Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 80, Issue 2
Displaying 1-45 of 45 articles from this issue
Message From the Editor-in-Chief
Reviews
  • John F. Beltrame, Filippo Crea, Juan Carlos Kaski, Hisao Ogawa, Peter ...
    Article type: REVIEW
    2016 Volume 80 Issue 2 Pages 289-298
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 18, 2015
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    Supplementary material
    Ischemic heart disease involves both “structural” and/or “functional” disorders of the coronary circulation. Structural atherosclerotic coronary artery disease (CAD) is well recognized, with established diagnostic and treatment strategies. In contrast, “functional CAD” has received limited attention and is seldom actively pursued in the investigation of ischemic heart disease. Vasospastic angina encompasses “functional CAD” attributable to coronary artery spasm and this “state of the art” consensus statement reviews contemporary aspects of this disorder. Patients with vasospastic angina typically present with angina at rest that promptly responds to short-acting nitrates and is associated with transient ischemic ECG changes. Although spontaneous episodes may be documented, provocative spasm testing may be required to confirm the diagnosis. It is important to diagnose vasospastic angina because it may be associated with major adverse events that can be prevented with the use of appropriate vasodilator therapy (eg, calcium-channel blockers) and the avoidance of aggravating stimuli (eg, smoking). Future studies are required to clarify the underlying pathophysiology, natural history and effective treatments for patients refractory to conventional therapy. (Circ J 2016; 80: 289–298)
  • Cristiana Vitale, Giuseppe MC Rosano, Juan Carlos Kaski
    Article type: REVIEW
    2016 Volume 80 Issue 2 Pages 299-305
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: January 13, 2016
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    Takotsubo cardiomyopathy (TTC) is a relatively frequent acute cardiac condition, but its pathogenesis has not been established as yet. Since the first descriptions of TTC, microvascular dysfunction has been advocated as a possible pathophysiological mechanism underlying the left ventricular wall motion abnormalities that characterize the syndrome. Several noninvasive and invasive methods have confirmed the involvement of coronary microvascular abnormalities in the pathogenesis of TTC, but whether microvascular dysfunction is the primary cause or a secondary phenomenon is still debated. The greater prevalence of TTC among postmenopausal women, along with the relationship identified between physical and emotional triggers and other “neuro-cardiac” mechanisms, suggest that increased microvascular reactivity, possibly sympathetically mediated, may play a pathogenic role in susceptible individuals. This review critically evaluates the possible role of microvascular dysfunction in the development of TTC. (Circ J 2016; 80: 299–305)
  • Li-Wei Lo, Yenn-Jiang Lin, Shih-Lin Chang, Yu-Feng Hu, Fa-Po Chung, Sh ...
    Article type: REVIEW
    2016 Volume 80 Issue 2 Pages 306-313
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: January 13, 2016
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    Catheter ablation of atrial fibrillation (AF) has evolved over the past 20 years from being a novel, unproven procedure to a commonly performed procedure. Triggers are important for the initiation of AF and a suitable substrate is important for perpetuation of AF. Remodeling, including electrical and structural remodeling, is common in patients with persistent AF. Therefore, targeting the remodeled atrium is a critical issue during persistent AF ablation. However, ablation outcomes remain suboptimal despite aggressive substrate modification. Empirical linear ablation is not recommended because of the difficulty in achieving complete linear block and it is recommended only if macroreentry tachycardia develops during the procedure. Complex fractionated atrial electrogram (CFAE) ablation is recommended in the Heart Rhythm Society Consensus Document but efficacy has been limited in long-term follow-up studies. Rotor ablation is controversial. A combined approach using CFAE, similarity and phase mappings with rotor identification may be helpful in searching for AF sources and subsequent substrate ablation. Nevertheless, more prospective randomized studies are required to validate efficacy and safety. (Circ J 2016; 80: 306–313)
Editorials
Original Articles
Aortic Disease
  • Atsuko Nakayama, Hiroyuki Morita, Naoto Hayashi, Yukihiro Nomura, Kats ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 332-339
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 07, 2015
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    Background:When the maximal diameter of an abdominal aortic aneurysm (AAA) exceeds a threshold, the likelihood of catastrophic rupture increases markedly. Therefore, surveillance at optimal intervals should be offered to patients with AAA. However, other than AAA diameter, there is no useful marker or index for predicting the expansion rate of an AAA or determining the optimal intervals for surveillance. The aim of this study was to evaluate the usefulness of calcium accumulation in the AAA for predicting its expansion rate.Methods and Results:We performed a retrospective cohort study in 414 patients with infrarenal AAA who visited The University of Tokyo Hospital. The maximal diameter and extent of calcification of each AAA were evaluated by multidetector-row computed tomography imaging. There was an inverse correlation between the extent of calcification and the subsequent AAA expansion. A lower extent of calcification in the AAA as well as the AAA diameter and absence of coronary artery disease correlated with an accelerated expansion of the AAA.Conclusions:In AAA, a lower extent of calcification correlated with accelerated expansion. The calcification index of an AAA can be a useful predictor of its expansion rate. The study findings also support the theory that the mechanisms for progression in atherosclerosis with calcification and external expansion of an aneurysm are distinct. (Circ J 2016; 80: 332–339)
