Differences in Intravascular Ultrasound Measurement Values Between Treatment Modalities for Restenosis in Femoropopliteal Lesions.

BACKGROUND: The risk of restenosis after intervention is higher in femoropopliteal than in aortoiliac lesions. However, the appropriate endovascular therapy (EVT) for preventing restenosis after intervention for femoropopliteal lesions remains unknown. This study aimed to elucidate the relationship between lesion characteristics and patency after EVT using intravascular ultrasound (IVUS) measurement and to determine the predictors of restenosis on IVUS.Methods and Results:This prospective observational study was performed at 18 Japanese centers. We evaluated the lesion characteristics before and after EVT for femoropopliteal lesion using IVUS. Angiographic or duplex ultrasound follow-up was performed at 1 year after EVT. A total of 263 lesions underwent EVT between December 2016 and December 2017. In total, 20 lesions (8 cases of isolated common femoral artery lesion and 12 cases of restenosis lesion) were excluded, and 243 lesions were enrolled in this study. A total of 181 lesions were treated with stent placement, and 62 lesions were treated only with balloon angioplasty. In the case of stent use, a larger distal plaque burden was associated with restenosis, while a lower calcification angle was associated with higher patency in the case of balloon angioplasty alone. CONCLUSIONS: The factors related to patency differed depending on the treating modality. The findings suggest that IVUS is a useful tool for predicting patency because it can provide a more accurate evaluation after EVT for femoropopliteal lesions.

Association between J-CTO score and long-term target lesion revascularization rate after successful chronic total coronary occlusion angioplasty (from the J-CTO Registry).

OBJECTIVES: The aim of this study was to evaluate the impact of the J-CTO score on long-term target lesion revascularization (TLR) after successful native chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). BACKGROUND: We previously reported that the J-CTO score could be used to stratify the lesion complexity and procedural success rate in CTO lesions. METHODS: We evaluated the prognostic significance of a high J-CTO score for long-term TLR rate in the J-CTO Registry. RESULTS: In the 425 lesions of 408 patients who underwent successful CTO-PCI during a median follow-up of 63.0 (interquartile range: 21.2-72.9) months in the J-CTO Registry, the cumulative incidence of TLR of lesions with a J-CTO score ≥ 2 (n = 216) was significantly higher than in those with a J-CTO score ≤ 1 (n = 209) (27.0 versus 19.4% at 5 years, respectively, P = 0.04). Among 323 lesions of 309 patients with a complete 5-year follow-up, the rate of TLR was 28% (n = 91). A J-CTO score ≥ 2 was independently associated with a higher risk of TLR (odds ratio, 1.73; 95% confidence interval, 1.01-2.99, P = 0.048) even after adjustment for clinically relevant baseline factors. CONCLUSIONS: Patients with high J-CTO score lesions had a higher 5-year risk of TLR.

Randomized comparison between 2-link cell design biolimus A9-eluting stent and 3-link cell design everolimus-eluting stent in patients with de novo true coronary bifurcation lesions: the BEGIN trial.

The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs.

The renoprotective effect and safety of a DPP-4 inhibitor, sitagliptin, at a small dose in type 2 diabetic patients with a renal dysfunction when changed from other DPP-4 inhibitors: REAL trial.

BACKGROUND: We conducted the multicenter, prospective, open-label study in type 2 diabetic (T2DM) patients with renal dysfunction, to clarify the efficacy and the safety in relation to renal function and glycemic control, and the economic effect when other dipeptidyl peptidase-4 (DPP-4) inhibitors were switched to a small dose of sitagliptin depending on their renal function. METHODS: Vildagliptin, alogliptin, or linagliptin received for more than 2 months were changed to sitagliptin at 25 or 12.5 mg/day depending on their renal function in 49 T2DMs. Renal function and glycemic control, and the drug cost were assessed during 6 months. RESULTS: Estimated glomerular filtration rate was not changed in patients not on hemodialysis (n = 29). The HbA1c levels were not altered in all of the patients including those on hemodialysis (n = 20). The active glucagon-like peptide-1 levels or other renal parameters were not altered significantly. There were no adverse events to be related to the drugs. The daily drug expense was reduced by 88.1 yen per patient. CONCLUSION: Switching to a small dose of sitagliptin according to the renal function in T2DM patients with renal dysfunction demonstrated the same efficacy and safety as those with other full-dose DPP-4 inhibitors, indicating a therapeutic option with a high cost performance.

