Impact of Periprocedural Myocardial Injury on Long-Term Outcomes After Percutaneous Coronary Intervention Requiring Atherectomy.

The prognostic implications of cardiac troponin elevation after percutaneous coronary intervention (PCI) with atherectomy have not been established. The aim of this study was to investigate the incidence of periprocedural myocardial injury (PMI) and its association with cardiovascular events in patients with severely calcified lesions who underwent PCI with atherectomy. The study analyzed 346 patients (377 lesions) who underwent PCI with atherectomy between January 2018 and December 2021. Peak post-PCI high-sensitivity cardiac troponin (hs-cTn) was measured. The primary outcome was target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction, and clinically driven target lesion revascularization. A lesion-based analysis was conducted to assess the association of PMI with TLF up to 5 years after PCI. Increase of hs-cTn was seen with 362 lesions (96%), and significant PMI, defined as hs-cTn increase ≥70 × upper reference limit, was seen with 83 lesions (22%). Significant PMI was associated with a significantly greater risk of TLF (adjusted hazard ratio 1.93, 95% confidence interval 1.12 to 3.30, p = 0.017), primarily driven by an increased risk of cardiovascular death (adjusted hazard ratio 5.29, 95% confidence interval 1.46 to 19.16, p = 0.011). In conclusion, hs-cTn increase was frequently observed in patients who underwent PCI with atherectomy, and significant PMI was associated with an increased risk of TLF and cardiovascular death.

Progressive worsening of aortic regurgitation due to detachment of the aortic valve commissure with multimodality imaging to elucidate pathogenesis: a case report.

Background: Aortic regurgitation (AR) associated with detachment of the aortic valve commissure is extremely rare. We present a case of progressively worsening severe chronic AR due to detachment of the aortic valve commissure during hospitalization that was confirmed with multimodality imaging. Case summary: A 50-year-old male with Marfan syndrome visited our hospital to receive treatment for cholelithiasis. Pre-operative examination revealed severe AR and aortic root aneurysm. Because the patient was asymptomatic, it was decided that cholecystectomy should be performed first. However, the patient's heart failure worsened acutely when his blood pressure increased just before induction of anaesthesia. The patient required intubation and management of heart failure. Five days later, the patient underwent cholecystectomy. He was treated for heart failure and underwent open heart surgery on the 35th hospital day. Intraoperative transoesophageal echocardiography revealed that his AR was caused by both enlargement of the aortic root and localized dissection of the aortic valve commissure, which was supported by intraoperative findings and histopathological evaluation. Aortic regurgitation was exacerbated by a new localized dissection, resulting in acute worsening of heart failure. Discussion: Aortic valve commissure detachment can easily lead to sudden onset of severe AR, deteriorating haemodynamics, and acute pulmonary oedema. Since delayed medical treatment leads to poor clinical outcomes, prompt and accurate diagnosis and appropriately timed surgical intervention are essential. This very rare case of severe AR worsening due to spontaneous aortic valve commissure dissection was evaluated with multiple modalities during hospitalization. Understanding this clinical condition will help cardiologists provide better medical care.

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

Intralesional pentraxin 3 increases with atherosclerotic disease progression, but may protect from thrombosis: Friend or foe?

AIM: To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). MATERIALS AND METHODS: PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. RESULTS: Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 ± 2.77 ng/100 mg tissue, n = 8 vs 0.24 ± 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry-positive area percentage: 2.88 ± 0.53 %, n = 22 vs 0.67 ± 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry-positive area percentage than those who would develop restenosis (n = 12) (2.32 ± 0.49 % vs 0.49 ± 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. CONCLUSIONS: PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects.

Guideline-Directed Medical Therapy for Elderly Patients With Acute Myocardial Infarction Who Undergo Percutaneous Coronary Intervention　- Insights From a Retrospective Observational Study.

