Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

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.

Quantitative Flow Ratio to Predict Nontarget Vessel-Related Events at 5 Years in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Angiography-Guided Revascularization.

Background In ST-segment-elevation myocardial infarction, angiography-based complete revascularization is superior to culprit-lesion-only percutaneous coronary intervention. Quantitative flow ratio (QFR) is a novel, noninvasive, vasodilator-free method used to assess the hemodynamic significance of coronary stenoses. We aimed to investigate the incremental value of QFR over angiography in nonculprit lesions in patients with ST-segment-elevation myocardial infarction undergoing angiography-guided complete revascularization. Methods and Results This was a retrospective post hoc QFR analysis of untreated nontarget vessels (any degree of diameter stenosis [DS]) from the randomized multicenter COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trial by assessors blinded for clinical outcomes. The primary end point was cardiac death, spontaneous nontarget vessel myocardial infarction, and clinically indicated nontarget vessel revascularization (ie, ≥70% DS by 2-dimensional quantitative coronary angiography or ≥50% DS and ischemia) at 5 years. Of 1161 patients with ST-segment-elevation myocardial infarction, 946 vessels in 617 patients were analyzable by QFR. At 5 years, the rate of the primary end point was significantly higher in patients with QFR ≤0.80 (n=35 patients, n=36 vessels) versus QFR >0.80 (n=582 patients, n=910 vessels) (62.9% versus 12.5%, respectively; hazard ratio [HR], 7.33 [95% CI, 4.54-11.83], P<0.001), driven by higher rates of nontarget vessel myocardial infarction (12.8% versus 3.1%, respectively; HR, 4.38 [95% CI, 1.47-13.02], P=0.008) and nontarget vessel revascularization (58.6% versus 7.7%, respectively; HR, 10.99 [95% CI, 6.39-18.91], P<0.001) with no significant differences for cardiac death. Multivariable analysis identified QFR ≤0.80 but not ≥50% DS by 3-dimensional quantitative coronary angiography as an independent predictor of the primary end point. Results were consistent, including only >30% DS by 3-dimensional quantitative coronary angiography. Conclusions Our study suggests incremental value of QFR over angiography-guided percutaneous coronary intervention for nonculprit lesions among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

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.

Pharmacological Prophylaxis of Atrial Fibrillation After Surgical Myocardial Revascularization.

INTRODUCTION: Postoperative Atrial Fibrillation (POAF) is associated with a higher rate of postoperative complications and mortality, as well as with longer hospitalization and increased treatment costs. We have designed and performed a randomized, trial of pharmacological prophylaxis in which the event of interest is POAF. AIM: The aim of this study is to reduce the risk of postoperative, complications associated with this arrhythmia. METHODS: We included 240 stable patients with a coronary heart disease, who were referred to elective surgical revascularization of the myocardium. The patients were assigned into three groups of 80 patients each: group A (BB, beta blocker, comparator), group B (BB+ Amiodarone) and group C (BB + Rosuvastatin). The goal was to establish whether intervention by combination therapy was more useful than a comparator. RESULTS: An event of interest (POAF) has occurred in 66 of the total 240 patients. Number of new POAF cases is the lowest in Group B, 14 (17.5%) compared to 25 (31.25%) new cases in the comparator group, and 27 new cases (33.75%) in group C. Absolute risk reduction was 13.75%, ≈14% less POAF in group B compared to comparator. Relative risk reduction was 56% (RR 0.56, p = 0.04). Number Needed to Treat was 7.27. In group C, 33.75% of patients developed POAF. Absolute risk was insignificantly higher in group C (2.5%, NS) compared to the comparator .The number needed to harm was high, 40. CONCLUSION: The results of our research show that prophylaxis of POAF with combined therapy BB + Amiodarone was the most efficient one.

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.

Rehospitalizations Following Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction: Results From a Multi-Center Randomized Trial.

