Drug intervention as an emerging concept for secondary prevention in patients with coronary disease.

Non-culprit lesion-related coronary events are a significant concern in patients with coronary artery disease (CAD) undergoing coronary intervention. Since several studies using intra-coronary imaging modalities have reported a high prevalence of vulnerable plaques in non-culprit lesions at the initial coronary event, the immediate stabilization of these plaques by intensive pharmacological regimens may contribute to the reduction in the adverse events. Although current treatment guidelines recommend the titration of statin and other drugs to attain the treatment goal of low-density lipoprotein cholesterol (LDL-C) level in patients with CAD, the early prescription of strong LDL-C lowering drugs with more intensive regimen may further reduce the incidence of recurrent cardiovascular events. In fact, several studies with intensive regimen have demonstrated a higher percentage of patients with the attainment of LDL-C treatment goal in the early phase following discharge. In addition to many imaging studies showing plaque stabilization by LDL-C lowering drugs, several recent reports have shown the efficacy of early statin and proprotein convertase subtilisin/kexin type 9 inhibitors on the immediate stabilization of non-culprit coronary plaques. To raise awareness regarding this important concept of immediate plaque stabilization and subsequent reduction in the incidence of recurrent coronary events, the term 'Drug Intervention' has been introduced and gradually applied in the clinical field, although a clear definition is lacking. The main target of this concept is patients with acute coronary syndrome as a higher prevalence of vulnerable plaques in non-culprit lesions in addition to the worse clinical outcomes has been reported in recent imaging studies. In this article, we discuss the backgrounds and the concept of drug intervention.

Consensus document on the clinical application of invasive functional coronary angiography from the Japanese Association of Cardiovascular Intervention and Therapeutics.

Invasive functional coronary angiography (FCA), an angiography-derived physiological index of the functional significance of coronary obstruction, is a novel physiological assessment tool for coronary obstruction that does not require the utilization of a pressure wire. This technology enables operators to rapidly evaluate the functional relevance of coronary stenoses during and even after angiography while reducing the burden of cost and complication risks related to the pressure wire. FCA can be used for treatment decision-making for revascularization, strategy planning for percutaneous coronary intervention, and procedure optimization. Currently, various software-computing FCAs are available worldwide, with unique features in their computation algorithms and functions. With the emerging application of this novel technology in various clinical scenarios, the Japanese Association of Cardiovascular Intervention and Therapeutics task force was created to outline expert consensus on the clinical use of FCA. This consensus document advocates optimal clinical applications of FCA according to currently available evidence while summarizing the concept, history, limitations, and future perspectives of FCA along with globally available software.

Sex Differences in 5-Year Outcomes After Deferral of Revascularization Following Physiological Coronary Assessment.

Background: The relationship between sex differences and long-term outcomes after fractional flow reserve (FFR)- and instantaneous wave-free ratio (iFR)-guided deferral of revascularization has yet to be elucidated. Methods and Results: From the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on FFR in a multicenter registry), this study included 432 lesions from 385 patients (men, 323 lesions in 286 patients; women, 109 lesions in 99 patients) with paired data of FFR and iFR. The primary endpoint was the cumulative 5-year incidence of target vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization. The median FFR value was lower in men than in women (0.85 [0.81, 0.88] vs. 0.87 [0.83, 0.91], P=0.002), but the iFR value was comparable between men and women (0.94 [0.90, 0.98] vs. 0.93 [0.89, 0.98], P=0.26). The frequency of discordance between FFR and iFR was comparable between men and women (19.5% vs. 23.9%, P=0.34), although with different discordance patterns (P=0.036). The cumulative incidence of 5-year TVF did not differ between men and women after adjustment for baseline characteristics (13.9% vs. 6.9%, adjusted hazard ratio 1.82 [95% confidence interval: 0.44-7.56]; P=0.41). Conclusions: Despite sex differences in the results for physiological indexes, the 5-year TVF in deferred lesions did not differ between men and women after adjustment for baseline characteristics.

