Prognostic implication of lung ultrasound in heart failure: pooled analysis of international cohorts.

BACKGROUND: Lung ultrasound (LUS) is often used to assess congestion in heart failure (HF). In this study, we assessed the prognostic role of LUS in HF patients at admission and hospital discharge, and in an out-patient setting and explored whether clinical factors (age, sex, left ventricular ejection fraction (LVEF) and atrial fibrillation) impact the prognostic value of LUS findings. Further, we assessed the incremental prognostic value of LUS on top of AHEAD and MAGGIC clinical risk scores. METHODS AND RESULTS: We pooled data of patients hospitalized for HF or followed-up in out-patient clinics from international cohorts. We enrolled 1,947 patients, at admission (n=578), discharge (n=389) and in out-patient clinic (n=980). Total LUS B-line count was calculated for the 8-zone scanning protocol. The primary outcome was a composite of re-hospitalization for HF and all-cause death. Compared to those in the lower tertiles of B-lines, patients in the highest tertile were older, more likely to have signs of HF and higher NT-proBNP levels. A higher number of B-lines was associated with increased risk of primary outcome at discharge (Tertile3 vs Tertile1: adjustedHR= 5.74 (3.26- 10.12), p<0.0001) and in out-patients (Tertile3 vs Tertile1: adjustedHR= 2.66 (1.08- 6.54), p=0.033). Age and LVEF did not influence the prognostic capacity of LUS in different clinical settings. Adding B-line count to MAGGIC and AHEAD scores improved net reclassification significantly in all three clinical settings. CONCLUSION: A higher number of B-lines in patients with HF was associated with increased risk of morbidity and mortality, regardless of the clinical setting.

The role of melatonin in preventing amiodarone-induced rat liver damage.

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50 mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70 mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

Exercise-induced B-lines for the diagnosis of heart failure with preserved ejection fraction: a two-centre study.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging despite the use of scores/algorithms. This study intended to assess the diagnostic value of exercise lung ultrasound (LUS) for HFpEF diagnosis. METHODS: We studied two independent case-control studies of HFpEF patients and control subjects undergoing different exercise protocols: (i) submaximal exercise stress echocardiography (ESE) with LUS performed by expert cardiologists (N = 116, HFpEF = 65.5%), and (ii) maximal cycle ergometer test (CET) (N = 54, HFpEF = 50%) with LUS performed by unexperienced physicians shortly trained for the study. B-line kinetics (i.e. peak values and their changes from rest) were assessed. RESULTS: In the ESE cohort, the C-index (95% CI) of peak B-lines for HFpEF diagnosis was 0.985 (0.968-1.000), whereas the C-index of rest and exercise HFA-PEFF scores (i.e. including stress echo findings) were < 0.90 (CI 0.823-0.949), and that of H2FPEF score was < 0.70 (CI 0.558-0.764). The C-index increase of peak B-lines on top of the above-mentioned scores was significant (C-index increase > 0.090 and P-value < 0.001 for all). Similar results were observed for change B-lines. Peak B-lines > 5 (sensitivity = 93.4%, specificity = 97.5%) and change B-lines > 3 (sensitivity = 94.7%, specificity = 87.5%) were the best cutoffs for HFpEF diagnosis. Adding peak or change B-lines on top of HFpEF scores and BNP significantly improved diagnostic accuracy. Peak B-lines showed a good diagnostic accuracy in the LUS beginner-led CET cohort (C-index = 0.713, 0.588-0.838). CONCLUSIONS: Exercise LUS showed excellent diagnostic value for HFpEF diagnosis regardless of different exercise protocols/level of expertise, with additive diagnostic accuracy on top of available scores and natriuretic peptides.

Validation of the MEDIA echo score for the prognosis of heart failure with preserved ejection fraction.

There is currently no widely used prognostic score in heart failure (HF) with preserved ejection fraction (HFpEF). The MEDIA echo score, including four variables (pulmonary arterial systolic pressure > 40 mmHg, inferior vena cava collapsibility index < 50%, average E/e' > 9, and lateral mitral annular s' < 7 cm/s), has been proposed as a useful risk stratification tool. This study aimed at further validating the MEDIA echo score in both hospitalised and ambulatory HFpEF patients. The MEDIA echo score ranges from 0 to 4 (each criterion scores 1 point). The associations between MEDIA echo score and cardiovascular outcomes were assessed in two independent HFpEF cohorts, namely patients hospitalised for worsening HFpEF (N = 242, mean age 78 ± 11), and stable ambulatory HFpEF patients (N = 76, mean age 65 ± 8). Using multivariable Cox models, in the worsening HFpEF cohort, patients with a MEDIA echo score of 3-4 displayed a significant increased risk of death (HR 2.10, 95%CI 1.02-4.33, P = 0.043, score 0-1 as reference). In the ambulatory HFpEF cohort, patients with a MEDIA echo score of 2 had a significantly higher risk of death or HF hospitalisation (HR 3.44, 95%CI 1.27-9.30, P = 0.015, score 0 as reference), driven by HF hospitalisation; in that cohort, adding the MEDIA echo score to the clinical model significantly improved reclassification for the combined endpoint (integrated discrimination improvement 6.2%, P = 0.006). The MEDIA echo score significantly predicted the outcome of HFpEF patients in both hospital and ambulatory settings; its use may help refine routine risk stratification on top of well-established prognosticators in stable HFpEF patients.