Fragmented QRS Is a Novel Risk Factor for Ventricular Arrhythmic Events After Receiving Cardiac Resynchronization Therapy in Nonischemic Cardiomyopathy.

INTRODUCTION: A fragmented QRS (fQRS) is reported to be associated with a poor prognosis or sudden cardiac death (SCD) in patients with Brugada syndrome or ischemic heart disease. However, no studies have clarified the impact of the presence of an fQRS on SCD or ventricular arrhythmic events in patients receiving cardiac resynchronization therapy (CRT). This study aimed to clarify this point in patients with nonischemic cardiomyopathy. METHODS AND RESULTS: This study included 137 heart failure patients with nonischemic cardiomyopathy who received CRT (NYHA functional class: II/III/IV = 25/84/28). The 12-lead ECGs before and after CRT were analyzed. The presence of an fQRS was decided in accordance with the definition in previous papers. Before the CRT, an fQRS was observed in 67 patients (fQRS-pre; 49%). However, it was masked in 35 (52% of fQRS-pre) patients after the CRT. Inversely, in 70 patients in whom an fQRS was absent before the CRT, it appeared after the CRT in 15 (21%) patients. As a result, 47 patients (34%) had an fQRS after the CRT (fQRS-post), and it was less than that before the CRT (P = 0.014). During 18 months of follow-up, SCD or ventricular arrhythmic events were observed more frequently in patients with an fQRS-post than in those without (36.2% vs. 3.3%, P < 0.001). A Cox regression analysis revealed that an fQRS-post was significantly associated with those events (hazard ratio = 9.18; 95% confidence interval = 2.45-34.48, P = 0.001). CONCLUSION: In patients with nonischemic cardiomyopathy who received CRT, an fQRS-post was independently associated with SCD or ventricular arrhythmic events.

Value of 3-Dimensional Speckle Tracking Echocardiography in the Prediction of Microvascular Obstruction and Left Ventricular Remodeling in Patients With ST-Elevation Myocardial Infarction.

BACKGROUND: In patients with myocardial infarction (MI), microvascular obstruction (MVO) determined by cardiac magnetic resonance imaging (CMR) is associated with left ventricular (LV) remodeling and worse prognosis.Methods and Results:In 71 patients with ST-segment elevation MI (STEMI) treated by primary percutaneous coronary intervention (PCI), speckle tracking echocardiography (STE) and CMR were performed early after PCI. All patients underwent CMR at 6 months after hospital discharge to assess the occurrence of LV remodeling. The values of 3-dimensional (3D)-circumferential strain (CS), area change ratio (ACR), and 2-dimensional (2D)-CS were significantly different for the transmural extent of infarct, whereas the values of 3D- and 2D- longitudinal strain (LS) were not significantly different. In transmural infarct segments, the values of 3D-CS and ACR were significantly lower in segments with MVO than in those without MVO. At 6-month follow-up, LV remodeling was observed in 22 patients. In multivariable logistic regression models, global 3D-CS and ACR were significant determinants of LV remodeling rather than the number of MVO segments. CONCLUSIONS: Regional 3D-CS and ACR reflected the transmural extent of infarct and were significantly associated with the presence of MVO. In addition, global 3D-CS and ACR were preferable to the extent of MVO in the prediction of LV remodeling.

Enhancement patterns detected by multidetector computed tomography are associated with microvascular obstruction and left ventricular remodelling in patients with acute myocardial infarction.

