Setsuya Okubo

Effects of Aging on Left Ventricular Relaxation in Humans Analysis of Left Ventricular Isovolumic Pressure Decay

BACKGROUND Some experimental studies in animals have shown that myocardial relaxation is prolonged with aging. However, it is not known whether aging alters ventricular isovolumic relaxation in human subjects. METHODS AND RESULTS We analyzed high-fidelity left ventricular pressures, measured by use of a catheter-tipped manometer, and biplane left ventriculograms in 55 normal subjects who underwent diagnostic cardiac catheterization but who were found to have normal cardiac anatomy and function. There were 38 men and 17 women, ranging in age from 20 to 77 years. Left ventricular isovolumic relaxation was assessed by the exponential time constants of isovolumic pressure decay with (Tb) and without (Tw) an asymptote pressure. Left ventricular volume, ejection fraction, and wall thickness or mass were calculated from left ventricular angiograms. Neither of the time constants of left ventricular relaxation correlated with age (Tb: r = .001 to .10, P = NS: Tw: r = .02 to .05, P = NS). Left ventricular systolic function (ie, ejection fraction and end-systolic volume index), heart rate, and left ventricular wall thickness or mass, which are major hemodynamic determinants of left ventricular relaxation, were not significantly affected by aging. The multivariate analysis of age and hemodynamic variables against the time constants of left ventricular relaxation also indicated that no significant relation was found between age and left ventricular relaxation. CONCLUSIONS In the absence of coronary artery disease, systemic hypertension, left ventricular systolic dysfunction, or hypertrophy, left ventricular relaxation assessed by the time constant of isovolumic pressure decay remains essentially unchanged with normal adult aging, at least until the eighth decade.

Electrophysiological features of Atrial tachycardia arising from the atrioventricular annulus

MATSUOKA, K., et al.: Electrophysiological Features of Atrial Tachycardia Arising from the Atrioven‐tricular Annulus. Atrial tachycardia (AT) arises from various sites in the atrium and the mechanisms are nonuniform. McGuire et al. reported that the cells around the atrioventricular annuli resembled nodal cells in their cellular electrophysiology. The purpose of this study was to delineate the electrophysiological features of AT arising from the atrioventricular (AV) annulus (AVAT). The study included five patients with six AVATs that were abolished by the radiofrequency energy delivery. The location of the AV annuli was defined by using the AV ratio of the local electrograms and the amplitude of the ventricular electrograms, in addition to the anatomic findings under fluoroscopic guidance. The tachycardia cycle lengths were 403 ± 117 ms. An AV ratio of the electrograms at the successful ablation sites was 0.4 ± 0.4 at the tricuspid annulus and 1.5 ± 0.3 at the mitral annulus. Small doses (mean 3.2 ± 1.8 mg) of adenosine triphosphate could terminate all the tachycardia episodes for five of the ATs without the development of AV nodal conduction block. The successful ablation sites were located at the right mid‐septum in 1 AT, right posteroseptum in 2 ATs, right posterolateral region in 1 AT, and left anteroseptum in 2 ATs. These findings suggest that the cells with nodal‐type action potentials around both annuli might play an important role in the genesis of AVAT.

Changes in autonomic nervous activity after catheter ablation of atrial tachycardia arising from the atrioventricular annulus

Radiofrequency (RF) catheter ablation of supraventricular tachycardias causes local parasympathetic denervation. This study used heart rate variability (HRV) to evaluate the effects of ablation of atrial tachycardia (AT) arising from the atrioventricular annulus (AVAT) on autonomic function. Ten patients with AVAT were referred for ablation (group AT) and compared with 8 patients with paroxysmal atrial fibrillation who underwent PV isolation (group Paf), and 13 patients with idiopathic ventricular tachycardia successfully treated by ablation (group VT). Time and frequency domain analysis of HRV on 24‐hour ambulatory ECG recordings was performed before and after ablation. Root mean square of differences of consecutive N‐N intervals (rMSSD), percentage of difference between consecutive N‐N intervals >50 ms (pNN50), and high frequency (HF) component were measured to examine the effects on parasympathetic nerve activity. In group AT, rMSSD, pNN50, and HF decreased significantly after ablation, while they remained unchanged in group Paf and group VT. These observations suggest that parasympathetic denervation after ablation was limited to group AT, and depended on the site of energy delivery along the tricuspid or mitral valve as opposed to atrial or ventricular muscle.

Effects of aliskiren on blood pressure and humoral factors in hypertensive hemodialysis patients previously on angiotensin II receptor antagonists.

