Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is the leading cause of ischemia with no obstructive coronary arteries disease (INOCA) disease. Diagnosis of CMD relies on surrogate physiological indices without objective proof of ischemia. OBJECTIVES: Intracoronary electrocardiogram (icECG) derived hyperemic indices may accurately and objectively detect CMD and reversible ischemia in related territory. METHODS: INOCA patients with proven ischemia by myocardial perfusion scan (MPS) and completely normal coronary arteries underwent simultaneous intracoronary electrophysiological (icECG) and physiological (intracoronary Doppler) assessment in all 3 coronary arteries during rest and under adenosine induced hyperemia. RESULTS: Sixty vessels in 21 patients were included in the final analysis. All patients had at least one vessel with abnormal CFR. 41 vessels had CMD (CFR < 2.5), of which 26 had increased microvascular resistance (structural CMD, HMR > 1.9 mmHg.cm-1.s) and 15 vessels had CMD (CFR < 2.5) with normal microvascular resistance (functional CMD, HMR <= 1.9 mmHg.cm-1.s). Only one-third of the patients (n = 7) had impaired CFR < 2.5 in all 3 epicardial arteries. Absolute ST shift between hyperemia and rest (∆ST) has shown the best diagnostic performance for ischemia (cut-off 0.10 mV, sensitivity: 95%, specificity: 72%, accuracy: 80%, AUC: 0.860) outperforming physiological indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002). CONCLUSIONS: In INOCA patients, CMD involves coronary artery territories heterogeneously. icECG can accurately detect CMD causing perfusion abnormalities in patients with INOCA outperforming physiological CMD markers, by demonstrating actual ischemia instead of predicting the likelihood of inducible ischemia based on violated surrogate thresholds of blunted flow reserve or increased minimum microvascular resistance. CONDENSED ABSTRACT: In 21 INOCA patients with coronary microvascular dysfunction (CMD) and myocardial perfusion scan proved ischemia, hyperemic indices of intracoronary electrocardiogram (icECG) have accurately detected vessel-specific CMD and resulting perfusion abnormalities & ischemia, outperforming invasive hemodynamic indices. Absolute ST shift between hyperemia and rest (∆ST) has shown the best classification performance for ischemia in no Obstructive Coronary Arteries (AUC: 0.860) outperforming Doppler derived CMD indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002).icECG can be used to diagnose CMD causing perfusion defects by demonstrating actual reversible ischemia at vessel-level during the initial CAG session, obviating the need for further costly ischemia tests. CLINICALTRIALS: GOV: NCT05471739.

The effect of body mass index on complications in cardiac implantable electronic device surgery.

BACKGROUND: Cardiac implantable electronic device (CIED) procedures are prone to complications. In our study, we investigated the effect of body mass index (BMI) on CIED-related complications. METHODS: 1676 patients who had undergone CIED surgery (de novo implantation, system upgrade, generator change, pocket revision or lead replacement) at two heart centers in Turkey and met the study criteria were included in our study. For analysis of primary and secondary endpoints, patients were classified as non-obese (BMI < 25 kg/m2 ), overweight (25 ≤ BMI < 30 kg/m2 ), and obese (BMI ≥ 30 kg/m2 ). The primary endpoint was accepted as cumulative events, including the composite of clinically significant hematoma (CSH), pericardial effusion or tamponade, pneumothorax, and infection related to the device system. Secondary outcomes included each component of cumulative events. RESULTS: The rate of cumulative events, defined as primary outcome, was higher in the obese patient group, and we found a significant difference between the groups (3.0%, 4.3%, 8.9%, p = .001). CSH and pneumothorax rates were significantly higher in the obese patient group (0.3%, 0.9%, 1.9%, p = .04; 1.0%, 1.4%, 3.3%, p = .04, respectively). According to our multivariate model analysis; gender (OR:1.882, 95%CI:1.156-3.064, p = .01), hypertension (OR:4.768, 95%CI:2.470-9.204, p < .001), BMI (OR:1.069, 95%CI:1.012-1.129, p = .01) were independent predictors of cumulative events rates. CONCLUSIONS: Periprocedural complications associated with CIED (especially hematoma and pneumothorax) are more common in the group with high BMI.

Primary versus iatrogenic (post-PCI) coronary microvascular dysfunction: a wire-based multimodal comparison.

