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Cardiac resynchronization therapy (CRT) has become a valuable addition to the treatment options for heart failure, in particular for patients with disturbances in electrical conduction that lead to regionally different contraction patterns (dyssynchrony). Dyssynchronous hearts show extensive molecular and cellular remodeling, which has primarily been investigated in experimental animals. Evidence showing that at least several miRNAs play a role in this remodeling is increasing. A comparison of results from measurements in plasma and myocardial tissue suggests that plasma levels of miRNAs may reflect the expression of these miRNAs in the heart. Because many miRNAs released in the plasma are included in extracellular vesicles (EVs), which protect them from degradation, measurement of myocardium-derived miRNAs in peripheral blood EVs may open new avenues to investigate and monitor (reverse) remodeling in dyssynchronous and resynchronized hearts of patients.

Cardiac resynchronization therapy (CRT) has become a valuable addition to the treatment options for heart failure, in particular for patients with disturbances in electrical conduction that lead to regionally different contraction patterns (dyssynchrony). Dyssynchronous hearts show extensive molecular and cellular remodeling, which has primarily been investigated in experimental animals. Evidence showing that at least several miRNAs play a role in this remodeling is increasing. A comparison of results from measurements in plasma and myocardial tissue suggests that plasma levels of miRNAs may reflect the expression of these miRNAs in the heart. Because many miRNAs released in the plasma are included in extracellular vesicles (EVs), which protect them from degradation, measurement of myocardium-derived miRNAs in peripheral blood EVs may open new avenues to investigate and monitor (reverse) remodeling in dyssynchronous and resynchronized hearts of patients.

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.

Background. Preconditioning of donor livers before organ retrieval may improve organ quality after transplantation. We investigated whether preconditioning with metformin reduces preservation injury and improves hepatobiliary function in rat donor livers during ex situ normothermic machine perfusion (NMP) and after orthotopic liver transplantation. Methods. Lewis rats were administered metformin via oral gavage, after which a donor hepatectomy was performed followed by a standardized cold storage period of 4 hours. Graft assessment was performed using NMP via double perfusion of the hepatic artery and portal vein. In an additional experiment, rat donor livers preconditioned with metformin were stored on ice for 4 hours and transplanted to confirm postoperative liver function and survival. Data were analyzed and compared with sham-fed controls. Results. Graft assessment using NMP confirmed that preconditioning significantly improved ATP production, markers for hepatobiliary function (total bile production, biliary bilirubin, and bicarbonate), and significantly lowered levels of lactate, glucose, and apoptosis. After orthotopic liver transplantation, metformin preconditioning significantly reduced transaminase levels. Conclusions. Preconditioning with metformin lowers hepatobiliary injury and improves hepatobiliary function in an in situ and ex situ model of rat donor liver transplantation.

Preeclampsia is a maternal hypertensive disease, complicating 2-8% of all pregnancies. It has been linked to a 2-7-fold increased risk for the development of cardiovascular disease, including heart failure, later in life. A total of 40% of formerly preeclamptic women develop preclinical heart failure, which may further deteriorate into clinical heart failure. Noninvasive cardiac imaging could assist in the early detection of myocardial abnormalities, especially in the preclinical stage, when these changes are likely to be reversible. Moreover, imaging studies can improve our insights into the relationship between preeclampsia and heart failure and can be used for monitoring. Cardiac ultrasound is used to assess quantitative changes, including the left ventricular cavity volume and wall thickness, myocardial mass, systolic and diastolic function, and strain. Cardiac magnetic resonance imaging may be of additional diagnostic value to assess diffuse and focal fibrosis and perfusion. After preeclampsia, sustained elevated myocardial mass along with reduced myocardial circumferential and longitudinal strain and decreased diastolic function is reported. These findings are consistent with the early phases of heart failure, referred to as preclinical (asymptomatic) or B-stage heart failure. In this review, we will provide an up-to-date overview of the potential of cardiac magnetic resonance imaging and echocardiography in identifying formerly preeclamptic women who are at high risk for developing heart failure. The potential contribution to early cardiac screening of women with a history of preeclampsia and the pros and cons of these imaging modalities are outlined. Finally, recommendations for future research are presented.