Arrhythmia/Electrophysiology
  • Moritoshi Funasako, Takeshi Aiba, Kohei Ishibashi, Ikutaro Nakajima, K ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 340-345
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 03, 2015
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    Background:Mexiletine is often used for medical therapy in LQT3 patients, however, the usefulness of mexiletine infusion test for LQT3 patients has not been reported. The aim of this study was to evaluate the usefulness of mexiletine infusion test for detecting LQT3 patients.Methods and Results:We analyzed response in 12-lead electrocardiogram parameters measured in II or V5 to i.v. mexiletine infusion (2 mg/kg) during sinus rhythm among 31 genotype-positive LQT patients (29±18 years, 12 male). Change in QTc interval after mexiletine was compared between LQT3 (n=15, 24±21 years, 9 male) and other LQT patients (4 LQT1 and 12 LQT2; 34±14 years, 3 male). Baseline RR, QT, and QTc interval were not different between the 2 groups (981±182 vs. 1,023±192 ms; 550±94 vs. 524±75 ms; 556±66 vs. 520±62 ms, respectively). While QTc interval was shortened with mexiletine in both groups (P<0.0001 vs. baseline), degree of QTc shortening (∆QTc) was significantly larger in LQT3 than in LQT1/LQT2 patients (99±39 vs. 48±32 ms; P=0.0004). The sensitivity, specificity and predictive accuracy of mexiletine infusion test for differentiating LQT3 from LQT1/LQT2 were 86.7%, 81.3% and 81.3%, respectively, and the optimal cut-off for ∆QTc was 69 ms on receiver operating characteristic analysis. No pro-arrhythmic event was observed.Conclusions:Pronounced shortening of QT interval with mexiletine may facilitate genetic testing in patients with LQT3 syndrome. (Circ J 2016; 80: 340–345)
  • Shinsuke Miyazaki, Akio Kuroi, Hitoshi Hachiya, Hiroaki Nakamura, Hiro ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 346-353
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 04, 2015
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    Supplementary material
    Background:Inflammation plays a prominent role in the etiology of the early recurrence of atrial fibrillation (ERAF). We prospectively compared the proportion of ERAF and time-course patterns of biomarkers between radiofrequency (RF) and cryoballoon (CB) ablation.Methods and Results:We enrolled 82 consecutive paroxysmal AF patients undergoing pulmonary vein (PV) isolation, performed with either a 28-mm 2nd-generation CB and 3-min freeze technique or point-by-point RF ablation. Each group had 41 patients. In the RF group, all PVs were successfully isolated with 28.9±6.5 min of RF delivery. In the CB group, a mean of 5.3±1.4 applications/patient was delivered. The proportion of ERAF was similar between the groups. The time-course patterns significantly differed between the groups for high-sensitivity C-reactive protein (hs-CRP) value (P=0.006) and myocardial injury markers (P<0.0001). Greater myocardial injury was observed in the CB than in the RF group (P<0.0001), whereas the peak hs-CRP value was comparable between the groups. The 2-day post-procedure hs-CRP value was the sole factor correlating with ERAF as identified by the multivariable analysis (hazard ratio 1.697; 95% confidence interval, 1.005–2.865; P=0.048) in the RF, but not the CB group.Conclusions:The proportion of ERAF was comparable after RF and 2nd-generation CB ablation. Despite CB ablation exhibiting greater myocardial injury than RF ablation, the inflammatory responses were comparable between the groups. The inflammatory response extent predicted ERAF post-RF ablation but not post-CB ablation. (Circ J 2016; 80: 346–353)
  • Antonia Sambola, Maria Mutuberría, Bruno García del Blanco, Albert Alo ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 354-362
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 25, 2015
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    Background:The effects of dual antiplatelet therapy (DAPT) and triple therapy (TT: DAPT plus oral anticoagulation) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) regarding to CHA2DS2-VASc score remain undefined.We compare the effect of TT vs. DAPT in this setting regarding the CHA2DS2-VASc score.Methods and Results:In a prospective multicenter registry, 585 patients (75.2% male, 73.2±8.2 years) with AF undergoing PCI were followed up during 1 year. Of them, 157 (26.8%) had a CHA2DS2-VASc=1, and 428 (73.2%) had a CHA2DS2-VASc ≥2. TT was prescribed in 51.6% with CHA2DS2-VASc=1 and in 55.5% with CHA2DS2-VASc ≥2. Patients with CHA2DS2-VASc=1 receiving TT had a similar thromboembolism rate to those on DAPT (1.2% vs. 1.3%, P=0.73), but more total (19.5% vs. 6.9%, P=0.01) and a tendency to more major (4.9% vs. 0%, P=0.06) bleeding. However, patients with CHA2DS2-VASc ≥2 receiving TT had a lower thromboembolism rate (1.7% vs. 5.3%, P=0.03) and a trend towards more bleeds (21.8% vs. 15.6%, P=0.06), with an excess of major bleeding (8.4% vs. 3.1%, P=0.01). Rates of major adverse cardiac events (MACE) in both CHA2DS2-VASc subgroups were similar, irrespective of treatment. In a Cox multivariate analysis, TT was associated to major bleeding, but not with MACE.Conclusions:In patients with AF and CHA2DS2-VASc=1 undergoing PCI, the use of TT involves a high risk of bleeding without a significant benefit in preventing thromboembolism. (Circ J 2016; 80: 354–362)
Cardiovascular Intervention
