Journal: Eur Heart J

Sorted by: date / impact
Abstract

Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy.

Li S, Liu Z, Joseph P, Hu B, ... Yusuf S, Li W
Aims
To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome.
Methods and results
In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%).
Conclusion
Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 22 Jun 2022; epub ahead of print
Li S, Liu Z, Joseph P, Hu B, ... Yusuf S, Li W
Eur Heart J: 22 Jun 2022; epub ahead of print | PMID: 35731140
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiovascular disease, mortality, and their associations with modifiable risk factors in a multi-national South Asia cohort: a PURE substudy.

Joseph P, Kutty VR, Mohan V, Kumar R, ... Gupta R, Yusuf S
Aim
To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia.
Methods and results
Prospective study of 33 583 individuals 35-70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%).
Conclusion
In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 22 Jun 2022; epub ahead of print
Joseph P, Kutty VR, Mohan V, Kumar R, ... Gupta R, Yusuf S
Eur Heart J: 22 Jun 2022; epub ahead of print | PMID: 35731159
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Implantable defibrillators in primary prevention of genetic arrhythmias. A shocking choice?

Corrado D, Link MS, Schwartz PJ
Many previously unexplained life-threatening ventricular arrhythmias and sudden cardiac deaths (SCDs) in young individuals are now recognized to be genetic in nature and are ascribed to a growing number of distinct inherited arrhythmogenic diseases. These include hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (VT), and short QT syndrome. Because of their lower frequency compared to coronary disease, risk factors for SCD are not very precise in patients with inherited arrhythmogenic diseases. As randomized studies are generally non-feasible and may even be ethically unjustifiable, especially in the presence of effective therapies, the risk assessment of malignant arrhythmic events such as SCD, cardiac arrest due to ventricular fibrillation (VF), appropriate implantable cardioverter defibrillator (ICD) interventions, or ICD therapy on fast VT/VF to guide ICD implantation is based on observational data and expert consensus. In this document, we review risk factors for SCD and indications for ICD implantation and additional therapies. What emerges is that, allowing for some important differences between cardiomyopathies and channelopathies, there is a growing and disquieting trend to create, and then use, semi-automated systems (risk scores, risk calculators, and, to some extent, even guidelines) which then dictate therapeutic choices. Their common denominator is a tendency to favour ICD implantation, sometime with reason, sometime without it. This contrasts with the time-honoured approach of selecting, among the available therapies, the best option (ICDs included) based on the clinical judgement for the specific patient and after having assessed the protection provided by optimal medical treatment.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 21 Jun 2022; epub ahead of print
Corrado D, Link MS, Schwartz PJ
Eur Heart J: 21 Jun 2022; epub ahead of print | PMID: 35725934
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hypertensive disorders of pregnant women with heart disease: the ESC EORP ROPAC Registry.

Ramlakhan KP, Malhamé I, Marelli A, Rutz T, ... Cornette J, Roos-Hesselink JW
Aims
Hypertensive disorders of pregnancy (HDP) occur in 10% of pregnancies in the general population, pre-eclampsia specifically in 3-5%. Hypertensive disorders of pregnancy may have a high prevalence in, and be poorly tolerated by, women with heart disease.
Methods and results
The prevalence and outcomes of HDP (chronic hypertension, gestational hypertension or pre-eclampsia) were assessed in the ESC EORP ROPAC (n = 5739), a worldwide prospective registry of pregnancies in women with heart disease.The overall prevalence of HDP was 10.3%, made up of chronic hypertension (5.9%), gestational hypertension (1.3%), and pre-eclampsia (3%), with significant differences between the types of underlying heart disease (P < 0.05). Pre-eclampsia rates were highest in women with pulmonary arterial hypertension (PAH) (11.1%), cardiomyopathy (CMP) (7.1%), and ischaemic heart disease (IHD) (6.3%). Maternal mortality was 1.4 and 0.6% in women with vs. without HDP (P = 0.04), and even 3.5% in those with pre-eclampsia. All pre-eclampsia-related deaths were post-partum and 50% were due to heart failure. Heart failure occurred in 18.5 vs. 10.6% of women with vs. without HDP (P < 0.001) and in 29.1% of those with pre-eclampsia. Perinatal mortality was 3.1 vs. 1.7% in women with vs. without HDP (P = 0.019) and 4.7% in those with pre-eclampsia.
Conclusion
Hypertensive disorders of pregnancy and pre-eclampsia rates were higher in women with CMP, IHD, and PAH than in the general population. Adverse outcomes were increased in women with HDP, and maternal mortality was strikingly high in women with pre-eclampsia. The combination of HDP and heart disease should prompt close surveillance in a multidisciplinary context and the diagnosis of pre-eclampsia requires hospital admission and continued monitoring during the post-partum period.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 21 Jun 2022; epub ahead of print
Ramlakhan KP, Malhamé I, Marelli A, Rutz T, ... Cornette J, Roos-Hesselink JW
Eur Heart J: 21 Jun 2022; epub ahead of print | PMID: 35727736
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.

Perea-Gil I, Seeger T, Bruyneel AAN, Termglinchan V, ... Mercola M, Karakikes I
Aims
Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. Despite significant progress in understanding the genetic aetiologies of DCM, the molecular mechanisms underlying the pathogenesis of familial DCM remain unknown, translating to a lack of disease-specific therapies. The discovery of novel targets for the treatment of DCM was sought using phenotypic sceening assays in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that recapitulate the disease phenotypes in vitro.
Methods and results
Using patient-specific iPSCs carrying a pathogenic TNNT2 gene mutation (p.R183W) and CRISPR-based genome editing, a faithful DCM model in vitro was developed. An unbiased phenotypic screening in TNNT2 mutant iPSC-derived cardiomyocytes (iPSC-CMs) with small molecule kinase inhibitors (SMKIs) was performed to identify novel therapeutic targets. Two SMKIs, Gö 6976 and SB 203580, were discovered whose combinatorial treatment rescued contractile dysfunction in DCM iPSC-CMs carrying gene mutations of various ontologies (TNNT2, TTN, LMNA, PLN, TPM1, LAMA2). The combinatorial SMKI treatment upregulated the expression of genes that encode serine, glycine, and one-carbon metabolism enzymes and significantly increased the intracellular levels of glucose-derived serine and glycine in DCM iPSC-CMs. Furthermore, the treatment rescued the mitochondrial respiration defects and increased the levels of the tricarboxylic acid cycle metabolites and ATP in DCM iPSC-CMs. Finally, the rescue of the DCM phenotypes was mediated by the activating transcription factor 4 (ATF4) and its downstream effector genes, phosphoglycerate dehydrogenase (PHGDH), which encodes a critical enzyme of the serine biosynthesis pathway, and Tribbles 3 (TRIB3), a pseudokinase with pleiotropic cellular functions.
Conclusions
A phenotypic screening platform using DCM iPSC-CMs was established for therapeutic target discovery. A combination of SMKIs ameliorated contractile and metabolic dysfunction in DCM iPSC-CMs mediated via the ATF4-dependent serine biosynthesis pathway. Together, these findings suggest that modulation of serine biosynthesis signalling may represent a novel genotype-agnostic therapeutic strategy for genetic DCM.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 21 Jun 2022; epub ahead of print
Perea-Gil I, Seeger T, Bruyneel AAN, Termglinchan V, ... Mercola M, Karakikes I
Eur Heart J: 21 Jun 2022; epub ahead of print | PMID: 35728000
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease.

Pandey AK, Bhatt DL, Cosentino F, Marx N, ... Butler J, Verma S
Despite existing treatments, patients with heart failure and chronic kidney disease (CKD) remain at high risk for adverse outcomes and progression to end-stage disease. Steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone reduce mortality but remain under-prescribed due to the perceived risk of hyperkalaemia and hormonal side effects. The discovery of non-steroidal MRAs represents a major new dimension in cardiorenal disease therapy. Non-steroidal MRAs have high affinity and specificity for the mineralocorticoid receptor (MR) and differ from both steroidal agents and each other with respect to important physiochemical, pharmacodynamic, and pharmacokinetic parameters. Similar to their steroidal counterparts, they have beneficial anti-inflammatory, anti-remodelling, and anti-fibrotic properties in the kidneys, heart, and vasculature. There are several non-steroidal MRAs under development and clinical assessment; of these, only esaxerenone and finerenone are approved for treatment globally. In Japan, esaxerenone is approved for essential hypertension and has been studied in diabetic nephropathy. Compared with steroidal MRAs, finerenone more potently inhibits MR co-regulator recruitment and fibrosis and distributes more evenly between the heart and kidneys. The landmark Phase III trials FIGARO-DKD and FIDELIO-DKD demonstrated that finerenone-reduced major kidney and cardiovascular events on top of maximally tolerated renin-angiotensin-aldosterone system inhibition in patients with CKD associated with Type 2 diabetes. Non-steroidal MRAs are currently under evaluation in heart failure and for synergistic treatment with sodium-glucose contransporter 2 inhibitors. These ground-breaking agents could become an important therapy across the spectrum of cardiorenal disease.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 17 Jun 2022; epub ahead of print
Pandey AK, Bhatt DL, Cosentino F, Marx N, ... Butler J, Verma S
Eur Heart J: 17 Jun 2022; epub ahead of print | PMID: 35713973
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Functional stress imaging to predict abnormal coronary fractional flow reserve: the PACIFIC 2 study.

