The consumption of omega-3 polyunsaturated fatty acids (PUFAs) reduces the incidence of cardiovascular events and sudden cardiac death. Coronary microvascular dysfunction (CMD) is a predictor of cardiac mortality, but little information is known on the relationship between CMD and omega-3 PUFAs. This study aimed to identify the relationship between the serum levels of omega-3 PUFAs and the CMD evaluated by the hyperemic microvascular resistance index (hMVRI) to assess coronary microvascular function in patients with stable coronary artery disease (CAD).

Intracoronary physiological variables (fractional flow reserve (FFR), hMVRI, mean distal coronary pressure (Pd), and average peak velocity (APV)) were measured in 108 patients. These parameters were evaluated in 150 coronary arteries with stenosis of intermediate severity and without significant ischemia (FFR > 0.80). The PUFA levels and atherosclerotic risk factors were also measured. Univariate analysis shows that hMVRI was negatively correlated with eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (β = −0.31, P = 0.001) and EPA (β = −0.25, P = 0.009) and was positively correlated with dihomo-γ-linolenic acid (β = 0.26, P = 0.006). Multivariate regression analysis shows that the EPA/AA ratio was the only independent determinant of hMVRI (β = −0.234, SE = 0.231, P = 0.024). Furthermore, hMVRI decreased significantly from the lowest to highest tertiles of the EPA/AA ratio (P = 0.007). The EPA/AA ratio was positively correlated with APV at hyperemia (β = 0.26, P = 0.008) but not with Pd at hyperemia.

A lower serum EPA/AA ratio may cause CMD in patients with stable CAD.

Chronic kidney disease (CKD) patients have worse adverse cardiovascular outcomes after percutaneous coronary intervention (PCI). Clinical outcomes comparing a limus-eluting stent (LES) to a paclitaxel-eluting stent (PES) in patients with CKD remain controversial.

A systematic search was conducted using PubMed, EMBASE, and Cochrane Library. A pooled odds ratio (OR) and 95% confidence interval (CI) were used to calculate original data. We conducted heterogeneity, quality assessment, and publication bias analyses.

A total of 17 trials involving 10,724 patients were included. No significant differences were found regarding target vessel revascularization, target lesion revascularization (TLR), stent thrombosis (ST), myocardial infarction (MI), all-cause mortality, and major adverse cardiac events (MACE) between first-generation LES implantation and PES implantation. Second-generation LES implantation was associated with lower rates of all-cause mortality (OR, 0.56; 95% CI, 0.39-0.82; P = 0.003), MACE (OR, 0.61; 95% CI, 0.38-0.97; P = 0.04), and ST (OR, 0.45; 95% CI, 0.26-0.77; P = 0.004) compared with PES implantation. In all, the long-term all-cause mortality rate was significantly lower after LES implantation than after PES implantation in patients with CKD (OR, 0.78; 95% CI, 0.66-0.93; P = 0.004). However, second-generation LES implantation resulted in a higher rate of TLR (OR, 2.23; 95% CI, 1.53-3.25; P < 0.001) than PES implantation in dialysis patients.

In patients with CKD, first-generation LES and PES implantation had comparable mortality and morbidity. Second-generation LES implantation was superior to PES in reducing long-term mortality, MACE, and ST. However, PES may be more effective than LES in dialysis patients.

The enormous majority of previous reports focused on evaluating the safety and efficacy of sequential saphenous vein (SV) coronary bypass grafting; however, no reports to date have revealed concern regarding the impacts of the number of distal anastomoses of sequential SV grafting on graft patency after coronary artery bypass grafting (CABG). This single-center retrospective study aimed to evaluate the impacts of three versus two distal anastomoses per single SV conduit on SV graft patency after off-pump CABG, and to determine the independent risk factors for sequential SV graft failure.

From January 2011 to December 2014, 1320 eligible patients were assigned to either a triple group (three distal anastomoses of sequential SV grafting, n = 758) or a double group (two distal anastomoses of sequential SV grafting, n = 562). The primary endpoint was over a 2-year follow-up SV graft failure after off-pump CABG.

The triple and double group received a similar total patency rate of sequential SV conduits (86.5% versus 87.1%, P = 0.757). The number of distal anastomoses of sequential SV grafting (three versus two) was not a predictive factor for the follow-up graft failure of sequential SV conduits (HR = 0.91, 95% CI: 0.66-2.29, P = 0.137). Moreover, the two groups received a similar follow-up survival freedom from repeat revascularization (χ² = 1.881, log-rank P = 0.170).

Three versus two distal anastomoses per single SV conduit received a similar SV graft patency. The number of distal anastomoses of sequential SV grafting was not an independent risk factor for graft failure.

The relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in non-culprit coronary lesions is not clearly understood.

Fifty-four consecutive patients/158 lesions with suspected coronary artery disease underwent computed tomography (CT) and 40 MHz intravascular ultrasound imaging (iMap-IVUS) in cardiac catheterization. Cross-sectional CT slices were semiautomatically traced from base to apex of the heart. Using a 3D workstation, EATV was measured as the sum of fat areas (−190 to −30 Hounsfield units [HU]). All coronary vessels were imaged using iMap-IVUS before stenting to analyze coronary plaques as fibrotic, lipidic, necrotic, or calcified tissue.

Mean EATV was 73.7 ± 24.6 (range: 30.2 to 131.8) mL. Patients were divided into two groups by mean EATV (group H: n = 27, EATV ≥ 73.7 mL; group L: n = 27, EATV < 73.7 mL). Total luminal volume, total vessel volume, and total plaque volume were significantly larger in group H. Fibrotic plaque and lipidic plaque volumes were also significantly larger in group H. There was a significant negative correlation between EATV and fibrous tissue (r = -0.31, P = 0.02) and a significant positive correlation between EATV and necrotic tissue (r = 0.37, P = 0.007). EATV was related to plaque with vulnerability in the right coronary artery (RCA) (r = 0.57, P = 0.04) and the left anterior descending artery (LAD) (r = 0.53, P = 0.02). In conclusion, increased EATV was associated with the total coronary plaque burden and composition, particularly in the RCA and LAD.

Low-level hemolysis (LLH) after left ventricular assist device implantation contributes to thromboembolic events (TE). Free plasma hemoglobin (fHb) scavenges nitric oxide (NO), which causes endothelial dysfunction and activates platelets. fHb also interacts with von Willebrand factor (vWF). We hypothesized that improved hemodynamic and enhanced NO signaling in HeartMate II (HMII) patients with LLH taking the phosphodiesterase-5 inhibitor sildenafil may reduce the risk of TE.

From 2011 to 2015, 83 patients underwent HMII implantation. Patients with LLH as defined by elevated lactate dehydrogenase (400 < LDH ≤ 700 U/L) at hospital discharge were identified. Patients were categorized into 4 groups: 1) LLH + sildenafil, 2) LLH no sildenafil, 3) no LLH + sildenafil, and 4) no LLH no sildenafil. Adverse event-free survival was compared between the groups.

