Usefulness of a simple prognostication score in prediction of the prognoses of patients with out-of-hospital cardiac arrests.

Sudden cardiac death is a serious problem in public health but the overall survival rate of out-of-hospital cardiac arrests (OHCAs) remains low. In this study, we identified clinical parameters to predict the prognosis of OHCA patients and proposed a simple prognostication score for prediction of their prognoses. The study population consisted of 750 consecutive patients with OHCAs of internal cause who were transported to our institute from July 2008 to June 2010. They were divided into survivors and nonsurvivors, and clinical parameters were compared between them to detect significant parameters for prediction of their prognoses. The population of those who survived at 1 month numbered 34. Multivariate analysis exhibited 10 independent predictive factors of survival, which included witnessed cardiac arrest and bystander-initiated CPR. When the prognostication score was calculated from these independent predictive factors, a score of ≥ 6 points indicated survival with a sensitivity of 88.6% and a specificity of 97.6%. When the patients were divided into younger and older populations with a threshold of 70 years, these values were 94.1% and 96.1% in younger but 70.0% and 98.4% in older patients, respectively. In retrospective observation, a simple prognostication score was useful to predict patient prognoses in OHCAs, but its usefulness was limited in an older population.

Initial experience of mobile cloud ECG system contributing to the shortening of door to balloon time in an acute myocardial infarction patient.

It is important for myocardial infarction patients to undergo immediate reperfusion of the affected coronary artery. In order to improve the prognosis, efforts to shorten the door to balloon time to within 90 minutes have been made. However, conventional methods such as faxing electrocardiograms (ECG) have not become widespread due to their high cost and lack of sharpness of the ECG. The "Doctor Car" (rapid response car system) of Kitasato University Hospital is now equipped with a Mobile Cloud ECG system. With this system, 12-lead ECG data obtained in the field are transmitted to the cloud server via a standard mobile telephone network. Since it uses an existing phone network, the cost of this system is low and it is fairly reliable. Cardiologists at the hospital read the ECG waveforms on the cloud server and decide whether emergency cardiac catheterization is necessary. In our fi rst case using this Mobile Cloud ECG system, the door to balloon time could be shortened.

Phosphoglucomutase activity as a novel biomarker in patients with acute myocardial infarction.

BACKGROUND: Phosphoglucomutase (PGM), a key enzyme in cellular glucose utilization and energy homeostasis, has been reported to show a relationship with oxidative stress. However, the clinical importance of PGM activity has not been investigated in patients with ischemic heart disease (IHD). The aim of the present pilot study was to clarify whether PGM activity has potential as a cardiovascular risk predictor in patients with IHD. METHODS AND RESULTS: The levels of serum PGM activity in 237 patients with IHD (63 patients with acute myocardial infarction (AMI) and 174 patients with stable effort angina pectoris (EAP)) were evaluated. PGM activity was compared with levels of various myocardial, thrombosis, and inflammatory biomarkers on admission. PGM activity in the AMI group was significantly increased relative to that in the EAP group on admission (AMI, 55.5 µmol·min(-1)·L(-1) (U/L); EAP, 14.4 U/L (P<0.001)), and was observed to increase in parallel with well-established myocardial markers (P<0.001). Moreover, PGM activity and the lipid, thrombosis, and inflammatory biomarkers in the AMI group were higher than those in the EAP group. CONCLUSIONS: PGM activity increased with levels of myocardial, thrombosis, and inflammatory biomarkers in patients with AMI, and might be useful in diagnostic applications during the acute phase in patients with AMI.

N-acetylcysteine suppresses the progression of ventricular remodeling in acute myocarditis: studies in an experimental autoimmune myocarditis (EAM) model.

BACKGROUND: Electrical and structural remodeling, characterized by prolonged action potential duration (APD), Kv4.2 downregulation and cellular infiltration were studied in rat experimental autoimmune myocarditis (EAM). Because the reactive oxygen species (ROS) has been speculated to play a role in the promotion of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of ventricular remodeling was evaluated. METHODS AND RESULTS: Six-week-old Lewis rats were immunized with porcine cardiac myosin. On Days 10-11 after the immunization, NAC (0, 1, 10, or 100mg) was injected intraperitoneally to EAM and control rats. On Day 14, the electrophysiological parameters were evaluated and the expression levels of the mRNA were examined by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR).The EAM rats exhibited a typical acute myocarditis with prolonged APD and reduced Kv4.2 expression as previously reported. The myocarditis and electrical changes were significantly suppressed by NAC-treatment in a dose-dependent manner (P<0.05). In rats with 100mg NAC, the myocarditis was almost totally negated although the mortality increased. In rats with 1mg NAC, the suppression of myocarditis was not obvious, but APD prolongation and Kv4.2 reduction was attenuated (P<0.05). CONCLUSIONS: The NAC treatment suppressed ventricular remodeling in the EAM rats. This may indicate the role of oxidative stress in causing remodeling and myocarditis itself in the acute phase of myocarditis.

