Adherence to the 4S-AF Scheme in the Balkan region: Insights from the BALKAN-AF survey.

BACKGROUND: The 4S-AF scheme includes stroke risk, symptoms, severity of burden, and substrate severity domain. AIM: We aimed to assess the adherence to the 4S-AF scheme in patients classified according to stroke risk in post hoc analysis of the BALKAN-AF dataset. METHODS: A 14-week prospective enrolment of consecutive patients with electrocardiographically documented atrial fibrillation (AF) was performed in seven Balkan countries from 2014 to 2015. RESULTS: Low stroke risk (CHA2DS2-VASc score, 0 in males or 1 in females) was present in 162 (6.0%) patients. 2 099 (77.4%) patients had CHA2DS2-VASc score ≥3 in females or ≥2 in males (high stroke risk), and 613 (22.6%) had CHA2DS2-VASc score <3 in females or <2 in males. Seventy-five (46.3%) patients with low stroke risk and 1555 (74.1%) patients with high stroke risk were prescribed oral anticoagulants (OAC). Two thousand six hundred and seventy-seven (98.6%) had data on European Heart Rhythm Association (EHRA) class. Among 2099 patients with high stroke risk, 703 (33.4%) had EHRA class ≥3. Two hundred and seven (29.4%) patients with EHRA class ≥3 and high stroke risk were offered rhythm control; 620 (55.2%) of individuals with first-diagnosed or paroxysmal AF with high stroke risk were offered rhythm control. Two or more comorbidities occurred in 1927 (91.8%) patients with high stroke risk. CONCLUSIONS: OAC overuse was observed in patients with low stroke risk, whilst OAC underuse was evident in those with high risk of stroke. The percentage of highly symptomatic patients with high risk of stroke who were offered a rhythm control strategy was low.

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.

Quality indicators in the management of atrial fibrillation: the BALKAN-AF survey.

BACKGROUND: The implementation of quality indicators in the atrial fibrillation (AF) care should be considered to improve quality of management and patient outcome. METHODS: In the post-hoc analysis of the BALKAN-AF dataset, we assessed concordance with quality indicators for AF management. Available domains for AF management [patient assessment (baseline), anticoagulation, rate control strategy, rhythm control strategy and risk factor management] were identified and assessed at baseline visit. RESULTS: Among 132 patients with a CHA2DS2-VASc score of 0 (men) or 1 (women), 75 (56.8%) were prescribed oral anticoagulation (OAC). Of 2539 patients with a CHA2DS2-VASc score ≥ 1 for men and ≥ 2 for women, 1890 (74.4%) were prescribed OAC. Among 1088 patients with permanent AF, 110 (10.1%) individuals were prescribed antiarrhythmic drugs (AADs). Of 1616 patients with structural heart disease, 37 (2.2%) were prescribed class IC AADs. Of 1624 patients with paroxysmal or persistent AF, 59 (3.6%) were offered catheter ablation. Among 2712 AF patients, 2121 (78.2%) had hypertension, 671 (24.7%) were obese, 53 (2.0%) had obstructive sleep apnoea, 110 (4.0%) had alcohol abuse and 340 (12.5%) were smokers. CONCLUSIONS: In the BALKAN-AF cohort, the use of OAC for stroke prevention was poorly associated with patients stroke risk. The use of AADs in patients with permanent AF was low. The prescription of class IC AADs to patients with structural heart disease was infrequent. A large proportion of AF patients had their modifiable risk factors identified.

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.

Symptom management strategies: Rhythm vs rate control in patients with atrial fibrillation in the Balkan region: Data from the BALKAN-AF survey.

BACKGROUND: Symptom-focused management is one of the cornerstones of optimal atrial fibrillation (AF) therapy. OBJECTIVES: To evaluate the use of rhythm control and rate control strategy. Second, to identify predictors of the use of amiodarone in patients with rhythm control and of the use of rhythm control strategy in patients with paroxysmal AF in the Balkans. METHODS: Prospective enrolment of consecutive patients from seven Balkan countries to the BALKAN-AF survey was performed. RESULTS: Of 2712 enrolled patients, 2522 (93.0%) with complete data were included: 1622 (64.3%) patients were assigned to rate control strategy and 900 (35.7%) to rhythm control. Patients with rhythm control were younger, more often hospitalised for AF and with less comorbidities (all P < .05) than those with rate control. Symptom score [European Heart Rhythm Association (EHRA)] was not an independent predictor of a rhythm control strategy [odds ratio (OR) 0.99, 95% confidence interval (CI) 0.90-1.10, P = .945]. The most commonly chosen antiarrhythmic agents were amiodarone (49.7%), followed by propafenone (24.3%). CONCLUSION: More than one-third of patients in the BALKAN-AF survey received a rhythm control strategy, and these patients tended to be younger with less comorbidities than those managed with rate control. EHRA symptom score is not significantly associated with rhythm control strategy. The most commonly used antiarrhythmic agents were amiodarone, followed by propafenone.