Thirty-four patients (40.9%) were discharged with LLH and 22 (64.7%) of them took sildenafil. LDH and fHb remained significantly elevated in both LLH groups compared to the no LLH patients (P < 0.0001). Overall incidence of pump thrombosis (PT) was 4.8% and of ischemic stroke (IS) was 8.4%. HMII patients with LLH not on sildenafil had higher risk of TE (hazard ratio (HR): 14.4, 95%-CI: 1.8-117.1, P = 0.001). vWF activity and bleeding incidence did not differ between the LLH and no LLH patients. Mean pulmonary artery pressure and pulmonary vascular resistance decreased significantly in HMII taking sildenafil (P < 0.0001) while cardiac index increased (P < 0.0001).

Sildenafil treatment among HMII patients with LLH reduced the risk of thromboembolic events and significantly improved and decompressed the pulmonary circulation during HMII support.

Slow flow is a serious complication in percutaneous coronary intervention (PCI) and is associated with poor clinical outcomes. Our previous study revealed that the ratio of stent diameter to vessel diameter was the determinant of slow flow in intravascular ultrasound (IVUS)-guided PCI to the culprit lesion of ST elevation myocardial infarction (STEMI). The purpose of this study was to verify whether the ratio of stent diameter to vessel diameter is the determinant of slow flow in IVUS-guided PCI to the culprit lesion of non-STEMI (NSTEMI). We included 150 NSTEMI patients and divided into the slow flow group (n = 17) and the non-slow flow group (n = 133). The ratio of stent diameter to vessel diameter was significantly larger in the slow flow group (0.77 ± 0.11) than the non-slow flow group (0.71 ± 0.11) (P = 0.03). Multivariate logistic regression analysis revealed that the ratio of stent diameter to vessel diameter (per 0.1 increase: OR 2.06, 95% CI 1.23-3.46, P = 0.006) was the determinant of slow flow after controlling covariates. In conclusion, the ratio of stent diameter to vessel diameter was the determinant of slow flow in IVUS-guided PCI to the culprit lesion of NSTEMI. Unlike other parameters, the ratio of stent diameter to vessel diameter is the modifiable parameters. We may consider the modest stent expansion strategy rather than the aggressive stent expansion strategy in IVUS-guided PCI to the culprit lesion of NSTEMI.

In this study, we aim to investigate the association of serum uric acid (SUA) with the prevalence of premature ventricular contraction (PVC). The relationship between SUA and the prevalence of PVC in 98,965 subjects (79,034 male subjects, mean age: 51.9 ± 12.6 years old) in the Kailuan cohort study (n = 101,510, age range: 18-98 years) from June 2006 to October 2007 was investigated. These subjects were divided into five groups on the basis of their SUA levels. A multivariate logistic regression model was constructed to evaluate the association between SUA and the prevalence of PVC. The prevalence of PVC was 1.1% in all subjects, 1.1% in male subjects, and 1.0% in female subjects. Compared with the first quintile of SUA, the odds ratio (OR) and 95% confidence interval (95% CI) of other quintiles were 1.33 (1.05-1.69), 1.14 (0.90-1.46), 1.37 (1.08-1.74), and 1.63 (1.30-2.06) in male subjects; 1.12 (0.68-1.87), 1.27 (0.77-2.09), 1.45 (0.90-2.36), and 1.33 (0.81-2.18) in female subjects; and 1.30 (1.04-1.61), 1.20 (0.96-1.50), 1.33 (1.07-1.66), and 1.57 (1.26-1.95) for all subjects. The correlation between SUA and the prevalence of PVC was significant in all subjects and in male subjects, but not in female subjects. We demonstrated that SUA was apparently associated with the prevalence of PVC. The significant relationship between SUA and PVC identified in male subjects suggests the potential involvement of a gender-specific mechanism. Prospective studies are needed to further corroborate our results.

The SelectSecure™ lead system (SSLS), which is composed of a thin lumenless, active-fixation lead and a deflectable catheter, is approved for use in Japan. This study aimed to evaluate the long-term clinical outcomes of right ventricular (RV) septal pacing with the SSLS along with the system's safety and electrical performance. A total of 129 patients were divided into the following 3 groups: the RV septal pacing with the SSLS group (SSP, n = 21); the RV septal pacing with the conventional lead group (Septal, n = 77); and the RV apical pacing with the conventional lead group (Apical, n = 31). All lead-related complications and pacing parameters during follow-up were compared among the groups. The clinical outcome was heart failure-associated hospitalization. The SSP and Septal groups showed significantly shorter paced QRS duration than the Apical group. During the follow-up for a mean of 49.5 ± 13.1 months, no lead-related complications occurred in any of the groups. A case of pericardial effusion occurred in the SSP group, but cardiac tamponade did not occur, and it spontaneously resolved. The ventricular pacing threshold after the follow-up period was higher in the SSP group than in the other 2 groups. There was no difference in the primary heart failure hospitalization among the 3 groups. The SSLS could be effective in producing a narrow QRS width with RV septal pacing, but its pacing threshold was higher than conventional leads in the chronic phase.

Interatrial block (IAB) is associated with a multitude of medical conditions. The aim of this retrospective study was to investigate whether CHADS₂ (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) score is positively associated with the development of IAB. A total of 1072 patients (men, 555; women, 517; mean age, 61 ± 14 years) were included in the study. P-wave duration was measured manually using a caliper. IAB was defined as a P-wave duration of ≥ 120 ms on a 12-lead electrocardiogram. CHADS₂ scores were calculated retrospectively. Among the 1072 patients, the prevalence of IAB was 36.1% (387/1072). In multivariate analysis, increased CHADS₂ score (odds ratio [OR], 1.810; 95% confidence interval [CI], 1.577-2.077; P < 0.001), coronary artery disease (OR, 1.536; 95% CI, 1.065-2.216; P = 0.022), and increased left atrial diameter (OR, 1.039; 95% CI, 1.008-1.071; P = 0.013) were independently associated with IAB. The percentages of patients with IAB among those with a CHADS₂ score of 0, 1, 2, 3, 4, 5, and 6 were 20.6%, 33.0%, 45.0%, 55.9%, 61.9%, 77.8%, and 100%, respectively (P < 0.001). There was a greater percentage of patients with a CHADS₂ score of ≥ 2 with IAB compared with a CHADS₂ score of < 2 (26.5% vsrsus 52.0%; P < 0.001). In receiver operating curve (ROC) analysis, CHADS₂ score (area under the curve, 0.670; 95% CI, 0.636-0.704; P < 0.001) was predictive of IAB. In conclusion, CHADS₂ score was significantly associated with the development of IAB in this study population.

