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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 Trials NCT02732080).

Fractional flow reserve (FFR) may not be immune from hemodynamic perturbations caused by both vessel and lesion related factors. The aim of this study was to investigate the impact of plaque- and vessel wall-related features of vulnerability on the hemodynamic effect of intermediate coronary stenoses. Methods and Results: In this cross-sectional study, patients referred to catheterization laboratory for clinically indicated coronary angiography were prospectively screened for angiographically intermediate stenosis (50–80%). Seventy lesions from 60 patients were evaluated. Mean angiographic stenosis was 62.1 ± 16.3%. After having performed FFR assessment, intravascular ultrasound (IVUS) was performed over the FFR wire. Virtual histology IVUS was used to identify the plaque components and thin cap fibroatheroma (TCFA). TCFA was significantly more frequent (65 vs. 38%, p = 0.026), and necrotic core volume (26.15 ± 14.22 vs. 16.21 ± 8.93 mm3, p = 0.04) was significantly larger in the positively remodeled than non-remodeled vessels. Remodeling index correlated with necrotic core volume (r = 0.396, p = 0.001) and with FFR (r = –0. 419, p = 0.001). With respect to plaque components, only necrotic core area (r = –0.262, p = 0.038) and necrotic core volume (r = –0.272, p = 0.024) were independently associated with FFR. In the multivariable model, presence of TCFA was independently associated with significantly lower mean FFR value as compared to absence of TCFA (adjusted, 0.71 vs. 0.78, p = 0.034). Conclusion: The current study demonstrated that for a given stenosis geometry, features of plaque vulnerability such as necrotic core volume, TCFA, and positive remodeling may influence the hemodynamic relevance of intermediate coronary stenoses.

The adjusted global antiphospholipid syndrome score (aGAPSS) is a recently developed thrombotic risk assessment score that considers the antiphospholipid antibody (aPL) profile and conventional cardiovascular risk factors. In this retrospective study, we aimed to evaluate the validity of the aGAPSS in predicting clinical manifestations (criteria and extra-criteria) of antiphospholipid syndrome (APS) in a single centre cohort of patients. Ninety-eight patients with APS ± systemic lupus erythematosus (SLE) were classified according to clinical manifestations as vascular thrombosis (VT), pregnancy morbidity (PM) or both (VT + PM). The aGAPSS was calculated for each patient as previously defined. Mean aGAPSS of the cohort was calculated as 10.2 ± 3.8. Significantly higher aGAPSS values were seen in VT (n = 58) and VT + PM (n = 29) groups when compared to PM (n = 11) group (10.6 ± 3.7 vs 7.4 ± 2.9, P = 0.005; 10.7 ± 4 vs 7.4 ± 2.9, P = 0.008, respectively), mainly due to lower frequencies of cardiovascular risk factors in PM. Higher aGAPPS values were also associated with recurrent thrombosis (11.6 ± 3.7 vs 9.9 ± 3.6, P = 0.04). Regarding extra-criteria manifestations, patients with livedo reticularis (n = 11) and APS nephropathy (n = 9) had significantly higher aGAPSS values (12.9 ± 3.4 vs 9.9 ± 3.7, P = 0.02; 12.4 ± 2.9 vs 10 ± 3.8, P = 0.04, respectively). The computed AUC demonstrated that aGAPSS values ≥10 had the best diagnostic accuracy for thrombosis. Our results suggest that patients with higher aGAPSS values are at higher risk for developing vascular thrombosis (either first event or recurrence) and extra-criteria manifestations, especially livedo reticularis and APS nephropathy.