Hemodialysis is an independent predictor of coronary in-stent restenosis after paclitaxel eluting stent implantation.

OBJECTIVE: A drug eluting stent is often used for high-risk patients with complications such as diabetes mellitus (DM) and hemodialysis (HD), however the factors to predict restenosis after paclitaxel-eluting stent (PES) placement have not been reported to date. METHODS: Between May 2007 and August 2009, 165 consecutive patients (231 stents) received PES in our hospital. Stent diameter and length were determined by the use of intravascular ultrasound (IVUS). All patients continued to take 2 types of anti-platelet agents (aspirin and Clopidogrel or Ticlopidine). Ninety percent of the subjects received a follow-up coronary angiogram 6 months later. RESULTS: Underlying diseases were hypertension in 75%, hyperlipidemia in 78% and DM in 60% (15% on insulin), and 14% of the subjects received HD. Eighty-three percent of the patients had orally taken Statin, 85% ACE/ARB and 68% had beta blockers. Mean length and diameter of PES were 21.6 ± 7.2 mm and 2.9 ± 0.3 mm, respectively. Target lesion revascularization (TLR) rate 6 months after PES placement was 14.6% overall. In HD patients TLR was 43%, hypertension 15.0%, hyperlipemia 12.4%, DM with oral medication 12.5%, DM with insulin 12.0%, respectively. In multivariate analysis, HD was an independent risk factor for TLR (p=0.0001, OR: 6.61, 95% C.I.: 2.34-18.6). CONCLUSION: HD had the greatest influence on TLR after PES even though risk factors were well controlled. It is necessary to develop new PCI techniques and stents that are useful for HD patients.

Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model.

INTRODUCTION: We examined the acute effects of neutral endopeptidase inhibitor on the hemodynamics and electrical properties of dogs subjected to rapid atrial pacing. METHODS: Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration. Before and after the 6 hours rapid atrial pacing from the right atrial appendage, the hemodynamics, atrial effective refractory period, and monophasic action potential duration of the right atrial appendage were measured and blood samples were collected. Atrial tissue was also excised after the experiment. RESULTS: Candoxatril significantly increased plasma ANP levels (Control: 88.4 +/- 50.25 vs. Candoxatril: 197.1 +/- 32.09 pg/ml, p = 0.004) and prevented reductions in atrial effective refractory period and monophasic action potential duration. We further demonstrated that the treated animals exhibited significantly higher levels of atrial tissue cyclic GMP (Control: 28.1 +/- 1.60 fmol/mg vs. Candoxatril: 44.5 +/- 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 +/- 5.5 vs. Candoxatril: 42 +/- 7.1 pg/ml, p = 0.028). CONCLUSION: Candoxatril suppressed the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model. As plasma ANP and the atrial tissue levels of cyclic GMP were higher in the Candoxatril group than the control, this effect was considered to appear through the reduction of calcium overload caused by ANP and cyclic GMP.

Role of electrophysiologic study (EPS)-guided preventive therapy for the management of ventricular tachyarrhythmias in patients with heart failure.

BACKGROUND: Ventricular tachyarrhythmias (VT/VF) are 1 of the most important factors determining the prognosis of patients with heart failure (HF). Although priority is given to implantable cardioverter defibrillator (ICD) therapy for the prevention of sudden cardiac death, electrophysiologic-study (EPS)-guided preventive therapy could be important for reducing the number of cardiac events. METHODS AND RESULTS: Of 864 patients with a history of HF, an EPS was performed in 168 and 121 had inducible VT/VF. Under the basic therapy of an ICD, additional catheter ablation was attempted for 95 of 124 monomorphic VT foci in 74 patients, and 78 of the VT were successfully ablated. The prognoses were compared among 5 patient groups with different results for the EPS and catheter ablation: (1) success group (n=43), (2) failure group (n=15), (3) not attempted group (n=16), (4) VF group (n=47), and (5) no inducible VT/VF group. During a follow-up period of 31+/-22 months, the incidence of VT/VF was lower in the success and no inducible VT/VF groups than in the other groups (p=0.0018), although a significant difference was not observed for the total deaths. CONCLUSION: EPS-guided preventive therapy using an ICD and catheter ablation can be useful, at least for the reduction of arrhythmic events in patients with HF.

