Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease.

BACKGROUND: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version. METHODS AND RESULTS: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively. CONCLUSIONS: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

Comprehensive genetic screening for vascular Ehlers-Danlos syndrome through an amplification-based next-generation sequencing system.

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys-Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.

Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort.

Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.

Geriatric Nutritional Risk Index Predicts Cardiovascular Events in Patients at Risk for Heart Failure.

BACKGROUND: The geriatric nutritional risk index (GNRI) is a simple and objective nutritional assessment tool for elderly patients. Lower GNRI values are associated with a worse prognosis in patients with heart failure (HF). However, few data are available regarding the prognostic effect of the GNRI value for risk stratification in patients at risk for HF.Methods and Results:We retrospectively investigated 1,823 consecutive patients at risk for HF (Stage A/B) enrolled in the IMPACT-ABI Study. GNRI on admission was calculated as follows: 14.89×serum albumin (g/dL)+41.7×body mass index/22. Patients were divided into 2 groups according to the median GNRI value (107.1). The study endpoint was a composite of cardiovascular (CV) events, including CV death and hospitalization for worsening HF. Over a 4.7-year median follow-up, CV events occurred in 130 patients. In the Kaplan-Meier analysis, patients with low GNRI (<107.1, n=904) showed worse prognoses than those with high GNRI (≥107.1, n=919) (20.2% vs. 12.4%, P<0.001). In the multivariable Cox proportional hazards analysis, low GNRI was significantly associated with the incidence of CV events (hazard ratio: 1.48, 95% confidence interval: 1.02-2.14; P=0.040). CONCLUSIONS: The simple and practical assessment of GNRI may be useful for predicting CV events in patients with Stage A/B HF.

Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts.

Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host­graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.

Prognostic value of ankle brachial index for future incident heart failure in patients without previous heart failure: data from the impressive predictive value of ankle brachial index for clinical long term outcome in patients with cardiovascular disease examined by ABI study.

The ankle brachial index (ABI) is regarded as a predictor of future cardiovascular events. However, the relationship between ABI and incident heart failure (HF) in patients without previous HF is poorly understood. This study aimed to assess the prognostic value of ABI for incident HF in patients without previous HF. The IMPACT-ABI study was a retrospective, single-center, cohort study that enrolled and measured ABI in 3131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 307 patients were excluded because of previous HF and high (>1.4) ABI. The remaining 2824 patients were stratified into three groups: low ABI (≤0.9), borderline ABI (0.91-0.99), and normal ABI (1.0-1.4). The primary endpoint was hospitalization for HF. Over a mean 4.8-year follow-up, 105 cases of HF occurred. The cumulative incidence of HF was significantly higher in patients with low and borderline ABIs than in those with normal ABI (19.3 vs. 21.0 vs. 10.4 %, log rank P <0.001). In multivariate Cox proportional hazard analysis, low ABI and borderline ABI were independent predictors of incident HF [hazard ratio (HR) 3.00; 95 % confidence interval (CI) 1.70-5.28; P < 0.001 and HR 2.68; 95 % CI 1.35-5.34; P = 0.005, respectively]. In conclusion, low and borderline ABI were strong predictors for future incident HF in patients without previous HF.

Prediction of 1-year clinical outcomes using the SYNTAX score in patients with prior heart failure undergoing percutaneous coronary intervention: sub-analysis of the SHINANO registry.

Although coronary artery disease (CAD) is common in patients with heart failure (HF), little is known about the prognostic significance of coronary lesion complexity in patients with prior HF undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate whether the coronary Synergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) score could improve risk stratification in HF patients with CAD. Two hundred patients (mean age 73 ± 11 years, left ventricular ejection fraction 49 ± 15 %) with prior HF who underwent PCI were divided into two groups stratified by SYNTAX score (median value 12) and tracked prospectively for 1 year. The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for worsening HF. Adverse events were observed in 39 patients (19.5 %). Patients with high SYNTAX scores (n = 100) showed worse prognoses than those with low scores (n = 100) (26.0 vs. 13.0 %, respectively, P = 0.021). In multivariate Cox-regression analysis, SYNTAX score ≥12 was significantly associated with MACE (hazard ratio: 1.99, 95 % confidence interval: 1.02-3.97; P = 0.045). In patients with prior HF and CAD, high SYNTAX scores predicted a high incidence of MACE. These results suggest that the SYNTAX score might be a useful parameter for improving risk stratification in these patients.

