Idiopathic Ventricular Arrhythmia Ablation Using Non-Fluoroscopic Catheter Visualization System.

A novel, sensor-based, electromagnetic, non-fluoroscopic catheter visualization (NFCV) system shows tracked catheters directly on pre-acquired fluoroscopy or cine loops. We aimed to evaluate the effectiveness of this system in the setting of catheter ablation for idiopathic premature ventricular contractions/ventricular tachycardia (i-PVC/VT).A total of 30 i-PVC/VT ablation procedures were performed using the NFCV system in conjunction with three-dimensional electroanatomic mapping system (3D-EMS) between January 2013 and April 2017. At the beginning of the procedure, cine loops of right and left anterior oblique views were obtained and replayed for subsequent mapping and ablation. Right ventriculography, aortography, or coronary angiography was performed, depending on the chamber of interest. We reviewed procedural parameters, comparing with the i-PVC/VT ablation procedure using conventional fluoroscopy (CvF) system (pre-, and post-NFCV implementation; 20 and 11 cases, respectively).I-PVC/VTs were successfully eliminated in 26 patients (87%) in the NFCV group and in 26 (84%) in the CvF group (P = 1.000). The procedure time in the NFCV group was comparable to that in the CvF group (119.8 versus 125.0 minutes, respectively, P = 0.868); the total fluoroscopy time was significantly shorter in the NFCV group (3.3 versus 16.6 minutes, P < 0.001). One patient in the CvF group experienced cardiac tamponade, requiring pericardial drainage. No major complications were encountered in the NFCV group.NFCV system, in conjunction with 3D-EMS, was safe and feasible for i-PVC/VT mapping and ablation. The system contributed to dramatically reduced fluoroscopy time, compared with CvF.

Considerations in cardio-oncology: Multiple mobile left-sided cardiac thrombi in chemotherapy-induced cardiomyopathy.

With advances in cancer chemotherapy, the importance of the new clinical discipline of cardio-oncology, which is concerned with the cardiac effects of chemotherapy, is increasing. Herein we describe the case of a 48-year-old woman with a history of breast cancer who presented with symptoms of heart failure due to chemotherapy-induced cardiomyopathy. Treatment for the patient's breast cancer had included surgery and chemotherapy with anthracyclines and trastuzumab. Echocardiography revealed multiple mobile thrombi in the left ventricle and atrium. In addition, brain magnetic resonance imaging revealed small acute cerebral infarctions due to embolization. Given the high risk of re-embolization, surgical thrombectomy was performed. Thus far, there are no standardized therapeutic guidelines for left-sided cardiac thrombi and the optimal treatment remains contentious. Although this patient was managed successfully with surgical thrombectomy, patients should be managed individually, taking into consideration embolization, bleeding, and surgical risks. With further improvements in cancer chemotherapy, there may be an increase in the incidence of complications such as multiple cardiac thrombi. From the cardio-oncology standpoint, we propose close interactions between cardiologists and oncologists for the optimal care of cancer patients.

Awareness and recommendation of home blood pressure measurement among physicians in India: Results from Asia HBPM survey 2020.

BACKGROUND: Awareness of hypertension and blood pressure (BP) control rates are still low in India. Home blood pressure monitoring (HBPM) is recognized as a valuable tool to diagnose and support hypertension treatment including the prevention of cardiovascular diseases(CVD) and target organ damage. We explored the prevailing knowledge and current recommendation of HBPM in daily practice by physicians in India. MATERIALS AND METHODS: As part of Asia HBPM Survey 2020, a cross-sectional survey was conducted among healthcare providers from India between June 2020 to June 2021. The questionnaire consisted of 37 questions and sub-questions related to HBPM awareness and recommendations to patients. RESULTS: A total of 832 physicians participated in the survey. Almost 83% were male, whereas age, specialty and workplace were well distributed. 31.3% of physicians instruct their patients to measure their BP before taking antihypertensive drugs, while around 30% of physicians gave no instructions. The reference value of hypertension diagnosis amongst the physicians was substantially low based on clinic BP (34.4%) and home BP (15.1%). Among physicians who manage hypertensive patients, nearly 88% recommend HBPM to their patients, however, only 34.9% of their patients own HBPM device and 30.4% of the patients measure their own BP at home. CONCLUSION: The survey reveals that HBPM instructions to the patients are either lacking or not well aligned with the local hypertension guidelines which may have led to the low HBPM use among patients. Clear and practical educational material and sessions are needed to improve the understanding of HBPM amongst physicians.

