ß 3-Adrenergic Receptor Agonist Prevents Diastolic Dysfunction in an Angiotensin II-Induced Cardiomyopathy Mouse Model.

ß3-Adrenergic receptor expression is enhanced in the failing heart, but its functional effects are unclear. We tested the hypothesis that a ß3-agonist improves left ventricular (LV) performance in heart failure. We examined the chronic effects of a ß3-agonist in the angiotensin II (Ang II)-induced cardiomyopathy mouse model. C57BL/6J mice were treated with Ang II alone or Ang II + BRL 37344 (ß3-agonist, BRL) for 4 weeks. Systolic blood pressure in conscious mice was significantly elevated in Ang II and Ang II + BRL mice compared with control mice. Heart rate was not different among the three groups. Systolic performance parameters that were measured by echocardiography and an LV catheter were similar among the groups. LV end-diastolic pressure and end-diastolic pressure-volume relationships were higher in Ang II mice compared with control mice. However, the increase in these parameters was prevented in Ang II + BRL mice, which suggested improvement in myocardial stiffness by BRL. Pathologic analysis showed that LV hypertrophy was induced in Ang II mice and failed to be prevented by BRL. However, increased collagen I/III synthesis, cardiac fibrosis, and lung congestion observed in Ang II mice were inhibited by BRL treatment. The cardioprotective benefits of BRL were associated with downregulation of transforming growth factor-ß1 expression and phosphorylated-Smad2/3. Chronic infusion of a ß3-agonist has a beneficial effect on LV diastolic function independent of blood pressure in the Ang II-induced cardiomyopathy mouse model. SIGNIFICANCE STATEMENT: Chronic infusion of a ß3-adrenergic receptor agonist attenuates cardiac fibrosis and improves diastolic dysfunction independently of blood pressure in an angiotensin II-induced hypertensive mouse model. This drug might be an effective treatment of heart failure with preserved ejection fraction.

Comparison of post-stent optical coherence tomography findings: Layered versus non-layered culprit lesions.

OBJECTIVES: This study aimed to investigate the vascular response of lesions with a layered phenotype. BACKGROUND: Recent studies have shown that layered plaques at culprit lesions detected by optical coherence tomography (OCT) have greater plaque burden and more inflammatory features than non-layered plaques. METHODS: This is a retrospective observational study. A total of 193 target lesions from 193 patients [100 patients with acute coronary syndromes (ACS) and 93 with stable angina pectoris (SAP)] who had undergone OCT imaging of the culprit lesion both before and after stenting were included. Layered plaques were identified by OCT as plaques with layers of different optical density. Patients were divided into two groups based on the presence or absence of a layered phenotype at the culprit lesion, and pre- and post-procedure OCT findings were compared. RESULTS: Among 193 patients, 36 (36.0%) lesions in ACS patients and 56 (60.2%) lesions in SAP patients were found to have a layered phenotype at the culprit lesion. At baseline, percent area stenosis was greater in layered plaque than in non-layered plaque (p = .019). Following stent implantation, the stent expansion ratio and mean stent eccentricity index were significantly lower in layered plaques than in non-layered plaques (p = .041, p = .017, respectively), mainly derived from ACS patients. CONCLUSION: Following stent implantation, plaques with a layered phenotype had less stent expansion and more eccentric lumens. Aggressive balloon dilation may be required to obtain optimal stent outcomes in patients with a layered plaque phenotype at the culprit lesion.

Degree of luminal narrowing and composition of thrombus in plaque erosion.

As the degree of luminal narrowing increases, shear stress increases, and high shear stress is known to activate platelets. However, the relationship between the degree of luminal narrowing and the composition of thrombus in patients with plaque erosion has not been studied. A total of 148 patients with plaque erosion and thrombus detected by optical coherence tomography were divided into tertiles based on the minimum lumen area (MLA) at the culprit lesion. Thrombus was categorized as platelet-rich or fibrin-rich. Among 148 patients, 50 (34%) were in the mild stenosis group, 49 (33%) were in the moderate stenosis group, and 49 (33%) were in the severe stenosis group. The composition of thrombus was significantly different among the 3 groups (prevalence of platelet-rich thrombus was 60% in the mild stenosis group; 78% in the moderate stenosis group; and 84% in the severe stenosis group; P = 0.021). The pattern of fibrin-rich thrombus showed the opposite: 40%, 22%, and 16%, respectively. In the multivariate analysis, current smoking was independently associated with fibrin-rich thrombus (odds ratio [OR] 2.364 [95% CI 1.004-5.567], P = 0.049). This study demonstrated that platelet-rich thrombus was the predominant type of thrombus in plaque erosion. The prevalence of fibrin-rich thrombus was highest in the mild stenosis group.

