Vladan Vukcevic

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).

A novel mobile transtelephonic system with synthesized 12-lead ECG

The problem of synthesizing the standard 12-lead electrocardiogram (ECG) from the signals recorded using three special ECG leads is studied in detail. The implementation of that concept into the design of a new mobile ECG transtelephonic system is presented. The system has two separate units: a stationary diagnostic-calibration center and a mobile ECG device with integrated electrodes. The patient records by himself three special leads with the mobile ECG recorder and sends data via cellular phone to the personal computer in the diagnostic center where standard 12-lead ECG is numerically reconstructed on the base of the patient transformation matrix previously calculated into the calibration process. The experimental study shows high accuracy of the reconstructed ECG.

The value of fractional and coronary flow reserve in predicting myocardial recovery in patients with previous myocardial infarction

AIMS The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS Study population consisted of 46 patients (mean age 53 +/- 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 +/- 0.14 vs. 0.70 +/- 0.07, P < 0.001), improvement of FFR (0.35 +/- 0.14 vs. 0.21 +/- 0.07, P < 0.001), improvement of CFRthermo (1.3 +/- 0.6 vs. 0.5 +/- 0.3, P < 0.001), and CFRthermo after PCI (2.6 +/- 0.7 vs. 2.0 +/- 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002). CONCLUSION Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

Prognostic implications of bleeding measured by Bleeding Academic Research Consortium (BARC) categorisation in patients undergoing primary percutaneous coronary intervention

Objective To investigate the relationship between inhospital bleeding as defined by Bleeding Academic Research Consortium (BARC) consensus classification and short-term and long-term mortality in unselected patients admitted for primary percutaneous coronary intervention (PCI). Methods We analysed data of all consecutive patients with ST segment elevation myocardial infarction (STEMI) admitted for primary PCI, enrolled in a prospective registry of a high volume centre. The BARC-defined bleeding events were reconstructed from the detailed, prospectively collected clinical data. The primary outcome was mortality at 1 year. Results Of the 1808 patients with STEMI admitted for primary PCI, 115 (6.4%) experienced a BARC type ≥2 bleeding. As the BARC bleeding severity worsened, there was a gradient of increasing rates of 1-year death. The 1-year mortality rate increased from 11.5% with BARC 0+1 type to 43.5% with BARC type 3b bleeding. After multivariable adjustment for demographic and clinical characteristics of patients, the independent predictors of 1-year death were BARC type 3a (HR 1.99; 95% CI 1.16 to 3.40, p=0.012) and BARC type 3b bleeding (HR 3.22; 95% CI 1.67 to 6.20, p<0.0001). Conclusions The present study demonstrated that bleeding events defined according to the BARC classification hierarchically correlate with 1-year mortality after admission for primary PCI. The strongest predictor of 1-year mortality is the BARC type 3b bleeding.

Efficiency, safety, and long-term follow-up of retrograde approach for CTO recanalization: initial (Belgrade) experience with international proctorship.

BACKGROUND  Retrograde approach increases the success rate for percutaneous recanalization of complex chronic total occlusion (CTO) of coronary arteries. OBJECTIVES  The purpose of this study was to describe our initial experience of retrograde percutaneous coronary intervention for CTO program, focusing on its safety and feasibility, and long-term clinical follow-up. METHODS  The study was a single center retrospective registry which included a total of 40 patients, of 590 CTO treated patients (6.7%), between January 2008 and October 2011, who underwent retrograde approach for CTO recanalization. RESULTS  Mean occlusion duration was 37.8 ± 40.3 months. Overall success recanalization rate was 87.5% (35/40). Septal collaterals were used to access the occlusion in all cases (100%). Retrograde guidewire crossing of collateral channels was successful in 36/40 (90.0%) patients with success rate of CTO recanalization in these patients of 97.2%. Retrograde approach as the primary strategy was applied in 23/40 (57.5%) patients, retrograde approach immediately after antegrade failure attempt was performed in 8/40 (20.0%) patients, and retrograde approach as elective procedure, after previously failed antegrade attempt, was performed in 9/40 (22.5%) patients. The success rate of these strategies was: 87.0% (20/23 patients) for primary, 87.5% (7/8 patients) for retrograde immediately after antegrade failure, and 88.9% (8/9 patients) for retrograde after previous failed antegrade attempt, respectively. Total in-hospital major adverse cardiac events (MACE) rate was 5.0% (2 non-Q-wave myocardial infarctions). The MACE free survival at median follow-up of 20 months was 89% (95% CI: 78-100%). CONCLUSIONS  This study has demonstrated that adequate training and international proctorship for this complex and demanding technique is a necessity and prerequisite to achieve high overall success rates, with acceptable complication rates and excellent long-term survival rate.

Regional difference of microcirculation in patients with asymmetric hypertrophic cardiomyopathy: transthoracic Doppler coronary flow velocity reserve analysis.

