Functional assessment of tandem coronary artery stenosis by intracoronary optical coherence tomography-derived virtual fractional flow reserve: a case series.

BACKGROUND: Optical coherence tomography (OCT)-derived fractional flow reserve (FFR)-which may be calculated using fluid dynamics-demonstrated an excellent correlation with the wire-based FFR. However, the applicability of the OCT-derived FFR in the assessment of tandem lesions is currently unclear. CASE SUMMARY: We present two cases of tandem lesions in the mid segment of the left anterior descending (LAD) artery which could have assessed accurately by OCT-derived FFR. The first patient underwent wire-based FFR at the far distal site of LAD, showed a value of 0.66. The OCT-derived FFR was calculated, yielding a value of 0.64. In the absence of stenosis at the proximal lesion, the OCT-derived FFR was calculated as 0.79, which was as same as the wire-based FFR obtained after stenting to the proximal lesion. Thus, additional stenting was performed at the distal lesion. The second patient underwent wire-based FFR at the far distal site of LAD, showed a value of 0.76 which was as same vale as OCT-derived FFR. Considering the absence of stenosis in the proximal lesion, the OCT-derived FFR was estimated as 0.88. After coronary stenting in the proximal lesion, the wire-based FFR yielded a value of 0.90. Therefore, additional intervention to the distal lesion was deferred. DISCUSSION: The described reports are the first two cases which performed physiological assessment using OCT in tandem lesions. The OCT-derived FFR might be able to estimate the wire-based FFR and the severity of each individual lesion in patients with tandem lesions.

Correction to: Percutaneous transcatheter closure of high-risk patent foramen ovale in the elderly.

In the original publication of the article, the below sentence were garbled.

Efficacy and safety of percutaneous transcatheter aortic valvuloplasty prior to non-cardiac surgery in Japanese patients with severe aortic stenosis.

This study aimed to investigate the efficacy of percutaneous transcatheter aortic valvuloplasty (PTAV) performed prior to non-cardiac surgery and the safety of non-cardiac surgery after PTAV in elderly Japanese patients. Between March 2012 and August 2018, 14 patients who underwent PTAVs prior to non-cardiac surgery were enrolled. The mean age was 82.2 ± 7.0 years. A total of 9 patients (64.3%) were women. A retrograde approach was selected for 57.1% of the patients. More than 75% of the procedures were performed using echocardiographic imaging. Echocardiographic data including the aortic valve area (AVA), peak aortic valve blood velocity flow (AVF), peak aortic valve pressure gradient (AVPG), and mean AVPG significantly improved after PTAV (AVA; from 0.54 ± 0.11 to 0.80 ± 0.13 cm2, peak AVF; from 4.6 ± 0.8 to 3.8 ± 0.7 m/s, peak AVG; from 87.9 ± 28.0 to 62.2 ± 19.9 mmHg, mean AVG; from 49.8 ± 18.9 to 35.7 ± 11.6 mmHg; p < 0.001, p < 0.001, p < 0.001, p = 0.0012, respectively). Neither complications related to the PTAV procedure nor procedural mortality were noted. Non-cardiac surgery after PTAV was safely performed; there were no significant adverse events during non-cardiac surgery and no in-hospital mortality occurred after non-cardiac surgery. PTAV prior to non-cardiac surgery in elderly Japanese patients with severe aortic stenosis is safe and effective. In addition, non-cardiac surgery after PTAV can be safety performed without adverse events.

Percutaneous transcatheter closure of high-risk patent foramen ovale in the elderly.