BACKGROUND: The efficacy of guideline-directed medical therapy (GDMT) in the elderly remains unclear. This study evaluated the impact of GDMT (aspirin or a P2Y12inhibitor, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ß-blocker, and statin) at discharge on long-term mortality in elderly patients with acute myocardial infarction (AMI) who had undergone percutaneous coronary intervention (PCI).Methods and Results: Of 2,547 consecutive patients with AMI undergoing PCI in 2009-2020, we retrospectively analyzed 573 patients aged ≥80 years. The median follow-up period was 1,140 days. GDMT was prescribed to 192 (33.5%) patients at discharge. Compared with patients without GDMT, those with GDMT were younger and had higher rates of ST-segment elevation myocardial infarction and left anterior descending artery culprit lesion, higher peak creatine phosphokinase concentration, and lower left ventricular ejection fraction (LVEF). After adjusting for confounders, GDMT was independently associated with a lower cardiovascular death rate (hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.16-0.81), but not with all-cause mortality (HR 0.77; 95% CI 0.50-1.18). In the subgroup analysis, the favorable impact of GDMT on cardiovascular death was significant in patients aged 80-89 years, with LVEF <50%, or with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2. CONCLUSIONS: GDMT in patients with AMI aged ≥80 years undergoing PCI was associated with a lower cardiovascular death rate but not all-cause mortality.

Effect of the Xanthine Oxidase Inhibitor, Febuxostat, on WBC Count in Asymptomatic Hyperuricemia: Subanalysis of the Randomized PRIZE Study.

AIMS: The anti-inflammatory effects of the xanthine oxidase inhibitor, febuxostat, a urate-lowering agent, have been reported in animal studies. However, the anti-inflammatory effects of urate-lo wering therapy and its associated cardiovascular protective effects have not been fully determined in actual clinical practice. This study aimed to investigate the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and to assess for potential correlations between changes in WBC count and inflammatory biomarkers and atherosclerosis in this patient population. METHODS: This was a post hoc subanalysis of the PRIZE study, a multicenter, prospective, randomized, open-label clinical trial. In the PRIZE study, asymptomatic hyperuricemia patients were randomized to febuxostat group or control group with non-pharmacological therapy and evaluated the effect on vascular. The primary endpoints of this study were the assessment of the time course of WBC count over 24 months and its changes from baseline. Correlations of WBC count with high-sensitivity C-reactive protein (hs-CRP) and mean common carotid artery ( CCA)-IMT were also exploratorily examined in the febuxostat group. RESULTS: A total of 444 patients (febuxostat group, n=223; control group, n=221) with WBC measurements available at baseline and at least one of the follow-up time points of 12 or 24 months, were enrolled. Febuxostat modestly, but significantly, reduced WBC counts at 12 and 24 months compared with the baseline levels (P=0.002 and P=0.026, respectively). Notably, the WBC count in the febuxostat group at 12 and 24 months was significantly lower than that in the control group (P=0.007 and P=0.023, respectively). The changes in WBC count were associated with those of hs-CRP (P=0.038), but not with CCA-IMT (P=0.727). CONCLUSIONS: Febuxostat therapy for 24 months modestly, but significantly, decreased WBC count in patients with asymptomatic hyperuricemia. This might potentially reflect a modest anti-inflammatory action of febuxostat in clinical settings.

One-year safety and effectiveness of the Agent paclitaxel-coated balloon for the treatment of small vessel disease and in-stent restenosis.

The Agent device consists of a semi-compliant balloon catheter, which is coated with a therapeutic low-dose formulation of paclitaxel (2 µg/mm2) blended with an inactive excipient acetyl-tri-n-butyl citrate (ATBC). AGENT Japan SV is a randomized controlled study that enrolled 150 patients from 14 Japanese sites treated with Agent or SeQuent Please paclitaxel-coated balloon. This study also includes a single-arm substudy evaluating the safety and effectiveness of Agent in patients with in-stent restenosis (ISR). Patients with a single de novo native lesion (lesion length ≤ 28 mm and reference diameter ≥ 2.00 to < 3.00 mm) were randomized 2:1 to receive either Agent (n = 101) or SeQuent Please (n = 49). The ISR substudy enrolled 30 patients with lesion length ≤ 28 mm and reference diameter ≥ 2.00 to ≤ 4.00 mm. In the SV RCT, target lesion failure (TLF) at 1 year occurred in four patients treated with Agent (4.0%) versus one patient with SeQuent Please (2.0%; P = 1.00). None of the patients in either treatment arm died. There were no significant differences in the rates of myocardial infarction, target lesion revascularization and target lesion thrombosis through 1 year. In the ISR substudy, the 1-year rates of TLF and target lesion thrombosis were 6.7% and 0.0%, respectively. These data support the safety and effectiveness of the Agent paclitaxel-coated balloon in patients with small vessels and ISR.

