Cardiovascular disease remains a leading cause of death for which current therapeutic regimens are limited. Following myocardial injury, endogenous cardiac fibroblasts, which account for more than half of the cells in the heart, proliferate and synthesize extracellular matrix, leading to fibrosis and heart failure. As terminally differentiated cardiomyocytes have little regenerative capacity following injury, development of cardiac regenerative therapy is highly desired. Embryonic stem (ES) and induced pluripotent stem (iPS) cells are promising tools for regenerative medicine; however, these stem cells demonstrate variable cardiac differentiation efficiency and tumorigenicity, which should be solved for clinical applications. Up until the last decade, it was an established theory that cardiomyocytes could only be produced from fibroblasts mediating through stem cells. However, in 2010, we reported for the first time a novel method of the direct reprogramming of fibroblasts into cardiomyocytes, demonstrating various reprogramming pathways exist. This review summarizes the latest trends in stem cell and regenerative research, touching upon iPS cells, partial reprogramming strategy, and direct cardiac reprogramming. Specifically, we examine the many recent advances in both in vitro and in vivo direct cardiac reprogramming, and explore the application of these methods to cardiovascular regenerative medicine.

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The angiographic features of restenosis contain prognostic information. However, restenosis patterns of the new generation drug-eluting stents (DES), everolimus-(EES) and resolute zotarolimus-eluting stent (ZES) have not been described.
A total of 210 consecutive patients with DES restenosis were enrolled from 2003 to 2012. We analyzed 217 restenotic lesions after DES implantation, and compared the morphologic characteristics of the 2nd generation DES restenosis to those of restenosis with 2 first generation DES, sirolimus-(SES) and paclitaxel-eluting stent (PES).
Baseline characteristics were comparable between the different stent groups. The incidence of focal restenosis was significantly lower for PES than the other stents (49.5% versus 87.0%, 76.2%, and 82.1% for PES versus SES, EES, and ZES, respectively, P < 0.001). When considering the pattern of restenosis solely within the stent margins, a further clear distinction between PES and other stents was observed (40.0% versus 92.9%, 88.9%, and 81.2% in PES versus SES, EES, and ZES, respectively, P < 0.001). There were no significant differences in restenosis patterns among SES, EES, and ZES. In multivariate analysis, PES implantation, hypertension, and age were associated with non-focal type of restenosis after DES implantation. After the introduction of EES and ZES into routine clinical practice in 2008, focal restenosis significantly increased from 63.9% to 76.7% and diffuse restenosis significantly decreased from 26.4% to 11.0% (P = 0.045).
Focal restenosis was the most common pattern of restenosis in the new generation DES and the incidence of diffuse restenosis significantly decreased with the introduction of the 2nd generation DES.

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Coronary optical coherence tomography (OCT) has the potential to identify in-stent neoatherosclerosis, which is a possible risk factor for late acute coronary events after drug-eluting stent implantation. The purpose of this study was to investigate differences between mid-term and late in-stent restenosis after stent implantation by quantitative and semiautomated tissue property analysis using OCT. In total, 1063 OCT image frames of 16 lesions in 15 patients were analyzed. This included 346 frames of 6 lesions in late in-stent restenosis, which was defined as restenosis that was not detected at 6 to 12 months but ≥ 12 months after follow-up coronary angiography. Signal attenuation was circumferentially analyzed using a dedicated semiautomated software. Attenuation was assessed along 200 lines delineated radially for analysis of the in-stent restenotic lesions (between the lumen and stent contours). All lines were anchored by the image wire to avoid artifacts resulting from wire location. Stronger signal attenuation at the frame level (2.46 ± 0.78 versus 1.47 ± 0.32, P < 0.001) and higher maximum signal intensity at the lesion level (9.19 ± 0.19 versus 8.84 ± 0.32, P = 0.018) were observed in late in-stent restenotic lesions than in mid-term in-stent restenotic lesions. OCT demonstrated stronger signal attenuation and higher maximum signal intensity in late in-stent restenotic lesions than in mid-term in-stent restenotic lesions, indicating the possibility of neoatherosclerosis.

