Cardiac resynchronization therapy for patients with cardiac sarcoidosis.

Aims: Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. Methods and results: We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Conclusions: Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias.

The ReACT Trial: Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial.

OBJECTIVES: The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan. BACKGROUND: The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately. METHODS: In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up. RESULTS: Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range [IQR]: 3.1 to 5.2 years), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p < 0.001), although the difference between the 2 groups attenuated over time with a similar cumulative 5-year incidence (19.6% vs. 18.1%; log-rank p = 0.92). CONCLUSIONS: No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial [ReACT]; NCT01123291).

HotBalloon Ablation of the Pulmonary Veins for Paroxysmal AF: A Multicenter Randomized Trial in Japan.

BACKGROUND: Point-by-point catheter ablation is an established treatment for drug-refractory paroxysmal atrial fibrillation (PAF). However, it is time consuming, requires excellent technique to achieve complete pulmonary vein (PV) isolation, and is associated with severe complications. OBJECTIVES: The purpose of this study was to evaluate the safety and effectiveness of a HotBalloon ablation (HBA) compared with antiarrhythmic drug therapy (ADT) for the treatment of PAF. METHODS: A prospective multicenter randomized controlled study was conducted in Japan. Patients with symptomatic PAF refractory to antiarrhythmic drugs (Class I to IV) were randomized to HBA or ADT at a 2:1 ratio and assessed for effectiveness in a comparable 9-month follow-up period. RESULTS: A total of 100 patients in the HBA group and 43 patients in the ADT group received treatment at 17 sites. HBA procedure produced acute complete PV isolation in 98.0% (392 of 400) of the PVs and in 93.0% (93 of 100) of patients in the HBA group. The chronic success rates after the 9-month effective evaluation period were 59.0% in the HBA group (n = 100) and 4.7% in the ADT group (n = 43; p < 0.001). The incidence of major complications was 11.2% (15 of 134 patients). The incidences of PV stenosis (>70%) and transient phrenic nerve injury were 5.2% and 3.7%, respectively. The mean fluoroscopy time was 49.4 ± 26.6 min (n = 134), and the mean procedure duration was 113.9 ± 31.9 min (n = 133). CONCLUSIONS: This study demonstrates the superiority of HBA compared with ADT for treatment of patients with PAF, and a favorable safety profile.

Don't expect left ventricular reverse remodeling after cardiac resynchronization therapy in patients with systolic heart failure and atrioventricular block: A multicenter study.

BACKGROUND: The BLOCK HF trial showed that heart failure patients with atrioventricular block (AVB) and left ventricular systolic dysfunction (LVSD) are considered good candidates for cardiac resynchronization therapy (CRT), even though they have a narrow QRS duration. We aimed to compare the clinical response to CRT between patients with AVB combined with LVSD and patients with pre-existing CRT indications. METHODS: We compared the clinical data on CRT across the following 3 groups in 3 cardiovascular centers; heart failure patients with an LV ejection fraction (LVEF) of ≤35% who had a QRS duration of ≥120ms (standard indication, n=125), those needing an upgrade to CRT (upgrade, n=49), and patients with an LVEF of ≤50% who had advanced AVB (AVB with LVSD, n=27). RESULTS: The prevalence of left bundle branch block differed significantly across the groups (87.2%, 98.0% and 40.7%; P<0.001). No inter-group difference was found in the percentage of patients in whom clinical composite score (CCS) assessed 6months after the CRT was improved (60.8%, 57.1% and 70.4%; P=0.67). Whereas, even among the patients with an improved CCS, a significantly smaller LV end-systolic volume reduction after the CRT was seen in the ABV with LVSD group (-35.3±34.7, -21.4±28.5 and -5.2±23.9%; P=0.001). The incidence of cardiovascular death or hospitalization from heart failure within 5years occurred with a similar frequency (44%, 55.1% and 44.4%; P=0.9). CONCLUSIONS: As compared to patients with preexisting CRT indications, CRT may be similarly effective for patients with AVB and LVSD, however, LV reverse remodeling may be uncommon among them.

Who is the operator, that is the question: a multicentre study of catheter ablation of atrial fibrillation.

