Long-term follow-up of patients with chronic total coronary artery occlusion previously randomized to treatment with optimal drug therapy or percutaneous revascularization of chronic total occlusion (COMET-CTO).

Background: The COMET-CTO trial was a randomized prospective study that assessed long-term follow-up in patients with chronic total occlusion (CTO) in coronary arteries treated with percutaneous coronary intervention (PCI) or with optimal medical therapy (OMT). During the 9-month follow-up, the incidence of major adverse cardiac events (MACE) did not differ between the two groups; no death or myocardial infarction (MI) was observed. There was a significant difference in quality of life (QoL), assessed by the Seattle Angina Questionnaire (SAQ), in favor of the PCI group. Here we report long-term follow-up results (56 ± 12 months). Methods: Between October 2015 and May 2017, a total of 100 patients with CTO were randomized into two groups of 50 patients: PCI CTO or OMT group. The primary endpoint of the current study was the incidence of MACE defined as cardiac death, MI, and revascularization [PCI or coronary artery bypass graft (CABG)]. As the secondary exploratory outcome, we analyzed all the cause-mortality rate. Results: Out of 100 randomized patients, 92 were available for long-term follow-up (44 in the PCI group and 48 in the OMT group). The incidence of MACE did not differ significantly between the two groups (p = 0.363). Individual components of MACE were distributed, respectively: cardiac death (OMT vs. PCI group, 6 vs. 3, p = 0.489), MI (OMT vs. PCI group, 1 vs. 0, p = 1), and revascularization (PCI: OMT vs. PCI group, 2 vs. 2, p = 1; CABG: OMT vs. PCI group, 1 vs. 1, p = 1). There was no significant difference between the two groups regarding the individual component of MACE. Six patients died from non-cardiac causes [five deaths were reported in the OMT group and one death in the PCI group (p = 0.206)]. Kaplan-Meier survival curves for MACE did not differ significantly between the study groups (log-rank 0.804, p = 0.370). Regarding the secondary exploratory outcome, a total of 15 patients died at 56 ± 12 months (11 in the OMT and 4 in the PCI group) (p = 0.093). The Kaplan-Meier survival curves for all-cause mortality rates did not differ significantly between the two groups (log rank 3.404, p = 0.065). There were no statistically significant differences between OMT and PCI groups in all five SAQ domains. There was a significant improvement in three SAQ domains in the PCI group: PL (p < 0.001), AF (p = 0.007), and QoL (p = 0.001). Conclusion: After 56 ± 12 months of follow-up, the incidence of MACE, as well as QoL measured by SAQ, did not differ significantly between the PCI and OMT groups.

Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Background Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 µg/kg per minute) and dobutamine (10-50 µg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia. Conclusions Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.

The Coronary ARteriogenesis with combined Heparin and EXercise therapy in chronic refractory Angina (CARHEXA) trial: A double-blind, randomized, placebo-controlled stress echocardiographic study.

BACKGROUND: Coronary collateral circulation exerts protective effects on myocardial ischaemia due to coronary artery disease and can be promoted by exercise with heparin co-administration. Whether this arteriogenetic effect is accompanied by functional improvement of left ventricle during stress and lessening of angina symptoms remains unknown. AIMS: To evaluate the anti-ischaemic efficacy of heparin plus exercise in coronary artery disease. METHODS: In a prospective, single-centre, randomized, double-blind study we recruited 32 'no-option' patients (27 males; mean age 61 ± 8 years) with stable angina, exercise-induced ischaemia and coronary artery disease not suitable for revascularization. All underwent a two-week cycle of exercise (two exercise sessions per day, five days per week) and were randomized (n = 16 per group) to intravenous placebo (0.9% saline) versus unfractionated heparin (5.000 IU intravenously), 10 min prior to exercise. We assessed Canadian Cardiovascular Society angina class, stress electrocardiogram and echo parameters (wall motion score index) and computed tomography angiography for collaterals. RESULTS: After two-week cycle, Canadian Cardiovascular Society class statistically decreased in both groups (heparin plus exercise group: 2.6 ± 0.7 to 1.9 ± 0.7, p < 0.001, exercise group: 2.4 ± 0.7 to 2.1 ± 0.9, p = 0.046). Only the heparin plus exercise group improved time-to-ST segment depression (before 270, 228-327 s vs. after 339, 280-360 s, p = 0.012) and wall motion score index (before 1.38 ± 0.25 vs. after 1.28 ± 0.18, p = 0.005). By multi-slice computed tomography angiography, collaterals improved in 12/15 (80%) in the heparin plus exercise group versus 2/16 (12.5%) in the exercise group (p < 0.001). CONCLUSION: A two-week, 10-test cycle of heparin plus exercise is better than exercise in improving angina class, myocardial ischaemia and collaterals by computed tomography angiography.

