Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease.

Haploinsufficiency of transcriptional regulators causes human congenital heart disease (CHD); however, the underlying CHD gene regulatory network (GRN) imbalances are unknown. Here, we define transcriptional consequences of reduced dosage of the CHD transcription factor, TBX5, in individual cells during cardiomyocyte differentiation from human induced pluripotent stem cells (iPSCs). We discovered highly sensitive dysregulation of TBX5-dependent pathways-including lineage decisions and genes associated with heart development, cardiomyocyte function, and CHD genetics-in discrete subpopulations of cardiomyocytes. Spatial transcriptomic mapping revealed chamber-restricted expression for many TBX5-sensitive transcripts. GRN analysis indicated that cardiac network stability, including vulnerable CHD-linked nodes, is sensitive to TBX5 dosage. A GRN-predicted genetic interaction between Tbx5 and Mef2c, manifesting as ventricular septation defects, was validated in mice. These results demonstrate exquisite and diverse sensitivity to TBX5 dosage in heterogeneous subsets of iPSC-derived cardiomyocytes and predicts candidate GRNs for human CHDs, with implications for quantitative transcriptional regulation in disease.

Long-term effects of low-dose 17beta-estradiol plus dydrogesterone on 24-h ambulatory blood pressure in healthy postmenopausal women: a 1-year, randomized, prospective study.

The aim of the present 12-month, randomized, prospective controlled study was to investigate the long-term effects of low-dose oral hormone replacement therapy (HRT) on 24-h blood pressure in healthy, normotensive postmenopausal women. A total of 80 postmenopausal women received either 1 mg micronized 17beta-estradiol daily, sequentially combined with 10 mg dydrogesterone for 14 days of each 28-day cycle (n = 44), or no treatment (n = 36). Ambulatory blood pressure was recorded for a 24-h period at baseline and after 12 months. After 12 months, mean 24-h systolic ambulatory blood pressure fell significantly in the HRT group (-5.4 mmHg; p < 0.01). The difference between the values in the HRT and control groups after 12 months was significant (p < 0.01). Mean 24-h heart rate also fell significantly with HRT (-4.9 beats/min; p < 0.05), and the value was significantly lower than in the control group (p < 0.05). Mean daytime systolic blood pressure fell significantly in the HRT group (-6.6 mmHg; p < 0.001), and the value was significantly lower than in the control group (p < 0.05). There were no significant changes in blood pressure in the control group. In conclusion, sequential low-dose oral HRT with 17beta-estradiol/dydrogesterone caused a significant decrease in 24-h and daytime systolic ambulatory blood pressure in normotensive postmenopausal women.

Intravascular volume dependency of left ventricular mass calculation by two-dimensional guided M-mode echocardiography.

BACKGROUND: Increased left ventricular mass (LVM) is an independent risk factor for cardiovascular morbidity and mortality, and may be used for risk stratification. Two-dimensional echocardiography, the most commonly used technique for estimation of LVM, uses the third power of the left ventricular internal diameter (LVID) for the calculation. OBJECTIVES: To determine whether a decrease in intravascular volume after dialysis may cause inaccurate estimation of LVM by echocardiography. METHODS: Thirty-eight patients undergoing hemodialysis due to chronic renal failure constituted the study group (14 women [37%] and 24 men [63%], mean age +/- SD 38.7+/-10.9 years). LVID, and interventricular and posterior wall thicknesses were measured by two-dimensionally guided M-mode echocardiography. Stroke volume and cardiac output were calculated using left ventricular outflow tract diameter and the pulsed-wave Doppler time-velocity integral obtained from left ventricular outflow tract. LVM was calculated by using Devereux's formula, and was indexed for body surface area and height. All echocardiographic parameters were measured or calculated before and after dialysis (on the same day), and then compared. RESULTS: There were no significant changes in wall thickness; however, LVID, LVM, the LVM/body surface index and the LVM/height index significantly decreased after dialysis (P<0.001 for each parameter). There was a significant correlation between the change in LVID and the change in LVM (P<0.001, r=0.59). Stroke volume and cardiac output also decreased significantly after hemodialysis (P<0.001 for each parameter). CONCLUSIONS: Intravascular volume-dependent change in LVID causes inaccurate estimation of LVM, so volume status should be kept in mind, especially in serial assessment of LVM.

Value of tissue Doppler myocardial velocities of tricuspid lateral annulus for the diagnosis of right heart failure in patients with COPD.

OBJECTIVE: Aim of this study was to investigate the value of systolic indices of tricuspid valve annular motion measured by tissue Doppler imaging for the diagnosis right ventricular failure in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD with right heart failure symptoms and/or right ventricular dilatation were enrolled for the study. The control group consisted of age and sex matched patients referred to the echocardiography laboratory who had normal echocardiographic examination. Tricuspid valve annulus peak systolic velocity and myocardial acceleration during isovolumic contraction were recorded by tissue Doppler imaging. RESULTS: IVA and Sa wave velocities were found to be significantly decreased in patients with right ventricular failure. For the prediction of right heart failure IVA <3.8 m/sec2 had 91% sensitivity, 80% specificity, 90% positive predictive value (PPV), and 82% negative predictive value (NPV) and Sa wave velocity <9.2 cm/sec had 80% sensitivity, 62% specificity, 75% PPV, and 68% NPV. CONCLUSION: Tricuspid valve annular velocities measured by tissue Doppler imaging especially IVA, offer potential diagnostic value for the diagnosis of right heart failure in patients with COPD.

DDD pacemaker implantation in a patient with persistent left superior vena cava and absent right superior vena cava: a four-year follow-up report.

Persistent left superior vena cava coexisting with the absence of right superior vena cava is an uncommon anomaly, and sometimes requires permanent pacemaker implantation due to the relatively high incidence of conduction disturbances and arrhythmias. This anomaly makes the implantation of pacemaker leads more difficult; therefore, accurate preintervention diagnosis of this anomaly is valuable for the interventionalist. A patient in which the diagnosis of persistent left superior vena cava coexisting with absent right superior vena cava was made echocardiographically before permanent pacemaker implantation is presented. Acetylsalicylic acid was prescribed after pacemaker implantation to prevent a potentially fatal complication of coronary sinus thrombosis, and no complication occurred during the four-year follow-up. Some clues for the noninvasive diagnosis of this anomaly and techniques of pacemaker implantation are also described briefly.

Three unusual myxomas originating from the left atrial appendage: a case report.

Most left atrial appendage masses have been reported to be thrombus, particularly in the presence of atrial fibrillation. The presence of any mass other than thrombus is extremely rare in the left atrial appendage. This report presents the rare case of a 70-year-old woman presenting with paroxysmal atrial fibrillation and syncope who was given the diagnosis of having 3 myxomas originating from the left atrial appendage. The diagnosis was established by the help of transesophageal echocardiography and confirmed by histologic examination after operation. The advantage of transesophageal echocardiography in this case and for patients with atrial fibrillation is emphasized.