Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 80 , Issue 10
Showing 1-34 articles out of 34 articles from the selected issue
Message From the Editor-in-Chief
Reviews
  • Kunihiro Shimamura, Giulio Guagliumi
    Type: REVIEW
    2016 Volume 80 Issue 10 Pages 2063-2072
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 09, 2016
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    Decision making on lesion preparation and stent/scaffold optimization are cornerstones of patient outcome. Intravascular imaging recently emerged as a critical modality to achieve better results of stent/scaffold implantation and superior clinical outcomes compared with coronary angiography alone. Optical coherence tomography (OCT), a light-based intravascular imaging modality with high frame rate in acquisition and very high speed pullback, can interrogate the target vessel in a couple of seconds, and immediately display a pristine longitudinal lumen contour with automatic detection of lesion severity, site and lumen/stent areas. Further, OCT provides pivotal information on sites of calcium, with accurate measurements of the minimum distance from the lumen, a major determinant of stent/scaffold underexpansion, malapposition and eccentricity. Finally, to guide the PCI procedure using OCT without operator misjudgment, a real-time point-to-point correspondence between angiographic and OCT images has been recently created. Co-registration of OCT with angiography with direct tableside control of acquisition and analysis enables the operator to plan and map optimal stent/scaffold implantation. To prove the clinical relevance of OCT-guided PCI, simple, standardized interventional planning, including pre- and postprocedural automatic lumen detection metrics, has to be translated into effective treatment flow algorithms. A similar OCT algorithm is being tested in the ongoing prospective, randomized, multicenter ILUMIEN III study, to demonstrate that OCT-guided stent placement is superior to angiography-guided and non-inferior to IVUS-guided stent implantation. (Circ J 2016; 80: 2063–2072)

  • Noriyuki Ouchi, Koji Ohashi, Rei Shibata, Toyoaki Murohara
    Type: REVIEW
    2016 Volume 80 Issue 10 Pages 2073-2080
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 01, 2016
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    Obesity is a major risk factor for progression of cardiovascular disease. Adipose tissue is recognized as an endocrine organ producing various secretory molecules, also known as adipocytokines, and dysregulated production of adipocytokines participates in the pathogenesis of obesity complications, including metabolic dysfunction and cardiovascular disorders. Recent evidence indicates that skeletal muscle also functions as an endocrine organ capable of secreting a number of bioactive substances, also referred to as myokines. Several myokines are involved in metabolic and cardiovascular regulation. This review will discuss the clinical and experimental studies that have investigated the protective role of several adipocytokines and myokines in cardiovascular diseases. (Circ J 2016; 80: 2073–2080)

  • Masaki Ieda
    Type: REVIEW FOR THE 2015 SATO AWARD
    2016 Volume 80 Issue 10 Pages 2081-2088
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 07, 2016
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    It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy. (Circ J 2016; 80: 2081–2088)

Editorials
Original Articles
Arrhythmia/Electrophysiology
  • María Asunción Esteve-Pastor, Amaya García-Fernández, Manuel Macías, F ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2016 Volume 80 Issue 10 Pages 2102-2108
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 24, 2016
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    Background:Several bleeding risk scores have been validated in patients with atrial fibrillation (AF). The ORBIT score has been recently proposed as a simple score with the best ability to predict major bleeding. The present study aimed to test the hypothesis that the ORBIT score was superior to the HAS-BLED score for predicting major bleeding and death in “real world” anticoagulated AF patients.

    Methods and Results:We analyzed the predictive performance for bleeding and death of 406 AF patients who underwent 571 electrical cardioversion procedures and 1,276 patients with permanent/persistent AF from the FANTASIIA registry. In the cardioversion population, 21 patients had major bleeding events and 26 patients died. The predictive performance for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.77 (95% CI 0.66–0.88) and 0.82 (95% CI 0.77–0.93), respectively; P=0.080). For the FANTASIIA population, 46 patients had major bleeding events and 50 patients died. The predictive performances for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.63 (95% CI 0.56–0.71) and 0.70 (95% CI 0.62–0.77), respectively; P=0.116). For death, the predictive performances of HAS-BLED and ORBIT were not significantly different in both populations. The ORBIT score categorized most patients as “low risk”.

