Efthimiadis I , Gardikiotis A , Kakouros S , Lampropoulos S , Barbetseas J , Sourgounis A
Published: October 2022

Background

Although ranolazine is available since years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on effectiveness, tolerability and safety of ranolazine are limited.

Methods

A non-interventional, prospective study conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. Primary endpoints comprised the weekly frequency of angina attacks, total adverse events and ranolazine discontinuation rate. Secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL).

Results

In total, 1,101 patients were enrolled in 214 sites. Mean weekly angina attacks were reduced from 3.6±2.9 to 0.4±0.9 (p<0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7±2.2 (p<0.0001). CCS class and QoL were also improved (p<0.0001). Adverse events were reported by 11 (1%) patients totally, while 2 of them (0.2%) were characterized as serious. Treatment was discontinued for any reason in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes.

Conclusion

Ranolazine was well-tolerated and effectively reduced angina attacks with simultaneous improvement of CCS class and QoL score in patients with stable angina.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): The study was sponsored by Menarini Hellas. The study sponsor was involved in the study concept and design and in the interpretation of the data included in this publication, but not in the data collection and analysis. Menarini Hellas also funded the medical writing support for this publication.
Temporal trends in complex PCI interventions
Authors: Kheifets M , Vons S A , Bental T , Vaknin-Assa H , Perl L , Kornowski R , Levi A
Published: October 2022

Background

Accumulated experience combined with technological advancements in the field of complex percutaneous coronary intervention (C-PCI), have led to a gradual increase in both quantity and complexity of PCI procedures over the last 20 years. Despite the amount and frequency of these complex interventions, data regarding outcomes is lacking.

Methods

The study was based on a prospective registry of 20,301 consecutive procedures with a follow up of at least 1 year. C-PCIs were defined as at least one of the following: Chronic total occlusion (CTO), left main (LM), bifurcation or saphenous vein graft (SVG) PCI. We compared trends during four different time periods (2008–2010, 2011–2013, 2014–2016, 2017–2019). Endpoints included mortality and major adverse cardiac events [MACE: death, repeat myocardial infarction (re-MI), and target vessel revascularization (TVR)] at 1 year.

Results

The rate of C-PCI procedures has risen significantly since 2017 (p<0.01), driven mainly by bifurcation and LM interventions (p<0.01). At 1-year, rates of death (p<0.001), re-MI (p<0.001), TVR (p=0.001) and MACE (p<0.001), were all significantly higher in the C-PCI group, as compared to the non-complex group. Rates of TVR (p=0.01) and MACE (p<0.001) at 1-year, were significantly higher in the C-PCIs which were performed between 2008–2010 and 2011–2013, as compared to C-PCIs performed between 2014–2016 and 2017–2019. Death rates did not significantly differ between C-PCI periods.

Conclusions

Although frequency of C-PCIs is on the rise, overall outcomes become increasingly better, as compared to earlier periods. Unfortunately, this has not translated into a decrease in mortality.

Funding Acknowledgement

Type of funding sources: None.
Isolated functional tricuspid regurgitation, how define patient at-risk for event?
Authors: L'official G , Vely M , Guerin A , Chen E , Dreyfus J , Sportouch C , Oger E , Donal E
Published: October 2022

Introduction

Functional tricuspid regurgitation (TR) is a turning point in cardiac diseases. Symptoms typically appear late, and the optimal timing for proposing a valve repair remains a challenge. We sought to analyse the characteristics of right heart remodelling in patients with significant functional TR to identify the parameters that could be used in an easily achievable and fair prognostic model predicting clinical events.

Methods

We designed a prospective observational French multicentre study including 160 patients with significant functional TR (effective regurgitant orifice area >30mm2) and LVEF >40%. Clinical, echocardiographic, and ECG data were collected at baseline, and at the 1- and 2-year follow-up. The primary outcome was all-cause death or hospitalization for heart failure.

