Impact of Serial Coronary Stenoses on Various Coronary Physiologic Indices.

BACKGROUND: Determining the functional significance of each individual coronary lesion in patients with serial coronary stenoses is challenging. It has been proposed that nonhyperemic pressure ratios, such as the instantaneous wave free ratio (iFR) and the ratio of resting distal to proximal coronary pressure (Pd/Pa) are more accurate than fractional flow reserve (FFR) because autoregulation should maintain stable resting coronary flow and avoid hemodynamic interdependence (cross-talk) that occurs during hyperemia. This study aimed to measure the degree of hemodynamic interdependence of iFR, resting Pd/Pa, and FFR in a porcine model of serial coronary stenosis. METHODS: In 6 anesthetized female swine, 381 serial coronary stenoses were created in the left anterior descending artery using 2 balloon catheters. The degree of hemodynamic interdependence was calculated by measuring the absolute changes in iFR, resting Pd/Pa, and FFR across the fixed stenosis as the severity of the other stenosis varied. RESULTS: The hemodynamic interdependence of iFR, resting Pd/Pa, and FFR was 0.039±0.048, 0.021±0.026, and 0.034±0.034, respectively (all P<0.001). When the functional significance of serial stenoses was less severe (0.70-0.90 for each index), the hemodynamic interdependence was 0.009±0.020, 0.007±0.013, and 0.017±0.022 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001). However, in more severe serial coronary stenoses (<0.60 for each index), hemodynamic interdependence was 0.060±0.050, 0.037±0.030, and 0.051±0.037 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001). CONCLUSIONS: When assessing serial coronary stenoses, nonhyperemic pressure ratios are affected by hemodynamic interdependence. When the functional significance of serial coronary stenoses is severe, the effect is similar to that which is seen with FFR.

Antiplatelet therapy after percutaneous coronary intervention: current status and future perspectives.

Antiplatelet therapy after percutaneous coronary intervention (PCI) has been changing in parallel with the development of drug-eluting stents (DES) and antiplatelet agents. The recommendation of dual antiplatelet therapy duration is getting shorter due to the decreased risk of stent thrombosis in new-generation DES, the use of a P2Y12 inhibitor as a monotherapy, and the increasing prevalence of high bleeding risk patients. Antithrombotic therapy after PCI has also changed due to the introduction of direct oral anticoagulants. Aspirin-free P2Y12 inhibitor monotherapy is now being evaluated in several prospective studies as a novel strategy of antiplatelet therapy after PCI. This review shows a current status and provides future perspectives for the antiplatelet therapy after PCI.

Invasive Coronary Imaging Assessment for Cardiac Allograft Vasculopathy: State-of-the-Art Review.

Heart transplantation is the standard of care treatment for end-stage heart failure. Therapeutic advances including enhanced immunosuppression and aggressive infectious prophylaxis have led to increased life-expectancy following transplantation; however, cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality. Although coronary angiography is the current guideline-recommended diagnostic modality for invasive CAV screening, it is limited in its ability to detect early and/or diffuse disease. Efforts to improve outcomes for heart transplant recipients with CAV have focused on developing diagnostic tools with greater sensitivity to capture early CAV in order to better understand the pathobiology and implement treatment to slow disease progression sooner after transplant. The contemporary invasive imaging armamentarium for CAV surveillance includes coronary angiography, intravascular ultrasound, and newer technologies including optical coherence tomography and near-infrared spectroscopy. The present review outlines the use of and data in support of these imaging platforms in the CAV arena and highlights the potential advantages and limitations of each of these modalities.

Extent of the difference between microcatheter and pressure wire-derived fractional flow reserve and its relation to optical coherence tomography-derived parameters.

