Cardiac pacemaker-related endocarditis complicated with pulmonary embolism: Case report.

Cardiac device-related endocarditis as a device-therapy complication is a growing problem due to higher life expectancy and the increasing number of abandoned leads and subclinical symptoms. We reported a case of a 47-year-old woman with an implanted pacemaker who was admitted to the clinic for cardiology due to the right-sided device-related infective endocarditis of the pacemaker leads with vegetations, predominantly in the right atrium and right ventricle and complicated by pulmonary embolism. Several years after pacemaker implantation, she was diagnosed with systemic lupus erythematosus and started immunosuppressive therapy. The patient was treated with prolonged intravenous antibiotic therapy. The atrial and ventricular lead was extirpated, and the posterior leaflet of the tricuspid valve was shaved.

Cardiac hypertrophy simulations using parametric and echocardiography-based left ventricle model with shell finite elements.

In our paper, we simulated cardiac hypertrophy with the use of shell elements in parametric and echocardiography-based left ventricle (LV) models. The hypertrophy has an impact on the change in the wall thickness, displacement field and the overall functioning of the heart. We computed both eccentric and concentric hypertrophy effects and tracked changes in the ventricle shape and wall thickness. Thickening of the wall was developed under the influence of concentric hypertrophy, while the eccentric hypertrophy produces wall thinning. To model passive stresses we used the recently developed material modal based on the Holzapfel experiments. Also, our specific shell composite finite element models for heart mechanics are much smaller and simpler to use with respect to conventional 3D models. Furthermore, the presented modeling approach of the echocardiography-based LV can serve as the basis for practical applications since it relies on the true patient-specific geometry and experimental constitutive relationships. Our model gives an insight into hypertrophy development in realistic heart geometries, and it has the potential to test medical hypotheses regarding hypertrophy evolution in a healthy and heart with a disease, under the influence of different conditions and parameters.

Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation.

The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions.

Prognostic Value of Transthoracic Doppler Echocardiography Coronary Flow Velocity Reserve in Patients With Asymmetric Hypertrophic Cardiomyopathy.

Background Microvascular dysfunction might be a major determinant of clinical deterioration and outcome in patients with hypertrophic cardiomyopathy (HCM). However, long-term prognostic value of transthoracic Doppler echocardiography (TDE) coronary flow velocity reserve (CFVR) on clinical outcome is uncertain in HCM patients. Therefore, the aim of our study was to assess long-term prognostic value of CFVR on clinical outcome in HCM population. Methods and Results We prospectively included 150 HCM patients (82 women; mean age 48±15 years). Patients' clinical characteristics, echocardiographic and CFVR findings (both for left anterior descending [LAD] and posterior descending artery [PD]), were assessed in all patients. The primary outcome was a composite of: HCM related death, heart failure requiring hospitalization, sustained ventricular tachycardia and ischemic stroke. Patients were stratified into 2 subgroups depending on CFVR LAD value: Group 1 (CFVR LAD>2, [n=87]) and Group 2 (CFVR LAD≤2, [n=63]). During a median follow-up of 88 months, 41/150 (27.3%) patients had adverse cardiac events. In Group 1, there were 8/87 (9.2%), whereas in Group 2 there were 33/63 (52.4%, P<0.001 vs. Group 1) adverse cardiac events. By Kaplan-Meier analysis, patients with preserved CFVR LAD had significantly higher cumulative event-free survival rate compared to patients with impaired CFVR LAD (96.4% and 90.9% versus 66.9% and 40.0%, at 5 and 8 years, respectively: log-rank 37.2, P<0.001). Multivariable analysis identified only CFVR LAD≤2 as an independent predictor for adverse cardiac outcome (HR 6.54; 95% CI 2.83-16.30, P<0.001), while CFVR PD was not significantly associated with outcome. Conclusions In patients with HCM, impaired CFVR LAD (≤2) is a strong, independent predictor of adverse cardiac outcome. When the aim of testing is HCM risk stratification and CFVR LAD data are available, the evaluation of CFVR PD is redundant.

Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis.

Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.

Impairment of coronary flow velocity reserve and global longitudinal strain in women with cardiac syndrome X and slow coronary flow.