Preeclampsia is a maternal hypertensive disease, complicating 2–8% of all pregnancies. It has been linked to a 2–7-fold increased risk for the development of cardiovascular disease, including heart failure, later in life. A total of 40% of formerly preeclamptic women develop preclinical heart failure, which may further deteriorate into clinical heart failure. Noninvasive cardiac imaging could assist in the early detection of myocardial abnormalities, especially in the preclinical stage, when these changes are likely to be reversible. Moreover, imaging studies can improve our insights into the relationship between preeclampsia and heart failure and can be used for monitoring. Cardiac ultrasound is used to assess quantitative changes, including the left ventricular cavity volume and wall thickness, myocardial mass, systolic and diastolic function, and strain. Cardiac magnetic resonance imaging may be of additional diagnostic value to assess diffuse and focal fibrosis and perfusion. After preeclampsia, sustained elevated myocardial mass along with reduced myocardial circumferential and longitudinal strain and decreased diastolic function is reported. These findings are consistent with the early phases of heart failure, referred to as preclinical (asymptomatic) or B-stage heart failure. In this review, we will provide an up-to-date overview of the potential of cardiac magnetic resonance imaging and echocardiography in identifying formerly preeclamptic women who are at high risk for developing heart failure. The potential contribution to early cardiac screening of women with a history of preeclampsia and the pros and cons of these imaging modalities are outlined. Finally, recommendations for future research are presented.

Aims The long-term outcomes of the intracoronary delivery of autologous bone marrow-derived cells (BMCs) after acute myocardial infarction are not well established. Following the promising 1 year results of the REGENERATE-AMI trial (despite it not achieving its primary endpoint), this paper presents the analysis of the 5 year clinical outcomes of these acute myocardial infarction patients who were treated with an early intracoronary autologous BMC infusion or placebo., Methods and results A 5 year follow-up of major adverse cardiac events (defined as the composite of all-cause death, recurrent myocardial infarction, and all coronary revascularization) and of rehospitalization for heart failure was completed in 85 patients (BMC n = 46 and placebo n = 39). The incidence of major adverse cardiac events was similar between the BMC-treated patients and the placebo group (26.1% vs. 18.0%, P = 0.41). There were no cases of cardiac death in either group, but an increase in non-cardiac death was seen in the BMC group (6.5% vs. 0%, P = 0.11). The rates of recurrent myocardial infarction and repeat revascularization were similar between the two groups. There were no cases of rehospitalization for heart failure in either group., Conclusion This 5 year follow-up analysis of the REGENERATE-AMI trial did not show an improvement in clinical outcomes for patients treated with cell therapy. This contrasts with the 1 year results which showed improvements in the surrogate outcome measures of ejection fraction and myocardial salvage index.

Genetic aortic diseases are a group of illnesses characterized by aortic aneurysms or dissection in the presence of an underlying genetic defect. They are part of the broader spectrum of heritable thoracic aortic disease, which also includes those cases of aortic aneurysm or dissection with a positive family history but in whom no genetic cause is identified. Aortic disease in these conditions is a major cause of mortality, justifying clinical and scientific emphasis on the aorta. Aortic valve disease and atrioventricular valve abnormalities are known as important additional manifestations that require careful follow-up and management. The archetype of genetic aortic disease is Marfan syndrome, caused by pathogenic variants in the Fibrillin-1 gene. Given the presence of fibrillin-1 microfibers in the myocardium, myocardial dysfunction and associated arrhythmia are conceivable and have been shown to contribute to morbidity and mortality in patients with Marfan syndrome. In this review, we will discuss data on myocardial disease from human studies as well as insights obtained from the study of mouse models of Marfan syndrome. We will elaborate on the various phenotypic presentations in childhood and in adults and on the topic of arrhythmia. We will also briefly discuss the limited data available on other genetic forms of aortic disease.

OBJECTIVE: Marfan syndrome is an autosomal-dominant genetic disorder caused by mutations in the fibrillin-1 gene. The condition is a connective tissue disease that frequently involves the cardiovascular system. The existence of a primary cardiomyopathy in Marfan syndrome, however, is controversial. The aims of this study were to investigate the prevalence of left ventricular dysfunction with both transthoracic echocardiography and cardiovascular magnetic resonance (CMR) in a cohort of Marfan syndrome patients and to investigate patterns of myocardial strain across the cohort.METHODS: We used an institutional database to identify all patients with a firm diagnosis of Marfan syndrome based on Ghent criteria. Inclusion required left ventricular ejection fraction (LVEF) to have been measured by both CMR and transthoracic echocardiography within 12 months of each other. Normal LVEF was defined as a value of >55% when measured by CMR. Velocity vector imaging was used to measure left ventricular longitudinal strain patterns by application of feature tracking to cine magnetic resonance images. Results were compared with data from 20 age-matched control subjects.RESULTS: Sixty-nine Marfan syndrome patients met the inclusion criteria. The mean age was 35.4 ± 15.0 years, and 56.5% were male. The mean LVEF was 59.0% ± 7.0% by CMR and 59.1% ± 5.8% by echo. One-fifth of Marfan syndrome patients (15/69; 21.7%) had reduced function with LVEF ≤55% by CMR, but only 5 of these were identified by echo. Furthermore, echo identified 5 Marfan syndrome patients as having reduced LVEF in the presence of a normal LVEF by CMR. Some Marfan syndrome patients had abnormal longitudinal strain patterns even with LVEF within the reference range.CONCLUSIONS: These data provide support for a primary cardiomyopathy in some Marfan syndrome patients. Cardiovascular magnetic resonance is more sensitive than echo for identifying cases with mild systolic dysfunction. Strain analysis may be more sensitive than simple LVEF assessment for identifying at-risk individuals.

