Taku Asano

The Significance of Cardiac Sympathetic Nervous System Abnormality in the Long-Term Prognosis of Patients with a History of Ventricular Tachyarrhythmia

Severe left ventricular dysfunction or cardiac sympathetic nervous system (SNS) abnormality predicts cardiac death in various heart diseases, including arrhythmogenic disorders. However, it is not clear whether SNS abnormality predicts sudden cardiac death during long-term follow-up in patients with a history of ventricular tachyarrhythmia. We hypothesized that SNS abnormality would be associated with recurrent ventricular arrhythmic events. Methods: 123I-metaiodobenzylguanidine (MIBG) scintigraphy was performed on 86 patients (mean age ± SD, 46 ± 19 y, 65.1% men) with a history of ventricular tachycardia or fibrillation. 123I-MIBG (111 MBq) was intravenously administered under resting conditions, and planar images were obtained 15 min and 4 h later (anterior view for 6 min; 512 × 512 matrices; zoom ratio, 1.0). SNS activity was assessed using the heart-to-mediastinum ratio on delayed imaging. Results: During about 11 y of follow-up (mean ± SD, 5.2 ± 3.7 y), 3 patients (3.5%) had sudden cardiac death and 21 patients (24.4%) had sustained ventricular tachyarrhythmic events. SNS abnormality, defined as a heart-to-mediastinum ratio of less than 2.8, and left ventricular dysfunction, defined as a left ventricular ejection fraction of less than 50%, were associated with sudden cardiac death or recurrent ventricular tachyarrhythmic events (18/40 patients [45%] with SNS abnormality, vs. 6/46 patients [13%] without, P = 0.004; 9/15 patients [60%] with left ventricular dysfunction, vs. 15/71 patients [21.1%] without, P = 0.008). After adjustment for potential confounding variables such as age, sex, coronary risk factors, medication use, history of structural heart disease, and left ventricular function, SNS abnormality was a powerful predictor of recurrent arrhythmic events, with a hazard ratio of 3.6 [95% confidence interval, 1.4–9.2, P = 0.007]). Further, SNS abnormality had incremental and additive prognostic power in combination with left ventricular dysfunction, with an adjusted hazard ratio of 4.4 [95% confidence interval, 1.9–9.9, P < 0.0001]). Conclusion: SNS abnormality predicted recurrent ventricular tachyarrhythmic events during long-term follow-up. 123I-MIBG scintigraphic evaluations for SNS abnormality may be an option for screening patients at high risk for sudden cardiac death.

Candesartan decreases type III procollagen-N-peptide levels and inflammatory marker levels and maintains sinus rhythm in patients with atrial fibrillation.

This study has evaluated whether candesartans prevent the recurrence of atrial fibrillation (AF) and decrease type III procollagen-N-peptide (PIIINP) levels. A total of 153 patients with AF were enrolled in this study. Three groups of patients were compared; candesartan group was treated with candesartan plus bepridil (n = 52); and carvedilol group with carvedilol plus bepridil (n = 51); and bepridil group with bepridil alone (n = 50). The primary end point was length of time to the recurrence of AF and all patients were ultimately followed-up for 730 days. Serum levels of the biomarkers were measured at baseline and after 24 months. Maintenance of sinus rhythm was achieved in 25 (50%) patients in bepridil group, 37 (73%) in candesartan group, and 34 (67%) in carvedilol group, giving a bepridil group/candesartan group hazard ratio of 0.36 (95% confidence interval 0.21-0.63; P = 0.03). Candesartan significantly decreased PIIINP levels at 24 months than at baseline in sinus rhythm group (0.57 ± 0.02 vs. 0.64 ± 0.05 U/mL, P = 0.04) and did not decrease PIIINP levels in the recurrence group. In conclusions, PIIINP might be related to the possibility of the atrial fibrosis for AF. However, further studies are needed to clarify the relationship between PIIINP and AF.

Late thrombotic events after bioresorbable scaffold implantation: a systematic review and meta-analysis of randomized clinical trials

Aims To compare the long-term safety and efficacy of bioresorbable vascular scaffold (BVS) with everolimus-eluting stent (EES) after percutaneous coronary interventions. Methods and results A systematic review and meta-analysis of randomized clinical trials comparing clinical outcomes of patients treated with BVS and EES with at least 24 months follow-up was performed. Adjusted random-effect model by the Knapp-Hartung method was used to compute odds ratios (OR) and 95% confidence intervals (CI). The primary safety outcome of interest was the risk of definite/probable device thrombosis (DT). The primary efficacy outcome of interest was the risk of target lesion failure (TLF). Five randomized clinical trials (n = 1730) were included. Patients treated with Absorb BVS had a higher risk of definite/probable DT compared with patients treated with EES (OR 2.93, 95%CI 1.37-6.26, P = 0.01). Very late DT (VLDT) occurred in 13 patients [12/996 (1.4%, 95%CI: 0.08-2.5) Absorb BVS vs. 1/701 (0.5%, 95%CI: 0.2-1.6) EES; OR 3.04; 95%CI 1.2-7.68, P = 0.03], 92% of the VLDT in the BVS group occurred in the absence of dual antiplatelet therapy (DAPT). Patients treated with Absorb BVS had a trend towards higher risk of TLF (OR 1.48, 95%CI 0.90-2.42, P = 0.09), driven by a higher risk of target vessel myocardial infarction and ischaemia-driven target lesion revascularization. No difference was found in the risk of cardiac death. Conclusion Compared with EES, the use of Absorb BVS was associated with a higher rate of DT and a trend towards higher risk of TLF. VLDT occurred in 1.4% of the patients, the majority of these events occurred in the absence of DAPT.