Prognostic Impact of Renal Function on 5-Year Outcomes After Fractional Flow Reserve-Guided Deferral of Revascularization.

Background Chronic kidney disease (CKD) might influence fractional flow reserve (FFR) value, potentially attenuating its prognostic utility. However, few large-scale data are available regarding clinical outcomes after FFR-guided deferral of revascularization in patients with CKD. Methods and Results From the J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1218 patients were divided into 3 groups according to renal function: (1) non-CKD (estimated glomerular filtration rate ≥60 mL/min per 1.73 m2), n=385; (2) CKD (estimated glomerular filtration rate 15-59 mL/min per 1.73 m2, n=763); and (3) end-stage renal disease (ESRD) (eGFR <15 mL/min per 1.73 m2, n=70). The primary study end point was the cumulative 5-year incidence of target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction, and clinical driven target vessel revascularization. Cumulative 5-year incidence of TVF was significantly higher in the ESRD group than in the CKD and non-CKD group, whereas it did not differ between the CKD and non-CKD groups (26.3% versus 11.9% versus 9.5%, P<0.001). Although the 5-year TVF risk increased as the FFR value decreased regardless of renal function, patients with ESRD had a remarkably higher risk of TVF at every FFR value than those with CKD and non-CKD. Conclusions At 5 years, patients with ESRD showed a higher incidence of TVF than patients with CKD and non-CKD, although with similar outcomes between patients with CKD and non-CKD. Patients with ESRD had an excess risk of 5-year TVF at every FFR value compared with those with CKD and non-CKD. Registration URL: https://www.umin.ac.jp; Unique identifier: UMIN000014473.

Ultrasound-guided stenting in the common femoral vein for accurate stent distal landing.

Objective/Background: Venous stenting has been reported with excellent clinical results; however, inadequate inflow can increase the risk of stent occlusion. When extending the stent into the common femoral vein (CFV), it is essential to ensure adequate inflow from the femoral vein, deep femoral vein (DFV), and great saphenous vein. Accurate identification of the distal landing zone (DLZ) of the stent is crucial to ensure adequate inflow. The DLZ is usually determined by venography or intravascular ultrasound (IVUS) with reference to bony landmarks. However, the uncertainty can lead to misidentification of the DLZ and inadequate stent placement, resulting in stent occlusion. Methods: From December 2016 to December 2022, 42 venous stent placements were performed in 40 patients with post-thrombotic iliofemoral vein obstruction and/or stenosis. Three patients had developed early stent occlusion owing to a misidentified DLZ. To improve accuracy in identifying the DLZ during venous stenting, ultrasound-guided placement was performed in the CFV of five patients (four on the left and one on the right) with post-thrombotic changes in the CFV and occlusion of the common iliac vein and external iliac vein. The distal end of the stent was adjusted just above the saphenofemoral junction in two cases and just proximal to the DFV confluence in three cases. Stent placement was verified using both long-axis ultrasound and fluoroscopy. Results: Ultrasound images of the CFV region provided clear visualization of the stent deployment site and accurate landmark locations, such as the saphenofemoral junction and DFV confluence, allowing for precise adjustments during stent deployment. This technique enabled easier and more definitive identification of other branches of the CFV than previously provided by IVUS and venography. No complications were observed in any of the 42 cases, and long-term patency was achieved at the final follow-up after stenting (average, 10 months; range, 3-14 months). Conclusions: Ultrasound-guided stenting in the CFV allows for real-time and accurate stent deployment with precise adjustment to the optimal DLZ. Using this technique, combined with venography and IVUS, missed distal lesions and subsequent stent occlusion can be prevented, potentially contributing to better treatment outcomes.

Anti-hypertensive medication adherence in the REQUIRE trial: post-hoc exploratory evaluation.