Determinants of ST-segment elevation myocardial infarction as clinical presentation of acute coronary syndrome.

Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the most frequent underlying mechanisms of acute coronary syndromes (ACS). The conditions and medications that are associated with ST-segment elevation myocardial infarction (STEMI) following PR or PE have not been systematically studied. A total of 838 ACS patients (494 with STEMI, 344 with NSTE-ACS) who were diagnosed with PR or PE by optical coherence tomography were included. The patients were categorized into two groups based on underlying pathology, and the baseline characteristics and culprit plaque morphology associated with STEMI were investigated within each group. Among 838 patients, 467 (55.7%) had PR, and 371 (44.3%) were diagnosed with PE. Among patients with PR, older age, hyperlipidemia, no antiplatelet therapy, higher level of low-density lipoprotein cholesterol, and greater lipid burden and macrophage infiltration were associated with increased probability of STEMI. Among patients with PE, no dual antiplatelet therapy and no statin therapy were associated with increased probability of STEMI. The incidence of STEMI caused by PR was significantly lower on antiplatelet therapy (P < 0.001), and the incidence of STEMI caused by PE was significantly lower on antiplatelet therapy (P < 0.001) or on statin therapy (P < 0.001). Antiplatelet therapy is associated with lower probability of STEMI, regardless of underlying pathology, and statin therapy is associated with lower probability of STEMI in PE as clinical presentation of ACS. Statin therapy prior to the onset of acute coronary syndromes (ACS) may reduce the probability of plaque rupture. Antiplatelet therapy prior to the onset of ACS is associated with reduced probability of ST-segment elevation myocardial infarction (STEMI) following both plaque rupture and plaque erosion, and dual antiplatelet therapy offers additional protection compared to a single antiplatelet agent in plaque erosion. The combination of statin and antiplatelet therapy may have an additive effect on reducing the probability of STEMI caused by plaque erosion. Yellow: lipid pool(necrotic core); red: fibrin-rich thrombus; gray; platelet-rich thrombus.

Initial responsiveness to darbepoetin alfa and its contributing factors in non-dialysis chronic kidney disease patients in Japan.

BACKGROUND: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN. METHODS: Of 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed. RESULTS: The mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15-900 µg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein-creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively). CONCLUSIONS: Non-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.

Clinical significance of healed plaque detected by optical coherence tomography: a 2-year follow-up study.

Recent studies have shown that healed plaque at the culprit lesion detected by optical coherence tomography (OCT) is a sign of pan-vascular vulnerability and advanced atherosclerosis. However, the clinical significance of healed plaque is unknown. A total of 265 patients who had OCT imaging of a culprit vessel and 2-year clinical follow-up data were included. Patients were stratified based on the presence or absence of a layered plaque phenotype, defined as layers of different optical density by OCT at either culprit or non-culprit lesions. The association between layered plaque and major adverse cardiac events (MACE), defined as cardiac death, acute coronary syndromes (ACS), or revascularization, was studied. Among 265 patients, 96 (36.2%) had the layered plaque phenotype. Layered plaque was more frequently observed in stable angina pectoris patients than in ACS patients (57.8%vs. 25.1%, p < 0.001). The average clinical follow-up period was 672 ± 172 days. Cumulative MACE was significantly higher in patients with layered plaque (p = 0.041), which was primarily driven by the high revascularization rate at 2 years (p = 0.002). Multivariate regression analysis showed that presence of layered plaque and low-density lipoprotein cholesterol levels were independently associated with an increased risk of revascularization (p = 0.026, p = 0.008, respectively). Patients with healed plaque in the culprit vessel had a higher incidence of revascularization, as compared to those without healed plaque, at 2 years.

Rationale and design of oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN Trial).

