Coronary microcirculation in nonculprit vessel territory in reperfused acute myocardial infarction.

BACKGROUND: There is an ongoing debate on the extension of reperfusion-related microvascular damage (MVD) throughout the remote noninfarcted myocardial regions in patients with ST-elevation myocardial infarction (STEMI) that undergo primary percutaneous intervention (pPCI). The aim of this study was to elucidate the impact of reperfusion on remote microcirculatory territory by analyzing hemodynamic alterations in the nonculprit-vessel in relation to reperfusion. METHODS: A total of 20 patients with STEMI undergoing pPCI were included. Peri-reperfusion temporal changes in hemodynamic parameters were obtained in angiographically normal nonculprit vessels before and 1-h after reopening of the culprit vessel. Intracoronary pressure and flow velocity data were compared using pairwise analyses (before and 1-h after reperfusion). RESULTS: In the non-culprit vessel, compared to the pre-reperfusion state, mean resting average peak velocity (33.4 ± 9.4 to 25.0 ± 4.9 cm/s, P < 0.001) and mean hyperemic average peak velocity (53.5 ± 14.4 to 42.1 ± 10.66 cm/s, P = 0.001) significantly decreased; whereas baseline (3.2 ± 1.0 to 4.0 ± 1.0 mmHg.cm-1.s, P < 0.001) and hyperemic microvascular resistance (HMR) (1.9 ± 0.6 to 2.4 ± 0.7 mmHg.cm-1.s, P < 0.001) and mean zero flow pressure (Pzf) values (32.5 ± 6.9 to 37.6 ± 8.3 mmHg, P = 0.003) significantly increased 1-h after reperfusion. In particular, the magnitude of changes in HMR and Pzf values following reperfusion were more prominent in patients with larger infarct size and with higher extent of MVD in the culprit vessel territory. CONCLUSION: Reperfusion-related microvascular injury extends to involve remote myocardial territory in relation to the magnitude of the adjacent infarction and infarct-zone MVD. (GUARD Clinical TrialsNCT02732080).

Endocan: a novel biomarker associated with well-developed coronary collateral circulation in patients with stable angina and chronic total occlusion.

Angiogenesis and arteriogenesis have a crucial role in the formation of coronary collateral vessels. It has been shown that endocan and vascular cell adhesion molecule-1 (VCAM-1) are potential angiogenetic factors. We investigated the relationship between serum endocan levels and grade of coronary collaterals, and also the correlation of endocan levels with serum VCAM-1 levels. Patients with stable angina and at least one total coronary occlusion at invasive coronary angiography were included in our study. Collateral degree was graded according to Rentrop and Cohen's classification. Patients who had grade 0 or 1 collateral vessels were included in the poorly-developed collateral group, and those with grade 2 or 3 coronary collateral vessels were included in the well-developed collateral group. Serum endocan and VCAM-1 levels were significantly higher in the well-developed collateral group (436.6 ± 213.3 ng/mL vs. 216.1 ± 78.5 ng/mL, p < .001; 11.02 ± 6.58 ng/mL vs. 6.78 ± 1.14 ng/mL, p < .001, respectively). In a logistic regression analysis, only serum endocan level remained as an independent predictor for good collateral development. In the ROC curve analysis, 282 ng/mL endocan level had an a 82 % sensitivity and 86 % specificity for prediction of the well-developed collateral group. Higher endocan level was related to better coronary collateral development. In the event that these results are confirmed in further studies, endocan may be considered as an anti-ischemic treatment strategy in order to improve collateral development.

Doppler-derived strain imaging detects left ventricular systolic dysfunction in children with Turner syndrome.

OBJECTIVES: Children with Turner syndrome (TS) are at increased risk of cardiovascular disease (CVD), but associations with subclinical CVD are not well-characterized. The purpose of this study was to assess myocardial function using strain imaging (SI) by echocardiography in children with TS and without known CVD. METHODS: The study included 48 children with TS aged 4-16 years and 20 healthy control children. Children with TS were excluded if they had a cardiac malformation, a decreased left ventricular (LV) systolic function, or any chronic disease. Each child had an echocardiographic examination with conventional echocardiography and one-dimensional longitudinal strain (1DST) echocardiography. RESULTS: Septal and lateral systolic strain (S) and strain rate (SR) values, which are indicative of longitudinal myocardial function, were significantly decreased in TS patients. However, LV ejection fraction (LVEF) and LV fractional shortening (LVFS) was not significantly different between groups. LV mass index (LVMi), interventricular septum (IVS) thickness, LV posterior wall (LVPW) thickness, and left atrial (LA) diameter index were significantly higher in TS children compared to controls. Peak transmitral flow velocity in late diastole (peak A) was significantly higher, whereas peak transmitral flow velocity in early diastole (peak E), deceleration time (DT), and the ratio of early to late diastolic filling were significantly lower, in TS patients. CONCLUSION: Reduced LV systolic S and SR in children with TS may indicate early myocardial dysfunction before any detectable change in LVEF.