Single or dual antiplatelet therapy after PCI

The optimal duration and type of antiplatelet therapy after implantation of a drug-eluting stent (DES) remains uncertain. At the time of the first-in-man implantation of the sirolimus DES in 1999, the protocol-defined dual antiplatelet therapy (DAPT) duration was only 2 months. Subsequently, DAPT duration was extended to 1 year on the basis of anecdotal historical data, and this practice was then incorporated into clinical guidelines. For >1 decade, trialists have sought to compare the safety and efficacy of abbreviated (<6 months) and prolonged (>12 months) DAPT regimens. However, the body of evidence is limited by the heterogeneity of end points, time of randomization, and bleeding criteria used in each trial. Pharmaceutical advances led to the introduction of new ADP-receptor antagonists, which are thought to be more effective than clopidogrel. The ADP-receptor antagonists moved the focus from the optimal duration of DAPT to the potential efficacy of single antiplatelet therapy after DES implantation. In this Review, we summarize the current evidence on the duration of DAPT and the risk of bleeding and adverse cardiac events after DES implantation, and describe the pitfalls of trial interpretation. The ongoing, prospective trials to test single antiplatelet therapy after DES implantation are also discussed.

Change in lumen eccentricity and asymmetry after treatment with Absorb bioresorbable vascular scaffolds in the ABSORB Cohort B trial: a five-year serial optical coherence tomography imaging study.

AIMS The aim of the study was to investigate long-term changes in lumen eccentricity and asymmetry at five years after implantation of the Absorb bioresorbable vascular scaffold (BVS). METHODS AND RESULTS Out of 101 patients from the ABSORB cohort B trial, 28 patients (29 lesions) with serial optical coherence tomography (OCT) examination at four different time points (cohort B1: post-procedure, six months, two, and five years [n=13]; cohort B2: post-procedure, one, three, and five years [n=16]) were evaluated. The longitudinal variance in lumen diameter was assessed by asymmetry index (AI). An asymmetric lesion was defined as AI >0.3. The circularity of the lumen or scaffold was evaluated by the eccentricity index calculated as minimal divided by maximal luminal or scaffold diameter per cross-section. The lowest lumen eccentricity index within a scaffold segment (EIL) <0.7 was defined as an eccentric lesion. Post procedure, an eccentric lesion was observed in 72.4% and became concentric in 93.1% at five years (post EIL 0.67±0.05 vs. five-year EIL 0.80±0.10, p=0.03) with a modest reduction of the lumen area from baseline to five years by 0.75±0.32 mm2. Asymmetric lumen morphology was observed in 93.1% (n=27) post implantation and persisted until five-year follow-up. On serial OCT analyses, there was a substantial increase in the scaffold EI during the first two years (post 0.70±0.06, six months 0.76±0.08, two years 0.85±0.07); then, it remained stable whereas the lumen circularity improved further. There were no significant differences in major adverse cardiac events regarding the lumen morphology over the five-year follow-up. CONCLUSIONS In patients treated with the Absorb BVS, the cross-sectional circularity improved over five years while the variance in longitudinal diameters remained. Regaining of lumen circularity is mainly caused by reshaping of the scaffold during the first two years.

Non-invasive Heart Team assessment of multivessel coronary disease with coronary computed tomography angiography based on SYNTAX score II treatment recommendations: design and rationale of the randomised SYNTAX III Revolution trial

AIMS The aim of this study was to investigate whether a Heart Team decision-making process regarding the choice of revascularisation strategy based on non-invasive coronary multislice computed tomography angiography (MSCT) assessment of coronary artery disease (CAD) is equivalent to the standard-of-care invasive angiography-based assessment in patients with multivessel CAD. METHODS AND RESULTS The SYNTAX III Revolution trial is a prospective, multicentre, all-comers randomised trial that will randomise two Heart Teams to select between surgical and percutaneous treatment according to either an invasive conventional angiography or a non-invasive MSCT angiography assessment in patients with multivessel CAD. The treatment selection by each Heart Team will be guided by the SYNTAX score II calculation. The primary endpoint is the level of agreement according to kappa of the initial decision by the Heart Teams on the modality of the revascularisation based on MSCT and angiography assessments. Secondary endpoints include agreement on the number of vessels requiring treatment and the coronary segments in need of revascularisation. CONCLUSIONS The SYNTAX III Revolution trial will provide valuable information regarding the ability of a purely non-invasive coronary anatomy assessment to select accurately the most appropriate revascularisation strategy for patients with multivessel CAD.

