Showing papers in "European Heart Journal in 2019"

How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Abstract: Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the 'HFA-PEFF diagnostic algorithm'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e'), LV filling pressure estimated using E/e', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1 : Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2 : Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

Cardiovascular disease burden from ambient air pollution in Europe reassessed using novel hazard ratio functions.

Abstract: Aims Ambient air pollution is a major health risk, leading to respiratory and cardiovascular mortality. A recent Global Exposure Mortality Model, based on an unmatched number of cohort studies in many countries, provides new hazard ratio functions, calling for re-evaluation of the disease burden. Accordingly, we estimated excess cardiovascular mortality attributed to air pollution in Europe. Methods and results The new hazard ratio functions have been combined with ambient air pollution exposure data to estimate the impacts in Europe and the 28 countries of the European Union (EU-28). The annual excess mortality rate from ambient air pollution in Europe is 790 000 [95% confidence interval (95% CI) 645 000-934 000], and 659 000 (95% CI 537 000-775 000) in the EU-28. Between 40% and 80% are due to cardiovascular events, which dominate health outcomes. The upper limit includes events attributed to other non-communicable diseases, which are currently not specified. These estimates exceed recent analyses, such as the Global Burden of Disease for 2015, by more than a factor of two. We estimate that air pollution reduces the mean life expectancy in Europe by about 2.2 years with an annual, attributable per capita mortality rate in Europe of 133/100 000 per year. Conclusion We provide new data based on novel hazard ratio functions suggesting that the health impacts attributable to ambient air pollution in Europe are substantially higher than previously assumed, though subject to considerable uncertainty. Our results imply that replacing fossil fuels by clean, renewable energy sources could substantially reduce the loss of life expectancy from air pollution.

Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans

Abstract: Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.

A population-based study of cardiovascular disease mortality risk in US cancer patients

Abstract: AIMS This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis. METHODS AND RESULTS The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973-2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at <35 years of age. Further, CVD mortality risk is highest (SMR 3.93, 95% confidence interval 3.89-3.97) within the first year after cancer diagnosis, and CVD mortality risk remains elevated throughout follow-up compared to the general population. CONCLUSION The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.

The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study.

Abstract: Aims Apnoea-hypopnoea index (AHI), the universal clinical metric of sleep apnoea severity, poorly predicts the adverse outcomes of sleep apnoea, potentially because the AHI, a frequency measure, does not adequately capture disease burden. Therefore, we sought to evaluate whether quantifying the severity of sleep apnoea by the 'hypoxic burden' would predict mortality among adults aged 40 and older. Methods and results The samples were derived from two cohort studies: The Outcomes of Sleep Disorders in Older Men (MrOS), which included 2743 men, age 76.3 ± 5.5 years; and the Sleep Heart Health Study (SHHS), which included 5111 middle-aged and older adults (52.8% women), age: 63.7 ± 10.9 years. The outcomes were all-cause and Cardiovascular disease (CVD)-related mortality. The hypoxic burden was determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline. Cox models were used to calculate the adjusted hazard ratios for hypoxic burden. Unlike the AHI, the hypoxic burden strongly predicted CVD mortality and all-cause mortality (only in MrOS). Individuals in the MrOS study with hypoxic burden in the highest two quintiles had hazard ratios of 1.81 [95% confidence interval (CI) 1.25-2.62] and 2.73 (95% CI 1.71-4.36), respectively. Similarly, the group in the SHHS with hypoxic burden in the highest quintile had a hazard ratio of 1.96 (95% CI 1.11-3.43). Conclusion The 'hypoxic burden', an easily derived signal from overnight sleep study, predicts CVD mortality across populations. The findings suggest that not only the frequency but the depth and duration of sleep related upper airway obstructions, are important disease characterizing features.

Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study

Abstract: Aims: The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results: Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion: Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

Sex Differences in Heart Failure

Abstract: The overall lifetime risk of heart failure (HF) is similar between men and women, however, there are marked sex differences in the landscape of this condition that are both important and under-recognized. Men are predisposed to HF with reduced ejection fraction (HFrEF), whereas women predominate in HF with preserved ejection fraction (HFpEF). Sex differences are also notable in the penetrance of genetic cardiomyopathies, risk factors, e.g. breast cancer which may be associated with cancer treatment-induced cardiomyopathy, as well as sex-specific conditions such as peripartum cardiomyopathy (PPCM). This review outlines the key sex differences with respect to clinical characteristics, pathophysiology, and therapeutic responses to HF treatments. Finally, we address important differences in the prognosis of HF. A central hypothesis is that the higher risk of HFrEF in men compared to women may be attributable to their predisposition to macrovascular coronary artery disease and myocardial infarction, whereas coronary microvascular dysfunction/endothelial inflammation has been postulated to play a key role in HFpEF and maybe the common link among HF syndromes that women are predisposed to Takotsubo cardiomyopathy, PPCM, and breast cancer radiotherapy-induced cardiomyopathy. Under-pinning current sex disparities in HF, there is a paucity of women recruited to HF clinical trials (20-25% of cohorts) and thus treatment guidelines are predominantly based on male-derived data. Large gaps in knowledge exist in sex-specific mechanisms, optimal drug doses for women and sex-specific criteria for device therapy.

Management of cardiogenic shock complicating myocardial infarction: an update 2019

Abstract: Cardiogenic shock (CS) remains the most common cause of death in patients admitted with acute myocardial infarction (AMI) and mortality remained nearly unchanged in the range of 40-50% during the last two decades. Early revascularization, vasopressors and inotropes, fluids, mechanical circulatory support, and general intensive care measures are widely used for CS management. However, there is only limited evidence for any of the above treatment strategies except for revascularization and the relative ineffectiveness of intra-aortic balloon pumping. This updated review will outline the management of CS complicating AMI with major focus on state-of-the art treatment.

Clinical applications of machine learning in cardiovascular disease and its relevance to cardiac imaging

Abstract: Artificial intelligence (AI) has transformed key aspects of human life. Machine learning (ML), which is a subset of AI wherein machines autonomously acquire information by extracting patterns from large databases, has been increasingly used within the medical community, and specifically within the domain of cardiovascular diseases. In this review, we present a brief overview of ML methodologies that are used for the construction of inferential and predictive data-driven models. We highlight several domains of ML application such as echocardiography, electrocardiography, and recently developed non-invasive imaging modalities such as coronary artery calcium scoring and coronary computed tomography angiography. We conclude by reviewing the limitations associated with contemporary application of ML algorithms within the cardiovascular disease field.

Recommendations for participation in competitive and leisure time sport in athletes with cardiomyopathies, myocarditis, and pericarditis: position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC)

Abstract: Myocardial diseases are associated with an increased risk of potentially fatal cardiac arrhythmias and sudden cardiac death/cardiac arrest during exercise, including hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, arrhythmogenic cardiomyopathy, and myo-pericarditis. Practicing cardiologists and sport physicians are required to identify high-risk individuals harbouring these cardiac diseases in a timely fashion in the setting of preparticipation screening or medical consultation and provide appropriate advice regarding the participation in competitive sport activities and/or regular exercise programmes. Many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to participate in leisure-time and amateur sport activities to take advantage of the multiple benefits of a physically active lifestyle. In 2005, The European Society of Cardiology (ESC) published recommendations for participation in competitive sport in athletes with cardiomyopathies and myo-pericarditis. One decade on, these recommendations are partly obsolete given the evolving knowledge of the diagnosis, management and treatment of cardiomyopathies and myo-pericarditis. The present document, therefore, aims to offer a comprehensive overview of the most updated recommendations for practicing cardiologists and sport physicians managing athletes with cardiomyopathies and myo-pericarditis and provides pragmatic advice for safe participation in competitive sport at professional and amateur level, as well as in a variety of recreational physical activities.

Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women

Abstract: AIMS Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metabolism and renal excretion. METHODS AND RESULTS Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metabolism. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05). Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat failed to impact TMAO or its metabolites. CONCLUSION Chronic dietary red meat increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.

Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis

Abstract: AIMS Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients. METHODS AND RESULTS The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.78-0.99], P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes [HR 0.81 (95% CI 0.68-0.98), P = 0.028]. Surgical aortic valve replacement was associated with a lower risk of major vascular complications [HR 1.99 (95% CI 1.34-2.93), P = 0.001] and permanent pacemaker implantations [HR 2.27 (95% CI 1.47-3.64), P < 0.001] compared to TAVI. CONCLUSION Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification

Abstract: Aims We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk

Abstract: Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

Canadian spontaneous coronary artery dissection cohort study: in-hospital and 30-day outcomes.

Abstract: Aims Spontaneous coronary artery dissection (SCAD) was underdiagnosed and poorly understood for decades. It is increasingly recognized as an important cause of myocardial infarction (MI) in women. We aimed to assess the natural history of SCAD, which has not been adequately explored. Methods and results We performed a multicentre, prospective, observational study of patients with non-atherosclerotic SCAD presenting acutely from 22 centres in North America. Institutional ethics approval and patient consents were obtained. We recorded baseline demographics, in-hospital characteristics, precipitating/predisposing conditions, angiographic features (assessed by core laboratory), in-hospital major adverse events (MAE), and 30-day major adverse cardiovascular events (MACE). We prospectively enrolled 750 SCAD patients from June 2014 to June 2018. Mean age was 51.8 ± 10.2 years, 88.5% were women (55.0% postmenopausal), 87.7% were Caucasian, and 33.9% had no cardiac risk factors. Emotional stress was reported in 50.3%, and physical stress in 28.9% (9.8% lifting >50 pounds). Predisposing conditions included fibromuscular dysplasia 31.1% (45.2% had no/incomplete screening), systemic inflammatory diseases 4.7%, peripartum 4.5%, and connective tissue disorders 3.6%. Most were treated conservatively (84.3%), but 14.1% underwent percutaneous coronary intervention and 0.7% coronary artery bypass surgery. In-hospital composite MAE was 8.8%; peripartum SCAD patients had higher in-hospital MAE (20.6% vs. 8.2%, P = 0.023). Overall 30-day MACE was 8.8%. Peripartum SCAD and connective tissue disease were independent predictors of 30-day MACE. Conclusion Spontaneous coronary artery dissection predominantly affects women and presents with MI. Despite majority of patients being treated conservatively, survival was good. However, significant cardiovascular complications occurred within 30 days. Long-term follow-up and further investigations on management are warranted.

A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography

Abstract: BACKGROUND Coronary inflammation induces dynamic changes in the balance between water and lipid content in perivascular adipose tissue (PVAT), as captured by perivascular Fat Attenuation Index (FAI) in standard coronary CT angiography (CCTA). However, inflammation is not the only process involved in atherogenesis and we hypothesized that additional radiomic signatures of adverse fibrotic and microvascular PVAT remodelling, may further improve cardiac risk prediction. METHODS AND RESULTS We present a new artificial intelligence-powered method to predict cardiac risk by analysing the radiomic profile of coronary PVAT, developed and validated in patient cohorts acquired in three different studies. In Study 1, adipose tissue biopsies were obtained from 167 patients undergoing cardiac surgery, and the expression of genes representing inflammation, fibrosis and vascularity was linked with the radiomic features extracted from tissue CT images. Adipose tissue wavelet-transformed mean attenuation (captured by FAI) was the most sensitive radiomic feature in describing tissue inflammation (TNFA expression), while features of radiomic texture were related to adipose tissue fibrosis (COL1A1 expression) and vascularity (CD31 expression). In Study 2, we analysed 1391 coronary PVAT radiomic features in 101 patients who experienced major adverse cardiac events (MACE) within 5 years of having a CCTA and 101 matched controls, training and validating a machine learning (random forest) algorithm (fat radiomic profile, FRP) to discriminate cases from controls (C-statistic 0.77 [95%CI: 0.62-0.93] in the external validation set). The coronary FRP signature was then tested in 1575 consecutive eligible participants in the SCOT-HEART trial, where it significantly improved MACE prediction beyond traditional risk stratification that included risk factors, coronary calcium score, coronary stenosis, and high-risk plaque features on CCTA (Δ[C-statistic] = 0.126, P < 0.001). In Study 3, FRP was significantly higher in 44 patients presenting with acute myocardial infarction compared with 44 matched controls, but unlike FAI, remained unchanged 6 months after the index event, confirming that FRP detects persistent PVAT changes not captured by FAI. CONCLUSION The CCTA-based radiomic profiling of coronary artery PVAT detects perivascular structural remodelling associated with coronary artery disease, beyond inflammation. A new artificial intelligence (AI)-powered imaging biomarker (FRP) leads to a striking improvement of cardiac risk prediction over and above the current state-of-the-art.