Randomized Controlled Comparison of Optimal Medical Therapy with Percutaneous Recanalization of Chronic Total Occlusion (COMET-CTO).

The aim of this randomized prospective study was to evaluate the quality of life (QoL) using the "Seattle Angina Questionnaire" (SAQ) in patients with chronic total occlusion (CTO) in coronary arteries treated with either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT), or only with OMT.The potential benefits of recanalization of CTO by PCI have been controversial because of the scarcity of randomized controlled trials.A total of 100 patients with CTO were randomized (1:1) prospectively into the PCI CTO or the OMT group (50 patients in each group). There were no baseline differences in the SAQ scores between the groups, except for physical limitation scores (P = 0.03). During the mean follow-up (FUP) of 275 ± 88 days, patients in the PCI group reported less physical activity limitations (72.7 ± 21.3 versus 60.5 ± 27, P = 0.014), less frequent angina episodes (89.8 ± 17.6 versus 76.8 ± 27.1, P = 0.006), better QoL (79.9 ± 22.7 versus 62.5 ± 25.5, P = 0.001), greater treatment satisfaction (91.2 ± 13.6 versus 81.4 ± 18.4, P = 0.003), and borderline differences in angina stability (61.2 ± 26.5 versus 51.0 ± 23.7, P = 0.046) compared to patients in the OMT group. There were no significant differences in SAQ scores in the OMT group at baseline and during the FUP. There was a statistically significant increase in all five domains in the PCI group.Symptoms and QoL measured by the SAQ were significantly improved after CTO PCI compared to OMT alone.

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging.

BACKGROUND: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. PURPOSE: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. METHODS: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27-74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10-40 µg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. RESULTS: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967-1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001-0.534; p = 0.019; OR: 1.147; 95% CI: 1.042-1.263; p = 0.005; respectively). CONCLUSIONS: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.

The prognostic value of stroke work/end-diastolic volume ratio during stress echocardiography.

BACKGROUND: The ventricular stroke work (SW) refers to the work done by the left ventricle to eject the volume of blood during one cardiac cycle. The cath-lab relationship between SW and end-diastolic volume (EDV) is the preload-recruitable SW (PRSW). Recently a non-invasive single-beat PRSW (SBPRSW) has been proposed. However, the single beat formula needs mathematical skillness, and extra software. Aim of this study was to compare the non-invasive SBPRSW with the simpler non-invasive SW/EDVratio in the stress-echo lab. METHODS: We studied 692 patients, age 62 ± 12 years, ejection fraction 50 ± 17%, with negative stress echo (SE)(exercise, n = 130, dobutamine, n = 124, dipyridamole, n = 438) and follow-up data. The PRSW was estimated at rest and at peak stress by the SBPRSW technique and compared with the SW/EDV. All patients were followed-up. Event rates were estimated with Kaplan-Meier curves. RESULTS: SBPRSW and SW/EDV were linearly correlated at rest (r = 0.842, p < .001) and at peak stress (r = 0.860, p < .001). During a median follow-up of 20 months (first quartile 8, third quartile 40 months), 132 major events were registered: at receiver operating characteristic (ROC) analysis rest SBPRSW vs. SW/EDV (AUC 0.691 vs. 0.722) and peak stress (AUC 0.744 vs. 0.800) demonstrated both a significant prognostic power (all p < .001) with non-inferior survival prediction of the simpler SW/EDV ratio at Kaplan-Meier curves (Chi-square rest = 38, peak = 56) vs. SBPRSW (Chi-square rest = 14, peak = 42). CONCLUSIONS: The data obtained with the non-invasive SBPRSW and by the simpler SW/EDV are highly comparable. PRSW with either SB or SW/EDV approach is effective in predicting follow-up events.