The efficacy of percutaneous transcatheter closure for preventing recurrent cerebrovascular events in elderly patients with high-risk patent foramen ovale (PFO) remains unclear, whereas in young patients, it has been shown to effectively prevent the recurrence of embolic stroke. The aim of this study was to investigate the safety and efficacy of percutaneous PFO closure in elderly patients with high-risk PFO. Between September 2012 and October 2018, 14 patients ≥ 60 years old with high-risk PFO underwent percutaneous closure to prevent recurrence of cerebrovascular events. The primary end point was recurrence of cerebrovascular events after closure in elderly patients with high-risk PFO, and the secondary end points were occurrence of device-related complications, cerebral hemorrhage, and new-onset atrial fibrillation (AF). The mean patient age and number of cerebrovascular events before closure were 75.2 ± 6.5 years and 1.7 ± 0.7, respectively. All procedures were successfully performed under general anesthesia by transesophageal echocardiography and using a 25-mm Amplatzer Cribriform device. No procedure-related complications occurred. Patients were followed up for a mean 2.6 ± 1.8 years. No patients experienced device-related complications or recurrent cerebrovascular events. However, one patient had AF-related device closure complications at 1 month postoperatively. In addition, other patient had a cerebral hemorrhage with unknown relationship to PFO closure 3 years postoperatively. Percutaneous closure of high-risk PFO in elderly patients may be as effective and safe as in younger patients. It is crucial to evaluate PFO morphology regardless of age in cases of paradoxical embolism.

Novel predictors of late lumen enlargement in distal reference segments after successful recanalization of coronary chronic total occlusion.

OBJECTIVES: Although successful recanalization of coronary chronic total occlusion (CTO) can induce subsequent positive vascular remodeling in the distal segment, the predictors are not fully understood. The aim of this study was to investigate the extent and predictors related to luminal gain after successful CTO recanalization. METHODS: A total of 134 patients who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for CTO and follow-up angiography were included. Angiographic parameters were assessed qualitatively and quantitatively at baseline and follow-up. Gray-scale IVUS images during the PCI procedure were also analyzed. Lumen diameter (LD) at distal reference on the post-PCI angiogram was compared with corresponding LD at follow-up coronary angiography. RESULTS: At the mean follow-up of 10.0 ± 2.7 months, LD at distal reference was significantly increased by 15.9% from baseline to follow-up (2.06 ± 0.62 vs. 2.30 ± 0.55 mm, p < 0.001). Univariable analysis indicated that the left anterior descending artery (LAD), no moderate or severe calcification, presence of peri-medial high-echoic band on IVUS, and impairment of final coronary flow and small distal reference diameter at baseline were associated with greater late lumen enlargement. Multivariable analysis showed the LAD, no moderate or severe calcification, and small LD at distal reference as independent predictors of greater late lumen enlargement. CONCLUSION: The segment distal to recanalized CTO showed significant late lumen enlargement, especially in the cases with small distal reference, in the LAD, and without moderate or severe calcification.

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.

Mortality impact of post-discharge myocardial infarction size after percutaneous coronary intervention: a patient-level pooled analysis from the 4 large-scale Japanese studies.

It is unknown whether there is a threshold of creatine kinase (CK) or CK-MB affecting the subsequent mortality for post-discharge myocardial infarction (PDMI) after percutaneous coronary intervention. Current study sought to evaluate the impact of PDMI. The study population included 30,051 patients with successful coronary stenting and discharged alive in the pooled patient-level database of 4 Japanese studies (j-Cypher registry, CREDO-Kyoto PCI/CABG registry cohort-2, RESET, and NEXT). During 4.4 ± 1.4 year follow-up, 915 patients experienced PDMI (cumulative 5-year incidence of 3.6%). Among 466 patients with available peak CK ratio (peak CK/upper limit of normal), peak CK ratio (< 3) was present in 21% of patients, while peak CK ratios (≥ 3 and < 5), (≥ 5 and < 10), (≥ 10 and < 30), and (≥ 30) were present in 17, 25, 30, and 7.3% of patients, respectively. The excess mortality risk of patients with relative to those without PDMI for subsequent mortality was significant (adjusted HR 5.12, 95% CI 4.52-5.80, P < 0.001) by the Cox model with PDMI incorporated as the time-updated covariate. However, the mortality risk of patients in the smallest peak CK ratio category (< 3) was insignificant (HR 0.85, 95% CI 0.43-1.71, P = 0.65). In conclusion, despite significant overall mortality risk of PDMI, the mortality risk of small PDMI was similar to that of no PDMI, suggesting the presence of some threshold about infarct size influencing mortality.Trial registrations The Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial (RESET); NCT01035450 and NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT); NCT01303640. J-Cypher and CREDO-Kyoto PCI/CABG registry cohort 2 were not registered into clinical trial database.