Driessen RS, van Diemen PA, Raijmakers PG, Knuuti J, ... Danad I, Knaapen P
Aims
The diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI).
Methods and results
In this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, [15O]H2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58-76%) for SPECT, 81% (72-87%) for PET, and 66% (56-75%) for MRI. Specificity was 61% (48-72%) for SPECT, 65% (53-76%) for PET, and 62% (49-74%) for MRI. Sensitivity of PET was higher than SPECT (P = 0.016) and MRI (P = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68-81%) did not statistically differ from SPECT (65%, 58-72%, P = 0.03) and MRI (64%, 57-72%, P = 0.052). Using FFR < 0.75 as a reference, accuracies increased to 69% (SPECT), 79% (PET), and 71% (MRI).
Conclusion
In this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 16 Jun 2022; epub ahead of print
Driessen RS, van Diemen PA, Raijmakers PG, Knuuti J, ... Danad I, Knaapen P
Eur Heart J: 16 Jun 2022; epub ahead of print | PMID: 35708168
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Single versus multiple arterial grafting in diabetic patients at 10 years: the Arterial Revascularization Trial.

Taggart DP, Audisio K, Gerry S, Robinson NB, ... Gaudino M, ART Investigators
Aims
To evaluate the impact of multiple arterial grafting (MAG) vs. single arterial grafting (SAG) in a post hoc analysis of 10-year outcomes in patients with diabetes mellitus (DM) from the Arterial Revascularization Trial (ART).
Methods and results
The primary endpoint was all-cause mortality and the secondary endpoint was a composite of major adverse cardiac events (MACE) at 10-year follow-up. Patients were stratified by diabetes status (non-DM and DM) and grafting strategy (MAG vs. SAG). A total of 3020 patients were included in the analysis; 716 (23.7%) had DM. Overall, 55.8% non-DM patients received MAG and 44.2% received SAG, while 56.6% DM patients received MAG and 43.4% received SAG. The use of MAG compared with SAG was associated with lower 10-year mortality for both non-DM [17.7 vs. 21.0%, adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.72-1.06] and DM patients (21.5 vs. 29.9%, adjusted HR 0.65, 95% CI 0.48-0.89; P for interaction = 0.12). For both groups, the rate of 10-year MACE was also lower for MAG vs. SAG. Overall, deep sternal wound infections (DSWIs) were uncommon but more frequent in the MAG vs. SAG group in both non-DM (3.3 vs. 2.1%) and DM patients (7.9 vs. 4.8%). The highest rates of DSWI were in insulin-treated patients receiving MAG (9.6 vs. 6.3%, when compared with SAG).
Conclusion
In this post hoc analysis of the ART, MAG was associated with substantially lower mortality rates at 10 years after coronary artery bypass grafting in patients with DM. Patients with DM receiving MAG had a higher incidence of DSWI, especially if insulin dependent.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 14 Jun 2022; epub ahead of print
Taggart DP, Audisio K, Gerry S, Robinson NB, ... Gaudino M, ART Investigators
Eur Heart J: 14 Jun 2022; epub ahead of print | PMID: 35699416
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled.

Ferreira JP, Zannad F, Butler J, Filipattos G, ... Anker SD, Packer M
Aims
Hyperkalaemia frequently leads to interruption and discontinuation of neurohormonal antagonists, which may worsen heart failure prognosis. Some studies suggested that sodium-glucose cotransporter 2 inhibitors reduce hyperkalaemia, an effect that may have important clinical implications. This analysis evaluates the effect of empagliflozin on the occurrence of hyper- and hypokalaemia in HF.
Methods and results
EMPEROR-Pooled (i.e. EMPEROR-Reduced and EMPEROR-Preserved combined) included 9583 patients with available serum potassium levels at baseline (98.6% of the total EMPEROR-Pooled population, n = 9718). Hyperkalaemia was identified by investigators\' reports of adverse events, and by a laboratory serum potassium value above 5.5 mmol/L and 6.0 mmol/L. The main outcome was a composite of investigator-reported hyperkalaemia or initiation of potassium binders. Patients with high potassium at baseline were more frequently diagnosed with diabetes and ischaemic HF aetiology and had lower left ventricular ejection fraction and estimated glomerular filtration rate but were more frequently treated with sacubitril/valsartan or mineralocorticoid receptor antagonists. Empagliflozin (compared with placebo) reduced the composite of investigator-reported hyperkalaemia or initiation of potassium binders [6.5% vs. 7.7%, hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71-0.95, P = 0.01]. Empagliflozin reduced hyperkalaemia rates regardless of the definition used (serum potassium >5.5 mmol/l: 8.6% vs. 9.9%, HR 0.85, 95% CI 0.74-0.97, P = 0.017; serum potassium >6.0 mmol/l: 1.9% vs. 2.9%, HR 0.62, 95% CI 0.48-0.81, P < 0.001). The incidence of hypokalaemia (investigator-reported or serum potassium <3.0 mmol/l) was not significantly increased with empagliflozin.
Conclusions
Empagliflozin reduced the incidence of hyperkalaemia without significant increase in hypokalaemia.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 10 Jun 2022; epub ahead of print
Ferreira JP, Zannad F, Butler J, Filipattos G, ... Anker SD, Packer M
Eur Heart J: 10 Jun 2022; epub ahead of print | PMID: 35687107
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A new score for life-threatening ventricular arrhythmias and sudden cardiac death in adults with transposition of the great arteries and a systemic right ventricle.

Ladouceur M, Van De Bruaene A, Kauling R, Budts W, ... Wong T, Gatzoulis MA
Aims
To investigate the incidence of major adverse ventricular arrhythmias and related events (MAREs) and to develop a stratification tool predicting MAREs in adults with a systemic right ventricle (sRV).
Methods and results
In a multicentre approach, all adults (≥16 years old) with a sRV undergoing follow-up between 2000 and 2018 were identified. The incidence of MAREs, defined as sudden cardiac death, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) therapy, was analysed. The association of MAREs with clinical, electrical, and echocardiographic parameters was evaluated. A total of 1184 patients (median age 27.1 years; interquartile range 19.9-34.9 years; 59% male; 70% with atrial switch repair for D-transposition of the great arteries) were included. The incidence of MAREs was 6.3 per 1000 patient-years. On multivariate analysis, age, history of heart failure, syncope, QRS duration, severe sRV dysfunction and at least moderate left ventricular outflow tract obstruction were retained in the final model with a C-index of 0.78 [95% confidence interval (CI) 0.72-0.83] and a calibration slope of 0.93 (95% CI 0.64-1.21). For every five ICDs implanted in patients with a 5-year MARE risk >10%, one patient may potentially be spared from a MARE.
Conclusion
Sudden cardiac death remains a devastating cause of death in a contemporary adult cohort with a sRV. A prediction model based on clinical, electrocardiographic, and echocardiographic parameters was devised to estimate MARE risk and to identify high-risk patients who may benefit from primary prevention ICD implantation.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 08 Jun 2022; epub ahead of print
Ladouceur M, Van De Bruaene A, Kauling R, Budts W, ... Wong T, Gatzoulis MA
Eur Heart J: 08 Jun 2022; epub ahead of print | PMID: 35673927
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Outcomes of culture-negative vs. culture-positive infective endocarditis: the ESC-EORP EURO-ENDO registry.

Kong WKF, Salsano A, Giacobbe DR, Popescu BA, ... Habib G, Lancellotti P
Aim
Fatality of infective endocarditis (IE) is high worldwide, and its diagnosis remains a challenge. The objective of the present study was to compare the clinical characteristics and outcomes of patients with culture-positive (CPIE) vs. culture-negative IE (CNIE).
Methods and results
This was an ancillary analysis of the ESC-EORP EURO-ENDO registry. Overall, 3113 patients who were diagnosed with IE during the study period were included in the present study. Of these, 2590 (83.2%) had CPIE, whereas 523 (16.8%) had CNIE. As many as 1488 (48.1%) patients underwent cardiac surgery during the index hospitalization, 1259 (48.8%) with CPIE and 229 (44.5%) with CNIE. The CNIE was a predictor of 1-year mortality [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.04-1.56], whereas surgery was significantly associated with survival (HR 0.49, 95% CI 0.41-0.58). The 1-year mortality was significantly higher in CNIE than CPIE patients in the medical subgroup, but it was not significantly different in CNIE vs. CPIE patients who underwent surgery.
Conclusion
The present analysis of the EURO-ENDO registry confirms a higher long-term mortality in patients with CNIE compared with patients with CPIE. This difference was present in patients receiving medical therapy alone and not in those who underwent surgery, with surgery being associated with reduced mortality. Additional efforts are required both to improve the aetiological diagnosis of IE and identify CNIE cases early before progressive disease potentially contraindicates surgery.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 08 Jun 2022; epub ahead of print
Kong WKF, Salsano A, Giacobbe DR, Popescu BA, ... Habib G, Lancellotti P
Eur Heart J: 08 Jun 2022; epub ahead of print | PMID: 35695691
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiopulmonary exercise testing and efficacy of percutaneous coronary intervention: a substudy of the ORBITA trial.