Efficacy and safety of edoxaban in patients with diabetes mellitus in the ENGAGE AF-TIMI 48 trial.

BACKGROUND: Diabetes mellitus is an independent risk factor for stroke and atrial fibrillation. Therefore, the risk/benefit profile of the oral factor Xa inhibitor edoxaban stratified by diabetes is of clinical interest. METHODS: 21,105 patients enrolled in ENGAGE AF-TIMI 48 were stratified into 2 pre-specified groups: without (N = 13,481) and with diabetes (N = 7,624). RESULTS: On average, patients with diabetes were younger, and had a higher body mass index, CHA2DS2-VASc score and baseline endogenous Factor Xa activity. After multivariate adjustments, patients with diabetes had a similar rate of stroke and systemic embolism compared to those without diabetes (adjusted hazard ratio (HRadj) 1.08; 95% confidence interval (CI) 0.94-1.24; p = 0.28). However, the risk of major bleeding was significantly higher in patients with diabetes (HRadj 1.28; 95% CI 1.14-1.44; p < 0.001). The treatment effect of edoxaban (vs warfarin) was not modified by diabetes (all p-interactions > 0.05), a finding supported by the preserved edoxaban concentrations and inhibition of Factor Xa regardless of diabetes. The HRs of stroke and systemic embolism in patients receiving the higher-dose edoxaban regimen vs warfarin were 0.93 and 0.84 (p-interaction = 0.54) in those with and without diabetes respectively. The higher-dose edoxaban regimen reduced major bleeding (by 19-21%) and cardiovascular death (by 7-17%) regardless of diabetes (p-interactions = 0.81 and 0.33 respectively). CONCLUSION: Patients with diabetes in ENGAGE AF-TIMI 48 had higher bleeding risk, but after adjustment similar stroke risk, compared to those without diabetes. The higher-dose edoxaban regimen had similar efficacy compared to warfarin, while reducing bleeding and cardiovascular mortality, irrespective of diabetes.

Relationship between community hospital versus pre-hospital location of randomisation and clinical outcomes in ST-elevation myocardial infarction patients: insights from the Stream study.

AIMS: The STREAM study randomly assigned ST-elevation myocardial infarction (STEMI) patients to receive a pharmacoinvasive versus primary percutaneous coronary intervention reperfusion strategy. We assessed whether there was an association between outcomes based on randomisation at a community hospital versus a prehospital location. METHODS/RESULTS: Community hospital patients (358/1866 (19.2%)) were compared to prehospital patients and their outcomes categorised into pharmacoinvasive according to their treatment assignment. Compared to prehospital patients, community hospital patients had more diabetes (17.8% vs. 11.5%, P=0.001), higher Killip Class >1 (9.4% vs. 5.0%, P=0.002) and thrombolysis in myocardial infarction risk scores ⩾5 (18.2% vs. 12.4%, P=0.005). The 30-day primary endpoint (death, shock, congestive heart failure and re-infarction) for community hospital patients was 14.9% versus 13.2% for prehospital patients ( P=0.403). Community hospital pharmacoinvasive patients tended to receive less rescue (35.1% vs. 42.8%, P=0.062); when deployed their rescue was delayed 43 minutes. Community hospital patients undergoing primary percutaneous coronary intervention experienced a delay of 31 minutes versus prehospital patients. Pharmacoinvasive patients receiving scheduled angiography from a community hospital and prehospital patients had comparable times to angiography (17.7 vs. 18.7 hours) and low event rates (6.2% vs. 8.0%). Although the interaction between randomisation location and treatment received on the primary endpoint was not significant ( Pinteraction=0.065) those pharmacoinvasive patients requiring rescue from community hospitals had worse outcomes than prehospital rescue patients (odds ratio 2.28, 95% confidence interval 1.16-4.49). CONCLUSION: Within STREAM, STEMI patients randomly assigned at community hospitals had a higher baseline risk but similar outcomes compared to those studied prehospital patients irrespective of successful pharmacoinvasive therapy or primary percutaneous coronary intervention. However, worse outcomes in the pharmacoinvasive patients requiring rescue in community hospitals emphasises their need for immediate transfer to a percutaneous coronary intervention-capable hospital.