AIMS: A worldwide survey reported that the success rate of atrial fibrillation (AF) ablation was higher in high-volume centers compared with low-volume centers. We tested whether the procedure volume of each operator was associated with the outcome of AF ablation in high-volume centres. METHODS AND RESULTS: We studied 471 patients with paroxysmal AF who underwent pulmonary vein (PV) isolation for the first time in three cardiovascular centers where the annual AF ablation volume was >100 procedures. We classified a total of 10 primary operators according to their operation volume on the basis of ACC/AHA/ACP CLINICAL COMPETENCE STATEMENT; high-volume operator (≥50 cases/year, N = 3) or low-volume operator (<50 cases/year, N = 7). The patients included were dichotomized according to the annual operation volume of their attending physician. The endpoints were the freedom from AF recurrence 1 year after the ablation, major complications including thromboembolisms, massive bleeding or death, and the procedural duration. RESULTS: A complete isolation of the four PVs was achieved in 99.1%. The freedom from AF recurrence was more common in patients treated by high-volume operators than those treated by low-volume operators (165/216 [76.4%] vs. 160/255 [62.8%]; P = 0.001). A high-volume operator was the only independent predictor of the freedom from AF recurrence (hazard ratio 1.73, 95% confidence interval 1.23-2.48; P = 0.002). The patients treated by high-volume operators were less likely to have major complications (1.4% vs. 7.8%; P = 0.001), and had a shorter procedural duration (139.9 ± 25.3 vs. 149.3 ± 27.1 min; P = 0.03). CONCLUSIONS: Operator proficiency may predict the outcome after AF ablation even in high-volume centres.

Evaluation of the safety and efficacy of TY-51924 in patients with ST elevated acute myocardial infarction - Early phase II first in patient pilot study.

BACKGROUND: In myocardial ischemia-reperfusion injuries, the involvement of the Na(+)/H(+) exchanger (NHE) is considered to be one of the pathogenic mechanisms following reperfusion. TY-51924 is a novel hydrophilic NHE inhibitor with a lower risk of central neurotoxicity than previous NHE inhibitors. This open-label, dose-escalating study was undertaken to investigate the safety, efficacy, and pharmacokinetics of TY-51924 in patients with ST-elevation myocardial infarction (STEMI). METHODS: Consent was obtained from a total of 30 patients with first anterior STEMI. After 12 patients were determined to be ineligible, the remaining 18 patients, each of whom was undergoing primary percutaneous coronary intervention (pPCI), received TY-51924 intravenously up to 10, 20, or 30mg/kg as the low-, medium-, or high-dose groups, respectively (n=6 in each group). The primary endpoints were safety (up to 7 days) and plasma drug concentration. The myocardial salvage index (MSI) was measured by (201)Tl/(123)I-beta-methyl-p-iodophenyl pentadecanoic acid single photon emission computed tomography (SPECT) 3-5 days after pPCI. RESULTS: No side effects were observed. Plasma drug concentrations increased dose-dependently, and were subsequently eliminated rapidly. MSIs were 0.118, 0.335, and 0.192 in the low-, medium-, and high-dose groups, respectively. In additional analysis, the combined MSIs in the medium- and high-dose groups were significantly higher than those in the low-dose group, in patients with a longer time from symptom onset to reperfusion (p=0.0247). CONCLUSIONS: No side effects were observed even at the highest dose with this novel hydrophilic NHE inhibitor. Therefore, TY-51924 is thought to be safe in patients with STEMI, even at the highest dose. Potential cardioprotective effects of intravenous TY-51924 might be expected based on the results obtained for the MSIs using SPECT at 20-30mg/kg. However, further large-scale, double-blind, placebo-controlled clinical studies are required to confirm the efficacy and safety implied in the current study.

Randomized controlled trial of TY-51924, a novel hydrophilic NHE inhibitor, in acute myocardial infarction.

BACKGROUND: In patients with ST-elevation acute myocardial infarction (STEMI), reperfusion therapy limits infarct size, but can directly evoke myocardial reperfusion injury. Activation of the Na(+)/H(+) exchanger (NHE) plays an important role in reperfusion injury. TY-51924, a novel NHE inhibitor, significantly reduced infarct size in animal studies and was well tolerated in early-phase clinical trials. This study aim was to evaluate the efficacy and safety of TY-51924 in patients with STEMI. METHODS: In this multicenter, randomized, double-blind, placebo-controlled Phase II trial, 105 patients with first anterior STEMI undergoing primary percutaneous coronary intervention (pPCI) were randomly assigned to receive an intravenous infusion of either TY-51924 or placebo. Primary endpoints were myocardial salvage index (MSI) as determined by single photon emission computed tomography (SPECT) 3-5 days after pPCI and safety up to 7 days. RESULTS: Baseline characteristics were similar in the two groups. MSI 3-5 days after pPCI (0.200 vs. 0.290, p=0.56), 3 months after pPCI (0.470 vs. 0.500, p=0.76), and the incidences of side effects did not differ between the two groups as a whole. However, on post hoc analysis of 52 patients with a large area at risk (AAR) (≥38%) and no antegrade coronary flow, MSI by SPECT at 3 months after pPCI was significantly higher in TY-51924 group (0.450 vs. 0.320, p=0.03). TY-51924 did not adversely influence hemodynamics. CONCLUSIONS: TY-51924 did not improve MSI or increase side effects as a whole. However, TY-51924 is potentially cardioprotective in the presence of a large AAR and no antegrade coronary flow.