BACKGROUND: Although previous studies demonstrated that microcatheter-derived fractional flow reserve (mc-FFR) tends to overestimate lesion severity compared to pressure wire-derived FFR (pw-FFR), the clinical utility of mc-FFR remains obscure. The extent of differences between the two FFR systems and its relation to a lesion-specific parameter remain unknown. In this study, we sought to compare mc-FFR with pw-FFR and determine the lower and upper mc-FFR cut-offs predicting ischemic and non-ischemic stenosis, using an ischemic and a clinical FFR threshold of 0.75 and 0.80 as references, respectively. We further explored optical coherence tomography (OCT) parameters influencing the difference in FFR between the two systems. METHODS AND RESULTS: In this study, 44 target vessels with intermediate de novo coronary artery lesion in 36 patients with stable ischemic heart disease were evaluated with mc-FFR, pw-FFR and OCT. Bland-Altman plots for mc-FFR versus pw-FFR showed a bias of -0.04 for lower mc-FFR values compared to pw-FFR values. The mc-FFR cut-off values of 0.73 and 0.79 corresponded to the 0.75 ischemic pw-FFR and 0.80 clinical pw-FFR thresholds with high predictive values, respectively. The differences in the two FFR measurements (pw-FFR minus mc-FFR) were negatively correlated with OCT-derived minimum lumen area (MLA) (R = -0.359, p = 0.011). The OCT-derived MLA of 1.36 mm2 was a cut-off value for predicting the clinically significant difference between the two FFR measurements defined as >0.03. CONCLUSION: Mc-FFR is clinically useful when the specific cut-offs are applied. An OCT-derived MLA accounts for the clinically significant difference in FFR between the two systems.

Reconsideration of Secondary Risk Management Strategies in Patients with Ischemic Heart Disease.

The main risk factors in ischemic heart diseases, including myocardial infarction, are hypertension, dyslipidemia, diabetes, obesity and smoking. The incidence of ischemic heart disease in Japan has been lower than that in Western countries because of differences in lifestyle and the anatomy of the coronary arteries, but the situation has been changing recently because of the westernization of lifestyle. Cardiovascular diseases have become the second most common cause of death in Japan, and 40% of those deaths are attributed to ischemic heart disease. Patients with a history of myocardial infarction, especially, have an increased risk of re-infarction, so strict management of coronary risk factors is important for the prevention of secondary ischemic heart disease. Although there are many guidelines about how to manage the risk factors, there are still many problems. Although lipid management has been demonstrated to have a protective effect against coronary artery disease and arteriosclerotic guidelines have been developed, it is reported that only about one third of patients achieved the low-density lipoprotein (LDL) target value under secondary prevention. Moreover, it is unclear whether the lower target value is required for high-risk patients. Recent research on diabetes has reported increased mortality in patients with intensive glycemic control. We should discuss when to start treatment, which medicine to use, and to what extent we should manage glycemic control. Strict management based on current therapeutic guidelines is effective for secondary prevention of ischemic heart disease, with target values of less than 135/85 mmHg for home blood pressure, less than 100 mg/dl for LDL-C, more than 40 mg/dl for HDL-C, less than 150 mg/dl for TG, and, for diabetic patients, less than 7.0% for HbA1c (NGSP).

Impact of additional intracoronary nicorandil administration during fractional flow reserve measurement with intravenous adenosine 5'-triphosphate infusion.

BACKGROUND: Fractional flow reserve (FFR) is a useful index for determining the functional severity of epicardial coronary artery stenosis as an invasive physiological method. Although intravenous adenosine 5'-triphosphate (ATP) is generally used as a hyperemic agent for FFR measurement in Japan, there are some concerns about the variability of FFR measurement (short half-life, effect of caffeine, cyclic change). It is difficult to confirm sufficient maximum hyperemia after ATP infusion. Recent studies reported that nicorandil (NIC) could be an alternative to ATP as a hyperemic agent. METHODS: Patients who underwent FFR assessments of angiographically intermediate lesions were included. All patients were asked to refrain from caffeine-containing products more than 12hours before FFR measurements. All patients first received intravenous (IV) ATP infusion (180µg/kg/min) for 3min to measure FFR (ATP-FFR). After additional intracoronary (IC) NIC administration (2mg/30s) during ATP infusion, FFR was measured again (NIC-FFR). To check cyclic change in FFR, we measured minimum and maximum FFR values during both ATP and NIC hyperemic phase. RESULTS: In this study, 94 patients with 94 lesions were enrolled. Mean FFR value was 0.81±0.10 in ATP-FFR infusion and 0.80±0.09 in NIC-FFR, respectively. ATP-FFR and NIC-FFR had a strong correlation on the whole (r=0.92, p<0.001). In 18 patients (19%), FFR values were significantly lower in NIC-FFR than in ATP-FFR. In one-third of those patients (6%), it was possible to change therapeutic strategy from deferral range (>0.80) to interventional range (≦0.80) after NIC-FFR measurements. Cyclic change in FFR was smaller in NIC-FFR than in ATP-FFR (0.03±0.02 vs. 0.06±0.05, p<0.0001). CONCLUSION: Additional IC NIC might be useful to confirm sufficient maximum hyperemia after IV ATP infusion in daily clinical practice. Furthermore, IC NIC could reduce cyclic change in FFR; thus, physicians might find it easier to determine FFR value during the procedure.