BACKGROUND: Microvascular dysfunction (MVD) is associated with adverse prognosis and may account for abnormal stress tests and angina symptoms in women with cardiac syndrome X (CSX). The aim of our study was to assess MVD by coronary flow velocity reserve (CFVR) and left ventricular (LV) contractile function by LV global longitudinal strain (LVGLS) in CSX patients with respect to presence of slow coronary flow (SCF). It was of additional importance to evaluate clinical status of CSX patients using Seattle Angina Questionnaire. METHODS AND RESULTS: Study population included 70 women with CSX (mean age 61 ± 7 years) and 34 age-matched controls. CSX group was stratified into two subgroups depending on SCF presence: CSX-Thrombolysis In Myocardial Infarction (TIMI) 3- normal flow subgroup (n = 38) and CSX-TIMI 2- SCF subgroup (n = 32) as defined by coronary angiography. LVGLS measurements and CFVR of left anterior descending (LAD) and posterior descending (PD) artery were performed. CFVR-LAD and PD were markedly impaired in CSX group compared to controls (2.34 ± 0.25 vs 3.05 ± 0.21, p < 0.001; 2.32 ± 0.24 vs 3.01 ± 0.13, p < 0.001), and furthermore decreased in CSX-TIMI 2 patients. Resting, peak, and ΔLVGLS were all significantly impaired in CSX group compared to controls (for all p < 0.001), and furthermore reduced in CSX-TIMI 2 subgroup. Strongest correlation was found between peak LVGLS and CFVR LAD (r = -0.784, p < 0.001) and PD (r = -0.772, p < 0.001). CSX-TIMI 2 subgroup had more frequent angina symptoms and more impaired quality of life. CONCLUSIONS: MVD in CSX patients is demonstrated by reduction in CFVR and LVGLS values. SCF implies more profound impairment of microvascular and LV systolic function along with worse clinical presentation.

ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on 'coronary microvascular dysfunction in cardiovascular disease'.

Although myocardial ischaemia usually manifests as a consequence of atherosclerosis-dependent obstructive epicardial coronary artery disease, a significant percentage of patients suffer ischaemic events in the absence of epicardial coronary artery obstruction. Experimental and clinical evidence highlight the abnormalities of the coronary microcirculation as a main cause of myocardial ischaemia in patients with 'normal or near normal' coronary arteries on angiography. Coronary microvascular disturbances have been associated with early stages of atherosclerosis even prior to any angiographic evidence of epicardial coronary stenosis, as well as to other cardiac pathologies such as myocardial hypertrophy and heart failure. The main objectives of the manuscript are (i) to provide updated evidence in our current understanding of the pathophysiological consequences of microvascular dysfunction in the heart; (ii) to report on the current knowledge on the relevance of cardiovascular risk factors and comorbid conditions for microcirculatory dysfunction; and (iii) to evidence the relevance of the clinical consequences of microvascular dysfunction. Highlighting the clinical importance of coronary microvascular dysfunction will open the field for research and the development of novel strategies for intervention will encourage early detection of subclinical disease and will help in the stratification of cardiovascular risk in agreement with the new concept of precision medicine.

Prosthetic valve endocarditis - A trouble or a challenge?

Prosthetic valve endocarditis (PVE) represents a rare and serious complication of valve replacement associated with high morbidity and mortality, which significantly differs from native valve endocarditis (NVE). There are two major problems: establishing diagnosis and treatment of PVE. Diagnosis in PVE is challenging and often requires several imaging methods besides standard microbiological analyzes. Transesophageal echocardiographic examination remains the widely used imaging technique in PVE diagnosis, but additional techniques such as computed tomography (CT) and 18F-fluodeoxyglucose positron emission tomography/CT are often necessary. Persistent fever, embolic complications, valve dehiscence, intracardial abscess, heart failure, as well as staphylococcal and fungal PVE require surgical treatment to avoid lethal outcome. The introduction of transcatheter valve implantations and devices significantly complicated the approach - diagnostic and therapeutic to PVE patients. Despite constantly increasing knowledge regarding pathogenesis and treatment of PVE, the optimal therapy remains a matter of debate. Additional studies are necessary to define therapeutic strategies for this potentially fatal complication.

Coronary Microcirculation in Heart Failure with Preserved Systolic Function.

BACKGROUND: The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. METHODS: The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. RESULTS: The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. CONCLUSION: There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.

Successful establishment of a left ventricular assist device program in an emerging country: one year experience.