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.

Stroke prevention in atrial fibrillation: comparison of recent international guidelines.

Stroke prevention is one of the cornerstones of management in patients with atrial fibrillation (AF). As part of the ABC (Atrial fibrillation Better Care) pathway (A: Avoid stroke/Anticoagulation; B: Better symptom control; C: Cardiovascular risk and comorbidity optimisation), stroke risk assessment and appropriate thromboprophylaxis is emphasised. Various guidelines have addressed stroke prevention. In this review, we compared the 2017 APHRS, 2018 ACCP, 2019 ACC/AHA/HRS, and 2020 ESC AF guidelines regarding the stroke/bleeding risk assessment and recommendations about the use of OAC. We also aimed to highlight some unique points for each of those guidelines. All four guidelines recommend the use of the CHA2DS2-VASc score for stroke risk assessment, and OAC (preferably NOACs in all NOAC-eligible patients) is recommended for AF patients with a CHA2DS2-VASc score ≥2 (males) or ≥3 (females). Guidelines also emphasize the importance of stroke risk reassessments at periodic intervals (e.g. 4-6 months) to inform treatment decisions (e.g. initiation of OAC in patients no longer at low risk of stroke) and address potentially modifiable bleeding risk factors.

Treatment implications of renal disease in patients with atrial fibrillation: The BALKAN-AF survey.

BACKGROUND: Atrial fibrillation (AF) often co-exists with renal function (RF) impairment. We investigated the characteristics and management of AF patients across creatinine clearance strata and potential changes in the use of nonvitamin K oral anticoagulants (NOAC) according to different equations for estimation of RF. METHODS: In this post hoc analysis of the BALKAN-AF survey, patients were classified according to RF (Cockcroft-Gault formula) as: preserved/mildly depressed RF (P-RF) ≥50 mL/min, moderately depressed RF (MD-RF) 30-49 mL/min, and severely depressed RF (SD-RF) <30 mL/min. RESULTS: Of 2712 enrolled patients, 2062 (76.0%) had data on RF. Patients with SD-RF and MD-RF were older, had higher mean value of European Heart Rhythm Association score, stroke and bleeding risk scores, and more comorbidities than patients with P-RF (all P < .05). They received oral anticoagulants (OAC), AF catheter ablation, and electrical cardioversion less often than those with P-RF (all P < .05). Rate control, no OAC, single-antiplatelet therapy (SAPT) alone, and loop diuretics were more prevalent in patients with SD-RF and MD-RF than in subjects with P-RF (all P < .005). An important change in NOAC therapy could appear in <1% of patients (Modification of Diet in Renal Disease formula) and in <1% of patients (Chronic Kidney Disease Epidemiology Collaboration group formula). CONCLUSIONS: Patients with SD-RF and MD-RF were older, more symptomatic, had higher stroke and bleeding risk and more comorbidities than those with P-RF. They were less likely to receive OAC and more likely to use rate control strategy, SAPT alone, and no OAC than subjects with P-RF.

Prompt and consistent improvement of coronary flow velocity reserve following successful recanalization of the coronary chronic total occlusion in patients with viable myocardium.