A novel synchronised diastolic injection method to reduce contrast volume during aortography for aortic regurgitation assessment : in vitro experiment of a transcatheter heart valve model

AIMS In the minimalist transcatheter aortic valve implantation (TAVI) era, the usage of transoesophageal echocardiography has become restricted. Conversely, aortography has gained clinical ground in quantifying prosthetic valve regurgitation (PVR) during the procedure. In a mock circulation system, we sought to compare the contrast volume required and the accuracy of aortographic videodensitometric PVR assessment using a synchronised diastolic and standard (non-synchronised) injection aortography. METHODS AND RESULTS Synchronised diastolic injection triggered by the signal stemming from the mock circulation was compared with standard non-synchronised injection. A transcatheter heart valve was implanted and was deformed step by step by advancing a screw perpendicularly to the cage of the valve in order to create increasing PVR. Quantitative measurement of PVR was derived from time-density curves of both a reference area (aortic root) and a region of interest (left ventricle) developed by a videodensitometric software. The volume of contrast required for the synchronised diastolic injection was significantly less than in the non-synchronised injection (8.1 [7.9-8.5] ml vs. 19.4 [19.2-19.9] ml, p<0.001). The correlation between the two methods was substantial (Spearmans coefficient rho ranging from 0.991 to 0.968). Intraobserver intra-class correlation coefficient for both methods of injection was 0.999 (95% CI: 0.996-1.000) for the synchronised diastolic and 0.999 (95% CI: 0.996-1.000) for the non-synchronised injection group. The mean difference in the rating was 0.17% and limits of agreement were ±1.64% for both groups. CONCLUSIONS A short synchronised diastolic injection enables contrast volume reduction during aortography without compromising the accuracy of the quantitative assessment of PVR using videodensitometry.

TCT-49 Two-year clinical outcome of Everolimus-eluting bioresorbable scaffold vs. durable polymer everolimus-eluting metallic stent in patients with ST-segment elevation myocardial infarction: results of the randomized ABSORB ST-segment elevation myocardial infarction-TROFI II trial.

In the TROFI II randomized trial, it was demonstrated that stenting of culprit lesions with bioresorbable vascular scaffolds (Absorb [Abbott Vascular, Santa Clara, CA, USA]) in the setting of ST-segment elevation myocardial infarction (STEMI) resulted in a nearly complete arterial healing and low

A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an everolimus-eluting durable polymer stent (Xience) after percutaneous coronary intervention (DESSOLVE III): a randomised, single-blind, multicentre, non-inferiority, phase 3 trial

BACKGROUND MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population. METHODS We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland. Eligible participants were any patients aged at least 18 years who underwent percutaneous coronary intervention in a lesion and had a reference vessel diameter of 2·50-3·75 mm. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus-eluting durable polymer stent (Xience). Randomisation was done by local investigators via web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint (DOCE)-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between the groups at 12 months after the procedure assessed by intention-to-treat. A margin of 4·0% was defined for non-inferiority of the MiStent group compared with the Xience group. All participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02385279. FINDINGS Between March 20, and Dec 3, 2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with 1037 lesions were assigned to MiStent, of whom 697 received the index procedure, and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received the index procedure. At 12 months, the primary endpoint had occurred in 40 patients (5·8%) in the sirolimus-eluting stent group and in 45 patients (6·5%) in the everolimus-eluting stent group (absolute difference -0·8% [95% CI -3·3 to 1·8], pnon-inferiority=0·0001). Procedural complications occurred in 12 patients (1·7%) in the sirolimus-eluting stent group and ten patients (1·4%) in the everolimus-eluting stent group; no clinical adverse events could be attributed to these dislodgements through a minimum of 12 months of follow-up. The rate of stent thrombosis, a safety indicator, did not differ between groups and was low in both treatment groups. INTERPRETATION The sirolimus-eluting bioabsorbable polymer stent was non-inferior to the everolimus-eluting durable polymer stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. MiStent seems a reasonable alternative to other stents in clinical practice. FUNDING The European Cardiovascular Research Institute, Micell Technologies (Durham, NC, USA), and Stentys (Paris, France).

EARLY, LATE AND VERY LATE INCIDENCE OF BIORESORBABLE SCAFFOLD THROMBOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS AND OBSERVATIONAL REGISTRIES

Background: The development of bioresorbable vascular scaffolds (BVS) aimed at improving the long-term safety profile of PCI. However, there is scarce data on the rate of late and very late thrombosis after BVS implantation. Methods: A systematic review of the published literature between October