BACKGROUND: Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified. METHODS: This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKD patients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index. RESULTS: The subjects consist of CKD patients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated. CONCLUSION: By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKD patients.

Assessment of vascular response after drug-eluting stents implantation in patients with diabetes mellitus: an optical coherence tomography sub-study of the J-DESsERT.

Even in the drug-eluting stent era, diabetes mellitus (DM) patients have high incidences of restenosis and repeat revascularization after percutaneous coronary intervention. The aim of this study was to compare vascular response after stent implantation between sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) by using optical coherence tomography (OCT) in DM patients as well as in non-DM patients. In the Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT), the OCT sub-study enrolled 75 patients who underwent 8 months follow-up imaging after SES or PES implantation. Mean neointimal hyperplasia (NIH) thickness was significantly thinner in SES than PES in the DM group (77 ± 47 vs. 201 ± 114 µm, p < 0.001) and in the non-DM group (84 ± 37 vs. 212 ± 128 µm, p < 0.001). Unevenness of NIH thickness in longitudinal axis was significantly smaller in SES than PES in the DM group (348 ± 191 vs. 726 ± 385 µm, p < 0.001) and in the non-DM group (344 ± 174 vs. 679 ± 314 µm, p < 0.001). The percentage of uncovered struts was significantly greater in SES than PES in the DM group (24 ± 4 vs. 9 ± 14 %, p < 0.001) and in the non-DM group (16 ± 16 vs. 3 ± 4 %, p = 0.002). Compared with PES, SES showed more potent NIH inhibition in DM patients as well as in non-DM patients.

Geographical predisposition influences on the distribution and tissue characterisation of eccentric coronary plaques in non-branching coronary arteries: cross-sectional study of coronary plaques analysed by intravascular ultrasound.

BACKGROUND: We investigated the influence of geographical predisposition on the spatial distribution and composition of coronary plaques. METHODS: Thirty coronary arteries were evaluated. A total of 1441 cross-sections were collected from intravascular ultrasound (IVUS) and radio-frequency signal-based virtual histology (VH-IVUS) imaging. To exclude complex geographical effects of side branches and to localise the plaque distribution, we analysed only eccentric plaques in non-branching regions. The spatial distribution of eccentric plaques in the coronary artery was classified into myocardial, lateral, and epicardial regions. The composition of eccentric plaques was analysed using VH-IVUS. RESULTS: The plaque was concentric in 723 sections (50.2%) and eccentric in 718 (49.9%). Eccentric plaques were more frequently distributed towards the myocardial side than towards the epicardial side (46.7 ± 7.5% vs. 12.5 ± 4.2%, p = 0.003). No significant difference was observed between the myocardial and lateral sides (46.7 ± 7.5% vs. 20.8 ± 5.0%) or between the lateral and epicardial sides. Eccentric thin-capped fibroatheromas were more frequently distributed towards the myocardial side than towards the lateral side (p = 0.024) or epicardial side (p = 0.005). CONCLUSION: Geographical predisposition is associated with distribution, tissue characterisation, and vulnerability of plaques in non-branching coronary arteries.

Ultrastructural features of cardiomyocytes in dilated cardiomyopathy with initially decompensated heart failure as a predictor of prognosis.

AIMS: The aim of the present study was to clarify the significance of myocardial ultrastructural changes in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: Endomyocardial biopsy of the left ventricle was performed in 250 consecutive DCM patients (54.9 ± 13.9 years, 79% men), presenting initially as decompensated heart failure (HF). Myofilament changes of cardiomyocytes were evaluated by electron microscopy and compared with clinical and morphometric data. Mortality and HF recurrence were evaluated during the follow-up period. During the follow-up period (4.9 ± 3.9 years), 24 patients (10%) died and 67 (27%) were readmitted because of HF recurrence, including those who had died because of HF. Myofilament changes, classified as either focal derangement of myofilaments (sarcomere damage) or diffuse myofilament lysis (disappearance of most sarcomeres in cardiomyocytes), were identified in 164 patients (66%). Multivariate analysis identified a family history of DCM [hazard ratio (HR) 4.763; 95% confidence interval (CI) 1.012-12.518], atrial fibrillation (HR 6.132; 95% CI 2.188-17.180), haemoglobin level (HR 0.685; 95% CI 0.528-0.889), and diffuse myofilament lysis (HR 4.048; 95% CI 1.427-11.481) as independent predictors of mortality. A family history of DCM (HR 2.268; 95% CI 1.276-4.030), haemoglobin level (HR 0.876; 95% CI 0.785-0.979), focal derangement of myofilaments (HR 7.431; 95% CI 2.916-18.934), and diffuse myofilament lysis (HR 6.480; 95% CI 2.403-17.473) were predictors of readmission due to HF recurrence. CONCLUSIONS: In DCM patients with first-decompensated HF, myofilament changes are strongly associated with mortality and HF recurrence.