Prognostic Impact of Diastolic Wall Strain in Patients at Risk for Heart Failure.

Diastolic wall strain (DWS) is based on the linear elastic theory, according to which decreased wall thinning during diastole reflects reduced left ventricular compliance and thus increased diastolic stiffness. Increased diastolic stiffness as assessed by DWS is associated with a worse prognosis in patients who have heart failure (HF) with preserved ejection fraction. However, there are no data about the prognostic value of DWS derived by M-mode echocardiography in patients at risk for HF. We retrospectively enrolled 1829 consecutive patients without prior HF who were hospitalized for cardiovascular (CV) diseases in our hospital between 2005 and 2012. Patients were divided into two groups stratified by DWS (median value 0.34). The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for HF. Over a 4.2-year median follow-up, adverse events were observed in 322 patients (17.6%). In Kaplan-Meier analysis, patients with low DWS (≤ 0.34, n = 915) showed worse prognoses than those with high DWS (> 0.34, n = 914) (MACE incidence 39.4% versus 31.9%, P = 0.011). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, and echocardiographic parameters, low DWS (≤ 0.34) was significantly associated with the incidence of MACE (hazard ratio: 1.26, 95% confidence interval: 1.01-1.59; P = 0 .045). In patients without prior HF, DWS is an independent predictor of MACE. Simple assessment of DWS might improve risk stratification for CV events in those patients.

Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction.

The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan-Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction.

Inflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). Kaplan- Meier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 - 1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ(2) = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF15 provided an incremental prognostic value over clinical features.

Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.

The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100µL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n≥12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n≥12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI.

Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction ­ ALPS-AMI study.

BACKGROUND: Statins reduce the incidence of cardiovascular events, but no randomized trial has investigated the best statins for secondary prevention. We compared the efficacy of hydrophilic pravastatin with that of lipophilic atorvastatin in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: A prospective, multicenter study enrolled 508 patients (410 men; mean age, 66.0 ± 11.6 years) with AMI who were randomly assigned to atorvastatin (n=255) or pravastatin (n=253). The target control level of low-density lipoprotein cholesterol (LDL-C) was <100 mg/dl, and patients were followed for 2 years. The primary endpoint was the composite of death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina or congestive heart failure requiring hospital admission, or any type of coronary revascularization. The primary endpoint occurred in 77 patients (30.4%) and in 80 patients (31.4%) in the pravastatin and atorvastatin groups, respectively (hazard ratio, 1.181; 95% confidence interval: 0.862-1.619; P=0.299), whereas greater reductions in serum total cholesterol and LDL-C were achieved in the atorvastatin group (P<0.001 for each). Changes in hemoglobin A1c, brain natriuretic peptide, and creatinine were not significant between the 2 regimens, and safety and treatment adherence were similar. CONCLUSIONS: On 2-year comparison of hydrophilic and lipophilic statins there was no significant difference in prevention of secondary cardiovascular outcome.

Prognostic Significance of Neuroadrenergic Dysfunction for Cardiovascular Events in Patients With Acute Myocardial Infarction.