    Conclusions:Despite the original claims in its derivation paper, the ORBIT score was not superior to HAS-BLED for predicting major bleeding and death in a “real world” oral anticoagulated AF population. (Circ J 2016; 80: 2102–2108)

  • Giulio Conte, Carlo de Asmundis, Juan Sieira, Giuseppe Ciconte, Giacom ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2016 Volume 80 Issue 10 Pages 2109-2116
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 25, 2016
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    Background:The phenotypic heterogeneity of Brugada syndrome (BrS) can lead some patients to show an additional inferolateral early repolarization pattern (ERP), or fragmented QRS (f-QRS). The aim of the study was to investigate the prevalence and clinical impact of f-QRS, ERP or combined f-QRS/ERP in high-risk patients with BrS.

    Methods and Results:Patients with spontaneous or drug-induced BrS and an indication to receive an implantable cardioverter-defibrillator (ICD) were considered eligible for this study. From 1992 to 2012, a total of 176 consecutive patients with BrS underwent ICD implantation. Among them, 48 subjects (27.3%) presented with additional depolarization and/or repolarization abnormalities. f-QRS was found in 29 (16.5%), ERP in 15 (8.5%), and combined f-QRS/ERP in 4 patients (2.3%). After a mean follow-up of 95.2±51.9 months, spontaneous sustained ventricular arrhythmias were documented in 8 patients (16.7%). No significant difference was found in the rate of appropriate shocks between patients presenting with f-QRS or ERP and those without abnormalities. Patients with both f-QRS and ERP had a significantly higher rate of appropriate shocks (HR: 4.1; 95% CI: 1.1–19.7; P=0.04).

    Conclusions:Fragmented QRS and ERP are common ECG findings in high-risk BrS patients, occurring in up to 27% of cases. When combined, f-QRS and ERP confer a higher risk of appropriate ICD interventions during a very long-term follow-up. (Circ J 2016; 80: 2109–2116)

  • Akira Fujii, Katsuji Inoue, Takayuki Nagai, Teruyoshi Uetani, Kazuhisa ...
    Type: ORIGINAL ARTICLE
    Subject area: Arrhythmia/Electrophysiology
    2016 Volume 80 Issue 10 Pages 2117-2123
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 02, 2016
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    Background:In patients who have atrial fibrillation (AF) with CHADS2score of 0–1 (categorized as low-to-intermediate risk), there is little information on stratifying the risk of stroke. This study aimed to determine whether impaired endothelial function assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT) predicted left atrial blood stagnation in these patients.

    Methods and Results:We enrolled 81 consecutive patients with nonvalvular AF. The reactive hyperemia index (RHI) was measured using RH-PAT. Transesophageal echocardiography was performed to determine spontaneous echo contrast (SEC) before direct-current cardioversion or radiofrequency catheter ablation. SEC was found in 49 patients (60%). The RHI was significantly lower in patients with than without SEC. Multivariate analysis demonstrated that RHI was one of the independent determinants of SEC (OR per 0.1, 1.26; 95% CI, 1.11–1.49; P=0.002) in all patients. In addition, RHI was a significant determinant of SEC (AUC, 0.73; 95% CI, 0.63–0.89; P=0.0017) in patients with low-to-intermediate risk. At an RHI cut-off <1.62, the sensitivity and specificity for the identification of patients with SEC were 58% and 89%, respectively.

    Conclusions:Impaired endothelial function assessed by RH-PAT might help to predict the presence of SEC in patients with low-to-intermediate risk of stroke. (Circ J 2016; 80: 2117–2123)

Critical Care
  • Atsushi Sugiyama, Sue Duval, Yuji Nakamura, Katsunori Yoshihara, Demet ...
    Type: ORIGINAL ARTICLE
    Subject area: Critical Care
    2016 Volume 80 Issue 10 Pages 2124-2132
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 09, 2016
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    Background:The quality of cardiopulmonary resuscitation (CPR) has been recently shown to affect clinical outcome. The Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation Impedance Valve and Early Versus Delayed Analysis (PRIMED) trial showed no differences in outcomes with an active vs. sham impedance threshold device (ITD), a CPR adjunct that enhances circulation. It was hypothesized the active ITD would improve survival with favorable neurological outcomes in witnessed out-of-hospital cardiac arrest patients when used with high-quality CPR.

    Methods and Results:Using the publicly accessible ROC PRIMED database, a post-hoc analysis was performed on all witnessed subjects with both compression rate and depth data (n=1,808) who received CPR within the study protocol definition of adequate CPR quality (compression rate 80–120/min and depth 4–6 cm; n=929). Demographics were similar between sham and active ITD groups. In witnessed subjects who received quality CPR, survival with favorable neurological function was 11.9% for the active ITD subjects (56/470) vs. 7.4% for the sham (34/459) (odds ratio 1.69 [95% confidence interval 1.08, 2.64]). There were no statistically significant differences for this primary outcome when CPR was performed outside the boundaries of the definition of adequate CPR quality. Multivariable models did not change these associations.