  • Dong-Yi Chen, Chun-Tai Mao, Ming-Lung Tsai, Ming-Jer Hsieh, Yu-Sheng L ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 363-370
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: November 19, 2015
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    Supplementary material
    Background:Data on the cardiovascular (CV) outcomes of drug-eluting stents (DES) vs. bare-metal stents (BMS) in patients with acute myocardial infarction (AMI) under dialysis are limited.Methods and Results:We analyzed the data from 42,592 AMI patients in the Taiwan National Health Insurance Research Database between 1 January 2007 and 31 December 2011. A total of 984 AMI patients under dialysis were selected as the study cohort. We evaluated the clinical outcomes by comparing 492 subjects who had DES to 492 matched subjects who had BMS. The primary composite outcomes, which included recurrent MI, coronary revascularization and CV death, were significantly lower in the DES group than in the BMS group (41.7% vs. 47.6%, hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.63–0.92, P=0.005) after mean 1.2 years. The patients who received DES had a lower risk of recurrent MI (HR, 0.63; 95% CI, 0.45–0.90), CV death (HR, 0.74; 95% CI, 0.56–0.98) and all-cause mortality (HR, 0.74; 95% CI, 0.61–0.89) than those who used BMS, but a similar risk of major bleeding (HR, 0.99; 95% CI, 0.69–1.42, P=0.952) and ischemic stroke (HR, 1.15; 95% CI, 0.66–2.01, P=0.631).Conclusions:Among AMI patients on dialysis undergoing percutaneous coronary interventions, DES implantation significantly reduced the risk of recurrent MI, CV death and all-cause mortality compared with BMS implantation. (Circ J 2016; 80: 363–370)
  • Toshiaki Toyota, Hiroki Shiomi, Tomohiko Taniguchi, Takeshi Morimoto, ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 371-378
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: November 20, 2015
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    Supplementary material
    Background:We assessed the current status of treatment strategy in ST-segment elevation myocardial infarction (STEMI) with multivessel disease (MVD) in real world practice, focusing on the benefit of staged percutaneous coronary intervention (PCI).Methods and Results:From the CREDO-Kyoto AMI Registry, 2,010 STEMI patients with MVD undergoing primary PCI were analyzed. Only 96 patients (4.8%) received acute multivessel PCI, and the majority of patients (n=1,914, 95.2%) had culprit-only PCI acutely. After excluding 699 patients (acute multivessel PCI, Killip class ≥3, age ≥90 years, coronary artery bypass grafting within 90 days, or clinical events within 90 days), 681 MVD patients underwent staged PCI for angiographically significant non-culprit lesions within 90 days (staged PCI group), while 630 MVD patients received primary PCI only (culprit-only PCI group). The cumulative 5-year incidence of and adjusted risk for all-cause death were significantly lower in the staged PCI group compared with the culprit-only PCI group (9.5% vs. 16.0%, P<0.001; HR, 0.69; 95% CI: 0.50–0.96, P=0.03). The risks for MI and any coronary revascularization favored the staged PCI strategy.Conclusions:The staged PCI strategy for angiographically significant non-culprit lesions was associated with lower 5-year mortality compared with the culprit-only PCI strategy in STEMI patients with MVD who underwent primary PCI. (Circ J 2016; 80: 371–378)
  • Madlen Uhlemann, Sven Möbius-Winkler, Jennifer Adam, Sandra Erbs, Norm ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 379-386
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 02, 2015
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    Background:Drug-eluting balloons (DEB) are an alternative treatment of in-stent restenosis (ISR), but data regarding outcomes of DEB in de novo lesions are lacking.Methods and Results:We investigated the effect of DEB on target lesion revascularization (TLR), procedural complications (coronary dissection/rupture, pericardial effusion, stent thrombosis, peri-interventional NSTEMI, stroke), major adverse cardiac and cerebrovascular events (all-cause mortality, myocardial infarction, TLR, stroke) in patients with ISR and de novo lesions in an all-comers setting. Between April 2009 and October 2013, 484 consecutive patients (mean age 68.4 years; 77.9% male) were enrolled in a prospective registry. TLR rate was 4.9% at 12 months and 8.7% at long-term follow-up of 2.3 years. Subgroup analysis confirmed a TLR rate of 8.9% after DEB treatment of ISR in bare-metal stents (21/235 lesions), 13.0% in drug-eluting stents (21/161 lesions) and 0% for de novo lesions (0/76 lesions). At long-term follow-up, all-cause mortality/cardiac mortality was 8.7% (42/484)/3.3% (16/484) and MACCE rate was 18.4% (89/484 patients), with no differences between DEB for ISR compared with de novo lesions.Conclusions:DEB for ISR resulted in a low rate of TLR. Our data support DEB in ISR as an effective treatment option. DEB in small coronary vessels in our limited cohort appeared to be safe. Larger, randomized trials in small coronary vessels should be undertaken to verify the long-term results of the current trial. (Circ J 2016; 80: 379–386)
Cardiovascular Surgery
  • Daisuke Nitta, Koichiro Kinugawa, Teruhiko Imamura, Miyoko Endo, Toshi ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 387-394
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 04, 2015