Results

At 2 years, 56 patients (35%) achieved the primary outcome. The subset with events showed more advanced right heart remodelling at baseline, but similar TR severity. Right atrial volume index (RAVI) and the TAPSE/sPAP ratio, reflecting right-ventricle-pulmonary artery coupling, were 73 mL/m2 and 0.40 versus 64.7 mL/m2 and 0.50 in the event vs event-free group, respectively (both p<0.05). None among all the clinical and imaging parameters tested had a significant group × time interaction. In multivariable analysis, the model including TAPSE/sPAP ratio >0.4 (OR=0.41, 95%CL 0.2 to 0.82) and RAVI >60 mL/m2 (OR=2.13, 95%CL 0.96 to 4.75) permitted the fairest and most parsimonious prognostic evaluation.

Conclusion

RAVI and TAPSE/sPAP are relevant for predicting the risk for event at 2-year follow-up in patient with an isolated functional TR.

Funding Acknowledgement

Type of funding sources: None.
Collaterals and extent of myocardial injury in patients with acute coronary syndromes – an analysis of the prospective SPUM-ACS cohort
Authors: Obeid S , Adjibodou B , Denegri A , Kraler S , Katsarov K , Roffi M , Raeber L , Muller O , Staehli B , Luescher T F
Published: October 2022

Introduction

The impact of collateral circulation in the presence of severe coronary artery disease such as chronic total occlusion (CTO) has been extensively studied, with results despite few discrepancies, supporting an overall benefit on preservation of myocardial tissue and left ventricular ejection fraction (LVEF). However, less is known about the protective effects of collaterals in the context of acute coronary syndromes (ACS). In the current study we sought to analyze the incidence, grade and impact of collateral circulation in a large prospectively recruited cohort of patients presenting with ACS with independent events adjudication.

Methods and results

4'546 ACS patients presenting with ACS, enrolled in the prospective Special Program University Medicine ACS (SPUM-ACS) cohort were included. The current analysis showed the presence of a collateralized culprit lesion in 12.9% (n=586) of patients, 84% (n=492) originating from the contralateral side and 16% (n=94) from the ipsilateral side. Of those 64.6% (n=378) were being graded as Rentrop 2 or more. There were no differences in baseline characteristics between the two groups including incidence of diabetes, coronary artery disease, age and gender. However, despite the presence of collaterals graded Rentrop 2 or more, those patients had a significantly lower LVEF mean 48,44% vs 51.6%, p=0.025 and higher creatinine Kinase levels, mean (CK) 981 U/I vs 957 UI, p<0.001 as compared to patients with absent collateral-circulation on admission. Interestingly a sub analysis of the STEMI population showed no significant differences in both LVEF and CK at presentation, while troponin (TNT) plasma levels were significantly lower in patients with collaterals (mean TNT 0.0031 ug/l vs 0.035 ug/l p=0.001). Additionally no differences in cardiovascular mortality, stent thrombosis or MI was seen at one year follow-up.

Conclusion

The current analysis highlights a possible protective impact of a pre-existing collateral circulation against myocardial injury in the setting of ACS and ST elevation myocardial infarction. However this was not translated into improvement in hard outcomes acutely and up to one year of follow up, but may be important in the long run.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Research Foundation - ZurichHeart House
Age as a prognostic modifier in anemic patients discharged after acute coronary syndrome
Authors: Cazorla-Morallon D , Cordero A , Tomas-Simon F J , Sanchez-Munuera S , Alvarez-Alvarez B , Cid-Alvarez B , Garcia-Acuna J M , Rodriguez-Manero M , Escribano D , Bertomeu-Gonzalez V , Zuazola P , Gonzalez-Juanatey J R
Published: October 2022

Introduction

The presence of anemia on admission is a poor long-term prognostic factor in patients diagnosed with acute coronary syndrome (ACS). However, it is unknown whether age is a factor modifying the effect of anemia on mortality.

Objective

To determine the effect of age on anemia in terms of long-term mortality in patients admitted for ACS.

Methods

This is an observational study in which we included all patients discharged from cardiology for ACS in two centers from 2003 to 2020. Patients with anemia were classified by hemoglobin values <13 g/dL in men and <12 g/dL in women in the first blood count performed during hospitalization. The interaction between age and anemia was analyzed using the Cox regression model and the chunk test. We analyzed the effect of anemia on mortality using the Cox regression model adjusted for several confounding variables and the interaction with age.