Intravascular Lithotripsy for Vessel Preparation in Calcified Coronary Arteries Prior to Stent Placement　- Japanese Disrupt CAD IV Study 2-Year Results.

Background: Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcification to enhance vessel compliance and optimize stent deployment. The Disrupt CAD IV study enrolled patients with severe coronary artery calcification. The primary safety (30-day major adverse coronary events [MACE], 6.3%) and effectiveness (procedural success, 93.8%) endpoints were achieved. The present analysis evaluated the 2-year outcomes of the study. Methods and Results: Disrupt CAD IV (NCT04151628) was a prospective, single-arm, multicenter study designed for regulatory approval of the Shockwave Coronary C2 IVL system in Japan. Angiographic outcomes were analyzed by an independent core laboratory and adverse events were adjudicated by a Clinical Events Committee. Kaplan-Meier analysis was performed for MACE (composite of cardiac death, MI or target-vessel revascularization [TVR]), target lesion failure (TLF: composite of cardiac death, TV-MI, and target lesion revascularization [TLR]), and stent thrombosis (ST). At 2 years, 62 subjects had completed follow-up. MACE occurred in 12.6% (cardiac death 0.0%, MI 6.3%, TVR 7.9%) and TLF occurred in 7.8% of patients, with both rates driven by non-Q-wave MI events (6.3%). TLR was 3.2%; no ST occurred through 2 years. Conclusions: Treatment with IVL in patients with severely calcified coronary lesions was associated with low rates of MACE, TLR, and ST at 2 years, demonstrating continued durable safety and effectiveness of coronary IVL in a Japanese population.

First randomised controlled trial comparing the sirolimus-eluting bioadaptor with the zotarolimus-eluting drug-eluting stent in patients with de novo coronary artery lesions: 12-month clinical and imaging data from the multi-centre, international, BIODAPTOR-RCT.

Background: The DynamX™ bioadaptor is the first coronary implant technology with a unique mechanism of unlocking the bioadaptor frame after polymer resorption over 6 months, uncaging the vessel while maintaining a dynamic support to the vessel. It aims to achieve the acute performance of drug-eluting stents (DES) with the advantages of restoration of vessel function. Methods: This international, single blinded, randomised controlled (1:1) trial compared a sirolimus-eluting bioadaptor with a contemporary zotarolimus-eluting stent (DES) in 34 hospitals in Europe, Japan and New Zealand. Patients with de novo coronary lesions and absence of acute myocardial infarction were enrolled from January 2021 to Feburary 2022. The implantation of the bioadaptor followed the standards of DES. An imaging subset of 100 patients had angiographic and intravascular ultrasound assessments, and 20 patients additionally optical coherence tomography. Data collection will continue through 5 years, we herein report 12-month data based on an intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT04192747). Findings: 445 patients were randomised between January 2021 and February 2022. Device, lesion and procedural success rates, and acute gain were similar amongst the groups. The primary endpoint, 12-month target lesion failure, was 1.8% [95% CI: 0.5; 4.6] (n = 4) versus 2.8% [95% CI: 1.0; 6.0] (n = 6), pnon-inferiority < 0.001 for the bioadaptor and the DES, respectively (Δ-1.0% [95% CI: -3.3; 1.4]). One definite or probable device thrombosis occurred in each group. The 12-month imaging endpoints showed superior effectiveness of the bioadaptor such as in-device late lumen loss (0.09 mm [SD 0.34] versus 0.25 mm [SD 0.39], p = 0.04), and restored compliance and cyclic pulsatility (%mid in-device lumen area change of 7.5% versus 2.7%, p < 0.001). Interpretation: This is the first randomised controlled trial comparing the novel bioadaptor technology against a contemporary DES. The bioadaptor demonstrated similar acute performance and 12-month clinical outcomes, and superior imaging endpoints including restoration of vessel function. Funding: The study was funded by Elixir Medical.