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    Background:Although destination therapy (DT) is now expected to be a promising strategy for those who are not suitable for heart transplantation in Japan, there has not been any investigation into ineligibility for bridging to implantable left ventricular assist device (I-LVAD) as DT among patients with extracorporeal LVAD.Methods and Results:We retrospectively studied 85 patients who had received an extracorporeal LVAD. To assess ineligibility for a bridge to I-LVAD for DT, we defined DT ineligibility (DTI) as BiVAD requirement, death within 6 months, and persistent end-organ dysfunction (medium or high J-VAD risk score) at 6 months after extracorporeal LVAD implantation. DTI was recorded for 32 patients. Uni/multivariate analysis showed that smaller left ventricular diastolic dimension (<64 mm; [odds ratio (OR) 4.522]), continuous hemodiafiltration (OR 4.862), past history of cardiac surgery (OR 6.522), and low serum albumin level (<3.1 g/dl; OR 10.064) were significant predictors of DTI. By scoring 2, 2, 3, 4 points, respectively, considering each OR, we constructed a novel scoring system for DTI (DTI score), which stratified patients into 3 risk strata: low (0–3 points), medium (4–6 points), and high (7–11 points), from the view point of DTI risk (low 8%, medium 46%, high 93%, respectively).Conclusions:DTI score is a promising tool for predicting ineligibility for I-LVAD as DT before extracorporeal VAD implantation. (Circ J 2016; 80: 387–394)
  • Takuma Sato, Osamu Seguchi, Hatsue Ishibashi-Ueda, Masanobu Yanase, No ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 395-403
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 22, 2015
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    Background:Cardiac allograft vasculopathy (CAV) limits long-term success after heart transplant. We assessed the post-transplant risk factors for CAV development.Methods and Results:Patients who underwent heart transplant between May 1999 and December 2013 were included in this study. Patients (n=54) were divided into 2 groups according to the presence or absence of CAV progression after transplant. Coronary angiogram and intravascular ultrasound were conducted within 5–11 weeks after transplant, at 12 months, and annually thereafter. Scheduled endomyocardial biopsies were performed after transplant or whenever acute cellular rejection (ACR) or antibody-mediated rejection was suspected. Twenty-five of 54 patients (46.2%) had CAV progression. ACR ≥International Society for Heart and Lung Transplantation grade 2 (ACR ≥2) and donor age >50 years were significantly associated with CAV development compared with ACR <2 and donor age <50 years. Patients with no history of ACR ≥2 and donor age ≤50 years had a significantly low risk of developing CAV compared with the other groups.Conclusions:Donor age and history of ACR ≥2 are independent risk factors for CAV development. Identifying patients at risk of developing CAV is important for appropriate direction of resources and intensity of follow-up. (Circ J 2016; 80: 395–403)
Heart Failure
  • Wei-Ming Huang, Pai-Feng Hsu, Hao-Min Cheng, Dai-Yin Lu, Yu-Lun Cheng, ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 404-410
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: November 20, 2015
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    Background:Hyperuricemia is a prognostic factor in patients with chronic heart failure, but whether uric acid level can predict clinical outcome of acute heart failure (AHF) remains to be elucidated. We therefore investigated the association of uric acid with mortality in patients hospitalized for AHF.Methods and Results:Data for patients hospitalized for AHF were drawn from an intramural registry. Biochemistry data, echocardiographic characteristics, and uric acid level were collected. National Death Registry was linked for the identification of mortality data. Among a total of 1,835 participants (age, 75±13 years, 68% men), 794 patients died during follow-up. Patients who died were older, had lower hemoglobin and estimated glomerular filtration rate, and higher pulmonary artery systolic pressure, NT-proBNP, and uric acid. Uric acid was a significant predictor of mortality on univariate analysis (HR per 1 SD, 1.18; 95% CI: 1.11–1.26) and in multivariate Cox models (HR, 1.15; 95% CI: 1.02–1.29). Survival analysis showed an increasing risk of death along the quartile distribution of uric acid level. Given renal function, cardiac performance, and kidney perfusion as major determinants of hyperuricemia, the prognostic impact of uric acid level was diminished as renal function deteriorated.Conclusions:Uric acid level was an independent predictor of mortality in patients hospitalized for AHF, but the prognostic impact of hyperuricemia was attenuated by worsening renal function. (Circ J 2016; 80: 404–410)
  • Hiroaki Kusaka, Seigo Sugiyama, Eiichiro Yamamoto, Eiichi Akiyama, Yas ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 411-417
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 03, 2015
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    Supplementary material
    Background:Hyponatremia has been shown to be a prognostic factor in heart failure (HF) with preserved ejection fraction (HFpEF). Serum sodium (sNa) cut-off, however, is not defined in HFpEF. Therefore, we investigated the relationship between sNa and HF-related events (cardiovascular death and hospitalization for HF decompensation) in HFpEF patients.Methods and Results:We assessed cardiac function using echocardiography and measured sNa in HFpEF patients with New York Heart Association class II (n=321) or III (n=84) in a compensated condition after implementing medical therapy for HF. During a mean follow-up of 27 months, 73 patients developed HF-related events. On multivariate Cox hazard analysis including established predictors in HF, sNa level as a continuous variable was identified as an independent predictor for HF-related events in HFpEF (per 1.0 mmol/L: HR, 0.93; 95% CI: 0.87–0.98; P<0.01). Kaplan-Meier analysis demonstrated significantly higher probability of HF-related events in the lower sNa group (sNa <140 mmol/L) than in the higher sNa group (sNa ≥140 mmol/L; P<0.001, log-rank test). Further, the low-normal sNa group (135 mmol/L<sNa<140 mmol/L) was significantly associated with HF-related events compared with the higher sNa group (P<0.001, log-rank test).Conclusions:sNa as a continuous variable was independently correlated with future HF-related events in HFpEF. Low-normal sNa could provide important prognostic information for practical risk stratification in HFpEF. (Circ J 2016; 80: 411–417)