The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials.

AIMS: The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. METHODS AND RESULTS: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98). CONCLUSION: In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.

Renal effects of added low-dose dopamine in acute heart failure patients with diuretic resistance to natriuretic peptide.

Worsening renal function during the early phase of hospitalization is related to adverse outcomes in acute heart failure (AHF). This study aimed to clarify whether added low-dose dopamine (DA) is clinically beneficial for AHF patients with diuretic resistance to human atrial natriuretic peptide (hANP). Twenty-four AHF patients, who did not have adequate diuresis by 4 hours after administration of hANP, were randomized to a low dose of DA (1-3 µg·kg·min, n = 12) or a low dose of furosemide (10-30 mg injection, n = 12). The significant increase in mean hourly urine volume from baseline (265% ± 204% with hANP + DA; 187% ± 118% with hANP + furosemide) and improvement of dyspnea were similarly observed in both groups. Significant decreases in serum creatinine levels were observed by -14.0% ± 14.2% in the hANP + DA group compared with the hANP + furosemide group (4.5% ± 9.6%, P = 0.0011) without increases in the renotubular and myocardial markers. The incidence of worsening renal function defined as a rise in serum creatinine of >0.3 mg/dL was not observed within 3 days of admission in both groups. Added low-dose DA might not have a harmful effect on renal function and effects of diuresis and symptom relief without a significant increase in troponin-T in AHF patients with diuretic resistance to hANP.

Seasonal variation in patients with acute heart failure: prognostic impact of admission in the summer.

There have been few reports discussing the clinical significance of the season of admission of acute heart failure (AHF) patients. The data of 661 patients with AHF admitted to the intensive care unit were analyzed. Patients were assigned to a summer admission (Group-S, n = 113, between July and September), a winter admission (Group-W, n = 214, between December and February), or to the other seasons admission group (Group-O, n = 334). We evaluated the relationships between the seasonal variations and the clinical profiles, and the long-term prognosis. There were significantly more patients with cardiomyopathy and New York Heart Association class 4, and the serum levels of total bilirubin were significantly higher in Group-S (85.8, 24.8 %, and 0.60 [0.50-0.90]) than in Group-W (75.2, 15.4 %, and 0.60 [0.40-0.78]). The left ventricular ejection fraction on admission was significantly reduced and intravenous administration of dobutamine was used more frequently in Group-S (30.0 [25.0-46.0], 31.9 %) than in Group-W (34.4 [25.2-48.0], 20.6 %) and Group-O (35.0 [25.0-46.0], 19.8 %). The multivariate Cox regression model found that summer admission was independently associated with cardiovascular death (HR: 1.58, 95 % CI 1.01-2.48; p = 0.044) and heart failure (HF) events (HR: 1.55, 95 % CI 1.05-2.28; p = 0.028). The Kaplan-Meier curves showed that the cardiovascular death rate was significantly higher in Group-S than in Group-W and Group-O, and the HF events were significantly higher in Group-S than in Group-O. The summer admission AHF patients included sicker patients, and the prognosis in these patients was worse than in the patients admitted at other times.

Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study.

