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.

Does coexistence of fragmented QRS and cardiovascular disease have the ability to predict the mortality in hospitalized, critically ill patients with COVID-19?

OBJECTIVE: In this study, we aimed to investigate the prognostic accuracy of the presence of fragmented QRS (fQRS) on baseline electrocardiogram on the adverse outcome in critical patients with coronavirus disease 2019 (COVID-19) with cardiovascular disease (CVD). METHODS: The current study was retrospective designed and included 169 patients who were critically ill with COVID-19 and CVD (mean age of 62±15 years). The patients were grouped into those who died (non-survivor group) and those who survived (survivor group). RESULTS: The non-survivors were older and more often had CVD (p=0.009), hypertension (p=0.046), diabetes (p=0.048), cancer (p=0.023), and chronic renal failure (p=0.001). Although the presence of fQRS on the basal electrocardiogram was more common in patients who died, this was not statistically significant (p=0.059). Furthermore, non-survivors had more frequent the coexistence of CVD and fQRS (p=0.029). In Model 1 multivariate regression analysis, CVD alone was not a predictor of mortality (p=0.078), whereas coexistence of CVD and fQRS was found to be an independent predictor of mortality in Model 2 analysis [hazard ratio (HR): 2.243; p=0.003]. Furthermore, older age (HR: 1.022; p=0.006 and HR: 1.023; p=0.005), cancer (HR: 1.912; p=0.021 and HR: 1.858; p=0.031), high SOFA score (HR: 1.177; p=0.003 and HR: 1.215; p<0.001), and increased CRP level (HR: 1.003; p=0.039 and HR: 1.003; p=0.027) independently predicted the mortality in both multivariate analysis models, respectively. CONCLUSION: fQRS may be a useful and handy risk-stratification tool for clinical outcomes by identifying high-risk individuals, especially among those with CVD.

Human neutrophil peptides 1-3 level in patients with acute myocardial infarction and its relation with coronary artery disease severity.

OBJECTIVE: Inflammation plays a crucial role in the pathogenesis and clinical outcome of atherosclerosis. Among the various inflammatory factors, antimicrobial peptides, such as alpha-defensins, seem to contribute to the development and progression of atherosclerosis. The aim of this study was to evaluate the plasma levels of human neutrophil peptide-1, -2, and -3 (HNP1-3) in patients with acute myocardial infarction (AMI) and to assess its relationship with the severity of coronary artery disease. METHODS: lasma HNP1-3 levels in patients with AMI and controls with angiographically normal coronary arteries were measured by solid-phase enzyme-linked immunosorbent assay. In the patient group, coronary artery disease severity was assessed using the SYNergy between percutaneous intervention with TAXus and cardiac surgery score (SS). RESULTS: HNP1-3 levels were significantly higher in the group with AMI than in the controls (6.5±5.8 ng/mL vs. 2.8±2.5 ng/mL, p<0.001). The receiver operator characteristic (ROC) analysis yielded a cut-off value of 3.13 ng/mL for differentiating patients with AMI from the controls (area under the curve: 0.739, 95% confidence interval: 0.629-0.831, p<0.001). HNP1-3 levels in the high SS tertile (≥33) were slightly but statistically nonsignificantly higher than that in the low (≤22) and intermediate SS tertiles (high SS: 7.0±6.1 ng/mL, intermediate SS: 5.9±6.2 ng/mL, low SS: 5.3±3.8 ng/mL; p=0.639). CONCLUSION: Patients with AMI had higher plasma HNP1-3 levels than the controls, but this did not show a significant correlation with angiographic disease severity. The nonsignificant trend toward higher SS in patients with higher HNP1-3 levels warrants future studies on larger populations.

The effect of postoperative positive end-expiratory pressure on postoperative bleeding after off-pump coronary artery bypass grafting.