High HDL cholesterol level after treatment with pitavastatin is an important factor for regression in carotid intima-media thickness.

This study is a prospective multicenter study designed to investigate the effects of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients with coronary heart disease, and to determine which factor is more closely associated with plaque regression. Participants (n = 63) were treated with pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was measured by ultrasound before and after treatment. Mean IMT slightly but significantly decreased (from 0.99 ± 0.33 to 0.94 ± 0.28 mm for overall, P = 0.01) regardless of the presence of pretreatment with other statins. There were no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases in mean IMT were observed significantly more frequently in subjects with high on-treatment HDL cholesterol levels than with low HDL cholesterol levels (P = 0.017). The change in mean IMT tended to be inversely correlated with increments in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often observed in the absence of diabetes and metabolic syndrome. In conclusion, we demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque. This effect was associated with the level of HDL cholesterol, and was stronger in the absence of diabetes and metabolic syndrome in our ischemic heart disease patients.

Impact of pulmonary vein isolation on fractionated atrial potentials and ganglionated plexi in patients with persistent atrial fibrillation.

Some patients with persistent atrial fibrillation (AF) acquire long-term freedom from AF by pulmonary vein (PV) isolation alone. The aim of the present study was to evaluate the characteristics of their atrial substrate.We studied 20 patients with persistent AF to examine the distribution of fractionated atrial potentials (FAP) and that of the anatomic sites of ganglionated plexi (GPs) with vagal reflexes elicited by high frequency stimulation (HFS) with the use of the CARTO system before and after the PV isolation.Both the %FAP area defined as a proportion of the FAP area to the total left atrial area (34.3 ± 10.3 to 21.5 ± 10.2%; P < 0.0001) and number of GP sites with vagal reflexes (4.0 [3.0, 5.0] to 2.0 [1.0, 2.8]; P < 0.0001) were markedly decreased after the PV isolation. Seven (35%) patients had AF recurrences, and they had a greater %FAP area after the PV isolation than those without (32.8 [22.1, 37.3] versus 13.8 [10.9, 19.9]%; P = 0.0049). A %FAP area after the PV isolation of > 20% was significantly associated with an AF recurrence (odds ratio 20.0, 95% confidence interval 2.26470.34; P = 0.018). No significant difference was found between the patients with and without AF recurrence in the reduction rate of anatomic sites of GPs with a vagal reflex induced by the HFS.A more marked reduction in the FAP area by the PV isolation was significantly associated with a better outcome in patients with persistent AF.

Comparison of the change in the dimension of the pulmonary vein ostia immediately after pulmonary vein isolation for atrial fibrillation-open irrigated-tip catheters versus non-irrigated conventional 4 mm-tip catheters.

INTRODUCTION: A difference in the lesion formation between open irrigated-tip (OITC) and non-irrigated 4-mm-tip catheters (NITC) may result in a difference in the dimension of the pulmonary vein (PV) ostia after PV isolation of atrial fibrillation (AF). This study evaluated the difference using intracardiac echocardiography (ICE) before and immediately after an extensive encircling PV isolation (EPVI) with an OITC and with an NITC. METHODS AND RESULTS: We studied 100 consecutive patients (OITC group, 54; NITC group, 46) who received EPVI. Changes in the vessel, lumen, and wall thickness areas of the PVs were evaluated at the PV ostia by ICE. There were no significant differences in the baseline characteristics and acute success rate of the EPVI between the OITC and NITC groups. The energy delivered to achieve EPVI was higher in the OITC group than that in the NITC group (34,967 ± 13,222 J vs. 28,300 ± 10,614 J; p=0.01). After the ablation, the reduction in the vessel and lumen cross-sectional areas was significantly smaller in the OITC group than that in the NITC group (-9.05 ± 28.4 % vs. -21.2 ± 28.8 %, p<0.001; -8.76 % vs. -17.7 ± 26.9 %, p=0.003). The wall thickness area slightly decreased in the OITC group, but increased in the NITC group (-2.96 ± 38.4 % vs. 10.5 ± 76.6 %, p=0.591). During a median follow-up of 234 days, there was no significant difference in the AF recurrence after the initial ablation procedure between the two groups. CONCLUSION: Greater PV ostial narrowing occurred with the NITC than OITC immediately after the EPVI. PV ostial wall edema was noted with only the NITC. These findings suggested that an OITC might reduce any acute PV narrowing and wall edema as compared with an NITC.