BACKGROUND: Rehospitalizations (RHs) after ST-elevation myocardial infarction carry a high economic burden and may deteriorate quality of life. Characterizing patients at higher risk may allow the design of preventive measures. We studied the frequency, reasons, and predictors for unplanned cardiac and noncardiac RHs in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: In this post-hoc analysis of the COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction; NCT00962416) trial including 1137 patients, unplanned cardiac and noncardiac RHs occurred in 133 (11.7%) and in 79 patients (6.9%), respectively, at 1 year. The most frequent reasons for unplanned cardiac RHs were recurrent chest pain without evidence of ischemia (20.4%), recurrent chest pain with ischemia and coronary intervention (16.9%), and ischemic events (16.9%). Unplanned noncardiac RHs occurred most frequently attributed to bleeding (24.5%), infections (14.3%), and cancer (9.1%). On multivariate analysis, left ventricular ejection fraction (22% increase in the rate of RHs per 10% decrease; P=0.03) and angiographic myocardial infarction Syntax score (34% increase per 10-point increase; P=0.01) were independent predictors of unplanned cardiac RHs. Age emerged as the only independent predictor of unplanned noncardiac RHs. Regional differences for unplanned cardiac RHs were observed. CONCLUSIONS: Among ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention in the setting of a randomized, clinical trial, unplanned cardiac RHs occurred in 12% with recurrent chest pain being the foremost reason. Unplanned noncardiac RHs occurred in 7% with bleeding as the leading cause. Left ventricular ejection fraction and Syntax score were independent predictors of unplanned cardiac RHs and identified patient subgroups in need for improved secondary prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962416.

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.

Very short/short-term benefit of inpatient/outpatient cardiac rehabilitation programs after coronary artery bypass grafting surgery.

BACKGROUND: Exercise-based rehabilitation is an important part of treatment patients following coronary artery bypass graft (CABG) surgery. HYPOTHESIS: To evaluate effect of very short/short-term exercise training on cardiopulmonary exercise testing (CPET) parameters. METHODS: We studied 54 consecutive patients with myocardial infarction (MI) treated with CABG surgery referred for rehabilitation. The study population consisted of 50 men and 4 women (age 57.72 ± 7.61 years, left ventricular ejection fraction 55% ± 5.81%), who participated in a 3-week clinical and 6-month outpatient cardiac rehabilitation program. The Inpatient program consisted of cycling 7 times/week and daily walking for 45 minutes. The outpatient program consisted mainly of walking 5 times/week for 45 minutes and cycling 3 times/week. All patients performed symptom-limited CPET on a bicycle ergometer with a ramp protocol of 10 W/minute at the start, for 3 weeks, and for 6 months. RESULTS: After 3 weeks of an exercise-based cardiac rehabilitation program, exercise tolerance improved as compared to baseline, as well as peak respiratory exchange ratio. Most importantly, peak VO2 (16.35 ± 3.83 vs 17.88 ± 4.25 mL/kg/min, respectively, P < 0.05), peak VCO2 (1.48 ± 0.40 vs 1.68 ± 0.43, respectively, P < 0.05), peak ventilatory exchange (44.52 ± 11.32 vs 52.56 ± 12.37 L/min, respectively, P < 0.05), and peak breathing reserve (52.00% ± 13.73% vs 45.75% ± 14.84%, respectively, P < 0.05) were also improved. The same improvement trend continued after 6 months (respectively, P < 0.001 and P < 0.0001). No major adverse cardiac events were noted during the rehabilitation program. CONCLUSIONS: Very short/short-term exercise training in patients with MI treated with CABG surgery is safe and improves functional capacity.

ApPropriateness of myocaRdial RevascularizatiOn assessed by the SYNTAX score II in a coUntry without cardiac Surgery faciliTies; PROUST study.