The burden of anticoagulation treatment affects patient satisfaction, which in turn affects adherence to treatment. Thus, we must thoroughly understand the advantages of direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs)/warfarin given for stroke prevention in patients with atrial fibrillation (AF). We compared satisfaction with anticoagulation therapy between 654 DOAC and 821 warfarin users enrolled in the SAKURA AF Registry. Satisfaction was assessed by means of the Anti-Clot Treatment Scale (ACTS), which includes 12-item burdens and 3-item benefits scales, and the treatment satisfaction questionnaire for medication II (TSQM II), which includes 2-item effectiveness, 3-item side effects, 3-item convenience, and 2-item global satisfaction domains. There were no significant between-group differences in TSQM II convenience (67.6 ± 14.5 versus 68.9 ± 14.5, P = 0.280), effectiveness (65.0 ± 13.3 versus 66.0 ± 15.0, P = 0.422), side effects (93.6 ± 13.7 versus 92.8 ± 14.4, P = 0.067), and global satisfaction (64.7 ± 14.9 versus 66.0 ± 14.6, P = 0.407) scores. In contrast, although there was no significant between-group difference in the ACTS benefits scores (9.8 ± 3.1 versus 10.1 ± 3.2, P = 0.051), the ACTS burdens scores (54.5 ± 6.3 versus 52.7 ± 6.9, P < 0.0001) were significantly higher in the DOAC users, independent of age, sex, and DOAC type. We can expect greater burden satisfaction with anticoagulation treatment in patients given a DOAC versus VKA/warfarin. The reduced burden of treatment will translate to greater patient adherence to their treatment plans and a positive effect on clinical outcomes.

Right ventricular apical (RVA) pacing often causes left ventricular (LV) mechanical asynchrony, which is enhanced by impaired cardiac contraction and intrinsic conduction abnormality. However, data on patients with normal cardiac function and under RV non-apical (non-RVA) pacing are limited.

We retrospectively investigated 97 consecutive patients with normal ejection fraction who received pacemaker implantation for atrioventricular block with the ventricular lead placed in a non-RVA position. We defined mechanical asynchrony as discoordinate contraction between opposing regions of the LV wall evaluated by echocardiography. Asynchrony was detected in 9 (9%) patients at baseline and in 38 (39%) under non-RVA pacing (P < 0.001). Asynchrony at baseline was significantly associated with complete left bundle branch block (CLBBB) [odds ratio (OR) = 20.8, P < 0.001]. Asynchrony under non-RVA pacing was significantly associated with left anterior fascicular block (LAFB) (OR = 7.14, P < 0.001) and CLBBB (OR = 13.3, P = 0.002) at baseline. New occurrence of asynchrony was significantly associated with LAFB at baseline (OR = 5.88, P = 0.001). During a median follow-up period of 4.8 years, the incidence of device-detected atrial fibrillation (AF) was more frequent in patients who developed asynchrony than in those who did not (53.3% versus 27.5%, hazard ratio = 2.17, 95% confidence interval = 1.02-4.61, P = 0.03).

In patients with normal cardiac function, LAFB at baseline was significantly associated with new occurrence of mechanical asynchrony under non-RVA pacing. Abnormal contraction had a significant influence on the incidence of device-detected AF.

There is limited information on long-term outcomes of mitral valve repair for mitral regurgitation (MR) caused by different degrees of myxomatous degeneration. The aim of this study was to compare the surgical results of patients with advanced and mild/moderate myxomatous mitral valve degeneration (MVD). We identified 130 patients (25 advanced and 105 mild/moderate MVD patients) who underwent mitral valve repair for MR and were pathologically diagnosed as myxomatous degeneration. Follow-up was 100% complete (mean length, 5.1 ± 1.8 years). Survival differed significantly between the advanced and mild/moderate MVD groups (76.0 ± 9.7% versus 95.0 ± 5.4% at 8 years, P < 0.001). The univariate predictors of mortality were advanced myxomatous degeneration, recurrent MR, and early series (surgeries before 2011). The mild/moderate MVD group had higher freedom from a moderate or severe MR rate compared with the advanced MVD group (77.4 ± 4.5% versus 50.5 ± 10.2% at 7 years, P = 0.003). Multivariable Cox analysis revealed advanced myxomatous degeneration and residual MR as independent predictors of recurrent moderate or severe MR. A total of 25 patients (19.2%) had persistent atrial fibrillation (AF) after repair. In multivariate analysis, advanced myxomatous degeneration was found to be an independent predictor of postoperative persistent AF.

In conclusion, the long-term outcomes of mitral valve repair in patients with advanced MVD are poorer than in those with mild/moderate MVD. Advanced myxomatous degeneration is an independent predictor of recurrent moderate or severe MR and postoperative persistent AF in MVD patients performing repair, which deserves more attention before and after surgery.

Our aim was to assess the clinical effects of myocardial injury after transcatheter aortic-valve implantation (TAVI). Between October 2013 and July 2016, 157 patients underwent TAVI with Sapien XT, Sapien 3, or CoreValve prostheses at our institute. Of these, 130 patients for whom the transapical approach was not used were included in this study. Myocardial injury was defined as a peak troponin I level of ≥1.5 ng/mL within 48 hours after TAVI. We evaluated the predictors of myocardial injury and compared the clinical outcomes of 82 patients classified as the myocardial injury group and 44 patients classified as the non-myocardial injury group. The patients were aged 85 ± 6 years. Myocardial injury occurred in 82 patients (65.1%). Age (per 1 increase) (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, P = 0.041), female sex (OR: 3.88, 95% CI: 1.23-12.22, P = 0.021), valve type (Sapien XT; OR: 4.22, 95% CI: 1.15-15.47, P = 0.03, Core valve; OR: 18.12, 95% CI: 2.86-114.59, P = 0.002), balloon aortic valvuloplasty as a bridge therapy (OR: 0.10, 95% CI: 0.02-0.42, P = 0.002), and left ventricular end-diastolic volume (LVEDV) (per 1 increase) (OR: 0.97, 95% CI: 0.95-0.99, P = 0.003) were associated with myocardial injury in a multivariate model. The myocardial injury group did not have a higher rate of midterm (365-day) mortality (log-rank test P = 0.57) than the non-myocardial injury group on Kaplan-Meier analysis. Myocardial injury after TAVI was not associated with midterm mortality.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as antidiabetic drugs. We recently reported that DPP-4 inhibition has beneficial effects on heart failure (HF) mice model. Furthermore, we confirmed that myocardial DPP-4 activity was significantly increased in HF mice compared with non-HF mice. The aim of this study was to investigate the level of myocardial CD26 (DPP-4) expression and its association to clinical parameters in HF patients.

Endomyocardial biopsy (EMB) specimens (n = 33) were obtained from HF patients who were admitted to Chiba University Hospital from June 2006 to July 2012. EMB specimens were fixed in formaldehyde and stained with Masson's trichrome staining or with anti-CD26 antibody. Patients were divided into the high CD26 density (CD26-H) or low CD26 density groups (CD26-L). DPP-4 density was compared with blood brain natriuretic peptide (BNP) level and echocardiographic parameters at one year after EMB. Although there were no significant differences in echocardiographic parameters between the CD26-H group and CD26-L group, blood BNP levels were higher in the CD26-H group than in the CD26-L group at one year after EMB. Multivariate regression analysis showed that CD26 density was also an independent determinant of blood BNP levels at one year after EMB.