Increased Carotid Intima-media Thickness and Its Association with Carbohydrate Metabolism and Adipocytokines in Children Treated with Recombinant Growth Hormone

Objective: Reports on the association between growth hormone (GH) therapy and cardiovascular risk factors in children are limited. This study aimed to evaluate carotid intima-media thickness (cIMT) in children treated with recombinant human GH (rhGH) and assess the effects of rhGH therapy and changes in serum carbohydrate metabolism, lipid profile and adipocytokines on cIMT. Methods: Seventy-one isolated idiopathic GH deficiency (GHD) children and 44 age- and sex-matched healthy controls were enrolled in this study. The study group was divided into two subgroups according to insulin resistance (IR) on oral glucose tolerance tests. Insulin secretion [homeostatic model assessment (HOMA) B, total insulin] and sensitivity (HOMA-IR, QUICKI, Matsuda) indices were calculated. cIMT was measured and the standard deviation scores (SDS) were calculated. Associations between cIMT-SDS and insulin secretion and sensitivity indices, serum lipid levels, adipocytokines (leptin, resistin, ghrelin), and other rhGH treatment-related factors were evaluated. Results: cIMT-SDS was increased in GHD children treated with rhGH compared to the controls [0.02 (2.27) vs. -1.01 (1.63), p=0.003]. cIMT-SDS did not differ between those children on rhGH treatment with or without IR. High cIMT-SDS was significantly associated with higher serum ghrelin levels and lower serum high density lipoprotein (HDL) levels (ß=0.491, p=0.001 and ß=-0.027, p=0.017), but not with BMI-SDS, blood pressure, insulin secretion and sensitivity indices, or the dose and duration of rhGH therapy. Conclusion: Our findings showed that GHD children treated with rhGH have increased cIMT. Alterations in carbohydrate metabolism were not associated with cIMT in children treated with rhGH. GH therapy per se appears to be associated with this increased cIMT but causality should be elucidated in further studies. cIMT also appears to be associated with higher ghrelin and lower HDL levels.

Reducing Aortic Barotrauma and Vascular Extracellular Matrix Degradation by Pacemaker-Mediated QRS Widening.

Background The extent of pressure-related damage might be related to acceleration rate of the applied pressure (peak dP/dt) in the vascular system. In this study, we sought to determine whether dP/dt applied to the aortic wall (aortic dP/dt) and in turn vascular extracellular matrix degradation can be mitigated via modulation of left ventricular (LV) contractility (LV dP/dt) by pacemaker-mediated desynchronization. Methods and Results First, in 34 patients, changes in aortic dP/dt values in 3 aortic segments in response to pacemaker-mediated stepwise QRS widening leading to gradual desynchronization of the LV contraction by means of steadily changed atrioventricular delay (AVD) with temporary dual-chamber pacing was examined before and after beta-blocker (15 mg IV metoprolol) administration. Second, serum matrix metalloproteinase-9 levels were measured in the 20 patients with permanent pacemaker while they were on sinus rhythm with normal QRS width and 3 weeks after wide QRS rhythm ensured by dual pacing, dual sensing, and dual response to sensing with short AVD. LV dP/dt substantially correlated with dP/dt measured in ascending (r=0.83), descending (r=0.89), and abdominal aorta (r=0.96). QRS width strongly correlated with dP/dt measured in ascending (r=-0.95), descending (r=-0.92), and abdominal (r=-0.96) aortic segments as well. In patients with permanent pacemaker, wide QRS rhythm led to a significant reduction in serum matrix metalloproteinase-9 levels (from 142.5±32.9 pg/mL to 87.5±32.4 pg/mL [P<0.001]) at the end of 3 weeks follow-up. Conclusions QRS prolongation by short AVD dual pacing, dual sensing, and dual response to sensing results in concomitant decreases in peak dP/dt values in the LV and in all aortic segments with or without background beta-blocker administration, which in turn led to a significant reduction in circulating matrix metalloproteinase-9 levels. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03665558.

Coronary microvascular dysfunction equivalent to left main coronary artery disease.

Coronary microvascular dysfunction, also known as cardiac syndrome X, is a clinical syndrome presenting with typical angina and evidence of myocardial ischemia in the absence of flow-limiting stenosis on coronary angiography. Of patients undergoing coronary angiography due to suspected myocardial ischemia, 50% are found to have normal or near-normal coronary arteries. Described in this case report is a patient who developed hypotension and ST segment depressions during treadmill exercise test. Left main coronary artery or multivessel disease was suspected. Coronary angiography was normal, but coronary flow reserve measurement revealed severe microvascular dysfunction.