European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism.

Abstract: The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence

Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study.

Abstract: Aims The CLIMA study, on the relationship between coronary plaque morphology of the left anterior descending artery and twelve months clinical outcome, was designed to explore the predictive value of multiple high-risk plaque features in the same coronary lesion [minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension, and presence of optical coherence tomography (OCT)-defined macrophages] as detected by OCT. Composite of cardiac death and target segment myocardial infarction was the primary clinical endpoint.Methods and results From January 2013 to December 2016, 1003 patients undergoing OCT evaluation of the untreated proximal left am :sults anterior descending coronary artery in the context of clinically indicated coronary angiogram were prospectively enrolled at 11 independent centres (clinicattriaLgov identifier NCT02883088). At 1-year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA 180' (HR 2.4, 95% CI 1.2-4.8), and OCT-defined macrophages (HR 2.7, 95% CI 1.2-6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1-18.6).Conclusion The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events.

Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany

Abstract: AIMS Pulmonary embolism (PE) is the third most common cardiovascular cause of death; systemic thrombolysis is potentially lifesaving treatment in patients presenting with haemodynamic instability. We investigated trends in the use of systemic thrombolysis and the outcome of patients with acute PE. METHODS AND RESULTS We analysed data on the characteristics, comorbidities, treatment, and in-hospital outcome of 885 806 PE patients in Germany between 2005 and 2015. Incidence of acute PE was 99/100 000 population/year and increased from 85/100 000 in 2005 to 109/100 000 in 2015 [β 0.32 (0.26-0.38), P < 0.001]. During the same period, in-hospital case fatality rates decreased from 20.4% to 13.9% [β -0.51 (-0.52 to -0.49), P < 0.001]. The overall proportion of patients treated with systemic thrombolysis increased from 3.1% in 2005 to 4.4% in 2015 [β 0.28 (0.25-0.31), P < 0.001]. Thrombolysis was associated with lower in-hospital mortality rates in patients with haemodynamic instability, both in those with shock not necessitating cardiopulmonary resuscitation (CPR) or mechanical ventilation [odds ratio (OR) 0.42 (0.37-0.48), P < 0.001], and in those who underwent CPR [OR 0.92 (0.87-0.97), P = 0.002]. This association was independent from age, sex, and comorbidities. However, systemic thrombolysis was administered to only 23.1% of haemodynamically unstable patients. CONCLUSION Although the proportion of PE patients treated with systemic thrombolysis increased slightly in Germany between 2005 and 2015, only the minority of haemodynamically unstable patients currently receive this treatment. In the nationwide inpatient cohort, thrombolytic therapy was associated with reduced in-hospital mortality rates in PE patients with shock, and also in those who underwent CPR.

Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials.

Abstract: AIMS: To investigate the safety and efficacy of double vs. triple antithrombotic therapy (DAT vs. TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome or who underwent percutaneous coronary intervention (PCI). METHODS AND RESULTS: A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials comparing DAT vs. TAT in AF patients undergoing PCI. Four trials encompassing 10 234 patients (DAT = 5496 vs. TAT = 4738) were included. The primary safety endpoint (ISTH major or clinically relevant non-major bleeding) was significantly lower with DAT compared with TAT [risk ratio (RR) 0.66, 95% confidence interval (CI) 0.56-0.78; P < 0.0001; I2 = 69%], which was consistent across all available bleeding definitions. This benefit was counterbalanced by a significant increase of stent thrombosis (RR 1.59, 95% CI 1.01-2.50; P = 0.04; I2 = 0%) and a trend towards higher risk of myocardial infarction with DAT. There were no significant differences in all-cause and cardiovascular death, stroke and major adverse cardiovascular events. The comparison of NOAC-based DAT vs. vitamin K antagonist (VKA)-TAT yielded consistent results and a significant reduction of intracranial haemorrhage (RR 0.33, 95% CI 0.17-0.65; P = 0.001; I2 = 0%). CONCLUSION: Double antithrombotic therapy, particularly if consisting of a NOAC instead of VKA and a P2Y12 inhibitor, is associated with a reduction of bleeding, including major and intracranial haemorrhages. This benefit is however counterbalanced by a higher risk of cardiac-mainly stent-related-but not cerebrovascular ischaemic occurrences.