Objectives Pregnancy complicated by pre-eclampsia (PE) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is associated with an increased risk of cardiovascular (CV) diseases later in life. Subclinical cardiac alterations precede eminent CV diseases. Speckle-tracking echocardiography (STE) is an effective method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to investigate the prevalence of subclinical myocardial dysfunction in former PE patients (with and without HELLP syndrome) compared to normotensive women affected by HELLP syndrome. Methods In this cross-sectional retrospective study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent conventional and STE as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. Results Women with a history of PE with HELLP syndrome were characterized by a higher prevalence of altered left ventricular circumferential and global longitudinal two-dimensional (2D) strain (74 and 20%, respectively), altered right ventricular longitudinal 2D strain (37%), and left atrial (LA) 2D strain (57%). Moreover, a higher proportion of alterations of biventricular and LA strains was also present in former PE without HELLP as well as in the normotensive HELLP group. Conclusions In the first years after a pregnancy complicated by HELLP syndrome, irrespective of whether there was concomitant PE, a higher rate of abnormal STE myocardial function is observed. Therefore, these women may benefit from CV risk management.

Background Beyond antihyperglycemic effects, metformin may improve cardiovascular outcomes. Patients with type 2 diabetes often have an elevated plasma level of N-terminal pro B-type as a marker of (sub) clinical cardiovascular disease. We studied whether metformin was associated with a reduction in the serum level of N-terminal pro B-type natriuretic peptide (NT-proBNP) in these patients. Methods In the HOME trial 390 insulin-treated patients with type 2 diabetes were randomized to 850 mg metformin or placebo three times daily. Plasma samples were drawn at baseline, 4, 17, 30, 43 and 52 months. In a post-hoc analysis we analyzed the change in NT-proBNP in both groups. We used a longitudinal mixed model analysis adjusting for age, sex and prior cardiovascular disease. In a secondary analysis we assessed a possible immediate treatment effect post baseline. Results Metformin did not affect NT-proBNP levels over time in the primary analysis (-1% [95%CI -4;3, p = 0.62]). In the secondary analysis there was also no sustained time independent immediate treatment effect (initial increase of 17% [95%CI 4;30, p = 0.006] followed by yearly decrease of -4% [95%CI -7;0, p = 0.07]). Conclusions Metformin as compared to placebo did not affect NT-proBNP plasma levels in this 4.3-year placebo-controlled trial. Potential cardioprotective effects of metformin cannot be explained by changes in cardiac pressures or volumes to the extent reflected by NT-proBNP.

Objective: Heart transplantation (HTx) is the treatment of choice for patients with end-stage heart failure. It is important to determine the factors related to long-term mortality at HTx. We aim to evaluate the effect of the first year clinical variables on 10-year survival at HTx. Methods: The data of 76 consecutive adult HTx recipients who survived more than 1 year after transplantation between April 1998 and July 2007 in a tertiary medical center were retrospectively evaluated. The survival status was checked for each patient at December 2018. We analyzed the effect of renal function through creatinine levels, average resting heart rate, acute rejection episodes, infections, and left ventricular ejection fraction (LVEF) within the first year after HTx on survival. Results: The mean age was 41 +/- 12 years. Percentage of male was 84%. Median survival was 145 +/- 32 months (95% CI, 80.72-209.27), and 36 out of 76 (47.3%) patients died during follow-up. LVEF was found lowered in nonsurvived group compared to survived ones [57.2 +/- 5.8% vs 59.3 +/- 2.1% (P = .043)]. Cox regression analyses revealed that only LVEF and creatinine at the end of the first year after HTx were found to be significantly associated with mortality [(HR = 0.91, 95% CI, 0.85-0.98, P = .012) and (HR = 1.09, 95% CI, 1.68-5.67, P < .001), respectively]. Conclusion: Decrease in LVEF and high serum creatinine level at the end of the first year after HTx were found to be associated with poor 10-year survival in HTx recipients.