Predictors of early restenosis after intracardiac echocardiography guided antegrade balloon aortic valvuloplasty in high-risk or inoperable patients.

Antegrade balloon aortic valvuloplasty (BAV) may be more effective than retrograde BAV. However, early restenosis is found inconstantly within three months after BAV. To evaluate the factor of ER after intracardiac echocardiogram (ICE) guided Antegrade BAV, fifty patients with severe aortic stenosis (AS) underwent BAV procedures with ICE. ER was defined as mean aortic valve pressure gradient (PG) >40 mmHg. During one-year follow-up period, 6 patients died and 2 patients underwent aortic valve replacement. ER was present in 13 patients (26%) at three months after BAV. Procedural, clinical, and hemodynamic data were collected. The mean age of the patient population was 85.4 ± 7.6 years; the mean STS score and EuroSCORE were 7.8 ± 1.1 and 14.6 ± 4.1, respectively. The mean aortic valve PG decreased from 63.4 ± 19.8 to 28.5 ± 10.1 mmHg (p < 0.0001). Baseline characteristics were similar between the two groups. There is no significant difference of mean aortic valve PG immediate after BAV(ER; 29 ± 8.8 mmHg, nonER; 21 ± 6.1 mmHg, p = ns). Univariate analysis showed patients with ER group had significantly higher rate of left ventricular hypertrophy, pulmonary hypertension, and high mean aortic valve PG at admission. Multivariate analysis revealed high mean aortic valve PG at admission as independent predictors of ER. Antegrade BAV may be effective for severe AS. Left ventricular hypertrophy, pulmonary hypertension and high mean PG were predictor of early restenosis. Early intervention should be considered for these patients.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

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.

Antiplatelet therapy discontinuation and stent thrombosis after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry.

BACKGROUND: The influence of antiplatelet therapy discontinuation on the incidence of stent thrombosis, especially very late stent thrombosis, after drug-eluting stent implantation has not been yet fully addressed. METHODS: Relationship between antiplatelet therapy discontinuation and stent thrombosis up to 5years was evaluated in 12,812 consecutive patients undergoing sirolimus-eluting stents (SES) implantation in the j-Cypher registry. Data on status of antiplatelet therapy during follow-up were collected prospectively. RESULTS: Median follow-up interval was 1699days (interquartile range, 1184-1928days). Incidences of definite stent thrombosis were 0.34% at 30days, 0.55% at 1year, and 1.6% at 5years. Dual antiplatelet therapy was maintained in 97.4%, 63%, and 43.9% of patients at 30days, 1year, and 5years, respectively. The rates of stent thrombosis in patients who discontinued both thienopyridine and aspirin were significantly higher in the time intervals of 31-365days, 2-3years and 3-4years, and tended to be higher in the time intervals of 1-2years and 4-5years than those in patients who continued both (31-365days: 1.26% versus 0.2%, P<0.001; 1-2years: 0.59% versus 0.15%, P=0.06; 2-3years: 1.35% versus 0.2%, P=0.004; 3-4years: 1.09% versus 0.25%, P=0.0496; 4-5years: 1.35% versus 0.43%, P=0.17). Patients who discontinued either thienopyridine or aspirin only did not have an excess of stent thrombosis in any time intervals. CONCLUSIONS: In conclusion, discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine or aspirin only, was associated with an increased incidence of late and very late stent thrombosis up to 5years after SES implantation.

A novel peptide of endothelin family, 31 amino-acid length endothelin in patients with acute myocardial infarction.