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In this study we aimed to investigate whether there is an association between the neutrophil to lymphocyte ratio (NLR) and severity of coronary artery disease (CAD) in patients with non-ST segment elevation myocardial infarction (NSTEMI) using the SYNTAX score (SXscore). A total of 414 patients with NSTEMI who underwent coronary angiography were enrolled in the study. NLR was measured for all patients at presentation. The study population was then divided into 3 tertiles based on the SYNTAX trial results.¹⁾ The low syntax group (n = 329) was defined as those with an SXscore ≤ 22, the intermediate syntax group (n = 58) was defined as an SXscore ≥ 23 and < 33, and the high syntax group (n = 27) as those with an SXscore ≥ 33. NLR was significantly lower in patients with a low SXscore compared to patients with an intermediate SXscore or high SXscore (3.7 ± 4 to 4.6 ± 2 and 7.9 ± 4, P < 0.001). Linear regression analysis revealed that NLR (coefficientβ = 0.380, 95%CI: 1.165-1.917, P < 0.001) was significantly associated with the SXscore in patients with NSTEMI. Our results indicate that NLR is independently associated with the severity of CAD in patients with NSTEMI.

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This study aimed to evaluate the potential associations of intermediate monocytes (CD14⁺⁺CD16⁺) with myocardial remodelling in ST segment elevation myocardial infarction (STEMI) patients with diabetes.
A total of 67 STEMI patients with diabetes were enrolled. The control group consisted of 65 STEMI patients without diabetes. All patients received emergency medical services for reperfusion therapy in less than 12 hours after onset of AMI. Blinded to patient clinical characteristics, monocyte subset analysis was performed using flow cytometry immediately after admission. mRNA of Chemokine Decoy Receptor D6 in each subset of monocytes was validated by Q-PCR. Expression of CCL2 in patient plasma was determined with an Elisa kit. Infarct size and left ventricular ejection fraction (LVEF) were measured using 3-dimensional echocardiography 3 days and 6 months after AMI. The incidences of recurrent cardiovascular events and death in each group were measured using the Kaplan–Meier estimator in follow-up during the next 24 months. Cox proportional-hazard models were further used to analyze the relationship of monocyte cell counts and event-free survival after adjusting for confounding factors.
The number of circulating intermediate monocytes was significantly correlated with LVEF% and infarct size (r = –0.32; P = 0.008; r = 0.57, P < 0.001) in STEMI patients with diabetes compared with those without diabetes 6 months after AMI. Chemokine Decoy Receptor D6 transcript levels were lower in intermediate monocytes of STEMI patients with diabetes compared to the subsets in STEMI patients without diabetes (P < 0.001). Higher levels of CCL2 (pg/mL) were observed in STEMI patients with diabetes compared to STEMI patients without diabetes (P < 0.001). During a mean follow-up period of 24 ± 1 month, recurrent cardiovascular events or death occurred in 23 patients belonging to the STEMI with diabetes group and 10 belonging to the control group. Univariate Kaplan–Meier analysis revealed that counts of the intermediate monocytes according to median showed statistical significance in STEMI patients with diabetes (P = 0.010). After full adjustment for confounding factors, the cells were found to remain independently related to recurrent cardiovascular events or death in this group (P = 0.004, 95% CI: 1.62–12.49).
Intermediate monocytes were associated with LV remodelling in STEMI patients with diabetes. The cells were predictive for recurrent cardiovascular events or death in these patients. A low level of D6 mRNA in the intermediate monocytes of STEMI patients with diabetes and high level of CCL2 in these patients may partially explain the causality.

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The aim of this study was to investigate the relationship between coronary microvascular function and smoking using the 3 parameters fractional flow reserve (FFR), coronary flow reserve (CFR_thermo), and index of microcirculatory resistance (IMR) in patients with coronary artery disease (CAD). A total of 97 CAD patients with 148 intermediate stenotic lesions were divided into two groups: current and former smokers (Smokers: n = 54), and those who had never smoked (Non-smokers: n = 43). Coronary physiology measurements were made following coronary angiography at rest and during hyperemia induced with intravenous adenosine triphosphate. If a patient had several intermediate lesions, the lesion producing the largest IMR value and minimum FFR_myo and CFR_thermo value was selected. Averaged over all patients, the FFR_myo, CFR_thermo, and IMR values were 0.86 ± 0.10, 2.66 ± 1.50, and 20.8 ± 10.7, respectively. There was no significant correlation between FFR_myoand IMR. There were no significant differences between smokers and non-smokers in FFR_myo value (median: 0.85 [IQR: 0.74-0.90] versus 0.87 [IQR: 0.83-0.90], P = 0.15) and CFR_thermo value (median: 1.90 [IQR: 1.56-3.16] versus 2.10 [IQR: 1.50-2.67] U, P = 0.95). The IMR value was significantly greater in smokers (median: 24.2 [IQR: 16.8-32.5] U versus 18.5 [IQR: 15.4-27.0] U, P = 0.04). In multivariate analysis, smoking was an independent predictor of increased IMR. Smoking appears to have a detrimental effect on coronary microvascular function as measured by IMR.