Don't move during ablation of atrial fibrillation!

BACKGROUND: Restless patient is recalcitrant during ablation of atrial fibrillation (AF). We aimed to assess the association between patient movements during AF ablation and its outcome. METHODS: We examined the body movement during AF ablation in 78 patients with the use of a novel portable respiratory monitor, the SD-101, which also has the ability to quantify the frequency of body movements. RESULTS: The body movement index, defined as the number of the units of time with body movement events divided by the recording time (11.4 ± 6.5 events/h), was significantly correlated with the ablation time defined as the time from the first point of the ablation to the end of the procedure (1.2 ± 0.3h) (r=0.35; p=0.0014) and a total radiofrequency energy applied (56.6 ± 17.7 kW) (r=0.36; p=0.0015). A multiple linear regression analysis showed that non-paroxysmal AF (ß=0.25; p=0.036) and the body movement index (ß=0.36; p=0.0019) were independent determinants of the ablation time. The body movement index was similar in patients with and without recurrence of AF. CONCLUSIONS: Keeping patients motionless may be important to reduce the procedural duration of AF ablation.

Patterns of pulmonary vein potential disappearance during encircling ipsilateral pulmonary vein isolation can predict recurrence of atrial fibrillation.

BACKGROUND: The relationship between pulmonary vein (PV) potential (PVP) disappearance patterns during encircling ipsilateral pulmonary vein isolation (EIPVI) of atrial fibrillation (AF), and outcome was examined. METHODS AND RESULTS: A total of 352 consecutive AF patients (age, 61±12 years; 269 men, 76.4%; paroxysmal AF, n=239; persistent AF, n=73; and long-standing persistent AF, n=40) who underwent initial AF ablation were studied. After EIPVI with a double Lasso technique, pacing was performed from the PV carina to confirm isolation of the carina. PVP disappearance patterns were classified into 3 types: A, both superior and inferior PVP disappeared simultaneously; B, superior and inferior PVP disappeared separately; and C, additional RF applications were required inside the encircling lesions to eliminate the PVP after creating anatomical encircling lesions. The relationship between these patterns and outcome was examined. Six groups were defined according to the combination of right and left ipsilateral PVP disappearance patterns. The incidence of A-A, A-B, B-B, A-C, B-C, and C-C was 7.1%, 14.2%, 16.2%, 15.3%, 27.3%, and 19.9%, respectively. AF recurrence-free rate at 2 years for these 6 groups was 96%, 81%, 78%, 64%, 64%, and 59%, respectively (P<0.02). The incidence of a carina isolation was 153/154 (99.4%) for type A, 221/259 (85.3%) for type B, and 145/290 (50.0%) for type C. CONCLUSIONS: PVP disappearance pattern during EIPVI was significantly associated with the incidence of residual PV carina conduction and AF recurrence.

Periprocedural coagulability in patients undergoing ablation of atrial fibrillation: lessons from a periablation anticoagulation strategy of a brief withdrawal of warfarin without heparin bridging.

We aimed to examine what becomes of the coagulable state when warfarin is interrupted in patients undergoing ablation of atrial fibrillation (AF). We studied 62 patients with a CHADS2 score of 0 or 1 who underwent ablation for paroxysmal AF. Warfarin was discontinued the day before the ablation without heparin-bridging, and intravenous heparin was administered during the procedure in a conventional manner, and warfarin was then resumed after achieving hemostasis of the access site. The international normalized ratio (INR) values or D-dimer levels were measured at five different time points during the periprocedural period, and the periprocedural hemorrhagic and thromboembolic complications were assessed. The INR value constantly decreased after withdrawal of warfarin, and did not recover to the level before its discontinuation at the time of hospital discharge despite a short interruption of warfarin (mean ± SD, 1.75 ± 0.52 to 1.41 ± 0.27, p < 0.0001). However, the D-dimer level continued to increase over a period of 48 h after the ablation in spite of the administration of a sufficient amount of heparin during the procedure and a quick resumption of warfarin (mean ± SD, 0.57 ± 0.19 to 0.85 ± 0.36 µg/mL, p < 0.0001). The INR value measured just before the ablation had a significant inverse correlation to the D-dimer levels assessed just before (r = -0.304), immediately after (r = -0.440), 24 h after (r = -0.442) and 48 h after the ablation (r = -0.463). In conclusion, the risk of hyper-coagulability may increase during the early postprocedural period of AF ablation in patients who were inappropriately anticoagulated with warfarin.

