Milan Dobric

Organization of heart failure management in European Society of Cardiology member countries: Survey of the Heart Failure Association of the European Society of Cardiology in collaboration with the Heart Failure National Societies/Working Groups

The aim of this document was to obtain a real‐life contemporary analysis of the demographics and heart failure (HF) statistics, as well as the organization and major activities of the Heart Failure National Societies (HFNS) in European Society of Cardiology (ESC) member countries.

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.

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.

Endothelial cell markers from clinician's perspective

Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their ability to form new blood vessels, the term vasculogenesis is not only reserved for the embryonic development. Possibility of de novo blood vessel formation from EPC is now widely explored in different ischemic conditions, especially in cardiovascular medicine. Numerous clinical trials have tested enhancing tissue vascularization by delivering hematopoietic cells that expressed endothelial markers. This therapeutic approach proved to be challenging and promising, particularly for patients who have exhausted all conventional therapeutic modalities. Angiogenesis, which refers to the formation of new blood vessels from existing vasculature, is indispensable process during tumor progression and metastasis. Blockage of tumor angiogenesis by targeting and inhibiting endothelial cell has emerged as novel safe and efficacious method to control many advanced malignant diseases. Numerous clinical studies are currently testing new antiangiogenic drugs which target and inhibit endothelial cell markers, receptors or molecules which transmit receptor-mediated signals, therefore inhibiting endothelial cell proliferation, migration and vascular tube formation. Many of these drugs are now widely used in clinical settings as first- or second-line chemotherapy in advanced malignant conditions. So far, these therapeutic approaches gave modest, yet encouraging clinical improvements, prolonging survival and improving functional capacity and quality of life for many terminally ill patients. Here we present the most commonly used endothelial cell markers along with their applicability in contemporary clinical practice.

Glycogen phosphorylase BB in myocardial infarction

Early experimental and clinical reports on glycogen phosphorylase BB (GPBB) kinetics following myocardial ischemic injury suggested that it could be a useful diagnostic marker for early detection of acute myocardial infarction (AMI). After more than two decades of investigation, there is now overwhelming body of evidence that do not support the use of GPBB measurement in diagnosis of acute AMI in patients presenting with acute chest pain. Currently, GPBB cannot be recommended as a diagnostic marker of AMI either as a stand-alone test or as an addition to (high-sensitive) troponin testing. It should be noted that these considerations apply to the early diagnosis of AMI, not to the prognostic stratification, which is also suggested but it warrants further investigation. The aim of this review is to summarize available evidence of GPBB measurement in early diagnosis of myocardial infarction.

Estimation of infarct size using transthoracic Doppler echocardiographic measurement of coronary flow reserve in infarct related and reference coronary artery.

BACKGROUND Patients in chronic phase of myocardial infarction (MI) have decreased coronary flow reserve (CFR) in infarct related artery (IRA) that is proportional to the extent of microvascular/myocardial damage. We proposed a novel model for the assessment of microvascular damage and infarct size using Doppler echocardiography evaluation of CFRs of the IRA (LAD) and reference artery (RCA). METHODS Our study included 34 consecutive patients (28 men, mean age 50 ± 11 years) with first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of infarct size (expressed as a percentage of myocardium with fixed perfusion abnormalities) and CFR evaluation of LAD and RCA. CFR derived percentage of microvascular damage (CFR PMD) was calculated as: CFR PMD=(CFR RCA-CFR LAD)/(CFR RCA-1)×100 (%). RESULTS CFR PMD correlated significantly with all parameters evaluating the severity of myocardial damage including: peak CK activity (r=0.632, p<0.001), WMSI (r=0.857, p<0.001), ejection fraction (r=-0.820, p<0.001), left ventricular end diastolic (r=0.757, p<0.001) and end systolic volume (r=0.794, p<0.001). Most importantly, CFR PMD (22 ± 17%) correlated significantly with infarct size by SPECT MPI (21 ± 17%) (r=0.874, p<0.001). CONCLUSIONS CFR PMD derived from the proposed model was significantly related to echocardiographic and enzymatic parameters of infarct size, as well as to myocardial damage assessed by SPECT MPI in patients with successfully reperfused first anterior STEMI.

The correlation of SYNTAX score by coronary angiography with breast arterial calcification by digital mammography

AIM To evaluate the hypothesis that breast arterial calcification (BAC) may predict coronary artery disease (CAD) severity. MATERIALS AND METHODS The study comprised 102 women >45 years (mean age 62±8 years) referred for digital mammography after coronary angiography. BAC was assessed using the Likert scale and CAD severity was assessed using the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery trial) score. RESULTS In comparison to the low SYNTAX score group (≤22) patients with a intermediate-to-high SYNTAX score (>22) were older (p=0.001), they more often had hypercholesterolaemia (p<0.001), diabetes (p=0.021), and a history of smoking (p=0.048). They also had a statistically higher level of fasting blood glucose (p<0.001), glycated haemoglobin (HbA1C; p<0.001), triglycerides (p=0.002), fibrinogen (p=0.001), whereas high-density lipoprotein (HDLc) was lower than in the group with a SYNTAX score ≤22 (p=0.005). BAC was significantly higher in patients with a SYNTAX score >22 (p<0.001). At multivariate analysis, BAC (odds ratio [OR] 34.24, 95% confidence interval [CI]: 8.05-145.7, p<0.001), hypercholesterolaemia (OR 22.65, 95% CI: 4.18-122.81, p<0.001) and fibrinogen (OR 2.55, 95% CI: 1.28-5.07, p=0.008) were independent predictive factors for patients with intermediate-to-high SYNTAX score. CONCLUSIONS In women >45 years, there was a significant correlation between the severity of CAD as evaluated by the SYNTAX score and BAC as evaluated by the Likert scale. BAC, hypercholesterolaemia, and fibrinogen may be used as an additional diagnostic tool to predict the presence and severity of CAD.

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.