Maintaining medication adherence is important in treating hypertension, especially resistant hypertension (RH), and variable medication adherence can confound results in blood pressure trials. This post-hoc analysis evaluated adherence at baseline and 3 months using available urine samples from the REQUIRE trial, comparing 24-h ambulatory systolic blood pressure (ASBP) lowering effects of ultrasound renal denervation (uRDN) versus sham in RH. At baseline, 45% (26/58) patients showed poor adherence. Among patients with good baseline adherence, adherence was unchanged at 3 months, and uRDN patients had a decreased ASBP whereas sham patients did not. In poorly adherent patients, sham patients showed a trend towards increased adherence and a significant ASBP reduction, whereas uRDN patients did not change. Accordingly, adherence changes and the resultant ASBP reduction in poorly adherent sham patients may explain the lack of between-group difference seen in REQUIRE. Monitoring and maintaining medication adherence is important for future interventional studies in RH.

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.

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.

Angioscopic evaluation after venous stents.

BACKGROUND: Venous stenting is increasingly used to manage femoro-ilio-caval venous outflow obstruction/stenosis due to post-thrombotic syndrome. Although the safety, efficacy, and long-term patency of venous stents have been reported, re-interventions due to stent occlusion and in-stent restenosis (ISR) have also been reported. The mechanism of ISR and the in-stent neointimal growth after venous stenting remains unclear. We performed angioscopy to evaluate intraluminal details after venous stenting, allowing real-time direct visualization of the vessel lumen. METHODS: Ten angioscopic procedures in four patients with post-thrombotic syndrome were performed. All evaluated vessels were stented iliac veins, and their native pathology was chronic post-thrombotic occlusion. Nine procedures in three patients underwent serial evaluation of the neointimal changes after stent implantation to study the natural time course of neointimal proliferation/coverage over the stent. The serial follow-up angioscopic evaluations were performed at the end of the venous stent deployment procedure, and at 6 months, 12 months, and 24 months. One procedure was performed 1 month after the stent implantation to evaluate ISR, which was observed at the first month of routine stent surveillance. A 5.7F angioscope was used to visualize the target veins. Continuous irrigation was used to displace blood and clear the visual field. RESULTS: At 6 months after stent implantation, stent struts were covered by a thin neointima in two of the three patients. The struts were partially covered in one patient, but there was little neointimal growth overall. Neointimal coverage increased over time, and at 12 months stent struts in 2 patients were almost completely covered. There was no significant change between the 12 and 24 months after stent implantation. In the ISR case, angioscopy demonstrated an overgrown thickened neointima, and the stent struts were fully embedded and invisible in the entire stented area. No thrombus and no webs or trabeculae were found in the area evaluated as an ISR lesion. CONCLUSIONS: At 6 months after stent placement, the stent struts were almost covered by a neointima. The stent struts were completely covered 1 year after stent implantation. Neointimal coverage was unchanged from the 1-year follow-up to the 2-year follow-up, suggesting that neointimal proliferation proceeded gradually with subsequent neointimal remodeling up to 1 year. The cause of ISR might be the overgrown thickened neointima rather than the formation of thrombosis.

Correlation between "Nutcracker phenomenon" and venous hypertension of the lower extremities: Three case reports.

We report three cases of left renal vein (LRV) compression resulting in deep venous insufficiency of the lower extremities, among which two patients showed clinical symptoms in both lower extremities. All patients were treated successfully with LRV stenting. The pathophysiology suggested that the secondary gonadal vein reflux owing to LRV compression drained into the iliac veins, resulting in a volume overload and venous hypertension in the iliocaval region. Computed tomography angiography was useful in diagnosing this condition, allowing the evaluation of LRV compression, identification of early opacification of the gonadal vein reflux, and exclusion of other pathologies resulting in deep venous insufficiency of the lower extremities.

Post-thrombotic syndrome of the lower extremity associated with arteriovenous fistula: Three case reports.

The post-thrombotic syndrome is a serious complication of deep vein thrombosis. Post-thrombotic iliac venous occlusion (PTIVO) is rarely associated with an arteriovenous fistula (AVF); however, the underlying mechanism remains unclear. We reported three PTIVO cases associated with an AVF, two symptomatic cases treated with venous stenting, and one asymptomatic case followed up conservatively. The essential imaging findings to diagnose PTIVO with an AVF were the presence of an arterial waveform on ultrasound examination and early opacification on contrast-enhanced computed tomography in the iliofemoral veins. Venous stenting resulted in the disappearance of the AVF, drastic improvement in symptoms, and an excellent long-term outcome.

