Search

This study used body surface mapping to evaluate the ventricular repolarization process in the absence of delta waves in 13 patients with the intermittent Wolff-Parkinson-White (WPW) syndrome. The findings were compared with data from 30 normal individuals and 50 patients with the overt WPW syndrome. The QRST isointegral maps of patients with the overt WPW syndrome exhibited abnormal areas and the QRST departure maps showed a peculiar distribution to each accessory pathway site. The QRST isointegral map exhibited abnormal areas in 11 of the 13 cases (85%) of the intermittent WPW syndrome in the absence of delta waves. In 8 of these 11 cases (73%), the distribution of the departure map resembled that in the overt WPW syndrome. These findings suggest that abnormal ventricular repolarization due to cardiac memory is present in patients with the intermittent WPW syndrome even in the absence of delta waves.

1. To determine the contribution of the various phosphodiesterase (PDE) isozymes to the regulation of the L-type calcium current (ICa(L)) in the human myocardium, we investigated the effect of selective and non-selective PDE inhibitors on ICa(L) in single human atrial cells by use of the whole-cell patch-clamp method. We repeated some experiments in rabbit atrial myocytes, to make a species comparison. 2. In human atrial cells, 100 microM pimobendan increased ICa(L) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4 +/- 45.0% (n = 15), with the concentration for half-maximal stimulation (EC50) being 1.13 microM. ICa(L) was increased by 100 microM UD-CG 212 by 174.5 +/- 30.2% (n = 10) with an EC50 value of 1.78 microM in human atrial cells. These two agents inhibit PDE III selectively. 3. A selective PDE IV inhibitor, rolipram (1-100 microM), did not itself affect ICa(L) in human atrial cells. However, 100 microM rolipram significantly enhanced the effect of 100 microM UD-CG 212 on ICa(L) (increase with UD-CG 212 alone, 167.9 +/- 33.9, n = 5; increase with the two agents together, 270.0 +/- 52.2%; n = 5, P < 0.05). Rolipram also enhanced isoprenaline (5 nM)-stimulated ICa(L) by 52.9 +/- 9.3% (n = 5) in human atrial cells. 4. In rabbit atrial cells, ICa(L) at +10 mV was increased by 22.1 +/- 9.0% by UD-CG 212 (n = 10) and by 67.4 +/- 12.0% (n = 10) by pimobendan (each at 100 microM). These values were significantly lower than those obtained in human atrial cells (P < 0.0001). Rolipram (1-100 microM) did not itself affect ICa(L) in rabbit atrial cells. However, ICa(L) was increased by 215.7 +/- 65.2% (n = 10) by the combination of 100 microM UD-CG 212 and 100 microM rolipram. This value was almost 10 times larger than that obtained for the effect of 100 microM UD-CG 212 alone. 5. These results imply a species difference: in the human atrium, the PDE III isoform seems dominant, whereas PDE IV may be more important in the rabbit atrium for regulating ICa(L). However, PDE IV might contribute significantly to the regulation of intracellular cyclic AMP in human myocardium when PDE III is already inhibited or when the myocardium is under beta-adrenoceptor-mediated stimulation.

We studied the influence of early coronary reperfusion on QT interval dispersion in patients with acute myocardial infarction (MI). There were 54 males and 18 females with a mean age of 60 +/- 10 years. Of the 51 patients with recanalization of the infarct related vessel in the recovery phase, 28 (group A) had early coronary reperfusion (5.5 +/- 2.7 hours), 23 other patients (group B) were not confirmed with early coronary reperfusion. Twenty-one patients (group C) did not undergo recanalization of the infarct related vessel in the recovery phase. Corrected QT (QTc) maximum, QTc minimum, and QTc dispersion calculated as the difference between the maximum and minimum QTc intervals, were compared among these three groups at both acute and recovery phase. At the acute phase after MI, there were no significant differences in the QTc maximum, QTc minimum, QT dispersion, and QTc dispersion among these three groups. At the recovery phase after MI, there were also no significant differences in the QTc maximum and QTc minimum. However, there were significant differences in the QT dispersion (0.035 +/- 0.010 in group A, 0.049 +/- 0.015 in group B, and 0.061 +/- 0.031 s in group C, respectively; P = 0.0001), and QTc dispersion (0.038 +/- 0.012 in group A, 0.050 +/- 0.015 in group B, and 0.063 +/- 0.032 s in group C, respectively; P = 0.0003) among the three groups. Comparison of QTc dispersion between acute and recovery phase revealed significant reduction from acute to recovery phase in group A. The number of premature ventricular contraction was lower in group A and B than group C. In summary, early coronary reperfusion may reduce electrophysiological instability by reducing QT dispersion in the recovery phase after acute MI.

We evaluated the effects of disopyramide in terms of the balance between myocardial oxygen supply and demand in patients with hypertrophic obstructive cardiomyopathy (HOCM). The myocardial oxygen supply was evaluated by measuring coronary flow velocity and the myocardial oxygen demand was assessed by the pressure-volume area (PVA). The time velocity integral of coronary flow did not change significantly (20 +/- 6 to 21 +/- 8 cm), but the peak left ventricular pressure and left ventricular external work decreased significantly (206 +/- 44 to 157 +/- 37 mmHg, P0.001; 1.09 +/- 0.33 to 0.80 +/- 0.23 J/beat, P0.001) after disopyramide administration. From theoretical analysis using these data, we concluded that disopyramide improves the myocardial oxygen supply-demand balance in patients with HOCM.