BACKGROUND: Coronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment, but data on coronary hemodynamic changes in relation to myocardial function are limited. We assessed changes in coronary flow velocity reserve (CFVR) by echocardiography in collateral donor and recanalized artery following successful opening of coronary CTO. METHODS: Our study enrolled 31 patients (60 ± 9 years; 22 male) with CTO and viable myocardium by SPECT scheduled for percutaneous coronary intervention (PCI). Non-invasive CFVR was measured in collateral donor artery before PCI, 24 h and 6 months post-PCI, and 24 h and 6 months in recanalized artery following successful PCI of CTO. RESULTS: Collateral donor artery showed significant increase in CFVR 24 h after CTO recanalization compared to pre-PCI values (2.30 ± 0.49 vs. 2.71 ± 0.45, p = 0.005), which remained unchanged after 6-months (2.68 ± 0.24). Baseline blood flow velocity of the collateral donor artery significantly decreased 24 h post-PCI compared to pre-PCI (0.28 ± 0.06 vs. 0.24 ± 0.04 m/s), and remained similar after 6 months, with no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24 h and 6 months post-PCI. CFVR of the recanalized coronary artery 24 h post-PCI was 2.55 ± 0.35, and remained similar 6 months later (2.62 ± 0.26, p = NS). CONCLUSIONS: In patients with viable myocardium, prompt and significant CFVR increase in both recanalized and collateral donor artery, was observed within 24 h after successful recanalization of CTO artery, which maintained constant during the 6 months. TRIAL REGISTRATION: ClinicalTrials.gov (Number NCT04060615 ).

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.

Management of patients with newly-diagnosed atrial fibrillation: Insights from the BALKAN-AF survey.

BACKGROUND: BALKAN-AF evaluated patterns of atrial fibrillation (AF) management in real-world clinical practice in the Balkans. The objectives were: to assess the proportion of patients with first-diagnosed AF in the BALKAN-AF cohort and to compare the management of patients with newly-diagnosed AF and those with previously known AF in clinical practice. METHODS: Consecutive patients from 7 Balkan countries were enrolled prospectively to the snapshot BALKAN-AF survey. RESULTS: Of 2712 enrolled patients, 2677 (98.7%) with complete data were included. 631 (23.6%) patients had newly-diagnosed AF and 2046 (76.4%) patients had known AF. Patients with newly-diagnosed AF were more likely to be hospitalized for AF and to receive single antiplatelet therapy (SAPT) alone and less likely to receive OACs than those with known AF (all p < 0.001). The use of OAC was not significantly associated with the CHA2DS2-VASc (p = 0.624) or HAS-BLED score (p = 0.225) on univariate analysis. Treatment in capital city, hypertension, dilated cardiomyopathy, mitral valve disease, country of residence or rate control strategy were independent predictors of OAC use, whilst non-emergency centre, treatment by cardiologist, paroxysmal AF, palpitations, symptoms attributable to AF (as judged by physician), mean heart rate and AF as the main reason for hospitalization were independent predictors of rhythm control strategy use. CONCLUSIONS: In BALKAN-AF survey, patients with newly-diagnosed AF were more often hospitalized, less often received OAC and were more likely to receive SAPT alone. The use of OAC for stroke prevention has not been driven by the individual patient stroke risk.

Stroke prevention in elderly patients with non-valvular atrial fibrillation in the BALKAN-AF survey.

BACKGROUND: Atrial fibrillation (AF) is common amongst the elderly, but this group tends to be suboptimally treated. Limited data are available on the stroke prevention strategies in the elderly, especially in the Balkan region. AIM: We investigated the use of oral anticoagulant therapy (OAC) amongst elderly AF patients in clinical practice in the Balkan region. METHOD: A 12-week prospective snapshot survey (2014-2015) of consecutive non-valvular AF patients was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia. Data were collected via an electronic case report form. RESULTS: Of 2671 patients, 418 (15.6%) were ≥80 years old. Overall, OAC was used in 1965 patients (73.6%). Compared with younger patients, the elderly (age ≥ 80) had a higher mean CHA2 DS2 -VASc score (3.22 ± 1.71 vs 4.89 ± 1.35, P < .001) and more often a HAS-BLED score of ≥3 (n = 198 [47.0%] vs n = 625 [27.3%], P < .001), but were less likely to receive OAC (n = 269 [64.4%] vs n = 1696 [75.3%], odds ratio [OR] 0.91; 95%CI 0.86-0.97, P = .003). There was no significant association between OAC use and mean CHA2 DS2 -VASc (OR 0.86; 95%CI 0.75-1.00, P = .053) or HAS-BLED score (OR 1.21; 95%CI 0.81-1.81, P = .349) in the elderly. CONCLUSION: In the BALKAN-AF Survey, elderly AF patients were less likely to receive the guideline-adherent treatment despite their less favourable risk profile. Since OAC nonuse among the elderly was not associated with increased HAS-BLED score, factors other than patients' risk profile could influence the implementation of guideline-adherent treatment for thromboprophylaxis in the elderly AF patients.

