The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye.

BACKGROUND: Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic or likely pathogenic sarcomeric and non-sarcomeric gene mutations and to confirm a final molecular diagnosis in patients diagnosed with hypertrophic cardiomyopathy. METHODS: A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye. All samples were analyzed with a 17-gene hypertrophic cardiomyopathy panel using next-generation sequencing technology. The gene panel includes ACTC1, DES, FLNC, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, PTPN11, TNNC1, TNNI3, TNNT2, TPM1, and TTR genes. RESULTS: The next-generation sequencing panel identified positive genetic variants (variants of unknown significance, likely pathogenic or pathogenic) in 12 genes for 121 of 392 samples, including sarcomeric gene mutations in 30.4% (119/392) of samples tested, galactosidase alpha variants in 0.5% (2/392) of samples and TTR variant in 0.025% (1/392). The likely pathogenic or pathogenic variants identified in 69 (57.0%) of 121 positive samples yielded a confirmed molecular diagnosis. The diagnostic yield was 17.1% (15.8% for hypertrophic cardiomyopathy variants) for hypertrophic cardiomyopathy and hypertrophic cardiomyopathy phenocopies and 0.5% for Fabry disease. CONCLUSIONS: Our study showed that the distribution of genetic mutations, the prevalence of Fabry disease, and TTR amyloidosis in the Turkish population diagnosed with hypertrophic cardiomyopathy were similar to the other populations, but the percentage of sarcomeric gene mutations was slightly lower.

Comparison of frequency of silent cerebral infarction as assessed by serum neuron specific enolase in patients with non-valvular atrial fibrillation: Warfarin versus direct oral anticoagulant.

BACKGROUND: Cerebral infarction in patients with atrial fibrillation (AF) may clinically vary from being silent to catastrophic. Silent cerebral infarction (SCI) is the neuronal injury in the absence of clinically appearent stroke or transient ischaemic attack. Serum neuron specific enolase (NSE) is suggested to be a valid surrogate biomarker that allows to detect recent neuronal injury. We aimed to evaluate the incidence of recent SCI by positive NSE levels in patients with non-valvular AF (NVAF) on oral anticoagulants. METHODS: Blood samples for NSE were collected from 197 consecutive NVAF patients. NSE levels of greater than 12 ng/ml was considered as positive and suggestive of SCI. RESULTS: Patients were mainly female with a mean age of 69 years. Ninety-eight of them (49.7%) were taking warfarin. Mean INR level was 2.3 ± 0.9. Mean CHA2DS2-VASc score of the study population was 3.5 ± 1.5. Seventy-two patients (36.5%) were found to have NSE elevation. They were more likely to have history of chronic heart failure and previous stroke/TIA. Increased left atrial diameter and higher CHA2DS2-VASc were other factors associated with SCI. Patients on DOACs and patients taking aspirin on top of oral anticoagulant treatment were less likely to have SCI. Multivariate analysis demonstrated that increased left atrial diameter (OR: 2.5; 95% CI: 1.52-4; p < 0.001) and use of warfarin (OR: 2.8; 95% CI: 1.37-5.61; p = 0.005) were detected as independent predictors of SCI. CONCLUSIONS: Our study revealed that DOACs were associated with significantly reduced SCIs compared with warfarin, probably due to more effective and consistent therapeutic level of anticoagulation.

A 24-Year-Old Woman With Dyspnea, Chest Pain, and Dry Cough.

CASE PRESENTATION: A 24-year-old woman, a baby-sitter with no known comorbidities, presented to the outpatient department with complaints of modified Medical Research Council grade IV breathlessness for 3 months, chest pain, and dry cough for 2 weeks. There was no known disease history, including respiratory, flu-like illness, or connective tissue disorder. There was no use of chemotherapeutic, oral contraceptive drugs, exposure to toxic substances, or smoking. A review of systems was negative for fever, arthralgia, myalgia, Raynaud phenomenon, skin thickening, rash, or leg swelling. The patient had no family history suggestive of a genetic syndrome.

Geriatric nutritional risk index is a predictor of recurrent percutaneous coronary intervention in patients with non-ST segment elevation myocardial infarction.