    Conclusions:An active ITD combined with adequate-quality conventional CPR has the potential to significantly improve survival after witnessed cardiac arrest. (Circ J 2016; 80: 2124–2132)

Epidemiology
  • Akinori Ochi, Taro Adachi, Koichiro Inokuchi, Ko Ogawa, Yuya Nakamura, ...
    Type: ORIGINAL ARTICLE
    Subject area: Epidemiology
    2016 Volume 80 Issue 10 Pages 2133-2140
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 29, 2016
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    Background:Although clinical trials demonstrate that the elderly with atrial fibrillation have risks of thrombosis and bleeding, the relationship between aging and coagulation fibrinolytic system in “real-world” cardiology outpatients is uncertain.

    Methods and Results:We retrospectively evaluated 773 patients (mean age: 58 years; 52% men; Asian ethnicity). To thoroughly investigate markers of coagulation and fibrinolysis, we simultaneously measured levels of D-dimer, prothrombin-fragment1+2 (F1+2), plasmin-α2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). There were correlations between aging and levels of F1+2, D-dimer, PIC, and TM (R=0.61, 0.57, 0.49, and 0.30, respectively). We compared 3 age groups, which were defined as the Y group (<64 years), M group (65–74 years), and the O group (>75 years). Levels of markers were higher in older individuals (D-dimer: 1.0±0.8 vs. 0.8±0.8 vs. 0.6±0.4 μg/ml, F1+2: 281.8±151.3 vs. 224.6±107.1 vs. 155.5±90.0 pmol/L, PIC: 0.9±0.3 vs. 0.8±0.3 vs. 0.6±0.5 μg/ml, and TM: 2.9±0.8 vs. 2.7±0.7 vs. 2.5±0.7FU/ml). We performed logistic regression analysis to determine F1+2 and PIC levels. Multivariate analysis revealed that aging was the most important determinant of high F1+2 and PIC levels.

    Conclusions:Hypercoagulable states develop with advancing age in “real-world” cardiology outpatients. (Circ J 2016; 80: 2133–2140)

Heart Failure
  • Atsushi Okada, Ikutaro Nakajima, Yoshiaki Morita, Yuko Y. Inoue, Tsuka ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2016 Volume 80 Issue 10 Pages 2141-2148
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 23, 2016
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    Background:Predicting tachycardia-induced cardiomyopathy (TIC) in patients presenting with left ventricular (LV) dysfunction and tachyarrhythmias remains challenging. We assessed the diagnostic value of early right ventricular (RV) dysfunction to predict TIC using cardiac magnetic resonance (CMR) imaging.

    Methods and Results:A total of 102 consecutive patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias were examined. Patients whose LV ejection fraction (EF) improved to ≥50% during a 1-year follow-up were diagnosed with TIC, and with dilated cardiomyopathy (DCM) in those whose did not improve. CMR was performed at a median of 23 days after admission, and the TIC and DCM patients exhibited different distributions of EF and end-diastolic volume (EDV) between the LV and RV (both P<0.001, ANCOVA). TIC patients had significantly lower RVEF/LVEF ratio (1.01±0.23 vs. 1.36±0.31, P<0.001) and higher RVEDV/LVEDV ratio (0.96±0.21 vs. 0.73±0.19, P<0.001) compared with DCM patients, suggesting that RV systolic dysfunction and RV dilatation were observed in TIC. In the multivariate analysis, age, RVEF/LVEF ratio, and RVEDV/LVEDV ratio were significant predictors of TIC, and RVEF/LVEF ratio of <1.05 most highly predicted TIC with a sensitivity of 69.1% and specificity of 91.5% (area under the curve 0.860).

    Conclusions:Among patients with newly diagnosed LV dysfunction and atrial tachyarrhythmias, age and coexistence of RV dysfunction was a strong predictor of TIC. (Circ J 2016; 80: 2141–2148)

    Editor’s picks

    Circulation Journal Awards for the Year 2016
    First Place in the Clinical Investigation Section

  • Shuji Joho, Takashi Akabane, Ryuichi Ushijima, Tadakazu Hirai, Koichir ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2016 Volume 80 Issue 10 Pages 2149-2154
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 08, 2016
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    Background:Although both β-blocker dose (BBD) and sympathetic activity efferent drive are associated with prognosis in chronic heart failure (HF), little is known about the prognostic value of the interaction between them.