Aims Cardiac remodelling is the process by which the heart adapts to its environment. Mechanical load is a major driver of remodelling. Cardiac tissue culture has been frequently employed for in vitro studies of load-induced remodelling; however, current in vitro protocols (e.g. cyclic stretch, isometric load, and auxotonic load) are oversimplified and do not accurately capture the dynamic sequence of mechanical conformational changes experienced by the heart in vivo. This limits translational scope and relevance of findings. Methods and results We developed a novel methodology to study chronic load in vitro. We first developed a bioreactor that can recreate the electromechanical events of in vivo pressure–volume loops as in vitro force–length loops. We then used the bioreactor to culture rat living myocardial slices (LMS) for 3 days. The bioreactor operated based on a 3-Element Windkessel circulatory model enabling tissue mechanical loading based on physiologically relevant parameters of afterload and preload. LMS were continuously stretched/relaxed during culture simulating conditions of physiological load (normal preload and afterload), pressure-overload (normal preload and high afterload), or volume-overload (high preload & normal afterload). At the end of culture, functional, structural, and molecular assays were performed to determine load-induced remodelling. Both pressure- and volume-overloaded LMS showed significantly decreased contractility that was more pronounced in the latter compared with physiological load (P Conclusion We have developed a proof-of-concept platform and methodology to recreate remodelling under pathophysiological load in vitro. We show that LMS cultured in our bioreactor remodel as a function of the type of mechanical load applied to them.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed. R.A.d.B. is supported by the Netherlands Heart Foundation (CVON DOSIS, grant 2014-40, CVON SHE-PREDICTS-HF, grant 2017-21, and CVON RED-CVD, grant 2017-11), and the European Research Council (ERC CoG 818715, SECRETE-HF). C.G.T. is supported by a Federico II University/Ricerca di Ateneo grant. Celutkiene, J (corresponding author), Vilnius Univ, Fac Med, Inst Clin Med, Clin Cardiac & Vasc Dis, Santariskiu 2, LT-08661 Vilnius, Lithuania. jelena.celutkiene@santa.lt

Background Angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and beta-blockers are guideline-recommended first-line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under-dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up-titration of ACEi/ARBs and beta-blockers with all-cause mortality and its combination with hospitalization for HF. Methods and results A total of 6787 HFrEF patients (mean age 62.6 +/- 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 +/- 7.2%) were enrolled in the prospective multinational European (BIOSTAT-CHF;n = 2100) and Asian (ASIAN-HF;n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline-recommended target doses (GRTD) of combination ACEi/ARB and beta-blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved >= 50% GRTD for both ACEi/ARB and beta-blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and beta-blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26-0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up-titrating beta-blockers was associated with a consistent and greater reduction in hazards of all-cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25-0.63) than corresponding ACEi/ARB up-titration (HR 0.75, 95% CI 0.53-1.07). Conclusion This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and beta-blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up-titrating beta-blockers to target dose was associated with greater mortality reduction than up-titrating ACEi/ARB.

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality., Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. In this Consensus Statement, the authors summarize the use of SPECT, PET, MRI, echocardiography, CT and invasive coronary flow and pressure measurement, and describe the relative strengths and weaknesses of each modality.

Background Echocardiographic reference intervals for Friesian horses are poorly described. Objectives To obtain reference intervals for echocardiographic measurements in Friesians and compare these with Warmbloods. Animals One hundred healthy adult Friesians and 100 healthy adult Warmblood horses. Methods Cross-sectional study. Two-dimensional and M-mode echocardiographic images were obtained. Echocardiographic measurements, including size, area, and volumetric measurements of left atrium, left and right ventricle, aorta, and pulmonary artery, were performed. Measurements were compared between the 2 breeds using an independent samples t test with Bonferroni correction for multiple comparisons. Results Reference ranges for standard echocardiographic measurements in Friesians were obtained. Several left ventricular measurements were significantly smaller in Friesians compared to Warmbloods, such as the left ventricular end-diastolic volume using the 4-chamber modified Simpsons' method (99.85% confidence interval for the difference [CI] = -245 to -63). Also the right ventricular end-diastolic and peak-systolic internal diameter were smaller in Friesians (99.85% CI = -1.33 to -0.6 and 99.85% CI = -1.54 to -0.76, respectively). Fractional shortening (99.85% CI = 0.61-6) and ejection fraction (99.85% CI = 0.21-4.6) were significantly larger. No structural effects of systemic hypertension, such as concentric hypertrophy, were detected. Conclusions and Clinical Importance Our study provides reference intervals for echocardiographic measurements in Friesians useful in a clinical setting. In general, the left ventricular dimensions in Friesians were significantly smaller compared to Warmbloods, emphasizing the need for breed-specific reference intervals.

