Clinical Efficacy of Intracoronary Papaverine After Nicorandil Administration for Safe and Optimal Fractional Flow Reserve Measurement.

Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.

Comparison between minimum lumen cross-sectional area and intraluminal ultrasonic intensity analysis using integrated backscatter intravascular ultrasound for prediction of functionally significant coronary artery stenosis.

Intravascular ultrasound (IVUS)-derived minimum lumen cross-sectional area (MLA) is useful to predict myocardial ischemia using fractional flow reserve (FFR). Recent studies reported an increase in the intraluminal ultrasonic integrated backscatter (IB) value using IVUS across the coronary artery stenosis (CAS) was significantly correlated with FFR. However, these details have not been fully understood. We evaluated the utility of intraluminal IB analysis for predicting myocardial ischemia based on FFR measurements by comparing that with conventional IVUS-derived MLA. A total of 65 patients with 75 intermediate lesions underwent both FFR and IB-IVUS simultaneously were analyzed. We measured IVUS-derived MLA and intraluminal IB value at the coronary ostial site, 5 mm distal site to the CAS, and far distal site, which is the same as the position of the pressure wire sensor. The increase in IB values was calculated as the distal IB value - the ostial IB value (focal ∆IB) and the far distal IB value - the ostial IB value (total ∆IB). MLA did not show a significant correlation with FFR (p = 0.13); however, focal ∆IB and total ∆IB showed significant correlations with FFR (p = 0.008 and p < 0.001, respectively). The receiver operating characteristic curve analysis shows that the best cut-off value of focal ∆IB and total ∆IB was 8 and 14, respectively. Although the diagnostic abilities to predict FFR ≤ 0.75 among IVUS-derived MLA ≤ 3.0 mm2, focal ∆IB ≥ 8, and total ∆IB ≥ 14 were similar, a multivariate analysis showed that total ∆IB was the most useful index (p < 0.001). In conclusion, total ∆IB, which is measured at the same as the position of FFR measurement, might be useful for functional assessment of intermediate CAS.

Impact of High-Sensitivity Cardiac Troponin Elevation in Relation to Diagnostic Invasive Intravascular Imaging for the Assessment of Coronary Artery Disease.

Recent studies reported that cardiac troponin elevation after percutaneous coronary intervention is related to adverse cardiac events. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are often used to assess lesion characteristics in the coronary arteries. However, little is known about the trend of cardiac troponin elevation after diagnostic invasive intracoronary examination and the prognostic influence. We assessed the relationship between myocardial injury manifested by the high-sensitivity cardiac troponin T (hs-cTnT) level after invasive intracoronary examination and future adverse cardiac outcomes. We evaluated 115 patients with stable coronary artery disease who underwent IVUS or OCT for detailed coronary assessment during coronary angiography (CAG). Baseline and post-procedural (within 24 hours after examination) hs-cTnT were measured. In consequence, post-procedural hs-cTnT level and percentage increase were higher in patients with IVUS or OCT during CAG than in those without. Periprocedural myocardial injury (PMI, defined as post-procedural hs-cTnT with upper reference limit greater than five-fold) occurred in 10 (8.6%) patients. There were no significant differences in baseline characteristics between patients with and without PMI, except for left-ventricular diastolic dimension. Only two major adverse cardiac events (MACE, defined as cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization) occurred in non-PMI during a mean observation period of 32 ± 18 months. On Kaplan-Meier analysis, MACE-free survival rate was similar between PMI and non-PMI. In conclusion, a few imperceptible PMI derived by hs-cTnT assay occurred after diagnostic invasive intracoronary examination. However, it was not associated with subsequent poor cardiac outcome.

Contribution of Poststent Irregular Protrusion to Subsequent In-Stent Neoatherosclerosis after the Second-Generation Drug-Eluting Stent Implantation.

Previous optical coherence tomography (OCT) study reported that irregular protrusion (IP) post drug-eluting stent (DES) implantation was an independent predictor of clinical outcome; however, the relationship between IP and the presence of subsequent in-stent neoatherosclerosis remains unclear. This study aimed to assess the relationship between IP and in-stent neoatheroscrerosis formation using OCT. We evaluated 83 patients (101 lesions) who underwent second-generation DES implantation and 8-month follow-up (8M-FU) using OCT. Lesions were divided into two groups in presence of IP (IP: n = 43, non-IP: n = 58). At prepercutaneous coronary intervention (pre-PCI), lipid-rich plaque, lesions with positive remodeling, and in-stent thrombus formation were more frequent in IP than in non-IP. On multivariate analysis, the thrombus at pre-PCI and the lesions with positive remodeling were independent predictors of IP. At 8M-FU, heterogeneous neointima, microvessel, lipid-laden neointima, and thin-cap fibro-atheroma like neointima were more frequent in IP than in non-IP (respectively, P < 0.05). On multivariate analysis, IP was associated with heterogeneous neointima. Binary restenosis was more frequent and late lumen loss tended to be larger in IP than in non-IP (19% versus 5%, P = 0.04; 1.25 ± 1.24 mm versus 0.91 ± 0.63 mm, P = 0.09); however, the target lesion revascularization rate was similar in both groups at 8M-FU. In conclusion, our study suggested that poststent IP was associated with subsequent neoatherosclerosis formation at 8M-FU after the second-generation DES implantation.