The level of myocardial CD26 expression might be a predictive marker of prognosis in patients with HF.

Changes of global and segmental ventricular strain at different deterioration levels of cardiac function in patients with dilated cardiomyopathy (DCM) using cardiac magnetic resonance (CMR) have not yet been explored. In total, 101 patients diagnosed with DCM consecutively underwent CMR. They were categorized according to the reduction in left ventricular ejection fraction (LVEF) into the following groups: moderately reduced (n = 43) and severely reduced group (n = 58). LV global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), and segmental strain values were assessed using tissue tracking technique. LV segmental circumferential strain (CS) and radial strain (RS) in healthy volunteers increased from base to apex stepwisely. The LV base-to-apex increasing pattern disappeared in the moderate DCM group (RS: 26.61% ± 20.63% versus 21.97% ± 4.85% versus 29.05% ± 9.90%, P > 0.05; CS: -13.16% ± 6.40% versus -12.96%± 2.45% versus -15.32% ± 3.89%, P > 0.05). While in the severe group, CS and RS of base segment had the highest values, there was no significant difference between mid and apex segments. GLS_LV, GRS_LV, and GCS_LV were significantly reduced in moderate and severe groups in steps, similar to the three parameters of RV. During a 17-month median follow-up, 25 patients had an index composite outcome event. GLS_LV > -11.62%, GCS_LV > -9.35%, and GRS_LV≤ 12.42% were significantly associated with the occurrence of cardiac events in DCM patients. LV segmental values reduce non-homogeneously in DCM patients with moderately and severely deteriorated heart function.

Cardiac resynchronization therapy (CRT) improves heart function and prognosis in third-degree atrioventricular block (AVB) patients with heart failure (HF). However, it is still unclear how to screen for appropriate patients before implantation. This study aimed to evaluate the value of using QRS duration to predict CRT efficacy.

This study enrolled a total of 72 third-degree AVB patients with HF who received CRT implantation. The patients were divided into Groups A (QRS duration < 120 ms, 33 cases), B (120 ms ≤ QRS duration < 150 ms, 22 cases), and C (QRS duration ≥ 150 ms, 17 cases) according to their baseline QRS duration. The effects of different QRS durations on CRT efficacy were analyzed.

The CRT response rate were 30.3%, 50.0%, and 76.5% in Groups A, B, and C, respectively (P = 0.008). The patients in the 3 groups showed significant changes in left ventricular (LV) end-diastolic volume, LV end-systolic volume, and LV ejection fraction over the baseline values at 12 months after the implantation (P < 0.05), with the greatest change observed in Group C. Survival analysis indicated statistically significant differences among Groups A, B, and C (P = 0.024). Multivariate logistic regression analysis suggested that QRS duration was an independent prognostic factor for CRT efficacy. Baseline QRS duration was associated with improved myocardial remodeling and reductions in the incidence rates of primary endpoint events.

QRS ≥ 150 ms is an effective predictor of postoperative outcome in patients with third-degree AVB and HF treated with CRT.

The benefits of patent foramen ovale (PFO) closure for cryptogenic stroke secondary prevention are still debated. The Risk of Paradoxical Embolism (RoPE) study developed a score to improve patient selection for this procedure. We proposed to assess the validity of this score to assess the prognostic impact of PFO closure.

From 2000 to 2014, all consecutive patients submitted to PFO closure were included in a prospective registry in a university center. The primary endpoint was recurrent ischemic cerebrovascular events and the secondary endpoints were all-cause, neurological, and cardiac mortality rates and new-onset atrial fibrillation (NOAF) rates. In total, 403 patients were included in the study (women: 52.1%; mean age: 44.7 ± 10.9 years). The mean follow-up period was 6.4 ± 3.7 years. Immediate success was achieved in 97% patients. There were 23 (5.8%) ischemic cerebrovascular events, 8 (2.0%) deaths, and 17 (4.3%) NOAFs. The mean RoPE score was 6.10 ± 1.79. Smoker status, coronary artery disease, lower RoPE score, and higher left atrial dimensions were predictors of the primary endpoint. However, a lower RoPE score and coronary artery disease remained independent predictors in multivariate analysis.

RoPE score was shown to be an independent predictor of recurrent ischemic cerebrovascular events, and a score of ≤ 6 was shown to identify patients with significantly higher risk of mortality and recurrent ischemic events.

Sildenafil is a pulmonary artery hypertension (PH)-targeted drug that finds an increased indiscriminate use in children with PH secondary to congenital heart disease (CHD).

We performed a meta-analysis to evaluate the effects of sildenafil on pediatric patients with PH secondary to CHD during perioperative period.

PubMed, EMBASE, the Cochrane Library, and the Google Scholar were searched up to May 2016 for randomized controlled trials (RCTs) assessing the perioperative treatment of sildenafil in pediatric patients with PH secondary to CHD. Major clinical outcomes were mortality before discharge, length of ICU stay, and length of hospitalization. The outcomes were analyzed as continuous and dichotomized variables by using fixed or random effect model, and we computed the pooled RR and MD with 95% confidence interval.

Five RCTs involving 238 pediatric patients with PH experienced CHD operation were included. Sildenafil was used in all trials. We observed no differences in mortality before discharge (RR 0.35; 95% CI 0.06-2.10; χ² = 1.31, I² = 0.24, P = 0.25) and length of hospitalization (MD −0.50; 95% CI −1.60 to 0.60; χ² = 5.29, I² = 62%, P = 0.38). There was a decrease in the length of ICU stay (MD −18.18; 95% CI −24.68 to −11.67; χ² = 12.61, I² = 84%, P < 0.00001), which had a high heterogeneity. The findings were robust after the sensitivity analyses.

The perioperative treatment of sildenafil for CHD pediatric patients is a potential method to reduce the length of ICU stay. We observed no differences with the use of it in the mortality before discharge and the length of hospitalization.

Adult patients with repaired coarctation of the aorta (r-CoA) show high prevalence of late hypertension, but the exact mechanisms of this phenomenon are unknown. Endothelial dysfunction has been implicated in this paradoxical hypertension. We evaluated the endothelial function of both conduit and resistance arteries by using flow-mediated dilation (FMD) and digital peripheral artery tonometry (PAT).

Seventeen patients with r-CoA and one patient with repaired interrupted aortic arch (r-CoA group) aged 22.0 ± 6.9 years (5 females) underwent FMD of the right brachial artery, PAT of the right finger, blood marker tests, ambulatory blood pressure monitoring, echocardiography, carotid ultrasonography, and brachio-ankle pulse wave velocity measurement. The median age at aortic arch reconstruction was 2.0 months (interquartile range: 15 days to 7.0 years). Results were compared with 17 age-matched healthy subjects (control group).