Abstract Background: A direct renin inhibitor (DRI), aliskiren, may be effective for blood pressure (BP) control in hemodialysis patients. However, it is unclear whether aliskiren has a greater beneficial effect on BP and humoral factors than angiotensin II receptor antagonists (ARBs) in hypertensive patients on hemodialysis. Methods: Eighteen hemodialysis patients (58 ± 14 years) on the recommended dose of an ARB were prospectively randomized into two groups: ARB and DRI groups. Patients in the ARB group continued taking their previous ARB, whereas those in the DRI group switched to aliskiren (150 mg/day) for 12 weeks. Baseline measurements of BP and humoral factors such as plasma renin activity (PRA), plasma aldosterone concentration (PAC) and brain natriuretic peptide (BNP) were performed. Measurements were repeated every 4 weeks. Results: At baseline, no differences were observed in age, gender or BP between the two groups. Systolic BP was unaffected by treatment in either groups (group effect, p = 0.26; time effect, p = 0.38; group × time effect, p = 0.24). PRA decreased in DRI (p ≦ 0.02, group effect, p = 0.65; time effect, p = 0.13; group × time effect, p = 0.048), but not in ARB (p ≧ 0.94). PAC increased only in DRI (p ≦ 0.03), whereas BNP was unaffected in either group. Conclusion: Aliskiren at a dose of 150 mg/day had a similar effect on BP compared with ARBs, but significantly lowered PRA.

Effect of Left Atrial-Coronary Sinus Musculature Connections on the Coronary Sinus Activation Pattern via Retrograde Conduction in Patients with WPW Syndrome

AbstractBackground: Double potential (DP) activation patterns observed in coronary sinus (CS) electrograms recorded during left lateral atrial pacing, were explained by an initial low-frequency left atrial (LA) activation potential and secondary high-frequency CS musculature activation potential in canine hearts. Moreover, the connections between the LA and CS musculature vary greatly in size and location in the human heart. The purpose of this study was to investigate the relationship between the CS activation pattern during retrograde conduction via an accessory pathway (AP) and the location of left-sided APs. Methods and Results: Fifty-one patients (31 males, mean age 48.6 years) who underwent radiofrequency catheter ablation of left-sided APs were divided into two groups according to the successful ablation site. The CS electrograms during retrograde AP conduction were classified into 3 types; single, fractionated, and DP activation patterns. A DP pattern was identified in 10 of 12 patients (83.3%) with posteroseptal to posterolateral APs, and in particular, 9 had a divergent sequence. Twenty-six of 39 patients (66.7%) with lateral to anterolateral APs, demonstrated a single pattern. The number of radiofrequency applications was significantly higher in patients with a DP pattern than in those with a single pattern (3.4 ± 3.3 vs. 7.8 ± 6.8, p < 0.01). Conclusion: Misleading information obtained when mapping for optimal ablation sites might result from DP patterns with a divergent sequence produced by discrete muscular connections between the LA and CS musculature. Ablation around left posterior APs may require meticulous observation of the CS activation patterns.

Kidney-protective effects of azelnidipine versus a diuretic in combination with olmesartan in hypertensive patients with diabetes and albuminuria: a randomized study

BACKGROUND A thiazide diuretic used in combination with benazepril is superior to amlodipine plus benazepril in reducing albuminuria in hypertensive patients with diabetes. However, calcium channel blockers have diverse characteristics. Thus, we investigated whether combining an angiotensin receptor blocker with either azelnidipine or a thiazide diuretic produced similar reductions in albuminuria in hypertensive diabetic patients for the same levels of blood pressure achieved. METHODS Hypertensive patients with type 2 diabetes and albuminuria (30-600 mg/g creatinine) under antihypertensive treatment (mean age 67.0±7.6 years) were instructed to stop all antihypertensive treatment and take a combination of olmesartan (20 mg/day) and amlodipine (5 mg/day) for 3 months (run-in period). Then, patients were randomly assigned to receive either olmesartan plus azelnidipine (16 mg/day; n=71) or olmesartan plus trichlormethiazide (1 mg/day; n=72) for an additional 6 months. The primary end point was urinary excretion of albumin at 6 months after randomization. RESULTS At the time of randomization, urinary albumin was 116.0 and 107.8 mg/g creatinine (geometric mean) in the azelnidipine and diuretic arms, respectively, and was reduced to a similar extent [79.8 (95% confidence interval 66.4-96.0) and 89.7 (74.6-107.7) mg/g creatinine, respectively, after adjustment for baseline values]. Blood pressure did not differ between the two groups throughout the study period. CONCLUSIONS Azelnidipine is equally effective as a thiazide diuretic in reducing urinary albumin when used in combination with olmesartan.

