Provisional drug-coated balloon treatment guided by physiology on de novo coronary lesion.

Although drug-eluting stents (DES) have become the mainstay of percutaneous coronary intervention, late and very late stent thrombosis remains a concern. Drug-coated balloons (DCB) have the advantage of preserving the anti-restenotic benefits of DES while minimizing potential long-term safety concerns. Currently the two methods to ensure successful DCB treatment of a stenotic lesion are angiography or physiology-guided DCB application. This review will evaluate these two methods based on previous evidence and make suggestions on how to perform DCB treatment more efficiently and safely.

Effect of Sex Difference of Coronary Microvascular Dysfunction on Long-Term Outcomes in Deferred Lesions.

OBJECTIVES: This study investigated the sex difference of long-term cardiovascular outcomes on coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with deferred coronary artery lesions. BACKGROUND: Coronary microvascular dysfunction is associated with poorer long-term outcomes. It can be assessed by CFR and the IMR. METHODS: The study prospectively enrolled 434 patients (133 women and 301 men) and analyzed CFR, IMR, fractional flow reserve, and quantitative coronary angiography. Clinical outcomes were assessed by major adverse cardiovascular event(s) (MACE) of cardiac death, myocardial infarction, and revascularization during 5 years of follow-up. The study protocol was approved by the Institutional Review Board or Ethics Committee at each participating center, and all patients provided written informed consent. The study protocol was in accordance with the Declaration of Helsinki. RESULTS: Women had milder epicardial disease compared with men (fractional flow reserve: 0.91 [interquartile range (IQR): 0.87 to 0.96] vs. 0.90 [IQR: 0.86 to 0.95]; p = 0.037). IMR was similar between the sexes, but CFR was lower in women (2.69 [IQR: 2.08 to 3.90] vs. 3.20 [IQR: 2.20 to 4.31]; p = 0.006) due to a shorter resting mean transit time, whereas hyperemic mean transit times were similar. At 5-year follow-up, MACE was significantly lower in women compared with men (1.1% vs. 5.5%; p = 0.017). Sex, diabetes mellitus, and CFR were independent predictors for MACE for all patients. The risk of MACE was significantly higher in men with low versus high CFR (hazard ratio: 4.58; 95% confidence interval: 1.85 to 11.30; p = 0.011) which was not seen in women. CONCLUSIONS: There was no sex difference in microvascular function by IMR. CFR was lower in women due to a higher resting coronary flow; however, long-term clinical outcomes in deferred lesions were better in women compared with men. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093).

Instantaneous wave-free ratio-guided paclitaxel-coated balloon treatment for de novo coronary lesions.

Paclitaxel-coated balloon (PCB) treatment guided by fractional flow reserve (FFR) is safe and effective for de novo coronary lesions. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR in de novo lesion treatment with PCB. Baseline, post-balloon and 9-month angiographical parameters were obtained from 116 lesions of 104 patients. The cutoff value of iFR after balloon angioplasty used to define functionally nonsignificant residual stenotic lesions was 0.86 and they were subdivided into PCB or Stent group according to the treated device. The primary endpoint was late lumen loss at 9 months and the secondary endpoint was target vessel failure (TVF) at 3 years. Fifty-eight lesions were treated with PCB only and 58 lesions were treated with metal stent implantation. There were no differences in iFR between PCB and Stent groups at baseline (0.76 ± 0.19 vs. 0.73 ± 0.23, p = 0.630) and after procedure (0.93 ± 0.04 vs. 0.94 ± 0.05, p = 0.574). At 9 months, late lumen loss was significantly lower in PCB group compared with Stent group (0.04 ± 0.32 mm vs. 0.59 ± 0.77 mm, p = 0.001). At 3-year follow-up, TVF were not different between the treatment groups (5.2% vs. 8.6%, p = 0.453). PCB treatment guided by iFR measured right after balloon angioplasty is safe and effective for de novo coronary lesions with good angiographic results at 9 months and similar clinical outcomes at 3 years compared to stent group.

Comparison of fractional flow reserve and angiographic characteristics after balloon angioplasty in de novo coronary lesions.