Eight (44%) patients of the r-CoA group were hypertensive (5 received antihypertensive drugs). Patients in the r-CoA group showed significantly lower FMD (3.8 ± 1.5 versus 6.6 ± 2.5%, P < 0.001), larger intima-media thickness (0.63 ± 0.17 versus 0.47 ± 0.09 mm, P = 0.001), and higher left ventricular mass index (91.4 ± 24.6 versus 73.4 ± 17.3 g/m², P = 0.017) than those in the control group. There were no significant differences in PAT (refractory hyperemia index, 1.86 ± 0.43 versus 1.99 ± 0.59, P = 0.48) and brachio-ankle pulse wave velocity between the two groups.

Vascular dysfunction in r-CoA patients, particularly endothelial dysfunction, tends to occur more significantly in conduit arteries than in resistance arteries.

Long QT syndrome is a rare but potentially lethal cardiac channelopathy. The primary aim of the study was to investigate the long-term effects of video-assisted thoracoscopic (VATS) left cardiac sympathetic denervation (LCSD) in Chinese patients with long QT syndrome.

VATS-LCSD was performed in eight Chinese patients with LQTS. Twelve-lead ECGs and 24-hour Holter monitoring ECGs were recorded before and after surgery. The medical charts were reviewed to obtain patient data, and the patients who had been lost to follow-up were contacted through telephone.

The average QTc was shortened from 534 ± 52.7 to 503 ± 43.7 ms (P = 0.030) 24 hours post-surgery and down to 486 ± 34.8 ms (P = 0.021) 1 week post-surgery, with the heart rate unchanged. The average QT dispersion was reduced from 67 ± 17.5 to 21 ± 3.9 ms (P < 0.001) 24 hours post-surgery and remained shortened 1 week later (30 ± 8.1 ms, P < 0.001). Moreover, the 24-hour ECG showed that the QTc was shortened from 552 ± 95.9 to 497 ± 19.7 ms at the minimum heart rate (P = 0.008), and was decreased from 594 ± 144 to 495 ± 74.1 ms at the maximum heart rate (P= 0.04), while the minimum and maximum heart rates were comparable before and after surgery. No death was observed during the follow-up period and the clinical symptoms improved in all patients. The annual event rate decreased from 4 ± 3.50 to 0.63 ± 1.37 events/year (P = 0.034) after surgery.

These findings indicate that LCSD shortens the QTc, with the heart rate remaining unchanged. QTd might be a useful parameter for evaluating the efficacy of VATS-LCSD. LCSD could improve patients' life quality by reducing cardiac events.

Although beta-blockade itself is not a first choice for chronic kidney disease (CKD) patients, alpha-beta-blockers (ABB) do improve their prognoses. This study's aim was to evaluate the effect of beta-selective-blockers (BSB) and ABB on circadian cardiac autonomic activity in CKD patients.

The study consisted of 496 non-diabetic individuals who underwent 24-hour Holter monitoring (149 CKD patients and 347 controls without CKD). Using heart rate variability analysis, we evaluated the proportion of NN50 and the high-frequency component (reflecting parasympathetic activity), and low- to high-frequency ratio (reflecting sympathovagal balance). These indices were evaluated by regression analysis incorporating gender, age, related comorbidities, and medications. BSB increased vagal activity only in the day-time and not the night-time in controls. In CKD patients, BSB was significantly related to higher vagal activity throughout the day and with lower sympathovagal balance at night. The night sympathovagal balance of CKD patients taking ABB was significantly higher than that of CKD patients taking BSB, which was the only significant difference between the effects of BSB and ABB.

The sympatholytic therapy effect is different depending on CKD presence and whether patients are treated with BSB or ABB. In CKD patients without severe heart failure, BSB could be associated with higher parasympathetic activity and lower sympathovagal balance compared to ABB.

Myocardial ischemic events after non-cardiac surgery is still a serious problem, especially in older, high-risk patients. However, the prevalence and risk factors of blood pressure (BP) abnormalities, which may possibly lead to myocardial ischemic attack, have not been reported. Our aim is to elucidate predictive factors of postoperative BP abnormalities following a minor-to-moderate surgery, employing preoperative left ventricular diastolic function. Patients who underwent cardiac echocardiogram examination and received oral and maxillofacial surgery under general anesthesia were enrolled. The echocardiographic parameters of diastolic function were compared between patients who had postoperative BP abnormalities (hypertension-systolic blood pressure [SBP] ≥ 170 mmHg-or hypotension-SBP < 80 mmHg-episode) that required therapeutic interventions until 7 days after surgery and those who had no BP abnormalities. Of the 173 patients analyzed, 25 (14.4%) had BP abnormalities. BP abnormalities patients were older, having a larger proportion of diabetes mellitus, lower E/A ratio and e', and larger E/e' and left atrial dimension than those without BP abnormalities. Subanalyses revealed that the independent risk factors responsible for hypertension episodes (14 patients) were the mean e' (odd ratio [OR]: 0.434; 95% confidence interval [CI]: 0.229-0.824), diabetes mellitus (OR: 5.018; 95% CI: 1.030-24.436), SBP at hospitalization (OR: 1.099; 95% CI: 1.036-1.165), and operation time (hour; OR: 1.326; 95%CI: 1.109-1.586), while hypotension episodes (11 patients) were associated solely with operation time (OR: 1.206; 95% CI: 1.046-1.391). In conclusion, left ventricular diastolic dysfunction, increased insulin resistance, boosted SBP at hospitalization, and prolonged operation should be taken into consideration as risk factors of postoperative BP abnormalities, especially hypertension, following minor-to-moderate surgery.

The present meta-analysis aimed to evaluate effects of tolvaptan on fluid retention in patients with heart failure who were non-responsive to conventional treatment and to assess differences between effects of low (≤ 15 mg/day) and high (> 15 mg/day) tolvaptan doses.

Randomized controlled trials comparing add-on tolvaptan therapy and placebo or therapy with other diuretics in patients with heart failure were identified through a database search. The primary outcomes were changes in body weight and urine volume, and the secondary outcomes were changes in serum sodium and creatinine levels.

In total, 14 reports were analyzed using a random effects model. Add-on tolvaptan was associated with increased urine volume [mean difference (MD), 1.44 L; 95% confidence interval (CI), 0.96 to 1.92], decreased body weight (MD, −0.99 kg; 95% CI, −1.24 to −0.74), and increased serum sodium levels (MD, 3.66 mEq/L; 95% CI, 3.43 to 3.88) within 2 days. Serum creatinine levels on day 7 were not different between the groups (MD, −0.03 mg/dL; 95% CI, −0.09 to 0.03). The high-dose group showed greater changes in urine volume, body weight, and serum sodium levels than the low-dose group. Serum creatinine levels slightly increased in the high-dose group (MD, 0.06; 95% CI, 0.04 to 0.08) and slightly decreased in the low-dose group (MD, −0.10; 95% CI, −0.19 to −0.01).