Impact of Antiplatelet Therapy on 5-Year Outcomes After Fractional Flow Reserve-Guided Deferral of Revascularization in Nonsignificant Obstructive Coronary Artery Disease.

Background: Because the clinical benefit of antiplatelet therapy (APT) for patients with nonsignificant coronary artery disease (CAD) remains poorly understood, we evaluated it in patients after fractional flow reserve (FFR)-guided deferral of revascularization. Methods and Results: From the J-CONFIRM (Long-Term Outcomes of Japanese Patients with Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), we investigated 265 patients with deferred lesions who did not require APT for secondary prevention of cardiovascular disease. A 2-year landmark analysis assessed the relationship between APT at 2 years and 5-year major cardiac adverse events (MACE: composite of all-cause death, target vessel-related myocardial infarction, clinically driven target vessel revascularization). Of the 265 patients, 163 (61.5%) received APT. The 5-year MACE did not significantly differ between the APT and non-APT groups after adjustment for baseline clinical characteristics (9.2% vs. 6.9%, inverse probability weighted hazard ratio, 1.40 [95% confidence interval, 0.53-3.69]; P=0.49). There was a marginal interaction between the effect of APT on MACE and FFR values (< or ≥0.84) (P for interaction=0.066). Conclusions: The 5-year outcomes after FFR-guided deferral of revascularization did not significantly differ between the APT and non-APT groups, suggesting that APT might not be a critical requirement for nonsignificant obstructive CAD patients not requiring APT for secondary prevention of cardiovascular disease.

Effects of contrast medium viscosity into flushing port on artefacts during optical coherence tomography imaging.

BACKGROUND: Optical coherence tomography (OCT) is becoming the standard imaging modality for percutaneous coronary intervention (PCI) because of its high resolution. To perform appropriate OCT-guided PCI, it is necessary to avoid artefacts and obtain high-quality images. We investigated the relationship between artefacts and the viscosity of contrast media, which were used to remove air before OCT imaging catheter was inserted into guiding catheter. METHODS: We retrospectively analyzed every pullback of OCT examinations from January 2020 to September 2021. Cases were divided into two groups according to the type of contrast media used for catheter flushing: low-viscosity (Iopamidol-300, Bayer, Nordrhein-Westfalen, Germany) vs. high-viscosity (Iopamidol-370, Bayer). We evaluated the artefacts and quality of each OCT image and performed ex vivo experiments to compare differences in artefact frequencies using the two contrast media. RESULTS: A total of 140 pullbacks in the low-viscosity group and 73 pullbacks in the high-viscosity group were analyzed. The percentage of grade 2 and 3 images (with good quality) in the low-viscosity group was significantly lower (68.1 % vs. 94.5 %, p < 0.001). Rotational artefacts were significantly more common in the low-viscosity group (49.3 % vs. 8.2 %, p < 0.001). In multivariate analysis, using low-viscosity contrast media was a significant factor influencing the appearance of rotational artefacts and affecting image quality (odds ratio, 9.42; 95 % confidence interval, 3.58 to 24.8; p < 0.001). In ex vivo experiments, using low-viscosity contrast media was also a significant predictor of artefact occurrence during OCT (p < 0.01). CONCLUSIONS: The viscosity of the contrast agent used while flushing the OCT imaging catheter contributes to the appearance of OCT artefacts.

Malnutrition leads to the progression of coronary artery calcification in hemodialysis patients.