GeogRaphic and socioecoNomic Distribution of real-world Indian data of home blood pressure monitoring (GRAND Study): Study protocol for an observational study in 18 medical centers across India.

One-fourth of death in India is attributed to cardiovascular disease (CVD) and more than 80% is related to ischemic heart disease and stroke. The main risk factor for CVD is hypertension. Every third person in India suffers from hypertension and the prevalence increased drastically in the past 20 years, especially among the youngest age group of 20 and 44 years. Regardless of being under anti-hypertension medication, the blood pressure (BP) control rate in the country is still low ranging between 6% and 28% only. Assessing the "true BP control rate" should be performed using both clinic BP measurement and out-of-office BP measurement as the latter shows better prognosis for patients' hypertension and CVD outcomes. Home blood pressure monitoring (HBPM) shows superiority over ambulatory BP measurement as multiple measurements can be collected at the patient's convenience. Only limited evidence on HBPM in India is available and it's either lacking in hypertension participants or of a small sample size. This study will investigate the real BP control status among 2000 hypertensive patients from 18 centers in 12 states across Pan-India. The outcome of this study will emphasize the value of establishing BP control management practice guidelines suitable for physicians and help policymakers in building proper strategies for hypertension management to reduce the CVD burden on the health situation in India.

Current realities of home blood pressure monitoring from physicians' perspectives: results from Asia HBPM survey 2020.

Uncontrolled hypertension is a significant problem in many parts of Asia. Effective management is essential to reduce the burden of hypertension. Home blood pressure monitoring (HBPM) is a promising tool that can aid in the diagnosis and management of hypertension. Experts from 11 countries/regions in Asia conceptualized a large-scale survey to examine the current realities of HBPM. A cross-sectional survey was conducted among health care professionals from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam between November 2019 and June 2021. Physicians' responses were summarized using descriptive statistics. A total of 7945 physicians participated in the survey. Among all respondents, 50.3% and 33.5% viewed HBPM as highly recognized by physicians and patients in their country/region, respectively. Lack of understanding of HBPM and concern with the accuracy and reliability of HBPM devices were identified as key barriers to HBPM recognition. Nearly all physicians (95.9%) reported recommending HBPM to their patients; however, they reported less than 50% of their patients measured home blood pressure (HBP). Among physicians who recommended HBPM, only 22.4% and 54.1% cited HBP diagnostic threshold values and timing of taking antihypertensive drugs that were consistent with available guidelines, respectively. The survey reveals that the recognition of HBPM as a valuable tool to diagnose and manage hypertension is suboptimal in most parts of Asia. Despite high recommendation of HBPM to hypertensive patients by physicians, there are considerable discrepancies between guidelines recommendations and practice realities. The recognition of HBPM as a valuable tool for the diagnosis and management of hypertension is suboptimal among both physicians and patients in Asia. A clear and consistent guidance for proper HBPM practice and use of validated and calibrated HBP monitors are among the top priorities to support the integration of HBPM into daily patient care. HBPM: home blood pressure monitoring, HBP: home blood pressure.

Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair.

Cardiac stem cells (CSCs) are promising candidates for use in myocardial regenerative therapy. We test the hypothesis that growing cardiac-derived cells as three-dimensional cardiospheres may recapitulate a stem cell niche-like microenvironment, favoring cell survival and enhancing functional benefit after transplantation into the injured heart. CSCs and supporting cells from human endomyocardial biopsies were grown as cardiospheres and compared with cells cultured under traditional monolayer condition or dissociated from cardiospheres. Cardiospheres self-assembled into stem cell niche-like structures in vitro in suspension culture, while exhibiting greater proportions of c-kit(+) cells and upregulated expression of SOX2 and Nanog. Pathway-focused polymerase chain reaction (PCR) array, quantitative real-time PCR, and immunostaining revealed enhanced expression of stem cell-relevant factors and adhesion/extracellular-matrix molecules (ECM) in cardiospheres including IGF-1, histone deacetylase 2 (HDAC2), Tert, integrin-α(2), laminin-ß(1), and matrix metalloproteinases (MMPs). Implantation of cardiospheres in severe combined immunodeficiency (SCID) mouse hearts with acute infarction disproportionately improved cell engraftment and myocardial function, relative to monolayer-cultured cells. Dissociation of cardiospheres into single cells decreased the expression of ECM and adhesion molecules and undermined resistance to oxidative stress, negating the improved cell engraftment and functional benefit in vivo. Growth of cardiac-derived cells as cardiospheres mimics stem cell niche properties with enhanced "stemness" and expression of ECM and adhesion molecules. These changes underlie an increase in cell survival and more potent augmentation of global function following implantation into the infarcted heart.