Our findings suggest that add-on tolvaptan therapy for heart failure improves fluid retention in the early therapy phase. However, this drug should be properly used to avoid the worsening of renal function, which may occur at high doses.

Activation of Janus kinase (JNK) is involved in the pathogenesis of cardiac ischemia reperfusion injury. We previously demonstrated that oral treatment of rats with high doses of berberine (BBR) improved cardiac function in ischemia reperfusion injury. It is unknown if BBR modulates JNK activation. We developed a new formula, solid dispersion of BBR with sodium caprate (HGSD), which increases its bioavailability and membrane permeability. The present study examined if HGSD-mediated inhibition of JNK protects the heart from ischemia reperfusion injury.

The cardioprotective effect of HGSD was examined in rat hearts subjected to global 45 minutes ischemia followed by 30 minutes reperfusion. Hemodynamic parameters and troponin levels in the perfusate, and TNF-α, IL-6, JNK, and NFκB levels in the heart were determined. To further explore the cardioprotective mechanism of HGSD, H9c2 cells subjected to hypoxia/reoxygenation were incubated with serum containing HGSD in the absence or presence of an activator or inhibitor of JNK.

Pretreatment of rats with HGSD for 7 days significantly improved recovery of heart function in animals subjected to ischemia reperfusion injury compared to untreated controls. In addition, HGSD pretreatment inhibited cardiac production of TNF-α and IL-6, and attenuated ischemia reperfusion induced cardiac JNK activation and nuclear translocation of NFκB compared to untreated controls. In H9c2 cells subjected to hypoxia/reoxygenation, the presence of JNK activator diminished the release of TNF-α and IL-6 and the nuclear translocation of NFκB.

HGSD treatment protects the heart from ischemia reperfusion injury through attenuation of NFκB and JNK signaling pathways.

The aim of the present study was to investigate the mechanisms of CCAAT/enhancer-binding protein β (C/EBPβ) in cardiac myofibroblast (CMF) differentiation and in a rat model of cardiac fibrosis induced by experimental autoimmune myocarditis (EAM).

In vitro studies performed in primary neonatal rat CMF revealed that silencing of C/EBPβ expression (via lentiviral mediated shRNA strategies) was sufficient to reduce C/EBPβ mRNA and protein levels as well as to decrease the expressions of actin cytoskeletal proteins, cofilin, and filamin A (FLNA). TGFβ increased IL-1β, IL-6 and TNF-a production in cardiac fibroblasts (CF), while C/EBPβ knockdown reduced the secretion of these inflammatory mediators. In vivo studies performed in rats exhibiting EAM revealed that lentiviral-mediated silencing of C/EBPβ was sufficient to reduce the expression of C/EBPβ as well as inflammation and fibrosis in the hearts of EAM rats, when compared to controls. Echocardiography further revealed that C/EBPβ knockdown was sufficient to significantly improve cardiac dimensions and function in EAM rats. Immunohistochemical results showed that C/EBPβ knockdown attenuated the expression of C/EBPβ protein as well as the expressions of collagen I, collagen III, MMP-2, MMP-9, and α-SMA in heart tissue sections from rats in the EAM + Lenti-shC/EBPβ group.

Strategies targeted at inhibiting C/EBPβ expression can be potentially exploited to regulate cofilin and FLNA expression, thereby regulating actin polymerization/depolymerization, cytoskeleton rearrangement, and CF differentiation into CMF and the production of inflammatory cytokines. C/EBPβ knock down reduces the degree of inflammation-mediated myocardial fibrosis in a rat model of EAM.

Angiotensin II (Ang II), an effective component of renin-angiotensin system, plays a pivotal role in cardiac fibrosis, which may further contribute to heart failure. Single-stranded DNA-binding protein 1 (SSBP1), a DNA damage response protein, regulates both mitochondrial function and extracellular matrix remodeling. In this study, we aim to investigate the role of SSBP1 in cardiac fibrosis that is induced by Ang II. We infused C57BL/6J mice with vehicle or Ang II and valsartan using implanted osmotic mini-pumps. Moreover, heart function was examined by echocardiography and cardiac fibrosis was analyzed via picrosirus red staining. The expression of COL1A1, COL3A1, SSBP1, p53, Nox1, and Nox4 was analyzed via qRT-PCR and/or immunoblots. The SSBP1 expression was manipulated via SSBP1 shRNA and pcDNA3.1/SSBP1 plasmids, while the p53 expression was enhanced via AdCMV-p53 infection. The exposure to Ang II increased the mouse heart weight, systolic blood pressure, interventricular septal thickness diastolic (IVSTD) and left ventricular end posterior wall dimension diastolic (LVPWD), which were counteracted by valsartan. While cardiac fibrosis was induced with Ang II treatment, it was relieved using valsartan. Furthermore, Ang II treatment caused mitochondrial dysfunction, oxidative stress, and down-regulated SSBP1 expression. The knockdown of SSBP1 increased cardiac fibroblast proliferation, collagen expression, and decreased p53 expression, which was impeded via SSBP1 overexpression. Moreover, the forced expression of p53 abated the fibroblast proliferation and collagen expression that was induced by Ang II. To summarize, SSBP1 was down-regulated by Ang II and implicated in cardiac fibroblast proliferation and collagen expression partly via the p53 protein.

Ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) is one of the deubiquitinating enzymes in the ubiquitin-proteasome system. It has been shown that UCH-L1 could markedly decrease neointima formation through suppressing vascular smooth muscle cell (VSMC) proliferation in the balloon-injured rat carotid. However, whether UCH-L1 plays roles in VSMC migration remains to be determined. In this study, the primary VSMCs were isolated from aortic media of rats and TNF-α to was used to induce VSMC migration. Using a modified Boyden chamber and wound healing assay, it was found that TNF-α can dose and time-dependently induce VSMC migration with a maximal effect at 10 ng/mL. Moreover, UCH-L1 expression increased gradually with the prolonged induction time at 10 ng/mL of TNF-α. UCH-L1 content in VSMC was then modulated by recombinant adenoviruses expressing UCH-L1 or RNA interference to evaluate its roles in cell migration. The results showed that over-expression of UCH-L1 attenuated VSMC migration, while knockdown of it enhanced cell migration significantly no matter whether TNF-α treatment or not. Finally, the effect of UCH-L1 on NF-κB activation was demonstrated by NF-κB nuclear translocation and DNA binding activity, and the levels of IL-6 and IL-8 in cell culture media were examined by ELISA. It was showed that UCH-L1 over-expression inhibited NF-κB activation and decrease IL-6 and IL-8 levels, while knockdown of it enhanced NF-κB activation and increase IL-6 and IL-8 levels during TNF-α treatment. These data suggest that UCH-L1 can inhibit TNF-α-induced VSMCs migration, and this kind of effect may partially due to its suppression role in NF-κB activation.

