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.

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.

Valvulo-arterial impedance is the best mortality predictor in asymptomatic aortic stenosis patients.

BACKGROUND AND AIM OF THE STUDY: Risk stratification is particularly complex in asymptomatic patients with significant aortic stenosis (AS). The study aim was to assess which hemodynamic/Doppler-echocardiographic parameter best predicts mortality in asymptomatic patients with severe AS and a normal left ventricular ejection fraction (LVEF). METHODS: This prospective study included 128 consecutive asymptomatic patients (75 males, 53 females; mean age 66.35 ± 10.51 years) with severe AS (aortic valve area (AVA) ± 1.0 cm2) and a normal LVEF (55%). The patients were followed up for 47 months (median 35.5 months, IQR 7 months). Clinical data at follow up were obtained from all patients by either direct examination or telephone interview. RESULTS: During the follow up, 55 patients (43.0%) underwent aortic valve replacement (AVR) surgery due to AS-related symptoms. Of the 12 patients that died (9.4%), eight deaths occurred before surgery (four patients refused operation), and one patient died after surgery due to postoperative infection. Those patients who died had a significantly higher valvulo-arterial impedance (Z(va)) (7.81 versus 4.86 mmHg x ml/m2, p < 0.001), a higher N-terminal pro-brain natriuretic peptide (NT-proBNP) level (1708.5 versus 376.5 pg/ml, p = 0.003) and a lower AVA (0.65 versus 0.86 cm2, p = 0.002), but there were no differences in LVEF, P(mean) or age between the groups (69.68% versus 72.24%, p = 0.206; 44.95 versus 41.75 mmHg; and 69 versus 66 years, p = 0.332, respectively). When parameters that were predictors of mortality according to univariate analysis were further analyzed with Cox multivariate analysis, Z(va) was found to be the best independent predictor (B = 0.460, HR = 1.584, 95% CI = 1.064-2.359, p = 0.024). A Z(va) value of 6.1 mmHg x ml/m2 was identified as the best (cut-off) predictive value for the occurrence of death, with a sensitivity 61.1% and a specificity 86.0%. CONCLUSION: Z(va) is the best mortality predictor in asymptomatic patients with severe AS and a normal LVEF. Future studies are required to focus further on predictors of outcome, the aim being to achieve an optimal selection of asymptomatic patients considered to be at risk and who would benefit from early AVR.

Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function.

BACKGROUND: Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). METHODS: In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices. RESULTS: IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026). CONCLUSION: IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

Ruptured giant mitral valve aneurysm: an unexpected finding in a diabetic patient with dyspnea and new-onset atrial fibrillation.

Mitral valve aneurysm (MVA) is a rare valve disease. The case is reported of pathologically proven MVA in a 61-year-old diabetic male with chronic alcoholic liver disease who presented with dyspnea and new-onset atrial fibrillation, without clinical elements of current or recent infection. Transthoracic echocardiography revealed a 'cystic' formation of the anterior mitral leaflet (AML) with mild mitral regurgitation (MR) and aortic regurgitation (AR) hitting the AML. Transesophageal echocardiography (TEE) showed clearly that the formation on the AML was a valve aneurysm, and depicted the site of aneurysm rupture with an additional jet of MR through the rupture. Following mitral valve replacement, pathology of the excised valve showed chronic bacterial endocarditis with calcified bacterial colonies, myxomatous changes with fibrinoid dissection of lamina fibrosa, and neovascularization of the leaflet. The mechanisms of MVA formation are discussed, together with its potential complications, diagnostic modalities and therapeutic strategies. The present case emphasizes that MVA is often a remnant of endocarditis, even when the latter is clinically silent and undiagnosed. The importance of chronic AR directed towards the AML as a predisposing condition for MVA formation is also underlined in this case. The superiority of TEE in providing a full exploration of the mitral valve morphology is verified.

Ketoacidosis at presentation of type 1 diabetes mellitus in children: a retrospective 20-year experience from a tertiary care hospital in Serbia.

