The Index of Exercise Tolerance in Heart Failure with Preserved Ejection Fraction is Gait Speed

Introduction: Exercise tolerance, an important factor affecting life prognosis and rehospitalization in patients with chronic heart failure, is a major outcome of cardiac rehabilitation. Heart failure with preserved ejection fraction (HFpEF) from reduced diastolic capacity has recently increased among patients with chronic heart failure. This study evaluated and clarified the factors indicating exercise tolerance in patients with HFpEF from various perspectives, including cardiac and skeletal muscle functions. Material and Methods: The subjects were 31 patients with HFpEF who underwent cardiac rehabilitation. Exercise tolerance was assessed using a 6-minute walking test. Physical function, physical activity, body composition test, baseline characteristics, blood data, and echocardiography results were extracted from medical records to identify the indicators of exercise tolerance. Results: Gait speed was significantly different in exercise tolerance for HFpEF patients (β=0.75, p<0.01). Unlike HFrEF, HFpEF were no significant differences in brain natriuretic peptide (BNP) levels and cardiac function. Conclusion: Gait speed is an indicator of exercise tolerance in HFpEF patients. However, its pathological course differs from HFrEF, indicating that it is poorly related to BNP, a biomarker for heart failure and cardiac function

出生児低体重モデルにおける、冠循環形態の変容

第3回日本DOHaD研究会学術集会　抄録集　【ポスター発表

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

PPARα Agonist Suppresses Inflammation after Corneal Alkali Burn by Suppressing Proinflammatory Cytokines, MCP-1, and Nuclear Translocation of NF-κB

We investigated the effect of a peroxisome proliferator-activated receptor &alpha; (PPAR&alpha;) agonist after corneal alkali injury. Fenofibrate 0.05% (PPAR&alpha; agonist group) or vehicle (Vehicle group) was topically instilled onto the rat cornea after injury. Histological, immunohistochemical, and real-time reverse transcription PCR analyses were performed. PPAR&alpha;-positive cells were observed among basal cells of the corneal epithelium in normal and alkali-burned corneas. The number of infiltrating neutrophils and macrophages at the corneal limbus was lower in the PPAR&alpha; agonist group. Interleukin-1&beta; (IL-1&beta;), IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor-An mRNA expression was suppressed in the PPAR&alpha; agonist group compared to the Vehicle group. mRNA levels of nuclear factor kappa B (NF-&kappa;B) in corneal tissue were not different. However, NF-&kappa;B was expressed in the cytoplasm of basal cells in the PPAR&alpha; agonist group and in the nucleus in the Vehicle group. MCP-1 was more weakly expressed in the PPAR&alpha; agonist group. The PPAR&alpha; agonist inhibited inflammation during the early phase after injury. Anti-inflammatory effects of the PPAR&alpha; agonist included prevention of up-regulation of proinflammatory cytokines and MCP-1, and prevention of inflammatory cell infiltration into the injured cornea. Thus, a PPAR&alpha; agonist may be a promising treatment for corneal injury

Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility

Abstract Atrial fibrillation (AF) and heart failure (HF) contribute to about 45% of all cardiovascular disease (CVD) deaths in the USA and around the globe. Due to the complex nature, progression, inherent genetic makeup, and heterogeneity of CVDs, personalized treatments are believed to be critical. To improve the deciphering of CVD mechanisms, we need to deeply investigate well-known and identify novel genes that are responsible for CVD development. With the advancements in sequencing technologies, genomic data have been generated at an unprecedented pace to foster translational research. Correct application of bioinformatics using genomic data holds the potential to reveal the genetic underpinnings of various health conditions. It can help in the identification of causal variants for AF, HF, and other CVDs by moving beyond the one-gene one-disease model through the integration of common and rare variant association, the expressed genome, and characterization of comorbidities and phenotypic traits derived from the clinical information. In this study, we examined and discussed variable genomic approaches investigating genes associated with AF, HF, and other CVDs. We collected, reviewed, and compared high-quality scientific literature published between 2009 and 2022 and accessible through PubMed/NCBI. While selecting relevant literature, we mainly focused on identifying genomic approaches involving the integration of genomic data; analysis of common and rare genetic variants; metadata and phenotypic details; and multi-ethnic studies including individuals from ethnic minorities, and European, Asian, and American ancestries. We found 190 genes associated with AF and 26 genes linked to HF. Seven genes had implications in both AF and HF, which are SYNPO2L, TTN, MTSS1, SCN5A, PITX2, KLHL3, and AGAP5. We listed our conclusion, which include detailed information about genes and SNPs associated with AF and HF

Amniogenic somatopleure: a novel origin of multiple cell lineages contributing to the cardiovascular system.

The somatopleure is the amniotic primordium in amniote development, but its boundary to the embryonic body at early embryonic stages and the fate of cells constituting this structure are not well characterized. It also remains unclear how cells behave during the demarcation between intra- and extra-embryonic tissues. Here we identify cellular alignments, which indicate two streams towards the sites of dorsal amniotic closure and ventral thoracic wall formation. A subpopulation of mesodermal cells moving ventrally from the somatopleural region adjacent to the base of the head fold enter the body of the embryo and distribute to the thoracic wall, pharyngeal arches and heart. These cells are induced to differentiate into vascular endothelial cells and cardiomyocytes possibly by FGF and BMP signaling, respectively. These results indicate that the somatopleure acting as the amniotic primordium also serves as a source of embryonic cells, which may contribute to cardiovascular development