The electrophysiological effect of extracellular ATP was investigated in voltage-clamped single cells from the rabbit sino-atrial node. External 0.5 mM ATP consistently activated a time-independent, weakly inwardly rectifying current (2.26 +/- 0.14 pA/pF at -100 mV, n = 23). This external ATP-activated current increased in a dose-dependent manner over the concentration range 0.01 to 1 mM ATP. However, non-hydrolysable ATP analogs (a, beta-methylene ATP and beta,r-methylene ATP) failed to activate this current. Moreover, adenosine, adenosine monophosphate and adenosine diphosphate were all ineffective in eliciting the ATP-activated current over the concentration range 0.5 to 1 mM, suggesting that it is regulated via the P2-purinoreceptor. The permeability sequence for the ATP-activated current among different cations (determined from reversal potential measurements) was 1.09: 1: 1: 0.24: 0.22 for K+, Na+, Cs+, Tris and N-methyl-D-glucamine. The current component was not affected by substitution of external Cl- by aspartate or by the application of a stilbene-derivative Cl- channel blocker. Thus, the ATP-activated current in rabbit sino-atrial node cells was non-selective for monovalent cations, and could be carried by large molecular ions, such as N-methyl-D-glucamine or Tris. We suggest that it might make some contribution to the chronotropic effects seen on release of transmitters from autonomic nerve endings in the heart.

Background Anxiety is often present in patients with depression. The aim of this study was to evaluate the impact of clustered depression and anxiety on mortality and rehospitalization in hospitalized patients with heart failure (HF). Methods A total of 221 hospitalized patients with HF, who completed the questionnaires, were analyzed in this prospective study (mean age 62 ± 13 years; 28% female). One-third patients had implanted cardiac devices. Depression was defined as a Zung Self-Rating Depression Scale index score of ≥60 and anxiety was defined as a State-Trait Anxiety Inventory score of ≥40 (male) or ≥42 (female). The primary outcome was the composite of death from any cause or rehospitalization due to worsened HF and refractory arrhythmia. Results Of the 221 HF patients, 29 (13%) had depression alone, 80 (36%) had anxiety alone, and 46 patients (21%) had both depression and anxiety. During an average follow-up of 41 ± 21 months, patients with depression alone and those with clustered depression and anxiety were at an increased risk of the primary outcome [hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.17–4.28, p = 0.01 and HR 2.75, 95% CI: 1.51–4.99, p = 0.01, respectively] compared to patients with no symptoms. Multivariate analysis after adjusting for age, gender, New York Heart Association functional class, B-type natriuretic peptide, device implantation, renal dysfunction, and left ventricular dysfunction showed clustered depression and anxiety, but not depression alone or anxiety alone, was an independent predictor of the primary outcome (HR 1.96, 95% CI: 1.00–3.27, p = 0.04). Conclusions Our results showed that clustered depression and anxiety were associated with worse outcomes in patients with HF.

Background The accuracy of electrocardiogram-gated CT for diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is uncertain. Objective We propose a comprehensive system for scoring characteristic CT findings to diagnose ARVC/D and discuss its utility. Methods Seventy-seven patients (mean age, 43.1 years; 48 male) diagnosed with ARVC/D or with suspected ARVC/D on the basis of ventricular tachyarrhythmias underwent CT with and without contrast enhancement. We retrospectively graded characteristic CT findings (fatty tissue, bulging appearance, and dilatation of the right ventricle) as minor (1 point) or major (2 points) and then validated our scoring system’s utility for diagnosing ARVC/D with the use of the modified 2010 Task Force criteria as the reference standard. Results We diagnosed 27 of 77 patients with ARVC/D (23 definite, 4 borderline), observing each CT finding more often in patients with ARVC/D than in patients without ARVC/D: fatty tissue, 74.1% versus 12.0%; bulging appearance, 74.1% versus 34.0%; and RV dilatation, 92.6% versus 44.0%. However, observation of each finding in both groups could cause false positive diagnosis. Recursive partitioning analysis showed the superiority of our CT scoring system over methods that used each CT finding and CT findings without fatty tissue for distinguishing ARVC/D and non-ARVC/D. For overall (definite and borderline) and definite ARVC/D diagnosis, sensitivities were 77.8% and 87.0%, specificities were 96.0% and 94.4%, positive predictive values were 91.3% and 87.0%, negative predictive values were 88.9% and 94.4%, and accuracies were 89.6% and 92.2%, respectively. Conclusions Our CT scoring system showed excellent diagnostic ability and might aid differentiation of ARVC/D from ventricular tachyarrhythmias.

Abstract Anion conductance is known to be activated by mechanical stimulation, such as osmotic cell swelling or cell inflation via the patch pipette, of canine or rabbit cardiac myocytes. The effects of mechanical stimulation on time-dependent currents, however, remain unsettled. Using the whole-cell voltage-clamp method, we have found that mechanical stimuli enhance the L-type Ca 2+ current (I Ca,L ) in rabbit cardiac myocytes. At every membrane potential, I Ca,L was reversibly increased by osmotic cell swelling and by cell inflation caused by applying a positive pressure of 10 to 15 cm H 2 O via the patch pipette. I Ca,L was increased during cell inflation by 37±21% (mean±SD, n=17) in atrial cells and by 37±8% (n=7) in sinoatrial node cells in solution containing 2 mmol/L Ca 2+ . The current-voltage relationship, the inactivation time constant, the steady state inactivation curve, and the conductance properties of I Ca,L were all virtually unaffected by mechanical stimulation except for the open probability, which appears to increase. The increase in I Ca,L was not dependent on protein kinase A, since an inhibitor peptide of cAMP-dependent protein kinase failed to prevent the increase in I Ca,L during mechanical stimuli (n=5). The increase in I Ca,L caused by cell inflation was unaffected by the chelation of intracellular Ca 2+ by the addition of 10 mmol/L EGTA or 10 mmol/L BAPTA to the pipette solution, suggesting that the effect was not mediated by changes in intracellular Ca 2+ . Thus, mechanical stimulation due to cell swelling or inflation may itself directly increase I Ca,L in rabbit cardiac myocytes.

