Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic cardiac disease that has been the subject of intense investigation for over 50 years. Most patients with HCM are asymptomatic, but some develop symptoms, often many years after the appearance of electrocardiographic or echocardiographic evidence of left ventricular hypertrophy. Symptoms due to the left ventricular outflow tract obstruction frequently worsen over time, requiring septal reduction therapy (SRT) despite optimal medical therapy. Percutaneous transluminal septal myocardial ablation (PTSMA) and surgical myectomy are collectively known as SRT. In this review, we will focus on the emerging concept and practical implication of SRT and the available evidence on either PTSMA or surgical myectomy in the literature.

The 82^nd Annual Scientific Meeting of the Japanese Circulation Society was held in Osaka, Japan, on March 23–25, 2018, when the cherry blossoms were just opening everywhere around the venue. This was the 5^th Annual Scientific Meeting of JCS in which a cardiovascular surgeon served as Congress Chairperson. The main theme of this meeting was “Futurability: Pioneering the Future of Circulatory Medicine”. The word, futurability, is a neologism of future ability, because we now have to contemplate what constitutes the essence of cardiovascular medicine, how it should develop as medicine for future generations, and how its ability should be displayed. The meeting was favored by splendid weather and the number of participants was recorded as being higher than 18,700. There were heated and profound discussions about the “futurability” of cardiology, cardiovascular surgery, and heart team medical care as well, in every session. The meeting was successfully completed and we sincerely appreciate the great cooperation and support from all affiliates.

Background:Both atrial fibrillation (AF) and osteoporosis are common in older adults. The purpose of this study was to investigate whether comorbid AF in patients with osteoporosis is associated with fracture incidence, or death after fracture.

Methods and Results:From the National Health Insurance Service database of Korea, we selected 31,778 patients with osteoporosis. During a median follow-up of 48 months, the incidence of bone fractures was higher in AF patients than in non-AF patients (3.20 vs. 2.18 per 100 person-years), respectively. In the multivariate Cox regression analysis, AF was associated with fracture independently of other risk factors with an adjusted hazard ratio (HR) of 1.21 (95% confidence interval [CI], 1.02–1.41; P=0.031). The mortality rate after fracture was significantly higher in AF patients than it was in non-AF patients (adjusted HR, 1.92; 95% CI, 1.35–3.27; P=0.016). After propensity score-matching, AF was consistently associated with a higher risk of osteoporotic fracture and subsequent death after fracture. In AF patients, older age, female sex, being underweight (body mass index <18.5 kg/m²), decreased physical activity (exercise <3 times/week), history of stroke or transient ischemic attack, thiazide use, sedative use, and higher CHADS₂(≥2 points) or CHA₂DS₂-VASc (≥2 points) scores were associated with the incidence of fractures.

Conclusions:Comorbid AF in patients with osteoporosis was associated with an increased risk of bone fracture and death after fracture.

Background:The aim of this study was to categorize the conduction patterns between the right atrium (RA) and the superior vena cava (SVC), and to determine the ideal procedure for SVC isolation using a novel high-resolution mapping system.

Methods and Results:RA-SVC conduction was evaluated using the RHYTHMIA system in 113 patients (age 62.8±11.5 years, paroxysmal: 67) with atrial fibrillation (AF) after pulmonary vein (PV) isolation. In 56 patients, a line of conduction block was found to run obliquely just above the sinus node (Block group). The remaining 57 patients did not have block (Non-block group). Non-PV foci were spontaneous or provoked with isoproterenol after electrical cardioversion of pacing-induced AF. In 43 patients with SVC foci (Block group: 22, Non-Block group: 21), SVC was isolated by radiofrequency applications delivered along the line connecting the open ends of the block line (Block group) or by conventional methods (Non-block group). The Block group required fewer radiofrequency deliveries for SVC isolation than the Non-Block group (4.2±0.9 vs. 10.2±2.8 times; P<0.0001). The isolated SVC area was larger in the Block group (15.7±3.7 vs. 10.5±3.1 cm²; P<0.0001).

Conclusions:We found that approximately half of patients with AF had a diagonal line of block at the RA-SVC junction that could be utilized to isolate the SVC with fewer radiofrequency deliveries.

Background:Whether direct oral anticoagulants (DOACs) are safer and more effective than vitamin K antagonist (VKA) for preventing thrombotic events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains unknown.