Regional differences in office and self-measured home heart rates in Asian hypertensive patients: AsiaBP@Home study.

Increased heart rate is a predictor of cardiovascular disease, heart failure, and all-cause mortality. In those with high heart rates, interventions for heart rate reduction have been associated with reductions in coronary events. Asia is a diverse continent, and the prevalences of hypertension and cardiovascular disease differ among its countries. The present analysis of AsiaBP@Home study data investigated differences among resting heart rates (RHRs) in 1443 hypertensive patients from three Asian regions: East Asia (N = 595), Southeast Asia (N = 680), and South Asia (N = 168). This is the first study to investigate self-measured RHR values in different Asian countries/regions using the same validated home BP monitoring device (Omron HEM-7130-AP/HEM-7131-E). Subjects in South Asia had higher RHR values compared with the other two regions, and the regional tendency found in RHR values was different from that found in BP values. Even after adjusting for age, sex, BMI, habitual alcohol consumption, current smoking habit, shift worker, hyperlipidemia, diabetes, chronic kidney disease, history of heart failure, and beta-blocker use, both office and home RHR values in South Asia were the highest among Asia (mean values ± SE of office: East Asia [E] 75.2 ± 1.5 bpm, Southeast Asia [Se] 76.7 ± 1.5 bpm, South Asia [S] 81.9 ± 1.4 bpm; home morning: [E] 69.0 ± 1.2 bpm, [Se] 72.9 ± 1.2 bpm, [S] 74.9 ± 1.1 bpm; home evening: [E] 74.6 ± 1.2 bpm, [Se] 78.3 ± 1.2 bpm, [S] 83.8 ± 1.1 bpm). Given what is known about the impact of RHR on heart disease, our findings suggest the possible benefit of regionally tailored clinical strategies for cardiovascular disease prevention.

Home blood pressure control status in 2017-2018 for hypertension specialist centers in Asia: Results of the Asia BP@Home study.

A self-measured home blood pressure (BP)-guided strategy is an effective practical approach to hypertension management. The Asia BP@Home study is the first designed to investigate current home BP control status in different Asian countries/regions using standardized home BP measurements taken with the same validated home BP monitoring device with data memory. We enrolled 1443 medicated hypertensive patients from 15 Asian specialist centers in 11 countries/regions between April 2017 and March 2018. BP was relatively well controlled in 68.2% of patients using a morning home systolic BP (SBP) cutoff of <135 mm Hg, and in 55.1% of patients using a clinic SBP cutoff of <140 mm Hg. When cutoff values were changed to the 2017 AHA/ACC threshold (SBP <130 mm Hg), 53.6% of patients were well controlled for morning home SBP. Using clinic 140 mm Hg and morning home 135 mm Hg SBP thresholds, the proportion of patients with well-controlled hypertension (46%) was higher than for uncontrolled sustained (22%), white-coat (23%), and masked uncontrolled (9%) hypertension, with significant country/regional differences. Home BP variability in Asian countries was high, and varied by country/region. In conclusion, the Asia BP@Home study demonstrated that home BP is relatively well controlled at hypertension specialist centers in Asia. However, almost half of patients remain uncontrolled for morning BP according to new guidelines, with significant country/regional differences. Strict home BP control should be beneficial in Asian populations. The findings of this study are important to facilitate development of health policies focused on reducing cardiovascular complications in Asia.

The Relationship between the Growth Hormone/Insulin-like Growth Factor System and the Histological Features of Nonalcoholic Fatty Liver Disease.

