Aortic stiffness is an independent determinant of B-type natriuretic peptide in patients with coronary artery disease.

Previous studies demonstrated that the B-type natriuretic peptide (BNP) level is high in some patients with coronary artery disease (CAD) despite a preserved left ventricular function, although the mechanism underlying this increase in patients with CAD has not been fully elucidated. Because aortic stiffness is greater in patients with CAD and increases with CAD severity, there is a possibility that an increased aortic stiffness in turn increases the elevation of the BNP level in patients with CAD. In this study, we measured BNP level and brachial-ankle pulse wave velocity (baPWV) in 134 patients with CAD, and evaluated the relationship between BNP and baPWV. The patients were classified on the basis of the quartiles of BNP level to identify the characteristics of patients with a high BNP level. baPWV was significantly greater in patients classified into the highest quartile of BNP level than in those classified into the other quartiles. Multivariate analysis demonstrated that baPWV and left ventricular ejection fraction independently correlated with BNP level. Logistic regression analysis demonstrated that the odds ratio for the highest quartile of BNP level increased with baPWV quartile. This association remained significant after adjustment for systolic and diastolic function. In conclusion, increased aortic stiffness possibly underlies the increase in the BNP level in patients with CAD.

Electrical storm in patients with brugada syndrome is associated with early repolarization.

BACKGROUND: Electrical storms (ESs) in patients with Brugada syndrome (BrS) are rare though potentially lethal. METHODS AND RESULTS: We studied 22 men with BrS and ES, defined as ≥3 episodes/d of ventricular fibrillation (VF) and compared their characteristics with those of 110 age-matched, control men with BrS without ES. BrS was diagnosed by a spontaneous or drug-induced type 1 pattern on the ECG in the absence of structural heart disease. Early repolarization (ER) was diagnosed by J waves, ie, >0.1 mV notches or slurs of the terminal portion of the QRS complex. The BrS ECG pattern was provoked with pilsicainide. A spontaneous type I ECG pattern, J waves, and horizontal/descending ST elevation were found, respectively, in 77%, 36%, and 88% of patients with ES, versus 28% (P<0.0001), 9% (P=0.003), and 60% (P=0.06) of controls. The J-wave amplitude was significantly higher in patients with than without ES (P=0.03). VF occurred during undisturbed sinus rhythm in 14 of 19 patients (74%), and ES were controlled by isoproterenol administration. All patients with ES received an implantable cardioverter defibrillator and over a 6.0±5.4 years follow-up, the prognosis of patients with ES was significantly worse than that of patients without ES. Bepridil was effective in preventing VF in 6 patients. CONCLUSIONS: A high prevalence of ER was found in a subgroup of patients with BrS associated with ES. ES appeared to be suppressed by isoproterenol or quinidine, whereas bepridil and quinidine were effective in the long-term prevention of VF in the highest-risk patients.

Right but not left ventricular function recovers early after living-donor lobar lung transplantation in patients with pulmonary arterial hypertension.

OBJECTIVE: The aim of this study was to evaluate right and left ventricular functions in patients with pulmonary arterial hypertension after living-donor lobar lung transplantation compared with those without hypertension. METHODS: Thirty-three recipients of living-donor lobar lung transplantation were divided into two groups: those with pulmonary arterial hypertension (PAH group; n = 12) and those without (non-PAH group; n = 21). Their systolic pulmonary artery pressure was 93.1 +/- 6.7 mm Hg versus 31.4 +/- 2.9 mm Hg, respectively. Right and left ventricular ejection fractions, systolic pulmonary artery pressure, and cardiac index were serially measured by radionuclide ventriculography and right heart catheterization, respectively. RESULTS: Pretransplant right and left ventricular ejection fractions were lower in the PAH group (29.8% +/- 7.0%, 49.9% +/- 6.6%) than in the non-PAH group (49.7% +/- 3.3%, 65.2% +/- 1.9%) (P = .010, .068). Two months after living-donor lobar lung transplantation, right ventricular ejection fraction and systolic pulmonary artery pressure in the PAH group (57.3% +/- 5.1%, 25.7 +/- 1.8 mm Hg) improved dramatically, equal to those in the non-PAH group. In contrast, left ventricular ejection fraction and cardiac index in the PAH group (50.9% +/- 3.7%, 2.66 +/- 0.12 L x min(-1) x m(-2)) were still significantly lower than in the non-PAH group (65.4% +/- 2.8%, 3.13 +/- 0.15 L x min(-1) x m(-2)) (P = .0038, .037). At 6 to 12 months, the PAH group demonstrated a significant rise in left ventricular ejection fraction and cardiac index that reached similar values in the non-PAH group measured at 2 months. These values were stable for up to 3 years. CONCLUSIONS: Right ventricular function recovered early after living-donor lobar lung transplantation in the PAH group. In contrast, recovery of left ventricular function required 6 to 12 months. Improved cardiac function was sustained for up to 3 years, suggesting long-term durability of cardiac function recovery after living-donor lobar lung transplantation.

Aortic stiffness is an independent predictor of left ventricular function in patients with coronary heart disease.

Although aortic stiffness plays an important role in patients with coronary artery disease (CAD), the influence of aortic stiffness on left ventricular systolic function has not yet been fully evaluated. In the present study, we measured brachial-ankle pulse wave velocity (baPWV), which is a new index of aortic stiffness, in patients with CAD (CAD group, n = 170, 67 +/- 9 years old) and without CAD (non-CAD group, n = 81, 63 +/- 8 years old), and evaluated the relationship between baPWV and left ventricular systolic function in patients with CAD. baPWV in the CAD group was significantly higher than that in the non-CAD group (1,794 +/- 350 vs. 1,469 +/- 292 cm/s, p < 0.05), although both systolic and diastolic blood pressure were comparable between the two groups. In the CAD group, the baPWV was higher in patients with three-vessel disease than that in patients with one-vessel disease (1,885 +/- 542 vs. 1,720 +/- 373 cm/s, p < 0.05). In the CAD group, multivariate analysis demonstrated that baPWV and pulse pressure independently correlated with left ventricular ejection fraction (LVEF). In conclusion, in patients with CAD, baPWV, which is a simple marker of aortic stiffness, increases with CAD severity and correlates with left ventricular systolic function independent of CAD severity.

Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy.

Hypertrophic cardiomyopathy and dilated cardiomyopathy are two major clinical phenotypes of "idiopathic" cardiomyopathy. Recent molecular genetic analyses have now revealed that "idiopathic" cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. A hypertrophic cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic cardiomyopathy and dilated cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.

An N-terminal sequence specific for a novel Homer1 isoform controls trafficking of group I metabotropic glutamate receptor in mammalian cells.

Homer proteins bind to a proline-rich region of the group I metabotropic glutamate receptors (mGluRs) and control their expression and localization at the excitatory postsynaptic density. We isolated a novel isoform of Homer1, Homer1d, from a mouse heart cDNA library. Its N-terminal end of 18 amino acids was unique among Homer1 variants (Homer1a-d), while the remainder of Homer1d was identical to that of Homer1b. To clarify the function of its N-terminus, we expressed Homer1b and 1d in the presence and absence of mGluR5b in HEK293T cells. When expressed alone, both Homer proteins were distributed diffusely in the cytoplasm and mGluR5b was on the plasma membrane (PM). When co-expressed, Homer1d and mGluR5b were co-localized on the PM, while Homer1b and mGluR5b were retained in the endoplasmic reticulum (ER). Both Homer proteins bound to mGluR5b in vitro. Therefore, the N-terminal portion of Homer1d may facilitate trafficking of Homer1-mGluR5 complex from the ER to the PM.