Methods and Results:Between April 2011 and March 2014, data from 2,045 consecutive patients who underwent PCI were retrospectively examined. Of them, 129 patients treated with oral anticoagulants (OACs) and antiplatelet agents because of AF were enrolled. Primary bleeding outcome was a composite of major and minor bleeding, as per the Thrombolysis in Myocardial Infarction criteria. Secondary efficacy outcome was a composite outcome of death, myocardial infarction (MI), stroke, and target-lesion revascularization (TLR). Of the 129 patients, VKA was used in 84 and DOACs in 45. The mean time in the therapeutic range for the VKA group was 52.6%. The ratio of CHA₂D₂-VASC and HAS-BLED scores ≥3 was similar between the groups (VKA, 90.5%; DOAC, 84.4%; P=0.31 and VKA, 79.8%; DOAC, 68.9%; P=0.17, respectively). During follow-up (median, 1,080 days), the primary bleeding outcome tended to occur less (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.24–1.11, P=0.10) and the composite secondary efficacy outcome significantly less frequently (HR, 0.40; 95% CI, 0.14–0.91; P=0.03) in the DOAC group.

Conclusions:Compared with DOACs, VKA with poorly controlled INR and antiplatelet agents correlated with adverse outcomes of death, MI, stroke, and TLR in patients undergoing PCI.

Background:The aim of this study was to investigate whether drug-coated balloon (DCB) treatment is effective for de novo coronary lesions that are unsuitable for drug-eluting stent (DES) implantation.

Methods and Results:This retrospective study included 118 de novo lesions that were not suitable for DES implantation. Of the lesions, 40% was treated because of very small vessel disease. Patients with planned non-cardiac surgery and at high bleeding risk were 3% and 19%, respectively, and lesions that easily develop stent fracture comprised 26%. Clinically driven target lesion revascularization (TLR) was the primary endpoint. The rate of suboptimal lesion preparation before DCB treatment was set as the secondary endpoint. Optimal lesion preparation was defined as acquisition of Thrombolysis in Myocardial Infarction flow grade 3, minor coronary dissection, and residual stenosis ≤30%. The rate of suboptimal lesion preparation was 2.5% and 3 patients needed bail-out stenting. Accordingly, 115 patients were treated with a DCB. Clinically driven TLR had occurred in 8 patients (7.0%) at the 8-month follow-up. The presence of chronic total occlusion was identified as an independent predictor for TLR (odds 11.57; 95% confidence interval, 1.38–135.54; P=0.02).

Conclusions:For lesions that are unsuitable for stent implantation, stent-less intervention using a DCB should be considered initially. The present study also highlighted that lesion preparation is key to a successful DCB strategy.

Background:The in vivo lesion morphologies and plaque components of coronary chronic total occlusion (CTO) lesions remain unclear.

Methods and Results:We investigated 57 consecutive CTO lesions in 57 patients with stable angina pectoris undergoing elective percutaneous coronary intervention with intravascular ultrasound (IVUS) and coronary angioscopy (CAS) examination. All CTO lesions were classified according to the proximal angiographic lumen pattern; tapered-type (T-CTO) and abrupt-type (A-CTO). The differences in the intracoronary images of these lesion types were evaluated according to the location within the CTO segment. A total of 35 lesions (61.4%) were T-CTO. T-CTO lesions had higher frequencies of red thrombi (proximal 71.4%; middle 74.3%; distal 31.4%; P<0.001) and bright-yellow plaques (yellow-grade 2–3) (48.6%; 74.3%; 2.9%; P<0.001) at the proximal or middle than at the distal subsegment; A-CTO lesions showed no significant differences among the 3 sub-segments. At the middle subsegment, T-CTO lesions showed higher frequencies of positive remodeling (51.4% vs. 18.2%, P=0.01) and bright-yellow plaques (74.3% vs. 13.6%, P<0.001) compared with A-CTO lesions. Multivariate analysis identified bright-yellow plaque as an independent predictor (odds ratio, 7.25; 95% confidence interval, 1.25–42.04; P=0.03) of the occurrence of periprocedural myocardial necrosis.

Conclusions:The combination of IVUS and CAS analysis may be useful for identifying lesion morphology and plaque components, which may help clarify the pathogenetic mechanism of CTO lesions.

Background:This study compared the long-term outcomes of prosthetic heart valve replacement with mechanical or bioprosthetic valves in patients with prior stroke.