Ganesananthan S, Rajkumar CA, Foley M, Thompson D, ... Howard J, Al-Lamee R
Aims
Oxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. The aim of this analysis was to examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome and to determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI).
Methods and results
Patients with severe single-vessel coronary artery disease (CAD) were randomized 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomization treadmill CPET, dobutamine stress echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period.A total of 195 patients with CPET data were randomized (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score [+0.82 segments; 95% confidence interval (CI): 0.40 to 1.25, P = 0.0068] and lower fractional flow reserve (-0.07; 95% CI: -0.12 to -0.02, P = 0.011) compared with those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score [oxygen-pulse plateau presence (Pinteraction = 0.026) and oxygen-pulse gradient (Pinteraction = 0.023)] and Seattle angina physical-limitation score [oxygen-pulse plateau presence (Pinteraction = 0.037)]. Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse, and oxygen uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI.
Conclusion
Although selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel CAD.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 26 May 2022; epub ahead of print
Ganesananthan S, Rajkumar CA, Foley M, Thompson D, ... Howard J, Al-Lamee R
Eur Heart J: 26 May 2022; epub ahead of print | PMID: 35639660
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.

van Smeden M, Heinze G, Van Calster B, Asselbergs FW, ... Boulesteix AL, Moons KGM
The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 26 May 2022; epub ahead of print
van Smeden M, Heinze G, Van Calster B, Asselbergs FW, ... Boulesteix AL, Moons KGM
Eur Heart J: 26 May 2022; epub ahead of print | PMID: 35639667
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Three-dimensional printing, holograms, computational modelling, and artificial intelligence for adult congenital heart disease care: an exciting future.

Chessa M, Van De Bruaene A, Farooqi K, Valverde I, ... Little SH, Gatzoulis MA
Congenital heart disease (CHD) is often comprised of complex three-dimensional (3D) anatomy that must be well understood to assess the pathophysiological consequences and guide therapy. Thus, detailed cardiac imaging for early detection and planning of interventional and/or surgical treatment is paramount. Advanced technologies have revolutionized diagnostic and therapeutic practice in CHD, thus playing an increasing role in its management. Traditional reliance on standard imaging modalities including echocardiography, cardiac computed tomography (CT) and magnetic resonance imaging (MRI) has been augmented by the use of recent technologies such as 3D printing, virtual reality, augmented reality, computational modelling, and artificial intelligence because of insufficient information available with these standard imaging techniques. This has created potential opportunities of incorporating these technologies into routine clinical practice to achieve the best outcomes through delivery of personalized medicine. In this review, we provide an overview of these evolving technologies and a new approach enabling physicians to better understand their real-world application in adult CHD as a prelude to clinical workflow implementation.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 24 May 2022; epub ahead of print
Chessa M, Van De Bruaene A, Farooqi K, Valverde I, ... Little SH, Gatzoulis MA
Eur Heart J: 24 May 2022; epub ahead of print | PMID: 35608227
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Characteristics and natural history of early-stage cardiac transthyretin amyloidosis.

Law S, Bezard M, Petrie A, Chacko L, ... Fontana M, Gillmore JD
Aims
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly diagnosed at an early stage of the disease natural history, defined as National Amyloidosis Centre (NAC) ATTR Stage I. The natural history of early-stage ATTR-CM remains poorly characterized.
Methods and results
A retrospective multi-centre observational study of 879 patients with ATTR-CM, either wild-type TTR genotype or carrying the p.V142I TTR variant, and NAC ATTR Stage I biomarkers at the time of diagnosis who did not receive disease-modifying therapy for amyloidosis. Disease characteristics at diagnosis that were independently associated with mortality by Cox regression analysis were N-terminal pro-B-type natriuretic peptide (NT-proBNP), TTR genotype, and troponin T. Patients were categorized into NAC ATTR Stage Ia, defined as a furosemide equivalent diuretic requirement of <0.75 mg/kg and an NT-proBNP ≤500 ng/L or ≤1000 ng/L in the presence of atrial fibrillation, and NAC ATTR Stage Ib comprising all remaining Stage I patients. Median estimated survival among the 88% NAC ATTR Stage Ib patients was 75 (95% CI 57-93) months compared with >100 months in the 12% with Stage Ia disease [hazard ratio for death 5.06 (95% confidence interval 1.23-20.87); P = 0.025] despite significant cardiovascular morbidity at the time of diagnosis which increased during follow-up, including among patients diagnosed in NAC ATTR Stage Ia. Estimated survival among UK NAC ATTR Stage Ia patients was comparable to UK general population controls (P = 0.297).
Conclusion
Patients with NAC ATTR Stage I ATTR-CM can be further stratified according to NT-proBNP concentration and diuretic requirement at diagnosis. Patients with Stage Ia ATTR-CM have significant cardiovascular morbidity despite good short- and mid-term survival.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 24 May 2022; epub ahead of print
Law S, Bezard M, Petrie A, Chacko L, ... Fontana M, Gillmore JD
Eur Heart J: 24 May 2022; epub ahead of print | PMID: 35608040
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial.

Metra M, Pagnesi M, Claggett BL, Díaz R, ... Malik FI, Teerlink JR
Aim
Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF).
Methods and results
The GALACTIC-HF enrolled patients with baseline SBP ≥85 mmHg with a primary outcome of time to cardiovascular death or first heart failure event. In this analysis, patients were divided according to their baseline SBP (≤100 vs. >100 mmHg). Among the 8232 analysed patients, 1473 (17.9%) had baseline SBP ≤100 mmHg and 6759 (82.1%) had SBP >100 mmHg. The primary outcome occurred in 715 (48.5%) and 2415 (35.7%) patients with SBP ≤100 and >100 mmHg, respectively. Patients with lower SBP were at higher risk of adverse outcomes. Omecamtiv mecarbil, compared with placebo, appeared to be more effective in reducing the primary composite endpoint in patients with SBP ≤100 mmHg [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.94] compared with those with SBP >100 mmHg (HR, 0.95; 95% CI, 0.88-1.03; P-value for interaction = 0.051). In both groups, omecamtiv mecarbil did not change SBP values over time and did not increase the risk of adverse events, when compared with placebo.
Conclusion
In GALACTIC-HF, risk reduction of heart failure outcomes with omecamtiv mecarbil compared with placebo was large and significant in patients with low SBP. Omecamtiv mecarbil did not affect SBP and was well tolerated independent of SBP values.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 22 May 2022; epub ahead of print
Metra M, Pagnesi M, Claggett BL, Díaz R, ... Malik FI, Teerlink JR
Eur Heart J: 22 May 2022; epub ahead of print | PMID: 35675469
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

Collet JP, Van Belle E, Thiele H, Berti S, ... Montalescot G, ATLANTIS Investigators of the ACTION Group
Aims
The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care.
Methods and results
After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban.
Conclusion
After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 18 May 2022; epub ahead of print
Collet JP, Van Belle E, Thiele H, Berti S, ... Montalescot G, ATLANTIS Investigators of the ACTION Group
Eur Heart J: 18 May 2022; epub ahead of print | PMID: 35583186
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Duration of Antiplatelet Therapy After Complex Percutaneous Coronary Intervention In Patients at High Bleeding Risk: a MASTER DAPT trial sub-analysis.

Valgimigli M, Smits PC, Frigoli E, Bongiovanni D, ... Vranckx P, MASTER DAPT Investigators
Aims
To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS).
Methods and results
In the MASTER DAPT trial, 3383 patients underwent noncomplex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, stroke, and Bleeding Academic Research Consortium [BARC] 3 or 5 bleeding events); major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and type 2, 3, or 5 BARC bleeding.NACE and MACCE did not differ with abbreviated versus standard DAPT among patients with complex (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.69-1.52, and HR: 1.24, 95% CI: 0.79-1.92, respectively) and noncomplex PCI (HR: 0.90, 95% CI: 0.71-1.15, and HR: 0.91, 95% CI: 0.69-1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3 or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42-0.98, and HR: 0.70; 95% CI: 0.55-0.89; Pinteraction = 0.72). Among the 2,816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3 or 5 was lower with abbreviated DAPT.
Conclusion
In HBR patients free from recurrent ischemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 17 May 2022; epub ahead of print
Valgimigli M, Smits PC, Frigoli E, Bongiovanni D, ... Vranckx P, MASTER DAPT Investigators
Eur Heart J: 17 May 2022; epub ahead of print | PMID: 35580836
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Twitter promotion is associated with higher citation rates of cardiovascular articles: the ESC Journals Randomized Study.