Reduction of in-stent thrombus immediately after percutaneous coronary intervention by pretreatment with prasugrel compared with clopidogrel: An optical coherence tomography study.

BACKGROUND: Prasugrel is a new-generation thienopyridine antiplatelet agent that provides more consistent and prompt platelet inhibition than clopidogrel. The aim of this study was to compare in-stent thrombus inhibition effect of pretreatment with prasugrel and clopidogrel by using optical coherence tomography (OCT) immediately after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). METHODS: We performed OCT immediately after PCI in 108 ACS patients pretreated with either prasugrel (n=51) or clopidogrel (n=57). OCT detected thrombus/plaque protrusion in all stented segments. RESULTS: Although stent volume (190.4±119.1mm3 vs. 189.4±95.8mm3, p=0.961), mean stent area (6.9±2.9mm2 vs. 7.1±2.0mm2, p=0.772), and minimum stent area (5.6±2.7mm2 vs. 5.4±1.7mm2, p=0.554) were not different between the two groups, in-stent thrombus/plaque protrusion volume (1.8±2.9mm3 vs. 4.5±5.3mm3, p=0.002), mean in-stent thrombus/plaque protrusion area (0.1±0.1mm2 vs. 0.2±0.2mm2, p=0.005), and maximum in-stent thrombus/plaque protrusion area (0.5±0.7mm2 vs. 0.8±0.6mm2, p=0.007) were significantly smaller in the prasugrel group compared with the clopidogrel group. CONCLUSIONS: Pretreatment with prasugrel was associated with significantly reduced in-stent thrombus/plaque protrusion immediately after PCI for ACS compared with that with clopidogrel.

Impact of functional focal versus diffuse coronary artery disease on bypass graft patency.

BACKGROUND: Pressure guidewire pullback recording can differentiate between functional focal and diffuse disease types in coronary artery disease. The aim of this study was to compare the outcome of coronary artery bypass graft (CABG) patency between patients with functional focal versus diffuse disease types in recipient coronary arteries. METHODS AND RESULTS: We investigated 89 patients who underwent pressure guidewire pullback in the left anterior descending (LAD) artery before CABG using internal mammary artery (IMA). Based on the pressure guidewire pullback data, the LAD lesions were classified into functional focal disease (abrupt pressure step-up; n=58) or functional diffuse disease (gradual pressure increase; n=31). Follow-up computed tomography (CT) angiography was conducted within 1year after CABG to assess the bypass graft patency. Pre CABG, LAD angiographic percent diameter stenosis (57±10% vs. 54±12%, p=0.228) and fractional flow reserve (FFR) (0.68±0.07 vs. 0.69±0.07, p=0.244) were not different between the functional focal and diffuse disease groups. The CABG procedure characteristics were similarly comparable between the two groups. In the follow-up CT angiography after CABG, occlusion or string sign of the IMA graft to LAD was more frequently observed in the functional diffuse disease group than in the functional focal disease group (26% vs. 7%, p=0.021). CONCLUSION: In CABG, functional diffuse disease in the recipient coronary artery was associated with an increased risk of the graft failure in comparison with functional focal disease.

Coronary plaque progression of non-culprit lesions after culprit percutaneous coronary intervention in patients with moderate to advanced chronic kidney disease: intravascular ultrasound and integrated backscatter intravascular ultrasound study.

Previous studies have suggested that the deterioration of renal function increases the risk of major adverse clinical events not only in culprit lesions but also in non-culprit lesions (NCLs) after percutaneous coronary intervention (PCI). This study evaluated serial coronary plaque change of NCL in patients with different stages of chronic kidney disease (CKD) using intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS). In 113 patients (113 NCLs) underwent both IVUS-guided PCI and follow-up IVUS, volumetric IVUS analyses were performed at proximal reference NCLs in de novo target vessels post PCI and at 8-month follow-up. NCLs were divided into 4 groups based on baseline CKD stage: CKD-1, n = 18; CKD-2, n = 42; CKD-3, n = 29; and CKD4-5, n = 24. We compared serial changes of plaque burden and composition among groups under statin treatment. Plaque progression occurred in CKD-3 (+4.6 mm(3), p < 0.001) and CKD4-5 (+9.8 mm(3), p < 0.001) despite anti-atherosclerotic treatment, whereas plaque regression occurred in CKD-1 (-5.4 mm(3), p = 0.002) and CKD-2 (-3.2 mm(3), p = 0.001) mainly due to initiate statin treatment after PCI. Plaque volume change was correlated with eGFR (p < 0.0001). Multivariate analysis showed CKD stage 3-5 was an independent predictor of plaque progression. Regarding IB-IVUS analyses, lipid plaque increased in CKD-3 (+4.6 mm(3), p < 0.001) and CKD4-5 (+5.4 mm(3), p < 0.001), but decreased in CKD-2 (-2.7 mm(3), p < 0.05). Fibrotic plaque also increased in CKD4-5 (+3.4 mm(3), p < 0.001). Moderate to advanced CKD was associated with coronary plaque progression characterized by greater lipid and fibrotic plaque volumes in NCL under statin treatment after culprit PCI.