Exercise-induced B-lines in heart failure with preserved ejection fraction occur along with diastolic function worsening.

AIMS: Pulmonary congestion during exercise assessed by lung ultrasound predicts negative outcome in patients with heart failure with preserved ejection fraction (HFpEF). We aimed at assessing predictors of exercise-induced pulmonary B-lines in HFpEF patients. METHODS AND RESULTS: Eighty-one I-II NYHA class HFpEF patients (65.0  ± 8.2 y/o, 56.8% females) underwent standard and strain echocardiography, lung ultrasound, and natriuretic peptide assessment during supine exercise echocardiography (baseline and peak exercise). Peak values and their changes were compared in subgroups according to exercise lung congestion grading (peak B-lines >10 or ≤10). Exercise elicited significant changes for all echocardiographic parameters in both subgroups [39/81 (48.1%) with peak B-lines >10; 42/81 (51.9%) with B-lines ≤10]. Peak values and changes of E-wave (and its derived indices) were significantly higher in patients with >10 peak B-lines compared with those with ≤10 B-line (all P-values <0.03), showing significant correlation with peak B-lines for all parameters; concomitantly, global longitudinal strain (GLS) and global strain rate (GSR) during systole (GSRs), early (GSRe) and late (GSRa) diastole, and isovolumic relaxation (GSRivr) were reduced in patients with B-lines >10 (all P-values <0.05), showing a negative correlation with peak B-lines. By adjusted linear regression analysis, peak and change diastolic parameters (E-wave, E/e', GSRivr, and E/GSRivr) and peak GLS were individually significantly associated with peak B-lines. By covariate-adjusted multivariable model, E/e' and GSRa at peak exercise were retained as independent predictors of peak B-lines, with substantial goodness of fit of model (adjusted R2 0.776). CONCLUSIONS: In HFpEF, development of pulmonary congestion upon exercise is mostly concomitant with exercise-induced worsening of diastolic function.

Prognostic Value of Dynamic Changes in Pulmonary Congestion During Exercise Stress Echocardiography in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) typically develop dyspnea and pulmonary congestion upon exercise. Lung ultrasound is a simple diagnostic tool, providing semiquantitative assessment of extravascular lung water through B-lines. It has been shown that patients with HFpEF develop B-lines upon submaximal exercise stress echocardiography; however, whether exercise-induced pulmonary congestion carries prognostic implications is unknown. This study aimed at evaluating the prognostic value of B-line assessment during exercise in patients with HFpEF. METHODS: Sixty-one New York Heart Association class I to II patients with HFpEF underwent standard echocardiography, lung ultrasound (28-scanning point method), and BNP (B-type natriuretic peptide) assessment during supine exercise echocardiography (baseline and peak exercise). The primary end point was a composite of cardiovascular death or HF hospitalization at 1 year. RESULTS: B-lines, E/e', and BNP significantly increased during exercise (P<0.001 for all). By multivariable analysis, both peak (hazard ratio, 1.50 [95% CI, 1.21-1.85], P<0.001), and change (hazard ratio 1.34 [95% CI, 1.12-1.62], P=0.002) B-lines were retained as independent predictors of outcome (hazard ratios per 1 B-line increment), along with BNP and E/e' ratio. Importantly, adding peak B-line on top of a clinical model significantly improved prognostic accuracy (C-index increase, 0.157 [0.056-0.258], P=0.002) and net reclassification (continuous net reclassification improvement, 0.51 [0.09-0.74], P=0.016), with similar results for B-line change. CONCLUSIONS: Detection of exercise-induced pulmonary congestion by lung ultrasound is an independent predictor of outcome in patients with HFpEF; its use may help refining the routine risk stratification of these patients on top of well-established clinical variables.

Effects of Music Therapy on Endothelial Function in Patients With Coronary Artery Disease Participating in Aerobic Exercise Therapy.