BACKGROUND: The primary goal of this study was to evaluate the outcomes of patients with end-stage heart failure (HF) who underwent continuous flow left ventricular assist device (CF-LVAD) in a developing country and to compare to those reported by more developed countries. The secondary goal was on determining factors that may be connected to improved survival. METHODS: We prospectively analyzed 47 consecutive patients who underwent CF-LVAD at our institution. After one year the survival and adverse event profiles of patients were evaluated. At 3, 6 and 12 months, the cardiac, renal and liver function outcomes were assessed. RESULTS: The 30-day, 6-month and 1-year survival rates were 89%, 85% and 80%, respectively. A significant improvement in dimensions and ejection fraction of left ventricle, BNP, functional capacity, blood urea nitrogen (BUN) and total bilirubin (P<0.05 for all) were noticed 3 months post-CF-LVAD implantation, and patients were stable throughout the entire first year follow up. In the group of patients with baseline renal dysfunction (RD) there were significant improvements of renal function (P=0.004), with no changes on follow up. 57% of patients exhibited some kind of adverse event, commonly in the form of bleeding. In multivariate Cox regression analysis renal failure was found to be as an independent risk factor for the overall survival (HR =13.1, P<0.001). CONCLUSIONS: In conclusion, our data extends previous findings from centers of developed countries, that CF-LVAD is an adequate treatment option for patients suffering from end-stage HF, and encourages expansion of CF-LVAD implantation in developing countries with nascent HT program.

The relationship between causative microorganisms and cardiac lesions caused by infective endocarditis: New perspectives from the contemporary cohort of patients.

BACKGROUND: The etiology of infective endocarditis (IE) is changing. More aggressive forms with multiple IE cardiac lesions have become more frequent. This study sought to explore the relationship between contemporary causative microorganisms and IE cardiac lesions and to analyze the impact of multiple lesions on treatment choice. METHODS: In 246 patients hospitalized for IE between 2008 and 2015, cardiac lesions caused by IE were analyzed by echocardiography, classified according to the 2015 European Society of Cardiology guidelines and correlated with microbiological data. We defined a new parameter, the Echo IE Sum, to summarize all IE cardiac lesions in a single patient, enabling comprehensive comparisons between different etiologies and treatment strategies. RESULTS: Staphylococcus aureus was associated with the development of large vegetation (OR 2.442; 95% CI 1.220-4.889; p=0.012), non-HACEK bacteria with large vegetation (OR 13.662; 95% CI 2.801-66.639; p=0.001), perivalvular abscess or perivalvular pseudoaneurysm (OR 5.283; 95% CI 1.069-26.096; p=0.041), and coagulase-negative staphylococci (CoNS) with leaflet abscess or aneurysm (OR 3.451; 95% CI 1.285-9.266, p=0.014), and perivalvular abscess or perivalvular pseudoaneurysm (OR 4.290; 95% CI 1.583-11.627; p=0.004). The Echo IE Sum significantly differed between different etiologies (p<0.001), with the highest value in non-HACEK and the lowest in streptococcal endocarditis. Patients operated for IE had a significantly higher Echo IE Sum vs those who were medically treated (p<0.001). CONCLUSION: None of the IE cardiac lesions is microorganism-specific. However, more severe lesions were caused by S. aureus, CoNS, and non-HACEK bacteria. The highest propensity to develop multiple lesions was shown by the non-HACEK group. Higher Echo IE Sum in patients sent to surgery emphasized the importance of multiple IE cardiac lesions on treatment choice and potential usage of Echo IE Sum in patient management.

N-terminal pro-brain natriuretic peptide is related with coronary flow velocity reserve and diastolic dysfunction in patients with asymmetric hypertrophic cardiomyopathy.

BACKGROUND: The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP. METHODS AND RESULTS: In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP. CONCLUSION: Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM.

Gauging the response to cardiac resynchronization therapy: The important interplay between predictor variables and definition of a favorable outcome.