OBJECTIVE: SSc causes intractable ischaemic ulcers. To avoid major amputation, we examined the safety and efficacy of therapeutic vascular angiogenesis for digital ulcers due to SSc. METHODS: A single-centre, open-label pilot study was conducted in patients with an ischaemic digital ulcer [n = 40, mean age 65 years (s.d. 8), Rutherford class III-5 or III-6) due to lcSSc (n = 11) or arteriosclerosis obliterans (ASO; n = 29). Bone marrow mononuclear cells (0.4-5.1 × 10(10) cells in total) were administered into the ischaemic limbs. We evaluated short-term safety and efficacy by means of a pain scale, (99m)Tc-tetrofosmin scintigraphy and transcutaneous oxygen tension (TcPO2) before and 4 weeks after treatment. Also, the 2-year outcome was compared. RESULTS: There was a case of amputation in each group within 4 weeks after therapy. The pain scale significantly decreased in both groups [lcSSc 93 mm (s.d. 9) to 11 (s.d. 16), P < 0.01; ASO 77 mm (s.d. 22) to 16 (s.d. 13), P < 0.01] and TcPO2 significantly improved [lcSSc 9.0 mmHg (s.d. 9) to 35 (s.d. 14), P < 0.01; ASO 18 mmHg (s.d. 10) to 29 (s.d. 21), P < 0.05). At the 2-year follow-up, the limb amputation rate was 9.1% in lcSSc and 20.7% in ASO (P = 0.36), while the recurrence rate was 18.2% in lcSSc and 17.2% in ASO (P = 0.95). All-cause mortality was 27.3% in lcSSc and 17.2% in ASO (P = 0.65). CONCLUSION: In patients with lcSSc, bone marrow mononuclear cell implantation provides clinical benefit and is safe, without major adverse reactions, and may become an effective strategy. TRIAL REGISTRATION: UMIN-CTR, http://www.umin.ac.jp/ctr/index-j.htm, no. UMIN000004112.

Urgent catheter ablation for sustained ventricular tachyarrhythmias in patients with acute heart failure decompensation.

AIMS: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are not uncommon in patients hospitalized with acute heart failure (AHF). We sought to evaluate the efficacy of urgent radiofrequency catheter ablation (RFCA) for recurrent VT/VF during AHF decompensations. METHODS AND RESULTS: The present study retrospectively analysed the data of 15 consecutive patients (69 ± 9 years, ischaemic heart disease in 10), who underwent urgent RFCA for frequent drug-refractory VT/VF episodes during an AHF decompensation with pulmonary congestion. The target arrhythmias were clinically documented monomorphic VTs in 10 patients, frequent premature ventricular contractions (PVCs) triggering VF in 4, and both in 1. The mean left ventricular ejection fraction was 26 ± 8%. The maximum number of arrhythmia episodes over 24 h was 9.1 ± 11.7. All RFCA sessions were completed without any major complications except for a temporary deterioration of pulmonary congestion in three patients (20%). Elimination and non-inducibility of the target arrhythmias were achieved in 13 patients (87%). Successful ablation site electrograms showed Purkinje potentials for all 5 PVCs triggering VF and 4 of 14 clinically documented monomorphic VTs (29%). Five patients (33%) underwent second sessions 10 ± 4 days after the first session for acute recurrences. Sustained VT/VF was completely suppressed during admission in 12 patients (80%), and the AHF ameliorated in 13 patients (93%). Twelve patients (80%) were discharged alive. CONCLUSION: Urgent RFCA for drug-resistant sustained ventricular tachyarrhythmias during AHF decompensations would be an appropriate therapeutic option. Purkinje fibres can be ablation targets not only in those with PVCs triggering VF, but also in those with monomorphic VT.

Delayed enhancement magnetic resonance imaging in hypertrophic cardiomyopathy with Basal septal hypertrophy and preserved ejection fraction: relationship with ventricular tachyarrhythmia.

OBJECTIVE: This study aimed to determine the relationship between delayed enhancement magnetic resonance imaging (DE MRI) and ventricular tachyarrhythmia in patients with hypertrophic cardiomyopathy (HCM) with basal septal hypertrophy and preserved ejection fraction (EF). METHODS: One hundred seven patients with HCM with basal septal hypertrophy and EF greater than 50% underwent cine and DE MRI. Myocardial scar was identified with DE MRI. We assessed whether patient,s background, cine MRI findings, presence of myocardial scar, or number of scarred myocardial segments was related to the occurrence of ventricular tachyarrhythmia. RESULTS: Patient,s age, family history of HCM, and number of scarred segments differed between the patients with and without the arrhythmia. A family history of HCM and number of scarred segments were significantly related to ventricular tachyarrhythmia (P < 0.01). CONCLUSIONS: The number of scarred segments is the significant DE MRI parameter related to ventricular tachyarrhythmia in HCM with basal septal hypertrophy and preserved EF.