    Methods and Results:Potential prognostic variables including resting muscle sympathetic nerve activity (MSNA) were investigated in 133 patients with HF (ejection fraction [EF] <0.45). BBD was normalized to therapeutically equivalent doses of carvedilol. Primary cardiovascular endpoints included cardiovascular death and HF hospitalization. Predictors for outcomes were assessed on univariate, multivariate, and Kaplan-Meier analysis. EF was followed for 9 months after MSNA measurement in 102 patients. During the 1,419±824-day follow-up period, 24 patients died (sudden death, n=10; progressive HF, n=14). On multivariate Cox proportional hazard analysis, higher MSNA (P=0.037; HR, 2.01) and lower BBD (<5.0 mg/day; P=0.041; HR, 1.94) were independent predictors of cardiovascular events. Patients were divided into higher MSNA (≥64 bursts/100 beats) and lower MSNA groups. Although lower BBD remained an independent predictor in patients with higher MSNA, BBD was not statistically significant in patients with lower MSNA on univariate analysis. Additionally, there was a lower EF change in patients with lower BBD and higher MSNA.

    Conclusions:Higher BBD might be necessary to avoid cardiovascular events in HF patients with central sympathetic overactivation. (Circ J 2016; 80: 2149–2154)

  • Masanobu Miura, Yasuhiko Sakata, Satoshi Miyata, Nobuyuki Shiba, Jun T ...
    Type: ORIGINAL ARTICLE
    Subject area: Heart Failure
    2016 Volume 80 Issue 10 Pages 2155-2164
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 15, 2016
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    Background:There is no robust evidence of pharmacological interventions to improve mortality in heart failure (HF) patients with preserved left ventricular ejection fraction (LVEF) (HFpEF). In this subanalysis study of the SUPPORT Trial, we addressed the influence of LVEF on the effects of olmesartan in HF.

    Methods and Results:Among 1,147 patients enrolled in the SUPPORT Trial, we examined 429 patients with reduced LVEF (HFrEF, LVEF <50%) and 709 with HFpEF (LVEF ≥50%). During a median follow-up of 4.4 years, 21.9% and 12.5% patients died in the HFrEF and HFpEF groups, respectively. In HFrEF patients, the addition of olmesartan to the combination of angiotensin-converting enzyme inhibitor (ACEI) and β-blocker (BB) was associated with increased incidence of death (hazard ratio (HR) 2.26, P=0.002) and worsening renal function (HR 2.01, P=0.01), whereas its addition to ACEI or BB alone was not. In contrast, in HFpEF patients, the addition of olmesartan to BB alone was significantly associated with reduced mortality (HR 0.32, P=0.03), whereas with ACEIs alone or in combination with BB and ACEI was not. The linear mixed-effect model showed that in HFpEF, the urinary albumin/creatinine ratio was unaltered when BB were combined with olmesartan, but significantly increased when not combined with olmesartan (P=0.01).

    Conclusions:LVEF substantially influences the effects of additive use of olmesartan, with beneficial effects noted when combined with BB in hypertensive HFpEF patients. (Circ J 2016; 80: 2155–2164)

Hypertension and Circulatory Control
  • Minako Inoue, Takuya Tsuchihashi, Yasuyuki Hasuo, Masanobu Ogawa, Mits ...
    Type: ORIGINAL ARTICLE
    Subject area: Hypertension and Circulatory Control
    2016 Volume 80 Issue 10 Pages 2165-2172
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 29, 2016
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    Background:The relationship between salt (sodium chloride) intake and pregnancy-induced hypertension (PIH) remains unclear. The aim of this study was therefore to investigate the current status of salt intake during pregnancy and identify effective predictors for PIH.

    Methods and Results:Participants were 184 pregnant women who collected 24-h home urine as well as early morning urine samples. We investigated urinary salt excretion, home blood pressure (HBP) measurements for 7 consecutive days before the 20th and after the 30th gestational week, and the development of PIH. Urinary salt excretion according to early morning urine before the 20th gestational week was 8.6±1.7 g/day, and was significantly correlated with that measured from 24-h collected urine. Early morning urine estimated urinary salt excretion was slightly but significantly increased during pregnancy. HBP was 102±10/63±8 mmHg before the 20th gestational week and 104±12/64±10 mmHg after the 30th gestational week. On multiple regression analysis, serum uric acid and body mass index, but not urinary salt excretion, contributed to HBP both before the 20th and after the 30th gestational week. Fourteen participants (7.6%) developed PIH. On multivariate analysis, higher HBP and older age, but not urinary salt excretion, were significantly associated with PIH.