BACKGROUND: Malnutrition is considered a risk factor for cardiovascular disease in patients with chronic kidney disease. However, no in vivo studies have reported on using optical coherence tomography to evaluate the effect of nutritional status on coronary atherosclerosis in hemodialysis patients. We aimed to conduct a detailed analysis of the effect of nutritional status on the coronary arteries in hemodialysis patients. METHODS: Among 64 hemodialysis patients who underwent percutaneous coronary interventions, 41 that underwent optical coherence tomography imaging were included in this study. And, among them, 24 patients that could also be evaluated using OCT also at the 6-month follow-up were included in this study. The patients were divided into two groups based on nutritional evaluation using the geriatric nutritional risk index. Culprit and non-culprit lesions were evaluated at baseline and after 6 months. RESULTS: In the culprit lesions at baseline, the length of the lipid plaque was significantly smaller in the malnutrition group. In contrast, the thickness and length of the calcified plaque and the angle of the calcified nodule were significantly larger (each p < 0.01). In the non-culprit lesions, the 6-month change in the angle of the calcified plaque was significantly greater in the malnutrition group (p = 0.02). The significant factors that affected the change in the angle of calcification were "malnutrition at geriatric nutritional risk index" [odds ratio, 8.17; 95% confidence interval, 1.79 to 37.33; p < 0.01] and "serum phosphorus level" (odds ratio, 3.73; 95% confidence interval, 1.42 to 9.81; p < 0.01). CONCLUSIONS: Appropriate management of nutritional status is crucial for suppressing the progression of coronary artery disease in hemodialysis patients.

Healed Erosion: The Role of Pre-interventional Optical Coherence Tomography in a Patient Clinically Suspected of Having Unstable Angina with Coronary Spasm.

A 46-year-old man complained of chest pain at rest for the past three months. His symptoms gradually exacerbated and were suspected of being due to unstable angina. A coronary angiogram revealed focal tight stenosis at the proximal left anterior descending coronary artery with gross spastic coronary findings. Optical coherence tomography (OCT) revealed layered low-intensity structures with microvessels and the accumulation of macrophages, which indicated progressive stenosis with multiple-layered organized thrombus caused by coronary erosion. We treated the stenosis using a drug-coated balloon instead of drug-eluting stents. There was no restenosis, and OCT revealed good plaque healing at follow-up. This case suggests that the pre-interventional OCT plaque morphology can have a positive impact on the revascularization strategy.

Drug-eluting stent thrombosis: current and future perspectives.

Over the past 40 years, the safety and efficacy of percutaneous coronary intervention has dramatically improved by overcoming several challenges. The introduction of drug-eluting stent (DES) in particular was a major breakthrough in interventional cardiology. Compared to bare-metal stents, first-generation DES (G1-DES) has dramatically reduced the rates of in-stent restenosis and subsequent target lesion revascularization. However, major safety concerns surrounding stent thrombosis (ST) emerged with G1-DES in clinical practice as a result of the high incidences of death, myocardial infarction, and repeat revascularization associated with ST. To overcome these limitations, second-generation DES (G2-DES) has been developed with an improved stent platform with thinner strut and biocompatible durable or biodegradable polymers. Indeed, G2-DES, when compared with G1-DES, has improved clinical outcomes by reducing the risk of late thrombotic events while maintaining anti-restenotic efficacy, whereas ST still occurs, even with the use of G2-DES. This review gives an overview of pathophysiology, risk factors, and outcomes of ST after DES implantation. Additionally, we discuss the management and prevention of ST.

Right ventricular branch compromise after percutaneous coronary intervention and baseline chronic kidney disease: A high-risk combination associated with long-term prognoses in acute inferior myocardial infarction.

BACKGROUND: Right ventricular branch compromise (RVBC) following percutaneous coronary intervention (PCI) in patients with acute inferior myocardial infarction (AIMI) is associated with short-term adverse clinical outcomes. Chronic kidney disease (CKD) is also known to be a major risk factor after PCI in AIMI. However, little is known about the impact of RVBC and CKD on long-term prognosis. METHODS: From January 2009 to January 2019, we retrospectively enrolled 90 consecutive patients with ST-elevation AIMI who had a culprit lesion in the proximal-to-mid right coronary arteries and underwent PCI in our institution. After the measurement of the Thrombolysis in Myocardial Infarction frame counts in RV branches using post-PCI angiography, we divided them into two groups (RVBC, n = 49; non-RVBC, n = 41), and investigated their long-term prognosis for 43±31 months. The primary endpoint was the incidence of major adverse cardiac events (MACEs), including all-cause death, nonfatal MI, congestive heart failure requiring hospitalization, and life-threatening arrhythmia. RESULTS: Both groups showed similar clinical characteristics; however, the baseline right ventricular function after PCI was significantly worse in RVBC than in non- RVBC. Twenty-four MACEs occurred during the follow-up (RVBC vs. non-RVBC: 37% vs. 14%, p = 0.002). In the multivariate analysis, both RVBC and baseline CKD were powerful predictors of MACEs (RVBC: hazard ratio [HR] 2.85, CKD: HR 2.29). Baseline CKD showed higher hazard ratios of MACEs in RVBC (CKD: HR 7.19 vs. non-CKD: HR 0.24). CONCLUSIONS: The prognoses of RVBC after primary PCI in patients with AIMI were poor. Baseline CKD and RVBC were associated with poor long-term clinical outcomes.