AIMS: This study evaluated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) for detecting microvascular obstruction (MVO) and left ventricular (LV) remodelling revealed by DE magnetic resonance imaging after acute myocardial infarction (AMI). METHODS AND RESULTS: In 92 patients with first AMI, MDCT without iodine reinjection was performed immediately following successful percutaneous coronary intervention (PCI). Delayed-enhancement magnetic resonance imaging performed in the acute and chronic phases was used to detect MVO and LV remodelling (any increase in LV end-systolic volume at 6 months after infarction compared with baseline). Patients were divided into two groups according to the presence (n = 33) or absence (n = 59) of heterogeneous enhancement (HE). Heterogeneous enhancement was defined as concomitant presence of hyper- and hypoenhancement within the infarcted myocardium on MDCT. Microvascular obstruction and LV remodelling were detected in 49 (53%) and 29 (32%) patients, respectively. In a multivariable analysis, HE and a relative CT density >2.20 were significant independent predictors for MVO [odds ratio (OR) 13.5; 95% confidence interval (CI), 2.15-84.9; P = 0.005 and OR 12.0; 95% CI, 2.94-49.2; P < 0.001, respectively). The presence of HE and relative CT density >2.20 showed a high positive predictive value of 93%, and the absence of these two findings yielded a high negative predictive value of 90% for the predictive value of MVO. Heterogeneous enhancement was significantly associated with LV remodelling (OR 6.75; 95% CI, 1.56-29.29; P = 0.011). CONCLUSION: Heterogeneous enhancement detected by MDCT immediately after primary PCI may provide promising information for predicting MVO and LV remodelling in patients with AMI.

Efficacy of Endeavor zotarolimus-eluting stent implantation for the treatment of very late stent thrombosis with late-acquired incomplete stent apposition after sirolimus-eluting stent implantation.

Very late stent thrombosis (VLST) is a serious complication after percutaneous coronary intervention. However, the best therapy for VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage remains unknown. In these cases, neointimal coverage was nearly complete and no late-acquired malapposition was detected at 18 months after Endeavor zotarolimus-eluting stent (ZES) implantation for the treatment of VLST with late-acquired incomplete stent apposition after sirolimus-eluting stent implantation. We presented that Endeavor ZES implantation may become an attractive therapeutic strategy for the treatment of VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage.

Difference in the Clinical Characteristics of Ventricular Fibrillation Occurrence in the Early Phase of an Acute Myocardial Infarction Between Patients With and Without J Waves.

INTRODUCTION: We recently showed that the presence of J waves increases the risk of ventricular fibrillation (VF) occurrence in the early phase of an acute myocardial infarction (AMI). This study aimed to evaluate the clinical characteristics of VF occurrences in the early phase of an AMI between patients with and without J waves. METHODS AND RESULTS: This retrospective, observational study included 281 consecutive patients with an AMI (69 ± 12 years; 207 men) in whom 12-lead ECGs before AMI onset could be evaluated. The patients were classified based on a VF occurrence <48 hours after AMI onset and the presence of J waves. J waves were electrocardiographically defined as an elevation of the terminal portion of the QRS complex of >0.1 mV from baseline in at least 2 contiguous inferior or lateral leads. VF occurred in 24 patients, and J waves were present in 37. VF occurrence was more prevalent in the patients with than without J waves (27% vs. 6%; P < 0.001). Among the 244 patients without J waves, peak creatine kinase level (P < 0.01), number of diseased coronary arteries (P < 0.01), and male sex (P < 0.05) were higher in the patients with than without VF occurrence. However, among the 37 patients with J waves, there was no significant difference in these variables. There was no association between the location of J waves and the infarct area. CONCLUSIONS: In patients with AMI, those with J waves were more likely to develop VF and less likely to have high-risk clinical characteristics than those without J waves.

Impaired subendocardial wall thickening and post-systolic shortening are signs of critical myocardial ischemia in patients with flow-limiting coronary stenosis.

BACKGROUND: The early diagnosis of myocardial ischemia is still challenging. The aim of the present study was to determine whether subendocardial hypokinesis and post-systolic contraction could be early markers of myocardial ischemia. METHODS AND RESULTS: Thirty-one consecutive patients with flow-limiting severe coronary stenosis but without visually abnormal left ventricular wall motion underwent quantitative echocardiography. Myocardial strain was measured using layer-by-layer analysis in severely hypoperfused segments. Radial strain (RS) was measured in the subendocardial, subepicardial, and total wall (innerRS, outerRS, and totalRS, respectively). Circumferential strain (CS) was also measured as 3 separate layers: subendocardial, mid-layer, and subepicardial layers (innerCS, midCS, and outerCS, respectively). Post-systolic shortening (PSS) was defined as the peak strain after end systole, and post-systolic strain index (PSI) was calculated as PSS divided by end-systolic strain. TotalRS was similar between ischemic and normally perfused segments, but innerRS and inner/outer RS ratio were significantly smaller in the ischemic segments than in corresponding segments in healthy subjects. Receiver operating characteristic analysis identified an optimum cut-off for PSI of 0.6. The combined criteria of inner/outer RS ratio <1.0 and PSI >0.6 achieved 95% specificity for the presence of flow-limiting stenosis. CONCLUSIONS: Combined assessment of both subendocardial contractile impairment and PSS is very useful in identifying a severely hypoperfused left ventricular wall even without visual wall motion abnormality.