BACKGROUND/OBJECTIVES: The SYNTAX Score II (SSII) was proposed as a novel approach for objective individualized decision-making for optimal myocardial revascularization i.e. percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. We sought to investigate how many lives may be saved by SSII use. METHODS: A total number of 651 consecutive SSII-naive-patients with complex coronary artery disease who were treated with PCI (n=409) or referred to other institutions for CABG (n=242) were included. All-cause mortality was ascertained in 96% of patients. The SSII was calculated for each patient. RESULTS: Based on the SSII treatment recommendation, CABG would have been the treatment of choice in 257/651 (39.5%) patients, PCI in 7/651 (1.1%) patients and CABG or PCI in 387/651 (59.4%) patients. Out of 257 patients in whom the treatment recommendation by SSII was CABG, 113/257 (44.0%) patients had actually CABG, while the remaining 144/257 (56.0%) underwent PCI. It was shown that 144/257 patients with treatment recommendations in favour of CABG who were treated with PCI had significantly higher mortality at 4years when compared with patients with SSII treatment recommendation for PCI or equally favouring CABG and PCI (12.5% vs. 0.0% vs. 6.9%, respectively, P=0.04). CONCLUSION: The intuitive decision-making for choosing the optimal myocardial revascularization method differed predominantly from the SSII recommendation for CABG. The discordance between the SSII recommended revascularization strategy and the clinical decision was associated with a higher 4-year mortality i.e. one life may be saved if SSII would be calculated and followed consequently in 18 patients.

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.

Risk factor indicators in offspring of patients with premature coronary heart disease in Banja Luka region/Republic of Srpska/Bosnia and Herzegovina.

INTRODUCTION: Risk factor differences among offspring of patients with premature coronary heart disease (CHD) have not been widely studiem. MATERIAL AND METHODS: We examined 161 persons from the region of Banja Luka, including 81 children (mean age: 25.9 years, 45.7% female) with a history of CHD and a control group of 80 persons (mean age: 24.1, 50% female). Medical history interviews and risk factor measurements were performed. RESULTS: There were differences in mean body amss index (BMI) (26.1 kg/m(2) vs. 23.1 kg/m(2), p < 0.0001), waist circumference (87.7 cm vs. 83.9 cm, p = 0.002), hip circumference (99.3 cm vs. 95.84 cm, p < 0.002), systolic blood pressure (BP) (128.09 mm Hg vs. 122.7 mm Hg, p = 0.007), and diastolic BP (99.3 mm Hg vs. 95.8 mm Hg, p = 0.07). Moreover, HDL-cholesterol was significantly lower (1.1 mmol/l vs. 1.4 mmol/l, p = 0.0001), triglycerides significantly higher (2.2 mmol/l vs. 1.6 mmol/l, p = 0.001), and TC/HDL-ratio was significantly higher (5.1 vs. 4.0, p < 0.001) comparing cases and controls, respectively, adjusted for age, gender, and standard CHD risk factors total cholesterol, LDL and HDL cholesterol, smoking, systolic and diastolic BP, and BMI, those with HDL-C > 1.0 mmol/l in men and 1.2 mmol/l in women had a reduced odds (OR = 0.08, 95% CI: 0.02-0.34 of CHD as well as those with change of fat type (OR = 0.26, 95% CI: 0.11-0.60). CONCLUSIONS: Children of parents with premature CHD have a significantly greater burden of CHD risk factors, with low HDL-C, in particular, being associated with an increased likelihood of being a child of a parent with premature CHD.

Co-expression of vascular and lymphatic endothelial cell markers on early endothelial cells present in aspirated coronary thrombi from patients with ST-elevation myocardial infarction.