Typical chest pain and precordial leads ST-elevation in patients with pacemakers--are we always looking at an acute myocardial infarction?

INTRODUCTION: Electrocardiographic (ECG) diagnosis of acute myocardial infarction (AMI) in patients with paced rhythm is difficult. Sgarbossa's criteria represent helpful diagnostic ECG tool. CASE REPORT: A 57-year-old female patient with paroxysmal atrial fibrillation and a permanent pacemaker presented in the Emergency Department with prolonged typical chest pain and ECG recording suggestive for AMI. Documented ECG changes correspond to the first Sgarbossa's criterion for AMI in patients with dual pacemakers (ST-segment elevation of 5 mn in the presence of the negative QRS complex). The patient was sent to catheterization lab where coronary angiogram reveled normal findings. ECG changes occurred due to pericardial reaction following two interventions: pacemaker implantation a month before and radiofrequency catheter ablation of AV junction two weeks before presentation in Emergency Department. CONCLUSION: This case report points out to the limitations of proposed criteria that aid in the recognition of AMI in patients with underlying paced rhythm and possible cause(s) of transient electrocardiographic abnormalities.

Relation of Biomarkers of Inflammation and Oxidative Stress with Hypertension Occurrence in Lone Atrial Fibrillation.

We compared plasma levels of biomarkers of inflammation (CRP) and oxidation (oxLDL), determined at study inclusion in lone atrial fibrillation (LAF) patients (48.6 ± 11.5 years; 74.0% men) and sinus rhythm controls (49.7 ± 9.3 years; 72.7% men, P > 0.05), and investigated the association of baseline CRP and oxLDL levels with the risk for vascular disease (VD) development (hypertension, cerebrovascular disease, coronary/peripheral artery disease, and pulmonary embolism) during prospective follow-up. Baseline CRP (1.2 [0.7-1.9] mg/L versus 1.1 [0.7-1.6] mg/L) and oxLDL levels (66.3 ± 21.2 U/L versus 57.1 ± 14.6 U/L) were higher in LAF patients (both P < 0.05). Following a median of 36 months, incident VD occurred in 14 (28.0%) LAF patients, all of whom developed arterial hypertension, and in 5 (11.4%) controls (hypertension, n = 4; coronary artery disease, n = 1), P < 0.05. LAF patients developed VD more frequently and at a younger age. Both CRP (HR, 2.54; 95% CI, 1.26-5.12; P = 0.009) and oxLDL (HR, 2.24; 95% CI, 1.14-4.40; P = 0.019) were multivariate predictors of incident hypertension in LAF patients, but not in the controls. Further research should clarify clinical relevance of investigated biomarkers for risk stratification and treatment of LAF patients.

Coronary vasomotion one year after drug-eluting stent implantation: comparison of everolimus-eluting and paclitaxel-eluting coronary stents.