Obesity, defined as a body mass index of >= 30 kg/m(2), is the most common chronic metabolic disease worldwide and its prevalence has been strongly increasing. Obesity has deleterious effects on cardiac function. The purpose of this review is to evaluate the effects of obesity and excessive weight loss due to bariatric surgery on cardiac function, structural changes and haemodynamic responses of both the left and right ventricle.

Targeted HFpEF therapy based on matchmaking of human and animal models. Am J Physiol Heart Circ Physiol 315: H1670-H1683, 2018. First published September 21, 2018; doi:10.1152/ajpheart.00024.2018. The diversity in clinical phenotypes and poor understanding of the underlying pathophysiology of heart failure with preserved ejection fraction (HFpEF) is the main reason why no effective treatments have been found yet. Targeted, instead of one size fits all, treatment seems the only promising approach for treating 1114pE14. To be able to design a targeted, phenotype-specific HFpEF treatment, the matrix relating clinical phenotypes and underlying pathophysiological mechanisms has to be clarified. This review discusses the opportunities for additional evaluation of the underlying pathophysiological processes, e.g., to evaluate biological phenotypes on top of clinical routine, to guide us toward a phenotype specific HFpEF treatment. Moreover, a translational approach with matchmaking of animal models to biological HFpEF phenotypes will be a valuable step to test the effectiveness of novel, targeted interventions in IIFpEF.

Aims: The New York Heart Association (NYHA) classification is frequently used in the management of heart failure but may be limited by patient and physician subjectivity. Cardiopulmonary exercise testing (CPET) provides a potentially more objective measurement of functional status. We aim to study the correlation between NYHA classification and peak oxygen consumption (pVO(2)) on Cardiopulmonary Exercise Testing (CPET) within and across published studies. Methods and results: A systematic literature review on all studies reporting both NYHA class and CPET data was performed, and pVO(2) from CPET was correlated to reported NYHA class within and across eligible studies. 38 studies involving 2645 patients were eligible. Heterogenity was assessed by the Q statistic, which is a chi(2) test and marker of systematic differences between studies. Within each NYHA class, significant heterogeneity in pVO(2) was seen across studies: NYHA I (n = 17, Q = 486.7, p

Aims: The New York Heart Association (NYHA) classification is frequently used in the management of heart failure but may be limited by patient and physician subjectivity. Cardiopulmonary exercise testing (CPET) provides a potentially more objective measurement of functional status. We aim to study the correlation between NYHA classification and peak oxygen consumption (pVO(2)) on Cardiopulmonary Exercise Testing (CPET) within and across published studies.Methods and results: A systematic literature review on all studies reporting both NYHA class and CPET data was performed, and pVO(2) from CPET was correlated to reported NYHA class within and across eligible studies. 38 studies involving 2645 patients were eligible. Heterogenity was assessed by the Q statistic, which is a chi(2) test and marker of systematic differences between studies. Within each NYHA class, significant heterogeneity in pVO(2) was seen across studies: NYHA I (n = 17, Q = 486.7, p Conclusion: There was a general inverse correlation between NYHA class and pVO(2); However, significant heterogeneity in pVO(2) exists across studies within each NYHA class. While the NYHA classification holds clinical value in heart failure management, died comparison across studies may have its limitations. (C) 2018 Elsevier B.V. All rights reserved.

PURPOSE An accurate evaluation of left ventricular volumes, mass, and ejection fraction (EF) and an early exclusion or detection of significant coronary artery disease or cardiac allograft vasculopathy are mandatory for clinical management and prognosis assessment of heart-transplanted patients (HTP). The purpose of this article was to evaluate the role of dual-step prospective electrocardiography-triggered Dual-Source CT (pECGdual-step-DSCT) in HTP for the assessment of left-ventricular function, in comparison with echocardiography (echo) and cardiac magnetic resonance (CMR) performed on the same day, and of the coronary arteries as well. MATERIALS AND METHODS Left-ventricular EF, end-diastolic volume, end-systolic volume, stroke volume, cardiac output (CO), and mass were assessed in 11 HTP by pECGdual-step-DSCT in comparison with CMR and echo performed on the same day. During all the examinations, the heart rate was recorded. CT coronary artery assessment was also performed. RESULTS Heart rate was lower during DSCT (75.6±7.8 bpm; P