BACKGROUND: The dysregulation of systemic blood pressure (BP) variation or cardiac neuroadrenergic dysfunction is associated with adverse cardiovascular events. We aimed to clarify the prognostic significance of neuroadrenergic dysfunction for cardiovascular events in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We enrolled 63 AMI patients (mean age, 67±12 years) underwent ambulatory BP monitoring (ABPM) and cardiac iodine-(123)metaiodobenzylguanidine (MIBG) imaging within 4 weeks after AMI onset. We analyzed the circadian BP pattern and heart-to-mediastinum (H/M) MIBG uptake ratio. All the patients were followed for 2 years. The study endpoint was a composite of major adverse cardiovascular events, including all-cause death, MI, coronary revascularization except for the MI culprit lesion, and stroke. Patients with a non-dipper pattern (n=29) or an H/M ratio <1.96 (n=28) had a worse prognosis than those with either a dipper pattern (n=34) or an H/M ratio ≥1.96 (n=35; log-rank, P=0.013 and 0.010, respectively). Patients with both a non-dipper pattern and an H/M ratio <1.96 (n=12) had a significantly worse prognosis than did the other patients (P=0.0020). CONCLUSIONS: Dysregulation of BP variation and cardiac MIBG uptake were associated with cardiovascular events following AMI. Examining ABPM with MIBG imaging may potentially improve risk stratification in these patients.

Electrocardiographic J waves are associated with right ventricular morphology and function: evaluation by cardiac magnetic resonance imaging.

We assessed the relationship between J waves and the ventricular morphology and function using cardiac magnetic resonance imaging (MRI). The 12-lead electrocardiograms (ECGs) of 105 consecutive patients who underwent cardiac MRI were reviewed, and those with signs of arrhythmogenic right ventricular cardiomyopathy, complete left bundle branch block, complete right bundle branch block, or chronic atrial fibrillation, where the J wave is difficult to distinguish, were excluded. The ECGs of the remaining 68 patients were analyzed for the presence of J waves. Ventricular morphologic abnormalities were identified on MRI, based on the largest short-axis diameter in the right and left ventricles (d-RVmax/d-LVmax), the area (a-RVmax/a-LVmax), and the ratio RV/LVmax. The percentage contraction of the RV (PC-RV) was used as a measure of ventricular function. Thirty-two patients (47.0 %) had J waves defined as QRS-ST junction elevation >0.1 mV from baseline in the inferior/lateral leads (J group; 56 ± 15 years; 19 males). Thirty-six patients (53.0 %) did not present J waves (NJ group; 58 ± 15 years; 27 males). The d-RVmax and a-RVmax in the J group were larger than those in the NJ group (41 ± 5.2 vs 36 ± 6.6 mm, P = 0.002 and 14 ± 2.9 vs 12 ± 3.4 cm(2), P = 0.022, respectively). The RV/LVmax ratio in the J group was larger than that in the NJ group (0.83 ± 0.15 vs 0.68 ± 0.15, P < 0.001). The PC-RV in the J group was smaller than that in the NJ group (0.28 ± 0.14 vs 0.36 ± 0.15, P = 0.013). J-wave amplitude was correlated positively with d-RVmax (P = 0.010) and negatively with PC-RV (P = 0.005). These results suggested that J waves are associated with right ventricular morphologic and functional abnormalities.

Diagnostic value of peripheral fractional flow reserve in isolated iliac artery stenosis: a comparison with the post-exercise ankle-brachial index.

PURPOSE: To examine in claudicant patients with aortoiliac lesions the relationship between the post-exercise ankle-brachial index (ABI) and the peripheral fractional flow reserve (p-FFR), a physiological test that has heretofore been used to assess coronary and renal artery stenosis. METHODS: Sixteen male patients (mean age 68.1±7.5 years) with isolated iliac artery lesions detected by ultrasound in 17 limbs were enrolled in this study. Resting ABI was measured and a treadmill test was administered to measure the post-exercise ABI. During angiography, the p-FFR was measured using a pressure guidewire after administration of papaverine to induce hyperemia. Changes in the ABI during exercise and p-FFR at hyperemia were calculated. RESULTS: The mean resting ABI and post-exercise ABI were 0.87±0.12 and 0.65±0.24, respectively. There was no complication during the measurement of p-FFR. The mean p-FFR at hyperemia was 0.71±0.14. A significant linear correlation was observed between post-exercise ABI and p-FFR at hyperemia (r=0.857, p<0.001), which was stronger than the correlation between post-exercise ABI and peak-to-peak pressure gradient at hyperemia (r= -0.626, p=0.013). CONCLUSIONS: Measuring p-FFR appears to be a feasible and safe procedure, and there is a significant linear correlation between post-exercise ABI and p-FFR in aortoiliac lesions. The p-FFR was more accurate than a peak-to-peak pressure gradient in assessing the physiological significance of a stenosis. Though larger studies are required, p-FFR might be used to physiologically assess stenosis in PAD patients with isolated aortoiliac lesions.