A rare case of myocardial infarction related to diagnostic intravascular ultrasound.

A 71-year-old man underwent intracoronary stent implantation for acute inferior myocardial infarction (MI). Immediately after diagnostic intravascular ultrasound (IVUS) at 8 months' follow-up, an acute occlusion of the sinus node (SN) artery appeared, which developed sinus arrest with junctional escape rhythm. The serum level of high-sensitivity troponin T (TpT) was markedly elevated on the day after the procedure (2.1-32.5 ng/l), which was indicative of MI related to IVUS. Under continuous intravenous infusion of unfractionated heparin, the escape rhythm changed to lower atrial rhythm on the 4th day, and recovered to sinus rhythm on the 14th day. Coronary angiography (CAG) on 15th day showed a recanalization of the SN artery, but optical coherence tomography identified that disrupted plaque and white thrombus still existed in the ostium of the SN artery. The patient was discharged on maintenance anticoagulation therapy. We hypothesized from this case that IVUS-related myocardial injury may exist without clinical problems. Our retrospective investigation showed that the median levels of high-sensitivity TpT in 20 patients who underwent CAG and subsequent diagnostic IVUS significantly increased from 0.6 (interquartile range 0.3-1.1) to 1.6 (0.7-3.6) ng/l (P < 0.05), suggesting that IVUS may induce very low levels of myocardial injury. In conclusion, we experienced a rare case of IVUS-related MI caused by an acute occlusion of the SN artery. This case reaffirms that we should pay more attention to manipulation of IVUS catheters.

Successful coronary intervention for spontaneous coronary dissection in a patient with fibromuscular dysplasia.

Spontaneous coronary artery dissection (SCAD) is a reported rare cause of acute coronary syndrome (ACS) and sudden death among middle-aged women. Some institutes have recently reported fibromuscular dysplasia (FMD) concomitant with SCAD. Therefore, a survey of the presence of comorbid FMD in SCAD patients is important to obtain a definitive diagnosis and for the prediction of possible SCAD recurrence. The optimal treatment of ACS due to SCAD remains undetermined, and technical failures are frequently encountered in primary percutaneous coronary intervention (PCI) owing to the unusual non-atherosclerotic cause of the disease. We report a case of SCAD successfully treated with cutting balloon PCI under intravascular ultrasound guidance without stent implantation, in which FMD was detected in the right external iliac artery through screening by noncoronary angiography, not duplex ultrasound. .

Coronary arterial remodeling and out-stent plaque change after drug-eluting stent implantation--comparison between zotarolimus-eluting stents and paclitaxel-eluting stents.

BACKGROUND: Out-stent plaque characteristics and eosinophilic inflammatory response, which correlates with positive remodeling after first-generation drug-eluting stent implantation, may be associated with late restenosis and very late stent thrombosis. The differences of out-stent plaque characteristics were compared between paclitaxel-eluting stents (PES) and zotarolimus-eluting stents (ZES), using integrated backscatter-intravascular ultrasound (IB-IVUS). METHODS AND RESULTS: Of 78 patients enrolled, 25 receiving PES and 25 receiving ZES had adequate IVUS assessment. Volumetric IVUS analysis was performed after stenting and at 8-month follow-up. Out-stent plaque change in the stented segment was compared on IB-IVUS. The relationship between systemic inflammatory response and out-stent plaque change was evaluated. In PES, vessel volume significantly increased (365-389 mm(3), P<0.0001), whereas it did not change in ZES (315-314 mm(3), P=0.81). In culprit lesions at baseline in PES, fibrous plaque tended to increase (3.1-3.6mm(2), P=0.051) and lipid plaque significantly increased (4.3-5.1mm(2), P=0.02), whereas in ZES the fibrous plaque significantly increased (2.9-4.0mm(2), P<0.0001) but lipid plaque significantly decreased (5.1-3.6mm(2), P<0.0001). Systemic eosinophil increase was significantly correlated with positive remodeling and out-stent lipid plaque increase. CONCLUSIONS: Chronic out-stent plaque change in ZES consisted of less positive remodeling and more favorable effects on out-stent plaque characteristics than PES. Systemic eosinophil change might be a marker of out-stent lipid plaque change.