BACKGROUND: Although there are studies examining each one separately, there are no data in the literature comparing the magnitudes of the iatrogenic, percutaneous coronary intervention (PCI)-induced, microvascular dysfunction (Type-4 CMD) and coronary microvascular dysfunction (CMD) in the setting of ischaemia in non-obstructed coronary arteries (INOCA) (Type-1 CMD). OBJECTIVES: We aimed to compare the characteristics of Type-1 and Type-4 CMD subtypes using coronary haemodynamic (resistance and flow-related parameters), thermodynamic (wave energy-related parameters) and hyperemic ECG changes. METHODS: Coronary flow reserve (CFR) value of <2.5 was defined as CMD in both groups. Wire-based multimodal perfusion markers were comparatively analysed in 35 patients (21 INOCA/CMD and 14 CCS/PCI) enrolled in NCT05471739 study. RESULTS: Both groups had comparably blunted CFR values per definition (2.03±0.22 vs 2.11±0.37; p: 0.518) and similar hyperemic ST shift in intracoronary ECG (0.16±0.09 vs 0.18±0.07 mV; p: 0.537). While the Type-1 CMD was characterised with impaired hyperemic blood flow acceleration (46.52+12.83 vs 68.20+28.63 cm/s; p: 0.017) and attenuated diastolic microvascular decompression wave magnitudes (p=0.042) with higher hyperemic microvascular resistance (p<0.001), Type-4 CMD had blunted CFR mainly due to higher baseline flow velocity due to post-occlusive reactive hyperemia (33.6±13.7 vs 22.24±5.3 cm/s; p=0.003). CONCLUSIONS: The perturbations in the microvascular milieu seen in CMD in INOCA setting (Type-1 CMD) seem to be more prominent than that of seen following elective PCI (Type-4 CMD), although resulting reversible ischaemia is equally severe in the downstream myocardium.

A novel method that can be used in both the diagnosis and treatment of peripheral arterial disease in diabetics: vibration-mediated dilation.

OBJECTIVE: The growing incidence of diabetes and the increasing life expectancy of the diabetic population worldwide has increased the number of diabetic vascular complications occurring in cardiology practice. As current treatment and prevention methods are less effective in this patient group, there is a need for new treatment methods in this area. Exercise, which reduces metabolic and vascular problems associated with diabetes, often becomes impossible, especially in advanced-stage patients who need exercise the most. Since exercise and flow-mediated dilation (FMD) are effective by stimulating mechanotransduction mechanisms on the endothelium, it can be expected that the same mechanisms could also be stimulated by direct vibration. METHODS: In order to test this hypothesis, in this study, a group of 20 type 2 diabetes patients (11 males, age 56.80 ± 11.05 years and diagnosed for 15.35 ± 8.61 years) were examined via the application of FMD and vibration-mediated dilation (VMD). We performed vibration for five minutes with 20-Hz frequency and 3-mm vertical amplitude, to the same side forearm, with a 30-minute interval. Using a 10-MHz linear echo probe, brachial artery diameter and flow velocities were recorded for 10 minutes before and at two-minute intervals after the FMD and VMD applications. Then brachial artery flow and resistance were calculated at each stage. RESULTS: In the first minute after FMD and VMD applications, brachial artery diameter and flow velocities increased significantly, and vascular resistance decreased significantly. None of the corresponding FMD or VMD parameters in the first minute was different. The artery diameters in the first minute after FMD and VMD were increased by 6.04 ± 5.29 and 5.49 ± 5.21%, respectively. At the tenth minute, these values decreased to 1.73 ± 3.21 and 2.05 ± 3.31%. In the FMD series, all parameters except brachial artery diameter returned to their baseline values after the fourth minute. After VMD, all parameters also decreased after the first minute, but the recovery was much slower. At each stage after the first minute, the VMD averages were higher than the baseline value and their corresponding FMD values. CONCLUSION: The results of this study indicated that vibration may be a powerful, long-lasting and feasible treatment option in patients with peripheral perfusion failure, developed due to diabetic macro- and microvascular complications.

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).

Cytokine storm and neuropathological alterations in patients with neurological manifestations of COVID-19.

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines such as TNF-α, IFN-γ, IL-6 IL-8, IL-10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients, which may persist even after apparent recovery from infection. Biomarker studies on CSF and plasma and serum from COVID-19 patients have also shown a high level of IL-6, intrathecal IgG, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and tau protein. Emerging evidence on the matter has established the concept of COVID-19 associated neuroinflammation, in the context of COVID-19 associated cytokine storm. While the short-term implications of this condition are extensively documented, its long-term implications are yet to be understood. The association of the aforementioned cytokines with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis, may increase COVID-19 patients' risk to develop neurodegenerative diseases. Analysis of proinflammatory cytokines and CSF biomarkers in patients with COVID-19 can contribute to the early detection of the disease's exacerbation, monitoring the neurological implications of the disease and devising risk scales, and identifying treatment targets.