  • Yuichi Kawase, Kazushige Kadota, Takeshi Tada, Reo Hata, Keiichiro Iwa ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 418-425
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 15, 2015
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    Background:Predictors of worsening renal function (WRF: increase in serum creatinine ≥0.3 mg/dl from the value on admission) in patients with acute decompensated heart failure (ADHF) treated by low-dose carperitide (0.01–0.05 μg/kg/min) are unclear.Methods and Results:We retrospectively investigated predictors of WRF within the first 24 h of low-dose carperitide therapy in 205 patients (mean age, 75.6±12.1 years) hospitalized for ADHF and treated with low-dose carperitide between January 2006 and April 2014. WRF occurred in 14 patients (7%). A multivariate adjustment analysis showed that independent predictors of WRF within 24 h were hypotension (systolic blood pressure <90 mmHg) within 12 h (odds ratio, 8.7; 95% confidence interval, 2.38–35.88; P=0.0012) and serum creatinine on admission (odds ratio, 3.64; 95% confidence interval, 1.84–7.67; P=0.0003). In patients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, the rate of WRF occurrence was higher in those complicated by hypotension than in those without hypotension (22.6% [7/31 patients] vs. 4.4% [5/113 patients], P=0.0041). In contrast, in patients with eGFR ≥60 ml/min/1.73 m2, hypotension did not influence the occurrence of WRF (0% [0/9 patients] vs. 3.9% [2/51 patients], P=NS).Conclusions:Hypotension within 12 h and renal dysfunction on admission are independent predictors of WRF within 24 h in patients with ADHF treated by low-dose carperitide. Hypotension may not cause WRF in patients with eGFR ≥60 ml/min/1.73 m2. (Circ J 2016; 80: 418–425)
Hypertension and Circulatory Control
  • Norihisa Toh, Katsuhisa Ishii, Hajime Kihara, Katsuomi Iwakura, Hiroyu ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 426-434
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 25, 2015
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    Supplementary material
    Background:Hypertension increases the risk of left ventricular (LV) diastolic dysfunction, and anti-hypertensive therapy may improve LV relaxation. The aim of this study was to investigate whether combining an angiotensin-receptor blocker (ARB) with either hydrochlorothiazide (HCTZ) or a calcium-channel blocker (CCB) improves LV relaxation in patients with hypertension and diastolic dysfunction.Methods and Results:Hypertensive patients who had not achieved their target blood pressure with at least 4 weeks of ARB therapy were randomly assigned to receive either a fixed-dose combination of losartan and HCTZ (losartan/HCTZ; n=110) or a combination of amlodipine and a typical ARB dosage (CCB/ARB; n=121) and followed for 24 weeks. The primary endpoint was change in early diastolic mitral annular velocity (e’, cm/s). Systolic blood pressure decreased in both groups after switch to the combination therapies. E’ velocity increased both in the losartan/HCTZ (0.52 cm/s) and in the CCB/ARB (0.59 cm/s) groups. The mean (95% CI) treatment difference was −0.02 (−0.37 to 0.34) cm/s, indicating that improvement in LV relaxation was similar between the groups. The ratio of early mitral inflow velocity to e’ velocity and left atrial volume index were significantly decreased in the losartan/HCTZ group.Conclusions:The combination of losartan and HCTZ is as effective as amlodipine plus ARB in improving LV relaxation in hypertensive patients. (Circ J 2016; 80: 426–434)
Imaging
  • Shinro Matsuo, Kenichi Nakajima, Tomoaki Nakata
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 435-441
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 04, 2015
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    Background:Although there are several known prognostic determinants in heart failure (HF), individual risk profiles can vary, in particular between ischemic and non-ischemic HF background. This study investigated the difference in prognostic efficacy of cardiac 123I-meta-iodobenzylguanidine (MIBG) imaging between the 2 etiologies.Methods and Results:All 1,322 patients with HF were enrolled and followed up at most after 10 years. The HF patients were divided into 2 groups: an ischemic group (n=362) and non-ischemic group (n=960), and Cox proportional hazards model was used for data analysis. During 10 years of follow-up, 296 (22.4%) of 1,322 patients died; the mortality rates were 21.8% and 22.6% for the ischemic and non-ischemic groups, respectively. The ischemic group had greater prevalence of sudden death and lethal acute myocardial infarction, and the non-ischemic group had a higher rate of pump failure death. On multivariate Cox proportional hazards analysis using categorized variables, in the ischemic group, delayed heart-to-mediastinum ratio (HMR; P<0.0001), age (P=0.0002) and LVEF (P=0.03) were the independent significant predictors of lethal events. In the non-ischemic group, delayed HMR (P<0.0001), NYHA class (P<0.0001) and age (P<0.0001) were significant determinants of lethal outcome.Conclusions:Cardiac MIBG imaging has nearly identical prognostic value in both ischemic and non-ischemic HF, independent of cause of cardiac death. (Circ J 2016; 80: 435–441)
Ischemic Heart Disease