心臓突然死の80～90%は心室細動(VF)ないし心室頻拍(VT)によると考えられているが,抗不整脈薬やカテーテルアブレーションや手術によるVT/VFの予防には限界がある.そのVT/VFによる突然死の予防を目的として電気的除細動器を体内に植込み, VT/VFを自動的に感知し,作動させるという植込み型除細動器(ICD)は画期的な治療法である. 1980年の臨床応用に始まり現在は第3世代の時代となり,欧米では植込み症例数は年間数万人に達している.わが国では1990年から臨床試験が行われ, 1996年4月ようやく保険適用が認められており,今後, VT/VFによる突然死予防の最終的治療法として普及していくものと考えられる.

Overdrive suppression test (OST) におけるSRTの反応から, 洞不全症候群 (SSS) をlow-rate反応群, high-rate反応群, 正常反応群, atrial standstill群の4群に分類し, OSTによるSSSの分類の意義を検討した.臨床所見および電気生理学的から, SSSの病変は, low-rate反応群では, 洞結節を含む心房筋にあり, high-rate反応群では洞房接合部に限局し, 正常反応群では洞結節に限局し, atrial standstill群では洞結節・洞房接合部・心房筋・His-PurkinJe系と広範に存在することが推測された.さらにSSSのOSTに対する反応の経時変化からは, 正常反応群→high-rate反応群, high-rate反応群→low-rate反応群, low-rate反応群→atrial standstill群への移行する症例がみられた.即ち, SSSでは, 洞結節から心房筋への連続性かつ進行性の病態を示す症例が存在し, SSSを洞結節, 洞房接合部に限局した病態から, 高度の心房筋病変を伴うatrial standstillに至る連続した病態として捉えることが可能と考えられた.

Accessory mitral valve (AMV) is a rare cause of left ventricular outflow tract (LVOT) obstruction and is extremely rare in adults. We report a case of an older adult with an AMV that caused severe LVOT obstruction. A parachute-like piece of tissue (the AMV) protruding into the LVOT during systole was first detected in a 45-year-old woman by echocardiography. Because the pressure gradient and dyspnea gradually progressed, she finally underwent a successful operation for removal when she was 48 years old.

We report four non-insulin-dependent diabetic (NIDDM) patients accompanied by a unique combination of sick sinus syndrome (SSS) and hyperinsulinemia of unknown etiology. SSS of all four cases was due to sinus arrest in association with paroxysmal atrial fibrillation (Rubenstein-III). Of special interest is that one patient showed a high prevalence of SSS and NIDDM among her close relatives. Hyperinsulinemia of moderate degree was seen at fasting state or after carbohydrate ingestion in the absence of obesity. The resistance to the action of insulin on glucose metabolism which was evaluated in three patients by the euglycemic hyperinsulinemic clamp study was found to be comparable to the lowest quartile level for common NIDDM patients. Because insulin is a physiological regulator of cell-membrane Na+/K+-ATPase, we speculate that malfunction of the sinus node automaticity may be caused by chronic exposure to hyperinsulinemia secondary to insulin resistance in these NIDDM patients.

近年, 各種抗不整脈剤の開発に伴い, ヒト心筋細胞の活動電位を構成するイオン電流の役割がより注目されるようになった.心筋細胞におけるクロール (Cl) 電流は, 特に活動電位の再分極相を形成する電流として重要であると考えられているが, ヒト心筋細胞において, どのようなCl電流が存在するか, 否かの報告はいまだに認められない.今回はヒト心房筋細胞にパッチクランプ法を応用して, Cl流の解析を行った.この結果, ヒト心房筋細胞には, モルモットや家兎心室筋細胞で認められるcyclic-AMP依存性Cl電流や細胞内Ca依存性Cl電流は認められず, 細胞腫大や伸展に伴って活性化されるCl電流のみが存在することが示唆された.

Biventricular pacing is currently being explored as a means to improve cardiac function among patients with congestive heart failure. The mechanism of efficacy of this therapy is still unknown, but in patients with left bundle branch block, biventricular pacing resolves ventricular dyssynchrony and ameliorates myocardial wall function. We present a successful aortic valve replacement and biventricular pacemaker implantation for a case of aortic regurgitation with severe left ventricular dysfunction and left bundle branch block.

For stable patients suspected of having coronary artery disease (CAD), myocardial perfusion imaging (MPI) or computed tomographic angiography (CT) is used for initial evaluation, while coronary angiography (CAG) is used for confirming the diagnosis. The choice of the initial diagnostic test might influence the treatment strategy.Patients scheduled for MPI, CT, or CAG as the initial diagnostic test were enrolled. The primary and secondary end-points were a major adverse cardiac event (MACE) and revascularization, respectively. Of the 2,878 patients enrolled, 2,825 underwent initial diagnostic tests, and 2,780 were followed up for 1.42±0.49 years. After adjustment for CAD severity, Cox proportional hazard regression analysis showed that the risk of MACE in the MPI and CT groups were similar and significantly less than that in the CAG group (hazard ratio, 0.82 vs. 2.19; 95% confidence interval [CI], 0.43-1.58 vs. 1.40-3.44). Furthermore, the rate of revascularization in the MPI group was less than that of the CT (odds ratio, 1.62; 95% CI, 1.20-2.18) and CAG (odds ratio, 5.36; 95% CI, 4.07-7.05) groups.These data indicate that for stable patients with suspected CAD, the use of MPI or CT as the initial diagnostic test was associated with better prognosis than the use of CAG, and that initial evaluation with MPI was associated with a lower requirement of coronary intervention.