Prognostic Value of Preserved Coronary Flow Velocity Reserve by Noninvasive Transthoracic Doppler Echocardiography in Patients With Angiographically Intermediate Left Main Stenosis.

BACKGROUND: The potential of angiography to evaluate the hemodynamic severity of a left main coronary artery (LM) stenosis is limited. Noninvasive transthoracic Doppler echocardiographic coronary flow velocity reserve (CFVR) evaluation of intermediate coronary stenosis has demonstrated remarkably high negative prognostic value. The aim of this study was to assess clinical outcomes in patients with angiographically intermediate LM stenosis and preserved CFVR (>2.0) as evaluated by transthoracic Doppler echocardiographic CFVR. METHODS: The initial study population included 102 patients with intermediate coronary stenosis of the LM referred for transthoracic Doppler echocardiographic CFVR assessment. Peak diastolic CFVR measurements were performed in the distal segment of the left anterior descending coronary artery after intravenous adenosine (140 µg/kg/min), and CFVR was calculated as the ratio between maximal hyperemic and baseline coronary flow velocity. Nineteen patients had impaired CFVR (≤2.0) and were excluded from further analysis, as well as two patients with poor acoustic windows. The final group consisted of 81 patients (mean age, 60 ± 9 years; 76 men) evaluated for adverse cardiac events including death, myocardial infarction, and revascularization. RESULTS: Mean follow-up duration was 62 ± 26 months. Mean CFVR was 2.4 ± 0.4. Total event-free survival was 75 of 81 (92.6%), as six patients were referred for revascularization (five patients with coronary artery bypass grafting, one patient with percutaneous coronary intervention). There were no documented myocardial infarctions or cardiovascular deaths in the follow-up period. CONCLUSIONS: In patients with angiographically intermediate and equivocal LM stenosis and preserved CFVR values of >2.0, revascularization can be safely deferred.

Improved Propensity-Score Matched Long-Term Clinical Outcomes in Patients with Successful Percutaneous Coronary Interventions of Coronary Chronic Total Occlusion.

The objective of the study was to evaluate major adverse cardiovascular events (MACE) after successful versus failed percutaneous coronary intervention for chronic total occlusion (PCI-CTO).Limited data are available on long-term clinical follow-up in the treatment of chronic total occlusion (CTO).Between January 2009 and December 2010 PCI-CTO was attempted in 283 consecutive patients with 289 CTO lesions. Procedural success was 62.3% and clinical follow-up covered 83% (235/283) of the study population with a median follow-up of 66 months (range, 59-74).The total incidence of MACE was 57/235 (24.3%), and was significantly higher in the procedural failure group than in the procedural success group (33/87 (37.9%) versus 24/148 (16.2%), P < 0.001). All-cause mortality was significantly lower in patients with successful PCI-CTO compared to failed PCI-CTO (10.8% versus 20.7%, P < 0.05). Also, the rate of cardiovascular death in the procedural failure group (14.9%) was slightly higher than that in the procedural success group (7.4%, P = 0.066). The rate of TVR was statistically higher in the procedural failure group (P < 0.009). Propensity score-adjusted Cox regression showed that procedural success remained a significant predictor of MACE (adjusted HR 0.402; 95% CI 0.196-0.824; P = 0.013).Our study emphasizes the importance of CTO recanalization in improving long-term outcome including all-cause mortality with a borderline effect on cardiovascular mortality.

Prognostic Value of Transthoracic Doppler Echocardiography Coronary Flow Velocity Reserve in Patients with Nonculprit Stenosis of Intermediate Severity Early after Primary Percutaneous Coronary Intervention.

