Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts.

Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans. Fibroblast-derived iPSCs were generated from a MHC haplotype (HT4) homozygous animal and subsequently differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intra-myocardial injection of iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection in monkeys treated with clinically relevant doses of methylprednisolone and tacrolimus, and showed electrical coupling with host cardiomyocytes as assessed by use of the fluorescent calcium indicator G-CaMP7.09. Additionally, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks after transplantation; however, the incidence of ventricular tachycardia was transiently, but significantly, increased when compared to vehicle-treated controls. Collectively, our data demonstrate that allogeneic iPSC-CM transplantation is sufficient to regenerate the infarcted non-human primate heart; however, further research to control post-transplant arrhythmias is necessary.

Intensive exercise therapy for restenosis after superficial femoral artery stenting: the REASON randomized clinical trial.

Endovascular treatment (EVT) is the main treatment for peripheral artery disease (PAD). Despite advances in device development, the restenosis rate remains high in patients with femoropopliteal lesions (FP). This study aimed to evaluate the effectiveness of exercise training in reducing the 1-year in-stent restenosis rate of bare metal nitinol stents for FPs. This prospective, randomized, open-label, multicenter study was conducted from January 2017 to March 2019. We randomized 44 patients who had claudication with de novo stenosis or occlusion of the FP into an intensive exercise group (n = 22) and non-intensive exercise group (n = 22). Non-intensive exercise was defined as walking for less than 30 min per session, fewer than three times a week. We assessed exercise tolerance using an activity meter at 1, 3, 6, and 12 months, and physiotherapists ensured maintenance of exercise quality every month. The primary endpoint was instant restenosis defined as a peak systolic velocity ratio > 2.5 on duplex ultrasound imaging. Kaplan-Meier analysis was used to evaluate the data. There were no significant differences in background characteristics between the groups. Six patients dropped out of the study within 1 year. In terms of the primary endpoint, intensive exercise significantly improved the patency rate of bare nitinol stents at 12 months. The 1-year freedom from in-stent restenosis rates were 81.3% in the intensive exercise group and 47.6% in the non-intensive exercise group (p = 0.043). No cases of stent fracture were observed in the intensive exercise group. Intensive exercise is safe and reduces in-stent restenosis in FP lesions after endovascular therapy for PAD. Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry (No. UMIN 000025259).

Prognostic ability of mid-term worsening renal function after percutaneous coronary intervention: findings from the SHINANO registry.

Chronic kidney disease is a prognostic factor for cardiovascular disease. Worsening renal function (WRF), specifically, is an important predictor of mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI). We evaluate the prognostic impact of mid-term WRF after PCI on future cardiovascular events. We examined the renal function data of 1086 patients in the first year after PCI using the SHINANO 5-year registry. Patients were divided into two groups, mid-term WRF and non-mid-term WRF, and primary outcomes were major adverse cardiovascular events (MACE) and death. Mid-term WRF was defined as an increase in creatinine (≥ 0.3 mg/dL) in the first year after PCI. Mid-term WRF was found in 101 patients (9.3%), and compared to non-mid-term WRF, it significantly increased the incidence of MACE (p < 0.001), and all-cause death (p < 0.001), myocardial infarction (p = 0.001). Furthermore, mid-term WRF patients had higher incidence of future heart failure (p < 0.001) and new-onset atrial fibrillation (p = 0.01). Patients with both mid-term WRF and chronic kidney disease had increased MACE compared to patients with either condition alone (p < 0.001). Similarly, patients with mid-term WRF and acute kidney injury had increased MACE compared to patients with either condition alone (p < 0.001). Multivariate Cox regression analysis revealed mid-term WRF as a strong predictor of MACE (hazard ratio: 2.50, 95% confidence interval 1.57-3.98, p < 0.001). Mid-term WRF after PCI negatively affects MACE, as well as future admission due to heart failure and new-onset atrial fibrillation, chronic kidney disease, and acute kidney injury.

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.

The usefulness of brachial-ankle pulse wave velocity in predicting long-term cardiovascular events in younger patients.

Brachial-ankle pulse wave velocity (baPWV) is known as a significant predictor of cardiovascular events. However, the previous studies have not considered age, which can affect the baPWV value. We evaluated the predictive value of baPWV for cardiovascular events in various age groups. From January 2005 to December 2012, all patients admitted to our department with any cardiovascular disease and underwent ankle-brachial index (ABI) measurement were enrolled in the IMPACT-ABI registry. The primary endpoints included major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke). Of the 3131 patients enrolled, 2554 were included in the analysis, whereas 577 were excluded due to missing baPWV data, ABI ≤0.9 and/or >1.4, and the previous endovascular therapy and/or surgical treatment for peripheral artery disease. Patients were divided according to age 30-59 years (n = 580), 60-69 years (n = 730), 70-79 years (n = 862), and ≥80 years (n = 330). The cumulative incidence of MACE through 5 year was significantly higher in the high baPWV group (>1644 cm/s) than in the low baPWV group (≤1644 cm/s; 8.7 vs. 4.6%; log-rank: p < 0.001). However, among the age groups, only the 30-59-year group showed a significant difference in MACE incidence between those with high and low baPWV (7.0 vs. 0.9%; log-rank: p = 0.001). In conclusion, the baPWV could serve as a useful marker to predict cardiovascular events, particularly among younger patients.

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 deteriorated calcium-phosphate homeostasis on amputation-free survival after endovascular revascularization in patients with critical limb ischemia on hemodialysis.