Recent studies have suggested that esmolol is the first choice for rate control in patients with postoperative atrial fibrillation (AF) after coronary artery bypass surgery, but side-effects of esmolol such as hypotension are problematic. To overcome this problem, landiolol, an ultra-short-acting β(1)-blocker with a less negative inotropic effect than esmolol, has been developed. The aim of the present study was to investigate whether landiolol was effective for both rate control and conversion to normal sinus rhythm (NSR).A prospective, randomized, open-label comparison between i.v. landiolol and diltiazem in patients with postoperative AF was undertaken between January 2008 and June 2009 in Japan. Of 335 patients included in the analysis, 71 patients went into AF. Among these 71 patients, conversion to NSR within 8h after onset of AF occurred in 19 of 35 patients (54.3%) in the landiolol group vs. 11 of 36 patients (30.6%) in the diltiazem group (P0.05). The incidence of hypotension was lower in the landiolol group (4/35, 11.4%) compared with the diltiazem group (11/36, 30.6%; P0.05). The incidence of bradycardia was also lower in the landiolol group (0%) compared with the diltiazem group (4/36, 11.1%; P0.05).Landiolol is more effective and safer than diltiazem for patients with postoperative AF after open heart surgery.

心筋細胞はさまざまな生理的, 非生理的条件下において機械的刺激を受けやすい組織である.特に, 洞結節細胞は伸展刺激によって陽性変時作用を示すことが知られているが, その機序に関する詳細な検討はなされていない.今回は, 家兎単一洞結節細胞を用いて伸展刺激に伴う電位および電流の変化を検討した.単一洞結節細胞にパッチ電極を用いてwhole-cell voltage clampを行ない, 電極を介した伸展刺激を加えると, 時間非依存性の膜コンダクタンス増大が認められた.この電流の逆転電位はClの平衡電位に従うことからC1電流であると確認された.洞結節細胞の活動電位は伸展刺激により, 膜電位の脱分極とともに心拍数の増大が認められ, 電流変化もClの平衡電位と一致したため, 伸展誘発性Cl電流が伸展刺激に伴う陽性変時作用の一機序として関与する可能性が示唆された.

心不全症例における死亡の約40%は突然死である.心不全には不整脈を増悪あるいは誘発させる多くの因子が存在し,心室性不整脈が高頻度に認められ,突然死は心室細動/持続性心室頻拍によると考えられている.近年,抗不整脈薬療法は著しい進歩をとげたが, class I薬による催不整脈作用と陰性変力作用が指摘され,その功罪が問い直されている.そしてclass III薬特にアミオダロンの突然死予防効果が注目されている.またβ遮断薬, ACE阻害薬及び抗アルドステロン薬の有効性が期待されている.さらに植込み型除細動器などの非薬物療法も著しい進歩をとげている.

陳旧性心筋梗塞 (OMI) と特発性心室頻拍 (VT) においてQRST isointegral mapと心室ペーシングによるVTの易誘発性との関連について検討した.対象は持続性VT (sVT) を伴うOMI 21例, 特発性sVT 26例および健常者40例であり, 体表面電位図を記録しQRST isointegral mapを作成した.OMIと特発性sVTに対してVT誘発試験を施行し, VTの易誘発性について検討した.多双極子性mapの頻度は, OMI 62%, 特発性sVT 8%, 健常者0%であり, OMIはほかの2群に比べ高頻度であった (p

The tissue distribution of amiodarone and desethylamiodarone, its active metabolite, was examined in an autopsied case, an 85-year-old man, with arrhythmogenic right ventricular cardiomyopathy (ARVC) who had been receiving amiodarone for 4 years. High concentrations of amiodarone, a very highly lipophilic compound, were found in adipose and bone marrow tissues. Despite a low dose (100 mg daily), the concentrations of amiodarone were higher in the epicardial fat (570.4 microg/g) and in the right atrium (165.3 microg/g) than previously reported in patients with other cardiac diseases. The ratios of amiodarone/ desethylamiodarone concentrations in both tissues were1. This unique distribution demonstrates the involvement of histological characteristics of ARVC, such as fatty replacement of myocardium. We anticipate that a low dose of amiodarone would be effective in preventing arrhythmia in some patients with ARVC.

Several studies have suggested that depression poses a risk in cardiovascular patients. The aim of the present study was to evaluate the prevalence of depression and its effect on cardiovascular events and mortality in Japanese inpatients with cardiovascular disease.A total of 505 patients hospitalized with cardiovascular disease (28% female; mean age, 61 ± 14 years; 31% ischemic heart disease; 47% New York Heart Association [NYHA] class II-IV; 25% implantation of pacing devices) were enrolled in the present prospective observational study. The Zung Self-Rating Depression Scale (SDS) was used to screen for depression. The primary outcome was the time to death or cardiovascular event, and the secondary outcome was death. In total, 109 patients (22%) were diagnosed with depression (Zung SDS index score ≥ 60). NYHA class III/IV, defibrillator implantation, and being unmarried were independently associated with depression. During an average follow-up period of 38 ± 15 months, 92 patients (18%) reached the primary outcome. There was a higher incidence of the primary outcome in patients with depression than in those who were not depressed (P0.01). Depressed patients had a significantly higher rate of mortality than non-depressed patients (P0.01). Depression was an independent predictor of the primary outcome (hazard ratio, 2.25; 95% confidence interval: 1.30-3.92, P0.01).Depression was not uncommon in Japanese inpatients with cardiovascular disease and was associated with cardiovascular outcomes.

We describe a 62-year-old man with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis, which involved the heart, lung, and kidneys. The patient's care was complicated by total occlusions of the brachiocephalic and right renal arteries and a stenosis of the left renal artery. Involvement of large-sized vessels has not been reported in patients with perinuclear-antineutrophil cytoplasmic antibodies-associated vasculitis.