Proposed cutoff level of waist circumference in Japanese men: evaluation by homeostasis model assessment of insulin resistance levels.

OBJECTIVE: The aim of this study is to propose the cutoff level of waist circumference (WC) on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) levels in order to diagnose metabolic syndrome (MetS). METHODS: We examined a total of 798 non-diabetic men (40-65 years of age) by using a receiver operating characteristic (ROC) curve to determine the cutoff level that yielded the maximum sensitivity plus specificity. According to the criteria proposed by the International Diabetes Federation (IDF), and the Japanese Society of Internal Medicine (JSIM), subjects with ≥ 2 metabolic components other than abdominal obesity, were considered to have MetS. RESULTS: The overall prevalence rates of IDF- and JSIM-MetS were 17.4% (n=139) and 15.5% (n=124), respectively. The median levels of WC and HOMA-IR were 83.1 [interquartile range (IQR): 78.5-88.4] cm and 0.84 (IQR: 0.61-1.19), respectively. HOMA-IR was highly correlated with each metabolic parameter (each p<0.05), and in addition, multiple linear regression analysis of HOMA-IR (adjusted R2=0.459) showed that WC level was the strongest independent predictors of HOMA-IR level (F=141.1, p<0.05). According to ROC curve analysis, the cutoff level of HOMA-IR for predicting IDF- and JSIM-MetS was 0.92 for both (sensitivity: 79.9% and 78.2%, specificity: 64.9% and 63.6%). Based on the HOMA-IR level, the proposed WC cutoff level was 82.7 cm (sensitivity: 75.4%, specificity: 63.8%). CONCLUSION: This study suggests that WC level should be more strictly managed than current criteria, for preventing the development of MetS in non-diabetic middle-aged Japanese men.

Intravascular ultrasound and histopathological observations in a patient with very late sirolimus-eluting stent thrombosis.

This case report describes an autopsy case of very late stent thrombosis, which was associated with intravascular ultrasound findings of late-acquired stent malapposition with thrombotic materials and marked positive vascular remodeling at the site of the sirolimus-eluting stent implantation. Histopathological examination showed both destructive and proliferative reactions had occurred in the same stented coronary arterial wall 44 months after sirolimus-eluting stent implantation. Long-lasting severe local inflammation beyond healing reaction, causing vessel enlargement, may be related to very late stent thrombosis.

Evaluation of in-stent neointimal tissue components using integrated backscatter intravascular ultrasound: comparison of drug-eluting stents and bare-metal stents.

Although in-stent restenosis (ISR) occurs after drug-eluting stents (DES) implantation, neointimal tissue characteristics have not been fully investigated. We assessed neointimal tissue components using integrated backscatter intravascular ultrasound (IB-IVUS) after DES and bare-metal stents (BMS) implantation. Fifty-seven consecutive patients with 61 lesions underwent repeated percutaneous coronary intervention (PCI) for the treatment of ISR (DES: 24 lesions, BMS: 37 lesions). PCI was performed using plain old balloon angioplasty (POBA). Before PCI, we assessed neointimal tissue characteristics using IB-IVUS. Neointima was divided into four categories: category 1 (-11 to -29 dB), category 2 (-29 to -35 dB), category 3 (-35 to -49 dB), and category 4 (-49 to -130 dB) according to IB values. We compared neointimal tissue components between DES and BMS. Thirty-three patients with 33 lesions (DES: 17, BMS: 16) were finally included. Neointima was predominantly composed of category 3 tissue in both groups (DES: 68 ± 8%, BMS: 73 ± 5%, P = 0.053). DES had a broader distribution of category 4 tissue component than BMS. After POBA, distal slow flow phenomenon occurred in 5 of DES (29%), whereas none of BMS. In DES, the optimal threshold of category 4 tissue to predict distal slow flow phenomenon after POBA was 30% (sensitivity: 100%, specificity: 92%). Neointima was mainly composed of category 3 tissue at ISR site, irrespective of DES or BMS. In DES, there was a subgroup with category 4 rich tissue, which caused distal slow flow phenomenon after POBA. IB-IVUS might be useful to identify vulnerable neointima in DES restenosis.