Procedural sedation with dexmedetomidine during ablation of atrial fibrillation: a randomized controlled trial.

AIMS: Procedural sedation by non-anaesthesiologists with GABAergic anaesthetics has the potential risk of fatal respiratory depression. Dexmedetomidine works its sedative action via α2-adrenergic receptors, and is less associated with respiratory depression. We tested the usability of dexmedetomidine as a procedural sedative during ablation of atrial fibrillation (AF). METHODS AND RESULTS: Consecutive patients were randomized to be treated with dexmedetomidine (n = 43) or thiamylal (n = 44) as sedatives during AF ablation. Apnoeic and body movement events were monitored using a novel portable respiratory monitor, the SD-101, during the procedure. Although the majority of the patients receiving dexmedetomidine required rescue sedations with thiamylal, the respiratory disturbance index (RDI) defined as the total number of sleep-disordered breathing events divided by the recording time (10.4 ± 5.1 vs. 18.2 ± 8.1 events/h; P < 0.0001) and movement index defined as the number of body movement events per hour (7.6 ± 6.1 vs. 11.0 ± 5.5 events/h; P = 0.0098) were both significantly lower in the dexmedetomidine arm than in the thiamylal arm. A multivariate linear regression analysis including potential factors revealed that dexmedetomidine vs. thiamylal was solely and independently associated with the RDI (ß = -0.62; P = 0.0031). The occurrence of hypotension [9 (21%) vs. 4 (9%); P = 0.14] and bradycardia [4 (9%) vs. 4 (9%); P = 1.0] were similar in the patients with dexmedetomidine and thiamylal. CONCLUSION: Procedural sedation with dexmedetomidine may assure safety and patient immobility during AF ablation, and therefore may be a potential alternative for that with GABAergic anaesthetics.

A head-to-head comparison of periprocedural coagulability under anticoagulation with rivaroxaban versus dabigatran in patients undergoing ablation of atrial fibrillation.

BACKGROUND AND OBJECTIVES: Two new oral anticoagulants, rivaroxaban and dabigatran, with no need for anticoagulation monitoring, are available for patients with atrial fibrillation (AF). We aimed to compare their anticoagulant effects and safety when used during the AF ablation periprocedural period. METHODS: Patients undergoing AF ablation were randomly assigned to receive rivaroxaban 15 mg once daily (N = 30) or dabigatran 110 mg twice daily (N = 30). Rivaroxaban was withheld on the morning of the day before the ablation, and dabigatran was discontinued from the evening of the day before the procedure. Both anticoagulants were then resumed after haemostasis of the access site. D-dimer levels were measured just before the ablation, at the end of the ablation, and at 24 h and 48 h after the procedure. RESULTS: The baseline D-dimer levels were identical in both groups. However, D-dimer levels increased more markedly following the ablation procedure in patients receiving rivaroxaban than in those receiving dabigatran (mean ± standard deviation from 0.62 ± 0.16 to 1.09 ± 0.38 µg/mL vs from 0.59 ± 0.08 to 0.75 ± 0.17 µg/mL; p < 0.0001). The rate of rebleeding from the access site was similar in patients receiving rivaroxaban and those receiving dabigatran (33 vs 27%; p = 0.78). CONCLUSION: As compared with dabigatran, rivaroxaban may increase the risk of hypercoagulability when used during the periprocedural period of AF ablation, suggesting a potential rebound effect of rivaroxaban or a mismatch between its half-life and dose regimen.

Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis.

BACKGROUND: Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. METHODS AND RESULTS: We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. CONCLUSIONS: The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.

Clinical significance of sleep-disordered breathing induced by sedatives during ablation of atrial fibrillation.