The phenotype shifting of vascular smooth muscle cells (VSMCs) was indicated to play a role during the initial stage of atherosclerotic plaque formation by facilitating extracellular matrix deposition. This study was aimed at investigating the involvement of the apoptosis signal-regulating kinase 1 (ASK1) /mitogen-activated protein kinase (MAPK) kinases (MKKs) /p38 MAPK pathway in the advanced glycation end product (AGE) -induced fibrotic response of VSMCs. The effect of the novel ASK1 inhibitor AGI-1067 was also studied.

Cultured human coronary smooth muscle cells (HCSMCs) were exposed to AGEs. AGI-1067 and siRNAs silencing mkk3, mkk6, and p38 mapk were used to treat the cells. The activation of MKK3, MKK6, and p38 MAPK was assessed by immunoblotting. Fibrotic response was assessed by the fluorescence immunohistochemistry staining of collagen I and collagen VIII. Activation of immunoprecipitation determined the association of ASK1 and its inhibitor thioredoxin. A kinase assay was used to determine ASK1 activity.

AGE incubation significantly activated ASK1, MKK3, and MKK6, which led to activation of p38 MAPK, resulting in upregulated fibrotic response in HCSMCs. However, siRNAs knocking down mkk3, mkk6, and p38 mapk impaired this fibrotic response. AGI-1067 administration not only dramatically inhibited the activation of ASK1/MKKs/p38 MAPK but also suppressed the expression of the downstream proteins, including transforming growth factor-β1, connective tissue growth factor, collagen I, and collagen VIII in HCSMCs exposed to AGEs.

The ASK1/MKKs/p38 MAPK pathway was activated by AGEs, leading to the fibrotic response in VSMCs. AGI-1067 reversed this process by maintaining the inactive state of ASK1.

For atherosclerotic cardiovascular diseases (ACD), gene therapy may be a potential therapeutic strategy; however, lack of effective and safe methods for gene delivery to atherosclerotic plaques have limited its potential therapeutic applications. To overcome this limitation, we developed a novel antibody-based gene delivery system (anti-HB-EGF/NA vector) by chemically crosslinking antibodies against human heparin-binding epidermal growth factor-like growth factor (HB-EGF). It has been shown to be excessively expressed in human atherosclerotic plaques and NeutrAvidin (NA) for conjugating biotinylated siRNA. Immunofluorescence staining and quantitative flow cytometry analysis using human HB-EGF-expressing cells showed both antibody-mediated selective cellular targeting and efficient intracellular delivery of conjugated biotin-fluorescence. Moreover, we demonstrated antibody-mediated significant and selective gene knockdown via conjugation with anti-HB-EGF/NA vector and biotinylated siRNA (anti-HB-EGF/NA/b-siRNA) in vitro. Furthermore, using high fat-fed human HB-EGF knock-in and apolipoprotein E-knockout (Hbegf hz/hz; Apoe-/-) mice, we demonstrated that the anti-HB-EGF/NA vector, conjugating biotin-fluorescence, increasingly accumulated within the atherosclerotic plaques of the ascending aorta in which human HB-EGF expression levels were highly elevated. Moreover, in response to a single intravenous injection of anti-HB-EGF/NA/b-siRNA in a dose-dependent manner, qPCR analysis of laser-dissected atherosclerotic plaques of the ascending aorta showed significant knockdown of the reporter gene expression. These results suggest that the anti-HB-EGF antibody-mediated siRNA delivery could be a promising delivery system for gene therapy of ACD.

Statins are known to improve pulmonary arterial hypertension (PAH) by their anti-inflammatory and anti-proliferative effects in animal models. However, recent clinical studies have reported that clinically approved statin doses failed to improve clinical outcomes in patients with PAH. We therefore hypothesized that nanoparticle (NP) -mediated targeting of pitavastatin could attenuate the progression of established PAH.

We induced PAH by subcutaneously injecting monocrotaline (MCT) in Sprague-Dawley rats. On day 14 after the MCT injection, animals that displayed established PAH on echocardiography were included. On day 17, they were randomly assigned to the following 5 groups: daily intravenous administration of (1) vehicle, (2) fluorescein-isothiocyanate-NP, (3) pitavastatin, (4) pitavastatin-NP, or (5) oral sildenafil. Intravenous NP was selectively delivered to small pulmonary arteries and circulating CD11b-positive leukocytes. On day 21, pitavastatin-NP attenuated the progression of PAH at lower doses than pitavastatin alone. This was associated with the inhibition of monocyte-mediated inflammation, proliferation, and remodeling of the pulmonary arteries. Interestingly, sildenafil attenuated the development of PAH, but had no effects on inflammation or remodeling of the pulmonary arteries. In separate experiments, only treatment with pitavastatin-NP reduced the mortality rate at day 35.

NP-mediated targeting of pitavastatin to small pulmonary arteries and leukocytes attenuated the progression of established MCT-induced PAH and improved survival. Therapeutically, pitavastatin-NP was associated with anti-inflammatory and anti-proliferative effects on small pulmonary arteries, which was completely distinct from the vasodilatory effect of sildenafil. Pitavastatin-NP can be a novel therapeutic modality for PAH.

Enhanced renin-angiotensin activity contributes to hypertension, albuminuria, and glomerular hypertrophy. The angiotensin (Ang)-converting enzyme (ACE) 2/Ang (1-7)/Mas axis pathway acts against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits albuminuria independently of blood pressure and elucidated the potential mechanisms.

Three- to 4-month-old male mice overexpressing renin in the liver (Ren-TG) were given olmesartan (5 mg/kg/day) or hydralazine (Hyd) (3.5 mg/kg/day) orally for 2 months. Ren-TG mice had higher systolic blood pressure (SBP) than wild-type (WT) mice (158.2 ± 6.3 versus 112.8 ± 8.8 mmHg, n = 3-4, P < 0.01). Ren-TG mice treated with Olm or Hyd for 2 months had lower SBP than untreated Ren-TG mice. Urinary albumin excretion (UAE) was significantly increased in Ren-TG mice compared with WT mice (78.2 ± 31.2 versus 28.6 ± 13.8 μg/day, n = 5-6, P < 0.01). Olm treatment for 2 months reduced UAE, whereas Hyd treatment did not. Olm treatment reversed decreased gene and protein expressions of ACE2 and Mas receptor (Mas 1) in the kidney of Ren-TG mice and inhibited enhanced NADPH oxidase (Nox) 4 expression, whereas Hyd treatment had no influence. Furthermore, increased reactive oxygen species (ROS) in the kidney of Ren-TG mice were decreased by Olm treatment but not by Hyd treatment.

Olm treatment inhibits albuminuria and glomerular hypertrophy independently of blood pressure not only through its original AT1R blockade but also partly through the enhancement of the ACE2/Ang (1-7)/Mas axis and suppression of ROS generation.

We report a case of successful percutaneous retrieval of an unexpectedly disrupted balloon catheter using GuideLiner and a low-profile balloon. The procedure and the mechanism of this novel technique were described in detail with ex-vivo testing. This case demonstrated the utility of the combination of GuideLiner and low-profile balloon as a bail-out for intravascular foreign body.