Lesion characteristics determined by angiography after balloon angioplasty such as residual dimeter stenosis (DS) or dissection type has been used to determine the treatment method of drug-coated balloon (DCB) or metal stent for de novo coronary lesions. The aim of this study is to identify angiographic and functional mismatch using residual DS, dissection type and fractional flow reserve (FFR). Baseline and post-balloon parameters were obtained from 151 patients with 167 lesions. Angiographically significant parameters after balloon angioplasty are residual DS > 30% or dissection type C or more. Post-balloon FFR cutoff value of 0.75 was used to define functionally significant lesions. The weak correlation was found between residual DS and post-balloon FFR (r =  - 0.317, p < 0.001). There were 68.7% of mismatch population (residual DS > 30% and post-balloon FFR ≥ 0.75) and 7.1% of reverse mismatch population (residual DS ≤ 30% and post-balloon FFR < 0.75). All reverse mismatch lesions were found in left anterior descending artery. There was no correlation between dissection severity and post-balloon FFR (p = 0.654). In high post-balloon FFR group, long-term clinical outcomes showed no difference between DCB and stent groups with (p = 0.788) or without (p = 0.426) the adjustment of lesion characteristics. There were high frequencies of mismatch between angiographic lesion characteristics and FFR values after balloon angioplasty. Post-balloon FFR measurements may be safe and effective compared to angiography-guided treatment if DCB only treatment is considered.

Prospective randomized trial of paclitaxel-coated balloon versus bare-metal stent in high bleeding risk patients with de novo coronary artery lesions.

BACKGROUND: In patients with high bleeding risk, percutaneous coronary intervention is still debated. This study compared 9-month angiographic and physiologic results in patients with high bleeding risk and de novo coronary lesions treated with either paclitaxel-coated balloon (PCB) or bare-metal stent (BMS). PATIENTS AND METHODS: A total of 40 patients (40 lesions) with high bleeding risk who underwent successful balloon angioplasty with fractional flow reserve (FFR) after balloon angioplasty more than 0.80 were randomized 1: 1 to treatment with PCB versus BMS. Dual antiplatelet therapy was limited to 1 month after the procedure. RESULTS: Baseline clinical and lesional characteristics were well balanced between the two groups. There was no significant difference in the postprocedural FFR (0.87 ± 0.06 in PCB vs. 0.89 ± 0.06 in BMS, P = 0.254). At 9 months, late luminal loss was significantly lower in the PCB group (0.2 ± 0.3 vs. 1.2 ± 0.8 mm, P < 0.001). Restenosis only occurred in the BMS group (0 vs. 25.0%, P = 0.049). CONCLUSION: In patients with high bleeding risk, FFR-guided PCB treatment showed superior efficacy in terms of angiographic and physiologic patency compared with BMS at mid-term follow-up with only 1 month of dual antiplatelet therapy (Clinicaltrials.gov identifier, NCT02456402).

Vasoconstrictor component of atherothrombotic culprit lesions in ST-segment elevation myocardial infarction.

OBJECTIVE: The vasoconstrictor component of atherothrombotic culprit lesions in ST-elevation myocardial infarction (STEMI) patients has not been fully investigated. This study was aimed at assessing the vasoconstrictor component of atherothrombotic culprit lesions in patients with STEMI receiving primary percutaneous coronary intervention (PCI). METHODS: A group of 100 patients with STEMI were enrolled prospectively. Baseline coronary angiography achieving normal antegrade flow was followed by 200 µg of intracoronary nitroglycerin (NTG) injection and repeat coronary angiography at the same projection view for culprit lesions was performed. End points were the changes in lesion length, reference vessel diameter, minimal lumen diameter, and diameter stenosis by quantitative coronary analysis before and after NTG injection. RESULTS: Reference vessel diameter (2.7 ±â€¯0.5 mm vs. 2.9 ±â€¯0.5 mm, p < 0.001) and minimal lumen diameter (0.9 ±â€¯0.4 mm vs. 1.2 ±â€¯0.5 mm, p < 0.001) increased after NTG injection, whereas lesion length (24.1 ±â€¯7.4 mm vs. 23.4 ±â€¯7.6 mm, p = 0.001) and diameter stenosis (66.6 ±â€¯14.8% vs. 58.3 ±â€¯16.1%, p < 0.001) decreased. The median percentage change of diameter stenosis was -4.0% (Interquartile range: -13.8% to -1.0%), which was used as the cut-off value to divide the cohort into NTG responder or nonresponder groups accordingly. Total stent length was significantly shorter in the responder group compared with the nonresponder group (27.4 ±â€¯11.6 mm vs. 33.7 ±â€¯16.8 mm, p = 0.042). CONCLUSION: This study showed the presence of a vasoconstrictor component in atherothrombotic culprit lesions in STEMI patients receiving primary PCI. Vasodilating effort by NTG may decrease stent length used for culprit lesions.