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Percutaneous coronary intervention (PCI) of ostial lesions is complex and is technically very demanding. Intravascular ultrasound (IVUS) is considered the gold standard method to guide PCI but has several limitations. Stent boost subtract (SBS) imaging is an enhancement of the radiologic edge of the stent by digital management of regular X-ray images. The purpose of this study was to determine the availability of stent enhancement with SBS during ostial PCI by comparison with IVUS.
We investigated SBS and IVUS after stent implantation in 58 ostial lesions in 55 patients. SBS and IVUS were performed in all patients to obtain improved stent location and to detect optimal release and deployment. We defined the SBS and IVUS criteria for accuracy of stent location and adequate stent deployment. IVUS findings showed that stent location was generally good. The location was accurate in 48 (82.8%) and inadequate stent deployment was observed in 10 of 58 (17.2%). Eight SBS images showed inadequate stent expansion. SBS predicted inadequate findings of IVUS with 100% specificity and 80% sensitivity, while a significant positive correlation was observed between SBS-MSA and MSA by IVUS with a regression coefficient of 0.95.
Imaging techniques have a primary role during ostial PCI. SBS is a simple and quick method that offers several advantages, enabling improved stent location, adequate stent expansion, and optimal apposition of the struts to the wall. SBS imaging could be conventionally used during ostial PCI, especially in centers where IVUS is not used routinely.

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Whether the effect of diabetes on patients with unprotected left main coronary artery (ULMCA) disease differs according to different strategies of revascularization was unknown. This study was conducted to evaluate the impact of diabetes on patients with ULMCA disease treated with either percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG).
A total of 922 patients with ULMCA disease who received drug-eluting stent (DES) (n = 465) implantation or underwent CABG (n = 457) were retrospectively analyzed. We compared the effects of these 2 treatments on clinical outcomes (death, myocardial infarction, stroke, repeat revascularization, and the composite of death, myocardial infarction, or stroke), according to diabetic status.
During the median follow-up of 7.1 years (interquartile range, 5.3 to 8.2 years), no difference was found between PCI and CABG in the adjusted occurrence of death (P = 0.112) and the composite endpoints of death, myocardial infarction, and stroke (P = 0.235). Significantly higher incidence of repeat revascularization (P < 0.001) was observed in the DES group, whereas the CABG group had a significantly higher rate of stroke (P = 0.001). These trends were consistent in both diabetic and nondiabetic patients. We did not observe significant interactions between treatment outcomes and the presence or absence of diabetes after adjustment for covariates (P_interaction = 0.580 for the composite of death, MI and stroke, P_interaction = 0.685 for death, P_interaction = 0.416 for MI, P_interaction = 0.470 for stroke, and P_interaction = 0.502 for repeat revascularization).
Presence of diabetes was not important for decision-making between CABG and PCI in patients with ULMCA disease.

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Cystatin-C, a marker of mild renal dysfunction, has been reported to be associated with cardiovascular diseases including vasospastic angina (VSA). We aimed to investigate the impact of cystatin-C level on the prevalence and angiographic characteristics of VSA in Korean patients.
A total of 549 patients in the VA-KOREA (Vasospastic Angina in KOREA) registry who underwent ergonovine provocation tests were consecutively enrolled. Estimated glomerular filtration rate (eGFR) and levels of serum creatinine (Cr) and cystatin-C were assessed before angiography.
The patients were classified into two groups: the VSA group (n = 149, 27.1%) and the non-VSA group (n = 400). Although eGFR and Cr levels were similar between the two groups, the VSA group had a significantly higher level of cystatin-C (P < 0.05). A high level of cystatin-C (second tertile, hazard ratio 1.432; 95% confidence interval [1.1491.805]; P = 0.026, third tertile, 1.947 [1.132-2.719]; P = 0.003) and current smoking (2.710 [1.415-4.098]; P < 0.001) were independently associated with the prevalence of VSA. Furthermore, the highest level of cystatin-C (> 0.96 ng/mL) had a significant impact on the incidence of multivessel spasm (2.608 [1.061-4.596]; P = 0.037).
A high level of cystatin-C was independently associated with the prevalence of VSA and with a high-risk type of VSA in Korean patients, suggesting that proactive investigation of VSA should be considered for patients with mild renal dysfunction indicated by elevated cystatin-C.