Atrial natriuretic peptide (ANP) suppresses acute atrial electrical remodeling in the canine rapid atrial stimulation model.

OBJECTIVES: Atrial electrical remodeling is considered to play an important role in the appearance of atrial fibrillation. The effect of atrial natriuretic peptide (ANP) on atrial electrical remodeling was evaluated in a canine atrial stimulation model. METHODS: In 15 beagle dogs, electrodes for pacing and recording were fixed on the atrial surface. In 10/15 dogs, rapid atrial stimulation (400 bpm) was performed for 7 h at the right atrial appendage (RAA) and the remaining 5 were used as the sham without rapid pacing. In 5/10 dogs with rapid pacing, human atrial natriuretic peptide (ANP) was infused (1.0 microg/kg/min). The effective refractory period (ERP) and the monophasic action potential duration (MAP) were evaluated at 0, 3, and 7 h after rapid pacing. The expression levels of mRNAs of ion channels or transporters were evaluated from the atrial samples of sham and after a 7 hour pacing. RESULTS: In the control group with rapid pacing (n=5), the atrial ERP and MAP duration were shortened at all atrial sites, e.g., ERP from 148+/-14 ms to 109+/-8 ms at RAA, P=0.006. In contrast in the ANP group, neither the ERP nor MAP duration showed a significant shortening and the effect of ANP on hemodynamic parameter was relatively small. Expression levels of the mRNA were not significantly different between the control and ANP groups. CONCLUSIONS: Administration of ANP prevented the shortening of the ERP and MAP duration in the rapid atrial stimulation model. The effect of ANP on atrial electrical remodeling was considered to be due to its direct action on the myocardium.

Clinical usefulness of electrophysiologic study (EPS)-guided risk stratification for life-threatening arrhythmia in patients with heart failure.

BACKGROUND: Ventricular tachyarrhythmia is one of the most important factors determining the prognosis of patients with heart failure and sudden death can be observed even during stable therapy controlling clinical heart failure. In this study, the usefulness of electrophysiologic study (EPS) for the prediction of a future arrhythmic event was evaluated in patients with heart failure. METHODS AND RESULTS: The patient population consisted of 474 patients with a history of clinical heart failure but without an episode of spontaneous sustained ventricular tachycardia or fibrillation (VT/VF). A Holter ECG was performed in all patients, and 177 of the 474 patients underwent EPS because of a recording of nonsustained VT (NSVT, > 5 beats). When sustained VT/VF was inducible in EPS, the patient was assigned to implantation of a defibrillation device. The patients were divided into 3 groups, ie, 1) no NSVT (n = 297), 2) NSVT + no inducible VT/VF (n = 134), and 3) NSVT + inducible VT/VF (n = 43), and were followed-up for > 12 months. All patients were followed-up under standard therapy for heart failure. There were no significant differences in basic clinical characteristics and therapies among the 3 groups. During the follow-up period of 32 +/- 18 months, 56/474 patients suffered a VT/VF episode, ie, 21/297 in no NSVT, 14/134 in NSVT + no inducible VT/VF, and 21/43 in NSVT + inducible VT/VF patients (P = 0.032). All patients were rescued from sudden death among patients with an implanted defibrillator, but 11 patients without a defibrillator died. CONCLUSION: In patients with heart failure, future arrhythmic events could be predicted by EPS and Holter ECG. EPS-guided risk stratification seems to be useful in managing patients with heart failure.

The anti-atherosclerotic effects of lipid lowering with atorvastatin in patients with hypercholesterolemia.

We investigated the lipid lowering and anti-atherosclerotic effects of atorvastatin in patients with hypercholesterolemia. Thirty patients were given atorvastatin 10 mg daily, and assessed for serum lipids, intima-media thickness (IMT), and brachial-ankle pulse wave velocity (ba-PWV) at the baseline, 6 months, and 12 months. Remnant-like particle-cholesterol (RLP-C), lipoprotein (a)(Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) were measured in some patients at the baseline and at 6 months. Total cholesterol, triglyceride and low-density lipoprotein cholesterol were significantly decreased by 32%, 23% and 44% at 6 months, respectively, and these effects were sustained at 12 months. There was no change in high-density lipoprotein cholesterol. IMT at the baseline was 0.88 +/- 0.16 mm and decreased to 0.76 +/- 0.13 mm at 6 months, remaining at 0.75 +/- 0.12 mm at 12 months. We did not observe any significant changes in ba-PWV. RLP-C and hs-CRP were significantly reduced from 7.3 +/- 10.8 mg/dL to 4.3 +/- 5.3 mg/dL and 0.075 +/- 0.065 mg/dL to 0.039 +/- 0.043 mg/dL at 6 months, respectively. There was no change in Lp(a). The observed decrease in IMT suggests that atorvastatin possibly improves atherosclerosis, in addition to the significant reduction of serum lipids.