Plaque modification and stabilization after paclitaxel-coated balloon treatment for de novo coronary lesions.

This study aimed to assess the healing response, as evidenced through temporal morphological and functional changes, following paclitaxel-coated balloon (PCB) treatment of de novo coronary lesions. This retrospective, observational study, included patients with significant de novo coronary lesions who were treated with PCB and had serial angiographic, intravascular ultrasound virtual histology (IVUS-VH), fractional flow reserve (FFR) measurements, and optical coherence tomography (OCT) performed before balloon angioplasty (BA), after BA, and at 9-month follow-up. A total of 20 patients (21 lesions) were included in this study. After PCB treatment, IVUS showed significant increases in the mean vessel area (12.0 ± 2.2 mm2 to 13.8 ± 2.5 mm2, p = 0.023), and mean lumen area (5.6 ± 1.2 mm2 to 7.0 ± 1.5 mm2, p = 0.003). Coronary flow was restored after BA with an FFR value of 0.87 ± 0.04 which was sustained at 9-month follow-up with no significant decrease (0.83 ± 0.08, p = 0.329). Serial OCT analysis showed that at 9-month follow-up dissections after BA sealed in 14 lesions (67%), whilst the macrophages decreased from 10 (50%) to 7 (35%) lesions, and the cap thickness of plaque increased from 0.12 ± 0.06 mm to 0.17 ± 0.09 mm (p = 0.007). PCB treatment for de novo coronary lesions showed persistent anatomical and functional patency at mid-term follow-up. Plaque modification, vascular remodeling, and plaque stabilization were also observed during follow-up.

Comparison of exercise electrocardiography and magnetocardiography for detection of coronary artery disease using ST-segment fluctuation score.

BACKGROUND: Exercise electrocardiography (ECG) is frequently used as a diagnostic measure in patients with suspected coronary artery disease (CAD). However, it has low sensitivity for the detection of CAD. Magnetocardiography (MCG) has been proposed as an alternative tool to accurately diagnose CAD. OBJECTIVE: To date, a direct comparison of MCG to ECG has not been performed. This study sought to compare them for predicting the presence of significantly obstructive CAD. METHODS: The patients with chest pain or other symptoms suggestive of CAD were enrolled in the analysis. All the patients underwent a clinical evaluation, exercise ECG, MCG test, and coronary angiography (CA). CAD was defined as stenosis ≥70% in at least one major coronary artery on quantitative analysis of CA. RESULTS: We prospectively enrolled 202 consecutive patients who suggested CAD. The prevalence of CAD on CA was 39.1%. Sensitivity and accuracy for CAD diagnosis was higher for MCG compared with exercise ECG (sensitivities 68.4% and 40.5%, p <0.001, specificities 95.1% and 91.1%, p = 0.267, and accuracies 84.7% and 71.3%, p <0.001, respectively). There was no incremental diagnostic value of combined MCG and ECG to detect coronary artery disease (p = 0.357). CONCLUSIONS: For the patients with intermediate to high risk of CAD, MCG exercise test provides better diagnostic accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG.

Coronary microvascular disease and clinical prognosis in deferred lesions: The index of microcirculatory resistance.

While fractional flow reserve (FFR) is a good diagnostic index to assess the myocardial ischemia, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) can be used to address microvascular status without any significant epicardial disease. The independent predictors for FFR and IMR are totally different and acts differently on the macro- and micro-vascular dysfunction. In high FFR patients, low CFR and high IMR which indicates the presence of overt microvascular disease demonstrated poor prognosis. Thus, comprehensive physiological assessments using FFR, CFR and IMR could improve the ability to discriminate patients at high risk of future events.

The clinical impact of sex differences on ischemic postconditioning during primary percutaneous coronary intervention: a POST (the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction) substudy.