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Anticoagulation of patients with cardiac tamponade (CT) complicating catheter ablation of atrial fibrillation (AF) is an ongoing problem. The aim of this study was to survey the clinical practice of periprocedural anticoagulation in such patients. This study analyzed the periprocedural anticoagulation of 17 patients with CT complicating AF ablation. Emergent pericardiocentesis was performed once CT was confirmed. The mean drained volume was 410.0 ± 194.1 mL. Protamine sulfate was administered to neutralize heparin (1 mg neutralizes 100 units heparin) in 11 patients with persistent pericardial bleeding and vitamin K1 (10 mg) was given to reverse warfarin in 3 patients with supratherapeutic INR (INR > 2.1). Drainage catheters were removed 12 hours after echocardiography confirmed absence of intrapericardial bleeding and anticoagulation therapy was restored 12 hours after removing the catheter. Fifteen patients took oral warfarin and 10 of them were given subcutaneous injection of LMWH (1 mg/kg, twice daily) as a bridge to resumption of systemic anticoagulation with warfarin. Two patients with a small amount of persistent pericardial effusion were given LMWH on days 5 and 13, and warfarin on days 6 and 24. The dosage of warfarin was adjusted to keep the INR within 2-3 in all patients. After 12 months of follow-up, all patients had no neurological events and no occurrence of delayed CT. The results showed that it was effective and safe to resume anticoagulation therapy 12 hours after removal of the drainage catheter. This may help to prevent thromboembolic events following catheter ablation of AF.

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Cardiac resynchronization therapy (CRT) is an established therapy in patients with severe heart failure due to left ventricular (LV) dyssynchrony. Increasing stimulus strength (SS) of LV pacing could capture an enlarged myocardial area and provide rapid electrical conduction. The aim of the present study was to investigate whether increasing SS of LV pacing improves LV mechanical dyssynchrony and cardiac function in patients treated with CRT.
We enrolled 26 patients with CRT and changed the SS of LV pacing: 2.5 V (standard SS) and 5 V (high SS). Electrocardiography and echocardiography were performed to assess QRS duration, LV mechanical dyssynchrony, and cardiac function under each condition.
The QRS duration (138.6 ± 21.4 ms versus 126.8 ± 23.1 ms, P < 0.001), septal-posterior wall motion delay (126.5 ± 42.7 ms versus 111.4 ± 55.3 ms, P = 0.012), standard deviation of time from QRS (69.6 ± 21.8 ms versus 55.6 ± 19.4 ms, P < 0.001), LV ejection fraction (29.4 ± 10.6% versus 33.4 ± 11.6%, P = 0.005), and LV stroke volume (50.7 ± 15.5 mL versus 63.8 ± 18.3 mL, P < 0.001) improved significantly in high SS compared with standard SS.
Increasing SS of LV pacing in CRT improves LV mechanical dyssynchrony and cardiac function. The capture of an enlarged myocardial area by increasing SS of LV pacing might offer an acute hemodynamic benefit to patients treated with CRT.

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Scheduled serial endomyocardial biopsies are executed by an internal jugular vein (IJV) or femoral vein (FV) approach to survey acute rejection after heart transplantation (HTx). However, a better approach site is needed. A total of 379 sessions consisting of 329 IJV approaches and 50 FV approaches in 48 HTx recipients executed at 75 ± 127 days (41182 days) after HTx between September 2007 and April 2014 at University of Tokyo Hospital were retrospectively analyzed. The IJV approach had shorter operation and radiation exposure times, and a lower dose of radiation exposure and lower usage of contrast agents than the FV approach (all P < 0.001). There were no fatal complications requiring surgical management or resulting in death during all sessions. The IJV approach had less complications than the FV approach (2.7% versus 10.0%, P = 0.011). Among the complications, atrial tachyarrhythmia occurred only with the IJV approach (0.9%), whereas transient ventricular tachyarrhythmia and bundle branch block were more frequently observed in the FV approach (8.0% versus 0.9%, P = 0.042). In conclusion, endomyocardial biopsy from the IJV approach was safer and less invasive than that of the FV approach if we only consider the incidence of atrial tachyarrhythmia.