AIMS: Selection of patients who are viable candidates for cardiac resynchronization therapy (CRT), prediction of the response to CRT as well as an optimal definition of a favorable response, all require further exploration. The purpose of this study was to evaluate the interplay between the prediction of the response to CRT and the definition of a favorable outcome. METHODS: Seventy patients who received CRT were included. All patients met current guideline criteria for CRT. Forty-three echocardiographic parameters were evaluated before CRT and at 1, 3, 6, and 12 months. M-mode, 2D echocardiography, and Doppler imaging were used to quantify left ventricular (LV) systolic and diastolic function, mitral regurgitation, right ventricular systolic function, pulmonary artery pressure, and myocardial mechanical dyssynchrony. The following definitions of a favorable CRT response were used: left ventricular ejection fraction (LVEF) improvement more >5% acutely following CRT, LVEF improvement >20% at 12-month follow-up, and a LV end-systolic volume (LVESV) decrease >15% at 12-month follow-up. RESULTS: For the LVEF improvement >5%, the best predictor was isovolumetric relaxation time (IVRT; P=.035). For improvement of LVEF >20%, the best predictors were left ventricular stroke index (LVSI; P=.044) and left ventricular fractional shortening (LVFS; P=.031). For the drop in left ventricular systolic volume (LVESV >15%), the best predictor was septal-to-lateral wall delay (ΔT) (P=.043, RR=1.023, 95% CI for RR=1.001-1.045). CONCLUSION: The definition of a favorable CRT response influenced the optimal predictor variable(s). Standardization of defining a favorable response to CRT is needed to guide clinical decision making processes.

Silent diabetic cardiomyopathy in everyday practice: a clinical and echocardiographic study.

BACKGROUND: Whether type 2 diabetes mellitus (DM) in the absence of hypertension (HTA) and coronary artery disease (CAD) affects left ventricular (LV) phenotype and function among asymptomatic DM patients that can be easily discovered in everyday practice, what is the clinical risk profile for diabetic cardiomyopathy and how HTA and CAD modulate LV structure and function above diabetic cardiomyopathy, are still incompletely answered questions. METHODS: In 210 DM patients (group I: 70 asymptomatic DM patients without HTA and CAD; group II: 70 DM patients with HTA and no CAD; group III: 70 DM patients with CAD and no HTA) and 80 healthy individuals, comprehensive echocardiography including speckle tracking strain and strain rate analysis, was done. RESULTS: Compared to control DM patients without HTA and CAD had increased LV mass, more frequently concentric remodeling, impaired LV relaxation and lower LV ejection fraction (EF), fraction of shortening (FS) and mitral annular plane excursion (MAPSE). Addition of HTA further impaired EF, FS and MAPSE and aggravated diastolic dysfunction, whereas concomitant CAD further impaired FS and MAPSE. Peak global longitudinal strain (Slong) and early diastolic longitudinal strain rate (SRlong E) were impaired in group I compared to control, even when EF was preserved. Peak circumferential strain (Scirc) was impaired only when DM was associated with HTA or CAD. In multivariate analysis DM was significantly and independently from HTA, CAD, age, gender and body mass index associated with: increased LV mass, concentric LV remodeling, lower EF, FS, MAPSE, Slong, SRlongE and distorted diastolic parameters. DM duration, glycosylated hemoglobin, microalbuminuria and retinopathy, were not independent predictors of LV geometry and function. CONCLUSION: DM per se has strong and independent influence on LV phenotype and function that can be detected by conventional and speckle tracking echocardiography in everyday clinical practice, even in asymptomatic patients. We could not confirm that these changes were independently related to duration of DM, quality of metabolic control and presence of microvascular complications. Concomitant HTA or CAD furthermore distorted LV systolic and diastolic function.

Sex and age differences and outcomes in acute coronary syndromes.

BACKGROUND: There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years). METHODS: From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality. RESULTS: The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients. CONCLUSIONS: In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less.

Sustained increase in platelet aggregation after the cessation of clopidogrel.

This study shows that the abrupt cessation of one-year clopidogrel treatment was not associated with thrombotic events in a prospective, multicentre study that enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel 1 year after the stent placement. The aim of the study was to investigate the causes of a sustained increase of platelet aggregability, considering that the values of platelet aggregation stimulated with ADP + PGE1 (ADPHS values) significantly increased 10-90 days after the cessation of clopidogrel. Values of platelet aggregation induced by thrombin receptor activating peptide (TRAP values) and arachidonic acid (ASPI values) were divided into quartiles on the basis of ADPHS values 10 days after stopping clopidogrel (ADPHS10 ). There was a significant difference between TRAP values divided into quartiles according to ADPHS10 , 10, 45 and 90 days after stopping clopidogrel (P < 0.001, all), and ASPI values across the same quartiles 10 and 45 days after the cessation of clopidogrel (P = 0.028 and 0.003). The results of the study indicate that patients with early pronounced rebound phenomena to clopidogrel termination have a long-term (at least 90 days) increased platelet aggregation to other agonists such as thrombin-related activated protein and arachidonic acid, suggesting the complex mutual relationship of various factors/agonists influencing the function of platelets.