  • Ioanna Xanthopoulou, Periklis Davlouros, Grigorios Tsigkas, Nikolaos K ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 442-449
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: November 24, 2015
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    Background:Delay in the onset of antiplatelet action occurs in patients with ST-elevation myocardial infarction (STEMI) and is likely due to disturbed absorption. We hypothesized that patients presenting relatively late after the onset of symptoms would have faster antiplatelet action.Methods and Results:We analyzed patient-level data from 5 studies of 207 P2Y12receptor antagonist-naïve patients with STEMI undergoing primary percutaneous coronary intervention (PCI). All patients had available platelet reactivity (PR) assessment with the VerifyNow assay (in P2Y12reaction units; PRU) prior to and 2 h after loading. High PR (HPR) was defined as ≥208 PRU. Pain-to-antiplatelet loading time independently predicted PR at 2 h after loading: every 1-h increase in pain-to-antiplatelet loading time produced a 7% decrease in PR (P=0.001). Pretreatment PR, body mass index, morphine and novel P2Y12receptor antagonist also affected PR 2 h after loading. Novel P2Y12receptor antagonist use and per hour increase in pain-to-antiplatelet loading time were independently associated with lower probability for HPR with an OR (95% CI) of 0.145 (0.095–0.220) and 0.776 (0.689–0.873), P<0.001 for both (C-statistic, 0.752; 95% CI: 0.685–0.819).Conclusions:In STEMI patients undergoing primary PCI, pain-to-antiplatelet loading interval is a newly described factor affecting PR shortly after P2Y12receptor antagonist loading, according to patient-level data pooled analysis. (Circ J 2016; 80: 442–449)
  • Toshiyuki Niki, Tetsuzo Wakatsuki, Koji Yamaguchi, Yoshio Taketani, Hi ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 450-460
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 11, 2015
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    Background:The effects of eicosapentaenoic acid (EPA) on coronary artery disease have been previously reported; however, those of the addition of EPA to strong statins on coronary plaque components and local inflammatory cytokines are not known.Methods and Results:A total of 95 patients who had been treated with strong statin for at least 6 months were randomized into 2 groups: an EPA group (additional treatment with EPA at 1,800 mg/day, n=48) or a control group (no additional treatment, n=47), for 6 months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein.A significant reduction in lipid volume (18.5±1.3 to 15.0±1.5 mm3, P=0.007) and a significant increase in fibrous volume (22.9±0.8 to 25.6±1.1 mm3, P=0.01) were observed in IB-IVUS image analyses in the EPA group, but no significant changes in the plaque components in the control group. CS levels of pentraxin 3 and monocyte chemoattractant protein-1 were lower after than before treatment with EPA (3.3±2.1 to 2.6±1.2 ng/ml, 120.4±26.2 to 110.2±26.8 pg/ml, P=0.015 and P=0.008, respectively); however, there were no significant changes in those inflammatory cytokines between pre- and post-treatment in the control group.Conclusions:The addition of EPA was associated with reduced lipid volume in coronary plaques and decreased inflammatory cytokines. (Circ J 2016; 80: 450–460)
  • Mizuki Miura, Masao Yamasaki, Yukari Uemura, Masatomo Yoshikawa, Katsu ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 461-468
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 08, 2015
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    Background:Previous trials have found that low low-density lipoprotein-cholesterol (LDL-C) on admission was associated with increased mortality in patients with acute myocardial infarction (AMI). There are few reports, however, on the effect of low LDL-C with or without in-hospital statin treatment on short-term prognosis in AMI patients.Methods and Results:A total of 9,032 AMI patients underwent primary PCI in 68 centers in the Tokyo CCU Network Registry during 2009–2012, in whom LDL-C was measured in 6,486. We divided them into 4 groups: statin-treated/LDL-C <100 mg/dl (n=1,236), statin-treated/LDL-C ≥100 mg/dl (n=3,671), statin-naïve/LDL-C <100 mg/dl (n=662), and statin-naïve/LDL-C ≥100 mg/dl (n=917). We assessed hospital mortality within 30 days. In-hospital all-cause mortality was significantly lower in the statin-treated/LDL-C ≥100-mg/dl group (3.2%, P<0.001). On multivariate Cox regression analysis, adjusted for age, gender, hypertension, diabetes mellitus, dyslipidemia and other clinical factors, the combination of statin treatment and LDL-C ≥100 mg/dl was an independent predictor of lower in-hospital mortality (adjusted HR, 0.211; 95% CI: 0.096–0.462; P<0.001). In the LDL-C <100-mg/dl patients, statin treatment also independently reduced in-hospital mortality (adjusted HR, 0.467; 95% CI: 0.223–0.976; P=0.043). Spontaneously low LDL-C was associated with increased short-term mortality.Conclusions:Statin treatment was associated with better short-term outcome in patients with AMI, even in patients with low LDL-C. (Circ J 2016; 80: 461–468)
  • Takayuki Mitsuhashi, Kiyoshi Hibi, Masaaki Konishi, Nobuhiko Maejima, ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 469-476
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 10, 2015