The exact mechanism of atrial fibrillation (AF) is still incompletely understood. A number of alterations that impact focal electrical discharge, the atrial substrate and modulating factors contribute to its pathogenesis. Atrial remodelling (resulting in atrial cardiomyopathy) sets the stage for AF development. Once present, AF results in the loss of synchronized atrial contraction, which affects ventricular filling and atrial reservoir and conduit functions. Passive atrial function is particularly important in patients with left ventricular diastolic dysfunction. AF can cause tachycardiomyopathy, a mostly reversible cardiac alteration induced by tachycardia. At a structural level, atrial support is also instrumental to the function of atrioventricular valves. All of these functions can be recovered to variable degrees via rhythm control strategies. Surgical and hybrid ablation show very promising results, especially in patients with a more advanced disease substrate. This review highlights the pathophysiological aspects of AF related to left atrial function and their practical implications for surgical rhythm management.

The exact mechanism of atrial fibrillation (AF) is still incompletely understood. A number of alterations that impact focal electrical discharge, the atrial substrate and modulating factors contribute to its pathogenesis. Atrial remodelling (resulting in atrial cardiomyopathy) sets the stage for AF development. Once present, AF results in the loss of synchronized atrial contraction, which affects ventricular filling and atrial reservoir and conduit functions. Passive atrial function is particularly important in patients with left ventricular diastolic dysfunction. AF can cause tachycardiomyopathy, a mostly reversible cardiac alteration induced by tachycardia. At a structural level, atrial support is also instrumental to the function of atrioventricular valves. All of these functions can be recovered to variable degrees via rhythm control strategies. Surgical and hybrid ablation show very promising results, especially in patients with a more advanced disease substrate. This review highlights the pathophysiological aspects of AF related to left atrial function and their practical implications for surgical rhythm management.

Background: There is limited information about the 6-min walk test (6MWT) in elderly patients with heart failure. We evaluated 6MWT and the effect of nebivolol on 6MWT from the SENIORS trial. Methods and results: The SENIORS trial evaluated nebivolol versus placebo on death and hospitalisation in patients aged ≥ 70 years with heart failure. A total of 1982 patients undertook a 6MWT at baseline and 1716 patients at 6 months. Patients were divided into tertiles (≤ 200 m, 201 to ≤ 300 m and > 300 m) and to change in distance walked between baseline and 6 months (< 0 m, 0 to < 30 m and ≥ 30 m). The primary outcome was all-cause mortality and cardiovascular hospital admission. Secondary endpoint was all-cause mortality. Baseline walk distance of ≤ 200 m incurred a greater risk of the primary and secondary outcomes (HR 1.41, CI 95% 1.17–1.69, p < 0.001) and (HR 1.37, CI 95% 1.05–1.78, p = 0.019). A decline in walk distance over 6 months was associated with increased risk of clinical events. Nebivolol had no influence on change in walk distance over 6 months. Conclusions: The 6MWT has prognostic utility in elderly patients. Those who walked less than 200 m were at highest risk. Nebivolol had no effect on 6MWT.

Objective The aim of this systematic review and meta-analysis was to describe comprehensively the pattern of cardiac remodeling during normotensive human singleton pregnancy and to compare it with that of pregnancy complicated by hypertension.Methods We performed a meta-analysis of the current literature on cardiac remodeling during normotensive and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies needed to report a reference measurement (matched non-pregnant control group, prepregnancy or postpartum) and measurements made during predetermined gestational-age intervals. Mean differences between reference and pregnancy data were calculated using the random-effects model described by DerSimonian and Laird.Results Forty-eight studies were included in the meta-analysis, with publication dates ranging from 1977 to 2016. During normotensive pregnancy, most geometric indices started to increase in the second trimester. Left ventricular mass (LVM) increased by 28.36 (95% CI, 19.73-37.00) g (24%), and relative wall thickness (RWT) increased by 0.03 (95% CI, 0.02-0.05) (10%) compared with those in the reference group. During hypertensive pregnancy, LVM and RWT increased more than during normotensive pregnancy (92 (95% CI, 75.46-108.54) g (95%) and 0.14 (95% CI, 0.09-0.19) (56%), respectively).Conclusions During normotensive pregnancy, most cardiac geometric indices change from the second trimester onwards. Both LVM and RWT increase, by 20% and 10%, respectively, consistent with concentric rather than eccentric remodeling. Cardiac adaptation in hypertensive pregnancy deviates from that in healthy pregnancy by a greater change in LVM (95% increase from reference) and RWT (56% increase from reference). Copyright (C) 2017 ISUOG. Published by John Wiley & Sons Ltd.