Methods and Results:In total, 1,984 patients with previous stroke who had received valve replacement between 2000 and 2011 were identified using the Taiwan National Health Insurance Research Database. Propensity score matching analysis was used. Ultimately, 547 patients were extracted from each group and were eligible for analysis. On survival analysis, the risks of all-cause mortality and recurrence of stroke were similar. The incidence of major bleeding was greater in the mechanical valve group than in the bioprosthetic valve group (P=0.040), whereas no difference was observed in re-do valve surgery. On subgroup analysis, the bioprosthetic valve was favored for older age (≥60 years) and previous gastrointestinal (GI) bleeding patients. The mechanical valve, however, was favored for younger patients (<60 years).

Conclusions:In patients with previous stroke, bioprosthetic valves had a lower incidence of complications connected to major bleeding than did the mechanical valves. Survival and stroke recurrence rates, however, did not differ between the 2 groups. We recommend bioprosthetic valves for patients >60 years or who have a history of GI bleeding.

Background:N-Terminal pro B-type natriuretic peptide (NT-proBNP) is widely used as a marker of ventricular dysfunction. However, data regarding the association of NT-proBNP with blood pressure (BP) and pulse pressure (PP) in the elderly population are limited.

Methods and Results:The present cross-sectional study involved 6,529 participants, aged ≥70 years, without cardiovascular disease (CVD), who underwent general health examinations. Serum NT-proBNP concentrations were determined, with high NT-proBNP concentrations defined as those ≥125 pg/mL. Subjects were divided into five groups based on PP (<50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 mmHg). NT-proBNP was positively associated with systolic BP, whereas a U-shaped association was found between diastolic BP and NT-proBNP. The odds ratios for high NT-proBNP concentrations in the PP ≥80 and ≥70 to <80 mmHg groups (OR 1.83 [P<0.001] and 1.40 [P<0.005], respectively) were significantly higher than in the PP <50 mmHg group. All data were adjusted for age, sex, body mass index, hemoglobin concentration, serum creatinine, pulse rate, smoking, alcohol intake, and antihypertensive medication intake, and the presence of diabetes and dyslipidemia.

Conclusions:The results suggest that NT-proBNP concentrations may be a marker of not only ventricular dysfunction, but also arterial stiffness in the elderly population without CVD.

Background:N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been used for risk stratification in heart failure or acute coronary syndrome, but the beyond 5-year predictive value of NT-proBNP for stroke remains an unsettled issue in Asian patients. The aim of the present study was to clarify this point.

Methods and Results:We followed 1,198 participants (33.4% men; mean age, 60.5±11.1 years old) in the Japanese general population for a median of 13.0 years. A first stroke occurred in 93 participants. Referencing previous reports, we stratified participants according to NT-proBNP 30.0, 55.0, and 125.0 pg/mL. Using the NT-proBNP <30.0 pg/mL group as a reference, adjusted HR for stroke (95% CI) in the NT-proBNP 30.0–54.9-pg/mL, 55.0–124.9-pg/mL, and ≥125.0-pg/mL groups were 1.92 (0.94–3.94), 1.77 (0.85–3.66), and 1.99 (0.86–4.61), respectively. With the maximum follow-up period set at 5 years, the hazard ratio of the NT-proBNP≥125.0-pg/mL group compared with the <30.0-pg/mL group increased significantly (HR, 4.51; 95% CI: 1.03–19.85). On extension of the maximum follow-up period, however, the association between NT-proBNP and stroke risk weakened.

Conclusions:NT-proBNP was significantly associated with an elevated stroke risk. Given, however, that the predictive power decreased with the number of years after NT-proBNP measurement, NT-proBNP should be re-evaluated periodically in Asian patients.

Background:Numerous studies have reported the association of cardiovascular risk factors with pulmonary embolism (PE), but the association of dietary factors, especially fish intake, with the risk of PE has not been fully established.

Methods and Results:Using a prospective design, we studied the risk of PE mortality in relation to fish intake in 90,791 community-dwelling men and women in Japan aged 40–79 years. The hazard ratios (HRs) and 95% confidence intervals (CIs) for PE death were estimated using the Cox proportional hazards model. Compared with participants in the lowest fresh fish intake group (<1 time/month), the HRs (95% CIs) for PE death for those in the other intake groups were 0.35 (0.08–1.59) for 1–2 times/month, 0.19 (0.05–0.69) for 1–2 times/week, 0.20 (0.06–0.74) for 3–4 times/week, and 0.18 (0.05–0.66) for fish intake every day. In addition to these findings, compared with the participants in the lowest 10% of ω3 polyunsaturated fatty acid intake, those in the other groups had a 60–76% lower risk of PE death.