Ladeiras-Lopes R, Vidal-Perez R, Santos-Ferreira D, Alexander M, ... Crea F, Lüscher TF
The association between the dissemination of scientific articles on Twitter and online visibility (as assessed by the Altmetric Score) is still controversial, and the impact on citation rates has never been rigorously addressed for cardiovascular medicine journals using a randomized design. The ESC Journals Study randomized 695 papers published in the ESC Journal Family (March 2018-May 2019) for promotion on Twitter or to a control arm (with no active tweeting from ESC channels) and aimed to assess whether Twitter promotion was associated with an increase in citation rates (primary endpoint) and of the Altmetric Score. This is the final analysis including 694 articles (one paper excluded due to retraction). After a median follow-up of 994 days (interquartile range: 936-1063 days), Twitter promotion of articles was associated with a 1.12 (95% confidence interval: 1.08-1.15) higher rate of citations, and this effect was independent of the type of article. Altmetric Attention Score and number of users tweeting were positive predictors for the number of citations. A social media strategy of Twitter promotion for cardiovascular medicine papers seems to be associated with increased online visibility and higher numbers of citations.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 14 May 2022; 43:1794-1798
Ladeiras-Lopes R, Vidal-Perez R, Santos-Ferreira D, Alexander M, ... Crea F, Lüscher TF
Eur Heart J: 14 May 2022; 43:1794-1798 | PMID: 35567549
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Vascular dysfunction and increased cardiovascular risk in hypospadias.

Lucas-Herald AK, Montezano AC, Alves-Lopes R, Haddow L, ... Ahmed SF, Touyz RM
Aims
Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease.
Methods and results
Our human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P < 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P < 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4-5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5-11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7-114.3, P = 0.02).
Conclusion
Hypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 14 May 2022; 43:1832-1845
Lucas-Herald AK, Montezano AC, Alves-Lopes R, Haddow L, ... Ahmed SF, Touyz RM
Eur Heart J: 14 May 2022; 43:1832-1845 | PMID: 35567552
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

Edsfeldt A, Swart M, Singh P, Dib L, ... Goncalves I, Monaco C
Aims
Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability.
Methods and results
Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE-/- mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE-/-Irf5-/- mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts.
Conclusion
Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 14 May 2022; 43:1864-1877
Edsfeldt A, Swart M, Singh P, Dib L, ... Goncalves I, Monaco C
Eur Heart J: 14 May 2022; 43:1864-1877 | PMID: 35567557
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Targeting the CCL2-CCR2 axis for atheroprotection.

Georgakis MK, Bernhagen J, Heitman LH, Weber C, Dichgans M
Decades of research have established atherosclerosis as an inflammatory disease. Only recently though, clinical trials provided proof-of-concept evidence for the efficacy of anti-inflammatory strategies with respect to cardiovascular events, thus offering a new paradigm for lowering residual vascular risk. Efforts to target the inflammasome-interleukin-1β-interleukin-6 pathway have been highly successful, but inter-individual variations in drug response, a lack of reduction in all-cause mortality, and a higher rate of infections also highlight the need for a second generation of anti-inflammatory agents targeting atherosclerosis-specific immune mechanisms while minimizing systemic side effects. CC-motif chemokine ligand 2/monocyte-chemoattractant protein-1 (CCL2/MCP-1) orchestrates inflammatory monocyte trafficking between the bone marrow, circulation, and atherosclerotic plaques by binding to its cognate receptor CCR2. Adding to a strong body of data from experimental atherosclerosis models, a coherent series of recent large-scale genetic and observational epidemiological studies along with data from human atherosclerotic plaques highlight the relevance and therapeutic potential of the CCL2-CCR2 axis in human atherosclerosis. Here, we summarize experimental and human data pinpointing the CCL2-CCR2 pathway as an emerging drug target in cardiovascular disease. Furthermore, we contextualize previous efforts to interfere with this pathway, scrutinize approaches of ligand targeting vs. receptor targeting, and discuss possible pathway-intrinsic opportunities and challenges related to pharmacological targeting of the CCL2-CCR2 axis in human atherosclerotic disease.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 14 May 2022; 43:1799-1808
Georgakis MK, Bernhagen J, Heitman LH, Weber C, Dichgans M
Eur Heart J: 14 May 2022; 43:1799-1808 | PMID: 35567558
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Bone marrow activation in response to metabolic syndrome and early atherosclerosis.

Devesa A, Lobo-González M, Martínez-Milla J, Oliva B, ... Ibanez B, Fuster V
Aims
Experimental studies suggest that increased bone marrow (BM) activity is involved in the association between cardiovascular risk factors and inflammation in atherosclerosis. However, human data to support this association are sparse. The purpose was to study the association between cardiovascular risk factors, BM activation, and subclinical atherosclerosis.
Methods and results
Whole body vascular 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) was performed in 745 apparently healthy individuals [median age 50.5 (46.8-53.6) years, 83.8% men] from the Progression of Early Subclinical Atherosclerosis (PESA) study. Bone marrow activation (defined as BM 18F-FDG uptake above the median maximal standardized uptake value) was assessed in the lumbar vertebrae (L3-L4). Systemic inflammation was indexed from circulating biomarkers. Early atherosclerosis was evaluated by arterial metabolic activity by 18F-FDG uptake in five vascular territories. Late atherosclerosis was evaluated by fully formed plaques on MRI. Subjects with BM activation were more frequently men (87.6 vs. 80.0%, P = 0.005) and more frequently had metabolic syndrome (MetS) (22.2 vs. 6.7%, P < 0.001). Bone marrow activation was significantly associated with all MetS components. Bone marrow activation was also associated with increased haematopoiesis-characterized by significantly elevated leucocyte (mainly neutrophil and monocytes) and erythrocyte counts-and with markers of systemic inflammation including high-sensitivity C-reactive protein, ferritin, fibrinogen, P-selectin, and vascular cell adhesion molecule-1. The associations between BM activation and MetS (and its components) and increased erythropoiesis were maintained in the subgroup of participants with no systemic inflammation. Bone marrow activation was significantly associated with high arterial metabolic activity (18F-FDG uptake). The co-occurrence of BM activation and arterial 18F-FDG uptake was associated with more advanced atherosclerosis (i.e. plaque presence and burden).
Conclusion
In apparently healthy individuals, BM 18F-FDG uptake is associated with MetS and its components, even in the absence of systemic inflammation, and with elevated counts of circulating leucocytes. Bone marrow activation is associated with early atherosclerosis, characterized by high arterial metabolic activity. Bone marrow activation appears to be an early phenomenon in atherosclerosis development.[Progression of Early Subclinical Atherosclerosis (PESA); NCT01410318].

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 14 May 2022; 43:1809-1828
Devesa A, Lobo-González M, Martínez-Milla J, Oliva B, ... Ibanez B, Fuster V
Eur Heart J: 14 May 2022; 43:1809-1828 | PMID: 35567559
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes.

Kraler S, Wenzl FA, Georgiopoulos G, Obeid S, ... Akhmedov A, Lüscher TF
Aims
The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its shedding product [soluble LOX-1 (sLOX-1)] are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Herein, we examined the relationship of sLOX-1 with both fatal events and plaque progression in patients with acute coronary syndromes (ACS).
Methods and results
Plasma sLOX-1 was assessed at baseline in ACS and chronic coronary syndrome (CCS) patients prospectively recruited in the multicentre SPUM-ACS study, with sex- and age-matched healthy subjects serving as additional controls (n = 2924). Compared with both CCS and controls, ACS patients showed markedly elevated sLOX-1 levels (median, 2.00 and 2.00 vs. 35.08 pg/mL; P < 0.0001) which were independently associated with increased mortality risk over 30-day [tertile (T)3: adjusted hazard ratio (HR), 3.11; 95% confidence interval (CI), 1.44-10.61; P = 0.0055] and 1-year intervals (T3: adjusted HR, 2.04; 95% CI, 1.19-3.92; P = 0.0098). Results remained consistent after adjustment for GRACE 2.0 (T3: adjusted HR, 1.86; 95% CI, 1.04-3.74; P = 0.0391) and were primarily driven by the pronounced relationship of sLOX-1 with cardiovascular mortality at 30 days (T3: adjusted HR, 3.81; 95% CI, 1.62-19.62; P = 0.0036) and at 1 year (T3: adjusted HR, 2.29; 95% CI, 1.19-5.34; P = 0.0148). In ACS patients undergoing serial intracoronary imaging and statin therapy, sLOX-1 dropped significantly in those with coronary plaque regression at 1 year (ΔsLOX-1: -4.64 ± 1.80; P = 0.0057), and showed a good discrimination for predicting plaque progression (area under the curve = 0.74; 95% CI, 0.59-0.86; P = 0.0031).
Conclusion
Plasma sLOX-1 levels are increased during ACS and predict fatal events beyond traditional and emerging risk factors. Persistently high sLOX-1 associates with coronary plaque progression in patients with established ASCVD.
Clinical trial registration
NCT01000701.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 14 May 2022; 43:1849-1860
Kraler S, Wenzl FA, Georgiopoulos G, Obeid S, ... Akhmedov A, Lüscher TF
Eur Heart J: 14 May 2022; 43:1849-1860 | PMID: 35567560
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Timing of cardiac surgery during pregnancy: a patient-level meta-analysis.

van Steenbergen GJ, Tsang QHY, van der Heijden OWH, Vart P, ... Li WWL, Verhagen AFTM
Aims
To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes.
Methods and results
Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality.
Conclusion
Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Eur Heart J: 13 May 2022; epub ahead of print
van Steenbergen GJ, Tsang QHY, van der Heijden OWH, Vart P, ... Li WWL, Verhagen AFTM
Eur Heart J: 13 May 2022; epub ahead of print | PMID: 35560020
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Integrated care for optimizing the management of stroke and associated heart disease: a position paper of the European Society of Cardiology Council on Stroke.