UNLABELLED: Diabetic ketoacidosis (DKA) has significant morbidity and mortality and is common at diagnosis in children. The aim of this study was to determine the frequency and clinical characteristics of DKA over a 20-year period among children diagnosed with type 1 diabetes mellitus (T1DM) at University children's hospital in Belgrade, Serbia. The study population comprised of 720 patients (366 boys) diagnosed with type 1 diabetes aged <18 years between January 1992 and December 2011. Of all patients diagnosed with T1DM, 237 (32.9 %) presented with DKA. The majority had either mild (69.6 %) or moderate (22.8 %) DKA. Sixty (55.0 %) of all children under 5 years had DKA compared to sixty-two (20.9 %) in the 5- to 10-year-old group and one hundred fifteen (36.6 %) in the 11- to 18-year-old patients (p<0.01), while 2.5 % of the entire DKA cohort were in real coma. During the later 10-year period, children less often had DKA at diagnosis compared with the earlier 10-year period (28.0 vs. 37.4 %) (p<0.01), but the frequency of severe DKA was higher in the age group <5 year and in the age group >11 year during 2002-2011, compared with the earlier 10-year period (12.9 vs. 3.4 %, p<0.01 and 17.1 vs. 3.8 %, p<0.01). CONCLUSION: The overall frequency of DKA in children with newly diagnosed type 1 diabetes decreased over a 20-year period at our hospital. However, children aged <5 years and adolescents are still at high risk for DKA at diagnosis.

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.

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.

Utility of lipoprotein-associated phospholipase A2 for prediction of 30-day major adverse coronary event in patients with the first anterior ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been suggested as an inflammatory marker of cardiovascular risk. The predictive value of Lp-PLA2 in ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) has not been established. The aim of this study was to determine whether plasma Lp-PLA2 is a predictor of a major adverse cardiac event (MACE) in patients with the first anterior STEMI treated by primary PCI. METHODS: This study consisted of 100 consecutive patients with first anterior STEMI who underwent primary PCI within 6 hours of the symptom onset. Plasma Lp-PLA2 level was measured on admission using a turbidimetric immunoassay (diaDexus, Inc., USA). The Receiver Operating Characteristic analysis was performed to identify the most useful Lp-PLA2 cut-off level for the prediction of MACE. The patients were divided into two groups according to the cut-off Lp-PLA2 level: high Lp-PLA2 group (> or = 463 ng/mL, n = 33) and low Lp-PLA2 group (< 463 ng/mL, n = 67). MACE was defined as cardiac death, non-fatal reinfarction, and target vessel revascularization. RESULTS: Patients in the high Lp-PLA2 group had significantly higher total-, LDL-cholesterol, apolipoprotein B levels, and significantly lower estimated glomerular filtration rates compared with the low Lp-PLA2 group. The incidence of 30-day mortality was 18.2% (6/33) in high Lp-PLA2 group, while in the low Lp-PLA2 group no patient died (p < 0.001). The 30-day MACE occurred in 24.2% of the high Lp-PLA2 group and 3% of the low Lp-PLA2 group (p = 0.001). Multiple logistic regression analysis identified the plasma Lp-PLA2 level as an independent predictor of MACE (OR 1.011, 95%CI 1.001 - 1.013, p = 0.037). CONCLUSIONS: In patients with first anterior STEMI treated by primary PCI, the plasma Lp-PLA2 level is an independent predictor of 30-day MACE.

Prediction of a good response to cardiac resynchronization therapy in patients with severe dilated cardyomyopathy: could conventional echocardiography be the answer after all?

OBJECTIVES: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). BACKGROUND: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. METHODS: The 12-month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler-based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. RESULTS: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver-operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m(2) (P = 0.045) and for LVFS was 13% (P = 0.032). CONCLUSIONS: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients.

High prevalence of risk factors for chronic kidney disease in Balkan endemic nephropathy foci.

BACKGROUND/AIMS: The aim of this study was to find out the prevalence of the most frequent risk factors for chronic kidney disease (CKD) and the prevalence of urinary abnormalities in adult inhabitants of three Balkan endemic nephropathy (BEN) villages near Bijeljina, Bosnia and Herzegovina. METHODS: The survey consisted of an interview, blood pressure measurement, and urine dipstick test for proteinuria, hematuria, and glycosuria. RESULTS: The study involved 1625 (739 males, aged 51 ± 16 years) subjects: 319 (19.6%) with positive family history for BEN, 585 (36%) with hypertension, 604 (37.2%) above 60 years, 146 (9%) with diabetes, and 566 (34.8%) with none of these risk factors. Proteinuria was present in 6.2-7.1% of the subjects with risk factors for CKD but in 3.4% of those without risk factors. Systolic blood pressure and BEN in brother/sister were found to be significant variables associated with proteinuria, but female gender and history of kidney disease with hematuria. CONCLUSION: In addition to a family burden for BEN, other risk factors for CKD were highly prevalent in BEN villages of the Bijeljina municipality. The frequency of proteinuria was higher in the at-risk group than in the group without risk factors and increased with the number of risk factors.