Conclusions:Fresh fish intake, even 1–2 times/week, is associated with a lower risk of death from PE among Japanese men and women.

Background:The outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) have been rarely studied, and follow-up data on left ventricular ejection fraction (LVEF) are scarse.

Methods and Results:Patients were selected from a prospective multicenter registry of patients hospitalized for acute HF and then classified in the improved group if they exhibited %LVEF change ≥5 with follow-up LVEF ≥50%. Follow-up LVEF reported at least 90 days after discharge was used for classification. Of the 3,085 patients with acute HF, 454 were classified in the HFmrEF, and 276 had follow-up data. Of these 276 patients, 34.1% were classified in the improved group. Multivariate analysis revealed that hypertension, higher heart rate, lower serum sodium level, and maintenance therapy with β-blocker were associated with improved LVEF. The survival rate was significantly higher in the improved group than in the other groups. Young age and maintenance therapy with renin-angiotensin system blockers or aldosterone antagonists were significantly associated with better survival in HFmrEF.

Conclusions:One-third of HFmrEF patients showed improved LVEF; moreover, the survival rate in the improved group was higher than the other groups. Renin-angiotensin system blockers and aldosterone antagonists could improve the survival of HFmrEF patients.

Background:Carperitide is used to treat acute heart failure (AHF) in Japan. Whether the degree of pulmonary congestion is associated with the effects of carperitide on AHF is unclear.

Methods and Results:We retrospectively investigated the in-hospital outcomes and prognoses of 742 patients hospitalized for AHF between February 2015 and January 2017 and classified them into carperitide and non-carperitide groups, stratified according to the degree of pulmonary congestion. The median follow-up duration after admission was 231 days. In patients with moderate–severe pulmonary congestion, the rate of remaining congestion on chest X-ray at discharge was lower in the carperitide group than in the non-carperitide group (1.5% vs. 9.0%, P=0.004). Also, the carperitide group had significant reduction in a composite of all-cause death or rehospitalization for HF (adjusted hazard ratio, 0.62; 95% CI: 0.41–0.93; P=0.02). In patients with no–mild pulmonary congestion, carperitide was not associated with better clinical outcome.

Conclusions:In the treatment of AHF with moderate–severe pulmonary congestion, carperitide is associated with more effective decongestion in the short term and better prognosis in the long term.

Background:Fulminant myocarditis (FM) presents various abnormal findings on ECG, the prognostic impact of which has not been not fully elucidated. The aim of this study was therefore to clarify the prognostic value of ECG data in FM patients supported by venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Methods and Results:In this multicenter chart review, we investigated 99 patients with FM supported by VA-ECMO. The final cohort consisted of 87 patients (mean age, 52±16 years; female, 42%) after 12 patients who required conversion to other forms of mechanical circulatory support were excluded. The median LVEF was 14.5%. At the time of VA-ECMO initiation, 38 patients (44%) had arrhythmias including atrial fibrillation (6%), complete atrioventricular block (CAVB; 17%), and ventricular tachycardia or fibrillation (VT/VF; 15%). Of the 49 patients with sinus rhythm (SR), 26 had QRS duration ≥120 ms (wide QRS). On logistic regression analysis, wide QRS predicted in-hospital death in patients with SR (OR, 3.6; 95% CI: 1.07–13.61, P=0.04). Compared with SR with narrow QRS (QRS duration <120 ms), CAVB and VT/VF had a higher risk of in-hospital death (CAVB: OR, 7.20; 95% CI: 1.78–34.15, P=0.005; VT/VF: OR, 8.10; 95% CI: 1.86–42.31, P=0.005).

Conclusions:In patients with FM, CAVB and VT/VF carried a higher risk of in-hospital death. Wide QRS also predicted a higher risk of in-hospital death in patients with SR.

Background:Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are prognostic biomarkers. Although these 2 peptides differ with regard to biological characteristics, there are few reports on the differences between BNP and NT-proBNP with regard to cardiovascular events or according to sex.