May measurement month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Abstract: AIMS: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. METHODS AND RESULTS: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. CONCLUSION: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.

Associations between vascular risk factors and brain MRI indices in UK Biobank

Abstract: AIMS: Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age. METHODS AND RESULTS: Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker. CONCLUSION: Higher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.

Deep learning for cardiovascular medicine: a practical primer.

Abstract: Deep learning (DL) is a branch of machine learning (ML) showing increasing promise in medicine, to assist in data classification, novel disease phenotyping and complex decision making. Deep learning is a form of ML typically implemented via multi-layered neural networks. Deep learning has accelerated by recent advances in computer hardware and algorithms and is increasingly applied in e-commerce, finance, and voice and image recognition to learn and classify complex datasets. The current medical literature shows both strengths and limitations of DL. Strengths of DL include its ability to automate medical image interpretation, enhance clinical decision-making, identify novel phenotypes, and select better treatment pathways in complex diseases. Deep learning may be well-suited to cardiovascular medicine in which haemodynamic and electrophysiological indices are increasingly captured on a continuous basis by wearable devices as well as image segmentation in cardiac imaging. However, DL also has significant weaknesses including difficulties in interpreting its models (the 'black-box' criticism), its need for extensive adjudicated ('labelled') data in training, lack of standardization in design, lack of data-efficiency in training, limited applicability to clinical trials, and other factors. Thus, the optimal clinical application of DL requires careful formulation of solvable problems, selection of most appropriate DL algorithms and data, and balanced interpretation of results. This review synthesizes the current state of DL for cardiovascular clinicians and investigators, and provides technical context to appreciate the promise, pitfalls, near-term challenges, and opportunities for this exciting new area.

Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy And Cardiac disease (ROPAC)

Abstract: Aims Reducing maternal mortality is a World Health Organization (WHO) global health goal. Although maternal deaths due to haemorrhage and infection are declining, those related to heart disease are increasing and are now the most important cause in western countries. The aim is to define contemporary diagnosis-specific outcomes in pregnant women with heart disease. Methods and results From 2007 to 2018, pregnant women with heart disease were prospectively enrolled in the Registry Of Pregnancy And Cardiac disease (ROPAC). Primary outcome was maternal mortality or heart failure, secondary outcomes were other cardiac, obstetric, and foetal complications. We enrolled 5739 pregnancies; the mean age was 29.5. Prevalent diagnoses were congenital (57%) and valvular heart disease (29%). Mortality (overall 0.6%) was highest in the pulmonary arterial hypertension (PAH) group (9%). Heart failure occurred in 11%, arrhythmias in 2%. Delivery was by Caesarean section in 44%. Obstetric and foetal complications occurred in 17% and 21%, respectively. The number of high-risk pregnancies (mWHO Class IV) increased from 0.7% in 2007–2010 to 10.9% in 2015–2018. Determinants for maternal complications were pre-pregnancy heart failure or New York Heart Association >II, systemic ejection fraction <40%, mWHO Class 4, and anticoagulants use. After an increase from 2007 to 2009, complication rates fell from 13.2% in 2010 to 9.3% in 2017. Conclusion Rates of maternal mortality or heart failure were high in women with heart disease. However, from 2010, these rates declined despite the inclusion of more high-risk pregnancies. Highest complication rates occurred in women with PAH.

Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction

Abstract: AIMS Prevalent right ventricular (RV) dysfunction (RVD) is associated with increased mortality in patients with heart failure with preserved ejection fraction (HFpEF), but no study has characterized long-term changes in RV structure and function within the same patient. METHODS AND RESULTS Patients with unequivocal HFpEF defined by either invasive haemodynamics or hospitalization for pulmonary oedema (n = 271) underwent serial echocardiographic evaluations >6 months apart. Clinical, structural, functional, and haemodynamic characteristics were examined. Over a median of 4.0 years (interquartile range 2.1-6.1), there was a 10% decline in RV fractional area change and 21% increase in RV diastolic area (both P < 0.0001). These changes greatly exceeded corresponding changes in the left ventricle. The prevalence of tricuspid regurgitation increased by 45%. Of 238 patients with normal RV function at Exam 1, 55 (23%) developed RVD during follow-up. Development of RVD was associated with both prevalent and incident atrial fibrillation (AF), higher body weight, coronary disease, higher pulmonary artery and left ventricular filling pressures, and RV dilation. Patients with HFpEF developing incident RVD had nearly two-fold increased risk of death (adjusted hazard ratio 1.89, 95% confidence interval 1.01-3.44; P = 0.04). CONCLUSION While previous attention has centred on the left ventricle in HFpEF, these data show that right ventricular structure and function deteriorate to greater extent over time when compared with changes in the left ventricle. Further study is required to evaluate whether interventions targeting modifiable risk factors identified for incident RVD, including abnormal haemodynamics, AF, coronary disease, and obesity, can prevent RVD and thus improve outcomes.

Tricuspid regurgitation is associated with increased mortality independent of pulmonary pressures and right heart failure: a systematic review and meta-analysis.

Abstract: Aims: To undertake a systematic review and meta-analysis to determine the influence of tricuspid regurgitation (TR) severity on mortality. Methods and results: We performed a systematic search for studies reporting clinical outcomes of patients with TR. The primary endpoint was all-cause mortality and secondary endpoints were cardiac mortality and hospitalization for heart failure (HF). Overall risk ratios (RR) and 95% confidence intervals (CIs) were derived for each endpoint according to the severity of TR by meta-analysing the effect estimates of eligible studies. Seventy studies totalling 32 601 patients were included in the analysis, with a mean (±SD) follow-up of 3.2 ± 2.1 years. Moderate/severe TR was associated with a two-fold increased mortality risk compared to no/mild TR (RR 1.95, 95% CI 1.75-2.17). Moderate/severe TR remained associated with higher all-cause mortality among 13 studies which adjusted for systolic pulmonary arterial pressures (RR 1.85, 95% CI 1.44-2.39), and 15 studies, which adjusted for right ventricular (RV) dysfunction (RR 1.78, 95% CI 1.49-2.13). Moderate/severe TR was also associated with increased cardiac mortality (RR 2.56, 95% CI 1.84-3.55) and HF hospitalization (RR 1.73, 95% CI 1.14-2.62). Compared to patients with no TR, patients with mild, moderate, and severe TR had a progressively increased risk of all-cause mortality (RR 1.25, 1.61, and 3.44, respectively; P < 0.001 for trend). Conclusions: Moderate/severe TR is associated with an increased mortality risk, which appears to be independent of pulmonary pressures and RV dysfunction.

Cardio-Oncology Services: rationale, organization, and implementation A report from the ESC Cardio-Oncology council

Abstract: Aims Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, mediastinal radiotherapy, the presence of CV risk factors, and comorbidities. A recent position paper from the European Society of Cardiology addressed the management of CV monitoring and management of patients treated for cancer. Methods and results The current document is focused on the basis of the Cardio-Oncology (C-O) Services, presenting their rationale, organization, and implementation. C-O Services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardiotoxicity and/or with concomitant CV diseases. These services require a multidisciplinary approach, with the aims of promoting CV health and facilitating the most effective cancer therapy. Conclusion The expected growing volume of patients with cancer at risk of developing/worsening CV disease, the advent of new technological opportunities to refine diagnosis, and the necessity of early recognition of cancer therapy-related toxicity mandate an integrative multidisciplinary approach and care in a specialized environment. This document from the ESC Cardio-Oncology council proposes the grounds for creating C-O Services in Europe based on expert opinion.