It is unclear whether depression persists in patients with implantable cardioverter defibrillators (ICDs). We evaluated the prevalence and persistence of depression in ICD patients over a 2-year period.The study included 90 consecutively hospitalized patients. Patients underlying heart disease was 24% coronary artery disease, 29% idiopathic dilated cardiomyopathy, 24% hypertrophic cardiomyopathy, 13% idiopathic VF/long QT syndrome and miscellaneous conditions 11%. A secondary indication for ICD implantation was present in 20 patients. All patients completed the Zung Self-Rating Depression Scale (SDS) at study baseline and at the their routine follow-up visit 2 years after the baseline questionnaire. Delivery of ICD therapies was tracked throughout the 2 years.Depression, indicated by a Zung SDS index score exceeding 60, was present in 29 (32%) of patients at study baseline. Depression was present in 11/51 (21%) patients scheduled to undergo ICD implantation, 2/2 (100%) patients whose device was upgraded to a CRT-D, 3/14 (21%) patients who had undergone pulse generator replacement, 7/14 (50%) patients who experienced electrical storm and 6/9 (66%) patients hospitalized with acute decompensated heart failure. NYHA functional class III was significantly associated with depression at baseline (HR 6.7, 95% CI 1.68-27.2, p = 0.0007). No differences were noted for female gender, demographics, β-blocker use, or LVEF ≤35% (p = ns). Depression was present in 25 (28%) of patients at 2 years follow-up, persisting in 21 (72%) of patients whose Zung SDS scores were elevated at baseline. The median time from ICD shock therapy to completion of the 2 year questionnaire was 9 months (range, 1-22). Patients who were depressed (9/25, 36%) experienced more shocks than non-depressed patients (6/65, 9%) after 2 years (p = 0.002).Depression is not uncommon among patients who meet criteria for ICD implantation and persists over time particularly when functional status is impaired. Depression is associated with a higher incidence shock therapy.

Background The effectiveness of cardiac resynchronization therapy (CRT) in preventing sudden cardiac death is controversial. Epicardial left ventricular pacing reverses the direction of activation of the left ventricular wall from the epicardium to the endocardium. We evaluated whether the interlead difference between T-peak to T-end (Tp-e) intervals determined by a 187-channel repolarization interval-difference mapping electrocardiograph (187-ch RIDM-ECG) is related to the occurrence of ventricular tachyarrhythmia requiring implantable cardioverter-defibrillator (ICD) therapy in heart failure patients receiving CRT with a defibrillator (CRT-D). Methods and Results Repolarization interval-difference mapping electrocardiograph (187-channel) was performed on 61 patients who received CRT-D. Twenty-one patients experienced appropriate ICD therapy. The interlead difference between corrected recovery time intervals was not significantly different between patients with and without appropriate ICD therapy (98 ± 24 milliseconds versus 88 ± 24 milliseconds). The interlead difference between corrected Tp-e intervals was significantly higher in patients with appropriate ICD therapy than in those without (88 ± 22 milliseconds versus 59 ± 23 milliseconds, P Conclusion The interlead difference between corrected Tp-e intervals determined by 187-ch RIDM-ECG may be related to appropriate ICD therapy in heart failure patients receiving CRT-D.

Negative inotropic agents are often administered to decrease the left ventricular (LV) pressure gradient in patients with obstructive hypertrophic cardiomyopathy (HC). Little information is available regarding comparisons of the effects on LV pressure gradient among negative inotropic agents. The present study compared the decrease in the LV pressure gradient at rest in patients with obstructive HC after treatment with pilsicainide versus treatment with disopyramide or cibenzoline. The LV pressure gradient and LV function were assessed before and after the intravenous administration of each drug. In 12 patients (group A, mean pressure gradient 90 ± 24 mm Hg), the effects of disopyramide, propranolol, and verapamil were compared. In another 12 patients (group B, mean pressure gradient 98 ± 34 mm Hg), a comparison was performed among disopyramide, cibenzoline, and pilsicainide. In group A, the percentage of reduction in the LV pressure gradient was 7.7 ± 9.9% with verapamil, 19.0 ± 20.2% with propranolol, and 58.6 ± 15.0% with disopyramide, suggesting that disopyramide was more effective than either verapamil or propranolol. In group B, the percentage of reduction in the LV pressure gradient was 55.3 ± 26.6% with disopyramide, 55.3 ± 20.6% with cibenzoline, and 54.7 ± 15.4% with pilsicainide, suggesting an equivalent effect on the LV pressure gradient for these 3 agents. In conclusion, these results indicate that the acute efficacy for the reduction of the LV pressure gradient at rest by pilsicainide (a pure sodium channel blocker) was equivalent to that of disopyramide or cibenzoline (combined sodium and calcium channel blockers). Accordingly, sodium channel blockade might be more important for reducing the LV pressure gradient at rest in patients with obstructive HC than calcium channel blockade or β blockade.