INTRODUCTION: To compare postoperative prophylactic use of two positive end-expiratory pressure (PEEP) levels in order to prevent postoperative bleeding in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery. MATERIAL AND METHODS: Sixty patients undergoing an elective off-pump CABG operation were included in this prospective, nonrandomized clinical trial. Patients were divided into two groups as receiving either 5 cm H2O (group 1) or 8 cm H2O PEEP (group 2) after the operation until being extubated. Chest tube outputs, use of blood products and other fluids, postoperative hemoglobin levels, accumulation of pleural and pericardial fluid after the removal of chest tubes, and duration of hospital stay were recorded and compared. RESULTS: Low- and high-pressure PEEP groups did not differ with regard to postoperative chest tube outputs, amounts of transfusions and crystalloid/colloid infusion requirements, or postoperative hemoglobin levels. However, low-pressure PEEP application was associated with significantly higher pleural (92 ±37 ml vs. 69 ±29 ml, p = 0.03) and pericardial fluid (17 ±5 ml vs. 14 ±6 ml, p = 0.04) accumulation. On the other hand, high-pressure PEEP application was associated with significantly longer duration of hospitalization (6.25 ±1.21 days vs. 5.25 ±0.91 days, p = 0.03). CONCLUSIONS: Prophylactic administration of postoperative PEEP levels of 8 cm H2O, although safe, does not seem to reduce chest-tube output or transfusion requirements in off-pump CABG when compared to the lower level of PEEP. Further studies with larger sample sizes are warranted to confirm the benefits and identify ideal levels of PEEP administration in this group of patients.

Evaluation of atrial conduction features with tissue Doppler imaging in patients with chronic obstructive pulmonary disease.

BACKGROUND: The electrical activity of atria can be demonstrated by P waves on surface electrocardiogram (ECG). Atrial electromechanical delay (AEMD) measured with tissue Doppler imaging (TDI) echocardiography can be a useful non-invasive method for evaluating atrial conduction features. We investigated whether AEMD is prolonged in patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Study consisted of 41 (15 female, 26 male, mean age 62 + 12 years) patients with COPD and 41 healthy subjects. Pulmonary function tests,12 lead surface ECG and echocardiographic examination were performed and recorded. P wave changes on surface ECG, minimum (P (min)) and maximum (P (max)) duration of P wave and its difference as P wave dispersion (P (wd)) were measured and recorded. Atrial electromechanic delay (AEMD) was calculated from colored-TDI recordings. RESULTS: Pulmonary functions were significantly lower in COPD group than the control group as expected. Right atrial areas and pulmonary arterial systolic pressures (PAP) were significantly higher in COPD group than the controls (right atrial area: 11.9 ± 3.4 cm(2) and 8.2 ± 2.2 cm(2), p < 0.0001 and PAP: 38.4 ± 12.2 and 19.0 ± 3.2 mmHg p < 0.0001, respectively). P wave intervals on surface ECG were significantly increased in COPD patients than the control group (P (max): 105 ± 11 and 90 ± 12 ms, p < 0.0001; P (min): 60 ± 12 and 51 ± 10 ms, p = 0.003 and P (wd): 39 ± 10 and 31 ± 7 ms, p < 0.0001). According to the AEMD measurements from different sites by TDI, there was a significant delay between the onset of the P wave on surface ECG and the onset of the late diastolic wave in patients with COPD when compared with controls measured from tricuspid lateral septal annulus (TAEMD) (COPD: 41.3 ± 9.8 ms, control: 36 ± 4.5 ms; p = 0.005). There was a positive correlation between TAEMD and right atrial area (r = 0.63, p < 0.0001) and also between TAEMD and PASP (r = 0.43, p < 0.0005) and a negative correlation between TAEMD and forced expiratory volume (FEV1) (r = -0.44, p = 0.04). CONCLUSIONS: Right atrial electromechanical delay is significantly prolonged in patients with COPD. The right atrial area, PAP and FEV1 levels are important factors of this prolonged delay. Also the duration of atrial depolarization is significantly prolonged and propagation of depolarization is inhomogeneous in patients with COPD. These may be the underlying mechanisms to explain the atrial premature beats, multifocal atrial tachycardia, atrial flutter and fibrillation often seen in patients with COPD secondary to these changes.