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.

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.

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.

Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study.

OBJECTIVES: This study aimed to assess the clinical impact of immediate versus delayed invasive intervention in patients with non-ST-segment myocardial infarction (NSTEMI). BACKGROUND: Previous studies found conflicting results on the effects of earlier invasive intervention in a heterogeneous population of acute coronary syndromes without ST-segment elevation. METHODS: We randomized 323 NSTEMI patients to an immediate-intervention group (<2 h after randomization, n = 162) and a delayed-intervention group (2 to 72 h, n = 161).The primary endpoint was the occurrence of death or new myocardial infarction (MI) at 30-day follow-up. RESULTS: Median time from randomization to angiography was 1.4 h and 61.0 h in the immediate-intervention group and the delayed-intervention group, respectively (p < 0.001). At 30 days, the primary endpoint was achieved less frequently in patients undergoing immediate intervention (4.3% vs. 13%, hazard ratio: 0.32, 95% confidence interval: 0.13 to 0.74; p = 0.008). At 1 year, this difference persisted (6.8% in the immediate-intervention group vs. 18.8% in delayed-intervention group; hazard ratio: 0.34, 95% confidence interval: 0.17 to 0.67; p = 0.002). The observed results were mainly attributable to the occurrence of new MI in the pre-catheterization period (0 deaths + 0 MIs in the immediate-intervention group vs. 1 death + 10 MIs in the delayed-intervention group). The rate of deaths, new MI, or recurrent ischemia was lower in the immediate-intervention group at both 30 days (6.8% vs. 26.7%; p < 0.001) and 1 year (15.4% vs. 33.1%; p < 0.001). CONCLUSIONS: Immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with the delayed invasive strategy at early and midterm follow-up, mainly due to a decrease in the risk of new MI in the pre-catheterization period. (Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients [RIDDLE-NSTEMI]; NCT02419833).

Prognostic value of calcium score and coronary flow velocity reserve in asymptomatic diabetic patients.

BACKGROUND: The risk stratification of patients with diabetes mellitus (DM) is a major objective for the clinicians, and it can be achieved by coronary flow velocity reserve (CFVR) or with coronary artery calcium score (CS). CS evaluates underlying coronary atherosclerotic plaque burden and CFVR estimates both presence of coronary artery stenosis and microvascular function. Consequently, CFVR may provide unique risk information beyond the extent of coronary atherosclerosis. AIM: Our aim is to assess joint prognostic value of CFVR and CS in asymptomatic DM patients. MATERIALS AND METHODS: We prospectively included 200 asymptomatic patients (45,5 % male, mean age 57,35 ± 11,25), out of which, there were 101 asymptomatic patients with DM and 99 asymptomatic patients without DM, but with one or more conventionally risk factors for coronary artery disease. We analyzed clinical, biochemical, metabolic, inflammatory parameters, CS by Agatston method, transthoracic Doppler echocardiography CFVR of left anterior descending artery and echocardiographic parameters. RESULTS: Total CS and CS LAD were significantly higher, while mean CFVR was lower in diabetics compared to the nondiabetics. During 1 year follow-up, 24 patients experienced cardio-vascular events (one cardiovascular death, two strokes, three myocardial infarctions, nine new onsets of unstable angina and nine myocardial revascularizations): 19 patients with DM and five non DM patients, (p = 0,003). Overall event free survival was significantly higher in non DM group, compared to the DM group (94,9 % vs. 81,2 %, p = 0,002 respectively), while the patients with CS ≥200 and CFVR <2 had the worst outcome during 1 year follow up in the whole study population as well as in the DM group. At multivariable analysis CFVR on LAD (HR 12.918, 95 % CI 3.865-43.177, p < 0.001) and total CS (HR 13.393, 95 % CI 1.675-107.119, p = 0.014) were independent prognostic predictors of adverse events in DM group of patients. CONCLUSION: Both CS and CFVR provide independent and complementary prognostic information in asymptomatic DM patients. When two parameters are analyzed together, the risk stratification ability improves, even when DM patients are analyzed together with non DM patients. As a result, DM patients with CS ≥200 and CFVR <2 had the worst outcome. Consequently, the use of two tests identified subset of patients who can derive the most benefit from the intensive prevention measures.