Lip GYH, Lane DA, Lenarczyk R, Boriani G, ... Ntaios G, Potpara T
The management of patients with stroke is often multidisciplinary, involving various specialties and healthcare professionals. Given the common shared risk factors for stroke and cardiovascular disease, input may also be required from the cardiovascular teams, as well as patient caregivers and next-of-kin. Ultimately, the patient is central to all this, requiring a coordinated and uniform approach to the priorities of post-stroke management, which can be consistently implemented by different multidisciplinary healthcare professionals, as part of the patient \'journey\' or \'patient pathway,\' supported by appropriate education and tele-medicine approaches. All these aspects would ultimately aid delivery of care and improve patient (and caregiver) engagement and empowerment. Given the need to address the multidisciplinary approach to holistic or integrated care of patients with heart disease and stroke, the European Society of Cardiology Council on Stroke convened a Task Force, with the remit to propose a consensus on Integrated care management for optimizing the management of stroke and associated heart disease. The present position paper summarizes the available evidence and proposes consensus statements that may help to define evidence gaps and simple practical approaches to assist in everyday clinical practice. A post-stroke ABC pathway is proposed, as a more holistic approach to integrated stroke care, would include three pillars of management: • A: Appropriate Antithrombotic therapy. • B: Better functional and psychological status. • C: Cardiovascular risk factors and Comorbidity optimization (including lifestyle changes).

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 13 May 2022; epub ahead of print
Lip GYH, Lane DA, Lenarczyk R, Boriani G, ... Ntaios G, Potpara T
Eur Heart J: 13 May 2022; epub ahead of print | PMID: 35552401
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Autopsy in the era of advanced cardiovascular imaging.

Basso C, Stone JR
Historically, autopsy contributed to our current knowledge of cardiovascular anatomy, physiology, and pathology. Major advances in the understanding of cardiovascular diseases, including atherosclerosis and coronary artery disease, congenital heart diseases, and cardiomyopathies, were possible through autopsy investigations and clinicopathological correlations. In this review, the importance of performing clinical autopsies in people dying from cardiovascular disease, even in the era of advanced cardiovascular imaging is addressed. Autopsies are most helpful in the setting of sudden unexpected deaths, particularly when advanced cardiovascular imaging has not been performed. In this setting, the autopsy is often the only chance to make the correct diagnosis. In previously symptomatic patients who had undergone advanced cardiovascular imaging, autopsies still play many roles. Post-mortem examinations are important for furthering the understanding of key issues related to the underlying diseases. Autopsy can help to increase the knowledge of the sensitivity and specificity of advanced cardiovascular imaging modalities. Autopsies are particularly important to gain insights into both the natural history of cardiovascular diseases as well as less common presentations and therapeutic complications. Finally, autopsies are a key tool to quickly understand the cardiac pathology of new disorders, as emphasized during the recent coronavirus disease 2019 pandemic.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 06 May 2022; epub ahead of print
Basso C, Stone JR
Eur Heart J: 06 May 2022; epub ahead of print | PMID: 35514073
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Timing of invasive strategy in non-ST-elevation acute coronary syndrome: a meta-analysis of randomized controlled trials.

Kite TA, Kurmani SA, Bountziouka V, Cooper NJ, ... McCann GP, Ladwiniec A
Aims
The optimal timing of an invasive strategy (IS) in non-ST-elevation acute coronary syndrome (NSTE-ACS) is controversial. Recent randomized controlled trials (RCTs) and long-term follow-up data have yet to be included in a contemporary meta-analysis.
Methods and results
A systematic review of RCTs that compared an early IS vs. delayed IS for NSTE-ACS was conducted by searching MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. A meta-analysis was performed by pooling relative risks (RRs) using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), recurrent ischaemia, admission for heart failure (HF), repeat re-vascularization, major bleeding, stroke, and length of hospital stay. This study was registered with PROSPERO (CRD42021246131). Seventeen RCTs with outcome data from 10 209 patients were included. No significant differences in risk for all-cause mortality [RR: 0.90, 95% confidence interval (CI): 0.78-1.04], MI (RR: 0.86, 95% CI: 0.63-1.16), admission for HF (RR: 0.66, 95% CI: 0.43-1.03), repeat re-vascularization (RR: 1.04, 95% CI: 0.88-1.23), major bleeding (RR: 0.86, 95% CI: 0.68-1.09), or stroke (RR: 0.95, 95% CI: 0.59-1.54) were observed. Recurrent ischaemia (RR: 0.57, 95% CI: 0.40-0.81) and length of stay (median difference: -22 h, 95% CI: -36.7 to -7.5 h) were reduced with an early IS.
Conclusion
In all-comers with NSTE-ACS, an early IS does not reduce all-cause mortality, MI, admission for HF, repeat re-vascularization, or increase major bleeding or stroke when compared with a delayed IS. Risk of recurrent ischaemia and length of stay are significantly reduced with an early IS.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 06 May 2022; epub ahead of print
Kite TA, Kurmani SA, Bountziouka V, Cooper NJ, ... McCann GP, Ladwiniec A
Eur Heart J: 06 May 2022; epub ahead of print | PMID: 35514079
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The European Heart Journal: fulfilling the mission.

Crea F, Badimon L, Berry C, De Caterina R, ... Tybjaerg-Hansen A, EHJ Editorial Board
In September 2020, the new Editors of the European Heart Journal (EHJ) wrote the following in their inaugural editorial: \"The fundamental mission of the Journal remains the reduction of the global burden of cardiovascular disease. We aspire to advance this aim by worldwide teamwork to communicate practice-changing research, inspire clinical cardiologists, and pursue rigour and transparency in the application of science at the service of human health. The Journal will strive to lead the field in its impact, influence, and reach\". After more than one year of experience the Editors hope the cardiological community will agree that they are fulfilling this mission. As stewards of the EHJ, the Editor\'s primary goal is not solely to achieve a high Impact Factor (which attests to the scientific quality and influence of our publications) but also to elevate the practice of cardiovascular medicine worldwide. Accordingly, various initiatives of the EHJ strive to strengthen further links among Editors, Authors, Reviewers and Readers through a series of coordinated and diverse activities, including webinars, active social media presence, and active participation at congresses worldwide. The Editors are proud to serve one of the most important scientific journals in cardiovascular medicine.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 05 May 2022; epub ahead of print
Crea F, Badimon L, Berry C, De Caterina R, ... Tybjaerg-Hansen A, EHJ Editorial Board
Eur Heart J: 05 May 2022; epub ahead of print | PMID: 35512309
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies.

Frantz S, Hundertmark MJ, Schulz-Menger J, Bengel FM, Bauersachs J
Most patients survive acute myocardial infarction (MI). Yet this encouraging development has certain drawbacks: heart failure (HF) prevalence is increasing and patients affected tend to have more comorbidities worsening economic strain on healthcare systems and impeding effective medical management. The heart\'s pathological changes in structure and/or function, termed myocardial remodelling, significantly impact on patient outcomes. Risk factors like diabetes, chronic obstructive pulmonary disease, female sex, and others distinctly shape disease progression on the \'road to HF\'. Despite the availability of HF drugs that interact with general pathways involved in myocardial remodelling, targeted drugs remain absent, and patient risk stratification is poor. Hence, in this review, we highlight the pathophysiological basis, current diagnostic methods and available treatments for cardiac remodelling following MI. We further aim to provide a roadmap for developing improved risk stratification and novel medical and interventional therapies.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 04 May 2022; epub ahead of print
Frantz S, Hundertmark MJ, Schulz-Menger J, Bengel FM, Bauersachs J
Eur Heart J: 04 May 2022; epub ahead of print | PMID: 35511857
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiac magnetic resonance identifies raised left ventricular filling pressure: prognostic implications.