    Conclusions:Higher HBP and older age, but not urinary salt excretion, are predictors of PIH. (Circ J 2016; 80: 2165–2172)

Ischemic Heart Disease
  • Hiroki Ikenaga, Satoshi Kurisu, Shingo Kono, Yoji Sumimoto, Noriaki Wa ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2016 Volume 80 Issue 10 Pages 2173-2182
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 31, 2016
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    Background:Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is considered to play an essential role in plaque destabilization. We aimed to investigate the association between the tissue characteristics of culprit plaque assessed by integrated backscatter (IB)-intravascular ultrasound (IVUS) and the serum MDA-LDL levels in patients with stable coronary artery disease.

    Methods and Results:The study group consisted of 179 patients undergoing IB-IVUS during elective percutaneous coronary intervention. Patients were classified into 2 groups based on serum MDA-LDL level: low MDA-LDL group (<102 U/L, n=88) and high MDA-LDL group (≥102 U/L, n=91). Plaques in the high MDA-LDL group had higher %lipid (45.2±12.5% vs. 54.9±14.5%, P<0.001) and lower %fibrosis (43.0±9.1% vs. 36.4±11.4%, P<0.001) than did plaques in the low MDA-LDL group. Lipid-rich plaque (%lipid >60% or %fibrosis <30%) was significantly more frequently found in the high MDA-LDL group than in the low MDA-LDL group (14.3% vs. 39.8%, P<0.001). The incidence of MACE (cardiac death, myocardial infarction and/or hospitalization for heart failure) during 3 years was significantly higher in the high MDA-LDL group than in the low MDA-LDL group (6.6% vs. 15.9%, P=0.02).

    Conclusions:Higher MDA-LDL might be associated with greater lipid and lower fibrous content, contributing to coronary plaque vulnerability. (Circ J 2016; 80: 2173–2182)

  • Nuno Cortez-Dias, Marina C. Costa, Pedro Carrilho-Ferreira, Doroteia S ...
    Type: ORIGINAL ARTICLE
    Subject area: Ischemic Heart Disease
    2016 Volume 80 Issue 10 Pages 2183-2191
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 02, 2016
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    Background:MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have a critical role in heart function. Recent studies have demonstrated that miR-122-5p, a hepatic miRNA, increases in the bloodstream during ischemic cardiogenic shock and it is upregulated in the infarcted myocardium. The aim of the present study was to determine the potential of circulating miR-122-5p as a biomarker for early prognostic stratification of ST-segment elevation acute myocardial infarction (STEMI) patients.

    Methods and Results:One hundred and forty-two consecutive STEMI patients treated with primary angioplasty were included in the study. Serum levels of miR-1-3p, -122-5p, -133a-3p, -133b, -208b-3p and -499a-5p were measured at the time of cardiac catheterization by quantitative polymerase chain reaction and related to in-hospital and long-term outcome. During a follow up of 20.8 months, 9 patients died, 6 had recurrence of myocardial infarction, and 26 patients suffered an adverse cardiovascular event. Event-free survival was significantly worse in patients with a higher miR-122-5p/133b ratio (3rd tertile distribution, above 1.42 Log(10)), having almost a 9-fold higher risk of death or myocardial infarction and a 4-fold higher risk of adverse cardiovascular events.

    Conclusions:This study showed that the miR-122-5p/133b ratio is a new prognostic biomarker for the early identification of STEMI patients at a higher risk of developing major adverse events after undergoing primary percutaneous coronary intervention. (Circ J 2016; 80: 2183–2191)

Myocardial Disease
  • Mélanie Girardey, Laurence Jesel, Umberto Campia, Nathan Messas, Sébas ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2016 Volume 80 Issue 10 Pages 2192-2198
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 01, 2016
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    Background:Although the relationship between malignancies and catecholamine-induced myocardial stunning remains largely speculative, it has been suggested that the presence of cancer may lower the threshold for stress stimuli and/or may aggravate cardiac adrenoreceptor sensitivity. We sought to investigate whether associations exist between a previous or current diagnosis of malignancy, diagnostic parameters during hospitalization and death in takotsubo.