Predictive impact of the inducibility of ventricular fibrillation in patients with Brugada-type ECG.

The natural history of asymptomatic individuals with a Brugada-type electrocardiogram (ECG) is still controversial. In this study, we evaluated ventricular fibrillation (VF) inducibility in Brugada-type ECG patients and compared it with other risk factors to clarify the significance of these data on their prognosis. The study population consisted of 38 patients who presented with a typical ST-segment elevation in the precordial leads and underwent an electrophysiological study (EPS). The patients were divided into 3 groups; group A: patients with spontaneous ventricular fibrillation (VF) (n = 5), group B: patients without clinical VF but with inducible VF in EPS (n = 16), and group C: patients with neither clinical nor inducible VF (n = 17). The clinical features, diagnostic results, and prognosis were compared among these groups. During the follow-up period of 26 +/- 19 months, 2/5 (group A), 1/16 (group B), and 0/17 (group C) patients suffered fatal arrhythmic events. None of the clinical features showed any significant difference, although the incidence of positive results in a drug challenge test was higher in groups A and B than in group C (P < 0.05). On the other hand, VF inducibility was higher in patients with positive results in the drug challenge test than in patients with negative results (59% versus 13%; P < 0.05). No VF episodes were observed in patients without VF induction, although one was observed in 1 of 16 patients with VF induction in asymptomatic Brugada syndrome. The drug challenge test appears to be useful for predicting VF inducibility even though it is a noninvasive test.

Clinical significance of the electrophysiologic study (EPS)-guided therapy for the secondary prevention of ventricular tachycardia.

BACKGROUND: Although electrophysiologic study (EPS) is one of the most reliable methods for selecting preventive therapy for patients with sustained ventricular tachycardia (VT), VT may recur during EPS-guided effective therapy; therefore, the importance of implantable cardioverter-defibrillator (ICD) has been emphasized. In this study, the prognoses of VT patients were evaluated to clarify the importance of EPS-guided therapy for the secondary prevention of VT. METHODS AND RESULTS: The study population consisted of 99 consecutive patients with a history of sustained VT, which was inducible in EPS. The VT induction protocol used 1-3 extrastimuli and rapid ventricular pacing at 2 right ventricular sites and included additional isoproterenol infusion. ICD implantation was applied to all patients with an episode of hemodynamically unstable VT, regardless of the result of preventive therapy. For preventive therapy, an antiarrhythmic drug and/or catheter ablation were selected, and they were defined as being effective in the EPS-guided therapy when the induction of VT was completely prevented. When no therapy was effective for prevention, an antiarrhythmic drug was prescribed under ICD implantation. During the follow-up period of 19+/-20 months, VT recurred in 17 of 32 patients (53%) in the ineffective group and in 10 of 67 patients (15%) in the effective group (p=0.0001). The therapies used in the effective group were class I antiarrhythmic drug in 9, class III in 15, and catheter ablation in 35 patients. Between the patients with and without VT recurrence, there were no significant differences in the left ventricular ejection fraction and the maximum number of repetitive ventricular responses that remained in VT induction in EPS. CONCLUSIONS: Although VT may recur in up to 15% of patients with EPS-guided effective therapy, the recurrence rate was significantly reduced in comparison to that in the ineffective group. EPS-guided therapy may be useful to reduce the clinical recurrence of VT, as well as the action of ICD.

Long-term follow-up of changes in fibrillation waves in patients with persistent atrial fibrillation: spectral analysis of surface ECG.