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Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immunosuppressant for heart transplant (HTx) recipients, and is expected to preserve renal function compared to conventional calcineurin inhibitors (CNIs). However, a considerable number of recipients treated with EVL were not free from worsening renal function regardless of CNI reduction. Data were collected retrospectively from 27 HTx recipients who had received EVL (trough concentration, 3.1-9.2 ng/mL) along with reduced CNIs (%decreases in trough concentration, 27.3 ± 13.0%) because of switching from mycophenolate mophetil due to digestive symptoms or neutropenia, progressive coronary artery vasculopathy, or persistent renal dysfunction, and had been followed over 1 year between August 2008 and January 2013. Estimated glomerular filtration rate (eGFR) decreased in 5 recipients (18.5%) during the study period. Univariate logistic regression analysis demonstrated that a higher plasma neutrophil gelatinase-associated lipocalin (P-NGAL) level was the only significant predictor for a decrease in eGFR over a 1-year EVL treatment period among all baseline parameters (P = 0.008). eGFR and proteinuria worsened almost exclusively in patients with baseline P-NGAL ≥ 85 ng/mL, which was the cutoff value calculated by an ROC analysis (area under the curve, 0.955; sensitivity, 1.000; specificity, 0.955). In conclusion, higher P-NGAL may be a novel predictor for the worsening of renal function after EVL treatment that is resistant to CNI reduction in HTx recipients.

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To evaluate independent risk factors for late right ventricular systolic dysfunction after correction of Tetralogy of Fallot (TOF) in a single-centre, retrospective and observational clinical trial.
Patients less than 3 years of age who underwent correction of TOF and subsequently routine clinical follow-up of more than 36 months were included in this study and were divided either into an experimental group (right ventricular systolic dysfunction) or a control group (normal right ventricular systolic function) according to the tricuspid annular peak systolic velocity (TAPSV) value measured by pulsed wave-tissue Doppler imaging (pulsed wave-TDI). The relevant data of all selected patients were investigated and analyzed
From January 2012 to December 2012, a total of 113 consecutive eligible patients were enrolled in this study and were divided either into an experimental group (n = 41) or control group (n = 72). Through univariate analysis and subsequent logistic regression, low preoperative arterial oxygen saturation (OR = 1.66, 95%CI 1.22-4.58, P = 0.0163), age less than 6 months at the time of surgery (OR = 3.45, 95%CI 1.87-9.17, P = 0.0021), and transannular patch (OR = 2.15, 95%CI 1.31-5.38, P = 0.0015) were 3 independent risk factors for late right ventricular systolic dysfunction after correction of TOF.
This clinical trial suggested low preoperative arterial oxygen saturation was associated with late right ventricular systolic dysfunction after correction of TOF, and appropriate age at the time of surgery and selection of a proper surgical method to reconstruct the right ventricular outflow tract contributed to improving late right ventricular systolic function in pediatric patients with repaired TOF.

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Background: Therapeutic strategies for pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) remain a matter of debate.
Methods and Results: We identified 5 outpatients who had been diagnosed with ASD–PAH and undergone ASD closure in combination with targeted therapy with certified PAH drugs. We assessed changes in hemodynamic parameters and exercise capacity. The combination of ASD closure and targeted therapy significantly increased systemic blood flow (Qs) from the baseline (from 3.3 ± 0.6 L/minute to 4.2 ± 1.0 L/minute, P < 0.05) with a significant improvement in the World Health Organization Functional Class (WHO-FC; from 2.8 ± 0.4 to 1.6 ± 0.5, P < 0.05). The hemodynamic data before and after ASD closure without targeted therapy showed further elevation of pulmonary vascular resistance shortly after ASD closure (678 dyne·s/cm⁵ to 926 dyne·s/cm⁵) in 1 case, as well as after a long time since ASD closure (491.0 ± 53.7 dyne·s/cm⁵ to 1045.0 ± 217.8 dyne·s/cm⁵) in 2 cases. This worsening was reversed after the targeted therapy, accompanied by an increase in Qs and an improvement in WHO-FC in all cases. Conclusions: Targeted therapy should be added to ASD closure in adult patients with ASD–PAH.