INTRODUCTION: Angiogenesis is the growth of both new vascular and lymphatic blood vessels from the existing vasculature. During this process, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs) express specific markers, which help their discrimination and easier identification. Since the coronary thrombi material aspirated from patients with ST-elevation myocardial infarction (STEMI) proved as good angiogenesis model, we investigated the expression of CD34 and CD31 as BECs markers, and D2-40, LYVE-1 and VEGFR3 as LEC markers in this material. MATERIALS AND METHODS: Aspirated thrombi were stained immunohistochemically for CD34, CD31, D2-40, LYVE-1 and VEGFR3. Organizational patterns of immunopositive cells were graded as single cells, clusters or microvessels. Double immunofluorescence for CD31, D2-40, LYVE-1 and VEGRF3 was done. Thrombi were also graded as fresh (<1day old), lytic (1-5days old) and organized (>5days old). RESULTS: Serial sections of aspirated thrombi showed concordant BEC and LEC markers immunopositivity. Double immunoflorescence proved co-expression of CD31 and LEC markers on the same cells. Cells expressing LEC markers organized in clusters and microvessels were mainly present in lytic and organized thrombi. CONCLUSION: Co-expression of BEC and LEC markers on the same non-tumorous cell during thrombus neovascularization indicates existing in vivo plasticity of endothelial cells under non-tumorous pathological conditions. It also points that CD34 and CD31 on one hand, and D2-40, LYVE-1 and VEGFR3 immunostaining on the other hand, cannot solely be a reliable indicators whether vessel is lymphatic or not.

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.

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.

OBJECTIVES: The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. BACKGROUND: Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. METHODS: Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. RESULTS: Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS: This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

Men with lower HDL cholesterol levels have significant increment of soluble CD40 ligand and high-sensitivity CRP levels following the cessation of long-term clopidogrel therapy.

AIM: The aim of this study was to examine whether the termination of long-term clopidogrel therapy results in a proinflammatory state and whether lipid parameters influence the inflammatory response after stopping the drug. METHODS: A prospective, multicenter study was conducted among 200 patients with implanted coronary stents who received dual antiplatelet therapy for one year, without ischemic or bleeding events. According to the guidelines, clopidogrel was discontinued after one year. In all patients, the high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand (sCD40L) and lipid [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] levels were measured twice: on the day of cessation of clopidogrel and 45 days after the termination of clopidogrel treatment. RESULTS: In men (n=151), the sCD40L serum levels were significantly higher 45 days after the discontinuation of clopidogrel (p=0.007), while the hsCRP levels were not significantly different (p=0.407). Furthermore, when analyzed across the HDL-C quartiles, the hsCRP and sCD40L values were found to be associated with the levels of HDL-C after the discontinuation of clopidogrel in men. In addition, the men in the first HDL-C quartile exhibited the most pronounced increase in the sCD40L levels (p=0.001) and had significantly higher hsCRP levels (p=0.001) compared to the subjects in the other quartiles. Other lipid parameters did not show any associations with the sCD40L or hsCRP levels. CONCLUSIONS: The discontinuation of clopidogrel is associated with higher increments in the sCD40L level, and a pronounced proinflammatory response is associated with a lower HDL-C concentration.

Coronary thrombi neovascularization in patients with ST-elevation myocardial infarction - clinical and angiographic implications.

INTRODUCTION: Coronary artery thrombosis in ST-elevation myocardial infarction (STEMI) is a dynamic process often preceded by episodes of silent plaque rupture and subocclusive thrombosis. Thrombus organization is achieved by ingrowth of endothelial and smooth muscle cells. Clinical significance and impact of thrombus neovascularization on primary percutaneous coronary intervention (pPCI) outcome remain unclear. Therefore we investigated composition and neovascularization of thrombi aspirated during pPCI and their association with clinical and angiographic parameters of STEMI patients. METHODS: Aspirated thrombi retrieved from 84 STEMI patients were classified as fresh (<1 day), lytic (1-5 days) or organized (>5 days). Thrombus neovascularization was evaluated immunohistochemically using CD34, CD31 and VEGF antibodies. CD34 and CD31 immunopositive (CD34/CD31+) cells were organized as single, clusters and microvessels. VEGF positivity was graded as low or high, based on thrombus surface immunopositive area. RESULTS: CD34/CD31+ cells were present in 67% of all aspirated thrombi. Thrombus CD34/CD31 positivity was associated with previous history of angina pectoris (χ(2)=6.142, p=0.013) and lower myocardial blush grade (MBG<3, χ(2)=12.602, p<0.001). Organization of CD34/CD31+ cells showed inverse association with the extent of VEGF positivity (χ(2)=10.607, p=0.005). Fresh thrombi were associated with shorter ischemic time (U=237.5, p=0.002) and MBG 3 (χ(2)=6.379, p=0.012). CONCLUSIONS: Older thrombus age and neovascularization are associated with suboptimal myocardial perfusion in STEMI patients. Thrombus VEGF expression is inversely associated with degree of CD34+ cell organization. Therefore, neovascularization of aspirated thrombi may indicate the duration of thrombosis, coronary microcirculation status and outcome in STEMI patients.