BACKGROUND: Little is known about the shortening of atrial refractoriness as a result of electrical remodeling in atrial fibrillation (AF) in clinical cases, especially in terms of long-term follow-up, because of a lack of noninvasive testing methods. METHODS AND RESULTS: The present study population comprised 38 consecutive patients with persistent AF (PAF, >1 month). Before and after the follow-up period of 1-14 months, surface ECGs were recorded for analysis. In each case, the fibrillation wave was purified by subtracting the QRS-T complex template and then power spectral analysis was performed. The mean fibrillation cycle length (FCL) and FCL coefficient of variation (FCL-CV) were determined from peak power frequency in 20 epochs in each recording. The change in FCL (FCL) was calculated by subtracting the baseline FCL from the FCL after the follow-up period. To correct for the difference in the follow-up period, DeltaFCL was divided by the follow-up period in each case. In 38 cases, mean FCL decreased from 160+/-20 ms to 151+/-19 ms (p<0.05), and the FCL-CV also decreased from 15+/-9% to 12+/-5% (p<0.05). The corrected DeltaFCL was -2.4+/-7.6 (ms/month) and there was a significant negative correlation between corrected DeltaFCL and baseline FCL (p<0.01). CONCLUSION: Shortening of the FCL during a relatively long-term follow-up period was observed in patients with PAF.

Bepridil inhibits sub-acute phase of atrial electrical remodeling in canine rapid atrial stimulation model.

Background The effect of bepridil, a multichannel blocker, on atrial electrical remodeling was evaluated in a canine rapid atrial stimulation model. Methods and Results In 10 beagle dogs, the right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. The atrial electrophysiological parameters, including effective refractory period (AERP), were evaluated at three atrial sites: RAA, the right atrium close to the inferior vena cava (IVC) and the left atrium (LA), during the time course of rapid pacing. Five of the dogs were given bepridil (10 mg . kg (-1) . day(-1) po). In the control group, AERP was significantly shortened at all atrial sites and the AERP shortening (DeltaAERP) was larger for the RAA and LA than at the IVC site (p<0.05). In the bepridil group, DeltaAERP was smaller than that of the controls at all atrial sites, and the AERP started to return slowly to the pre-pacing level in the second week, regardless of the continuation of rapid pacing. Conclusions In a canine rapid atrial stimulation model, bepridil suppressed AERP shortening. Bepridil might have a reverse electrical remodeling effect, at least for AERP shortening, because it showed slow recovery of AERP in the subacute phase of rapid atrial pacing. (Circ J 2006; 70: 206 - 213).

Mexiletine protects myocardium during acute ischemia by opening sarcolemmal K-ATP channel: studies in closed-chest acute ischemia model in rabbits.

OBJECTIVES: Although we have previously shown that mexiletine might protect myocardium during acute ischemia, the precise mechanism was unclear. In the present study, the mechanism of this effect was examined by using selective K-ATP channel blockers in closed-chest acute ischemia model in rabbits. METHODS: In 40 rabbits, the large left ventricular branch (LLVB) of the left coronary artery was occluded for 30 minutes by inserting a catheter bead (varphi0.5-0.7 x 1.5 mm) through the left carotid artery and was then reperfused. The rabbits were divided into the following 5 groups: (1) control group (n = 8); (2) mexiletine (Mex) group (n = 8, continuous infusion of Mex 24 mg/kg/h); (3) Mex + 5-hydroxydecanoate (5HD) group (n = 8, preadministration of 5HD, 5 mg/kg, followed by Mex infusion); (4) Mex + HMR1098 (selective sarcolemmal K-ATP channel blocker) group (n = 8, preadministration of HMR1098, 3 mg/kg, followed by Mex infusion); and (5) pilsicainide (Pil) group (n = 8, continuous infusion of Pil 18 mg/kg/h). The incidence of ventricular arrhythmia, hemodynamics, left ventricular ejection fraction (LVEF), and infarction size were evaluated and compared among the 5 groups. RESULTS: The incidence of ventricular arrhythmia was lower in groups treated with Mex than the control. The hemodynamics did not show significant differences among the 5 groups. Although the LVEF at 30 minutes after reperfusion was lower in the Mex group (41 +/- 3%, P < 0.001) than the control group (48 +/- 3%), the LVEF at 360 minutes after reperfusion had recovered and became higher in the Mex group (62 +/- 3%, P < 0.001) than the control group (55 +/- 3%). The infarction size was smaller in the Mex group (30 +/- 5%, P = 0.028) than the control group (51 +/- 8%). These effects of Mex were negated by HMR1098 but not by 5HD and were larger than the effects of Pil. CONCLUSIONS: Mex showed improvement in the LVEF in the later phase after reperfusion as well as a reduction in ventricular arrhythmia. The cardioprotective effect of Mex was considered to appear through its action on the sarcolemmal K-ATP channel.