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.

Factors associated with pulmonary hypertension and long-term survival in bronchiectasis subjects.

BACKGROUND: The development of pulmonary hypertension (PH) and its effect on long-term survival in bronchiectasis subjects has not been explored. The present study aims to analyze the factors associated with PH and its effect on long-term survival in bronchiectasis subjects. METHODS: We prospectively evaluated 23 bronchiectasis subjects without PH and 16 with PH, as well as 20 healthy volunteers. RESULTS: Bronchiectasis subjects with PH were more hypoxemic and had a greater number of involved lobes in high resolution computed tomography (HRCT) than did the bronchiectasis subjects without PH (P < 0.001 and P < 0.001, respectively). At three years, the survival rate was 95.7% for bronchiectasis subjects without PH and 56.3% for bronchiectasis with PH, and at 5 years, these rates were 95.7% and 62.5%, respectively (P = 0.002). Multivariate Cox regression analysis revealed that only the Medical Research Council (MRC) dyspnea score was independently related to poor survival in all bronchiectasis subjects (hazard ratio: 6.98; 95% CI: 2.41-20.23; P < 0.00001). CONCLUSIONS: Subjects with PH are more hypoxemic and have a greater number of involvements in the lobes of the lungs. Bronchiectasis subjects with PH have worse survival than do bronchiectasis subjects without PH. MRC dyspnea score is an independent predictor of long-term survival.

The impact of hypertension and hypertension-related left ventricle hypertrophy on right ventricle function.

AIM: The aim of our study is to determine the effect of hypertension and hypertension-related left ventricle hypertrophy on right ventricle (RV) morphology and function by using RV standard Doppler echocardiographic indices, myocardial Doppler imaging, and strain/strain rate imaging indices. METHODS: We studied 35 patients with arterial hypertension and 30 age- and sex-adjusted control subjects who had no other pathological conditions. Standard transthoracic Doppler echocardiographical measurements, pulsed-wave tissue Doppler from tricuspid anulus (Peak systolic-st, peak early diastolic-et, peak late diastolic velocity-at), reconstructed spectral pulsed-wave tissue Doppler velocities (peak systolic-S, peak early-E, peak late diastolic velocity-A), and strain/strain rate imaging of RV free wall mid region (peak systolic strain-in, peak systolic strain rate-SR) were obtained. RESULTS: Age, body surface area, blood pressure, and heart rate were comparable between two groups. Hypertensive subjects had significantly increased LV end-diastolic septal and posterior wall thickness, left atrial diameter, LV mass, LV mass index, and relative wall thickness during diastole. At the level of right ventricular lateral tricuspid annulus without systolic changes, the majority of diastolic measurements were altered in hypertensives (early diastolic velocity et; 13 +/- 2 vs. 18 +/- 4 m/sec, P < 0.0001, late diastolic velocity at; 20 +/- 4 vs. 14 +/- 3 m/sec, P < 0.0001, early to late diastolic velocity ratio; 0.69 +/- 0.14 vs. 1.32 +/- 0.38, P < 0.0001). The velocity data from two-dimensional color myocardial imaging at the level of RV free wall mid region again showed altered diastolic measurements in hypertensives (E; 8.01 +/- 2.6 vs. 10.4 +/- 3.14 m/sec, P < 0.001, A; 11.5 +/- 2.6 vs. 9.12 +/- 3.7 m/sec, P < 0.0001, E/A ratio; 0.75 +/- 0.41 vs. 1.87 +/- 0.48, P < 0.00). The peak systolic strain of RV free wall mid region was significantly lower in hypertensive individuals than controls (25.666 +/- 5.64 vs. 30.03 +/- 6.78%, P < 0.05). No significant differences were found in other parameters of RV function between hypertensive and control subjects. CONCLUSIONS: The present study demonstrates that besides the manifest morphologic LV adaptations, significant RV functional alterations can be determined by TDI and strain/strain rate imaging in patients arterial hypertension. Both tissue velocities by TDI and strain imaging may be new tools to define and quantitate subtle change in systolic and diastolic function of right ventricular function in arterial hypertension that cannot be determined in standard echocardiographic parameters.

Assessment of the relationship between functional capacity and right ventricular ultrasound tissue characterization by integrated backscatter in patients with isolated mitral stenosis.

AIM: The aim of the present study was to investigate right ventricular (RV) myocardial textural properties in asymptomatic and symptomatic mitral stenosis (MS) patients with normal RV systolic function using integrated backscatter (IBS). METHODS: The study included 40 patients with MS of moderate or severe degree. Patients were classified into 2 groups according to NYHA class (asymptomatic group, NYHA class I, symptomatic group, NYHA class II-III). RV pulsed-wave tissue Doppler imaging (TDI) and IBS analyses were performed in all patients. Isovolumic contraction time (IVCT), systolic wave velocity (S), isovolumic relaxation time (IVRT), early diastolic wave velocity (E), and late diastolic wave velocity (A) were measured by TDI. IBS amplitude (IB) and cyclic variation (CV) of the RV lateral wall in the parasternal long-axis view were measured by IBS. CV was calculated by subtracting systolic IB from diastolic IB. RESULTS: IVRT (54.2 +/- 11.9 ms versus 86.2 +/- 16.2 ms, P < 0.001) and A wave amplitude (10.2 +/- 2.1 cm/s versus 13.6 +/- 1.8 cm/s, P < 0.05) were higher whereas E wave amplitude (11.7 +/- 1.6 cm/s and 10.3 +/- 1.5 cm/s, P < 0.05) and E/A ratio (1.3 +/- 0.3 versus 0.7 +/- 0.1, P < 0.001) were lower in group 2. Symptomatic patients had a lower CV value of RV (9.5 +/- 3.4 dB versus 6.7 +/- 1.9 dB, P = 0.004). There was a positive correlation between CV and E/A (r = 0.964, P < 0.001) CONCLUSION: Symptomatic isolated MS patients had RV echo texture changes and diastolic dysfunction in comparison to asymptomatic ones with similar mitral valve areas in the presence of normal RV systolic function. In isolated MS, both pulsed-wave TDI and IBS may aid in the detection of RV diastolic pathology.