BACKGROUND: Treatment of nonculprit coronary stenosis during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction may be beneficial, but the mode and timing of the intervention are still controversial. The aim of this study was to examine the significance and prognostic value of preserved coronary flow velocity reserve (CFVR) in patients with nonculprit intermediate stenosis early after primary percutaneous coronary intervention. METHODS: Two hundred thirty patients with remaining intermediate (50%-70%) stenosis of non-infarct-related arteries, in whom CFVR was performed within 7 days after primary percutaneous coronary intervention, were prospectively enrolled. Twenty patients with reduced CFVR and positive results on stress echocardiography or impaired fractional flow reserve underwent revascularization and were not included in further analysis. The final study population of 210 patients (mean age, 58 ± 10 years; 162 men) was divided into two groups on the basis of CFVR: group 1, CFVR > 2 (n = 174), and group 2, CFVR ≤ 2 (n = 36). Cardiac death, nonfatal myocardial infarction, and revascularization of the evaluated vessel were considered adverse events. RESULTS: Mean follow-up duration was 47 ± 16 months. Mean CFVR for the whole group was 2.36 ± 0.40. There were six adverse events (3.4%) related to the nonculprit coronary artery in group 1, including one cardiac death, one ST-segment elevation myocardial infarction, and four revascularizations. In group 2, there were 30 adverse events (83.3%, P < .001 vs group 1), including two cardiac deaths, two ST-segment elevation myocardial infarctions, and 26 revascularizations. CONCLUSIONS: In patients with CFVR > 2 of the intermediate nonculprit coronary lesion, deferral of revascularization is safe and associated with excellent long-term clinical outcomes.

Endothelial dysfunction of coronary arteries in subjects without diabetes: An association with both insulin resistance and impaired insulin secretion response.

AIMS: This study was aimed to compare insulin sensitivity and secretion response, lipoprotein and plasminogen activator inhibitor 1 (PAI-1) levels between the subjects with and without coronary artery endothelial dysfunction (ED). METHODS: ED was detected by intracoronary injection of acetylcholine (ACh) in 47 nondiabetes subjects without stenotic coronary arteries, selected from 316 consecutive patients with coronary angiography performed for suspected coronary artery disease. The subjects were divided into two groups: presence of ACh-induced coronary spasm (group ED+, N = 30) and absence of ACh-induced coronary spasm (group ED-, N = 17). Insulin sensitivity (Si) was evaluated by frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis and by HOMA-IR, insulin secretion by acute insulin response (AIR) (calculated from the first 8 min of FSIGTT) and by disposition index (DI) (Si × AIR). Lipids and PAI-1 levels were determined enzymatically, and LDL particle size by gradient gel electrophoresis. RESULTS: Si was significantly lower (4.22 ±â€¯0.62 vs 6.98 ±â€¯1.47 min-1/mU/l × 104; p < 0.05) while HOMA-IR was significantly higher in ED + group vs ED- group (2.8 ±â€¯0.3 vs 1.7 ±â€¯0.2; p < 0.05). Simultaneously, AIR and DI was significantly lower in ED + vs ED- groups (p < 0.05 and p < 0.01, respectively). Investigated groups did not differ in fasting lipid levels but ED+ group had significantly smaller LDL particles (p < 0.01) and higher PAI-1 levels (p < 0.05). Regression analysis shown that DI was a strong independent predictor of appearance of ED, together with PAI-1 and LDL particle size. CONCLUSIONS: Both insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes.

Decision-Making in Clinical Practice: Oral Anticoagulant Therapy in Patients with Non-valvular Atrial Fibrillation and a Single Additional Stroke Risk Factor.

Approximately 1 in 3-4 patients presenting with an ischemic stroke will also have atrial fibrillation (AF), and AF-related strokes can be effectively prevented using oral anticoagulant therapy (OAC), either with well-controlled vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs). In addition, OAC use (both VKAs and NOACs) is associated with a 26% reduction in all-cause mortality (VKAs) or an additional 10% mortality reduction with NOACs relative to VKAs. The decision to use OAC in individual AF patient is based on the estimated balance of the benefit from ischemic stroke reduction against the risk of major OAC-related bleeding [essentially intracranial hemorrhage (ICH)]. Better appreciation of the importance of VKAs' anticoagulation quality [a target time in therapeutic range (TTR) of ≥70%] and the availability of NOACs (which offer better safety compared to VKAs) have decreased the estimated threshold for OAC treatment in AF patients towards lower stroke risk levels. Still, contemporary registry-based data show that OAC is often underused in AF patients at increased risk of stroke. The uncertainty whether to use OAC may be particularly pronounced in AF patients with a single additional stroke risk factor, who are often (mis)perceived as having a "borderline" or insufficient stroke risk to trigger the use of OAC. However, observational data from real-world AF cohorts show that the annual stroke rates in such patients are higher than in patients with no additional stroke risk factors, and OAC use has been associated with reduction in stroke, systemic embolism, or death in comparison to no therapy or aspirin, with no increase in the risk of bleeding relative to aspirin. In this review article, we summarize the basic principles of stroke risk stratification in AF patients and discuss contemporary real-world evidence on OAC use and outcomes of OAC treatment in AF patients with a single additional stroke risk factor in various real-world AF cohorts.