Item does not contain fulltext OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 +/- 0.51 vs. 0.43 +/- 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 +/- 0.09 vs. 0.91 +/- 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 +/- 0.09 vs. 0.85 +/- 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

Objective : The aim of this cross-sectional, retrospective, descriptive study was to review and classify cardiac masses systematically and to determine their frequencies.Methods : The medical records of 64,862 consecutive patients were investigated within 12 years. Every patient with a cardiac mass imaged by transthoracic echocardiography (TTE) and confirmed with an advanced imaging modality such as transesophageal echocardiography (TEE), computed tomography (CT) and / or cardiac magnetic resonance imaging (CMR) was included. Acute coronary syndromes triggering thrombus formation, vegetations, intracardiac device and catheter related thrombi were excluded.Results : Data demonstrated 127 (0.195 %) intracardiac masses consisting of 33 (0.050 %) primary benign, 3 (0.004 %) primary malignant, 20 (0.030 %) secondary tumors, 3 (0.004 %) hydatid cysts and 68 (0.104 %) thrombi respectively. The majority of primary cardiac tumors were benign (91.67 %), predominantly myxomas (78.79 %), and the less malignant (8.33 %). Secondary cardiac tumors were common than the primary malignant tumors (20:3), with male dominancy (55 %), lymphoma and lung cancers were the most frequent. Intracardiac thrombi was the majority of the cardiac masses, thrombi accompanying malignancies were in the first range (n=17, 25%), followed by autoimmune diseases (n=13, 19.12 %) and ischemic heart disease with low ejection fraction (n=12, 17.65 %).Conclusion: This retrospective analysis identified 127 patients with cardiac masses. The majority of benign tumors were myxoma, the most common tumors that metastasized to the heart were lymphoma and lung cancers, and the thrombi associated with malignancies and autoimmune diseases were the most frequent.

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 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: NCT 03665558.

Understanding the coupling between heme reduction and proton translocation in cytochrome c oxidase (CcO) is still an open problem. The propionic acids of heme a3 have been proposed to act as a proton loading site (PLS) in the proton pumping pathway, yet this proposal could not be verified by experimental data so far. We have set up an experiment where the redox states of the two hemes in CcO can be controlled via external electrical potential. Surface enhanced resonance Raman (SERR) spectroscopy was applied to simultaneously monitor the redox state of the hemes and the protonation state of the heme propionates. Simulated spectra based on QM/MM calculations were used to assign the resonant enhanced CH2 twisting modes of the propionates to the protonation state of the individual heme a and heme a3 propionates respectively. The comparison between calculated and measured H2OD2O difference spectra allowed a sound band assignment. In the fully reduced enzyme at least three of the four heme propionates were found to be protonated whereas in the presence of a reduced heme a and an oxidized heme a3 only protonation of one heme a3 propionates was observed. Our data supports the postulated scenario where the heme a3 propionates are involved in the proton pathway.

Background and Aims Ankylosing spondylitis (AS) is a multisystem disorder with ocular, pulmonary, and cardiovascular involvement. The incidence of pulmonary involvement varies from 1 to 52%. Abnormal T-cell function-derived immune responses are involved in AS pathogenesis. Numerous genes such as CTLA4 and CD28 control T-cell functions. In this study, we aimed to address the relationship between CTLA4 and CD28 polymorphisms and lung involvement in Turkish patients with AS. Methods A cross-sectional evaluation of 80 healthy and 89 AS subjects with no active infection or malignancy was performed to determine the relationship between pulmonary involvement and CTLA4 and CD28 gene polymorphisms. All patients were assessed for clinical, radiological, and spirometric findings. Descriptive statistics, chi-square tests, and independent-sample t-tests were used for statistical analyses. Results All patients with the CD28 CC genotype (n = 4) had abnormal HRCT, but it was not significant (p = 0.47). All of the normal HRCT patients have CD 28 T alleles. In addition to this data ; 4 patients who have not any T alleles have abnormal HRCT finding. It was significant and was considered that T genotype have protective effect (p= 0,047) on radiologic involvement but no other association was found between CTLA4 and CD28 gene polymorphism with respect to pulmonary function tests (PFT), diffusion capacity, and clinical characteristics in the Turkish patients with AS. Conclusion Our results suggest a possible association of CTLA4 and CD28 variants with AS pulmonary involvement. Furthermore, these results may lead to the development of new therapeutic agents to control more aggressive forms of the disease. However, further studies are needed in larger populations.

