Toru Ohe

Idiopathic sustained left ventricular tachycardia: clinical and electrophysiologic characteristics.

Electrophysiologic studies were performed in 16 patients 11 to 45 years old (mean 33 years) with idiopathic sustained (lasting more than 5 min) ventricular tachycardia (VT) originating from the left ventricle. Endocardial mapping during VT showed that the earliest site of activation was at the apical inferior portion of the left ventricle in 14 patients whose QRS morphology during VT showed a right bundle branch block pattern and left-axis deviation, but at the apical anterosuperior portion of the left ventricle in two patients whose QRS morphology during VT showed a right bundle branch block and right-axis deviation. Single programmed ventricular stimulation induced VT in 13 patients, and rapid ventricular pacing induced VT in the remaining three patients. Rapid ventricular pacing terminated VT in all patients. The relationship between the coupling interval and the echo interval was inverse in all eight patients with a wide VT inducible zone. Entrainment was recognized in three of six patients. The initiation of VT by constant pacing depended on the number of pacing beats but not the duration of pacing in all four patients tested. Intravenous verapamil terminated the VT in 13 of 14 patients. Long-term oral verapamil was also effective in all five patients who required long-term oral therapy for their symptoms associated with VT. In conclusion (1) idiopathic left ventricular tachycardia has unique electrocardiographic, electrophysiologic, and electropharmacological properties, (2) the electrophysiologic characteristics suggest that the mechanism is reentry, and (3) verapamil is effective in both the short- and long-term treatment of VT.

Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome.

Background Several recent experimental and clinical studies have shown that early afterde-polarizations (EADs) are important in the genesis of QTU prolongation and ventricular tachyarrhythmias (VTs) in patients with long QT syndrome. On the other hand, sympathetic stimulation is well known to contribute to the genesis of QTU prolongation and VTs in patients with congenital long QT syndrome. The present study was performed to examine the influence of isoproterenol on the genesis of EADs and on the action potential durations and QTU intervals in patients with congenital long QT syndrome. Methods and Results We recorded monophasic action potentials (MAPs) with a contact electrode during right atrial pacing at a constant cycle length of 500 msec before and after continuous isoproterenol infusion (1 μg/min). MAPs were obtained from the right and left ventricular endocardium in six patients with congenital long QT syndrome (LQT group, 18 recording sites) and in eight control patients (control group, 19 recording sites). Although no EADs were recorded from either group during the control state, MAP duration at 90% repolarization (MAPD90) was significantly longer in the LQT group (n = 18) than in the control group (n = 19) (275 ± 36 versus 231 ± 22 msec;p < 0.0005). Isoproterenol induced EADs in four of the six LQT patients (five of 18 recording sites) but not in the eight control patients (zero of 19 recording sites). The appearance of EADs in the LQT group was associated with an increased amplitude of the late component of the TU complex, and the corrected QT (QTj) interval was prolonged by isoproterenol from 543 ± 53 to 600 ± 30 msec12 (n = 6; p < 0.05). Isoproterenol also prolonged the MAPD90 from 275 ± 36 to 304 ± 50 msec in the LQT group (n = 18; p< 0.005), whereas it shortened the MAPD90 from 231 ± 22 to 224 ± 25 msec in the control group (n = 19; p< 0.05). Moreover, isoproterenol increased the dispersion of MAPD90 (difference between the longest MAPD90 and the shortest MAPD90 in each patient) from 30 ± 5 to 62 ± 35 msec in the LQT group (n = 6; p=0.08), whereas it did not change the dispersion of MAPD90 in the control group (n = 8; 25 ± 14 versus 27 ± 14 msec). Conclusions. These results suggest that patients with congenital long QT syndrome have primary repolarization abnormalities and that EADs induced by isoproterenol play an important role in the exaggeration of these repolarization abnormalities.

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.

The role of initial minimum potentials on body surface maps in predicting the site of accessory pathways in patients with Wolff-Parkinson-White syndrome.

Forty-one patients (23 men and 18 women, ages 20 to 66 years) with Wolff-Parkinson-White syndrome were studied with isopotential body surface maps during sinus rhythm to find the most reliable index for predicting the sites of single accessory pathways. The sites predicted by surface maps were compared with those confirmed by multicatheter electrophysiologic study or in the course of surgical operation. Location of the initial minimum by a time criterion, 40 msec after onset of the QRS complex, was not reliable enough for prediction in patients with the small delta wave on their electrocardiograms, because ventricular activation via the normal conduction pathway significantly influenced the location of the minimum. Location of the minimum by an amplitude criterion, -0.15 mV or slightly deeper, was influenced minimally by fusion of ventricular activation, the patients body size, or age and corresponded well to the site of the accessory pathway in 36 of 41 patients. Those minima appeared on circumscribed areas of the map in accordance with the anatomic subdivisions of the atrioventricular ring. Thus location of the minimum by the amplitude criterion was an excellent index for predicting the site of the accessory pathway, regardless of the degree of ventricular fusion. These amplitude-based map features suggest that nonstandard electrocardiograms recorded from selected positions on the body surface can be used as accurate predictors of the sites of accessory pathways.

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.

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.

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.

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.

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.

Spectral analysis of signal-averaged electrocardiograms in patients with idiopathic ventricular tachycardia of left ventricular origin.

BackgroundThe signal-averaged ECG has been used to detect late potentials, and it is considered a noninvasive marker for areas of slow conduction requisite for reentrant arrhythmia. Late potentials are not usually found in patients with idiopathic ventricular tachycardia (VT); nevertheless, fragmented electrograms are often recorded in those patients during endocardial mapping. The purpose of this study was to investigate the spectral content of the signal-averaged ECGs with use of fast Fourier transform analysis (FFT) in patients with idiopathic VT of left ventricular origin. Methods and ResultsSignal-averaged ECGs were recorded in 12 patients with idiopathic VT originating from the left ventricle (group 1) and 25 age-matched normal volunteers (group 2). Frequency analysis with FFT1 was performed with a Blackman-Harris window in a segment length of 120 msec from 40 msec before the end of the QRS complex, and the frequency spectrum was displayed in a three-dimensional graph. Area ratio 1 (area of 20–50 Hz/area of 10–50 Hz) and area ratio 2 (area of 40–100 Hz/area of 0–40 Hz) were calculated in all subjects. Late potentials defined by the time domain were negative in all subjects. The area ratios of group 1 were significantly higher than those of group 2. High-frequency components in the three-dimensional graph were confined within the QRS complex. ConclusionsThese results suggest that frequency analysis of signal-averaged ECGs with FFT is an available method for detecting the high-frequency component within the QRS complex in some patients with idiopathic VT of left ventricular origin.