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.

Serum choline levels in patients with stable angina and acute coronary syndromes: relation to the severity of coronary artery disease.

OBJECTIVE: We sought to investigate whether serum choline levels are increased across the spectrum of coronary artery disease (CAD) manifestations and correlate with the severity of coronary stenosis. METHODS: A total of 36 patients with acute coronary syndrome (ACS) [22 patients with non-ST-segment elevation ACS and 14 patients with ST-segment elevation acute myocardial infarction (STEMI)], 22 patients with stable angina pectoris (SAP), and 18 controls were recruited for the study. In ACS patients, serum choline levels were measured on admission, and at 24 and 48 h thereafter, using high-performance liquid chromatography. The severity of CAD was assessed using the Gensini score. RESULTS: Serum choline levels on admission were significantly higher in the entire group of patients with ACS than in controls. The highest level of choline was observed in the STEMI group, followed by the SAP, and the non-ST-segment elevation ACS groups. Serum choline levels decreased gradually in patients with STEMI over the 48-h period. Serum choline levels on admission, and at 24 or 48 h thereafter, did not correlate with the presence of CAD neither in patients with ACS (P=0.78, 0.98 and 0.98, respectively) nor in those with SAP (P=0.92). CONCLUSION: Our results suggest that serum choline levels are increased in ACS patients. However, there was no clear correlation between levels of choline and the severity and extent of CAD in this patient group.

Serial changes in circulating M30 antigen, a biomarker of apoptosis, in patients with acute coronary syndromes: relationship with the severity of coronary artery disease.

OBJECTIVES: Growing evidence has indicated the potential clinical usefulness of measuring different forms of cytokeratin 18 in patient sera (M30 antigen for apoptosis and M65 antigen for necrosis) for distinguishing different forms of cell death. Preliminary data have reported altered levels of cytokeratin 18 fragments in patients with acute coronary syndrome (ACS) and ischemic heart disease. In this study, serum levels of M30 and M65 were measured in 74 patients with ACS [including 17 cases with unstable angina and 57 patients with acute myocardial infarction (AMI)], 25 patients with stable angina, and 23 controls. METHODS: In patients with ACS, serial measurements of M30 and M65 were obtained, and for each patient, the following values were determined: (i) values at admission, (ii) values obtained 24 h after symptom onset, and (iii) values obtained at 48 h after symptom onset. The severity of coronary atherosclerosis was expressed using the Gensini score. RESULTS: On admission, M30 and M65 levels in ACS patients were similar to those observed in stable angina patients and control participants. In AMI patients, serum levels of M30 peaked at 24 h and declined thereafter at 48 h. Notably, serum levels of M30 measured at 24 h correlated significantly and positively with the extent of coronary artery disease as measured by the Gensini score in AMI patients (r = 0.253, P<0.05). CONCLUSION: Serum levels of the apoptotic marker M30 peak at 24 h after AMI and reflects the extent of coronary artery disease in this patient group.

Serum arylesterase activity is negatively correlated with inflammatory markers in patients with acute coronary syndromes.

OBJECTIVES: To examined whether serum paraoxonase (PON1) and arylesterase (ARE) activities are correlated with inflammatory biomarkers (procalcitonin and high sensitivity C-reactive protein (hs-CRP) in patients with acute coronary syndrome (ACS). METHODS: This cross-sectional study was conducted at the Departments of Cardiology and Biochemistry, Uludag University School of Medicine, Bursa, Turkey, from April 2007 to December 2007. Seventy-eight consecutive patients with ACS and 39 healthy controls were investigated. Acute coronary syndrome patients were divided into 3 groups according to their clinical presentation: unstable angina pectoris (UAP) (Braunwald III-B, n=25), non-ST elevation myocardial infarction (NSTEMI) (n=18), and ST-elevation myocardial infarction (STEMI) (n=35). Serum PON1/ARE activities were measured spectrophotometrically. Levels of procalcitonin and hs-CRP were measured by immunoassay. RESULTS: Paraoxonase/ARE activities were significantly lower in all patient groups compared to controls. No correlation between PON1/ARE activities and high-density-cholesterol levels was seen. Among ACS patients, serum ARE activity correlated inversely with baseline and 48-hour procalcitonin (r=-0.577, p=0.009, and r=-0.642, p=0.019) and hs-CRP levels (r=-0.614, p=0.03, and r=-0.719, p=0.044). CONCLUSION: Serum ARE activity is reduced in ACS patients and inversely correlated with inflammatory markers.