Association of Left Atrial Size With Stroke or Systemic Embolism in Patients With Atrial Fibrillation Having Undergone Bioprosthetic Valve Replacement From the BPV-AF Registry.

Background: The left atrial volume index (LAVI) is important for predicting thromboembolism in patients with non-valvular atrial fibrillation (AF), but the utility of LAVI for predicting thromboembolism in patients with both bioprosthetic valve replacement and AF remains unclear. Methods and Results: Of 894 patients from a previous multicenter prospective observational registry (BPV-AF Registry), 533 whose LAVI data had been obtained by transthoracic echocardiography were included in this subanalysis. Patients were divided into tertiles (T1-T3) according to LAVI as follows: T1 (n=177), LAVI=21.5-55.3 mL/m2; T2 (n=178), LAVI=55.6-82.1 mL/m2; T3 (n=178), LAVI=82.5-408.0 mL/m2. The primary outcome was defined as either stroke or systemic embolism for a mean (±SD) follow-up period of 15.3±4.2 months. Kaplan-Meier curves indicated that the primary outcome tended to occur more frequently in the group with the larger LAVI (log-rank P=0.098). Comparison of T1 with T2 plus T3 using Kaplan-Meier curves indicated that patients in T1 experienced significantly fewer primary outcomes (log-rank P=0.028). Furthermore, univariate Cox proportional hazard regression showed that 1.3- and 3.3-fold more primary outcomes occurred in T2 and T3, respectively, than in T1. Conclusions: Larger LAVI was associated with stroke or systemic embolism in patients who had undergone bioprosthetic valve replacement and with a definitive diagnosis of AF.

Direct Oral Anticoagulants Would Be Best Choice for Atrial Fibrillation Patients After Coronary Stenting: Retrospective Study in a Japanese Population.

BACKGROUND: The combination of dual antiplatelet therapy (DAPT) plus warfarin in atrial fibrillation (AF) patients after coronary stenting has been reported to confer a significant risk of bleeding complications. Direct oral anticoagulants (DOAC) reduce the risk of stroke and bleeding complications in AF patients compared to warfarin. The optimal anticoagulation strategy for Japanese non-valvular AF patients after coronary stenting remains unclear. METHODS: A total of 3230 patients who underwent coronary stenting were retrospectively reviewed. Of these, 284 cases (8.8%) were complicated by AF. Following coronary stenting, 222 patients received triple antithrombotic therapy (TAT) by DAPT plus oral anticoagulants; 121 patients received DAPT plus warfarin, and 101 patients received DAPT plus DOAC. We compared the clinical data between the two groups. RESULTS: The median International normalized ratio (INR) in the DAPT plus warfarin group was 1.61. Bleeding complications occurred in both groups. No cerebral infarction occurred in the DAPT plus DOAC group, while 4.1% of the DAPT plus warfarin group experienced cerebral infarction during follow-up (P=0.04). Twelve-month freedom from cerebral infarction, myocardial infarction, and cardiovascular death was significantly higher in the DAPT plus DOAC group than in the DAPT plus warfarin group [100% vs. 93.4%, P=0.009]. CONCLUSIONS: DOAC might be an optimal selection as an oral anticoagulant for Japanese AF patients who are receiving DAPT after PCI. A larger, longitudinal follow-up should be performed to clarify the clinical advantage of DOAC over warfarin, including among patients who receive single antiplatelet after coronary stent implantation.

Device indication for calcified coronary lesions based on coronary imaging findings.