Determinants of Drug-Coated Balloon Failure in Patients Undergoing Femoropopliteal Arterial Intervention.

BACKGROUND: Drug-coated balloons (DCB) are frequently used to treat femoropopliteal artery disease. However, patency loss occurs in ≥10% of patients within 12 months posttreatment with poor understanding of the underlying mechanisms. OBJECTIVES: The authors sought to investigate the determinants of DCB failure in femoropopliteal disease. METHODS: Data from randomized clinical trials (IN.PACT SFA, MDT-2113 SFA Japan) and 2 prespecified imaging cohorts of the IN.PACT Global Clinical Study were included. Influential procedural characteristics were evaluated by an independent angiographic core laboratory. The primary endpoint was DCB failure (patency loss during follow-up). Additional endpoints were binary restenosis and clinically driven target lesion revascularization. Multivariable analyses evaluated the clinical, anatomical, and procedural predictors of DCB failure. RESULTS: Included were 557 participants with single lesions and 12-month core laboratory-adjudicated duplex ultrasonography. Key clinical characteristics were as follows: mean age 68.8 years, 67.5% male, 87.6% with hypertension, 76.9% with hyperlipidemia, 40.5% with diabetes mellitus, 90.5% in Rutherford Classification Category (RCC) 2 to 3, and 9.5% in RCC 4 to 5. Average length and reference vessel diameter (RVD) were 16.37 cm and 4.66 mm, respectively; 49.7% of lesions were totally occluded. In multivariable analysis, only residual stenosis >30% was associated with patency loss, whereas residual stenosis >30% and smaller preprocedure RVD were associated with increased binary restenosis risk. RCC >3 and residual stenosis >30% were associated with increased 12-month clinically driven target lesion revascularization risk. CONCLUSIONS: Patency loss after DCB treatment was influenced by procedural and clinical factors. Residual stenosis >30%, smaller preprocedure RVD, and higher RCC may be considered predictors of increased risk of DCB failure and its components in femoropopliteal artery disease. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA]; NCT01947478; IN.PACT Global Clinical Study; NCT01609296).

Clinical Characteristics and Outcomes of Patients Presenting With Acute Myocardial Infarction Without Cardiogenic Shock.

BACKGROUND: Most patients with acute myocardial infarction (AMI) present in the emergency department in a hemodynamically stable condition (i.e., non-cardiogenic shock) (AMI-NCS). However, few studies specifically focused on the clinical characteristics and outcomes of AMI-NCS patients. Temporal trends in clinical characteristics, in-hospital occurrence of in-hospital adverse outcomes, and the effect of primary percutaneous coronary intervention (PPCI) were examined.Methods and Results: Between April 2012 and March 2018, 176,275 AMI-NCS patients (67.7% of the total AMI population; 25.4% female; mean age 68.6±13.1 years) were identified in a nationwide Japanese administrative database. During the 6-year study period, AMI-NCS patients have been getting older and had an increasing burden of comorbidities. The rates of 30-day all-cause mortality and in-hospital complications were 2.6% and 30.5%, respectively. Thirty-day all-cause mortality did not change significantly over time, whereas in-hospital complications, especially major non-cardiac events, increased progressively. On multivariable analyses, higher age, higher Killip class, atrial fibrillation, chronic renal failure, and malignancy were independently associated with both increased 30-day mortality and in-hospital complications. PPCI was independently associated with lower mortality and in-hospital complications. CONCLUSIONS: The clinical background of AMI-NCS patients has been becoming more complex with increasing age and the burden of comorbidities, with increased in-hospital complications. More active and appropriate application of PPCI may further decrease adverse events and improve survival of AMI-NCS patients.

Resources for cardiovascular healthcare associated with 30-day mortality in acute myocardial infarction with cardiogenic shock.