Impact of endovascular therapy on oxidative stress in patients with peripheral artery disease.

BACKGROUND: Atherosclerosis is believed to be caused by oxidative stress. Endovascular therapy (EVT) is effective for claudication of patients with peripheral artery disease (PAD). However, its effect on oxidative stress in PAD patients is unknown. Here, the impact of EVT on oxidative stress in PAD patients is investigated. METHODS AND RESULTS: Twenty-five PAD patients (Rutherford stage II or III) who underwent EVT were enrolled. The levels of diacron-reactive oxygen metabolite (d-ROM; an oxidative stress marker), ankle-brachial index (ABI), and maximum walking distance at baseline and at 3 months after EVT were measured. As compared with baseline values, the maximum walking distance and ABI improved significantly after EVT (109.9±104.2 vs. 313.7±271.8m, P<0.0001; 0.61±0.15 vs. 0.91±0.13m, P<0.0001, respectively). The improved exercise capacity and arterial flow induced a significant decrease in d-ROM levels (from 472.8±64.8 to 390.2±46.7U.CARR; P<0.0001). The decrease in d-ROM levels after EVT was more prominent in PAD patients with a high baseline d-ROM level. The increased ABI (r=0.524, P=0.0007) and maximum walking distance (r=-0.416, P=0.039) after EVT were significantly correlated with the decreased d-ROM levels. CONCLUSIONS: The improved exercise capacity and peripheral blood flow induced by EVT decreases oxidative stress in PAD patients.

In-hospital clinical outcomes of elderly patients (≥80 years) undergoing percutaneous coronary intervention.

BACKGROUND: The clinical outcomes of elderly patients (≥80 years old) undergoing percutaneous coronary intervention (PCI) has not been well established, despite recent advances in both devices and techniques. METHODS AND RESULTS: We recruited patients from the SHINANO Registry, a prospective, observational, multicenter, cohort study. From August 2012 to July 2013, a total of 1,923 consecutive patients with 2,250 elective/urgent PCIs (2,105 admissions) (mean age, 71±11 years; ≥80 years, 23%; men, 77%) were enrolled. The primary endpoint was procedural success. The secondary endpoints were in-hospital death and in-hospital major adverse cardiovascular events (MACE). The procedural success rate was significantly lower (83.7% vs. 89.1%, P=0.0001), and the rates of in-hospital mortality and MACE were significantly higher in elderly than in non-elderly patients (3.6% vs. 1.5%, P=0.005; 4.4% vs. 2.3%, P=0.016, respectively). For elective PCI, the rates of procedural success and in-hospital MACE were similar between groups (90.3% vs. 91.3%, P=0.65, 2.3% vs. 1.2%, P=0.2, respectively). On multivariate analysis, being elderly was not an independent predictor of procedural failure (OR, 1.15; CI, 0.81-1.61; P=0.43). CONCLUSIONS: In elderly patients, PCI is safe and feasible. The presence of comorbidities is a more important factor than age alone.

Impact of azelnidipine and amlodipine on left ventricular mass and longitudinal function in hypertensive patients with left ventricular hypertrophy.