Stenting a myocardial bridge: a wrong decision in STEMI?

In a STEMI setting, stent implantation for a myocardial bridge (MB) with significant systolic compression in the mid LAD, is a challenging issue.The risk of coronary rupture during stent implantation arises from: (i) a thin intima of the bridged artery; (ii) a thin myocardial layer toward the right ventricle; (iii) a smaller LAD diameter in the MB; (iv) high inflation pressure in the balloon. Perforation with a coronary fistula resolving spontaneously within several months is one of the possible scenarios. We report a case of a coronary fistula between mid LAD and right ventricle after MB stenting in a patient with STEMI, with spontaneous angiographic deterioration after several days. Stent graft implantation in case of a coronary fistula with increasing flow is an effective therapeutic concept.

[The degree of coronary atherosclerosis as a marker of insulin resistance in non-diabetics].

INTRODUCTION: The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. OBJECTIVE: The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. METHODS: The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (GO), insulin (10) and lipid panel measurements (TC, HDL, LDL, TG) were taken after a 12-hour fasting. RESULTS: The protocol encompassed 40 patients (19 men and 21 women) treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis), Group B (18 patients, 45%, with a single-vessel disease) and Group C (16 patients, 40%, with multi-vessel disease). Presence of lower insulin sensitivity, higher 10 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F = 4.279, p = 0.023, A vs. C p = 0.012, B vs. C p = 0.038; 10: F = 3.461 p = 0.042, A vs. B p = 0.045, A vs. C p = 0.013; TC: F = 2.572, p = 0.09), while no significant difference was found for GO, LDL, HDL and TG. CONCLUSION: Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

Systemic rapamycin without loading dose for restenosis prevention after coronary bare metal stent implantation.

OBJECTIVES: The aim of this study was to assess the role of short oral administration of rapamycin, without loading dose, in the reduction of restenosis rate after bare metal stent implantation. BACKGROUND: Previous studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. METHODS: This was prospective, open-label study of 80 patients randomized to either oral rapamycin (2 mg/day for 30 days, starting within 24 hr of stent implantation) or no therapy after implantation of a coronary bare metal stent. The primary study end point was incidence of angiographic binary restenosis and late loss at six months. The secondary end points were target lesion revascularization (TLR), target vessel revascularization (TVR), and incidence of major adverse cardiovascular events (MACE) at 6 months. RESULTS: Angiographic follow up was completed in 72/80 (90%) of patients. In the rapamycin group, the drug was well tolerated (22.5% minor side effects) and was maintained in 100% of patients. At six months, the in-segment binary restenosis was 10.5% in rapamycin group vs. 51.4% in no-therapy group, P < 0.001) and the in-stent binary restenosis was 7.9% in rapamycin group vs. 48.7% in no-therapy group, P < 0.001. The in-segment late loss was also significantly reduced with oral therapy (0.29 + or - 0.39 vs. 0.86 + or - 0.64 mm, respectively, P < 0.001). Similarly, after six months, patients in the oral rapamycin group also showed a significantly lower incidence of TLR and TVR (7% vs. 22.7%, respectively, P = 0.039) and MACE (7% vs. 22.7%, respectively, P = 0.039). CONCLUSIONS: This study showed that the administration of oral rapamycin (2 mg/day, without loading dose) during 30 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Quantitative evaluation of collateral circulation in patients with previous myocardial infarction: relation to myocardial ischemia, angiographic appearance and functional improvement of myocardium.

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/- 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of 0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P(w)/P(a) was significantly higher in comparison to patients with ECG changes (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P(w)/P(a) was significantly higher than in the patients without echo improvement (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P(w)/P(a) are associated with ECG changes during balloon occlusion. Higher P(w)/P(a) was associated with better functional improvement of myocardium.