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    Background:The relationship between plasma glucagon-like peptide-1 (GLP-1) and coronary plaque characteristics in humans remains unclear.Methods and Results:A total of 85 culprit coronary vessels excluding the 10-mm culprit segments in non-diabetic patients with acute coronary syndrome (ACS) were examined using integrated backscatter intravascular ultrasound, performed using a 40-MHz intravascular catheter before PCI. All patients underwent 75-g oral glucose tolerance test (OGTT), and the plasma GLP-1 response was evaluated on the basis of the area under the GLP-1 concentration-time curve (GLP-1 AUC) from 0 to 120 min. Patients in the low GLP-1 AUC tertile had a significantly greater percentage lipid area than did patients in the intermediate and high tertiles (low tertile vs. intermediate tertile vs. high tertile: 57.3±12.1% vs. 47.2±15.4% vs. 46.3±12.7%, P<0.01, ANOVA) and a smaller percentage fibrosis area (38.1±9.4% vs. 44.6±11.5% vs. 45.7±9.0%; P=0.01, ANOVA). On multiple regression analysis, low GLP-1 AUC tertile was independently associated with percentage lipid area.Conclusions:Low plasma GLP-1 during 75-g OGTT is associated with increased lipid content in non-diabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients. (Circ J 2016; 80: 469–476)
  • Kenji Nakatsuma, Hiroki Shiomi, Takeshi Morimoto, Kenji Ando, Kazushig ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 477-484
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 15, 2015
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    Supplementary material
    Background:In the setting of elective percutaneous coronary intervention (PCI), intravascular ultrasound (IVUS)-guided PCI is associated with a reduction in the incidence of target vessel revascularization (TVR), but the impact of IVUS on long-term clinical outcome in the setting of emergency PCI for ST-segment elevation acute myocardial infarction (STEMI) is still unclear.Methods and Results:The subjects consisted of 3,028 STEMI patients who underwent primary PCI within 24 h of symptom onset in the CREDO-Kyoto acute myocardial infarction registry. Of these, 932 patients (31%) underwent IVUS-guided PCI. Compared with the angiography-guided PCI without IVUS, IVUS-guided PCI was associated with significantly lower incidences of TVR (primary outcome measure; 22% vs. 27%, log-rank P<0.001) and definite stent thrombosis (ST; 1.2% vs. 3.1%, log-rank P=0.003). The cumulative incidence of all-cause death was not significantly different between the 2 groups. After adjusting for confounders, however, there were no significant differences between the 2 groups in risk for TVR (adjusted HR, 1.14; 95% CI: 0.86–1.51, P=0.38) and definite ST (adjusted HR, 0.58; 95% CI: 0.19–1.72, P=0.33).Conclusions:IVUS-guided PCI was not associated with a lower risk for TVR or ST in STEMI patients undergoing primary PCI. (Circ J 2016; 80: 477–484)
  • Mario Petretta, Wanda Acampa, Stefania Daniele, Emilia Zampella, Rober ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 485-493
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 18, 2015
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    Supplementary material
    Background:We assessed the relationship between clinical outcome and coronary revascularization according to stress-gated myocardial perfusion single-photon emission computed tomography (MPS) in an observational series of patients with suspected or known coronary artery disease (CAD), on long-term follow-up.Methods and Results:The study group consisted of 2,059 patients. During a median follow-up of 61 months, 184 events occurred (126 cardiac deaths and 58 non-fatal MI). The impact of revascularization during follow-up on event-free survival was evaluated using an extended Cox regression model, adjusting for potential clinical and MPS confounders. Revascularization was treated as a binary non-reversible time-dependent covariate. Predefined interactions tested were: (1) revascularization and summed difference score (SDS); (2) revascularization and post-stress left ventricular (LV) ejection fraction (EF); and (3) SDS and post-stress LVEF. Revascularization had a significant effect on event-free survival (adjusted HR, 0.19; P<0.001). Significant interactions were found between revascularization and SDS (P=0.045), and between LVEF and SDS (P=0.015). The protective effect of revascularization increased as SDS increased. For SDS <6 the reduction in HR was detectable only for reduced LVEF.Conclusions:Both the degree of stress-induced ischemia and LVEF predict the effect of revascularization on outcome in patients with suspected or known CAD. The protective effect of revascularization appears to be greater in patients with severe ischemia and preserved LVEF. (Circ J 2016; 80: 485–493)
  • Hsin-Ru Li, Tse-Min Lu, Hao-Min Cheng, Dai-Yin Lu, Chuen-Wang Chiou, S ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 494-501
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 22, 2015
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    Supplementary material
    Background:Heart rate variability (HRV) is usually reduced in patients with CAD. We therefore investigated whether reduced HRV is predictive of angiographic CAD beyond Framingham risk in patients with stable angina.Methods and Results:A total of 514 patients (age, 66.1±14.3years, 358 men) were enrolled. Holter ECG was performed before catheterization, and 24-h HRV was analyzed in both the frequency domain (VLF, LF, HF and total power) and the time domain (SDNN, SDANN, RMSSD and pNN20). Angiographic CAD was defined as ≥50% diameter reduction of 1 or more coronary arteries. On coronary angiography 203 patients (39.6%) had angiographic CAD. Patients with CAD had significantly higher Framingham risk and lower HRV according to both frequency and time domain parameters. After controlling for age, gender, heart rate, SBP, renal function, lipids and Framingham risk, reduced HRV indices remained predictors of CAD (OR, 95% CI for LF, HF, SDNN, RMSSD and pNN20: 0.81, 0.66–0.99; 0.77, 0.63–0.94; 0.75, 0.59–0.96; 0.72, 0.58–0.88; and 0.76, 0.62–0.94, respectively). On subgroup analysis, HRV parameters appeared to be predictive of CAD only in subjects with high Framingham risk or diabetes.Conclusions:Reduced HRV is predictive of CAD in patients with stable angina, independent of traditional risk factors and Framingham risk. The predictive value of HRV may be relevant only in subjects with high Framingham risk or diabetes. (Circ J 2016; 80: 494–501)
