Myocardial velocity gradient as a noninvasively determined index of left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy

AbstractObjectivesWe investigated the utility of the peak negative myocardial velocity gradient (MVG) derived from tissue Doppler imaging (TDI) for evaluation of diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM).BackgroundHypertrophic cardiomyopathy is characterized by impaired diastolic function with abnormal stiffness and prolonged relaxation. However, it remains difficult to evaluate these defects noninvasively.MethodsBoth TDI and conventional echocardiography were performed in 36 patients with HCM and in 47 control subjects. Left ventricular (LV) pressure was measured simultaneously in all HCM patients and in 26 controls.ResultsThe peak negative MVG occurred soon after the isovolumic relaxation period during the initial phase of rapid filling (auxotonic relaxation). It was significantly smaller in HCM patients than in control subjects (2.32 ± 0.52/s vs. 4.82 ± 1.15/s, p < 0.0001); the cutoff value for differentiation between all HCM patients and 47 normal individuals was determined as 3.2/s. Both the left ventricular end-diastolic pressure (LVEDP) (19.6 ± 6.1 mm Hg vs. 6.5 ± 1.7 mm Hg, p < 0.0001) and the time constant of LV pressure decay during isovolumic diastole (tau) (44.0 ± 6.7 ms vs. 32.1 ± 5.5 ms, p < 0.0001) were increased in HCM patients compared with controls. The peak negative MVG was negatively correlated with both LVEDP (r= −0.75, p < 0.0001) and tau (r= −0.58, p < 0.0001).ConclusionsA reduced peak negative MVG reflects both prolonged relaxation and elevated LVEDP. The peak negative MVG might thus provide a noninvasive index of diastolic function, yielding unique information about auxotonic relaxation in patients with HCM

Wounding triggers callus formation via dynamic hormonal and transcriptional changes

Wounding is a primary trigger of organ regeneration, but how wound stress reactivates cell proliferation and promotes cellular reprogramming remains elusive. In this study, we combined transcriptome analysis with quantitative hormonal analysis to investigate how wounding induces callus formation in Arabidopsis (Arabidopsis thaliana). Our time course RNA-seq analysis revealed that wounding induces dynamic transcriptional changes, starting from rapid stress responses followed by the activation of metabolic processes and protein synthesis and subsequent activation of cell cycle regulators. Gene ontology analyses further uncovered that wounding modifies the expression of hormone biosynthesis and response genes, and quantitative analysis of endogenous plant hormones revealed accumulation of cytokinin prior to callus formation. Mutants defective in cytokinin synthesis and signaling display reduced efficiency in callus formation, indicating that de novo synthesis of cytokinin is critical for wound-induced callus formation. We further demonstrate that type-B ARABIDOPSIS RESPONSE REGULATOR-mediated cytokinin signaling regulates the expression of CYCLIN D3;1 (CYCD3;1) and that mutations in CYCD3;1 and its homologs CYCD3;2 and 3 cause defects in callus formation. In addition to these hormone-mediated changes, our transcriptome data uncovered that wounding activates multiple developmental regulators, and we found novel roles of ETHYLENE RESPONSE FACTOR 115 and PLETHORA3 (PLT3), PLT5, and PLT7 in callus generation. All together, these results provide novel mechanistic insights into how wounding reactivates cell proliferation during callus formation

Increase in serum triglyceride was associated with coronary plaque vulnerability in a patient with rheumatoid arthritis

AbstractRates of morbidity and mortality from cardiovascular disease are high in patients with rheumatoid arthritis (RA); however, the mechanisms and biomarkers that reflect coronary plaque vulnerability have not yet been established. We present a case of acute coronary syndrome (ACS) presumably caused by exacerbation of chronic inflammation of RA, in which an abrupt increase in serum triglyceride was seen on the day of onset of ACS but not during effort angina. This case suggests that RA patients with an abrupt increase in triglyceride need intensive care including anti-platelet and statin therapy for the prevention of coronary plaque rupture.<Learning objective: Triglyceride might be a sensitive biomarker of activated macrophages and plaque vulnerability in patients with RA. RA patients with an abrupt increase in triglyceride might need intensive care including anti-platelet and statin therapy for the prevention of coronary plaque rupture.