Assessment of clinical features and renal functions in Coronavirus disease-19: A retrospective analysis of 96 patients.

BACKGROUND: The most common extra pulmonary organ dysfunction in acute respiratory distress syndrome is acute kidney injury. Current data so far indicate low incidence of AKI in Covid-19 disease. OBJECTIVE: In this retrospective study, we analysed the clinical features of patients diagnosed with Covid-19 and investigated the effect of Covid-19 on kidney function. METHODS: Ninety-six patients diagnosed with Covid-19 were included in our study. Demographic features (Age, gender, co-morbidities), symptoms, thorax CT findings, Covid-19 PCR results and laboratory findings were recorded. The clinical features of the patients were analysed and kidney function values before Covid-19 diagnosis were compared with kidney function values after Covid-19 diagnosis. RESULTS: Most presenting symptom was fever (51%). Most accompanying co-morbidity was hypertension (56%). According to laboratory findings; ferritin, D-dimer and C-reactive protein levels were statistically significantly higher in ARDS group than severe pneumonia and pneumonia group (P = .002, P = .001 and P < .001, respectively). Also lymphocyte levels were statistically significantly lower in ARDS group than severe pneumonia and pneumonia group (P = .042). According to KDIGO criteria 3 (3.1%) patients had AKI during the hospital stay. For all patients, there was statistically significant difference between basal, 1st, 5th and 10th day BUN and SCr levels (P = .024 and P = .018, respectively). For severe pneumonia group there was statistically significant difference between basal, 1st, 5th and 10th day SCr levels (P = .045). CONCLUSION: Our study demonstrated that Covid-19 can cause renal impairment both with pneumonia and ARDS. A large-scale prospective randomised studies are needed to reach final judgement about this topic.

Minimal water-jet hydrodissection.

This paper presents a hydrodissection technique performed with high-speed pulse injection of only 0.1 cc liquid and assess its efficacy, safety, and the level of reduction in posterior capsule rupture complications in phacoemulsification cataract surgery. The kinetic energy of moving objects is directly proportional to the mass and to the square of its velocity. The high energy obtained by high-speed pulse injection of a small amount of liquid ensures highly effective dissection. Since the amount of liquid is very small, the increase in intraocular pressure and the risk of rupture in the posterior capsule due to anterior capsular block are greatly reduced. More importantly, several rotations of the lens material in the capsule with effective hydrodissection facilitate the phases of phacoemulsification and irrigation/aspiration. As most capsule ruptures occur during these phases, the complication rate is thus reduced.

The association of profilin-1 levels with survival in chronic kidney disease.

BACKGROUND: Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. MATERIALS AND METHODS: Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. RESULTS: Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114 pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P < .001). CONCLUSIONS: This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients.

INTRODUCTION: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. METHODS: Forty-five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. FINDINGS: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT-1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. DISCUSSION: In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.

Polycystic Ovary Syndrome and Increased Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis Levels Are Independent Predictors of Dyslipidemia in Youth.

BACKGROUND/AIMS: Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) irrespective of age. Our aim was to investigate soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK), a cardiovascular risk marker in PCOS, and to determine if it is associated with dyslipidemia in youth. METHODS: A prospective-observational study was carried out including 35 PCOS patients and 35 healthy controls. Serum sTWEAK levels were measured using commercially available kits. Multiple logistic regression analysis was then performed to verify the statistically significant differences in the possible predictors of dyslipidemia. RESULTS: Serum sTWEAK levels and the percentage of women with dyslipidemia were significantly higher in the PCOS group (p = 0.024 and p < 0.001, respectively). Participants were further divided into 2 subgroups based on the presence of dyslipidemia. The percentage of women with PCOS was significantly higher in the dyslipidemic group when compared with controls; 70.7 vs. 20.7%, respectively (p < 0.001). Multiple logistic regression analysis revealed that both the presence of PCOS (OR 7.924, 95% CI 2.117-29.657, p = 0.002) and increased levels of sTWEAK (>693 pg/ml; OR 3.810, 95% CI 1.075-13.501, p = 0.038) were independently associated with dyslipidemia. CONCLUSIONS: Increased levels of both sTWEAK and PCOS were found to be independently associated with dyslipidemia in youth.