Methods and Results:Between 2005 and 2012, this study analyzed 3,610 of 4,310 Japanese outpatients (mean age, 65 years; men, n=1,664; women, n=1,947) with a history of at least one cardiovascular event who were recruited to the Japan Morning Surge-Home Blood Pressure Study. During an average 4-year follow-up, there were 129 cardiovascular events. Both median BNP (21.1 pg/mL; IQR, 10.9–40.6 pg/mL vs. 16.2 pg/mL, IQR, 7.2–36.2 pg/mL, P<0.001) and median NT-proBNP (54.7 pg/mL; IQR, 30.2–102.6 pg/mL vs. 44.9 pg/mL, IQR, 20.7–92.6 pg/mL, P<0.001) were significantly higher in women than in men. A 1-SD increment in log-transformed BNP (hazard ratio [HR], 2.18; 95% CI: 1.53–3.10) and NT-proBNP (HR, 2.39; 95% CI: 1.73–3.31) was associated with a significant increase in cardiovascular events in women; in men, only NT-proBNP showed this association. There was an interaction between log-transformed BNP (P=0.007) or NT-proBNP (P=0.001) and cardiovascular events according to sex.

Conclusions:Both BNP and NT-proBNP predicted cardiovascular outcomes in a large Japanese clinical population. BNP and NT-proBNP were significantly stronger predictors in women than in men.

Background:High prevalence of frailty and of diastolic dysfunction (DD) in heart failure and high mortality in frail adults have been noted. We characterized frailty by quantifying differences on echocardiography, and assessed the added prognostic utility of frailty and DD grade in an elderly population.

Methods and Results:One hundred and ninety-one patients ≥65 years who had at least 1 cardiovascular risk factor were prospectively recruited for clinically indicated echocardiography at the present institute. Weight loss, exhaustion, and deficits in physical activity, gait speed, and handgrip strength were used to categorize patients as frail (≥3 features), intermediately frail (1 or 2 features), or non-frail (0 features). DD grade ≥2 was defined as severe. Frailty was associated with larger left atrial volume, smaller stroke volume, and worse DD grade after adjustment for age. In a period of 14 months, 29 patients (15%) had cardiovascular events. The addition of frailty score and severe DD significantly improved the prognostic power of a model containing male gender (model 1, male gender, χ²=6.4; model 2, model 1 plus frailty score, χ²=16.7, P=0.004; model 3, model 2 plus severe DD, χ²=25.5, P=0.015).

Conclusions:Both frailty and DD grade were significantly associated with future cardiovascular events in an elderly population with preserved ejection fraction and ≥1 risk factor of cardiovascular disease.

Background:Septal leftward motion followed by a counter motion during early systole is known as septal flash (SF) in patients with isolated complete left bundle-branch block (cLBBB). This study aimed to determine the predictive value of SF for reduction of left ventricular (LV) global systolic function using 2D speckle-tracking echocardiography (2D STE) in cLBBB patients.

Methods and Results:The study group of 41 patients with isolated cLBBB and preserved LV ejection fraction and 41 age- and sex-matched control subjects were studied. The presence of SF and LV global longitudinal strain (GLS) were defined and measured using 2D STE. Multivariate logistic regression analysis identified the presence of SF as an independent factor predicting LV GLS >−20% in isolated cLBBB patients (odds ratio, 1.38; 95% confidence interval, 1.10–1.72; P=0.005). LV GLS in cLBBB patients with SF further decreased over time, whereas LV GLS did not decrease in patients without SF. The presence of SF was shown to be an independent factor predicting the reduction of LV global systolic function (relative reduction in LV GLS >15% from baseline to 2-year follow-up) (odds ratio, 1.27; 95% confidence interval, 1.06–1.50; P=0.008).

Conclusions:Assessment of SF by 2D STE may be an easy and effective method of predicting the reduction in LV global systolic function in isolated cLBBB patients.

Background:The present study was conducted to assess the cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP4i) on coronary flow reserve (CFR), left ventricular (LV) function and endothelial function of the peripheral artery by comparison with those of α-glucosidase inhibitors (αGI) in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).

Methods and Results:We randomly assigned 30 patients with T2DM and CAD to receive either sitagliptin or voglibose, and 28 patients (age 69±9 years, 75% male, hemoglobin A1c [HbA1c] 6.62±0.48%) completed the study (14 in each group). CFR and LV function, assessed by cardiac magnetic resonance imaging, and endothelial function, assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT), were measured at baseline and 24 weeks after treatment. Clinical and laboratory parameters, including HbA1c level, plasma active glucagon-like peptide-1 concentrations, and biomarkers of inflammation, were unchanged in both groups after 24 weeks of treatment. CFR were unchanged in both the αGI group (3.01±0.98 at baseline and 3.06±0.8 after treatment, P=NS) and the DPP4i group (4.29±2.04 at baseline and 3.63±1.31 after treatment, P=NS), with no interaction effect. LV functional parameters and the reactive hyperemia index also remained unchanged after the 24-week treatment.