Context • Pleasant music that evokes a positive emotional response may activate brain pathways of the insular cortex, central nucleus of the amygdala, and lateral hypothalamus, which are involved in the integration of emotional and ambient sensory input, with corresponding autonomic responses. Exercise training can improve endothelium-dependent vasodilatation, both in epicardial coronary vessels and in resistance vessels, for patients with coronary heart disease. Objective • The aim of the present study was to evaluate the effects on endothelial function when patients with stable coronary artery disease (CAD) listened to their favorite music. Design • The study was a randomized controlled trial. Setting • The study occurred at the Institute of Cardiology, Niska Banja, Faculty of Medicine, University of Nis (Nis, Serbia). Participants • Participants were 74 patients with stable CAD. Intervention • Participants were randomly assigned to 1 of 3 groups: (1) exercise training only (T) group (n = 33), (2) listening to music and exercise training (MT) group (n = 31), and listening to music only (M) group (n = 10). Participants in the T and MT groups received usual medical care and underwent 3 wk of supervised aerobic exercise training. In addition to the exercise training, participants in the MT group listened to their favorite music for 1.5 h every day. Participants in the M group received the usual medical care and listened to their favorite music for 1.5 h every day. Outcome Measures • At baseline and postintervention, outcomes were assessed through measurement of the changes in circulating blood markers of endothelial function-the stable end product of nitric oxide (NOx), asymmetric dimethylarginine, symmetric dimethylarginine, and xanthine oxidase-and through the results of submaximal or symptom-limited exercise test. Results • After 3 wk, the NOx significantly increased in both in MT and T groups, with P < .001 and P < .01, respectively. The level of NOx was associated with an improvement in exercise capacity, which increased in the T, MT, and M groups, with P < .001, P < .001, and P < .05, respectively. At the end of the study, the xanthine oxidase was significantly lower in the T, MT, and M groups, with P < .001 and P < .05, respectively. Conclusions • The patients with stable CAD significantly improved their endothelial function by listening to their favorite music in addition to participating in regular exercise training. Having a patient listen to his or her favorite music can be proposed as an additional nonpharmacologic intervention for improving a CAD patient's endothelial function. The music program should be adjusted individually to fit with a well-established training program for aerobic exercise, according to a patient's preferences.

Prevalence of arterial hypertension in Serbia: PAHIS study.

BACKGROUND: Arterial hypertension (AH) is the most common cardiovascular disease risk factor, affecting between 30 and 50% of the adult population in developed countries. A steady increase of the prevalence of AH by about 60% is expected by year 2025. METHODS: Serbian Society of Hypertension conducted a prevalence study from February to May 2012 on a sample of 3878 adult respondents. The study included 2066 women (53.3%) and 1812 men (46.7%). Average age was 48.89 ±â€Š17.48 years. Most participants resided in urban areas (2956 people, 76.2%), whereas 922 resided in rural areas (23.8%). RESULTS: The prevalence of AH in Serbia is 42.7%. Hypertension is more frequently diagnosed among women (53.3%), than among men (46.7%). One thousand, four hundred and twelve respondents were previously diagnosed and treated for hypertension. The estimated awareness of the presence of AH was 42.99% (i.e. 40.00% among male and 45.41% among female participants). Out of all diagnosed cases of hypertension, 390 persons (27.7%) have well regulated blood pressure values, whereas 1022 persons (72.3%) do not have their blood pressure under control. CONCLUSION: Serbia belongs to countries with a high prevalence of AH. A poor control of AH may be explained in view of socioeconomic problems. High prevalence of AH may indicate a remarkably high cardiovascular disease mortality in Serbia.

Administration and effects of secondary prevention measures in coronary heart disease patients from Serbia according to gender and cardiometabolic risk.

BACKGROUND: The EUROASPIRE surveys showed high rates of modifiable cardiovascular risk factors in patients with coronary heart disease, identified after coronary artery bypass graft, percutaneous coronary intervention or myocardial infarction, with time trends in preventive cardiology over more than a decade. AIM: The aim of this study was to test the implementation of European recommendations for cardiac rehabilitation and secondary risk prevention programmes in the population of coronary heart disease patients from Serbia. SUBJECTS AND METHODS: A total of 665 consecutive coronary heart disease patients (432 men, 233 women, aged 59.43 +/- 11.62 years), admitted for specialized cardiovascular rehabilitation, interviewed and examined in relation to the presence of coronary risk factors and administration of secondary prevention measures, were enrolled in the study. RESULTS: High rates of smoking (27.67%), central obesity (58.05%), physical inactivity (61.50%) and adverse dietary habits (61.50%) were observed, as well as low frequency of patients who have reached recommended targets for waist circumference (41.95%), total cholesterol (40%), LDL-cholesterol (39.25%), HDL-cholesterol (59.69%) and triglycerides (59.25%), while systolic (82.26%) and diastolic blood pressures (95.49%) were well regulated. A significantly lower rate of achieved therapeutic targets, despite widely used cardioprotective drugs, was observed in diabetic patients and patients with the metabolic syndrome. CONCLUSION: The results have shown a low proportion of coronary heart disease patients, especially with diabetes mellitus and metabolic syndrome, who reached the recommended therapeutic targets for cardiometabolic risk profile parameters, in spite of widely used cardioprotective drugs, and therefore clearly demonstrated the compelling need for more effective lifestyle management in the secondary prevention of coronary heart disease.