Human chymase converts big endothelin (ET)-1 to 31-amino acid length ET-1 {ET-1(1-31)} that also possesses a potent vasoconstrictive action. In addition, ET-1(1-31) is an intermediate peptide, which is then readily transformed to mature ET-1 by the neutral endopeptidase 24-11. To investigate the relevance of pathophysiology of ET-1(1-31) in vivo, we have developed specific sandwich-type, enzyme-linked immunosorbent assay to measure the plasma concentration of ET-1(1-31) in healthy volunteers and patients with myocardial infarction. The plasma concentrations of ET-1(1-31) in healthy volunteers were 24.8 ± 5.2 pg/ml (n=11). ET-1(1-31) concentration in plasma was elevated in patients with acute myocardial infarction, and its elevation was several times higher and lasted longer than that of ET-1. In addition, tissue concentration of ET-1(1-31) in the myocardium from a patient with acute myocardial infarction was extremely high (12729.8 ± 2617.7 pg/mg protein). These results suggest that ET-1(1-31) may play some pathological roles in the remodeling, especially in sites where inflammatory cells produced a large amount of proteases, such as myocardial infarction.

Comparison of 5-year outcomes in patients with and without unprotected left main coronary artery disease after treatment with sirolimus-eluting stents: insights from the j-Cypher registry.

OBJECTIVES: This study assessed 5-year outcomes after implantation of sirolimus-eluting stents (SES) for unprotected left main coronary artery (ULMCA) disease in comparison with that for non-left main disease. BACKGROUND: More information on long-term outcomes after ULMCA stenting is needed. METHODS: The j-Cypher is a multicenter prospective registry of consecutive patients undergoing SES implantation in Japan. RESULTS: Among 12,812 patients enrolled in the j-Cypher registry, the unadjusted mortality rate at 5 years was significantly higher in patients with ULMCA stenting than in patients without ULMCA stenting (22.8% vs. 14.1%; p < 0.0001); however, the risk for death with ULMCA stenting was no longer significant after adjusting for confounders (hazard ratio: 1.18, 95% confidence interval: 0.95 to 1.46; p = 0.14). In the lesion-level comparison, the nonbifurcation ULMCA lesions treated exclusively with SES had a significantly lower rate of target lesion revascularization (TLR) than those in non-ULMCA nonbifurcation lesions (2.4% vs. 12.7%; p = 0.04). Among bifurcation lesions, those treated with a provisional 2-stent approach had similar rates of TLR (12.1% vs. 11.4%; p = 0.79) between the ULMCA and non-ULMCA groups. Lesions treated with an elective 2-stent approach had higher TLR rates in the ULMCA group as compared with the non-ULMCA group (33.5% vs. 19.7%; p = 0.002). CONCLUSIONS: The safety of ULMCA stenting relative to non-LMCA stenting was maintained through 5 years follow-up. In terms of efficacy, SES implantation in nonbifurcation ULMCA lesions was associated with an extremely low cumulative incidence of TLR, whereas the elective 2-stent approach for ULMCA bifurcation lesions was associated with a markedly higher cumulative incidence of TLR as compared with that for non-ULMCA bifurcation lesions.

Very late stent thrombosis and late target lesion revascularization after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry.

BACKGROUND: There is a scarcity of long-term data from large-scale drug-eluting stent registries with a large enough sample to evaluate low-frequency events such as stent thrombosis (ST). METHODS AND RESULTS: Five-year outcomes were evaluated in 12 812 consecutive patients undergoing sirolimus-eluting stent (SES) implantation in the j-Cypher registry. Cumulative incidence of definite ST was low (30 day, 0.3%; 1 year, 0.6%; and 5 years, 1.6%). However, late and very late ST continued to occur without attenuation up to 5 years after sirolimus-eluting stent implantation (0.26%/y). Cumulative incidence of target lesion revascularization within the first year was low (7.3%). However, late target lesion revascularization beyond 1 year also continued to occur without attenuation up to 5 years (2.2%/y). Independent risk factors of ST were completely different according to the timing of ST onset, suggesting the presence of different pathophysiological mechanisms of ST according to the timing of ST onset: acute coronary syndrome and target of proximal left anterior descending coronary artery for early ST; side-branch stenting, diabetes mellitus, and end-stage renal disease with or without hemodialysis for late ST; and current smoking and total stent length >28 mm for very late ST. Independent risk factors of late target lesion revascularization beyond 1 year were generally similar to those risk factors identified for early target lesion revascularization. CONCLUSION: Late adverse events such as very late ST and late target lesion revascularization are continuous hazards, lasting at least up to 5 years after implantation of the first-generation drug-eluting stents (sirolimus-eluting stents), which should be the targets for developing improved coronary stents.