    Methods and Results:The 154 takotsubo patients were retrospectively identified between May 2008 and December 2014. Previous history of malignancy was identified in 44 patients (28.5%). Cardiac arrest was present at admission in 13 patients (8.4%). Intra-aortic balloon pump was inserted in 16 patients (10.4%). In patients with malignancy, higher B-type natriuretic peptide (BNP), leukocyte and C-reactive protein (CRP) peaks could be observed during the hospital phase. Initial impairment of left ventricular ejection fraction was negatively related to BNP, leukocyte, and CRP peaks. At a median follow-up of 364 days, all-cause death occurred in 41 patients (26.6%) and cardiac death in 12 patients (7.7%). Multivariate Cox regression analysis identified malignancy (hazard ratio 4.77 (1.02–22.17), leukocyte peak and age as independent predictors of cardiac death. Malignancy (2.62 (1.26–5.44), leukocyte peak (1.05 (1.01–1.08) and initial cardiac arrest (6.68 (2.47–18.01) were identified as independent predictors of overall mortality.

    Conclusions:In the present takotsubo patients, the prevalence of malignancy was high and may have affected cardiovascular outcomes through the activation of inflammatory and neurohormonal mechanisms. (Circ J 2016; 80: 2192–2198)

  • Hideo Okamura, Paul A. Friedman, Yuko Inoue, Takashi Noda, Takeshi Aib ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2016 Volume 80 Issue 10 Pages 2199-2203
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 26, 2016
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    Background:Single-coil defibrillator leads have gained favor because of their potential ease of extraction. However, a high defibrillation threshold remains a concern in patients with hypertrophic cardiomyopathy (HCM), and in many cases, dual-coil leads have been used for this patient group. There is little data on using single-coil leads for HCM patients.

    Methods and Results:We evaluated 20 patients with HCM who received an implantable cardioverter-defibrillator (ICD) on the left side in combination with a dual-coil lead. Two sets of defibrillation tests were performed in each patient, one with the superior vena cava (SVC) coil “on” and one with the SVC coil “off”. ICDs were programmed to deliver 25 joules (J) for the first attempt followed by maximum energy (35 J or 40 J). Shock impedance and shock pulse width at 25 J in each setting as well as the results of the shock were analyzed. All 25-J shocks in both settings successfully terminated ventricular fibrillation. However, shock impedance and pulse width increased substantially with the SVC coil programmed “off” compared with “on” (66.4±6.1 ohm and 14.0±1.3 ms “off” vs. 41.9±5.0 ohm and 9.3±0.8 ms “on”, P<0.0001 respectively).

    Conclusions:Biphasic 25-J shocks with the SVC coil ‘off’ successfully terminated ventricular fibrillation in HCM patients, indicating a satisfactory safety margin for 35-J devices. Single-coil leads appear appropriate for left-sided implantation in this patient group. (Circ J 2016; 80: 2199–2203)

  • Damiano Magrì, Federica Re, Giuseppe Limongelli, Piergiuseppe Agostoni ...
    Type: ORIGINAL ARTICLE
    Subject area: Myocardial Disease
    2016 Volume 80 Issue 10 Pages 2204-2211
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 13, 2016
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    Background:Heart failure (HF) progression and its complications represent major emergent concerns in hypertrophic cardiomyopathy (HCM). We investigated the possible adjunctive role of cardiopulmonary exercise testing (CPET) in predicting HF-related events. An exercise-derived risk model, theHYPertrophicExercise-derivedRiskHF(HYPERHF), has been developed.

    Methods and Results:A multicenter cohort of 620 consecutive HCM outpatients was recruited and followed (2007 to 2015). The endpoint was death from HF, cardiac transplantation, NYHA III–IV class progression, severe functional deterioration leading to hospitalization for septal reduction, and hospitalization for HF worsening. During a median follow-up of 3.8 years (25–75th centile: 2.3–5.3 years), 84 patients reached the endpoint. Peak circulatory power (peak oxygen consumption * peak systolic blood pressure), ventilatory efficiency and left atrial diameter were independently associated with the endpoint and, accordingly, integrated into the HYPERHFmodel (C index: 0.849; best cutoff value equal to 15%).