Conclusions:DPP4i did not improve CFR, LV function or endothelial function of the peripheral artery in patients with relatively well-controlled T2DM and CAD.

Background:Adhesion molecules have essential roles in the development of atherosclerosis. We investigated whether P-selectin glycoprotein ligand-1 (PSGL-1)-expressing CD4 T cells contribute to plaque instability in acute coronary syndrome (ACS).

Methods and Results:We studied the adhesion molecules on CD4 T cells from consecutive patients with ACS treated with thrombus-aspirating device and compared them with healthy controls (n=48 each). Blood, thrombi, and plaque samples from the culprit coronary arteries were collected by thrombus aspiration performed during emergency coronary artery angiography. According to flow cytometry results, peripheral CD4 T cells from ACS patients strongly expressed PSGL-1 and integrin β2 (P<0.05 for both) more than those from controls; culprit coronary arteries contained an abundance of PSGL-1⁺(P<0.001) but not integrin β2⁺CD4 T cells. In addition, immunohistochemical analysis of the thrombus-aspirating device samples revealed numerous PSGL-1⁺CD4 T cells in plaques from the culprit lesions. Results from the selectin-binding assay demonstrated that activated PSGL-1⁺CD4 T cells from ACS patients bound to P- or E-selectin after triggering the T-cell receptor, and adhered to endothelial cells under laminar flow conditions (P<0.05 and P<0.05, respectively), inducing their apoptosis (P<0.01) via activated caspase-3, which correlated with PSGL-1 expression (R=0.788, P=0.021) and was suppressed by application of a PSGL-1-specific antibody (P<0.05).

Conclusions:PSGL-1 contributed to cytotoxic CD4 T cell homing to the culprit coronary artery and promoted plaque instability in ACS.

Background:We investigated whether the outcome of revascularization differed from the outcome of medical therapy in chronic kidney disease (CKD) and non-CKD patients with chronic total occlusion (CTO).

Methods and Results:A total of 2,010 patients with CTO who underwent revascularization (n=1,355), including percutaneous coronary intervention (n=878) and coronary artery bypass grafting (n=477), or had medical therapy alone (n=655) were examined. The primary outcome was all-cause death during follow-up. Among the non-CKD patients (n=1,679), revascularization had a lower incidence of all-cause death (adjusted hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41–0.72, P<0.001) compared with medical therapy. Among the CKD patients (n=331), the difference in the incidence of all-cause death was not as marked between the 2 treatments (adjusted HR 0.71, 95% CI 0.48–1.06, P=0.09). There was a significant interaction between kidney function and treatment strategy (revascularization vs. medical therapy) on all-cause death (P for interaction=0.014).

Conclusions:Based on the clinical outcomes, in CTO patients with preexisting CKD, revascularization via PCI or bypass surgery might not be as effective as in non-CKD patients.

Background:Long-term hepatic dysfunction is an increasingly recognized complication of the Fontan operation for univentricular hearts. The purpose of this study was to determine whether Fontan-associated liver disease (FALD) could be predicted by flow dynamics in the right atrium (RA) of Fontan circulation.

Methods and Results:Cardiac MRI and the serum levels of total bilirubin (TBil) and hyaluronic acid (HA) were analyzed in 36 patients who underwent an atriopulmonary connection type of Fontan operation. The mean follow-up period was 53 months. Three views (axial, coronal, and sagittal) of the cine images were scanned for the maximum cross-section of the RA obtained with1.5-Tesla scanner. We developed a “vortex flow map” to demonstrate the ratio of the circumferential voxel movement in each phase to the total movement throughout a cardiac cycle towards the center of the RA. The maximum ratio was used as the magnitude of vortex flow (MVF%) in the 3 views of the RA cine imaging. Patients with coronal MVF ≥13.6% had significantly lower free rates of TBil ≥1.8 mg/dL than those with coronal MVF <13.6% (log-rank value=4.50; P<0.05; hazard ratio=4.54). Patients with sagittal MVF ≥14.0% had significantly lower free rates of HA ≥50 ng/mL than those with coronal MVF <14.0% (log-rank value=4.40; P<0.05; hazard ratio=4.12).