ICTP and vulnerable plaque

Evaluation of atherosclerotic plaques depends on invasive intravascular ultrasonography (IVUS). Carboxy-terminal telopeptide of type I collagen (ICTP) is produced by matrix metalloproteinase (MMP)-dependent digestion of type I collagen. Because vulnerable plaques are rich in type I collagen and MMPs from macrophages, we examined the association between serum ICTP and coronary plaques in patients with coronary disease. We recruited 46 men and 17 women without renal failure or bone diseases affecting serum ICTP, who underwent coronary IVUS. Serum ICTP levels were higher in patients with coronary plaques containing more than 10% necrotic core area than in patients with less than 10% necrotic core area. A positive correlation was found between serum ICTP and necrotic core area. Only serum ICTP was positively correlated with necrotic core area by multivariate analysis (p<0.05). These results suggest that serum ICTP can be used as a non-invasive marker of vulnerable plaques in atherosclerotic patients

マッショウ タンカクキュウ サイボウ オ モチイタ マッショウ ドウミャク ヘイソクショウ ニ タイスル アラタナ ケッカン シンセイ リョウホウ ノ ココロミ

Earlier studies have shown that bone marrow-derived mononuclear cell（BM-MNC）implantation induces therapeutic angiogenesis in patients with peripheral arterial disease（PAD）. However, the invasiveness of bone marrow collection limits clinical application of BM-MNC implantation.We performed peripheral blood-derived mononuclear cell（PB-MNC）implantation in ischemic limbs of five patients with PAD. After implantation, clinical symptoms such as rest pain and numbness were relieved in four patients. Maximal walking distance markedly increased from 160 m to 915 m in one patient. Non-healing ulcers were cured after repeated cell implantation in one patient with Burger disease. There was no adverse event. These findings suggest that PB-MNC implantation is a safe and noninvasive strategy for therapeutic angiogenesis for the treatment of severe PAD

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

Shoshin Beriberi Induced by Long-Term Administration of Diuretics: A Case Report

Previous studies have suggested that diuretic therapy for heart failure may lead to thiamine deficiency due to the increased urinary thiamine excretion. Herein, we present the case of a 61-year-old man with shoshin beriberi, a fulminant form of wet beriberi, induced by long-term diuretic therapy. The patient had a history of heart failure with preserved ejection fraction and was receiving furosemide and trichlormethiazide therapy. He presented with worsening exertional dyspnea and was admitted for heart failure exacerbation. His condition failed to improve even after intensive treatment. A hemodynamic evaluation with the Swan-Ganz catheter revealed high-output heart failure with low peripheral vascular resistance. Thiamine was administered for suspected shoshin beriberi; his hemodynamic status improved dramatically within the next six hours. The serum thiamine level was below the normal range; the patient was therefore diagnosed with shoshin beriberi. The common causes of thiamine deficiency were not identified. Long-term diuretic therapy with furosemide and thiazide was thought to have played a major role in the development of thiamine deficiency. This case illustrates the importance of considering wet beriberi as a possible cause of heart failure exacerbation in patients taking diuretics, even when the common thiamine deficiency causes are not identified with history-taking

Age-related reduction and independent predictors of toe flexor strength in middle-aged men

Abstract Background Toe flexor muscles play an important role in posture and locomotion, and poor toe flexor strength is a risk factor for falls. In this cross-sectional study, we estimated the age-related change in toe flexor strength and compared it with that of handgrip strength. Independent factors predicting toe flexor and handgrip strength were also determined. Methods A total of 1401 male (aged 35–59 years) study participants were divided into five groups according to their chronological age; 35–39, 40–44, 45–49, 50–54, and 55–59 years. Toe flexor and handgrip strength, anthropometry, and resting blood pressure were measured. Fasting blood samples were collected to measure blood glucose, triglycerides, high- and low-density lipoprotein-cholesterols, and albumin. A self-administered lifestyle questionnaire was conducted. Results Decline in absolute toe flexor and handgrip strength began in the age groups 50–55 and 55–59 years, respectively. In comparison to the mean values of the youngest group, relative toe flexor strength (87.0 ± 26.6%) was significantly lower than handgrip strength (94.4 ± 13.1%) for the oldest group. Multiple regression analyses showed that independent factors predicting both toe flexor and handgrip strength were lean body mass, age, serum albumin, drinking habit, and fat mass. Additionally, fasting blood glucose, diastolic blood pressure, sleeping time and exercise habit were predicting factors of toe flexor strength but not of handgrip strength. Conclusions Age-related reduction in toe flexor strength was earlier and greater than handgrip strength, and toe flexor strength reflects body composition and metabolic status