    Conclusions:CPET is useful in the evaluation of HCM patients. In this context, the HYPERHFscore might allow early identification of those patients at high risk of HF progression and its complications. (Circ J 2016; 80: 2204–2211)

Pediatric Cardiology and Adult Congenital Heart Disease
  • Yohei Akazawa, Akira Hachiya, Shoko Yamazaki, Yoichiro Kawasaki, Chizu ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2016 Volume 80 Issue 10 Pages 2212-2220
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 18, 2016
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    Background:The purpose of this study was to clarify cardiovascular structure and function in small for gestational age (SGA) infants across a range of intrauterine growth restriction (IUGR) severity.

    Methods and Results:This prospective study included 38 SGA infants and 30 appropriate for gestational age (AGA) infants. SGA infants were subclassified into severe and mild SGA according to the degree of IUGR. Cardiovascular structure and function were evaluated using echocardiography at 1 week of age. Compared with the AGA infants, both the severe and mild SGA infants showed increased left ventricular diastolic dimensions (severe SGA 10.2±2.4, mild SGA 8.2±1.3, and AGA 7.3±0.7 mm/kg, P<0.05 for all) and decreased global longitudinal strain (severe −21.1±1.6, mild −22.5±1.8, and AGA −23.8±1.8%, P<0.05 for all). Severe SGA infants showed a decreased mitral annular early diastolic velocity (severe 5.6±1.4 vs. AGA 7.0±1.3 cm/s, P<0.01) and increased isovolumic relaxation time (severe 51.3±9.2 vs. AGA 42.7±8.2 ms, P<0.01). Weight-adjusted aortic intima-media thickness and arterial wall stiffness were significantly greater in both SGA infant groups. These cardiovascular parameters tended to deteriorate with increasing IUGR severity.

    Conclusions:SGA infants, including those with mild SGA, showed cardiovascular remodeling and dysfunction, which increased with IUGR severity. (Circ J 2016; 80: 2212–2220)

  • Kayo Tanaka, Hiroaki Tanaka, Chizuko Kamiya, Shinji Katsuragi, Masami ...
    Type: ORIGINAL ARTICLE
    Subject area: Pediatric Cardiology and Adult Congenital Heart Disease
    2016 Volume 80 Issue 10 Pages 2221-2226
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 02, 2016
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    Background:The effects of β-adrenergic blockers on the fetus are not well understood. We analyzed the maternal and neonatal outcomes of β-adrenergic blocker treatment during pregnancy to identify the risk of fetal growth restriction (FGR).

    Methods and Results:We retrospectively reviewed 158 pregnancies in women with cardiovascular disease at a single center. Maternal and neonatal outcomes were analyzed in 3 categories: the carvedilol (α/β-adrenergic blocker; α/β group, n=13); β-adrenergic blocker (β group, n=45), and control groups (n=100). Maternal outcome was not significantly different between the groups. FGR occurred in 1 patient (7%) in the α/β group, in 12 (26%) in the β group, and in 3 (3%) in the control group; there was a significant difference between the incidence of FGR between the β group and control group (P<0.05). The β group included propranolol (n=22), metoprolol (n=12), atenolol (n=6), and bisoprolol (n=5), and the individual incidence of FGR with these medications was 36%, 17%, 33%, and 0%, respectively.

    Conclusions:As a group, β-adrenergic blockers were significantly associated with FGR, although the incidence of FGR varied with individual β-blocker. Carvedilol, an α/β-adrenergic blocker, had no association with FGR. More controlled studies are needed to fully establish such associations. (Circ J 2016; 80: 2221–2226)

Pulmonary Circulation
  • Tatsuo Aoki, Koichiro Sugimura, Kotaro Nochioka, Masanobu Miura, Shuns ...
    Type: ORIGINAL ARTICLE
    Subject area: Pulmonary Circulation
    2016 Volume 80 Issue 10 Pages 2227-2234
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: September 01, 2016
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    Background:Although balloon pulmonary angioplasty (BPA) improves the hemodynamics and prognosis of patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), the mechanisms of improvement in oxygenation remain to be elucidated.