Mechanistic implication of decreased plasma atrial natriuretic peptide level for transient rise in the atrial capture threshold early after ICD or CRT-D implantation.

PURPOSE: Despite the use of steroid-eluting leads, a transient but not persistent rise in the atrial/ventricular capture threshold (TRACT/TRVCT) can occur early after pacemaker implantation in patients with sick sinus syndrome. This study aimed to assess the prevalence, predictors, and mechanisms of TRACT/TRVCT in patients with heart failure undergoing implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) implantation. METHOD: One hundred twenty consecutive patients underwent ICD (N = 70) or CRT (N = 50) implantation. Capture threshold was measured at implantation, 7-day, 1-month, and 6-month post-implantation. TRACT/TRVCT was defined as a threshold rise at 7 days by more than twice the height of the threshold at implantation, with full recovery during follow-up. Atrial and brain natriuretic peptide (ANP and BNP) levels were measured before implantation. RESULTS: TRACT and TRVCT were observed in 13 (11%) and 10 (8%) patients, respectively. Patients with TRACT had lower ANP level (median 72 [42-105] vs. 99 [49-198] pg/mL, P = 0.06), lower ANP/BNP ratio (0.29 [0.20-0.36] vs. 0.50 [0.33-0.70], P < 0.01), lower atrial sensing amplitude (2.0 ± 0.8 vs. 2.7 ± 1.3 mV, P = 0.02), and lower left ventricular ejection fraction (32 ± 12 vs. 40 ± 14%, P = 0.04) than those without TRACT. TRACT recovered within 1 month, whereas TRVCT recovered within 6 months. In multivariable analysis, ANP/BNP ratio was the only independent predictor of TRACT (OR, 0.018; 95% CI, 0.001-0.734; P = 0.034). CONCLUSIONS: Atrial degenerative change characterized by lower ANP/BNP ratio was associated with the occurrence of TRACT in patients with heart failure. TRVCT could also occur, but it required a longer recovery time than TRACT.

Intrinsic insulin secretion capacity might be preserved by discontinuing anti-programmed cell death protein 1 antibody treatment in 'anti-programmed cell death protein 1 antibody-induced' fulminant type 1 diabetes.

Intrinsic insulin secretion capacity may be preserved by discontinuing anti-PD-1 antibody treatment in 'anti-PD-1 antibody-induced'fulminant type 1 diabetes.

Is renoprotection by angiotensin receptor blocker dependent on blood pressure?: the Saitama Medical School, Albuminuria Reduction in Diabetics with Valsartan (STAR) study.

To explore the effects of various antihypertensive regimes on microalbuminuria, an angiotensin II receptor blocker (ARB), valsartan, was substituted for or added to treatment with a calcium channel blocker (CCB). After a 6-month CCB baseline period, 28 Japanese hypertensive patients with incipient diabetic nephropathy (defined as a urinary albumin excretion [UAE] of 30-300 mg/g creatinine), were assigned to two groups according to their blood pressure (BP) levels: in patients with a BP of more than 130/85 mmHg (n=17), valsartan was added to the CCB (Group A), while in patients with a BP <130/85 mmHg, valsartan alone was given (Group B: n=11) for 12 months. UAE was determined before and at 3, 6 and 12 months after the initiation of ARB. Although the initial BP was significantly higher in Group A (150/83 mmHg) than Group B (127/77 mmHg), BP was decreased to 141/78 mmHg in Group A and slightly, but not significantly, increased to 130/82 mmHg in Group B. In both groups, UAE was significantly decreased after ARB treatment (to 89% of the basal value in Group A and to 40.5% of the basal value in Group B) and did not differ each other and the amount of decrease did not differ significantly between the two groups. These results suggest that combination therapy with an ARB and CCB is very effective in lowering BP and UAE in cases in which BP is not well controlled, while, even in patients with a sufficient BP control of <130/85 mmHg, the use of ARB singly resulted in a significant decrease in UAE without a further decrease in BP, implying that the ARB had a renoprotective action independent of changes in BP.