The POST (the effects of postconditioning on myocardial reperfusion in patients with ST-Segment elevation myocardial infarction) study showed that ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, it has not been determined whether postconditioning is effective in women. This study sought to evaluate the impact of sex differences on ischemic postconditioning during the primary PCI. We analyzed clinical outcomes at 1 year in the 537 men and 163 women with STEMI, who were randomized to the postconditioning or to the conventional PCI group. Women were older, had higher rates of hypertension, were less likely to be current smokers, and had longer symptom-to-reperfusion time. The rate of major adverse cardiac events (MACE: a composite of death, myocardial infarction, severe heart failure, stent thrombosis, or target vessel revascularization) at 1 year was higher in women compared to men (9.8% vs. 5.4%, p = 0.044). MACE was significantly higher in women compared to men in the postconditioning group (12.2% vs. 5.4%, p = 0.042), but not in the conventional PCI group (7.9% vs. 5.4%, p = 0.391). However, women was not an independent predictor after adjusting baseline risk factors, angiographic and procedural parameters (HR 2.67, 95% CI 0.68-10.5, p = 0.158). Despite women having more adverse clinical characteristics, their prognosis was similar to men in the conventional group. Although women showed a higher rate of the MACE compared to men, women were not an independent predictor in the postconditioning group.

Plaque Characteristics and Ruptured Plaque Location according to Lesion Geometry in Culprit Lesions of ST-Segment Elevation Myocardial Infarction.

BACKGROUND AND OBJECTIVES: The correlations between plaque characteristics and plaque rupture location according to segmental lesion analysis have not been well defined. The aim of this study was to assess those characteristics of ST-segment elevation myocardial infarction (STEMI) culprit lesions according to segmental lesion geometry using virtual histology intravascular ultrasound (VH-IVUS). METHODS: Sixty single discrete lesions found in the left anterior descending (LAD) coronary arteries of 60 patients with STEMI were included. Each lesion was divided into 3 segments based on lumen area (LA) index, calculated by dividing the lesion LA by the reference LA. RESULTS: Among the 3 segments, the mid-segment showed the highest proportion of necrotic core (NC; proximal, mid-, and distal segments: 20.9±11.8%, 22.7±11.3%, and 17.5±11.2%, respectively, p=0.044). VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) was also more frequently found in the mid-segment than in proximal and distal segments (36.7%, 58.3%, and 16.7%, p<0.001). The mid-segment also showed the highest prevalence of plaque rupture (45.0%, 78.3% and 11.7%, p<0.001) and thrombus (61.7%, 95.0%, and 41.7%, p<0.001) compared to proximal or distal segments. When the lesions were divided into 2 groups according to the median value (4.0 mm²) of minimum lumen area (MLA), plaque rupture at the distal segment was observed only in high MLA lesions (23.3% vs. 0.0%, p=0.011). CONCLUSION: Analysis of longitudinal lesion geometry using the LA index can be useful in evaluating plaque vulnerability and the incidence of plaque rupture and thrombus in STEMI patients.

Diagnostic Performance of a Novel Method for Fractional Flow Reserve Computed from Noninvasive Computed Tomography Angiography (NOVEL-FLOW Study).

Coronary computed tomography angiography (CCTA)-derived fractional flow reserve from computed tomography (CT-FFR) may provide better diagnostic performance over CCTA alone, but the complexity of its method limits the use in clinical environment. The aim of the present study is to validate a newly developed vessel-length based computational fluid dynamics scheme for the computation of FFR based on CCTA data, compare them with invasively measured FFR, and evaluate its diagnostic performance with that of CCTA. One hundred seventeen patients from 4 medical institutions who had clinically indicated invasive coronary angiography for suspected coronary artery disease (CAD) were enrolled. Invasive FFR measurement was performed in 218 vessels and these measurements were regarded as the reference standard. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CT-FFR on a per-vessel basis were 85.8%, 86.2%, 85.5%, 79.8%, and 90.3%, respectively, for CT-FFR ≤0.80, and 66.1%, 75.9%, 59.5%, 55.5%, and 78.8%, respectively, for CCTA ≥50%. A higher area under the receiver operating characteristic curve for CT-FFR was observed compared with CCTA (0.93 vs 0.74, p <0.0001). The CT-FFR and FFR correlated well (r = 0.76, p <0.001) with slight underestimation by CT-FFR (0.014 ± 0.077, p = 0.007). With a novel method of vessel-length based computational fluid dynamics scheme, CT-FFR can be performed at a personal computer enhancing its applicability in clinical situation. The diagnostic accuracy of CT-FFR for the detection of functionally significant CAD was good and was superior to that of CCTA within a population of suspected CAD.

A patient-specific virtual stenotic model of the coronary artery to analyze the relationship between fractional flow reserve and wall shear stress.