Garg P, Gosling R, Swoboda P, Jones R, ... Alabed S, Swift AJ
Aims
Non-invasive imaging is routinely used to estimate left ventricular (LV) filling pressure (LVFP) in heart failure (HF). Cardiovascular magnetic resonance (CMR) is emerging as an important imaging tool for sub-phenotyping HF. However, currently, LVFP cannot be estimated from CMR. This study sought to investigate (i) if CMR can estimate LVFP in patients with suspected HF and (ii) if CMR-modelled LVFP has prognostic power.
Methods and results
Suspected HF patients underwent right heart catheterization (RHC), CMR and transthoracic echocardiography (TTE) (validation cohort only) within 24 h of each other. Right heart catheterization measured pulmonary capillary wedge pressure (PCWP) was used as a reference for LVFP. At follow-up, death was considered as the primary endpoint. We enrolled 835 patients (mean age: 65 ± 13 years, 40% male). In the derivation cohort (n = 708, 85%), two CMR metrics were associated with RHC PCWP:LV mass and left atrial volume. When applied to the validation cohort (n = 127, 15%), the correlation coefficient between RHC PCWP and CMR-modelled PCWP was 0.55 (95% confidence interval: 0.41-0.66, P < 0.0001). Cardiovascular magnetic resonance-modelled PCWP was superior to TTE in classifying patients as normal or raised filling pressures (76 vs. 25%). Cardiovascular magnetic resonance-modelled PCWP was associated with an increased risk of death (hazard ratio: 1.77, P < 0.001). At Kaplan-Meier analysis, CMR-modelled PCWP was comparable to RHC PCWP (≥15 mmHg) to predict survival at 7-year follow-up (35 vs. 37%, χ2 = 0.41, P  = 0.52).
Conclusion
A physiological CMR model can estimate LVFP in patients with suspected HF. In addition, CMR-modelled LVFP has a prognostic role.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 04 May 2022; epub ahead of print
Garg P, Gosling R, Swoboda P, Jones R, ... Alabed S, Swift AJ
Eur Heart J: 04 May 2022; epub ahead of print | PMID: 35512290
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Characteristics, management, and outcomes of patients with multiple native valvular heart disease: a substudy of the EURObservational Research Programme Valvular Heart Disease II Survey.

Tribouilloy C, Bohbot Y, Kubala M, Ruschitzka F, ... Vahanian A, Iung B
Aims
To assess the characteristics, management, and survival of patients with multiple native valvular heart disease (VHD).
Methods and results
Among the 5087 patients with ≥1 severe left-sided native VHD included in the EURObservational VHD II Survey (maximum 3-month recruitment period per centre between January and August 2017 with a 6-month follow-up), 3571 had a single left-sided VHD (Group A, 70.2%), 363 had one severe left-sided VHD with moderate VHD of the other ipsilateral valve (Group B, 7.1%), and 1153 patients (22.7%) had ≥2 severe native VHDs (left-sided and/or tricuspid regurgitation, Group C). Patients with multiple VHD (Groups B and C) were more often women, had greater congestive heart failure (CHF) and comorbidity, higher left atrial volumes and pulmonary pressures, and lower ejection fraction than Group A patients (all P ≤ 0.01). During the index hospitalization, 36.7% of Group A (n = 1312), 26.7% of Group B (n = 97), and 32.7% of Group C (n = 377) underwent valvular intervention (P < 0.001). Six-month survival was better for Group A than for Group B or C (both P < 0.001), even after adjustment for age, sex, body mass index, and Charlson index [hazard ratio (HR) 95% confidence interval (CI) 1.62 (1.10-2.38) vs. Group B and HR 95% CI 1.72 (1.32-2.25) vs. Group C]. Groups B and C had more CHF at 6 months than Group A (both P < 0.001). Factors associated with mortality in Group C were age, CHF, and comorbidity (all P < 0.010).
Conclusion
Multiple VHD is common, encountered in nearly 30% of patients with left-sided native VHD, and associated with greater cardiac damage and leads to higher mortality and more heart failure at 6 months than single VHD, yet with lower rates of surgery.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 02 May 2022; epub ahead of print
Tribouilloy C, Bohbot Y, Kubala M, Ruschitzka F, ... Vahanian A, Iung B
Eur Heart J: 02 May 2022; epub ahead of print | PMID: 35511056
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study.

Valerio L, Mavromanoli AC, Barco S, Abele C, ... Rosenkranz S, FOCUS Investigators
Aims
To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria.
Methods and results
A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2-4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8-20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73-2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI.
Conclusion
In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 28 Apr 2022; epub ahead of print
Valerio L, Mavromanoli AC, Barco S, Abele C, ... Rosenkranz S, FOCUS Investigators
Eur Heart J: 28 Apr 2022; epub ahead of print | PMID: 35484821
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Which patients with aortic stenosis should be referred to surgery rather than transcatheter aortic valve implantation?

Windecker S, Okuno T, Unbehaun A, Mack M, Kapadia S, Falk V
Transcatheter aortic valve implantation (TAVI) has matured into a standard treatment option for patients with severe symptomatic aortic valve stenosis (AS) across the whole spectrum of risk. The advances in the interventional treatment of AS raise the question of which patients with severe AS should be referred to surgery. The myriad of clinical permutations does not allow providing a single, uniform treatment strategy. Rather, the advent of TAVI along with established surgical aortic valve replacement (SAVR) fundamentally enforces the role of the multidisciplinary heart team for decision-making recommending the best individual choice of the two options based on a thorough review of clinical and anatomical factors as well as lifetime management considerations. Involvement of the informed patient expressing treatment preferences is a key for a shared decision-making process. Herein, we provide an in-depth review of evidence informing the decision-making process between TAVI and SAVR and key elements for treatment selection. Special attention is given to the populations that have been excluded from randomized clinical trials, and also lifetime management strategies of patients with severe AS are proposed.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 25 Apr 2022; epub ahead of print
Windecker S, Okuno T, Unbehaun A, Mack M, Kapadia S, Falk V
Eur Heart J: 25 Apr 2022; epub ahead of print | PMID: 35466382
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Accelerated and personalized therapy for heart failure with reduced ejection fraction.

Shen L, Jhund PS, Docherty KF, Vaduganathan M, ... Zhang X, McMurray JJV
Aims
Previously, guidelines recommended initiating therapy in patients with heart failure and reduced ejection fraction (HFrEF) in a sequence that follows the chronological order in which trials were conducted, with cautious up-titration of each treatment. It remains unclear whether this historical approach is optimal and alternative approaches may improve patient outcomes.
Methods and results
The potential reductions in events that might result from (i) more rapid up-titration of therapies used in the conventional order (based on the chronology of the trials), and (ii) accelerated up-titration and using treatments in different orders than is conventional were modelled using data from six pivotal trials in HFrEF. Over the first 12 months from starting therapy, using a rapid up-titration schedule led to 23 fewer patients per 1000 patients experiencing the composite of heart failure hospitalization or cardiovascular death and seven fewer deaths from any cause. In addition to accelerating up-titration of treatments, optimized alternative ordering of the drugs used resulted in a further reduction of 24 patients experiencing the composite outcome and six fewer deaths at 12 months. The optimal alternative sequences included sodium-glucose cotransporter 2 inhibition and a mineralocorticoid receptor antagonist as the first two therapies.
Conclusion
Modelling of accelerated up-titration schedule and optimized ordering of treatment suggested that at least 14 deaths and 47 patients experiencing the composite outcome per 1000 treated might be prevented over the first 12 months after starting therapy. Standard treatment guidance may not lead to the best patient outcomes in HFrEF, though these findings should be tested in clinical trials.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 25 Apr 2022; epub ahead of print
Shen L, Jhund PS, Docherty KF, Vaduganathan M, ... Zhang X, McMurray JJV
Eur Heart J: 25 Apr 2022; epub ahead of print | PMID: 35467706
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study.

Eckhardt CM, Balte PP, Barr RG, Bertoni AG, ... Yende S, Oelsner EC
Aims
The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF).
Methods and results
Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking.
Conclusion
Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 25 Apr 2022; epub ahead of print
Eckhardt CM, Balte PP, Barr RG, Bertoni AG, ... Yende S, Oelsner EC
Eur Heart J: 25 Apr 2022; epub ahead of print | PMID: 35467708
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Electromechanical reciprocity and arrhythmogenesis in long-QT syndrome and beyond.

Odening KE, van der Linde HJ, Ackerman MJ, Volders PGA, Ter Bekke RMA
An abundance of literature describes physiological and pathological determinants of cardiac performance, building on the principles of excitation-contraction coupling. However, the mutual influencing of excitation-contraction and mechano-electrical feedback in the beating heart, here designated \'electromechanical reciprocity\', remains poorly recognized clinically, despite the awareness that external and cardiac-internal mechanical stimuli can trigger electrical responses and arrhythmia. This review focuses on electromechanical reciprocity in the long-QT syndrome (LQTS), historically considered a purely electrical disease, but now appreciated as paradigmatic for the understanding of mechano-electrical contributions to arrhythmogenesis in this and other cardiac conditions. Electromechanical dispersion in LQTS is characterized by heterogeneously prolonged ventricular repolarization, besides altered contraction duration and relaxation. Mechanical alterations may deviate from what would be expected from global and regional repolarization abnormalities. Pathological repolarization prolongation outlasts mechanical systole in patients with LQTS, yielding a negative electromechanical window (EMW), which is most pronounced in symptomatic patients. The electromechanical window is a superior and independent arrhythmia-risk predictor compared with the heart rate-corrected QT. A negative EMW implies that the ventricle is deformed-by volume loading during the rapid filling phase-when repolarization is still ongoing. This creates a \'sensitized\' electromechanical substrate, in which inadvertent electrical or mechanical stimuli such as local after-depolarizations, after-contractions, or dyssynchrony can trigger abnormal impulses. Increased sympathetic-nerve activity and pause-dependent potentiation further exaggerate electromechanical heterogeneities, promoting arrhythmogenesis. Unraveling electromechanical reciprocity advances the understanding of arrhythmia formation in various conditions. Real-time image integration of cardiac electrophysiology and mechanics offers new opportunities to address challenges in arrhythmia management.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 21 Apr 2022; epub ahead of print
Odening KE, van der Linde HJ, Ackerman MJ, Volders PGA, Ter Bekke RMA
Eur Heart J: 21 Apr 2022; epub ahead of print | PMID: 35445703
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

Cadrin-Tourigny J, Bosman LP, Nozza A, Wang W, ... Te Riele ASJM, James CA
Aims
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.
Methods and results
Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001).
Conclusion
Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J: 20 Apr 2022; epub ahead of print
Cadrin-Tourigny J, Bosman LP, Nozza A, Wang W, ... Te Riele ASJM, James CA
Eur Heart J: 20 Apr 2022; epub ahead of print | PMID: 35441664
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Data standards for heart failure: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart).