Angiopoietins in Human Breast Milk.

INTRODUCTION: Angiogenesis is an important process after birth for neonates. Vascular endothelial growth factor is a potent proangiogenic protein, which stimulates endothelial cell proliferation, survival, and migration. For vessel maturation, all components have to move together. Angiopoietins (ANG) are very important signal proteins for pericytes and have not yet been determined in human breast milk. The aim of this study was to show whether there were ANG in human breast milk. METHODS: Human breast milk samples were collected from 9 mothers of preterm (≤33 weeks) and 17 mothers of term and late preterm (>33 weeks). Milk samples were collected on 3rd, 7th, and 28th days from delivery. We analyzed ANG-1 and ANG-2 levels in human milk and compared these levels considering the gestational age and day of lactation from delivery. RESULTS: There was a significant difference between the ANG-1 levels of the two groups of gestational age (p = 0.008), while ANG-2 levels were not significantly different (p = 0.821), without considering the days of lactation from delivery. ANG-1 and 2 levels of milk samples of 3rd, 7th, and 28th days from lactation showed no significant difference in both gestational age groups. CONCLUSION: The presence of ANG in human breast milk was proved with this study and ANG-1 levels were found to be lower in preterm group. These results may be important for neonates in terms of angiogenesis and also lymphangiogenesis.

Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival.

BACKGROUND AND AIMS: Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. MATERIALS AND METHOD: A total of 519 CKD pre-dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively RESULTS: The mean age of the patients was 52.2±12.3years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR=1.88, 95% CI 1.37-2.41 for a 1 SD increase in log endostatin values). CONCLUSION: Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors.

Interleukin-8 and Its Receptors in Human Milk from Mothers of Full-Term and Premature Infants.

In addition to its nutritional benefits, human milk also has bioactive elements. Limited immunological functions of newborns are supported and altered by the immunological elements of mother milk. Chemokines are of importance among these immune factors. Interleukin-8 (IL-8) has been demonstrated in mother's milk, and its receptors, CXC chemokine receptors (CXCR)-1 and CXCR-2, were detected on cells, responsible for immunological reactions and mammary glandular cells. The soluble forms of these receptors are yet to be described in human milk. In this study, it was aimed to assess the IL-8 levels and the concentrations of its receptors in colostrum and mature mother's milk in regard to preterm and term delivery. The results of this study indicated a decline in IL-8 levels with the lactation stage, but no difference was observed between term and preterm mother's milk. Regarding the CXCR-1 and CXCR-2, the concentrations of these receptors were similar in both colostrum and mature milk. Furthermore, there was not any significant difference between term and preterm mother's milk. In conclusion, this is the first study to investigate the concentrations of CXCR-1 and CXCR-2 with the levels of IL-8 in colostrum and mature human milk of term and preterm newborns. The alterations in IL-8 levels were similar in some of the studies reported. CXCR-1 and CXCR-2 levels did not demonstrate any significant difference. Further studies are required to investigate the soluble forms of these receptors and their relation to IL-8 with larger cohort.

Eyelid tumors: clinical data from an eye center in Ankara, Turkey.

INTRODUCTION: The aim of the study was to explore the distribution of eyelid tumors in Ankara, the capital city of Turkey, from a histopathological point of view. MATERIALS AND METHODS: Medical records of 1,502 patients who had eyelid surgery because of tumoral lesions were retrospectively reviewed after obtaining institutional review board approval. A total of 1,541 lesions with histopathologic diagnosis were included. Inflammatory tumoral lesions were excluded. The lesions were categorized into three groups according to the origin: epidermal, adnexal tumors and 'others', including melanocytic, neural and vascular lesions. RESULTS: Of the total of 1,541, 908 lesions were epidermal in origin. Only 22 (1.5%) were malignant, and 6.0% was premalignant lesions such as actinic keratosis and Bowen's disease. Twenty-one of 22 malignant lesions were basal cell carcinoma. There was only one patient with squamous cell carcinoma and no sebaceous cell carcinoma. Among the benign tumors (92.5%), squamous papilloma was the most frequent (21.8% of all lesions). The other frequent lesions were nevus (17.6%), seborrheic keratosis (17.3%), hydrocystomas (10.6%), xanthelasma (7.6%) and epidermal cysts (7.2%). CONCLUSIONS: The results of this study are in accordance with published literature. The absence of sebaceous cell carcinomas needs to be stressed.