Objective Growth hormone (GH) deficiency has recently been reported as a cause of nonalcoholic fatty liver disease (NAFLD), and GH supplementation has been shown to improve the histology of NAFLD. The aim of the present study was to clarify the relationship between the histological severity of NAFLD and production of the GH/insulin-like growth factor 1 (IGF-1) axis. Methods A total of 222 Japanese patients with liver biopsy-confirmed NAFLD and 55 patients with hepatitis C virus (HCV)-related chronic liver disease (CLD) were enrolled in the present study. The serum levels of GH, IGF-1, and IGF-binding protein 3 (IGFBP-3) were measured and their relationships with the histological severity of liver disease were assessed. To exclude age- and sex-related differences, the IGF-1 standard deviation score (IGF-1:SDS) was determined for each patient. Results With respect to the stage of fibrosis in patients with NAFLD, the serum GH levels were higher and the serum IGFBP-3 levels and IGF-1:SDSs were lower in patients with cirrhosis (grade F4 fibrosis) than in patients grade F1-F3 fibrosis; moreover, these differences were statistically significant (all p<0.01). The GH, IGF-1, and IGFBP-3 levels were not correlated with fibrosis in patients with HCV-related CLD. Furthermore, the GH levels were lower and the IGFBP-3 levels were significantly higher in patients with severe steatosis (S3) than in patients with mild to moderate steatosis (S1-S2) (p<0.05). Conclusion Increased GH levels and decreased IGF-1 and IGFBP-3 levels might contribute to the progression of NAFLD. The GH/IGF-1 axis may be important in the development of NAFLD, but not in patients with HCV-related CLD.

Gender difference in NASH susceptibility: Roles of hepatocyte Ikkß and Sult1e1.

Myeloid cell and hepatocyte IKKß may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKß deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKß deficiency (IkbkbΔhep) in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1), which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKß of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKß is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients.

Elongated ascending aorta predicts a short distance between his-bundle potential recording site and coronary sinus ostium.

BACKGROUND: When performing catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT), it can be difficult to maintain a safe distance from the His recording site to avoid AV block in patients with a short distance between this recording site to the coronary sinus (CS) ostium (small triangle of Koch [TOK]). In this study, we sought to identify parameters predicting small TOK and test these parameters in patients undergoing AVNRT catheter ablation. METHODS: Twenty-eight patients who underwent catheter ablation of atrial fibrillation using a three-dimensional (3D) electroanatomical mapping system (EAM) with computed tomography (CT) merge (23 males; mean age, 65.8±12.1 years) were included. The shortest distance between the CS ostium and His recording sites (His-CSd) was measured on the EAM. Aortic (Ao) unfolding in chest X-ray scan, Ao angle to the LV, Ao length, Ao to the right ventricular distance, size of the Valsalva in the CT scan, and parameters of echocardiogram were evaluated. The identified parameters were subsequently tested as predictors for small TOK in patients undergoing AVNRT ablation. RESULTS: The size of TOK was associated with Ao length (r = -0.70, p<0.01), left ventricular end-systolic dimension (LVDs) (r = -0.51, p<0.01), and Ao unfolding. In patients with AVNRT, only Ao unfolding predicted a smaller TOK. CONCLUSIONS: Small TOK was associated with longer Ao, larger LVDs, and Ao unfolding. Of these, Ao unfolding was associated with smaller TOK in patients with AVNRT.

Outcomes of single- or dual-chamber implantable cardioverter defibrillator systems in Japanese patients.

BACKGROUND: There are no criteria for selecting single- or dual-chamber implantable cardioverter defibrillators (ICDs) in patients without a pacing indication. Recent reports showed no benefit of the dual-chamber system despite its preference in the United States. As data on ICD selection and respective outcomes in Japanese patients are scarce, we investigated trends regarding single- and dual-chamber ICD usage in Japan. METHODS: Data from a total of 205 ICD recipients with structural heart disease (median age, 63 years) in two Japanese university hospitals were reviewed. Patients with bradycardia with a pacing indication and permanent atrial fibrillation at implantation were excluded. RESULTS: Single- and dual-chamber ICDs were implanted in 36 (18%) and 169 (82%) patients, respectively. Non-ischemic cardiomyopathy dominated both groups. Seventeen dual-chamber patients developed atrial pacing-dependency over 4.5 years, and it developed immediately after implantation in 14. Although preoperative testing showed no sign of bradycardia in these patients, their pacing rate was set higher than it was in patients who were pacing-independent (61 vs. 46 paces per min, p<0.01). Two single-chamber patients (5%) underwent atrial lead insertion. While inappropriate shock equally occurred in both groups (7 vs. 21 patients, single- vs. dual-chamber, P=0.285), device-related infection occurred only in dual-chamber patients (0 vs. 9 patients, P=0.155). No differences in death or heart failure hospitalization were observed between groups. CONCLUSIONS: Dual-chamber ICDs were four-fold more common in Japanese patients without a pacing indication. No benefit over single-chamber ICD was observed. Newly developed atrial pacing-dependency seemed to be limited and could have been overestimated due to higher pacing rate settings in dual-chamber patients.