Aims: Although primary percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS), such as extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pumping (IABP), have been widely used for acute myocardial infarction (AMI) patients with cardiogenic shock (AMICS), their in-hospital mortality remains high. This study aimed to investigate the association of cardiovascular healthcare resources with 30-day mortality in AMICS. Methods and results: This was an observational study using a Japanese nationwide administrative data (JROAD-DPC) of 260 543 AMI patients between April 2012 and March 2018. Of these, 45 836 AMICS patients were divided into three categories based on MCS use: with MCS (ECMO with/without IABP), IABP only, or without MCS. Certified hospital density and number of board-certified cardiologists were used as a metric of cardiovascular healthcare resources. We estimated the association of MCS use, cardiovascular healthcare resources, and 30-day mortality. The 30-day mortality was 71.2% for the MCS, 23.9% for IABP only, and 37.8% for the group without MCS. The propensity score-matched and inverse probability-weighted Cox frailty models showed that primary PCI was associated with a low risk for mortality. Higher hospital density and larger number of cardiologists in the responsible hospitals were associated with a lower risk for mortality. Conclusion: Although the 30-day mortality remained extremely high in AMICS, indication of primary PCI and improvement in providing cardiovascular healthcare resources associated with the short-term prognosis of AMICS.

Clinical expert consensus document on standards for lower extremity artery disease of imaging modality from the Japan Endovascular Treatment Conference.

Imaging modalities have developed to provide precise information in the assessment of lower extremity artery disease (LEAD), including both quantitative measurements and morphological assessment. However, a lack of standardization for the evaluation methods introduces inconsistency and potential risk. This consensus document from Japan Endovascular Treatment Conference (JET) summarizes the methods of measurement and assessment of intravascular ultrasound (IVUS), optical frequency domain imaging (OFDI), and angioscopy. We propose standardized approaches for the evaluation of these modalities in endovascular therapy (EVT).

Changes in Antithrombotic Therapy Over Time and Durability of a Prasugrel WOEST-Like Regimen for Percutaneous Coronary Intervention Patients With Atrial Fibrillation　- Post Hoc Analysis of the PENDULUM Mono and PENDULUM Registries.

Background: Previously published randomized atrial fibrillation (AF) percutaneous coronary intervention (PCI) trials have demonstrated the safety and efficacy of a WOEST-like regimen (oral anticoagulant [OAC] plus P2Y12 inhibitor) in patients with AF PCI within 1 year. However, the efficacy of this regimen in real-world practice has not been fully confirmed, especially the efficacy of the WOEST-like regimen using the approved dose of prasugrel in Japan. Methods and Results: This post hoc analysis included 186 and 220 patients from the PENDULUM mono and PENDULUM registries, respectively. Endpoints were the cumulative incidences of clinically relevant bleeding (CRB) and major adverse cardiac and cerebrovascular events (MACCE) at 12 months after PCI. Differences in the enrollment period led to an increase in OAC prescriptions (from 64.7% to 81.2%) and a reduction in the median duration of triple antithrombotic therapy (from 203.0 to 32.0 days) in the PENDULUM vs. PENDULUM mono registries, respectively. After adjustment by the inverse probability of treatment method, in patients with OAC, PENDULUM mono AF significantly reduced CRB without increasing MACCE compared with PENDULUM AF. Conclusions: A WOEST-like regimen with prasugrel may reduce CRB, without increasing MACCE, in Japanese patients with AF and high bleeding risk undergoing PCI.

Clinical use of physiological lesion assessment using pressure guidewires: an expert consensus document of the Japanese association of cardiovascular intervention and therapeutics-update 2022.

Fractional flow reserve and instantaneous wave-free ratio are widely accepted and recommended in Western and Japanese guidelines for appropriate percutaneous coronary intervention. There are, however, many differences in clinical situations between Japan and Western countries. Therefore, the Task Force on coronary physiology of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has proposed an expert consensus document to summarize current evidence and suggest the practical use of physiological lesion assessment in Japan.