Aim To investigate the relationship between malnutrition and follow-up cardiovascular (CV) events in non-ST-segment elevation myocardial infarction (NSTEMI).Material and methods A retrospective study was performed on 298 patients with NSTEMI. The baseline geriatric nutritionalrisk index (GNRI) was calculated at the first visit. The patients were divided into three groups accordingto the GNRI: >98, no-risk; 92 to ≤98, low risk; 82 to <92, moderate to high (MTH) risk. The studyendpoint was a composite of follow-up CV events, including all-cause mortality, non-valvular atrialfibrillation (NVAF), hospitalizations, and need for repeat percutaneous coronary intervention (PCI).Results Follow-up data showed that MTH risk group had significantly higher incidence of repeat PCI and all-cause mortality compared to other groups (p<0.001). However, follow-up hospitalizations and NVAFwere similar between groups (p>0.05). The mean GNRI was 84.6 in patients needing repeat PCI and99.8 in patients who did not require repeat PCI (p<0.001). Kaplan Meier survival analysis showed thatpatients with MTH risk had significantly poorer survival (p<0.001). According to multivariate Coxregression analysis, theMTH risk group (hazard ratio=5.372) was associated with increased mortality.Conclusion GNRI value may have a potential role for the prediction of repeat PCI in patients with NSTEMI.

Prediction of Lipoprotein-Associated Phospholipase A2 and Inflammatory Markers in Subclinical Atherosclerosis in Premature Ovarian Failure Patients.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been associated with the risk of clinical cardiovascular events. OBJECTIVES: In this study, we aimed to investigate whether the activity of Lp-PLA2 presents a risk for subclinical atherosclerosis in young patients with premature ovarian failure (POF). METHODS: Consecutive patients with clinical and biochemical evidence of naïve POF (n = 66) in January and February 2018 and age-matched healthy controls (n = 73) were enrolled. Lp-PLA2 activity, fibrinogen concentrations, high- sensitivity C-reactive protein (Hs-CRP) levels, and carotid intima-media thickness (CIMT) were measured in all participants. RESULTS: Plasma Lp-PLA2 activity (24.6 ± 3.2 nmol/mL vs. 18.6 ± 1.6 nmol/mL; p < 0.001), mean Hs-CRP (0.620 ± 0.26 mg/dL vs. 0.450 ± 0.28 mg/dL; p < 0.001) and fibrinogen (0.310 ± 0.12 g/dL vs. 0.24 ± 0.11 g/dL; p < 0.001) levels were significantly higher in the patients with POF than control subjects. Mean CIMT was significantly higher in the POF patients than in controls (0.499 ± 0.122 mm vs. 0.323 ± 0.079 mm; p < 0.001). There was a possitive and strong correlation between CIMT and Lp-PLA2 activity (r = 0.548; 95% CI 0.445-0.644; p < 0.001) and a weak correlation Hs-CRP (r = 0.228, 95% CI 0.060-0.398; p = 0.007). In multivariate analysis, Lp-PLA2 activity (B = 1.456, 95% CI 0.908-2.003; p < 0.001) and 17ß-E2 (B = -0.077, 95% CI -0.131 - -0.023; p = 0.006) were found to be independently associated with CIMT (R2 = 0.46). CONCLUSIONS: The present study showed that mean CIMT and Lp-PLA2 activity were significantly higher in POF subjects than control subjects. Moreover, Lp-PLA2 activity and 17ß-E2 levels were independently associated with CIMT in young POF patients.

Assessment of subclinical left ventricular dysfunction with speckle-tracking echocardiography in hyperthyroid and euthyroid Graves' disease and its correlation with serum TIMP-1.

BACKGROUND: Graves' disease has a multitude of effects on the cardiovascular system. In the detection of subclinical left ventricular dysfunction, speckle-tracking echocardiography is more useful than conventional echocardiography. The aim of the present study was to compare the longitudinal global strain values and venous blood concentration of (tissue inhibitor of metalloproteinase-1) TIMP-1, a regulator of the extracellular matrix, among hyperthyroid patients with Graves' disease, euthyroid patients with Graves' disease and healthy control subjects. MATERIALS AND METHODS: The study enrolled 40 hyperthyroid patients with newly diagnosed Graves' disease, 40 patients with Graves' disease who were euthyroid for at least 6 months and 40 control subjects with normal thyroid function. Participants underwent conventional echocardiography and speckle-tracking echocardiography to obtain segmental and global longitudinal strain values. In addition, the serum TIMP-1 value was assessed in the venous blood samples of the participants. RESULTS: The hyperthyroid Graves' patients showed greater serum TIMP-1 levels versus the control group and the euthyroid Graves' group. Compared to the control group, the TIMP-1 level was also significantly higher in the euthyroid Graves' group. Lower GLS (global longitudinal strain) average and GLS2C, GLS3C, GLS4C values were observed in both the hyperthyroid and euthyroid Graves' patients compared to the control group. The euthyroid Graves' patients and hyperthyroid Graves' patients had similar GLS values. The serum TIMP-1 level was negatively correlated with global strain values. CONCLUSION: Graves' disease coexists with impaired segmental and global longitudinal strain and increased TIMP-1 levels. This coexistence seems to be independent of serum thyroid hormone levels.