Investigation of ornithine carbamoyltransferase as a biomarker of liver cirrhosis.

OBJECTIVE: Ornithine carbamoyltransferase (OCT) is a liver-specific mitochondrial matrix enzyme and potential biomarker of liver fibrosis. This study investigated the OCT levels in patients with chronic liver disease with or without cirrhosis in order to assess the usefulness of OCT as a biomarker of cirrhosis. METHODS: The subjects included 440 Japanese patients with chronic liver disease and 80 control subjects. The patients were divided into two groups, those with and without cirrhosis, both of which were further stratified into high-OCT and low-OCT subgroups. RESULTS: In the non-cirrhosis group, the patients with non-alcoholic steatohepatitis (NASH), alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis (PSC) comprised the high-OCT subgroup, while the patients with hepatitis B, hepatitis C and autoimmune hepatitis formed the low-OCT subgroup. There were significant differences in the OCT levels, OCT/aspartate aminotransferase ratios and OCT/alanine transaminase (ALT) ratios between these two subgroups (p<0.001). The same findings were observed in the cirrhosis group. The OCT levels were markedly higher in the cirrhosis group than in the non-cirrhosis group, particularly among the patients with PSC (p<0.001). The most useful biomarker for predicting cirrhosis was the OCT/ALT ratio in the patients with hepatitis C and NASH and the OCT level in patients with PSC. CONCLUSION: The OCT level differs among patients with different chronic liver diseases. The role of OCT should be further evaluated in order to improve our understanding of the pathogenesis of these diseases. The OCT level is a useful surrogate marker of cirrhosis, particularly in PSC patients.

Targeted MicroRNA Interference Promotes Postnatal Cardiac Cell Cycle Re-Entry.

Mammalian heart cells undergo a marked reduction in proliferative activity shortly after birth, and thereafter grow predominantly by hypertrophy. Our understanding of the molecular mechanisms underlying cardiac maturation and senescence is based largely on studies at the whole-heart level. Here, we investigate the molecular basis of the acquired quiescence of purified neonatal and adult cardiomyocytes, and use microRNA interference as a novel strategy to promote cardiomyocyte cell cycle re-entry. Expression of cyclins and cyclin-dependent kinases (CDKs) and positive modulators were down-regulated, while CDK inhibitors and negative cell cycle modulators were up-regulated during postnatal maturation of cardiomyocytes. The expression pattern of microRNAs also changed dramatically, including increases in miR-29a, miR-30a and miR-141. Treatment of neonatal cardiomyocytes with miRNA inhibitors anti-miR-29a, anti-miR-30a, and antimiR-141 resulted in more cycling cells and enhanced expression of Cyclin A2 (CCNA2). Thus, targeted microRNA interference can reactivate postnatal cardiomyocyte proliferation.

Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease.

BACKGROUND: Biomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. METHODS: (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups. RESULTS: 1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3ß ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC. CONCLUSION: Several metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.

Magnetic enhancement of cell retention, engraftment, and functional benefit after intracoronary delivery of cardiac-derived stem cells in a rat model of ischemia/reperfusion.

The efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres were injected into the left ventricular cavity of syngeneic rats during brief aortic clamping. Placement of a 1.3 Tesla magnet ~1 cm above the heart during and after cell injection enhanced cell retention at 24 h by 5.2-6.4-fold when 1, 3, or 5 × 10(5) cells were infused, without elevation of serum troponin I (sTnI) levels. Higher cell doses (1 or 2 × 10(6) cells) did raise sTnI levels, due to microvascular obstruction; in this range, magnetic enhancement did not improve cell retention. To assess efficacy, 5 × 10(5) iron-labeled, GFP-expressing cells were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left anterior coronary artery, with and without a superimposed magnet. By quantitative PCR and optical imaging, magnetic targeting increased cardiac retention of transplanted cells at 24 h, and decreased migration into the lungs. The enhanced cell engraftment persisted for at least 3 weeks, at which time left ventricular remodeling was attenuated, and therapeutic benefit (ejection fraction) was higher, in the magnetic targeting group. Histology revealed more GFP(+) cardiomyocytes, Ki67(+) cardiomyocytes and GFP(-)/ckit(+) cells, and fewer TUNEL(+) cells, in hearts from the magnetic targeting group. In a rat model of ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is safe and improves cell therapy outcomes.