A 77-year-old man was referred to our hospital for angina on effort. Coronary angiography and computed tomography demonstrated a single coronary artery arising from the right sinus of Valsalva. The left circumflex coronary artery (LCx) anomalously deriving near from the ostium of right coronary artery exhibited severe stenosis in the bifurcation of the obtuse marginal branch. Although the bifurcation lesion still remains a therapeutic challenge for guide extension catheter (GEC)-based percutaneous coronary intervention, under the guidance of intravascular ultrasound imaging, we successfully implanted an everolimus-eluting stent at the bifurcated LCx lesion and performed kissing balloon inflation using 0.014- and 0.010-inch systems through GECs.

Non-obstructive angioscopy has become a novel method of evaluating atheromatous plaques of the aortic intimal wall. A 77-year-old man with coronary artery disease underwent percutaneous coronary intervention in the left descending artery. We subsequently used non-obstructive angioscopy to identify aortic atheromatous plaques and incidentally diagnosed an aortic dissecting aneurysm. Non-obstructive angioscopy demonstrated a great fissure in severe atheromatous plaques at the entry site of the aortic dissection identified by enhanced computed tomography. This is the first report to describe the aortic intimal findings of an aortic dissecting aneurysm in vivo by using trans-catheter angioscopy.

Gitelman syndrome (GS) is an inherited renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and low urinary calcium excretion. While it is considered a benign disease, severe ventricular arrhythmia and sudden cardiac death related to the prolongation of the QT interval have been reported in rare cases. Herein we report a 13-year-old girl with GS who presented with persistent prolongation of the QT interval, even after being treated for hypokalemia and hypomagnesemia. Genetic analysis identified SCN5A H558R polymorphism, which modulates the function of myocardial sodium channel, and SLC12A3 A588V mutation, which causes GS. The SCN5A polymorphism and GS-related electrolyte disturbance might have contributed to the persistent QT prolongation in this patient. Although no ventricular arrhythmias were recorded in this case, careful cardiac surveillance should be applied for avoiding life-threatening cardiac events.

The therapeutic role of transcatheter aortic valve implantation (TAVI) in high surgical risk or inoperable cases has been established. Most of the candidates for TAVI are elderly and have multiple comorbidities including chronic kidney disease. However, contrast-enhanced computed tomography and coronary angiography, both of which require iodine contrast media, are essential for pre-procedural planning. In addition, TAVI could have adverse effects on kidney function including contrast media-induced nephrotoxicity. Acute kidney injury following TAVI has been reported to be related to poor prognosis. In a case with advanced renal dysfunction, we successfully avoided post-procedural acute kidney injury by performing pre-procedural evaluation using minimal contrast and TAVI without contrast media. If anatomical conditions and experiences of the heart team are adequate, renoprotective TAVI should be a favorable therapy for patients with aortic stenosis complicated by renal dysfunction.

A 52-year-old woman with intermittent complete atrioventricular (AV) block detected on exercise was admitted to the hospital. Echocardiography revealed lesions on the right ventricular side of the interventricular septum and free wall of the basal inferolateral area. Gadolinium-enhanced cardiovascular magnetic resonance (CMR) imaging revealed the mass and wall thickening at the same locations with late gadolinium enhancement (LGE). Focal uptake at the septal lesion was detected using 67Ga scintigraphy. Focal on diffuse intense uptake in the lesions was observed on Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging. Whole-body CT and laboratory evaluations uncovered no signs of malignant tumors in other organs. Ophthalmologic evaluation revealed ophthalmologic sarcoidosis. Although the result of endomyocardial biopsy was negative, the presence of cardiac sarcoidosis was strongly suggested on the basis of the new Japanese guidelines published in 2017. AV conduction disturbance and tracer accumulation on 67Ga scintigraphy completely disappeared after 2 weeks of steroid therapy. The size of mass, inferolateral wall thickness in echocardiography and CMR, and standardized uptake value (SUV) of the masses on 18F-FDG PET also decreased over time.

In patients with an atrial septal defect (ASD) and left ventricular (LV) dysfunction associated with coronary artery disease (CAD), to avoid the development of acute left heart failure (HF) and an increase in myocardial oxygen consumption following ASD closure, it is conceivable that coronary artery revascularization should be performed prior to ASD closure. We report the case of a 67-year-old man with a large secundum ASD and LV ejection fraction of 15.6% resulting from severe ischemic cardiomyopathy and triple-vessel CAD, both of which contributed to biventricular HF characterized by high left-to-right shunt (Qp:Qs of 7.1:1) and low systemic cardiac output. After evaluating his hemodynamics and biventricular function with cardiac catheterization and cardiovascular magnetic resonance imaging, we successfully conducted an inverse, stepwise strategy of transcatheter ASD closure using anti-congestive therapies, intraaortic balloon pumping, and subsequent balloon occlusion testing, followed by on-pump beating-heart coronary artery bypass grafting.

Infective endocarditis (IE) caused by Serratia liquefaciens has been reported in only 2 adults. We experienced the first pediatric (neonatal) case of IE caused by S. liquefaciens, with mitral valve vegetation 4 days after a palliative heart surgery. This report underscores the importance of treating for both gram-positive and gram-negative bacteria in IE cases until the blood cultures elucidate the details.

A 24-year-old Japanese man with type 2 diabetes mellitus and diabetic neuropathy was admitted to our ward to evaluate the cause of orthostatic intolerance. During a head-up tilt test, his heart rate increased from 105 to 155 beats/minute within 3 minutes, and chest discomfort began. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), and orthostatic intolerance disappeared after β-blocker treatment. Scintigraphy using ¹²³I-metaiodobenzylguanidine showed decreased cardiac uptake. Power spectral analysis of heart rate variability for 24 hours in Holter electrocardiography demonstrated decreases in both sympathetic and parasympathetic nervous system activities, with a greater decrease in parasympathetic activity than sympathetic activity. The relative sympathetic hyperactivity in the present patient with diabetic neuropathy seemed to be related to POTS.

We are pleased to announce that the following 2 articles have been selected for the the UEDA Heart Awards for the Year 2018.

First Place

Role of Right Ventricular Dysfunction and Diabetes Mellitus in N-terminal pro-B-type Natriuretic Peptide Response of Patients With Severe Mitral Regurgitation and Heart Failure After MitraClip

Hidehiro Kaneko, Michael Neuss, Jens Weissenborn, Christian Butter

Int Heart J 2017; 58 (2): 225-231.

Second Place

Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Left Ventricular Remodeling After Acute Myocardial Infarction by Inhibiting Monocyte-Mediated Inflammation

Yajing Mao, Jun-ichiro Koga, Masaki Tokutome, Tetsuya Matoba, Gentaro Ikeda, Kaku Nakano, Kensuke Egashira

Int Heart J 2017; 58 (4): 615-623.

November 2018

International Heart Journal Association