Background The long-term prognosis of diabetic patients with acute myocardial infarction (AMI) treated by acute revascularization is uncertain, and the optimal pharmacotherapy for such cases has not been fully evaluated. Methods To elucidate the long-term prognosis and prognostic factors in diabetic patients with AMI, a prospective, cohort study involving 3021 consecutive AMI patients was conducted. All patients discharged alive from hospital were followed to monitor their prognosis every year. The primary endpoint of the study was all-cause mortality, and the secondary endpoint was the occurrence of major cardiovascular events. To elucidate the effect of various factors on the long-term prognosis of AMI patients with diabetes, the patients were divided into two groups matched by propensity scores and analyzed retrospectively. Results Diabetes was diagnosed in 1102 patients (36.5%). During the index hospitalization, coronary angioplasty and coronary thrombolysis were performed in 58.1% and 16.3% of patients, respectively. In-hospital mortality of diabetic patients with AMI was comparable to that of non-diabetic AMI patients (9.2% and 9.3%, respectively). In total, 2736 patients (90.6%) were discharged alive and followed for a median of 4.2 years (follow-up rate, 96.0%). The long-term survival rate was worse in the diabetic group than in the non-diabetic group, but not significantly different (hazard ratio, 1.20 [0.97-1.49], p = 0.09). On the other hand, AMI patients with diabetes showed a significantly higher incidence of cardiovascular events than the non-diabetic group (1.40 [1.20-1.64], p < 0.0001). Multivariate analysis revealed that three factors were significantly associated with favorable late outcomes in diabetic AMI patients: acute revascularization (HR, 0.62); prescribing aspirin (HR, 0.27); and prescribing renin-angiotensin system (RAS) inhibitors (HR, 0.53). There was no significant correlation between late outcome and prescription of beta-blockers (HR, 0.97) or calcium channel blockers (HR, 1.27). Although standard Japanese-approved doses of statins were associated with favorable outcome in AMI patients with diabetes, this was not statistically significant (0.67 [0.39-1.06], p = 0.11). Conclusions Although diabetic patients with AMI have more frequent adverse events than non-diabetic patients with AMI, the present results suggest that acute revascularization and standard therapy with aspirin and RAS inhibitors may improve their prognosis.

A multicenter double-blind controlled study was conducted in 109 patients with supraventricular premature contractions (SVPC) to find an optimal dose regimen for pilsicainide hydrochloride, a new antiarrhythmic agent.Patients were administered any one of daily oral doses of 75mg (low), 150mg (intermediate) and 225mg (high) of pilsicainide hydrochloride divided into three times a day for two weeks after one to two weeks of control period.Improvement of arrhythmia was assessed by the reduction in frequency and the grade of premature contractions, and global improvement was assessed from the results of improvement of arrhythmia and subjective symptoms. In the improvement of arrhythmia as well as global improvement, the high and intermediate dose groups showed significantly higher response rate than that in the low dose group, whereas no significant difference was observed between the intermediate and high dose groups.There were no significant differences in the overall safety rating among the three dose levels. Incidence of the cases in which some problems concerning safety was pointed out in the low, intermediate and high dose groups, were 6%, 11% and 21% respectively, and no serious case was observed.The clinical usefulness of the drug was assessed, based on the results of global improvement and the overall safety. The drug was assessed to be useful or better in 29% of the patients of low dose group, 61% of intermediate dose group, 70% of high dose group. The intermediate dose group showed significantly higher usefulness rating than that in the low dose group, but no significant difference was observed between the high and intermediate dose group.In conclusion, pilsicainide hydrochloride was shown to be useful in the supraventricular premature contractions, and an optimal dose of 150mg/day was suggested.

リエントリーの形成に関与する再分極過程の不均一性とORST isointegral mapとの関係に着目し, 急性心筋梗塞63例についてORST isointegral mapを経時的に記録し同時期の重症心室性不整脈の出現の有無をみることにより, ORST isointegral mapと重症心室性不整脈との関連について検討した.マップ記録の前後24時間以内の重症心室性不整脈の出現の有無により178枚のマップをVT群39枚, 非VT群139枚に分けた.I期 (第1～3病日) では多極性マップの出現頻度および平均pint scoreについて両群に有意差はみられなかった.II期以降 (第4病日以降) では多極性マップの出現頻度はVT群57.1%, 非VT群22.9% (p

The usefulness and limitations of antiarrhythmic drugs in ventricular tachycardias (VT) associated with congestive heart failure remain uncertain. The purpose of this study is to evaluate the proarrhythmic effects of antiarrhythmic drugs in patients with refractory VT associated with left ventricular dysfunction using electrophysiologic study (EPS). Twenty-four patients with left ventricular dysfunction, defined by left ventricular ejection fraction (LVEF) lower than 40% using left ventriculography, were studied. The average LVEF was 29.5%. As for underlying heart disease, 14 had old myocardial infarction, 8 cases had dilated cardiomyopathy and 2 had aortic regurgitation. As a control to this group, 23 cases with underlying heart disease and LVEF higher than 40%, and 27 cases with no obvious heart disease were studied. We considered a drug to have proarrhythmic effects if 1) it de-creased by one the number of stimuli needed to induce VT, 2) induced non-sustained VT in the control study which changed to induced sustained VT, 3) the sustained VT or ventricular fibrillation was newly induced, or 4) the induced sustained VT which was stopped by pacing in the control study changed to induced VT which could not be terminated by pacing and required DC shock. Proarrhythmic effects were recognized in 17 of 24 cases with left ventricular dysfunction. Of the 67 drug trials, proarrythmic effects were seen in 26. Proarrhythmias were observed in 9 of 23 cases (39.1%) with organic heart disease associated with LVEF higher than 40%. In 12 of 69 drug trials (17.4%) proarrhythmias were observed. Of 27 cases with no obvious heart disease 10 cases (37%) had proarrhythmias. In 14 of 130 drug trials (10.8%), proarrhythmias were recognized. In conclusion, the incidence of ventricular arrhythmias on EPS in cases with low LVEF was 70.8%, and 33.8% in drug trial, higher than in cases with organic heart disease and LVEF higher than 40%. Although the relation to spontaneous occurrence is not always clear, the effects of antiarrhythmic drugs therapy on ventricular arrhythmias in patients with congestive heart failure needs careful consideration and should be an interesting topic for future research.