Conclusions:A reduced vortex flow in the RA during the late phase of the Fontan operation was associated with the development of FALD. MVF can be used as an imaging biomarker to predict FALD.

Background:Sudden infant death syndrome mainly occurs during night-time sleep. Approximately 10% of cases are thought to involve infants with long QT syndrome (LQTS). Autonomic function and QT interval in night-time sleep in early infancy in LQTS infants, however, remain controversial.

Methods and Results:Holter electrocardiography was performed in 11 LQTS infants before medication in early infancy, and in 11 age-matched control infants. Control infants were re-evaluated in late infancy. The power spectral density was calculated and parasympathetic activity and sympathovagal balance were obtained. Electrocardiograms of a representative hour during night-time sleep, daytime sleep, and daytime activity, were chosen and QT/RR intervals were manually measured. LQTS infants had significantly lower parasympathetic activity and higher sympathovagal balance during night-time sleep than control infants in early infancy. These autonomic conditions in early infancy were significantly depressed compared with late infancy. Corrected QT interval (QTc) during night-time sleep (490±20 ms) was significantly longer than that in daytime sleep (477±21 ms, P=0.04) or daytime activity (458±18 ms, P=0.003) in LQTS infants, and significantly longer than that during night-time sleep in controls.

Conclusions:A combination of the longest QTc and autonomic imbalance during night-time sleep in early infancy may be responsible for development of life-threatening arrhythmia in LQTS infants. Critical cases should be included in future studies.

Background:Endovascular therapy has become the first-line treatment for most peripheral artery diseases, but re-entry into the true lumen is not always possible, particularly in some cases of chronic total occlusion (CTO). We previously reported a novel hybrid Viabahn-assisted bypass (VAB) technique to facilitate revascularization of the femoro-popliteal CTO. This study assessed the midterm results of VAB technique.

Methods and Results:Between January 2013 and April 2017, 440 patients received femoro-popliteal intervention and 17 of them (mean age, 76.2 years; 11 male patients) were treated using the VAB technique. The technical success was 100%. The mean follow-up period was 27.4±14.4 months (range, 6–50 months). Two patients underwent major amputation at 6 and 11 months postoperatively, but they died of acute myocardial infarction and of sepsis, respectively. Another 3 patients received re-intervention because of edge stenosis of the Viabahn stent graft. Another patient had acute Viabahn thrombosis and was treated using open thrombectomy. The primary and secondary patency rates at 12 months were both 88.2%, and at 24 months they were 69.2% and 84.6%, respectively.

Conclusions:The VAB technique could be a safe and feasible alternative treatment for long femoro-popliteal CTO when conventional treatments fail. The technical success is high, and the midterm patency rates are acceptable.

Background:The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.

Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II–IV and Rutherford category 1–5) caused by arteriosclerosis obliterans or Buerger’s disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious.

Conclusions:In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

Background:Excessive daytime sleepiness (EDS) is a significant public health concern, with sleep-disordered breathing (SDB) being a common cause. However, their precise relationship in patients with cardiovascular disease (CVD) is unclear. Furthermore, whether comorbid psychological disorders could contribute to EDS remains unknown. We aimed to assess the prevalence of EDS and its related factors, including SDB and depression, in patients with CVD.

Methods and Results:We analyzed data from 1,571 patients admitted for various CVDs in a single university hospital (median age, 67 [56–76] years; 29.6% women). We assessed EDS using the Japanese version of the Epworth Sleepiness Scale (ESS; median 6.0 [4.0–9.0]). The presence of EDS (ESS >10, n=297 [18.9%]) did not differ between patients with and without SDB, which was screened with nocturnal pulse oximetry. In contrast, the patients with EDS had higher depression scores (Hospital Anxiety and Depression Scale subscore for depression [HADS-D] and Patient Healthcare Questionnaire [PHQ]-9). The depression scores, measured by HADS-D (odds ratio [OR] 1.14; 95% confidence interval [CI], 1.07–1.22) and PHQ-9 (OR, 1.14; 95% CI, 1.07–1.20) were independent determinants of EDS. These relationships among EDS, SDB, and depression were consistent among the subgroups with cardiovascular comorbidities.