Aktaa S, Batra G, Cleland JGF, Coats A, ... Gale CP, Heart Failure Association of the European Society of Cardiology
Standardized data definitions are essential for assessing the quality of care and patient outcomes in observational studies and randomized controlled trials. The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create contemporary pan-European data standards for cardiovascular diseases, including heart failure (HF). We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group including experts in HF registries, representatives from the Heart Failure Association of the ESC, and the EuroHeart was formed. Using Embase and Medline (2016-21), we conducted a systematic review of the literature on data standards, registries, and trials to identify variables pertinent to HF. A modified Delphi method was used to reach a consensus on the final set of variables. For each variable, the Working Group developed data definitions and agreed on whether it was mandatory (Level 1) or additional (Level 2). In total, 84 Level 1 and 79 Level 2 variables were selected for nine domains of HF care. These variables were reviewed by an international Reference Group with the Level 1 variables providing the dataset for registration of patients with HF on the EuroHeart IT platform. By means of a structured process and interaction with international stakeholders, harmonized data standards for HF have been developed. In the context of the EuroHeart, this will facilitate quality improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies across Europe.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 20 Apr 2022; epub ahead of print
Aktaa S, Batra G, Cleland JGF, Coats A, ... Gale CP, Heart Failure Association of the European Society of Cardiology
Eur Heart J: 20 Apr 2022; epub ahead of print | PMID: 35443059
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart transplantation: focus on donor recovery strategies, left ventricular assist devices, and novel therapies.

Crespo-Leiro MG, Costanzo MR, Gustafsson F, Khush KK, ... Zuckermann A, Mehra MR
Heart transplantation is advocated in selected patients with advanced heart failure in the absence of contraindications. Principal challenges in heart transplantation centre around an insufficient and underutilized donor organ pool, the need to individualize titration of immunosuppressive therapy, and to minimize late complications such as cardiac allograft vasculopathy, malignancy, and renal dysfunction. Advances have served to increase the organ donor pool by advocating the use of donors with underlying hepatitis C virus infection and by expanding the donor source to use hearts donated after circulatory death. New techniques to preserve the donor heart over prolonged ischaemic times, and enabling longer transport times in a safe manner, have been introduced. Mechanical circulatory support as a bridge to transplantation has allowed patients with advanced heart failure to avoid progressive deterioration in hepato-renal function while awaiting an optimal donor organ match. The management of the heart transplantation recipient remains a challenge despite advances in immunosuppression, which provide early gains in rejection avoidance but are associated with infections and late-outcome challenges. In this article, we review contemporary advances and challenges in this field to focus on donor recovery strategies, left ventricular assist devices, and immunosuppressive monitoring therapies with the potential to enhance outcomes. We also describe opportunities for future discovery to include a renewed focus on long-term survival, which continues to be an area that is under-studied and poorly characterized, non-human sources of organs for transplantation including xenotransplantation as well as chimeric transplantation, and technology competitive to human heart transplantation, such as tissue engineering.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 20 Apr 2022; epub ahead of print
Crespo-Leiro MG, Costanzo MR, Gustafsson F, Khush KK, ... Zuckermann A, Mehra MR
Eur Heart J: 20 Apr 2022; epub ahead of print | PMID: 35441654
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Adult T-cells impair neonatal cardiac regeneration.

Dolejsi T, Delgobo M, Schuetz T, Tortola L, ... Campos Ramos G, Haubner BJ
Aims
Newborn mice and humans display transient cardiac regenerative potential that rapidly declines postnatally. Patients who survive a myocardial infarction (MI) often develop chronic heart failure due to the heart\'s poor regeneration capacity. We hypothesized that the cardiac \'regenerative-to-scarring\' transition might be driven by the perinatal shifts observed in the circulating T-cell compartment.
Methods and results
Post-MI immune responses were characterized in 1- (P1) vs. 7-day-old (P7) mice subjected to left anterior descending artery ligation. Myocardial infarction induced robust early inflammatory responses (36 h post-MI) in both age groups, but neonatal hearts exhibited rapid resolution of inflammation and full functional recovery. The perinatal loss of myocardial regenerative capacity was paralleled by a baseline increase in αβ-T cell (CD4+ and CD8+) numbers. Strikingly, P1-infarcted mice reconstituted with adult T-cells shifted to an adult-like healing phenotype, marked by irreversible cardiac functional impairment and increased fibrosis. Infarcted neonatal mice harbouring adult T-cells also had more monocyte-derived macrophage recruitment, as typically seen in adults. At the transcriptome level, infarcted P1 hearts that received isolated adult T-cells showed enriched gene sets linked to fibrosis, inflammation, and interferon-gamma (IFN-γ) signalling. In contrast, newborn mice that received isolated Ifng-/- adult T-cells prior to MI displayed a regenerative phenotype that resembled that of its age-matched untreated controls.
Conclusion
Physiological T-cell development or adoptive transfer of adult IFN-γ-producing T-cells into neonates contributed to impaired cardiac regeneration and promoted irreversible structural and functional cardiac damage. These findings reveal a trade-off between myocardial regenerative potential and the development of T-cell competence.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 13 Apr 2022; epub ahead of print
Dolejsi T, Delgobo M, Schuetz T, Tortola L, ... Campos Ramos G, Haubner BJ
Eur Heart J: 13 Apr 2022; epub ahead of print | PMID: 35417553
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of aspirin on dementia and cognitive function in diabetic patients: the ASCEND trial.

Parish S, Mafham M, Offer A, Barton J, ... Armitage J, ASCEND Study Collaborative Group
Aims
Aspirin is widely used in cardiovascular disease prevention but is also associated with an increased risk of bleeding. The net effect of aspirin on dementia and cognitive impairment is uncertain.
Methods and results
In the ASCEND trial, 15 480 people from the UK with diabetes and no history of cardiovascular disease were randomized to aspirin 100 mg daily or matching placebo for a mean of 7.4 years. The 15 427 ASCEND participants with no recorded dementia prior to baseline were included in this cognitive study with a primary pre-specified outcome of \'broad dementia\', comprising dementia, cognitive impairment, or confusion. This was ascertained through participant, carer, or general practitioner report or hospital admission diagnosis, by 31 March 2019 (∼2 years beyond the scheduled treatment period). The broad dementia outcome occurred in a similar percentage of participants in the aspirin group and placebo group: 548 participants (7.1%) vs. 598 (7.8%), rate ratio 0.91 [95% confidence interval (CI), 0.81-1.02]. Thus, the CI excluded proportional hazards of >2% and proportional benefits of >19%.
Conclusion
Aspirin does not have a large proportional effect on the risk of dementia. Trials or meta-analyses with larger total numbers of incident dementia cases to increase statistical power are needed to assess whether any modest proportional 10-15% benefits of 5-7 years of aspirin use on dementia exist.
Clinical trial registration
Current Controlled Trials number, ISRCTN60635500; ClinicalTrials.gov number: NCT00135226.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 08 Apr 2022; epub ahead of print
Parish S, Mafham M, Offer A, Barton J, ... Armitage J, ASCEND Study Collaborative Group
Eur Heart J: 08 Apr 2022; epub ahead of print | PMID: 35393614
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Global disparities in prescription of guideline-recommended drugs for heart failure with reduced ejection fraction.

Tromp J, Ouwerkerk W, Teng TK, Cleland JGF, ... Filippatos G, Lam CSP
Background
Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines.
Methods and results
This analysis assessed prescription rates and doses of renin-angiotensin system (RAS) inhibitors, β-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias.Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on ≥50% of guideline-recommended doses of RAS inhibitors, and β-blockers were independently associated with better 1-year survival, regardless of country income level.
Conclusion
Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 08 Apr 2022; epub ahead of print
Tromp J, Ouwerkerk W, Teng TK, Cleland JGF, ... Filippatos G, Lam CSP
Eur Heart J: 08 Apr 2022; epub ahead of print | PMID: 35393622
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Twitter promotion is associated with higher citation rates of cardiovascular articles: the ESC Journals Randomized Study.