Objectives Preclinical and clinical studies suggested cardioprotective effects of metformin treatment. In the GIPS-III trial, 4 months of metformin treatment did not improve left ventricular ejection fraction in patients presenting with ST-elevation myocardial infarction (STEMI). Here, we report the 2-year follow-up results. Methods Between January 2011 and May 2013, 379 STEMI patients without diabetes undergoing primary percutaneous coronary intervention were randomized to a 4-month treatment with metformin (500 mg twice daily) (N = 191) or placebo (N = 188) in the University Medical Center Groningen. Two-year follow-up data was collected to determine its effect on predefined secondary endpoints: the incidence of major adverse cardiac events (MACE), its individual components, all-cause mortality, and new-onset diabetes. Results For all 379 patients all-cause mortality data were available. For seven patients (2%) follow-up data on MACE was limited, ranging from 129 to 577 days. All others completed the 2-year follow-up visit. Incidence of MACE was 11 (5.8%) in metformin and 6 (3.2%) in placebo treated patients [hazard ratio (HR) 1.84, confidence interval (CI) 0.68–4.97, P = 0.22]. Three patients died in the metformin group and one in the placebo treatment group. Individual components of MACE were also comparable between both groups. New-onset diabetes mellitus was 34 (17.8%) in metformin and 32 (17.0%) in placebo treated patients (odds ratio 1.15, CI 0.66–1.98, P = 0.84). After multivariable adjustment the incidence of MACE was comparable between the treatment groups (HR 1.02, CI 0.10–10.78, P = 0.99). Conclusions Four months metformin treatment initiated at the time of hospitalization in STEMI patients without diabetes did not exert beneficial long-term effects. Trial registration clinicaltrials.gov Identifier: NCT01217307. Electronic supplementary material The online version of this article (doi:10.1007/s00392-017-1140-z) contains supplementary material, which is available to authorized users.

Aims: The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European Society of Cardiology (ESC) vs. non-ESC countries. Methods and results: Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with completed case record forms (from 43 countries) entered into this ongoing registry. There were marked differences in socio-demographic parameters such as Human Development Index, GINI index on inequality, and Health Expenditure in PPCM patients from ESC vs. non-ESC countries (P

Compared to healthy individuals, obese have significantly higher systolic and diastolic blood pressure, mean arterial pressure, heart rate, and cardiac output. The aim of this study was to evaluate cardiovascular hemodynamic changes before and 3 months after bariatric surgery.Patients scheduled for bariatric surgery between the 29th of September 2016 and 24th of March 2016 were included and compared with 24 healthy individuals. Hemodynamic measurements were performed preoperatively and 3 months after surgery, using the NexfinA (R) non-invasive continuous hemodynamic monitoring device (Edwards Lifesciences/BMEYE B.V., Amsterdam, the Netherlands).Eighty subjects were included in this study, respectively, 56 obese patients scheduled for bariatric surgery and 24 healthy individuals. Baseline hemodynamic measurements showed significant differences in cardiac output (6.5 +/- 1.6 versus 5.7 +/- 1.6 l/min, p = 0.046), mean arterial pressure (107 +/- 19 versus 89 +/- 11 mmHg, p = 0.001), systolic (134 +/- 24 versus 116 +/- 18 mmHg, p = 0.001) and diastolic blood pressure (89 +/- 17 versus 74 +/- 10 mmHg, p = 0.001), and heart rate (87 +/- 12 versus 76 +/- 14 bpm, p = 0.02) between obese and healthy subjects. Three months after surgery, significant changes occurred in mean arterial pressure (89 +/- 17 mmHg, p = 0.001), systolic (117 +/- 24 mmHg, p = 0.001) and diastolic blood pressure (71 +/- 15 mmHg, p = 0.001), stroke volume (82.2 +/- 22.4 ml, p = 0.03), and heart rate (79 +/- 17 bpm, p = 0.02)Three months after bariatric surgery, significant improvements occur in hemodynamic variables except cardiac output and cardiac index, in the patient group.