First-generation drug-eluting stents (DES) have been associated with impaired localized coronary vasomotion and delayed endothelialization. We aimed to compare coronary vasomotion after implantation of a newer-generation everolimus-eluting stent (EES), with a first-generation paclitaxel-eluting stent (PES). Coronary vasomotion was studied in 19 patients with EES and 13 with PES. Vasomotor response was measured proximally and distally to the stent and in a remote vessel (reference segment). Quantitative coronary angiography was performed offline. Endothelium independent vasomotion did not differ significantly between the two groups. EES showed significant vasodilatation while PES showed vasoconstriction at both proximal (+4.5 ± 3.6 vs -4.2 ± 6.9, p < 0.001) and distal (+4.6 ± 7.9 vs -4.8 ± 9.3, p = 0.003) segments. The reference segment did not show any significant difference in vasodilatation between the two groups (+9.8 ± 6.4 vs +7.2 ± 5.2, p = 0.17). Endothelium-dependent vasomotion at adjacent stent segments is relatively preserved after EES implantation while vasoconstriction was observed after PES implantation.

Risk factors clustering within the metabolic syndrome: a pattern or by chance?

INTRODUCTION: An accumulation of various cardiovascular risk factors has been noted to occur within the clinical diagnosis of metabolic syndrome. However, it remains unclear whether specific risk factors aggregate following a predefined pattern or whether this happens by chance. METHODS: This cross-sectional study involved 1715 adults, 37% males and 63% females, aged 34-80 years, who were consecutively recruited from cardiology and endocrinology outpatient clinics, and from internal medicine specialists in the primary healthcare physician office setting in Serbia, on a one-third basis. According to the AHA/NHLBI criteria, the actual prevalence of a combination of 3 or more of the following risk factors was determined: abnormal waist circumference, hypertension, high triglycerides, low high-density lipoprotein cholesterol, and abnormal fasting glucose. In addition, the prevalence of a corresponding combination of 3 factors was predicted from the prevalence of each factor in a given population, assuming that their combination occurred as the result of chance. RESULTS: The most frequent risk factor was hypertension (87%), followed by waist circumference (60%), dyslipidemia (55%), and abnormal fasting glucose level (50%). Metabolic syndrome was identified in 1135 participants (66.2%). The actual prevalence of the combination of increased waist circumference, elevated blood sugar and hypertension was found to be 5 times more frequent than would be expected to occur by chance (10% actual vs. 2% predicted; p<0.0001). CONCLUSIONS: A predefined aggregation pattern of risk factors within the metabolic syndrome was found for abdominal obesity, abnormal fasting glucose and hypertension. These risk factors do cluster more frequently than coincidental phenomena in the subjects of the given population, implying common underlying pathophysiological mechanisms.

The interface of hypothalamic-pituitary-adrenocortical axis and circulating brain natriuretic peptide in prediction of cardiopulmonary performance during physical stress.

Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. However, HPA axis activation in different physical stress models and its interface with NT-pro-BNP in the prediction of cardiopulmonary performance is unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary age-matched subjects (C). Plasma levels of NT-pro-BNP, cortisol and adrenocorticotropic hormone (ACTH) were measured using immunoassay sandwich technique, radioimmunoassay and radioimmunometric techniques, respectively, 10min before test (1), at beginning (2), at maximal effort (3), at 3rdmin of recovery (4). In all groups, NT-pro-BNP decreased between 1 and 2; increased from 2 to 3; and remained unchanged until 4. ACTH increased from 1 to 4, whereas cortisol increased from 1 to 3 and stayed elevated at 4. In all groups together, ΔNT-pro-BNP2/1 predicted peak oxygen consumption (B=37.40, r=0.38, p=0.007); cortisol at 3 predicted heart rate increase between 2 and 3 (r=-0.38,B=-0.06, p=0.005); cortisol at 2 predicted peak carbon-dioxide output (B=2.27, r=0.35, p<0.001); ΔACTH3/2 predicted peak ventilatory equivalent for carbon-dioxide (B=0.03, r=0.33, p=0.003). The relation of cortisol at 1 with NT-pro-BNP at 1 and 3 was demonstrated using logistic function in all the participants together (for 1/cortisol at 1 B=63.40, 58.52; r=0.41, 0.34; p=0.003, 0.013, respectively). ΔNT-pro-BNP2/1 linearly correlated with ΔACTH4/3 in WP and W (r=-0.45, -0.48; p=0.04, 0.04, respectively). These results demonstrate for the first time that HPA axis and NT-pro-BNP interface in physical stress probably contribute to integrative regulation of cardiopulmonary performance.