OBJECTIVE To evaluate, by noninvasive coronary flow velocity reserve (CFVR), whether patients with asymmetric hypertrophic cardiomyopathy (HC), with or without left ventricular outflow tract obstruction, demonstrate significant regional differences of CFVR. METHODS We evaluated 61 patients with HC (27 men; mean age 49 ± 16 years), including 20 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 41 patients without obstruction (HCM). The control group included 20 age- and sex-matched subjects. Transthoracic Doppler echocardiography CFVR of the left anterior descending coronary artery (LAD) and the posterior descending coronary artery (PD) were performed, including calculation of relative CFVR as the ratio between CFVR LAD and CFVR PD. RESULTS Compared with the controls, all the patients with HC had lower CFVR LAD (2.12 ± 0.53 vs 3.34 ± 0.67; P < .001) and CFVR PD (2.29 ± 0.49 vs 3.21 ± 0.65; P < .001). CFVR LAD in HOCM group in comparison with the HCM group was significantly lower (1.93 ± 0.42 vs 2.22 ± 0.55; P = .047), due to higher basal diastolic coronary flow velocities (0.40 ± 0.09 vs 0.33 ± 0.07 m/sec; P = .002), with similar hyperemic diastolic flow velocities (0.71 ± 0.16 vs 0.76 ± 0.19 m/sec; P = .330), respectively. There was no significant difference in CFVR PD between patients with HOCM and those with HCM (2.33 ± 0.46 vs 2.27 ± 0.50; P = .636), respectively. Relative CFVR was lower in the HOCM group compared with the HCM group (0.84 ± 0.16 vs 0.98 ± 0.14; P = .001). By multivariable regression analysis, left ventricular outflow tract gradient was the independent predictor of CFVR LAD (B = -0.24; P = .008) and relative CFVR (B = -0.34; P = .016). CONCLUSIONS CFVR LAD and relative CFVR were significantly lower in patients with HOCM compared with patients with HCM. Regional differences of CFVR are present only in patients with significant left ventricular outflow tract obstruction, which suggests that obstruction per se, by increasing wall stress in basal conditions, leads to higher basal diastolic coronary flow velocities and results in lower CFVR in LAD compared with PD.

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 ± 0.39 vs. 0.86 ± 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.

Prediction of Myocardial Functional Recovery by Noninvasive Evaluation of Basal and Hyperemic Coronary Flow in Patients with Previous Myocardial Infarction

BACKGROUND The aim of this study was to evaluate the relation of basal and hyperemic coronary flow with myocardial functional improvement in patients with previous myocardial infarction undergoing elective percutaneous coronary intervention (PCI). METHODS Coronary flow was measured using transthoracic Doppler echocardiography in 50 patients (41 men; mean age, 53 ± 8 years) with previous myocardial infarction before, 24 hours, and 3 months after elective PCI. Diastolic deceleration time (DDT) was measured from the peak diastolic velocity to the point of intercept of initial decay slope with baseline. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal peak diastolic flow velocities. RESULTS In comparison with patients without improvements in left ventricular function, patients with recovered left ventricular function had longer DDTs before angioplasty (841 ± 286 vs. 435 ± 80 msec, P < .001). CFR was significantly higher in recovered compared with nonrecovered patients (2.60 ± 0.70 vs. 2.16 ± 0.34, P = .034) 24 hours after PCI. Global and regional wall motion scores before PCI, end-diastolic and end-systolic volumes, and CFR 24 hours after PCI and DDT before PCI were univariate predictors of left ventricular functional recovery. By multivariate analysis, DDT and regional wall motion score before PCI were independent predictors of left ventricular recovery in the follow-up period (P = .003 and P = .007, respectively). CONCLUSIONS In patients with previous myocardial infarction undergoing elective PCI, evaluation of basal coronary flow pattern and measurement of DDT before angioplasty may predict functional improvement of myocardium in the follow-up period and could be useful quantitative parameters in the evaluation of potential improvement in myocardial function.

Mental stress-induced ischemia in patients with coronary artery disease: echocardiographic characteristics and relation to exercise-induced ischemia.

Objective The aims of this study were to investigate the incidence and parameters associated with myocardial ischemia during mental stress (MS) as measured by echocardiography and to evaluate the relation between MS-induced and exercise-induced myocardial ischemia. Methods Study participants were 79 patients (63 men; mean [M] [standard deviation {SD}] age = 52 [8] years) with angiographically confirmed coronary artery disease and previous positive exercise test result. The MS protocol consisted of mental arithmetic and anger recall task. The patients performed a treadmill exercise test 15 to 20 minutes after the MS task. Data of post–MS exercise were compared with previous exercise stress test results. Results The frequency of echocardiographic abnormalities was 35% in response to the mental arithmetic task, compared with 61% with anger recall and 96% with exercise (p < .001, exercise versus MS). Electrocardiogram abnormalities and chest pain were substantially less common during MS than were echocardiographic abnormalities. Independent predictors of MS-induced myocardial ischemia were: wall motion score index at rest (p = .02), peak systolic blood pressure (p = .005), and increase in rate-pressure product (p = .004) during MS. The duration of exercise stress test was significantly shorter (p < .001) when MS preceded the exercise and in the case of earlier exercise (M [SD] = 4.4 [1.9] versus 6.7 [2.2] minutes for patients positive on MS and 5.7 [1.9] versus 8.0 [2.3] minutes for patients negative on MS). Conclusions Echocardiography can be successfully used to document myocardial ischemia induced by MS. MS-induced ischemia was associated with an increase in hemodynamic parameters during MS and worse function of the left ventricle. MS may shorten the duration of subsequent exercise stress testing and can potentiate exercise-induced ischemia in susceptible patients with coronary artery disease.