Increased double product on Monday morning during work

It has been reported that cardiovascular events often occur on Monday morning, especially in the young working population. Because hypertension is a major cardiovascular risk, we examined whether blood pressure was elevated on Monday, especially in the morning during work. However, there were no weekly rhythms in blood pressure itself. Instead, we found significant interactions between the double product (systolic blood pressure × heart rate) and weekly (high on Monday) and circadian (high in the morning) rhythms. Further studies are required to determine whether Monday morning preference in cardiovascular events is caused by increased double product.

Radiofrequency catheter ablation for intra-atrial reentrant tachycardia after surgery of atrial septal defect: use of isopotential mapping (QMS system) to demonstrate bidirectional complete block.

A 51 year-old Japanese man who had undergone surgical correction of an atrial septal defect at the age of 18 years old was referred to our institute for evaluation of his atrial arrhythmia. The conventional electrophysiological study was combined with a new technique utilizing an isopotential and isochronal mapping system (QMS) to visualize the electrical signals recorded with a 64-electrode basket catheter. Using this system, an intra-atrial reentrant tachycardia (IART) was demonstrated. The isopotential map recorded with the QMS (QMS-isoP) rapidly revealed a clockwise global reentrant circuit in the mid free wall of the right atrium and a narrowest activation isthmus between the lower end of the atriotomy scar and the inferior vena cava (IVC). After confirming entrainment with concealed fusion at the lower end of the atriotomy scar, radiofrequency energy was delivered linearly from this site to the IVC by slowly dragging the catheter. The elimination of the IART was defined by the QMS-isoP which demonstrated bidirectional block during pacing from both sides of the ablated linear lesion. The conventional technique of entrainment with concealed fusion combined with the QMS-isoP may result in a highly sophisticated method for identifying global reentrant circuits and for defining bidirectional block after eliminating the IART.

Smooth Muscle Myosin Phosphatase

The endogenous phosphatase of chicken gizzard actomyosin contains two subunits of 58 and 38kDa, respectively, as we showed previously. This phosphatase was active with both isolated myosin light chain and intact myosin that had been phosphorylated by myosin light chain kinase as substrates, suggesting that phosphorylated myosin might be a substrate in situ. The 38-kDa subunit was identified as a catalytic subunit of a type lδ protein phosphatase (PP1δc), and the 58-kDa subunit was revealed to play a regulatory role in the binding of myosin. Studies with a monoclonal antibody (MoAb) to the 58-kDa subunit revealed that the 58-kDa protein was a product of proteolytic degradation of a protein of 130–133 kDa. The distribution of the 130-kDa component in chicken tissues was examined with the MoAb. An immunoreactive band of appropriate mobility was detected in analyses of all tissues except liver and skeletal muscle, and higher concentrations of the 130-kDa component were found in samples of smooth muscle. Intact myosin phosphatase was purified from chicken gizzard with the MoAb as probe. The purified holoenzyme was a heterotrimer that consisted of PP1bc (38kDa) and regulatory subunits of 130/133 kDa and 20 kDa. cDNA clones encoding the 130/133-kDa subunits were isolated from chicken gizzard cDNA libraries. The isolation of overlapping clones suggested the presence of the two isoforms. There were open reading frames of 2889 and 3012 bases that encoded proteins of 963 and 1004 amino acids with masses of 106.7 and 111.6 kDa, respectively. The deduced sequence of the larger isoform was 123 nucleotides longer in its central coding region than the other isoform. The characteristic N-terminal region was almost entirely composed of eight tandem repeats of 33 amino acids, which have been called the cdcl0/SWI6, or ankyrin, repeat. The 58-kDa fragment with the ability to bind to both myosin and the catalytic subunit was revealed to be located in the N-terminal half of the molecule. A cDNA clone (1338 bp) encoding chicken gizzard PPlδc was also isolated and sequenced. This clone contained an open reading frame that encoded a protein of 327 amino acids with a calculated molecular mass of 37kDa. Its amino acid sequence was identical to the analogous isoform from rats. These results suggest that smooth muscle myosin phosphatase is a novel holoenzyme composed of a type 1δ protein phosphatase and unique regulatory subunits.

Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension

This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker. The primary end point was the mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks. An efficacy analysis was performed in 195 patients (98 in the eplerenone group and 97 in the thiazide group). Systolic and diastolic blood pressures at 48 weeks were similar in the two groups. The mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks was similar in the two groups (P=.804). In the safety analysis, the withdrawal rates for adverse events were similar in both groups. The antialbuminuric effects and safety of eplerenone therapy were similar to those of thiazide diuretics when combined with an angiotensin II receptor blocker in patients with hypertension and albuminuria.