Noninvasive assessment of myocardial bridging by coronary flow velocity reserve with transthoracic Doppler echocardiography: vasodilator vs. inotropic stimulation.

BACKGROUND: To consider hemodynamic assessment of myocardial bridging (MB) adequate, it is believed that inotropic stimulation with dobutamine should be estimated because its dynamic nature depends on the degree of extravascular coronary compression. This study evaluated comparative assessment of hemodynamic relevance of MB using coronary flow velocity reserve (CFVR) measurements by transthoracic Doppler echocardiography (TTDE) with vasodilatative and inotropic challenges. METHODS: This prospective study included forty-four patients with angiographic evidence of isolated MB of the left anterior descending coronary artery (LAD) and systolic compression of ≥50% diameter stenosis. All patients were evaluated by exercise stress-echocardiography (ExSE) test for signs of myocardial ischemia, and CFVR of the distal segment of LAD during iv.infusion of adenosine (ADO:140µg/kg/min) and iv.infusion of dobutamine (DOB:10-40µg/kg/min), separately. RESULTS: Exercise-SE was positive for myocardial ischemia in 8/44 (18%) of patients. CFVR during ADO was significantly higher than CFVR during peak DOB (2.85±0.68 vs. 2.44±0.48, p=0.002). CFVR during peak DOB was significantly lower in SE-positive group in comparison to SE-negative group (2.01±0.16 vs. 2.54±0.47, p<0.001), but not for ADO (2.47±0.51 vs. 2.89±0.70, p=0.168), respectively. Multivariable logistic analysis showed that CFVR peak DOB was the most significant predictor of functional significant MB (OR 0.011, 95%CI: 0.001-0.507, p=0.021). Receiver-operating characteristic curves have shown that TTDE-CFVR obtained by high-dose of dobutamine infusion is better than those by adenosine regarding to functional status of MB (AUC 0.861, p=0.004; AUC 0.674, p=0.179, respectively). CONCLUSIONS: Non-invasive CFVR measurement by TTDE during inotropic stimulation, in comparison to vasodilation, provides more reliable functional evaluation of MB.

Percutaneous implantation of self-expandable aortic valve in high risk patients with severe aortic stenosis: The first experiences in Serbia.

BACKGROUND/AIM: Aortic stenosis (AS) is the most common valvular heart disease in elderly people, with rather poor prognosis in symptomatic patients. Surgical valve replacement is the therapy of choice, but a significant number of patients cannot undergo surgical procedure. We presented initial experience of transcatheter aortic valve implantation (TAVI) performed in Catheterization Laboratory of the Clinic for Cardiology, Clinical Center of Serbia. METHODS: The procedures were performed in 5 patients (mean age 76 ± 6 years, 2 males, 3 female) with severe and symptomatic AS with contraindication to surgery or high surgical risk. The decision to perform TAVI was made by the heart team. Pre-procedure screening included detailed clinical and echocardiographic evaluation, coronary angiography and computed tomography scan. In all the patients we implanted a self-expandable aortic valve (Core Valve, Medtronic, USA). Six months follow-up was available for all the patients. RESULTS: All interventions were successfully performed without significant periprocedural complications. Immediate hemodynamic improvement was obtained in all the patients (peak gradient 94.2 ± 27.6 to 17.6 ± 5.2 mmHg, p < 0.001, mean pressure gradient 52.8 ± 14.5 to 8.0 ± 2.1 mmHg, p < 0.001). None of the patients developed heart block, stroke, vascular complication or significant aortic regurgitation. After 6 months, the survival was 100% with New York Heart Association (NYHA) functional improvement in all the patients. CONCLUSION: This successful initial experience provides a solid basis to treat larger number of patients with symptomatic AS and high surgical risk who are left untreated.