Effect of new oral anticoagulants on platelet indices in non-valvular atrial fibrillation patients.

New-generation oral anticoagulants (NOACs) are now preferred as a first-line treatment in the management of atrial fibrillation for prevention of thromboembolic complications. Mean platelet volume (MPV), one of the indicators of increased platelet activity, is also associated with an increased stroke risk in atrial fibrillation patients. The aim of this study was to evaluate changes in MPV, platelet distribution width (PDW) and plateletcrit following use of NOACs. The study included 116 patients with non-valvular atrial fibrillation without previous NOAC use. Complete blood counts, biochemical analyses and echocardiography were performed for all patients. No significant differences were observed in MPV or other platelet indices at 6 months compared to baseline. Our results indicate that MPV and other platelet indices are not affected by NOAC use in non-valvular atrial fibrillation patients.

Prediction of coronary artery disease severity in lower extremity artery disease patients: A correlation study of TASC II classification, Syntax and Syntax II scores.

BACKGROUND: Lower extremity arterial disease (LEAD) is a well-established risk factor for concomitant coronary artery disease (CAD). There are no published data combining all three lower limb arterial segments (aortoiliac, femoropopliteal and below the knee vessels) in order to estimate CAD severity in LEAD patients. Herein has been derived a new scoring system for this purpose, which uses the wellknown TASC II classification, Syntax score and, for the first time in medical literature, a Syntax II score. METHODS: The study population consisted of 178 patients who underwent lower limb and coronary diagnostic angiography for assessment of LEAD and CAD at the same session. Syntax and Syntax II scores were calculated. TASC II classifications of the lower limb arteries were done. A new scoring system, called "Total Peripheral Score" (TPS), for lower limbs was also calculated. RESULTS: A positive correlation was found between TPS and Syntax score and a less prominent positive correlation between TPS and Syntax II score (p < 0.001). A cut-off value of '6' for the new score was found for estimating high risk subgorup of CAD (Syntax score > 32; p < 0.001). Critical femoropopliteal arterial segment stenosis was the most predictive lower limb arterial zone for presence of severe CAD (Syntax score > 32; p = 0.011). CONCLUSIONS: Taking into account all lower limb arterial segments for predicting CAD during lower limb arterial angiography was recommended. A TPS of more than '6' is the practical cut-off value for estimating severe CAD. Femoropopliteal arterial critical stenosis is the most predictive arterial zone for estimating severe CAD.

Carotid artery stenting with double cerebral embolic protection in asymptomatic patients - a diffusion-weighted MRI controlled study.

BACKGROUND: The aim of this study was to compare the simultaneous double-protection method (proximal balloon plus distal filter) with distal-filter protection or proximal-balloon protection alone in asymptomatic patients during carotid artery stenting. PATIENTS AND METHODS: 119 consecutive patients were investigated for carotid artery stentings in the extracranial internal carotid artery with the use of distal filters (n = 41, 34.4 %), proximal balloon (MoMa) protection (n = 40, 33.6 %) or double protection (n = 38, 31.9 %). Magnetic resonance imaging (MRI) was performed on all patients before the procedure, and control diffusion-weighted MRI (DW-MRI) was obtained within 24-48 h after the procedure. Procedural data, complications, success rate, major adverse cardiovascular events, and MRI findings were collected. RESULTS: New cerebral high-intensity (HI) lesions were observed in 47 (39.4 %) patients. HI lesions were observed in 22 (53.6 %), 15 (37.5 %), and 10 (26.3 %) of the patients with distal filters, proximal protection, and double protection, respectively (p = 0.004). The average number of HI lesions on DW-MRI was 1.80 in the distal-filter group, 0.90 in the proximal-balloon group, and 0.55 in the double-protection group (p < 0.001). Procedure and fluoroscopy times were slightly longer in the double-protection group compared to the distal- or proximal-protection groups (p = 0.001). CONCLUSIONS: The double (proximal plus distal) cerebral embolic protection technique is safe and effective for minimizing the risk of cerebral embolization, even in patients with asymptomatic carotid artery stenosis, despite slightly longer procedure and fluoroscopy times.
.

Serum Bilirubin Levels and the Presence and Progression of Abdominal Aortic Aneurysms.