Results

We included 8872 patients diagnosed with ACS, with a mean age of 66.38 (SD ±12.76) years, 27.1% female and 34.3% diagnosed with ST-segment elevation ACS. The mean hemoglobin value was 13.88 (SD ±1.85) g/dL and 20.5% of patients were anemic on admission.

During follow-up (median 1764 days, IQR 694–2439 days) there was an increased risk of all-cause mortality in patients with anemia adjusted for age and other risk factors (sex, renal function, GRACE score, atrial fibrillation, LVEF and previous revascularization), HR 15.5 (CI 5.77–41.75; p>0.005). We found a significant interaction between age and anemia (p<0.01). As represented in the figure, the adjusted risk of mortality decreased at older ages; in patients whose age was >80 anemia was not associated to higher mortality risk. Similar results were observed for cardiovascular mortality, HR 21.36 (CI 6.13–74.43, p>0.005).

Conclusion

Age modifies the risk of mortality in patients discharged after an ACS being the risk of mortality higher in youngest ages and disappearing in octogenearians. There results should be taken under consideration for the treatment and management of ACS patients.

Funding Acknowledgement

Type of funding sources: None.
Trends in mortality and ischemic outcomes in patients with ST-segment elevation myocardial infarction following implementation of a primary percutaneous coronary intervention strategy, 2003–2017
Authors: Thrane P , Olesen K K W , Thim T , Gyldenkerne C , Kristensen S D , Maeng M
Published: October 2022

Introduction

In Denmark, primary percutaneous coronary intervention (pPCI) has served as the national reperfusion strategy in ST-segment elevation myocardial infarction (STEMI) since 2003. Since then, extensive changes in management and treatment of patients with STEMI have been introduced. We investigated the temporal trends in one-year mortality and ischemic outcomes after STEMI.

Methods

We included all first-time STEMI patients treated with pPCI in Western Denmark from 2003 to 2017. Patients were categorized into four time periods based on year of pPCI treatment (2003–2006, 2007–2010, 2011–2014, 2015–2017) and followed for one year. Outcomes included all-cause death, recurrent myocardial infarction (MI: follow-up started after 30 days post-pPCI since the validity of recurrent MI is low in the first 30 days), and ischemic stroke. We also identified a sex and age matched comparison cohort without prior cardiovascular disease from the Western Denmark general population. Groups were compared using sex- and age-adjusted hazard ratios (aHRs) by Cox regression with the first period as reference.

Results

A total of 18,538 STEMI patients and 92,690 individuals from the general population were included. One-year mortality in STEMI patients decreased from 10.8% in 2003–2006 to 7.8% in 2015–2017 (aHR 0.70, 95% CI 0.60–0.80), while it was steady in the general population cohort (figure). The one-year risk of recurrent MI and ischemic stroke also decreased from 2003–2006 to 2015–2017 (MI: 3.5% vs. 2.4%, aHR: 0.66, 95% CI 0.51–0.86; ischemic stroke: 2.5% vs. 1.9%, aHR 0.58, 95% CI 0.42–0.80). These improvements coincided with increased up-take of evidence-based treatments, especially drug-eluting stents (39% vs. 90%), high-intensity statins (3% vs. 87%), and newer antiplatelet agents.

Conclusions

From 2003 to 2017, the one-year risk of death, recurrent MI, and ischemic stroke decreased substantially among patients with STEMI. These improvements occurred simultaneously with the gradual implementation of evidence-based guideline-directed treatments.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Aase and Ejnar Danielsen foundation
Right ventricular versus left ventricular global longitudinal strain for association with all-cause mortality after transcatheter aortic valve implantation
Authors: Winkler N , Anwer S , Tanner F C
Published: October 2022

Introduction

Speckle-tracking echocardiography plays an increasingly important role in the assessment of aortic stenosis (AS), the most common valvular heart disease in the Western population. Right ventricular (RV) and left ventricular (LV) global longitudinal strain (GLS) were studied for their association with all-cause mortality in AS patients undergoing transcatheter aortic valve implantation (TAVI).