Continuous intravenous infusion of prostacyclin (epoprostenol) as a treatment for primary pulmonary hypertension (PPH) definitely improves the patient's quality of life, but few accurate parameters have been found to evaluate the efficacy of the treatment. We observed a patient with severe PPH whose plasma brain natriuretic peptide (BNP) level changed significantly as her condition and symptoms changed. Plasma BNP may be considered as one of the parameters for assessing the efficacy of prostacyclin treatment.

A 32-year-old woman was admitted with the diagnosis of congestive heart failure (CHF) without organic heart disease after peripheral blood stem cell transplantation (PBSCT) for malignant lymphoma. Various cytokines have been reported to be released from stem cells after PBSCT and some have a suppressive effect on myocardial contractility; elevated levels of cytokines have been reported in dilated cardiomyopathy (DCM) and/or CHF patients. In the present case, elevated levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) were observed, and there was a parallel relationship between the recovery of cardiac function and the decrease of these cytokines, strongly suggesting that the release of IL-6 and TNF-alpha after PBSCT might have been important in the pathogenesis of the CHF.

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

The noninvasive evaluation of ventricular T-wave alternans (TWA) in patients with lethal ventricular arrhythmias is an important issue. In this study, we propose a novel algorithm to identify T-wave current density alternans (TWCA) using synthesized 187-channel vector-projected body surface mapping (187-ch SAVP-ECG). We recorded 10 min of 187-ch SAVP-ECG using a Mason–Likar lead system in the supine position. A recovery time (RT) dispersion map was obtained by averaging the 187-ch SAVP-ECG. The TWCA value was determined from the relative changes in the averaged current density in the T-wave zone (Tpeak ± 50 ms) for two T-wave types. We registered 20 ECG recordings from normal controls and 11 ECG recordings from nine subjects with long QT syndrome (LQT). We divided LQT syndrome subjects into two groups: group 1 provided 9 ECG recordings without visually apparent TWAs, and group 2 provided 2 ECG recordings with visually apparent TWAs. The QTc interval values in the LQT groups were higher than those in the control (515 ± 60 ms in LQT G-1, 600 ± 27 ms in LQT G-2 vs. 415 ± 19 ms in control, P

近年のペースメーカ療法の進歩は著しい.生理的ペースメーカ,レート答型ペースメーカ,抗頻拍ペースメーカの開発,普及により, mortalityの改善からmorbidityの改善へと適応は拡大されている.その適応決定にあたっては医学的のみならず,社会的適応を含めて十分な検討が必要である.そして各種ペースメーカの特徴を熟知し,その有用性と限界を考慮した上で,個々の症例において最も適切な機種を選択することが重要である.

We describe a 72-year-old woman with aortic, mitral, and tricuspid valve incompetence secondary to a rheumatoid granulomata. The cardiac valvular lesions developed simultaneously and deteriorated rapidly. The patient died after a transient relief of symptoms by high dose steroid therapy.

Although sleep apnea is closely associated with cardiovascular disease, it remains underdiagnosed and undertreated. Obstructive sleep apnea elicits a cascade of harmful cardiovascular stimuli, and central sleep apnea is a prognostic factor for heart failure and may exert adverse effects on outcomes. The adverse effects of obstructive sleep apnea can promote the development of atherosclerosis and have also been implicated in the pathogenesis of cardiovascular disease. Sleep apnea characterized by variables of the autonomic nervous system may have a direct association with arrhythmia. Polysomnography with electroencephalography is the gold standard for assessing sleep apnea. Alternative methods of screening for OSA have recently become available. Continuous positive airway pressure for obstructive sleep apnea reduces cardiac risk and cardiovascular disease mortality. Targeting sleep apnea in the primary and/or secondary prevention of cardiovascular disease may lead to better outcomes.

Cardiac progenitor cells are a potential source of cell therapy for heart failure. Although recent studies have shown that transplantation of cardiac stem/progenitor cells improves function of infarcted hearts, the precise mechanisms of the improvement in function remain poorly understood. The present study demonstrates that transplantation of sheets of clonally expanded stem cell antigen 1-positive (Sca-1-positive) cells (CPCs) ameliorates cardiac dysfunction after myocardial infarction in mice. CPC efficiently differentiated into cardiomyocytes and secreted various cytokines, including soluble VCAM-1 (sVCAM-1). Secreted sVCAM-1 induced migration of endothelial cells and CPCs and prevented cardiomyocyte death from oxidative stress through activation of Akt, ERK, and p38 MAPK. Treatment with antibodies specific for very late antigen-4 (VLA-4), a receptor of sVCAM-1, abolished the effects of CPC-derived conditioned medium on cardiomyocytes and CPCs in vitro and inhibited angiogenesis, CPC migration, and survival in vivo, which led to attenuation of improved cardiac function following transplantation of CPC sheets. These results suggest that CPC transplantation improves cardiac function after myocardial infarction through cardiomyocyte differentiation and paracrine mechanisms mediated via the sVCAM-1/VLA-4 signaling pathway.

It was recognized that sleep-disordered breathing (SDB) is associated with cardiac arrhythmia and sudden cardiac death. However, it was unclear whether the presence of SDB increased the risk of life-threatening ventricular arrhythmia in patients with heart failure (HF) with an implantable cardioverter-defibrillator (ICD). Seventy-one patients with HF and an ICD who were followed up for 180 days after a sleep study were prospectively studied. All patients had an ejection fractionor=35%. SDB was defined as an apnea-hypopnea indexor=10 events/hour on the sleep study. The frequency of appropriate ICD therapy and the day-night pattern of ICD therapies were compared between patients with and without SDB. SDB was diagnosed in 47 of 71 patients (66%). There were no statistical differences between patients with and without SDB in baseline cardiac function. However, appropriate ICD therapies occurred more frequently in patients with (43%) than without SDB (17%; p = 0.029). On multivariate analysis, the presence of SDB was an independent predictor for appropriate ICD therapy (hazard ratio 4.05, 95% confidence interval 1.20 to 13.65, p = 0.015). Moreover, the rate of total ICD therapy from midnight to 6 A.M. was significantly higher in patients with (34%) than without SDB (13%; p = 0.046). In conclusion, in patients with HF with an ICD, the presence of SDB was common and an independent predictor of life-threatening ventricular arrhythmias that were more likely to occur during sleep.