Immobilization of Cytochrome c oxidase (CcO) on electrodes makes voltage-driven reduction of oxygen to water possible. Efficient catalytic turnover in CcO/electrode systems is, however, often observed at large overpotentials that cannot be rationalized by the redox properties of the enzyme itself. To understand the structural basis for this observation, CcO was electrostatically adsorbed on amino-functionalized Ag electrodes, and the redox transitions of heme a and a3 were monitored via surface enhanced resonance Raman spectroscopy (SERRS) as a function of applied potential. Under completely anaerobic conditions, the reduction of heme a3 could be seen at potentials close to those measured in solution indicating an intact catalytic center. However, in the immobilized state, a new non-native heme species was observed that exhibited a redox potential much more negative than measured for the native hemes. Analysis of the high and low frequency SERR spectra indicated that this new species is formed from heme a upon axial loss of one histidine ligand. It is concluded that the formation of the non-native heme a species alters the potential-dependent electron supply to the catalytic reaction and, thus, can have a impact on the applicability of this enzyme in biofuel cells.

Objective Histologic plaque characteristics may influence the hemodynamic effect generated by physiologically significant unstable coronary lesions where plaque content and surface related factors are expected to contribute to the maximum translesional pressure drop. In this study, we aimed to identify local lesion specific virtual histological characteristics that may potentially affect hemodynamic outcome measures. Methods Forty-eight consecutive patients with non-ST-elevation acute coronary syndrome (NSTEACS) having paired hemodynamic and morphological data were enrolled. A dual sensor guide-wire was used for the assessment of fractional flow reserve (FFR) and stenosis resistance (HSR) in the culprit vessel. Virtual histology intravascular ultrasound imaging was performed after obtaining hemodynamic data. Results In a hemodynamically significant lesion subset (FFR n =34]), after controlling for lesion length, MLA and coronary artery compliance, FFR correlated with necrotic core (NC) area ( r =−0.423, p =0.028) at MLA and NC volume ( r =−0.497, p =0.008) and dense calcium (DC) volume ( r =−0.332, p =0.03) across the entire lesion segment. Likewise, NC ( r =−0.544, p =0.005) and DC ( r =0.376, p =0.03) areas at MLA and NC ( r =0.545, p =0.005) and DC ( r =0.576, p =0.003) volumes across the entire lesion segment were associated with HSR in the hemodynamically significant lesion group (HSR>0.80 [ n =33]). However, no correlation has been observed between intracoronary hemodynamic end-points and plaque components in hemodynamically insignificant lesions. Conclusions This study demonstrated that for a given coronary stenosis geometry and arterial compliance, plaque composition may influence hemodynamic outcome measures in functionally significant stenoses in patients with NSTEACS.

There is a well-known relationship between sleep quality and body position during sleep in patients with obstructive sleep apnea (OSA). In this study, we aimed to investigate the effects of body position on sleep architecture and sleep quality in subjects without sleep apnea. One hundred and one subjects between 24 and 77 years of age, who had undergone polysomnography and had a respiratory disturbance index (RDI) below 5 were included in the study. Sleep stages and sleep parameters in the right, left, supine and prone positions were examined. Mean sleep duration in S2, S3 and rapid eye movement (REM) were 110, 39 and 20.7 min in supine position and 61, 28 and 17 min in right position, respectively. Mean RDI at supine position was higher than other positions. Mean minimal oxygen saturation at supine position was significantly lower than other positions. Maximal heart rate and mean arousal index were significantly higher in the supine position. Duration of sleep was highest in the right position in those older than 60 years. Subjects with 40–60 years age had higher duration of sleep in right and supine positions. Female subjects slept more in supine position whereas male ones slept more in right position. Stages of sleep may change according to position. Deteriorations in the parameters of sleep quality (RDI, lowest saturation, arousal index, heart rate) occur in individuals with RDI < 5 as well as in patients with OSA in the supine position.