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.

Abrupt cessation of one-year clopidogrel treatment is not associated with thrombotic events.

We aimed to examine the rate of thrombotic events after discontinuation of one year clopidogrel therapy in patients with implanted coronary stent, and to determine platelet aggregability by multiple electrode analyzer after cessation of clopidogrel. This prospective, multicenter study enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel one year after the stent placement. Platelet aggregation was measured using 3 agonists [adenosine diphosphate with PGE(1) (ADPHS), arachidonic-acid (ASPI), and thrombin receptor activating peptide (TRAP)] on the day of cessation of clopidogrel and at 10, 45, and 90 days after clopidogrel was stopped. Two thrombotic events were registered during the 6-months follow up (one ischemic stroke and one myocardial infarction; incidence of 1%). The mean values of ADP + PGE(1)- and ASPI-induced aggregation 10 - 90 days after the cessation of clopidogrel were significantly higher than values obtained before the termination of the drug (P < 0.001, all). Cessation of clopidogrel did not influence the TRAP-induced aggregation, which reached the plateau in all measurements. In conclusion, the incidence of thrombotic events after the cessation of one-year clopidogrel treatment might be lower than expected in patients with implanted coronary stent.

Coronary flow reserve in patients with aortic stenosis and nonobstructed coronary arteries.

OBJECTIVE: Patients with moderate and severe aortic stenosis (AS) and without obstructive epicardial coronary disease have been shown to have an impairment of coronary flow velocity reserve (CFVR). Recently, it has been shown that CFVR is an independent predictor for future cardiovascular events in AS patients. We investigated parameters representing left ventricular (LV) mass and wall thickness, diastolic dysfunction, LV workload and haemodynamic indexes of AS severity to determine which contributes the most to impaired CFVR in patients with AS and a nonobstructed coronary angiogram. METHOD AND RESULTS: A total of 77 patients with moderate or severe AS, mean age 65.66 +/- 11.02 y (57.14% males), were enrolled in this prospective study. All patients had standard Doppler-echo study, coronary angiography and adenosine-stress transthoracic Doppler-echo for CFVR measurement. We took 2.5 as a cut-off value for impaired CFVR. Univariate analysis showed that aortic valve area (AVA), maximal velocity (Vmax), mean pressure gradient (Pmean), energy loss index (ELI), aortic valve resistance (AVR) and stroke work loss (SWL) were associated (P = 0.05) with impaired CFVR. Multivariate analysis showed that AVR was the best predictor of impaired CFVR (RR 0.900, Cl: 0.983-0.997, P = 0.007). Using ROC analysis, the AVR value of 211.22 dynes x s x cm(-5) had the highest accuracy in predicting the impaired CFVR (AUC-0.681, P=0.007, sensitivity 72%, specificity 52%, CI: 0.561-0.800). CONCLUSION: Haemodynamic indices of AS severity, together with LV workload parameters, are the main determinants of CFVR. Among all parameters, AVR is the strongest predictor of CFVR in patients with moderate or severe AS and a nonobstructed coronary angiogram.

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.

Multimodality imaging in the assessment of cardiac lymphoma presented as new-onset atrial fibrillation.

Cardiac involvement by non-Hodgkin's lymphoma is not uncommon, however rarely diagnosed during life due to nonspecific clinical presentation. We report a case of secondary cardiac lymphoma in patient who presented with new-onset atrial fibrillation. Cardiac lymphoma was in a form of bulky right atrial mass, infiltrating the atrial septum and cavo-atrial junction with concomitant mild pericardial effusion. In the present case, we illustrate complementary role of transthoracic, transesophageal echocardiography and multislice CT scan with three-dimensional reconstruction, in detection and evaluation of secondary cardiac tumor. Usefulness of echocardiography to follow up the effects of chemotherapy is also shown.

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.