Aims: Correction of mitral and/or tricuspid regurgitation (MR, TR) frequently leads to poor outcomes in the days following intervention. We sought to understand how abrupt correction of MR and TR affects ventricular load and to investigate if gradual correction is beneficial.Methods and results: MR and TR were simulated using the CircAdapt cardiovascular system model with effective regurgitant orifice (ERO) areas of 0.5 cm(2) and 0.7 cm(2). Ventricular and atrial contractility reductions to 40% of normal and pulmonary hypertension were simulated. Abrupt and gradual ERO closure were simulated with homeostatic regulation of blood pressure and volume. Abrupt correction of MR increased left and right ventricular fibre stress by 40% and 15%, respectively, whereas TR correction increased left and right ventricular fibre stress by 26% and 19%, respectively. This spike was followed by a rapid drop in fibre stress. Myocardial dysfunction prolonged the spike but reduced its amplitude. Right ventricular fibre stress increased more with pulmonary hypertension and TR. Gradual correction demonstrated no spike in tissue load.Conclusions: Simulations demonstrated that abrupt ERO closure creates a transient increase in ventricular load that is prolonged by worsened myocardial condition and exacerbated by pulmonary hypertension. Gradual closure of the ERO abolishes this spike and merits clinical investigation.

Background Women with a history of preeclampsia are at increased risk of cardiovascular morbidity and mortality. However, the underlying mechanisms of disease association, and the ideal method of monitoring this high‐risk group, remains unclear. This review aims to determine whether women with a history of preeclampsia show clinical or subclinical cardiac changes when evaluated with an echocardiogram. Methods and Results A systematic search of MEDLINE , EMBASE, and CINAHL databases was performed to identify studies that examined cardiac function in women with a history of preeclampsia, in comparison with those with normotensive pregnancies. In the 27 included studies, we found no significant differences between preeclampsia and nonpreeclampsia women with regard to left ventricular ejection fraction, isovolumetric relaxation time, or deceleration time. Women with a history of preeclampsia demonstrated a higher left ventricular mass index and relative wall thickness with a mean difference of 4.25 g/m 2 (95% CI , 2.08, 6.42) and 0.03 (95% CI , 0.01, 0.05), respectively. In comparison with the nonpreeclampsia population, they also demonstrated a lower E/A and a higher E/e′ ratio with a mean difference of −0.08 (95% CI , −0.15, −0.01) and 0.84 (95% CI , 0.41, 1.27), respectively. Conclusions In comparison with women who had a normotensive pregnancy, women with a history of preeclampsia demonstrated a trend toward altered cardiac structure and function. Further studies with larger sample sizes and consistent echocardiogram reporting with the use of sensitive preclinical markers are required to assess the role of echocardiography in monitoring this high‐risk population group.

Haemodynamic monitoring is the cornerstone in the optimization of tissue perfusion and the prevention of deteriorating metabolism. Haemodynamic alterations could be summarized in terms of cardiac dysfunction, changes of loading conditions (preload or/and afterload), and patient related issues. This review aims to present the clinical applications of different haemodynamic monitoring techniques, discuss advantages and disadvantages, and provide guidance to help the clinician select those techniques suitable to optimize haemodynamics in individual patients during the perioperative period. ispartof: ANAESTHESIOLOGY INTENSIVE THERAPY vol:51 issue:2 pages:147-158 ispartof: location:Poland status: published

Introduction: The revised Ghent nosology presents the classical features of Marfan syndrome. However, behind its familiar face, Marfan syndrome hides less well-known features. Areas covered: The German Marfan Organization listed unusual symptoms and clinical experts reviewed the literature on clinical features of Marfan syndrome not listed in the Ghent nosology. Thereby we identified the following features: (1) bicuspid aortic valve, mitral valve prolapse, pulmonary valve prolapse, tricuspid valve prolapse, (2) heart failure and cardiomyopathy, (3) supraventricular arrhythmia, ventricular arrhythmia, and abnormal repolarization, (4) spontaneous coronary artery dissection, anomalous coronary arteries, and atherosclerotic coronary artery disease, tortuosity-, aneurysm-, and dissection of large and medium-sized arteries, (5) restrictive lung disease, parenchymal lung disease, and airway disorders, (6) obstructive- and central sleep apnea, (7) liver and kidney cysts, biliary tract disease, diaphragmatic hernia, and adiposity, (8) premature labor, and urinary incontinence, (9) myopathy, reduced bone mineral density, and craniofacial manifestations, (10) atrophic scars, (11) caries, and craniomandibular dysfunction, (12) headache from migraine and spontaneous cerebrospinal fluid leakage, (13) cognitive dysfunction, schizophrenia, depression, fatigue, and pain, (14) and activated fibrinolysis, thrombin, platelets, acquired von Willebrand disease, and platelet dysfunction. Expert commentary: Future research, nosologies, and guidelines may consider less well-known features of Marfan syndrome.