Comparison of post-stent irregular protrusion and subsequent neointimal characteristics between second- and third-generation drug-eluting stent implantation.

BACKGROUND: Third-generation drug-eluting-stents (3rd DES) may improve coronary arterial healing and reduce neoatherosclerosis formation. We evaluated post-stent findings and subsequent vascular healing of 3rd DES by comparing to second-generation drug-eluting-stents (2nd DES) at intermediate-term follow-up using optical coherence tomography (OCT). METHOD: We evaluated 170 patients with 170 lesions who underwent DES implantation (2nd DES, n = 98; 3rd DES, n = 72) and OCT-guided follow-up examination. After propensity score (PS) matching for baseline clinical characteristics, OCT findings from 56 pairs of patients with 2nd DES and 3rd DES implants were compared. Post-stent irregular protrusion (IP) was defined as the protrusion of material with an irregular surface into the lumen between the stent struts. Neoatheroscleosis was defined as neointima contained heterogeneous pattern, rupture, lipid-laden, thin-cap fibroatheroma, or calcification. The presence of peri-strut low-intensity area (PLIA) and in-stent neointimal tissue characteristics were also analyzed at 6- to 8-month follow-up. RESULTS: There were no significant differences between the incidence of post-stent IP or neoatherosclerosis formation in the 2nd DES and the 3rd DES (45% vs. 38%, p = 0.44; 30% vs. 20%, p = 0.19, respectively). However, the incidences of PLIA and layered neointimal pattern, which indicate immature neointimal healing, were significantly lower in the 3rd DES compared to the 2nd DES (41% vs. 61%, p = 0.04; 2% vs. 11%, p = 0.04, respectively). As comparing intermediate-term follow-up OCT neointimal findings in patients with IP between 2nd DES and 3rd DES, most neointima tended to have a homogeneous pattern (95% versus 76%, p = 0.06) in the 3rd DES than in the 2nd DES. CONCLUSIONS: The incidence of post-stent IP and subsequent neoatherosclerosis formation at intermediate-term follow-up after stent implantation were similar between patients with 2nd DES and 3rd DES, however, vascular healing might be favorable when using 3rd DES.

Bleeding and ischemic events during dual antiplatelet therapy after second-generation drug-eluting stent implantation in hemodialysis patients.

BACKGROUND: Dual-antiplatelet therapy (DAPT) after second-generation drug-eluting stent (2nd-DES) implantation reduces the risk of stent thrombosis and subsequent ischemic events, with an increase in bleeding risk. Although chronic kidney disease patients have both high ischemic and bleeding events, little is known about both risks during DAPT in hemodialysis (HD) patients. METHODS: From July 2009 to March 2017, we retrospectively analyzed bleeding events and major adverse cardiac and cerebrovascular events (MACCE) in 644 consecutive patients who underwent successful percutaneous coronary intervention (PCI) with 2nd-DES implantation in our institution. We divided the patients into 2 groups [102 HD and 518 non-HD patients] after excluding 24 patients. The primary endpoint was bleeding events of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5. The secondary endpoint was MACCE. We also investigated potential bleeding risk factors in those patients. RESULTS: At a median follow-up of 49 months, bleeding events occurred in 76 (12.3%) patients. Critical bleeding events of BARC type 3 or 5 occurred more frequently in HD (HD vs. non-HD: 16.7% vs. 7.1%; p=0.004). Most events tended to occur within 6 months post PCI. Multivariate analysis demonstrated that HD [hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.03-3.16; p=0.04], body mass index (BMI) (HR 0.91, 95%CI 0.87-0.99, p=0.02), and serum albumin (HR 0.35, 95%CI 0.34-0.96, p=0.03) were independent predictors of bleeding events. MACCE also occurred more frequently in HD (HD vs. non-HD: 53.9% vs. 29.3%; p<0.001). Multivariate analysis demonstrated that pre-dialysis systolic blood pressure (HR 1.03, 95%CI 1.00-1.06, p=0.02) and high-sensitive C-reactive protein level (HR 1.76, 95%CI 1.06-2.72, p=0.03) were independent predictors of bleeding events in HD. CONCLUSIONS: HD displayed more adverse bleeding and ischemic events compared with non-HD. Therefore, practitioners should reconsider the current regimen of DAPT in this patient cohort to prevent critical bleeding complications and spates of ischemic events.