The relationship between bilirubin levels and peripheral artery disease has been documented. Our aim was to demonstrate the possible relationship between serum bilirubin levels and abdominal aortic aneurysms (AAAs). The study included 219 patients, 110 had a previous diagnosis of AAA and 109 patients were normal controls. Only patients with AAAs which had a size of 40 to 54 mm were included in the study. Baseline laboratory values and 2 computerized tomographic measurements 12 months apart were recorded. Patients with AAA had significantly higher white blood cell (WBC) counts and neutrophil-lymphocyte ratio (NLR) but lower total and direct bilirubin levels compared with the control patients ( P < .05). Multivariate logistic regression analysis showed that WBC, NLR, and total and direct bilirubin levels were independent predictors of the presence of an AAA ( P = .03, P = .001, P = .001, and P = .001, respectively). White blood cells and total bilirubin level were independent predictors of a rapidly enlarging AAA (>10 mm/y, P = .002 and P < .001, respectively). This study demonstrated that increased WBC and decreased total bilirubin levels were independent predictors of an AAA, especially the subgroup in which the AAA was rapidly expanding.

Association between serum total antioxidant status and flow-mediated dilation in patients with systemic lupus erythematosus: an observational study.

OBJECTIVE: Endothelial dysfunction (ED) is a condition that involves increased oxidative stress and decreased total antioxidant status (TAS) levels. Systemic lupus erythematosus (SLE) is also associated with ED. We aimed to determine the association between serum TAS and ED as assessed by flow-mediated dilation (FMD) in patients with SLE. METHODS: Thirty-four patients with stable SLE who were not undergoing any treatment and 39 healthy volunteers without any overt cardiovascular disease were included in this cross-sectional study. Doppler ultrasound was used to measure FMD to assess ED in the study groups. Serum TAS levels were measured using a TAS kit. High-sensitivity C-reactive protein (hs-CRP) and anticardiolipin antibody (aCLA) levels were also measured to assess the inflammatory state. The SLE group further was divided into 2 groups according to presence or absence of aCLA. SLE disease activity was assessed using the SLE disease activity index (SLEDAI). Regression analysis was used to define independent predictors. RESULTS: The mean TAS levels were significantly lower in patients with SLE than in controls (1.60±0.11 versus 1.73±0.15 mmol/L, p<0.001). hs-CRP levels were significantly higher in patients with SLE than in controls (8.2±6.0 vs. 2.9±4.0 mg/L; p<0.001), particularly in SLE patients with positive aCLA when compared with SLE patients with negative aCLA (13.8±4.3 vs. 5.6±4.8 mg/L, p<0.001). The FMD percent was significantly lower in patients with SLE than in controls (8.1±4.9 vs. 10.6±4.7, p=0.04). There was a significant positive correlation between FMD and TAS in the SLE group (r=0.448, p=0.008) and the control group (r=0.367, p=0.03) and a significant negative correlation between FMD and serum hs-CRP (r=-0.368, p=0.04) in only the SLE group. In multiple linear regression analysis, TAS, hs-CRP, and SLEDAI were independently correlated with FMD (ß=0.50, p=0.003; ß=-0.33, p=0.03; and ß=-0.36, p=0.03; respectively). CONCLUSION: Patients with SLE who have no overt cardiovascular disease are at increased risk for ED and this may be associated with underlying inflammation and impairment of TAS.

Impact of genetic variations of the CYP1A1, GSTT1, and GSTM1 genes on the risk of coronary artery disease.

Carcinogenic and toxic molecules produce DNA adducts that contribute to the development of atherosclerosis. Genetic polymorphisms of xenobiotic-detoxified enzymes, which control the level of DNA adducts, may affect both enzymatic activity and individual susceptibility to coronary artery disease (CAD). In this study we investigated the effects of genetic polymorphisms of the CYP1A1*2C, GSTT1, and GSTM1 enzymes on CAD risk in a Turkish population. Genotypes were determined for 132 CAD patients and 151 healthy controls by the polymerase chain reaction/restriction fragment length polymorphism method. There were no significant differences between patients and controls in terms of CYP1A1, GSTT1, and GSTM1 genotypes. Analysis of the possible interactions between the genotypes, after adjustment for the risk factors, demonstrated that individuals carrying CYP1A1 variant GSTT1 null genotypes had an 8.907-fold increased CAD risk compared to their wild status (p<0.05). We suggest that genetic polymorphisms of xenobiotic-metabolizing enzymes could play an important role in CAD. Therefore, CYP1A1 and GSTM1 polymorphisms should be considered as important parameters for the prediction of CAD.