Brain natriuretic peptide predicts forced vital capacity of the lungs, oxygen pulse and peak oxygen consumption in physiological condition.

Brain natriuretic peptide (NT-pro-BNP) is used as marker of cardiac and pulmonary diseases. However, the predictive value of circulating NT-pro-BNP for cardiac and pulmonary performance is unclear in physiological conditions. Standard echocardiography, tissue Doppler and forced spirometry at rest were used to assess cardiac parameters and forced vital capacity (FVC) in two groups of athletes (16 elite male wrestlers (W), 21 water polo player (WP)), as different stress adaptation models, and 20 sedentary subjects (C) matched for age. Cardiopulmonary test on treadmill (CPET), as acute stress model, was used to measure peak oxygen consumption (peak VO2), maximal heart rate (HRmax) and peak oxygen pulse (peak VO2/HR). NT-pro-BNP was measured by immunoassey sandwich technique 10min before the test - at rest, at the beginning of the test, at maximal effort, at third minute of recovery. FVC was higher in athletes and the highest in W (WP 5.60±0.29 l; W 6.57±1.00 l; C 5.41±0.29 l; p<0.01). Peak VO2 and peak VO2/HR were higher in athletes and the highest in WP. HRmax was not different among groups. In all groups, NT-pro-BNP decreased from rest to the beginning phase, increased in maximal effort and stayed unchanged in recovery. NT-pro-BNP was higher in C than W in all phases; WP had similar values as W and C. On multiple regression analysis, in all three groups together, ΔNT-pro-BNP from rest to the beginning phase independently predicted both peak VO2 and peak VO2/HR (r=0.38, 0.35; B=37.40, 0.19; p=0.007, 0.000, respectively). NT-pro-BNP at rest predicted HRmax (r=-0.32, B=-0.22, p=0.02). Maximal NT-pro-BNP predicted FVC (r=-0.22, B=-0.07, p=0.02). These results show noticeable predictive value of NT-pro-BNP for both cardiac and pulmonary performance in physiological conditions suggesting that NT-pro-BNP could be a common regulatory factor coordinating adaptation of heart and lungs to stress condition.

Mentality and organisational changes are key to developing primary angioplasty.

At the moment of signing the Stent for Life (SFL) Initiative on August 31st, 2009, it was shown that, in Serbia during 2008, 48% of patients with ST-elevation myocardial infarction (STEMI) did not receive any reperfusion and only 19% and 33% received primary percutaneous coronary intervention (p-PCI) or hospital thrombolysis, respectively. However, during 2009, there was a trend towards a substantial increase in p-PCI procedures. This was the result of the commitment of cardiologists, the contract signed by the Health Insurance Fund (HIF) for remuneration of catheterisation laboratory (cathlab) staff for each p-PCI procedure (2005), and the provision of new cathlabs by the Ministry of Health (MOH). The number of PCI centres and trained cardiologists has been rising simultaneously. Direct mobile telephone contact with interventional cardiologists has facilitated the transport of patients directly to cathlabs (from 7.5% before 2009 to 34.2% in 2010 and 2011). Although the number of patients treated with p-PCI is increasing (2006 - 647 p-PCIs; 2007 - 1,248 p-PCIs; 2008 -1,794 p-PCIs; 2009 - 2,468 p-PCIs; 2010 - 3,216 and 2011 - 3,498 p-PCIs), the percentage of patients who are treated within 120 minutes of establishing a diagnosis (first medical contact) is still not satisfactory (38%).

A 12-year follow-up study of patients with newly diagnosed lone atrial fibrillation: implications of arrhythmia progression on prognosis: the Belgrade Atrial Fibrillation study.