Ladeiras-Lopes R, Vidal-Perez R, Santos-Ferreira D, Alexander M, ... Crea F, Lüscher TF
The association between the dissemination of scientific articles on Twitter and online visibility (as assessed by the Altmetric Score) is still controversial, and the impact on citation rates has never been rigorously addressed for cardiovascular medicine journals using a randomized design. The ESC Journals Study randomized 695 papers published in the ESC Journal Family (March 2018-May 2019) for promotion on Twitter or to a control arm (with no active tweeting from ESC channels) and aimed to assess whether Twitter promotion was associated with an increase in citation rates (primary endpoint) and of the Altmetric Score. This is the final analysis including 694 articles (one paper excluded due to retraction). After a median follow-up of 994 days (interquartile range: 936-1063 days), Twitter promotion of articles was associated with a 1.12 (95% confidence interval: 1.08-1.15) higher rate of citations, and this effect was independent of the type of article. Altmetric Attention Score and number of users tweeting were positive predictors for the number of citations. A social media strategy of Twitter promotion for cardiovascular medicine papers seems to be associated with increased online visibility and higher numbers of citations.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 07 Apr 2022; epub ahead of print
Ladeiras-Lopes R, Vidal-Perez R, Santos-Ferreira D, Alexander M, ... Crea F, Lüscher TF
Eur Heart J: 07 Apr 2022; epub ahead of print | PMID: 35388421
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Data standards for acute coronary syndrome and percutaneous coronary intervention: the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart).

Association of Cardiovascular Nursing and Allied Professions (ACNAP), Association for Acute CardioVascular Care (ACVC), European Association of Percutaneous Cardiovascular Interventions (EAPCI), EURObservational Research Programme (EORP), ... Casadei B, Gale CP
Standardized data definitions are essential for monitoring and benchmarking the quality of care and patient outcomes in observational studies and randomized controlled trials. There are no contemporary pan-European data standards for the acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aimed to develop such data standards for ACS and PCI. Following a systematic review of the literature on ACS and PCI data standards and evaluation of contemporary ACS and PCI registries, we undertook a modified Delphi process involving clinical and registry experts from 11 European countries, as well as representatives from relevant ESC Associations, including the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and Acute CardioVascular Care (ACVC). This resulted in final sets of 68 and 84 \'mandatory\' variables and several catalogues of optional variables for ACS and PCI, respectively. Data definitions were provided for these variables, which have been programmed as the basis for continuous registration of individual patient data in the online EuroHeart IT platform. By means of a structured process and the interaction with major stakeholders, internationally harmonized data standards for ACS and PCI have been developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 05 Apr 2022; epub ahead of print
Association of Cardiovascular Nursing and Allied Professions (ACNAP), Association for Acute CardioVascular Care (ACVC), European Association of Percutaneous Cardiovascular Interventions (EAPCI), EURObservational Research Programme (EORP), ... Casadei B, Gale CP
Eur Heart J: 05 Apr 2022; epub ahead of print | PMID: 35380662
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Survival of patients undergoing cardiac resynchronization therapy with or without defibrillator: the RESET-CRT project.

Hadwiger M, Dagres N, Haug J, Wolf M, ... Frielitz FS, Hindricks G
Aims
Cardiac resynchronization therapy (CRT) is an established treatment for heart failure. There is contradictory evidence whether defibrillator capability improves prognosis in patients receiving CRT. We compared the survival of patients undergoing de novo implantation of a CRT with defibrillator (CRT-D) option and CRT with pacemaker (CRT-P) in a large health claims database.
Methods and results
Using health claims data of a major German statutory health insurance, we analysed patients with de novo CRT implantation from 2014 to 2019 without indication for defibrillator implantation for secondary prevention of sudden cardiac death. We performed age-adjusted Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances. The analysis comprised 847 CRT-P and 2722 CRT-D patients. Overall, 714 deaths were recorded during a median follow-up of 2.35 years. A higher cumulative incidence of all-cause death was observed in the initial unadjusted Kaplan-Meier time-to-event analysis [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.38-1.92]. After adjustment for age, HR was 1.13 (95% CI: 0.95-1.35) and after entropy balancing 0.99 (95% CI: 0.81-1.20). No survival differences were found in different age groups. The results were robust in sensitivity analyses.
Conclusion
In a large health claims database of CRT implantations performed in a contemporary setting, CRT-P treatment was not associated with inferior survival compared with CRT-D. Age differences accounted for the greatest part of the survival difference that was observed in the initial unadjusted analysis.
Key question
Is the defibrillator capability needed in cardiac resynchronization therapy (CRT)?Aim: Compare survival of patients receiving de novo CRT with and without defibrillator option between 2014 and 2019.Health claims data, same inclusion and exclusion criteria as in RESET-CRT randomized trial.
Key finding
CRT-P patients 6.7 years older than CRT-D patients.Comparable aetiology of heart failure.Median follow-up 2.35 years: 203 (24%) deaths in CRT-P and 511 (19%) deaths in CRT-D patients.Age differences accounted for the greatest part of the survival difference.
Take-home message
No survival differences between CRT-D and CRT-P after adjustment for age and entropy balancing.Results corroborate the hypothesis of the RESET-CRT randomized clinical trial.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 03 Apr 2022; epub ahead of print
Hadwiger M, Dagres N, Haug J, Wolf M, ... Frielitz FS, Hindricks G
Eur Heart J: 03 Apr 2022; epub ahead of print | PMID: 35366320
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Importance of genetic testing in unexplained cardiac arrest.

Grondin S, Davies B, Cadrin-Tourigny J, Steinberg C, ... Krahn AD, Tadros R
Aims
Genetic testing is recommended in specific inherited heart diseases but its role remains unclear and it is not currently recommended in unexplained cardiac arrest (UCA). We sought to assess the yield and clinical utility of genetic testing in UCA using whole-exome sequencing (WES).
Methods and results
Survivors of UCA requiring external defibrillation were included from the Cardiac Arrest Survivor with Preserved Ejection fraction Registry. Whole-exome sequencing was performed, followed by assessment of rare variants in previously reported cardiovascular disease genes. A total of 228 UCA survivors (mean age at arrest 39 ± 13 years) were included. The majority were males (66%) and of European ancestry (81%). Following advanced clinical testing at baseline, the likely aetiology of cardiac arrest was determined in 21/228 (9%) cases. Whole-exome sequencing identified a pathogenic or likely pathogenic (P/LP) variant in 23/228 (10%) of UCA survivors overall, increasing the proportion of \'explained\' cases from 9% only following phenotyping to 18% when combining phenotyping with WES. Notably, 13 (57%) of the 23 P/LP variants identified were located in genes associated with cardiomyopathy, in the absence of a diagnosis of cardiomyopathy at the time of arrest.
Conclusions
Genetic testing identifies a disease-causing variant in 10% of apparent UCA survivors. The majority of disease-causing variants was located in cardiomyopathy-associated genes, highlighting the arrhythmogenic potential of such variants in the absence of an overt cardiomyopathy diagnosis. The present study supports the use of genetic testing including assessment of arrhythmia and cardiomyopathy genes in survivors of UCA.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 30 Mar 2022; epub ahead of print
Grondin S, Davies B, Cadrin-Tourigny J, Steinberg C, ... Krahn AD, Tadros R
Eur Heart J: 30 Mar 2022; epub ahead of print | PMID: 35352813
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Middle age serum sodium levels in the upper part of normal range and risk of heart failure.

Dmitrieva NI, Liu D, Wu CO, Boehm M
Aims
With increasing prevalence of heart failure (HF) owing to the ageing population, identification of modifiable risk factors is important. In a mouse model, chronic hypohydration induced by lifelong water restriction promotes cardiac fibrosis. Hypohydration elevates serum sodium. Here, we evaluate the association of serum sodium at middle age as a measure of hydration habits with risk to develop HF.
Methods and results
We analysed data from Atherosclerosis Risk in Communities study with middle age enrolment (45-66 years) and 25 years of follow-up. Participants without water balance dysregulation were selected: serum sodium within normal range (135-146 mmol/L), not diabetic, not obese and free of HF at baseline (N = 11 814). In time-to-event analysis, HF risk was increased by 39% if middle age serum sodium exceeded 143 mmol/L corresponding to 1% body weight water deficit [hazard ratio 1.39, 95% confidence interval (CI) 1.14-1.70]. In a retrospective case-control analysis performed on 70- to 90-year-old attendees of Visit 5 (N = 4961), serum sodium of 142.5-143 mmol/L was associated with 62% increase in odds of left ventricular hypertrophy (LVH) diagnosis [odds ratio (OR) 1.62, 95% CI 1.03-2.55]. Serum sodium above 143 mmol/L was associated with 107% increase in odds of LVH (OR 2.07, 95% CI 1.30-3.28) and 54% increase in odds of HF (OR 1.54, 95% CI 1.06-2.23). As a result, prevalence of HF and LVH was increased among 70- to 90-year-old participants with higher middle age serum sodium.
Conclusion
Middle age serum sodium above 142 mmol is a risk factor for LVH and HF. Maintaining good hydration throughout life may slow down decline in cardiac function and decrease prevalence of HF.

Published by Oxford University Press on behalf of European Society of Cardiology 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Eur Heart J: 29 Mar 2022; epub ahead of print
Dmitrieva NI, Liu D, Wu CO, Boehm M
Eur Heart J: 29 Mar 2022; epub ahead of print | PMID: 35348651
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.