OBJECTIVE: As the stenotic severity of a patient increases, fractional flow reserve (FFR) decreases, whereas the maximum wall shear stress (WSSmax) increases. However, the way in which these values can change according to stenotic severity has not previously been investigated. The aim of this study is to devise a virtual stenosis model to investigate variations in the coronary hemodynamic parameters of patients according to stenotic severity. METHODS: To simulate coronary hemodynamics, a three-dimensional (3D) coronary artery model of computational fluid dynamics is coupled with a lumped parameter model of the coronary micro-vasculature and venous system. RESULTS: To validate the present method, we first simulated 13 patient-specific models of the coronary arteries and compared the results with those obtained clinically. Then, virtually narrowed coronary arterial models derived from the patient-specific cases were simulated to obtain the WSSmax and FFR values. The variations in FFR and WSSmax against the percentage of diameter stenosis in clinical cases were reproducible by the virtual stenosis models. We also found that the simulated FFR values were linearly correlated with the WSSmax values, but the linear slope varied by patient. CONCLUSION: We implemented 130 additional virtual models of stenosed coronary arteries based on data from 13 patients and obtained statistically meaningful results that were identical to the large-scale clinical studies. And the slope of the correlation line between FFR and WSSmax may help clinicians to design treatment plans for patients.

Segmental assessments of coronary plaque morphology and composition by virtual histology intravascular ultrasound and fractional flow reserve.

Fractional flow reserve (FFR) is an index for identifying functionally significant stenotic lesions. A FFR value of ≤0.75 is considered clinically significant and indicative of physiological ischemia. Focal lesions with 30-80 % stenosis by angiography with lesion lengths of less than 20 mm were selected from left anterior descending arteries of 74 patients. The analysis for the total lesion was processed first, and then each lesion was divided into three segments to assess the each segment. Data on plaque geometry and composition of two FFR groups, FFR ≤ 0.75 and FFR > 0.75, were compared by total and segmental analysis. Lesions with FFR ≤ 0.75 had more fibrofatty tissue (13.5 ± 7.4 vs. 10.2 ± 6.5%, p = 0.05) and less dense calcium (7.2 ± 5.3 vs. 11.9 ± 7.5%, p = 0.01) compared to lesions with FFR > 0.75. The content of necrotic core in mid segments was higher compared to proximal and distal segments (22.9 ± 10.6, 20.2 ± 10.9, 17.1 ± 11.2%, respectively, p = 0.032) in lesions with FFR > 0.75 but the difference was less obvious in lesions with FFR ≤ 0.75 (17.9 ± 9.9, 18.7 ± 9.9, 15.8 ± 9.0%, respectively, p = 0.533). Coronary lesions with FFR > 0.75 have larger content of dense calcium and slightly less fibrofatty tissue compared to lesions with FFR ≤ 0.75. While segmental plaque compositions for each segment show noticeable variations in lesions with FFR > 0.75 such as high concentrations of necrotic core in mid segment, these differences in each segment become obscure in FFR ≤ 0.75 and are evenly distributed across the lesion.

Assessment of stent edge dissections by fractional flow reserve.

BACKGROUNDS: Edge dissections after intervention have been studied with imaging techniques, however, functional assessment has not been studied yet. We investigated the relationship between fractional flow reserve (FFR) and the angiographic type of stent edge dissections and tried to assess the use of FFR-guided management for edge dissection. METHODS: 51 edge dissections assessed by FFR were included in this prospective observational study. FFR was measured for each type of edge dissection and compared with quantitative coronary angiographic findings. Clinical outcomes were evaluated based on FFR measurements. RESULTS: Edge dissections were classified as type A (47.1%; 24/51), type B (41.2%; 21/51), type C (2.0%; 1/51) and type D (9.8%; 5/51). Mean FFR in type A dissection was 0.87 ± 0.09, in type B 0.86 ± 0.07, in type C 0.72 and in type D 0.57 ± 0.08. All type C and D dissections (6/51) had FFR ≤ 0.8 and were treated with additional stents. Among the 45 type A and B dissections, 8 had a FFR ≤ 0.8 (17.8%), and 50% received additional stenting. All dissections with FFR >0.8 were left untreated except one long dissection case. There was no death, myocardial infarction or target lesion revascularization during hospitalization or the follow-up period (median 152 days; IQR 42-352 days). CONCLUSIONS: FFR correlates well with an angiographic type of edge dissection. Angiographic findings are sufficient for deciding the treatment of severe dissections such as types C and D, while FFR-guided management may be safe and effective for mild edge dissections such as types A and B.