Conclusions:The presence of EDS is associated with depressive symptoms, but not with SDB, in patients with CVD, suggesting that these patients should be thoroughly assessed for psychological disturbances.

Background:Acute pulmonary embolism (PE) is a major threat to the health and lives of hospitalized patients. This study was conducted to clarify the real-world outcomes of pulmonary embolectomy.

Methods and Results:Retrospective investigation of 355 patients who underwent pulmonary embolectomy for acute PE was conducted using the Japanese Cardiovascular Surgery Database. Risk factors for operative death within 30 days after pulmonary embolectomy and major adverse cardiovascular events (MACE), including operative death, postoperative stroke and postoperative coma, were analyzed. Cardiopulmonary resuscitation (CPR) was required preoperatively in 27.6%, and preoperative veno-arterial extracorporeal membrane oxygenation was performed in 26.5%. Urgent or emergency operation was performed in 93% of patients. Operative mortality rate was 73/355 (20.6%). Incidence of MACE was 97/355 (27.3%). In univariate analysis, preoperative predictors of death were obesity, renal dysfunction, chronic obstructive pulmonary disease, liver injury, recent myocardial infarction, shock, refractory shock, CPR, heart failure, inotrope use, poor left ventricular function, preoperative arrhythmia and tricuspid regurgitation. In multivariate analysis, independent risk factors for operative death were heart failure (P=0.013), poor left ventricular function (P=0.007), and respiratory failure (P=0.001). Poor left ventricular function (P=0.033), preoperative CPR (P=0.002) and respiratory failure (P=0.007) were independent risk factors for MACE.

Conclusions:The outcomes of pulmonary embolectomy were acceptable, considering the urgency and preoperative comorbidities of patients. Early triage of patients with hemodynamically unstable PE is important.

Background:Various frailty markers have been developed to guide better patient selection for transcatheter aortic valve implantation (TAVI). This study aimed to investigate the frequency and specific causes of unplanned hospital readmission after TAVI, and to investigate which frailty markers better predicted outcomes.

Methods and Results:We retrospectively reviewed 155 patients for whom we calculated their Short Physical-Performance Battery (SPPB), Placement of AoRTic TraNscathetER Valve (PARTNER) frailty scale, frailty index, clinical frailty scale, modified Fried scale, and gait speed. The primary endpoint was unplanned readmission following TAVI. The clinical model was established using variables that were identified as independent predictors in multivariate analysis. Incremental values were assessed after adding each frailty marker to the clinical model, and were compared between frailty markers. Although unplanned readmission <30 days was 1.9%, 23% of patients had an unplanned readmission following TAVI mainly because of heart failure and pneumonia within 1 year. Frailty markers other than the modified Fried scale were independently associated with unplanned readmission. The SPPB and the PARTNER frailty scale significantly increased discriminatory performance for predicting unplanned readmission.

Conclusions:Unplanned readmissions following TAVI in the present study were fewer than previously reported. There seems to be a difference between frailty markers in their predictive performance. Precise frailty assessment may result in reducing unplanned admissions after TAVI and therefore better quality of life.

Background:Low flow (LF; i.e., reduced left ventricular stroke volume index <35 mL/m²) can occur with severe aortic stenosis (AS). However, few studies have investigated the effects of LF on early and late outcomes after aortic valve replacement (AVR) for severe AS.

Methods and Results:In all, 285 severe AS patients undergoing isolated AVR at Juntendo University Hospital between August 2002 and August 2015 were enrolled in the study. In this cohort, 52 patients (18%) had LF. Compared with patients with normal flow (NF) severe AS, early postoperative mortality (9.6% vs. 1.2%; P=0.006), gastrointestinal complications (5.7% vs. 0.8%; P=0.04), and the duration of the intensive care unit (ICU) stay (81.7 vs. 35.3 h; P=0.02) were increased in LF patients with severe AS. LF was an independent predictor of early mortality (Model A, odds ratio [OR] 6.81, P=0.01; Model B, OR 6.69, P=0.01) and composite complications (Model A, OR 2.44, P=0.02). In propensity score-matched comparisons, early mortality (12.8% vs. 0%; P=0.02), composite complications (28.2% vs. 10.2%; P=0.04), and duration of ICU stay (97.4 vs. 22.1 h; P=0.006) were significantly increased in LF than NF patients.

Conclusions:LF, as an important independent risk factor for postoperative mortality and morbidity, should be included in risk stratification and assessment in severe AS patients.