Performing percutaneous coronary intervention (PCI) for calcified lesions is still a major challenge. Calcified lesions are a cause of inadequate dilatation, leading to poor short- and long-term PCI outcomes. It has been suggested that modification for calcification before stent implantation might improve outcomes by providing adequate dilation. Intravascular lithotripsy (IVL) is available under insurance reimbursement in December 2022 in Japan. IVL is one candidate for a treatment device to modify calcified lesions in addition to atherectomy, such as rotational and orbital atherectomy, and special balloons, such as scoring and cutting balloons. Although the evidence for the indications, of these devices is insufficient, they must be used appropriately in clinical practice. In this report, we propose a method for determining an indication of these devices solely as per the coronary imaging findings with intravascular ultrasound or optical coherent tomography. This consensus document represents the collective opinion of experts on the best current indications and should be changed based on future evidence. However, we believe that it represents the optimal criteria for selecting treatment options in the current situation.

Shorter door-to-balloon time, better long-term clinical outcomes in ST-segment elevation myocardial infarction patients: J-MINUET substudy.

BACKGROUND: The impact of shorter door-to-balloon (DTB time on long-term outcomes in ST-segment elevation myocardial infarction (STEMI treated with primary percutaneous coronary intervention (PPCI has not been fully elucidated. METHODS: We investigated 3283 consecutive patients with acute myocardial infarction selected from a prospective, nationwide, multicenter registry (J-MINUET database comprising 28 institutions in Japan between July 2012 and March 2014. Among the study population, we analyzed 1639 STEMI patients who had PPCI within 12 h of onset. Patients were stratified into four groups (DTB time < 45 min, 45-60 min, 61-90 min, >90 min. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. We performed landmark analysis for incidence of the primary endpoint from 31 days to 3 years among the four groups. RESULTS: The primary endpoint rate from 31 days to 3 years increased significantly and time-dependently with DTB time (10.2 % vs. 15.3 % vs. 16.2 % vs. 19.3 %, respectively; log-rank p = 0.0129. Higher logarithm-transformed DTB time was associated with greater risk of a primary endpoint from 31 days to 3 years, and the increased number of adverse long-term clinical outcomes persisted even after adjusting for other independent variables. CONCLUSION: Shorter DTB time was associated with better long-term clinical outcomes in STEMI patients treated with PPCI in contemporary clinical practice. Further efforts to shorten DTB time are recommended to improve long-term clinical outcomes in STEMI patients. TRIAL REGISTRATION: UMIN Unique trial Number: UMIN000010037.

Calcium Fracture After Intravascular Lithotripsy as Assessed With Optical Coherence Tomography.

BACKGROUND: Plaque characteristics associated with effective intravascular lithotripsy (IVL) treatment of calcification have not been investigated. This study identified calcified plaque characteristics that favor the use of IVL.Methods and Results: Optical coherence tomography (OCT) was performed in 16 calcified lesions in 16 patients treated with IVL and coronary stenting. Cross-sectional OCT images in 262 segments matched across pre-IVL, post-IVL, and post-stenting time points were analyzed. After IVL, 66 (25%) segments had calcium fracture. In multivariable analysis, calcium arc (odds ratio [OR] 1.22; 95% confidence interval [CI] 1.13-1.32; P<0.0001), superficial calcification (OR 6.98; 95% CI 0.07-55.57; P=0.0182), minimum calcium thickness (OR 0.66; 95% CI 0.51-0.86; P=0.0013), and nodular calcification (OR 0.24; 95% CI 0.08-0.70; P=0.0056) were associated with calcium fracture. After stenting, stent area was larger for segments with fracture (8.0 [6.9-10.6] vs. 7.1 [5.2-8.9] mm2; P=0.004). CONCLUSIONS: Post-IVL calcium fracture is more likely in calcified lesions with lower thickness, a larger calcium arc, superficial calcification, and non-nodular calcification, leading to a larger stent area.

Clinical expert consensus document on rotational atherectomy from the Japanese association of cardiovascular intervention and therapeutics: update 2023.

The Task Force on Rotational Atherectomy of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed the expert consensus document to summarize the techniques and evidences regarding rotational atherectomy (RA) in 2020. Because the revascularization strategy to severely calcified lesions is the hottest topic in contemporary percutaneous coronary intervention (PCI), many evidences related to RA have been published since 2020. Latest advancements have been incorporated in this updated expert consensus document.