Patients on hemodialysis (HD) have abnormalities of calcium-phosphate (CaP) homeostasis and high CaP product contributes to atherosclerosis pathogenesis and adverse events. Patients on HD with critical limb ischemia (CLI) are at risk for major amputation and death because of advanced systemic atherosclerotic disease. The aim of this study was to evaluate the relationship between CaP product and amputation-free survival (AFS) in CLI after endovascular treatment (EVT). We retrospectively analyzed 221 CLI patients on HD. In Kaplan-Meier analysis, AFS was significantly lower in patients with CaP product ⩾ 55 mg(2)/dL(2) compared to those with CaP product <55 mg(2)/dL(2) (54.3% vs 78.5%, p = 0.002). However, neither serum phosphate nor calcium levels were individually associated with AFS. In multivariate analysis, CaP product ⩾ 55 mg(2)/dL(2) was an independent predictor for AFS in CLI patients on HD (hazard ratio, 3.03; 95% confidence interval, 1.78-5.15; p-value < 0.001). We concluded abnormal CaP homeostasis was associated with lower AFS after EVT in CLI patients on HD, and can serve for their risk stratification.

Characterization of cardiac oxidative stress levels in patients with atrial fibrillation.

Atrial fibrillation (AF) is associated with oxidative stress and elevated brain natriuretic peptide (BNP) levels. However, the exact cardiac origin of oxidative stress and its association with BNP levels in AF patients remain unclear. Therefore, we investigated the chamber-specific plasma oxidative stress levels in patients with paroxysmal AF (PAF) and persistent AF (PSAF). Diacron-reactive oxygen metabolite (dROM) levels were measured in patients with PAF (n = 50) and PSAF (n = 35) at different cardiac sites before ablation and in peripheral vein 3 months after ablation. For all sites, dROM levels were higher in PSAF patients than in PAF patients; the levels were the highest in the coronary sinus at 429.0 (interquartile range: 392.0-449.0) vs. 374.0 (357.0-397.8) Carratelli units (P < 0.05). dROM levels in the coronary sinus were related to the BNP levels (r = 0.436, P < 0.001). Furthermore, the reduction in the peripheral dROM levels was related to that in the peripheral BNP levels in patients with symptomatic improvement (r = 0.473, P < 0.001). Cardiac oxidative stress may either be a cause or consequence of prolonged AF, and cardiac oxidative stress levels correlated with BNP levels, though a possible source of oxidative stress in AF patients may be systemic circulation.

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.

Echocardiographic assessment of the cardiac amyloidoses.

Cardiac amyloidosis is a cardiomyopathy characterized by increased left ventricular (LV) wall thickness and normal or decreased LV cavity size. Congestive heart failure in cardiac amyloidosis is generally considered a predominantly diastolic phenomenon, with systolic dysfunction only occurring in late-stage disease. Echocardiography is a noninvasive, reproducible method of assessing cardiac features and function in cardiac amyloidosis, and some echocardiographic indices are prognostic for the amyloidoses, with M-mode and 2-dimensional echocardiography able to detect increased LV wall thickness. Moreover, Doppler flow measurements can incrementally assess diastolic LV dysfunction, which is characteristic of cardiac amyloidosis, and provide important prognostic information. Additionally, tissue Doppler imaging can detect subtle changes in both systolic and diastolic LV function, which cannot be detected by Doppler flow measurements, and LV longitudinal strain assessed by color tissue Doppler and speckle tracking echocardiography can provide more accurate LV functional and prognostic information than tissue Doppler imaging. This review describes the advances in echocardiography and its crucial role in the diagnosis and management of cardiac amyloidosis.

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.

Five-year prognosis after endovascular therapy in claudicant patients with iliofemoral artery disease.

PURPOSE: To examine the prognosis of patients with intermittent claudication who received treatment with endovascular techniques. METHODS: A retrospective multicenter study was performed involving 2930 consecutive patients (2307 men; mean age 71.5±8.9 years) with intermittent claudication who underwent an endovascular procedure for a de novo iliofemoral artery lesion. The primary outcome measure was overall survival. The secondary outcomes were freedom from major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, and stroke) and from major adverse cardiovascular and limb events (MACE with repeat revascularization or above-knee amputation of the target limb). Cox multivariate regression analysis of selected baseline characteristics, procedure-related complications, and medication use was performed to determine predictors for all-cause mortality. Positive predictors from this analysis were used to stratify patients into low- (1410, 48.1%), moderate- (1406, 48.0%), and high-risk (114, 3.9%) categories. RESULTS: The overall survival rates were 97.2%, 90.8%, and 83.4% at 1, 3, and 5 years, respectively. The cause of death was cardiovascular in 42.8% of cases. Freedom from MACE was 96.7%, 88.6%, and 77.3% at 1, 3, and 5 years, respectively. Cox multivariate regression analysis identified age, dialysis, left ventricular dysfunction, insulin-dependent diabetes, hematoma prolonging hospitalization, coronary artery disease, and superficial femoral plus iliac lesions as positive predictors of all-cause mortality. In the risk stratification analysis, the overall 5-year survival rate was significantly lower in high-risk patients compared to the other groups (90.1% vs. 78.6% vs. 53.5%, p<0.0001). CONCLUSION: The prognosis in patients with intermittent claudication after endovascular therapy was relatively good but extremely poor for the high-risk patient subgroup.

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.