Evaluation of the relationship between functional capacity and right ventricular diastolic function in patients with isolated mitral stenosis and sinus rhythm: a tissue Doppler study.

AIM: The right ventricular (RV) systolic function is an important determinant of clinical symptoms and exercise capacity in patients with mitral stenosis. No sufficient data are available concerning the effect of RV diastolic function on symptoms of patients with mitral stenosis. In the presence of normal RV systolic function, RV diastolic functions of asymptomatic patients with mitral stenosis of moderate or severe degree were compared to symptomatic ones by pulsed-wave tissue Doppler echocardiography in this study. MATERIALS AND METHODS: The study included 40 patients with mitral stenosis. Patients were classified into two groups according to New York Heart Association (NYHA) class (asymptomatic group NYHA class I, symptomatic group NYHA class II-III). RV diastolic functions were evaluated via pulsed-wave tissue Doppler in terms of isovolumic contraction time (IVCT), systolic wave velocity (S), isovolumic relaxation time (IVRT), early diastolic wave velocity (E'), and late diastolic wave velocity (A'). RESULTS: Statistical difference was not determined in systolic parameters (S, IVCT) between the two groups. However, IVRT (54.21 +/- 11.93 msec vs 86.19 +/- 16.23 msec, P < 0.0001) and A' wave amplitude (10.16 +/- 2.14 cm/sec vs 13.55 +/- 3.35 cm/sec, P < 0.0001) were higher whereas E' wave amplitude (11.68 +/- 1.60 cm/sec and 10.25 +/- 2.73 cm/sec, P = 0.009) and E'/A' ratio (1.18 +/- 0.23 vs 0.76 +/- 0.17, P < 0.0001) were lower in group 2. CONCLUSION: In isolated mitral stenosis, pulsed-wave tissue Doppler may be used for the detection of RV diastolic pathology. Diastolic functions of RV may deteriorate in the presence of normal systolic functions in symptomatic patients with isolated mitral stenosis.

Diurnal variation of the P-wave dispersion in chronic ischemic heart diseases.

OBJECTIVE: Electrocardiographic indices like maximum P-wave duration (P(max)) and P-wave dispersion (PD) can be used to detect patients with atrial conduction disorders, myocardial ischemia and those at risk for atrial fibrillation. Considering the diurnal variation of ischemia in patients with significant coronary lesions, this study was designed to investigate the diurnal variation of eventual atrial conduction abnormalities. METHODS: Forty-eight patients (31 male) with typical angina were grouped according to coronary angiography results as group 1 - 70% or more luminal reduction in at least one of the coronary arteries (n=28), and group 2 - normal coronary arteries (n=20). The difference between the P(max) and minimum P-wave durations (P(min)) is designated as PD. The diurnal P(max), P(min) and PD values were compared between and within the groups. RESULTS: The morning P(max) value of group 1 was significantly higher than the value of group 2 (112+/-1 vs. 102+/-1 ms, P<0.001). The morning PD of group 1 was significantly higher than that of group 2 (54+/-9 vs. 48+/-1 ms, P<0.05). The morning P(max) of group 1 (112+/-1 ms) was significantly higher than its afternoon (102+/-9 ms) and night (102+/-1 ms) values (P<0.001). The morning PD of group 1 (54+/-9 ms) was higher than the afternoon (40+/-10 ms) and night (43+/-9 ms) PD (P<0.001). No significant difference was observed between the P(max), P(min) and PD values in group 2 (P>0.05). CONCLUSION: This study demonstrated that coronary heart disease patients have higher morning P(max) and PD values that may be important regarding prediction of timing and treatment of atrial conduction disorders in myocardial ischemia.

Right bundle branch block: a new parameter revealing the progression rate of mitral stenosis.

BACKGROUND: Mitral stenosis has a generally slow but often variable clinical course. However, the factors that influence the rate of stenosis progression have not been completely identified. The aim of this study was to evaluate whether right bundle branch block (RBBB) may be related to the rapid progression of pure mitral stenosis besides echocardiographic parameters. METHODS: Four hundred and thirty-six patients (300 females) were reviewed retrospectively. The patients were classified according to RBBB existence in electrocardiography: group A included 83 patients with RBBB existence, and group B contained 353 patients without RBBB. The patients were further classified as subjects who had an echocardiographic valve score < or =8 (325 patients, group 1) and those with a valve score >8 (111 patients, group 2). RESULTS: The mean age of the patients was similar in groups A and B. In group A, the mean mitral valve gradient was higher (12.63 +/- 4.43 vs. 10.58 +/- 3.37 mm Hg; p < 0.0001), the mitral valve area smaller (1.05 +/- 0.2 vs. 1.14 +/- 0.52 cm2; p = 0.011), and the systolic pulmonary artery pressure higher (53.5 +/- 16.2 vs. 46.9 +/- 13.2 mm Hg; p = 0.001) than in group B. The mean age and mitral valve area were similar in groups 1 and 2. The mean mitral valve gradient (10.5 +/- 3.7 vs. 12.3 +/- 3.0 mm Hg; p < 0.0001) and systolic pulmonary artery pressure were higher in group 2 (46.7 +/- 13.3 vs. 52.5 +/- 15 mm Hg; p < 0.0001). CONCLUSION: These findings indicate that RBBB existence correlates with the severity of the disease and the grade of valve calcification in moderate and severe pure mitral stenosis.