Impact of high serum Immunoglobulin E levels on the risk of atherosclerosis in humans.

BACKGROUND: Epidemiological studies show that immunoglobulin E (IgE) levels were higher in subjects with acute coronary events. However, it is unknown if the increased IgE level is a marker of future coronary incidents and whether it may be regarded as a risk factor of an ischemic heart disease. OBJECTIVE: Our aim was to investigate the relationship between IgE levels and some atherosclerotic markers in patients without known atherosclerotic disease. METHODS: Fifty patients (mean age, 40.96 ± 10.8 years) with high serum IgE levels due to various conditions who did not display evidence of an atherosclerotic disease and 30 healthy control subjects (mean age, 47 ± 8.27 years) were included in the study. Atherosclerotic disease markers including adhesion molecules like vascular cell adhesion molecule-1, intercellular adhesion molecule-1, proinflammatory cytokines such as interleukin-6, endothelin-1, and systemic inflammatory markers such as high sensitivity C-reactive protein were determined by enzyme-linked immunosorbent assay (ELISA). Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurements and carotid intima media thickness using transthoracic Doppler echocardiography. RESULTS: CFR was significantly lower in the patient group when compared with the control group (p<0.001; 95% confidence interval, -0.79 to-0.20) while carotid media thicknesses were not different between 2 groups. There were no differences in ELISA test results between the 2 groups. CONCLUSION: Our results showed that CFR as an early marker of endothelial dysfunction was significantly lower in patients with high IgE levels. This finding seems to support the role of IgE in the vascular pathology of atherosclerosis.

Bimodal Pattern of Coronary Microvascular Involvement in Diabetes Mellitus.

BACKGROUND: The contribution of functionally disturbed coronary autoregulation and structurally impaired microvascular vasodilatory function to reduced coronary flow velocity reserve, reflecting impaired coronary microcirculation in diabetes mellitus (DM), has not been clearly elucidated. The objective of this study was to identify the mechanism of coronary microvascular impairment in DM in relation to duration of disease. METHODS AND RESULTS: Coronary flow velocities in the anterior descending coronary artery were assessed by transthoracic echocardiography following angiography revealing normal epicardial coronary arteries in 55 diabetic and 47 nondiabetic patients. Average peak flow velocities, coronary flow velocity reserve, and microvascular resistance in baseline and hyperemic conditions (baseline and hyperemic microvascular resistance, respectively) were assessed. Reduced coronary flow velocity reserve in patients with short duration (<10 years) of DM compared with nondiabetic patients was primarily driven by increased baseline average peak flow velocity (26.50±5.6 versus 22.08±4.31, P=0.008) in the presence of decreased baseline microvascular resistance (3.69±0.86 versus 4.34±0.76, P=0.003). In contrast, decreased coronary flow velocity reserve in patients with long-standing (≥10 years) DM compared with nondiabetic patients was predominantly driven by reduced hyperemic average peak flow velocity (41.57±10.01 versus 53.47±11.8, P<0.001) due to increased hyperemic microvascular resistance (2.13±0.42 versus 1.69±0.39, P<0.001). CONCLUSIONS: Both altered coronary autoregulation and impaired microvascular vasodilatory function contribute to DM-related coronary microvascular impairment in a time-dependent manner. DM-induced early functional microvascular autoregulatory impairment seems to evolve into structural microvascular impairment in the initially overperfused microvascular territory at the later stage of disease.

Serum Endocan Level and the Severity of Coronary Artery Disease: A Pilot Study.

Endothelial-specific molecule 1 (endocan) is expressed in endothelial cells. We investigated the relationship between acute coronary syndrome (ACS) and serum endocan levels. We included 30 individuals as a control group and 53 patients diagnosed with ACS. The severity of coronary artery disease was assessed by a modified Gensini stenosis and SYNTAX scoring system. There was a significant difference in serum endocan levels between the control group and the ACS group (0.75 ± 0.13 vs 0.86 ± 0.25 ng/mL, P = .014). There was also a significant difference in serum endocan levels between diabetic patients with ACS and nondiabetic patients with ACS (1.02 ± 0.33 vs 0.81 ± 0.21 ng/mL, P = .016). There was no significant correlation between serum endocan level, Gensini, and SYNTAX score (r = .11, P = .53 and r = .16, P = .37). Endocan, a new biomarker of endothelial pathology, is significantly increased in patients with ACS.

An aortic dissection treated with left main coronary artery stent implantation.

Retrograde coronary aortic dissection is a rare but dangerous complication of coronary angioplasty. Mostly seen in right coronary artery procedures, especially in chronic total oclussion lesions, and rarely seen in left side procedures. This is a case report of an aortic dissection complicated by coronary angioplasty of the left circumflex artery. Immediate stenting of the left main coronary artery successfully sealed the entry point of dissection and stabilized the patient.