BACKGROUND: Lone atrial fibrillation (AF) has been suggested to have a favorable long-term prognosis. Significant interest has been directed at factors predicting arrhythmia progression, and the HATCH score (hypertension, age ≥ 75 years, transient ischemic attack or stroke [2 points], COPD, and heart failure [2 points]) recently has been proposed as a predictive score for AF progression. We investigated long-term outcomes in a large cohort of newly diagnosed lone AF and whether progression from paroxysmal to permanent AF confers an adverse impact on outcomes, including stroke and thromboembolism. METHODS: The study was an observational cohort of 346 patients with newly diagnosed lone AF with a mean follow-up of 12.1 ± 7.3 years. RESULTS: Baseline paroxysmal AF was confirmed in 242 patients, and of these, 65 (26.9%) subsequently experienced progression to permanent AF. Older age and development of congestive heart failure during follow-up were the multivariate predictors of AF progression (both P < .01), which was documented in 19.8% of patients with a HATCH score of 0 vs 63.2% with a score of 2 (P < .001), although the predictive validity of the HATCH score per se was modest (C statistic, 0.6). The annual rate of thromboembolism and heart failure during follow-up were low (0.4% each), and five patients (1.4%) died. AF progression, development of cardiac diseases, and older age were multivariate predictors of adverse outcomes, including thromboembolism (all P < .05). Baseline CHADS(2) (congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischemic attack) score was not predictive for thromboembolism (C statistic, 0.50; 95% CI, 0.31-0.69). CONCLUSIONS: This 12-year follow-up study provides confirmatory evidence of a generally favorable prognosis of lone AF, but adverse outcomes (including stroke and thromboembolism) are significantly influenced by age and the (new) development of underlying heart disease. Arrhythmia progression in lone AF is a marker of increased risk for adverse cardiovascular events.

Gender-related differences in presentation, treatment and long-term outcome in patients with first-diagnosed atrial fibrillation and structurally normal heart: the Belgrade atrial fibrillation study.

BACKGROUND: Several studies have investigated gender-related differences in atrial fibrillation (AF), but limited data are available in relation to gender-related differences in presentation, treatment and long-term outcomes of patients with first-diagnosed AF and structurally normal heart. OBJECTIVE: To compare gender-related clinical characteristics, presentation, treatment and long-term outcomes in a cohort of patients with first-diagnosed non-valvular AF and a structurally normal heart, following a 10-year follow-up. METHODS: Observational cohort study of patients with AF between 1992 and 2007. RESULTS: Of 862 patients (mean age 52.2±12.1 years), 315 (36.5%) were female. Paroxysmal AF and hypertension were significantly more prevalent in females, while persistent AF was more common amongst males (all p<0.001). Female patients were more symptomatic (p=0.002). After a mean follow-up of 10.1±6.1 years, more male patients developed tachycardiomyopathy (6.0% vs. 1.9%, p=0.02). In multivariate analysis, male gender remained significantly associated with tachycardiomyopathy (HR 3.1, 95% CI: 1.3-7.4, p=0.012). The rate of transition to permanent AF, thromboembolism, hemorrhage, all-cause mortality, cardiovascular and sudden death did not significantly differ between male and female patients. CONCLUSIONS: Gender differences are evident in AF. Male patients were less asymptomatic or more frequently developed persistent AF. Male patients were also at higher risk of tachycardiomyopathy, suggesting that these patients require more attention to rate control during follow-up.

Brachial approach to NOGA-guided procedures: electromechanical mapping and transendocardial stem-cell injections.

Several methods are available for delivering stem cells to the heart. Recent studies have highlighted the advantages of injecting the cells directly into the myocardium in order to increase myocardial retention of cells. A particular focus has been on percutaneous transendocardial injection, facilitated by electromechanical mapping.The NOGA XP Cardiac Navigation System has a multicomponent catheter that is designed to guide and deliver transendocardial injections via a transfemoral approach, without a guidewire. However, this method may not be feasible in some patients who have peripheral vascular disease. Herein, we describe the case of a 68-year-old man whose tortuous, sharply angled iliac arteries precluded a femoral approach to transendocardial injection. To overcome the anatomic and mechanical challenges, we used a brachial approach. We believe that this is the 1st report of using the brachial route for transendocardial injection, and that it can be a viable alternative to the transfemoral approach in selected patients.