Cyclical mechanical stretch enhances degranulation and IL-4 secretion in RBL-2H3 mast cells.

Mast cells are widely distributed in the body and affect their surrounding environment through degranulation and secretion of cytokines. Conversely, mast cells are influenced by environmental stimuli such as cyclical mechanical stretch (CMS), such as that induced by heartbeat and respiration. Peripherally distributed mast cells are surrounded by extracellular matrix, where they bind IgE on their surface by expressing the high-affinity Fc receptor for IgE (FcεRI), and they release mediators after cross-linking of surface-bound IgE by allergen. To analyse how CMS affects mast cell responses, we examined the effect of applying CMS on the behaviour of IgE-bound mast cells (RBL-2H3 cell line) adhering to fibronectin as a substitute for extracellular matrix. We found that CMS enhanced FcεRI-mediated secretion in the presence of antigen (2,4-dinitrophenol-bovine serum albumin). CMS increased expression of IL-4 mRNA and secretion of IL-4 protein. Western blot analysis showed that CMS changes the signal transduction in mitogen-activated protein kinases and AKT, which in turn alters the regulation of IL-4 and increases the secretion of IL-4. These results suggest that CMS modulates the effect of mast cells on inflammation and resultant tissue remodelling. Understanding how CMS affects mast cell responses is crucial for developing therapies to treat mast cell-related diseases.

Greater insulin resistance indicates decreased diurnal variation in the QT interval in patients with type 2 diabetes.

Circadian variations in the QT interval (QT) and QT dispersion are decreased in patients with type 2 diabetes because of cardioneuropathy. Insulin resistance has been recently identified as an independent determinant of QT prolongation in normoglycemic women. However, the relationship between QT prolongation and the degree of insulin resistance as well as circadian variation remains unclear in diabetic patients. This study was designed to assess the relationship between insulin resistance and the circadian variation in QT measurements in patients with type 2 diabetes. In 14 patients with diabetes, QT, corrected QT (QTc), QT dispersion, QTc dispersion, and RR interval (RR) were analyzed using 12-lead Holter monitoring and commercial software. The degree of diurnal variation in each measurement was defined as the amplitude between the maximum and mean values on curves fitted using the mean cosinor method (A_QT, A_QTc, A_QT dispersion, A_QTc dispersion, and A_RR). The cosine curve was fitted to all measured values in each QT measurement and RR for 24 h. Insulin resistance (glucose infusion rate (GIR)) was measured using the euglycemic hyperinsulinemic glucose clamp method. The maximum QT, QTc, QT dispersion, and QTc dispersion were >450 ms. GIR was significantly correlated with A_QT only (r = 0.59, P < 0.05). GIR was not correlated with other variables, and was dependent only on the circadian variation in QT.

Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study.

BACKGROUND: The prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients. METHODS: A total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone (n = 3966) or the diet plus pravastatin (n = 3866) and followed for 5 years. The incidences of coronary heart disease (CHD), CHD plus cerebral infarction (CI), cardiovascular disease (CVD), and cancer were calculated using the Cox proportional hazards model according to the level of HDL cholesterol (HDL-C). RESULTS: CHD incidence was lower in patients with HDL-C >60-90 mg/dL (-52%, p = 0.0018) and HDL-C > 90 mg/dL (-46%, p = 0.4007) than in patients with HDL-C ≤ 60 mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in patients with HDL-C >60-90 mg/dL than in those with HDL-C ≤ 60 mg/dL in both diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased in patients with HDL-C >60-90 mg/dL. CONCLUSION: Patients not receiving statin therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a significant reduction in CHD without the occurrence of adverse events. TRIAL REGISTRATION: Clinical trials.gov NCT00211705.

[From the Point of View of Health Evaluation and Promotion (Ningen Dock) Facilities].

Since the direct method of LDL measurement is easy and convenient, many health evaluation and promotion facilities adopted it without sufficient discussion after specific health checkups started in Japan. For the purpose of reliable, specific health checkup data, we must review the methods and standardization of LDL measurement. I hope that medical societies, the Ministry of Health, Labour and Welfare, and reagent manufacturers will collaborate.