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The objective of the study was to determine the effects of nasal continuous positive airway pressure (nCPAP) therapy on left ventricular (LV) function and electrocardiographic parameters in newly diagnosed moderate/severe obstructive sleep apnea (OSA) patients without cardiovascular comorbidities and medical treatments. We examined 44 patients who underwent overnight polysomnography together with 24-hour Holter electrocardiography, cardiopulmonary exercise testing including heart rate recovery at 1 minute (HRR-1), echocardiography, surface electrocardiography, and those who were diagnosed with moderate/severe OSA apnea—hypopnea index ≥ 15. After 3 months of nCPAP treatment, the above-mentioned examinations were repeated. Forty-four patients completed the treatment period. Twelve weeks on effective nCPAP induced a significant increase in the mitral E/A ratio (P = 0.001), as well as reductions in isovolumic relaxation time (P = 0.001) and mitral deceleration time (DT) (P = 0.002). There were no significant differences in LV ejection fraction, LV mass index, and pulsed wave Doppler parameters. Mean heart rate was 79.2 ± 12.5 pulses/minute, maximum P-wave duration 117.5 ± 8.6 msec, P-wave dispersion (PWd) 54.6 ± 10.2 msec, corrected QT interval (QTc) 436.5 ± 40.5 msec, and QT dispersion (QTd) 46.3 ± 7.1 msec, which significantly decreased to 70.4 ± 9.6 pulses/minute (P < 0.001), 111.5 ± 8.7 msec (P < 0.001), 51.6 ± 8.9 msec (P < 0.001), 418.4 ± 31.2 msec (P < 0.001), and 33.8 ± 3.4 msec (P < 0.001), respectively. Exercise capacity at baseline determined as 10.5 ± 2.2 metabolic equivalents (METS) and HRR-1 (20.6 ± 11.7 bpm) significantly increased (12.1 ±1.5 METS and 27.4 ± 8.6 bpm). There was no significant difference in aortic root parameters. Three-month nCPAP therapy significantly increased LV shortening fraction, with no effect on systolic function or aortic root diameters and a positive effect on heart rate, PWd, HRR-1, QTc and QTd time following nCPAP therapy.

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Recently two-dimensional (2D) speckle tracking echocardiography (STE) derived from right ventricular (RV) free wall has been shown to be a very useful tool for the estimation of RV performance. The purpose of this study was to examine whether RV basal free wall strain can detect increased mean pulmonary arterial pressure (mPAP) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We investigated a total of 126 patients with CTEPH (mean age, 56 ± 12 years). They underwent echocardiography and right heart catheter examination. 2D STE-derived longitudinal strain was measured by placing 2 regions of interests (ROIs) on the RV basal free wall in RV-focused apical 4-chamber view. Peak strain (RV-PS) was acquired between the 2 ROIs. Conventional echocardiographic RV parameters (RV fractional area change, RV myocardial performance index, tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity, and tricuspid regurgitant pressure gradient) were evaluated as well. Right heart catheterization was performed on the day following of echocardiographic evaluation. Among RV echo parameters, RV-PS showed the best correlation with mPAP (r = 0.75, P < 0.0001). Receiver operating characteristic analysis revealed that a cut-off value of RV-PS -20.8% could detect mPAP ≧ 25 mmHg (sensitivity 78%, specificity 93%, area under the curve 0.90, P < 0.001). RV basal free wall strain was a useful tool for the non-invasive detection of increased mPAP in patients with CTEPH.

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Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m² who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m² to 67 ± 17 mL/minute/1.73 m², P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ΔACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.

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In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.

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We describe a case of a 41-year-old woman with acute exacerbation of chronic thromboembolic pulmonary hypertension (CTEPH) complicated by rapidly progressive respiratory failure and right heart failure with cardiogenic shock. A computed tomography (CT) showed thrombi in the right main pulmonary artery and bilateral peripheral pulmonary arteries, and echocardiography showed right ventricular dilatation and tricuspid regurgitation, with an estimated pressure gradient of 80 mmHg. The patient was initially diagnosed with acute pulmonary thromboembolism, and thrombolytic therapy was administered. Her condition subsequently deteriorated, however, necessitating mechanical ventilation and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We performed emergency catheter-directed thrombectomy and thrombus aspiration. Pulmonary hypertension (PH) temporarily improved, but subsequently worsened, and the patient was diagnosed with CTEPH. Pulmonary endarterectomy (PEA) was performed. After PEA, we were unable to wean the patient off VA-ECMO, and rescue balloon pulmonary angioplasty (BPA) to the middle and inferior lobe branches of the right lung was performed. Five days after BPA, the patient was removed from VA-ECMO and on the 57th day of hospitalization, she was weaned off the ventilator. The patient was discharged after 139 days of hospitalization. Rescue BPA represents a useful intervention for improving PH and weaning off VA-ECMO in a patient with acute exacerbation of CTEPH.

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