Mitral annular calcification predicts cardiovascular morbidity and mortality in middle-aged patients with atrial fibrillation: the Belgrade Atrial Fibrillation Study.

BACKGROUND: Mitral annular calcification (MAC) has been suggested as a reliable, time-averaged marker of atherosclerosis and is associated with coronary artery disease, heart failure, ischemic stroke, and increased mortality. Data on the relationship between MAC and cardiovascular morbidity and mortality in atrial fibrillation (AF) are sparse, with the exception of the relationship between MAC and stroke. We investigated the association of MAC with cardiovascular morbidity, stroke, cardiovascular mortality, and all-cause death in a cohort of middle-aged patients with AF with a mean 10-year follow-up. METHODS: This was an observational study of patients with nonvalvular AF between 1992 and 2007. RESULTS: Of 1,056 patients, 33 (3.1%) had MAC; they were more likely to be older and female and to have a dilated left atrium, reduced left ventricular ejection fraction, permanent AF, hypertension, and/or diabetes mellitus (all P < .05). Total follow-up was 10,418.5 years (mean, 9.9 ± 5.9 years), and the mean age was 52.7 ± 12.2 years. In univariate analysis, MAC was associated with all-cause death, cardiovascular death, stroke, new cardiac morbidity (all P < .05), and the composite end point of ischemic stroke, myocardial infarction (MI), and all-cause death (P < .001). In multivariate analyses, MAC was related to all-cause death (hazard ratio [HR], 4.3; 95% CI, 1.8-10.0; P < .001), cardiovascular death (HR, 3.5; 95% CI, 1.2-10.4; P = .025), the composite end point (HR, 2.1; 95% CI, 1.0-4.3; P = .048), and new cardiac morbidity (HR, 2.4; 95% CI, 1.3-4.5; P = .005). There was no significant relationship between MAC and stroke or MI in the multivariate analyses. CONCLUSIONS: MAC is associated with increased cardiovascular morbidity, cardiovascular mortality, and all-cause mortality of patients with AF. MAC should be acknowledged as a marker of increased cardiovascular risk in middle-aged patients with AF.

Assessment of the left ventricular chamber stiffness in athletes.

Since diastolic dysfunction is an early sign of the heart disease, detecting diastolic disturbances is predicted to be the way for early recognizing underlying heart disease in athletes. So-called chamber stiffness index (E/e')/LVDd was predicted to be useful in distinguishing physiological from pathological left ventricular hypertrophy, because it was shown to be reduced in athletes. It remains unknown whether it is reduced in all athletic population. Standard and tissue Doppler were used to assess cardiac parameters at rest in 16 elite male wrestlers, 21 water polo player, and 20 sedentary subjects of similar age. In addition to (E/e')/LVDd index, a novel (E/e')/LVV, (E/e')/RVe'lat indices were determined. Progressive continuous maximal test on treadmill was used to assess the functional capacity. VO(2) max was the highest in water polo players, and higher in wrestlers than in controls. LVDd, LVV, LVM/BH(2.7) were higher in athletes. Left ventricular early diastolic filling velocity, deceleration and isovolumetric relaxation time did not differ. End-systolic wall stress was significantly higher in water polo players. RV e' was lower in water polo athletes. Right atrial pressure (RVE/e') was the highest in water polo athletes. (E/e'lat)/LVDd was not reduced in athletes comparing to controls (water polo players 0.83 ± 0.39, wrestlers 0.73 ± 0.29, controls 0.70 ± 0.28; P = 0.52), but (E/e's)/RVe'lat better distinguished examined groups (water polo players 0.48 ± 0.37, wrestlers 0.28 ± 0.15, controls 0.25 ± 0.16, P = 0.015) and it was the only index which predicted VO(2) max. In conclusion, intensive training does not necessarily reduce (E/e'lat)/LVDd index. A novel index (E/e's)/RVe'lat should be investigated furthermore in detecting diastolic adaptive changes.