Metabolic Disorder
  • Francesca Santilli, Maria Teresa Guagnano, Paolo Innocenti, Liberato A ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 502-511
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 03, 2015
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    Background:Circulating pentraxin 3 (PTX3), the main regulator of the inflammatory response, rapidly increases following cardiovascular events, and low PTX3 is associated with high body mass index.Methods and Results:We conducted a 12-month longitudinal study, to test the hypothesis that laparoscopic adjustable gastric banding (LAGB)-induced weight loss was associated with changes in platelet activation markers and PTX3. Twelve obese patients, scheduled to undergo LAGB, were enrolled at the University Obesity Center. Urinary 11-dehydro-thromboxane (Tx)B2excretion rate was measured on radioimmunoassay, and PTX3 and CD40L were determined on immunoassay. Plasma PTX3 increased by 178.8 and 214.9% (P<0.0001), respectively, 6 and 12 months after LAGB. High-sensitivity CRP decreased by 24 and 29.7% (P<0.0001), whereas CD40L decreased by 64.3 and 58.6% (P=0.002), respectively. Urinary 11-dehydro-TxB2decreased from 1,443 to 715 and 564 pg/mg creatinine, respectively 6 months and 12 months after LAGB (P<0.0001). PTX3 was inversely related to platelet activation markers, 11-dehydro-TxB2and CD40L. Moreover, multiple regression analysis on pooled data showed that plasma PTX3 was an independent predictor of urinary 11-dehydro-TxB2.Conclusions:There is an association between inflammation, platelet activation and metabolic dysfunction in obesity, and PTX3 is a key player within these circuits. (Circ J 2016; 80: 502–511)
  • Hayato Tada, Masa-aki Kawashiri, Taiji Yoshida, Ryota Teramoto, Atsush ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 512-518
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 02, 2015
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    Supplementary material
    Background:It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mutation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene.Methods and Results:We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4–33.9], 21.1 mg/dl [IQR:11.7–34.9], and 5.0 mg/dl [IQR:2.7–8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL).Conclusions:These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations. (Circ J 2016; 80: 512–518)
Valvular Heart Disease
  • Kentaro Shibayama, Masao Daimon, Hiroyuki Watanabe, Takayuki Kawata, S ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 519-525
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: December 24, 2015
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    Background:Because the covariates of cardiovascular events in unoperated patients with asymptomatic aortic stenosis (AS) have not been adequately evaluated, we aimed to identify them.Methods and Results:A total of 230 patients with asymptomatic severe AS were retrospectively enrolled. The patients were divided into 2 groups based on aortic valve replacement (AVR) after enrollment: a non-AVR group (n=112), and an AVR group (n=118). The primary clinical endpoint was cardiovascular events, which were defined as cardiovascular death or hospitalization. Coronary artery disease [hazard ratio (HR): 3.62, 95% confidence interval (CI): 1.585–8.245, P<0.01] and high valvulo-arterial impedance (HR: 3.08, 95% CI: 1.261–7.532, P<0.05) were identified as independent covariates of cardiovascular events in the non-AVR group. The relative risk of cardiovascular events rose with an increase in the number of risk factors (P<0.0001).Conclusions:In unoperated patients with asymptomatic AS, the presence of coronary artery disease and increased global left ventricular afterload may be associated with a poor prognosis. (Circ J 2016; 80: 519–525)
  • Tomohiko Taniguchi, Hiroki Shiomi, Masami Kosuge, Takeshi Morimoto, Ke ...
    Article type: ORIGINAL ARTICLE
    2016 Volume 80 Issue 2 Pages 526-534
    Published: January 25, 2016
    Released on J-STAGE: January 25, 2016
    Advance online publication: January 08, 2016
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    Supplementary material
    Background:ST-segment elevation (STE) in leads V1–2is often observed in patients with severe aortic stenosis (AS), but its significance remains unknown.Methods and Results:We retrospectively evaluated baseline ECGs and 5-year clinical outcomes in 211 consecutive patients with severe AS, defined as peak aortic jet velocity (Aortic Vmax) >4.0 m/s, or mean aortic pressure gradient >40 mmHg, or aortic valve area (AVA) <1.0 cm2. The primary outcome measure was a composite of death or surgical aortic valve replacement (AVR). Patients with STE in leads V1–2(≥0.15 mV) had greater Aortic Vmaxand smaller AVA than patients without. With a median follow-up of 4.9 years, the cumulative 5-year incidence of death or AVR was significantly higher in patients with STE in leads V1–2than in patients without (91.4% vs. 77.1%; P=0.003). After adjusting for confounders, STE in leads V1–2was independently associated with higher risk for death or AVR (hazard ratio, 1.53; 95% confidence interval, 1.06–2.22; P=0.02). In 64 asymptomatic patients without any indication for AVR at initial diagnosis of severe AS, the cumulative incidence of AVR was significantly higher in patients with STE in leads V1–2than in patients without (57.6% vs. 30.5%; P<0.001).Conclusions:STE in leads V1–2independently predicted poorer prognosis and more frequent need for AVR in patients with severe AS. (Circ J 2016; 80: 526–534)
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