Isolated adrenocorticotropin deficiency associated with delirium and takotsubo cardiomyopathy.

We report a 65-year-old woman with isolated adrenocorticotropic hormone (ACTH) deficiency. The patient was transported to the emergency outpatient department by ambulance complaining of malaise and nausea. Because her laboratory data revealed hyponatremia, we performed endocrinological examinations and diagnosed isolated ACTH deficiency. After admission, she went into a delirious state and suffered from takotsubo cardiomyopathy due to adrenal insufficiency. Replacement therapy with hydrocortisone sufficiently improved her delirium and cardiomyopathy. We conclude that her unstable mental state and myocardial dysfunction were closely related to adrenal insufficiency and suggest that adrenal crisis may cause delirium and Takotsubo cardiomyopathy.

Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells.

OBJECTIVES: The goal of this study was to conduct a direct head-to-head comparison of different stem cell types in vitro for various assays of potency and in vivo for functional myocardial repair in the same mouse model of myocardial infarction. BACKGROUND: Adult stem cells of diverse origins (e.g., bone marrow, fat, heart) and antigenic identity have been studied for repair of the damaged heart, but the relative utility of the various cell types remains unclear. METHODS: Human cardiosphere-derived cells (CDCs), bone marrow-derived mesenchymal stem cells, adipose tissue-derived mesenchymal stem cells, and bone marrow mononuclear cells were compared. RESULTS: CDCs revealed a distinctive phenotype with uniform expression of CD105, partial expression of c-kit and CD90, and negligible expression of hematopoietic markers. In vitro, CDCs showed the greatest myogenic differentiation potency, highest angiogenic potential, and relatively high production of various angiogenic and antiapoptotic-secreted factors. In vivo, injection of CDCs into the infarcted mouse hearts resulted in superior improvement of cardiac function, the highest cell engraftment and myogenic differentiation rates, and the least-abnormal heart morphology 3 weeks after treatment. CDC-treated hearts also exhibited the lowest number of apoptotic cells. The c-kit(+) subpopulation purified from CDCs produced lower levels of paracrine factors and inferior functional benefit when compared with unsorted CDCs. To validate the comparison of cells from various human donors, selected results were confirmed in cells of different types derived from individual rats. CONCLUSIONS: CDCs exhibited a balanced profile of paracrine factor production and, among various comparator cell types/subpopulations, provided the greatest functional benefit in experimental myocardial infarction.

Expansion of human cardiac stem cells in physiological oxygen improves cell production efficiency and potency for myocardial repair.

AIMS: the ex vivo expansion of cardiac stem cells from minimally invasive human heart biopsies yields tens of millions of cells within 3-4 weeks, but chromosomal abnormalities were frequently detected in preliminary production runs. Here we attempt to avoid aneuploidy and improve cell quality by expanding human cardiac stem cells in physiological low-oxygen (5% O(2)) conditions, rather than in traditional culture in a general CO(2) incubator (20% O(2)). METHODS AND RESULTS: human heart biopsies (n = 16) were divided and processed in parallel to expand cardiac stem cells under 5% or 20% O(2). Compared with 20% O(2), 5% O(2) culture doubled the cell production and markedly diminished the frequency of aneuploidy. Cells expanded in 5% O(2) showed lower intracellular levels of reactive oxygen species, less cell senescence, and higher resistance to oxidative stress than those grown in 20% O(2), although the expression of stem cell antigens and adhesion molecules was comparable between groups, as was the paracrine secretion of growth factors into conditioned media. In vivo, the implantation of 5% O(2) cells into infarcted hearts of mice resulted in greater cell engraftment and better functional recovery than with conventionally cultured cells. CONCLUSION: the expansion of human adult cardiac stem cells in low oxygen increased cell yield, and the resulting cells were superior by various key in vitro and in vivo metrics of cell quality. Physiological oxygen tensions in culture facilitate the ex vivo expansion of healthy, biologically potent stem cells.