    Methods and Results:From August 2013 to May 2015, we performed a total of 113 BPA procedures in 24 patients with inoperable CTEPH (mean 4.7 procedures per patient). Median age was 70 [60, 74] years and 18 were female (75%). We examined hemodynamics, respiratory functions, and intrapulmonary shunt before and after the BPA procedure. Mean pulmonary arterial pressure (37 [28, 45] to 23[19, 27] mmHg, P<0.01), pulmonary vascular resistance (517 [389, 696] to 268 [239, 345] dyne/s/cm5) and 6-min walk distance (390 [286, 484] to 490 [411, 617] m, P<0.01) were significantly improved after BPA therapy. Furthermore, arterial oxygen partial pressure (PaO2, 54.8 [50.0, 60.8] to 65.2 [60.6, 73.2] %, P<0.01) and intrapulmonary shunt (23.4±6.0% to 19.3±5.0%, P<0.01) were also significantly ameliorated. In the multivariate analysis, decrease in intrapulmonary shunt after BPA was significantly correlated with improvement of both PaO2(r2=0.26, P<0.01) and SaO2(r2=0.49, P<0.01) after BPA.

    Conclusions:These results indicated that BPA improved not only pulmonary hemodynamics but also oxygenation with a resultant decrease in intrapulmonary shunt. (Circ J 2016; 80: 2227–2234)

Stroke
  • Liqiang Zheng, Zhengrong Sun, Zhaoqing Sun, Xingang Zhang, Kai Jing, J ...
    Type: ORIGINAL ARTICLE
    Subject area: Stroke
    2016 Volume 80 Issue 10 Pages 2235-2239
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 08, 2016
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    Background:The cause-and-effect relationship between human cytomegalovirus (HCMV) and stroke has not been widely elucidated. We aimed to determine if HCMV infection has an increased risk of future stroke in hypertensive patients in rural areas of China.

    Methods and Results:This was a nested case-control study from a prospective cohort study. A total of 300 newly diagnosed stroke cases with a median follow-up period of 8.4 years and 300 matched controls were selected for the present analysis. Adjusted odds ratio (OR) for stroke associated with HCMV DNA seropositivity was calculated by conditional logistic regression. HCMV DNA was detected in 38 of 300 samples from stroke patients and in 17 of 300 control samples (12.7% vs. 5.7%; P=0.023). Seropositivity for HCMV DNA increased the risk of incident stroke (unadjusted OR, 1.437; 95% confidence interval (CI), 1.023–2.020, P=0.037) and adjustment for other potential cardiovascular confounders only slightly changed the OR (1.464; 95% CI, 1.003–2.137, P=0.048). After controlling for potential cardiovascular confounders, the OR for hemorrhagic stroke associated with HCMV DNA was 1.718 (95% CI, 1.042–2.832), whereas the OR for ischemic stroke was 0.450 (95% CI, 0.142–1.428).

    Conclusions:Seropositivity for HCMV DNA was positively associated with total and hemorrhagic but not ischemic stroke, which persisted after controlling for other cardiovascular factors. (Circ J 2016; 80: 2235–2239)

Valvular Heart Disease
  • Tomoko Machino-Ohtsuka, Yoshihiro Seo, Tomoko Ishizu, Kimi Sato, Akino ...
    Type: ORIGINAL ARTICLE
    Subject area: Valvular Heart Disease
    2016 Volume 80 Issue 10 Pages 2240-2248
    Published: September 23, 2016
    Released: September 23, 2016
    [Advance publication] Released: August 17, 2016
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    Background:Left atrial remodeling caused by persistent atrial fibrillation (AF) causes atrial functional mitral regurgitation (MR), even though left ventricular (LV) remodeling and organic changes of the mitral leaflets are lacking. The detailed mechanism of atrial functional MR has not been fully investigated.

    Methods and Results:Of 1,167 patients with AF who underwent 3D transesophageal echocardiography, 75 patients were retrospectively selected who developed no, mild, or moderate-to-severe atrial functional MR (n=25 in each group) despite an LV ejection fraction ≥50% and LV volumes within the normal range. Mitral valve morphology and dynamics were analyzed. Patients with moderate-to-severe MR had a larger mitral annulus (MA) area, smaller MA area fraction, and greater nonplanarity angle and tethering angle of the posterior mitral leaflet (PML) compared with other groups (all P<0.001). In the multiple regression analysis, the MA area, MA area fraction, nonplanarity angle, and PML angle were independent determinants of the effective regurgitant orifice area of MR after adjusting for LV parameters (adjusted R2=0.725, P<0.001). The PML angle and MA area had a higher standardized regression coefficient (β=0.403, P<0.001, β=0.404, P<0.001, respectively) than the other variables.

    Conclusions:Functional atrial MR in persistent AF is caused by not only MA dilatation, but also by multiple factors including the MA contractile dysfunction, disruption of the annular saddle shape, and atriogenic PML tethering. (Circ J 2016; 80: 2240–2248)

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