Efficiency of Ergonovine Echocardiography in Detecting Angiographically Assessed Coronary Vasospasm

C vasospasm plays a major role in provoking myocardial ischemia in patients with variant angina, but also in some patients with acute coronary syndrome including unstable angina, myocardial infarction, and sudden death. Ergonovine provocation has been used for 20 years for detection of coronary artery spasm. Most data on ergonovine testing have been reported in the preselected group of patients with variant angina, establishing ergonovine as a test of high diagnostic confidence. In current clinical practice, when a marked decline in the use of ergonovine testing in the catheterization laboratory is observed, accompanied by promising reports on ergonovine echocardiography, a question remains on the incidence, safety, and usefulness of provocative testing for coronary vasospasm in patients with chest pain syndrome and nonsignificant coronary artery stenosis. Thus, the objectives of our study were to evaluate (1) the incidence of angiographically assessed coronary vasospasm in a consecutive population of patients with nonsignificant coronary artery disease, (2) the efficiency of simultaneously performed ergonovine echocardiography in identifying coronary vasospasm, and (3) the relation between ergonovine echocardiographic and angiographic results. • • • The vasomotor response to ergonovine was studied in 100 consecutive patients (45 men and 55 women, mean age 52 8 years) with chest pain syndrome and hemodynamically nonsignificant coronary stenosis (diameter stenosis, mean 26 10%). No patient had previous myocardial infarction, congestive heart failure, severe congenital or valvular heart disease, or documented cardiomyopathy. Patients with severe hypertension (systolic pressure 180 mm Hg and diastolic pressure 110 mm Hg), recent malignant ventricular arrhythmia, or conduction abnormalities were not considered for the study. All drug medications were stopped 48 hours before testing, except angiotensin-converting enzyme inhibitors and short-acting nitrates. Our institution’s human use committee approved the study, and all patients gave informed consent. According to predominant clinical symptoms, patients were classified into the following categories: chest pain during rest (n 18), chest pain during effort and rest (n 10), nocturnal chest pain (n 9), chest pain in the cold (n 19), and chest pain during stressful situations (n 44). The pretest probability of having coronary artery disease was 60 15%. In 84 patients, submaximal Bruce treadmill, exercise stress electrocardiographic testing was performed before diagnostic angiography; in 16 patients exercise testing was not performed because of poor patient motivation or physical inability to perform adequate exercise tests. No patient developed significant ST-segment changes during and after stress testing, defined as a decrease or increase in ST segment of 0.1 mV 0.08 second after the J point, or rhythm and conduction abnormalities. The ergonovine test was performed in consecutive patients at the end of diagnostic catheterization showing nonsignificant coronary artery stenosis and a normal left ventriculogram. All patients underwent selective coronary angiography using the Judkins technique, and multiple views of each coronary artery were obtained. Angiographic evaluation during ergonovine testing was performed in the view that best showed the coronary lesion. Doses of 0.05, 0.10, and 0.20 mg of ergonovine maleate (total cumulative dose 0.35 mg) were given intravenously in succession at 3-minute intervals, followed by intracoronary injection of nitroglycerin. Angiography was performed before the study, at the end of each stage, and after administration of nitroglycerin. Systemic blood pressure, electrocardiography, and echocardiography for wall motion changes were monitored continuously and recorded at the end of each stage. Electrocardiography was considered positive for myocardial ischemia when 0.1 mV elevation or depression of the ST segment was found 0.08 second after the J point. Coronary arteriographic images were digitized and analyzed (off-line) with the quantitative coronary angiography imaging system (Medis CMS software, version 1.11, Nuenen, The Netherlands) by an observer unaware of patient clinical data and echocardiographic results. After visual inspection of the coronary artery, the frame of optimal clarity in the end-diastolic part of From the University Institute for Cardiovascular Diseases, Department for Diagnostic and Catheterization Laboratories, Clinical Center of Serbia, Belgrade, Yugoslavia. Dr. Ostojic’s address is: University Institute for Cardiovascular Diseases, Department for Diagnostic and Catheterization Laboratories, Clinical Center of Serbia, 8 Koste Todorovica, Belgrade, Yugoslavia. E-mail: miodrag.ostojic@kcs.ac.yu. Manuscript received March 16, 2001; revised manuscript received and accepted July 3, 2001.