Epoprostenol infusion therapy changes angiographic findings of pulmonary arteries in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: The pulmonary vascular changes induced by epoprostenol in patients with idiopathic pulmonary artery hypertension (IPAH) have not been reported by a clinical study. METHODS AND RESULTS: Analysis 1 compared the wedged pulmonary angiography (PAG) findings prior to initiation of epoprostenol therapy (n=24) with those after initiation (n=16). Analysis 2 compared the PAG findings prior to and after initiation of epoprostenol therapy (n=9) in the same pulmonary arteries in the same subjects. In analysis 1, a "cotton grass-like" stain originating from the peripheral pulmonary vessels (each vessel could not be distinguished on angiography) was not observable in any of 24 cases before initiation of epoprostenol therapy, but was visible in 13 of 16 cases after (p<0.0001). In analysis 2, the diameter of subsegmental arteries changed from 3.0+/-0.9 mm (mean +/- standard deviation) to 3.7+/-1.2 mm (p=0.004) between the 2 time periods. Cotton grass-like stain was not found in any cases before epoprostenol, but in all 9 cases after chronic use (p=0.004). CONCLUSIONS: After initiating epoprostenol therapy, cotton grass-like stain appeared in most patients with IPAH. The possible reason for this is release of severe vasoconstriction and/or emergence of neovascularization.     

Short-term fluctuations in sinus cycle length after premature ventricular beats in patients with hypertrophic cardiomyopathy and myocardial infarction

BACKGROUND: Sinus cycle length has been reported to fluctuate after a ventricular premature beat (VPB). The purpose of this study was to assess the short-term fluctuations of sinus cycle length in patients with hypertrophic cardiomyopathy (HCM) and prior myocardial infarction (MI). METHODS: The relative deviation of RR intervals from the mean of the last two RR intervals preceding a VPB were calculated during the 20 subsequent beats following the VPB from Holter recordings in 92 patients with non-obstructive HCM, 57 patients with prior MI and 54 healthy controls. RESULTS: In controls, the deviations of the RR intervals were negative for several beats after a VPB and subsequently changed to positive before returning to the baseline. Similar changes in RR intervals following a VPB were exhibited in HCM patients; however, the late positive deviations of RR intervals were more marked than in controls. By contrast, in patients with prior MI, the early negative deviations of RR intervals were smaller compared with controls, and the deviations returned to the baseline without incidence of the positive changes. CONCLUSIONS: Short-term fluctuations in sinus cycle length after a VPB differed exclusively among HCM patients, prior MI patients, and healthy controls.     

Cowden’s disease with a defined genetic alteration—Chromosomal duplication at 15q11–q13

Cowden’s disease, multiple hamartoma syndrome, is a dominantly inherited disorder characterized by multiple hamartomas of ectodermal, endodermal, and mesodermal origin and also by a high incidence of malignant tumors. Despite many efforts to identify the genetic alterations responsible for the syndrome, the molecular mechanism remains unclear. We report a case of Cowden’s disease in which karyotype analysis revealed a small duplication (about 1 Mb) at 15q11–q13. This part of the genome is a region that is deleted in the Prader-Willi/Angelman syndrome and is a “hot spot” of chromosomal duplication.     

Reproducibility of diurnal variation of heart rate

Heart rate variation has been utilized as a parameter for validating autonomic nerve and sinus node function. However, few reports are available on the reproducibility of such data. In the present study, we studied the reproducibility of the diurnal variation of heart rate in 15 patients, and the effect of age differences on the variation in 30 normal men using a Holter ECG monitoring method. For investigating reproducibility, Holter ECG monitoring was performed twice, the two measurements being separated by a short interval. A moving average method applied on heart rate of every 3h exhibited essentially the same diurnal pattern of heart rate between two records in each patient. Excellent reproducibility of the pattern was also demonstrated by a lag correlation analysis. Variability of heart rate in normal men was independent of age. These results suggest that heart rate variation was essentially constant in each subject, at least within a short period.     

CYP11B2 polymorphisms and home blood pressure in a population-based cohort in Japanese: the Ohasama study.

Genetic polymorphisms of the aldosterone synthase gene (CYP11B2) have been major targets of studies into the genetic factors involved in hypertension. We have identified three genetic variants of CYP11B2, -344C/T at the promoter region, a conversion in intron 2 from the CYP11B2 sequence to the CYP11B1 sequence, and R173K in exon 3, in the Japanese population. -344C/T and R173K were in complete linkage disequilibrium in CYP11B2, and -344C/T was in strong, but not complete, linkage disequilibrium with the polymorphism in intron 2. Thus, two genetic polymorphisms, -344C/T and the gene conversion in intron 2, were investigated in association with home blood pressure (BP) values and clinical parameters in 1,242 subjects aged 40 and over in Ohasama, a rural Japanese community. Hypertension was defined as being treated with antihypertensive medication and/or having home BP values of more than 135 mmHg in systole and/or 85 mmHg in diastole. The results demonstrated that the -344T allele was significantly associated with increased prevalence of hypertension (p=0.015 in multiple logistic regression analysis, adjusted by age, gender, BMI, and smoking status), though BP level was unaltered. This allele was also significantly related to the prevalence of cardiovascular diseases in the older population (60 < or = age, p=0.014). The resting polymorphism, a gene conversion in CYP11B2 intron 2, was not associated with any clinical parameters. Therefore, -344C/T polymorphism in CYP11B2 was considered an independent genetic factor possibly associated with hypertension or atherosclerotic diseases in the Japanese population.     

Improved systolic ventricular function with normal myocardial mechanics in compensated cardiac hypertrophy

There is still controversy about the relation between changes in myocardial contractile function and global left ventricular (LV) performance during stable concentric hypertrophy. To clarify this, we analyzed LV function in vivo and myocardial mechanics in vitro in rats with pressure overload-induced cardiac hypertrophy. Male Wistar rats (70 g) underwent ascending aortic stenosis for 8 weeks (group AAS, n = 9). LV performance was assessed by transthoracic echocardiography under anesthesia. Myocardial function was studied in isolated papillary muscle preparations during isometric contraction. The data were compared with age- and sex-matched sham-operated rats (group C, n = 9). LV weight-to-body weight ratio (C: 2.13 +/- 0.14 mg/g; AAS: 3.24 +/- 0.44 mg/g), LV relative wall thickness (C: 0.18 +/- 0.02; AAS: 0.33 +/- 0.09), and LV fractional shortening (C: 54 +/- 5%; AAS: 70 +/- 8%) were increased in group AAS (P < 0.05). Echocardiographic analysis also indicated a significant association (r = 0.74; P < 0.001) between the percent fractional shortening index and LV relative wall thickness. The performance of AAS isolated muscle revealed that active tension (C: 6.6 +/- 1.7 g/mm2; AAS: 6.5 +/- 1.5 g/mm2) and maximum rate of tension development (C: 69 +/- 21 g/mm2/s; AAS: 69 +/- 18 g/mm2/s) were not significantly different from group C (P > 0.05). In conclusion, compensated pressure-overload myocardial hypertrophy is associated with preserved myocardial function and increased ventricular performance. The improved LV function might be due to the ventricular remodeling characterized by an increased relative wall thickness.