Coronary flow of the infarct artery assessed by transthoracic Doppler after primary percutaneous coronary intervention predicts final infarct size.

Coronary microcirculatory function after primary percutaneous coronary intervention (pPCI) in patients with acute myocardial infarction is important determinant of infarct size (IS). Our aim was to investigate the utility of coronary flow reserve (CFR) and diastolic deceleration time (DDT) of the infarct artery (IRA) assessed by transthoracic Doppler echocardiography after pPCI for final IS prediction. In 59 patients, on the 2nd day after pPCI for acute anterior myocardial infarction, transthoracic Doppler analysis of IRA blood flow was done including measurements of CFR, baseline DDT and DDT during adenosine infusion (DDT adeno). Killip class, myocardial blush grade, resolution of ST segment elevation, peak creatine kinase-myocardial band and conventional echocardiographic parameters were determined. Single-photon emission computed tomography myocardial perfusion imaging was done 6 weeks later to define final IS (percentage of myocardium with fixed perfusion abnormality). IS significantly correlated with CFR (r = -0.686, p < 0.01), DDT (r = -0.727, p < 0.01), and DDT adeno (r = -0.780, p < 0.01). CFR and DDT adeno in multivariate analysis remained independent IS predictors after adjustment for other covariates and offered incremental prognostic value in models based on conventional clinical, angiographic, electrocardiographic and enzymatic variables. In predicting large infarction (IS > 20 %), the best cut-off for CFR was <1.73 (sensitivity 65 %, specificity 96 %) and for DDT adeno ≤720 ms (sensitivity 81 %, specificity 96 %). CFR and DDT during adenosine are independent and powerful early predictors of final IS offering incremental prognostic information over conventional parameters of myocardial and microvascular damage and tissue reperfusion.

Ruptured giant mitral valve aneurysm: an unexpected finding in a diabetic patient with dyspnea and new-onset atrial fibrillation.

Mitral valve aneurysm (MVA) is a rare valve disease. The case is reported of pathologically proven MVA in a 61-year-old diabetic male with chronic alcoholic liver disease who presented with dyspnea and new-onset atrial fibrillation, without clinical elements of current or recent infection. Transthoracic echocardiography revealed a 'cystic' formation of the anterior mitral leaflet (AML) with mild mitral regurgitation (MR) and aortic regurgitation (AR) hitting the AML. Transesophageal echocardiography (TEE) showed clearly that the formation on the AML was a valve aneurysm, and depicted the site of aneurysm rupture with an additional jet of MR through the rupture. Following mitral valve replacement, pathology of the excised valve showed chronic bacterial endocarditis with calcified bacterial colonies, myxomatous changes with fibrinoid dissection of lamina fibrosa, and neovascularization of the leaflet. The mechanisms of MVA formation are discussed, together with its potential complications, diagnostic modalities and therapeutic strategies. The present case emphasizes that MVA is often a remnant of endocarditis, even when the latter is clinically silent and undiagnosed. The importance of chronic AR directed towards the AML as a predisposing condition for MVA formation is also underlined in this case. The superiority of TEE in providing a full exploration of the mitral valve morphology is verified.