The ReACT Trial: Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial.

OBJECTIVES: The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan. BACKGROUND: The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately. METHODS: In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up. RESULTS: Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range [IQR]: 3.1 to 5.2 years), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p < 0.001), although the difference between the 2 groups attenuated over time with a similar cumulative 5-year incidence (19.6% vs. 18.1%; log-rank p = 0.92). CONCLUSIONS: No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial [ReACT]; NCT01123291).

Impact of J-CTO score on procedural outcome and target lesion revascularisation after percutaneous coronary intervention for chronic total occlusion: a substudy of the J-CTO Registry (Multicentre CTO Registry in Japan).

AIMS: We investigated the impact of the J-CTO score, a pre-procedural risk score for successful guidewire crossing within 30 minutes through chronic total occlusion (CTO) lesions, on procedural and midterm clinical outcomes in terms of target lesion revascularisation (TLR) after CTO recanalisation. METHODS AND RESULTS: The primary endpoint of this substudy was midterm TLR. The net midterm success rate was calculated by multiplying the lesion success rate by the TLR-free survival rate. The initial lesion success rates according to the J-CTO score categories of 0, 1, 2, and ≥3 were 97.0%, 92.1%, 86.5%, and 73.6%, respectively (p<0.001). The TLR rates at one year according to the J-CTO score categories of 0, 1, 2, and ≥3 were 5.3%, 11.1%, 16.7%, and 13.4%, respectively (p=0.082). The net midterm success rates according to the J-CTO score categories of 0, 1, 2, and ≥3 were 91.9%, 81.9%, 72.1%, and 63.7%, respectively (p<0.001). CONCLUSIONS: Patients with CTO lesions with lower J-CTO scores are expected to achieve a high procedural success rate and an increased TLR-free survival rate. Patients with high J-CTO scores still remain an issue.

Postmortem magnetic resonance imaging (PMMRI) demonstration of reversible injury phase myocardium in a case of sudden death from acute coronary plaque change.

We report a case of sudden death from acute coronary plaque change in which postmortem magnetic resonance imaging (PMMRI) detected reversible injury phase myocardium. Postmortem computed tomography (PMCT) of the chest showed diffuse ground-glass attenuation (GGA) in both lungs, suggesting pulmonary edema due to cardiac pump failure. T2-weighted imaging (T2WI) of PMMRI delineated the left anterior descending coronary artery (LAD) territory as showing high signal intensity relative to the remaining myocardium. Therefore, we presumed the cause of death was myocardial infarction (MI) of the LAD territory. Autopsy showed acute plaque change in the LAD, however, there were no indications of MI. In this case, autopsy imaging using PMCT and PMMRI was useful as a guide for autopsy.

Physiological changes in circulating mannose levels in normal, glucose-intolerant, and diabetic subjects.

Mannose is an essential hexose that is required for glycoprotein synthesis. Although circulating mannose levels are known to be influenced by metabolic disorders, how physiological levels of mannose fluctuate in normal and diabetic subjects is largely unknown. We describe a new accurate and sensitive assay for determining circulating mannose levels, which we used to measure plasma mannose levels in 273 normal and diabetic (DM) subjects. Our results revealed a clear correlation (r = 0.754) between fasting plasma mannose (FPM) and fasting plasma glucose (FPG) levels. Our mannose assay showed sensitivity and specificity comparable to that seen for hemoglobin A(1c) (HbA(1c)) assay in subjects with impaired glucose tolerance (IGT) or DM whose FPG levels were normal. Mannose levels were found to increase less than glucose levels in response to an oral glucose tolerance test (OGTT). Furthermore, plasma mannose levels did not significantly change following a meal and more closely correlated with the coefficient of variation (CV) of daily glucose levels than did glucose itself. In conclusion, the close correlation between FPM and FPG levels taken together with the small fluctuations seen in plasma mannose in response to glucose suggests that the measurement of mannose using our assay could potentially play a supplementary role in the diagnosis and screening of patients with mild DM.