BACKGROUND: Sleep-disordered breathing (SDB) frequently is induced by sedation during ablation of atrial fibrillation (AF). We tested whether or not sedative-induced SDB is associated with clinical sleep apnea syndrome (SAS). METHODS: We examined SDB observed during intra-ablation sedation with a novel portable respiratory monitor (PM), SD-101, in 140 patients undergoing AF ablation without any known SAS. A sleep study was repeated the next night of the ablation with the simultaneous use of the SD-101 and type 3 PM, APNOMONITOR V. RESULTS: The respiratory disturbance index (RDI) during sedation (20.0±7.8 events/h) was significantly correlated with the RDI measured by the SD-101 during the night (15.8±13.7 events/h; r=0.50) and the RDI assessed by the APNOMONITOR V during the night (12.7±12.3 events/h; r=0.55). An excellent agreement was found between the RDIs simultaneously measured with the 2 PMs (intraclass correlation coefficient, 0.84), especially for an RDI of ≥30 events/h (κ statistic value, 0.82). The area under the receiver-operating characteristic curve for the RDI with the use of the SD-101 during sedation to identify the patients with an RDI of ≥30 events/h by both PMs during the night was 0.92. A left atrial diameter of >40 mm (odds ratio [OR], 4.10) and an RDI during sedation of >20 events/h (OR, 17.75) were independently associated with having an RDI of ≥30 events/h with both PMs during the night. CONCLUSIONS: Frequent episodes of sedative-induced SDB may have a diagnostic value for SAS in patients with AF.

Usefulness of scintigraphy to predict electrical storms in severe idiopathic dilated cardiomyopathy.

BACKGROUND: Although several predictors of an electrical storm (ES) are indicated in patients with idiopathic dilated cardiomyopathy (IDCM), whether the severity of the myocardial tissue damage (SMTD) evaluated by myocardial perfusion SPECT (MPS) has an association with an ES remains unclear. The purpose of this study was to elucidate the clinical significance of SMTD for the prediction of ES in IDCM patients with an ICD. METHODS: Thirty-seven (27 men, mean age 58 ± 15 years) IDCM patients receiving ICD implantations for secondary prevention with preoperative MPS were enrolled in this study. The medical history, physical and laboratory findings, electrocardiograms, echocardiograms and MPS findings were evaluated. The SMTD was assessed by the summed scores of 17 segments using a 4-point system (0, normal ~3, severe defect). RESULTS: During a mean follow-up of 43.9 ± 30.7 months, an ES developed in 12/37 (32.4 %) patients. The SMTD score predicted an ES with a 92 % sensitivity and 56 % specificity, at a cut-off score of 10. In addition, a multivariate analysis showed that the SMTD score remained an independent predictor of an ES (HR 1.09/score 1 increase, 95 % CI 1.01-1.19, p = 0.02). The SMTD score was significantly associated with three indices of late potentials on the signal-averaged electrocardiograms, and was significantly higher in patients with positive late potentials (p = 0.0006). CONCLUSION: SMTD score assessed by MPS has a strong correlation to the late potentials and higher SMTD score may increase the risk of ES among patients with IDCM and an ICD.

Treatment of sirolimus-eluting stent restenosis: additional stent, balloon angioplasty, and coronary artery bypass graft.

OBJECTIVE: Sirolimus-eluting stent (SES) has shown a significant efficacy in reducing restenosis after percutaneous coronary interventions. However, an increase in total number of SES use along with targeting more complex lesions generated a large number of SES restenosis. This study aimed to investigate the clinical and angiographic outcomes of different revascularization strategies for SES restenosis. METHODS AND RESULTS: A total of 176 lesions in 149 patients were included in the study. Fifteen patients underwent coronary artery bypass graft surgery (CABG group) and the remaining patients were treated with percutaneous coronary intervention (PCI). Stent reimplantation was performed in 88 patients (Stent group), whereas 46 patients received balloon therapy (Balloon group). Among 176 lesions, major cardiac adverse event (MACE) occurred in 41 lesions (23.3%) during a median follow-up of 310 days (interquartile range: 146-517 days). The Kaplan-Meier method with a log-rank test revealed no significant difference in MACE rates between the three groups (6%, 25%, 26%, p = 0.13; CABG group, Stent group, Balloon group, respectively). However, when the Balloon group and Stent group were combined together as a PCI group, PCI group had a significantly higher rate of MACE compared with the CABG group (p = 0.04). In addition, angiographic restenosis was significantly less prevalent in the CABG group when compared with the other two groups (8%, 57%, 46%, p = 0.006; CABG group, Stent group, Balloon group, respectively). CONCLUSIONS: CABG surgery for patients with SES restenosis is associated with the better clinical outcomes as well as better angiographic outcomes when compared with that of PCI.