Sudden cardiac death (SCD) accounts for approximately one-third of all deaths in patients with heart failure, and is generally the result of ventricular tachycardia (VT) and/or ventricular fibrillation (VF). The mechanisms of VT/VF associated with heart failure are complex and heterogeneous; they include functional and structural remodeling, as well as neurohormonal activation. The implantable cardioverter-defibrillator is very useful for preventing SCD, but the improvement of outcome is limited in patients with cardiac dysfunction and advanced heart failure. This article reviews the current status of drug therapy for the treatment of VT/VF in patients with heart failure. Chronic beta-blocker therapy reduces SCD and improves survival. Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers and aldosterone antagonists are thought to reduce SCD by preventing ventricular remodeling. Amiodarone is potentially effective for preventing VT/VF in patients at high risk, especially those with nonischemic heart failure. This may be a result of the complex pharmacodynamics of amiodarone, which affects many kinds of ion channels/transporters, as well as thyroid function. The pure class III antiarrhythmic drug, nifekalant, is useful in the emergency treatment of VT/VF.

We have already confirmed that cell sheet transplantation can improve damaged heart function via continuous cytokine secretion. In this study, we hypothesized that cytokine-secreting cell sheets co-cultured with an endothelial cell source may be more effective for repairing ischemic myocardium. Confluent rat fibroblasts cultured on temperature-responsive culture dishes were harvested as contiguous cell sheets by temperature reduction. Green fluorescent protein (GFP)-positive endothelial progenitor cells (EPCs) were seeded on fibroblast sheets to create co-cultured cell sheets, and sandwich-like constructs were engineered by stacking of the co-cultured cell sheets. These constructs were transplanted into rat myocardial infarction models. Cardiac function and histology were assessed in four groups: the sham operation (C) group, the isolated EPC injection (E) group, the transplantation of triple-layer fibroblast sheets (F) group, and the transplantation of triple-layer sandwich-like constructs (E + F) group. Echocardiography showed significant improvement of the fractional shortening in the E + F group in comparison with the C group (0.25 +/- 0.05 vs. 0.16 +/- 0.02). On histological examination, significantly less connective tissue formation was observed in the E, F, and E + F groups when compared to the C group (C, E, F, and E + F groups: 53 +/- 2%, 41 +/- 4%, 40 +/- 4%, and 32 +/- 7%, respectively). Additionally, increased blood vessel formation was detected in the E, F, and E + F groups compared with the C group (C, E, F, and E + F groups: 1.9% +/- 0.6%, 6.7% +/- 0.6%, 7.8% +/- 0.9%, and 10.2% +/- 2.4%, respectively). Furthermore, GFP-staining demonstrated that the newly formed blood vessels were composed of the co-cultured EPCs. Transplantation of cell sheets co-cultured with an endothelial cell source may be a new therapeutic strategy for myocardial tissue regeneration.

Background: Implantable Cardioverter Defibrillator (ICD) prevent sudden cardiac death in high risk patients with heart failure. The presence of coexisting conditions has a substantial effect on the rate of arrhythmic events in heart failure patients. Renal dysfunction is associated with mortality in patients with myocardial infarction or heart failure, but the influence of degrees of renal impairment is less well defined. Methods: A total of 221 patients who underwent ICD implantation were included between 1990 and 2006. Gromerular Filteration Rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and renal insufficiency was defined as MDRD GFR2 . Differences in arrhythmia recurrences according to the MDRD GFR were compared by Kaplan-Meier survival curves. Results: During a mean follow-up time of 3.7±2.8 years, 82 (37%) of 221 patients (mean age; 4.7±1.3 years, 71% male) experienced appropriate ICD shock therapy. There was a trend of higher cumulative rate of appropriate ICD shock therapies in patients with renal insufficiency than other patients (p2 , each reduction of the MDRD GFR by 10 units was associated with a HR for appropriate shock of 1.40 (95% CI, 1.00 to 1.95). Conclusion: Renal insufficiency is associated with increased rate of arrhythmic event in nonischemic HF patients. Especially, those patients with low LVEF and renal dysfunction experience more frequent ICD shocks.

Backgrounds: Combinations of dual antiplatelet therapy (aspirin with thienopyridine derivatives) plus warfarin sodium are often used in various cardiac conditions. The purpose of this study was to evaluate bleeding complications associated with combinations of dual antiplatelet plus anticoagulant therapy in patients who underwent percutaneous coronary intervention (PCI) with drug eluting stents (DES). Methods and Results : We reviewed 563 PCI cases with DES between August 2004 and March 2007 in our hospital either in the setting of elective situation or acute coronary syndrome. On discharge, 515 patients (91.5%) were prescribed dual antiplatelet therapy alone, while 48 patients (8.5%) were discharged receiving dual antiplatelet plus anticoagulant therapy. Major and minor bleeding complications were observed in 90 patients (17.8%). Rates of bleeding complications were significantly higher among patients receiving triple therapy compared to those with dual antiplatelet alone (37.5% vs. 13.9%, P Conclusions : Triple therapy, dual antiplatelet plus anticoagulant combination, was associated with significant increase in bleeding risk for patients who underwent PCI with DES. Our results also suggest that caution should be paid especially in those patients with CKD, that is a strongest predictor of major bleeding when the triple antithrombotic regimen was prescribed.