In vivo optical coherence tomography of very late drug-eluting stent thrombosis compared with late in-stent restenosis.

BACKGROUND: Autopsy findings have suggested delayed arterial healing as a primary cause of very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation. METHODS AND RESULTS: Optical coherence tomography of DES-treated lesions that developed VLST (n = 6) was compared with that of DES-treated lesions that developed late in-stent restenosis (L-ISR: n = 32) among patients with recurrent ischemia >1 year after DES implantation (mean, 37 ± 17 months), and with the stented segment without any evidence of VLST or L-ISR (no-event: n = 20; mean, 38 ± 19 months). The proportion of uncovered and malapposed struts in each stented segment was evaluated. A total of 961 frames, 9,763 struts were analyzed. The proportion of uncovered struts was higher in the VLST group than in the L-ISR group and the no-event group (29.2 ± 22.8%, 7.9 ± 9.7%, and 7.6 ± 8.0%, respectively; P = 0.0002). The proportion of malapposed struts was higher in the VLST group than in the no-event group (7.3 ± 8.7% vs 1.1 ± 2.4%, P = 0.01). Two patients in the VLST group had lower rates of uncovered and malapposed struts, but this involved lipid-laden-like neointima with disruptions. CONCLUSIONS: Delayed neointimal coverage and incomplete stent apposition were frequently observed in the DES-treated lesions that developed very late thrombosis. Lipid-laden-like neointima with disruption within the DES may be another possible mechanism for very late thrombosis.

Sirolimus-eluting stent implantation for ostial left anterior descending coronary artery lesions: three-year outcome from the j-Cypher Registry.

BACKGROUND: Ostial left anterior descending coronary artery (LAD) lesion has been regarded as a lesion subset unsuitable for coronary stenting. Long-term outcomes of sirolimus-eluting stent (SES) implantation for ostial LAD lesions have not been adequately evaluated. METHODS AND RESULTS: Among 12 824 patients enrolled in the j-Cypher Registry, 3-year outcomes were compared between 481 patients with SES-treated ostial LAD lesions and 5369 patients with SES-treated nonostial proximal LAD lesions. Patients with ostial LAD lesions had similar incidences of target lesion revascularization (TLR) as those with nonostial proximal LAD lesions (9.4% versus 9.7%; P=0.98; adjusted hazard ratio [HR], 0.99; 95% CI, 0.7 to 1.36; P=0.94) and death/myocardial infarction (MI) (10.7% versus 11.4%; P=0.82; adjusted HR, 1.05; 95% CI, 0.76 to 1.4; P=0.77). Among the patients with ostial LAD lesions, those undergoing both main and side branch stenting (n=62) compared to main branch stenting alone (n=419) had a higher risk for TLR (adjusted HR, 4.65; 95% CI, 2.32 to 9.25; P<0.0001) but similar risk for death/MI (adjusted HR, 1.15; 95% CI, 0.49 to 2.41; P=0.73). In patients with main branch stenting alone, outcomes after crossover stenting across the circumflex coronary artery (n=225) were not different from those after ostial stenting (n=194) for TLR (adjusted HR, 0.77; 95% CI, 0.33 to 1.82; P=0.55) and for death/MI (adjusted HR, 1.54; 95% CI, 0.78 to 3.2; P=0.22). CONCLUSIONS: In terms of both safety and efficacy, 3-year outcomes of percutaneous coronary intervention using SES for ostial LAD lesions were comparable to those for nonostial proximal LAD lesions. Crossover stenting with a 1-stent approach might be a reasonable option in treating ostial LAD lesions.