Purpose

To investigate whether simultaneous assessment of RV and LV GLS provides a better association with all-cause mortality during long-term follow-up after TAVI.

Methods

In our prospective registry we identified 109 patients with severe AS who underwent TAVI and had a pre-procedural echocardiography within three months of the procedure allowing complete assessment of RV and LV GLS using TomTec Image Arena. All-cause mortality was defined as endpoint.

Results

RV GLS was lower among non-survivors (N=36; median [IQR]: −13.94 [−16.31 to −12.62]; p<0.001) than survivors (N=73; −17.04 [−20.16 to −15.22]; p<0.001), while LV GLS did not differ (p=0.249). RV GLS >−16.6% differentiated survivors from non-survivors (sensitivity 78%; specificity 63%; ROC AUC 71%; p<0.001), while LV GLS did not (p=0.243). Kaplan Meier curves showed good differentiation of survivors and non-survivors with the RV GLS (p<0.001; Figure 1), but not the LV GLS cut-off (p=0.058). In univariable Cox regression models, RV GLS was associated with all-cause mortality (HR 1.10 [95% CI 1.02 to 1.18]; χ2=6.64; p=0.01), while LV GLS was not (HR 1.05 [0.96 to 1.16]; χ2=1.08; p=0.299). In bivariable models, association of RV GLS with all-cause mortality was independent of LV GLS or LV ejection fraction (LVEF; Table 1). ANOVA likelihood ratios revealed that inclusion of RV GLS to LV GLS or LVEF improved their model fitness, while that of LV GLS did not (Table).

Conclusion

RV GLS was associated with all-cause mortality after TAVI, while LV GLS and LVEF were not. The association of RV GLS was independent of LV GLS and LVEF and showed potential incremental value for assessment of outcome association, while LV GLS did not.

Funding Acknowledgement

Type of funding sources: None.
Peak atrial longitudinal strain as an independent predictor of composite endpoint in patients received aortic valve replacement for severe aortic stenosis: a prospective cohort study
Authors: Tsui L , Tse Y K , Yu S Y , Li H L , Ren Q W , Wu M Z , Yu S Y , Tse H F , Yiu K H
Published: October 2022

Objective

Severe aortic stenosis (AS) is the primary valvular heart disease, treatable only by aortic valve replacement (AVR). The prognostic value of pre-operative left atrial (LA) function on post-AVR clinical outcomes is uncertain. The study aims to evaluate the prognostic value of pre-operative peak atrial longitudinal strain (PALS) as a surrogate of LA function on post AVR all-cause mortality and heart failure hospitalisation.

Methods

Patients aged 18 years old or above with severe AS were recruited and assessed using speckle-tracking echocardiography pre-operatively. Severe AS was defined according to 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. PALS was measured. Based on the median value of PALS, patients were stratified into PALS <15.94% and PALS >15.94%. Patients with underlying pre-operative atrial fibrillation, other moderate to severe valvular heart diseases and cancers were excluded. Patients were followed up until death, heart failure hospitalisation or end of the study. The primary outcome is a composite endpoint of all-cause mortality and heart failure hospitalisation. The association of PALS with the composite endpoint was evaluated by Cox Proportional Hazards analysis.

Results

A total of 128 patients (mean age 65.32±9.42 years, 56.3% male) were prospectively analyzed. Patients were followed up for a mean period of 3.9±2.4 years. A total of 65 of 128 patients (50.8%) belonged to PALS<15.94%. During the study period, 23 patients developed the adverse events. A lower pre-operative PALS, both as a continuous or a categorical variable, were associated with a higher unadjusted risk of adverse events (Continuous; HR, 0.93; 95% CI 0.88–0.98; p=0.011; PALS <15.94%; HR, 4.94; 95% CI, 1.67–14.58; p=0.004).

Conclusion

The study demonstrated a lower pre-operative PALS is associated with all-cause mortality and heart failure admission in patients with severe AS undergoing AVR. Evaluation of LA function by assessing speckle tracking derived PALS may aid in prognostication for patients undergoing AVR.

Funding Acknowledgement

Type of funding sources: None.