BACKGROUND: The impact of long-acting calcium channel blocker (CCB) administration on serial changes in left ventricular (LV) function and morphology in hypertensive patients with LV hypertrophy remains unclear. This study attempted to clarify this impact by comparing the effects of administration of azelnidipine with that of amlodipine using conventional and speckle tracking echocardiography. METHODS: An equal number (16) of 32 hypertensive patients was prospectively assigned to a group administered 5 mg of amlodipine/day or a group administered 16 mg of azelnidipine/day. LV function and morphology was examined by conventional and speckle tracking echocardiography at baseline and at 1, 3, 6, and 12 months after treatment initiation. RESULTS: Both groups were found to have experienced a significant decrease in systolic blood pressure by 1 month after treatment initiation; a significant reduction in septal thickness and LV mass index at 6 and 12 months. Transmitral flow E/A ratio and early diastolic mitral annular velocity at lateral wall significantly improved at 12 months. On the other hand, a significant improvement of global longitudinal strain was observed earlier than the above indexes at 3, 6, and 12 months. Ar-A duration difference was significantly decreased at 3 months. The global circumferential strain improved significantly at 3 months, but there were no significant changes in mid-/apical circumferential and radial strains throughout the study period. CONCLUSION: Azelnidipine has beneficial effects on LV mass regression, transmitral flow, tissue Doppler, and LV longitudinal strain that are comparable to those of amlodipine on the same parameters.

High concentrations of omega-3 fatty acids are associated with the development of atrial fibrillation in the Japanese population.

The favorable effect of fish oils rich in n-3 polyunsaturated fatty acids (PUFAs) on the development of atrial fibrillation (AF) is controversial. The relationship between the serum concentrations of n-3 PUFAs and the incidence of AF is unclear; therefore, in the present study, we aimed to elucidate this relationship. We evaluated the serum concentrations of n-3 PUFAs in 110 patients with AF, 46 patients with ischemic heart disease (IHD) and no AF, and 36 healthy volunteers. Thirty-six patients had a history of IHD (IHD-AF group) and 74 did not (L-AF group). The eicosapentaenoic acid (EPA) levels in the L-AF group were higher than those in the IHD-AF and control groups (117 ± 64, 76 ± 30, and 68 ± 23 µg/ml, respectively); the docosahexaenoic acid (DHA) levels showed the same pattern (170 ± 50, 127 ± 27, and 126 ± 35 µg/ml, respectively). In both the L-AF and IHD-AF groups, the EPA levels in patients with persistent and permanent AF were higher than those in patients with paroxysmal AF (L-AF 131 ± 74 vs. 105 ± 51 µg/ml; IHD-AF 82 ± 28 vs 70 ± 33 µg/ml). Multivariate analysis showed that cases of AF were associated with higher levels of EPA but not DHA. In this Japanese population study, the EPA and DHA levels in patients with L-AF were higher than those in normal subjects. In particular, the EPA level was associated with the incidence of AF. These findings suggest that an excess of EPA might be a precipitating factor of AF.

Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury.

Background- Inflammation plays a key role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury; however, the mechanism by which myocardial I/R induces inflammation remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple-protein complex called the inflammasome. Therefore, we hypothesized that the inflammasome is an initial sensor for danger signal(s) in myocardial I/R injury. Methods and Results- We demonstrate that inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, is crucially involved in the initial inflammatory response after myocardial I/R injury. We found that inflammasomes are formed by I/R and that its subsequent activation of inflammasomes leads to interleukin-1ß production, resulting in inflammatory responses such as inflammatory cell infiltration and cytokine expression in the heart. In mice deficient for apoptosis-associated speck-like adaptor protein and caspase-1, these inflammatory responses and subsequent injuries, including infarct development and myocardial fibrosis and dysfunction, were markedly diminished. Bone marrow transplantation experiments with apoptosis-associated speck-like adaptor protein-deficient mice revealed that inflammasome activation in bone marrow cells and myocardial resident cells such as cardiomyocytes or cardiac fibroblasts plays an important role in myocardial I/R injury. In vitro experiments revealed that hypoxia/reoxygenation stimulated inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, and that hypoxia/reoxygenation-induced activation was mediated through reactive oxygen species production and potassium efflux. Conclusions- Our results demonstrate the molecular basis for the initial inflammatory response after I/R and suggest that the inflammasome is a potential novel therapeutic target for preventing myocardial I/R injury.