Real-World Effectiveness of Statin Therapy in Adult Asthma.

BACKGROUND: Blood lipids affect airway inflammation in asthma. Although several studies have suggested anti-inflammatory effects of statins on asthmatic airways, further studies are needed to clarify the long-term effectiveness of statins on asthma control and whether they are an effective treatment option. OBJECTIVE: To evaluate the long-term effectiveness of statins in the chronic management of adult asthma in real-world practice. METHODS: Electronic medical record data spanning 28 years, collected from the Ajou University Medical Center in Korea, were used to conduct a retrospective study. Clinical outcomes were compared between patients with asthma who had maintained statin use (the statin group) and those not taking statins, whose blood lipid tests were always normal (the non-statin group). We performed propensity score matching and calculated hazard ratios with 95% CIs using the Cox proportional hazards model. Severe asthma exacerbation was the primary outcome; asthma exacerbation, asthma-related hospitalization, and new-onset type 2 diabetes mellitus and hypertension were secondary outcomes. RESULTS: After 1:1 propensity score matching, the statin and non-statin groups each included 545 adult patients with asthma. The risk of severe asthma exacerbations and asthma exacerbations was significantly lower in the statin group than in the non-statin group (hazard ratios [95% CI] = 0.57 [0.35-0.90] and 0.71 [0.52-0.96], respectively). There were no significant differences in the risk of asthma-related hospitalization or new-onset type 2 diabetes mellitus or hypertension between groups (0.76 [0.53-1.09], 2.33 [0.94-6.59], and 1.71 [0.95-3.17], respectively). CONCLUSION: Statin use is associated with a lower risk of asthma exacerbation, with better clinical outcomes in adult asthma.

A randomized, double-blind, multicenter, phase III study on the efficacy and safety of a combination treatment involving fimasartan, amlodipine, rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy.

BACKGROUND: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. METHODS: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. RESULTS: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions. CONCLUSIONS: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. TRIAL REGISTRATION: NCT03156842, Registered 17 May 2017.

Epicardial Adipose Tissue Thickness Is Related to Plaque Composition in Coronary Artery Disease.

(1) Background: Currently, limited data are available regarding the relationship between epicardial fat and plaque composition. The aim of this study was to assess the relationship between visceral fat surrounding the heart and the lipid core burden in patients with coronary artery diseases; (2) Methods: Overall, 331 patients undergoing coronary angiography with combined near-infrared spectroscopy and intravascular ultrasound imaging were evaluated for epicardial adipose tissue (EAT) thickness using transthoracic echocardiography. Patients were divided into thick EAT and thin EAT groups according to the median value; (3) Results: There was a positive correlation between EAT thickness and maxLCBI4mm, and maxLCBI4mm was significantly higher in the thick EAT group compared to the thin EAT group (437 vs. 293, p < 0.001). EAT thickness was an independent predictor of maxLCBI4mm ≥ 400 along with age, low-density lipoprotein-cholesterol level, acute coronary syndrome presentation, and plaque burden in a multiple linear regression model. Receiver operating characteristic curve analysis showed that EAT thickness was a predictor for maxLCBI4mm ≥ 400; (4) Conclusions: In the present study, EAT thickness is related to the lipid core burden assessed by NIRS-IVUS in patients with CAD which suggests that EAT may affect the stability of the plaques in coronary arteries.

Performance evaluation of biodegradable polymer sirolimus and ascorbic acid eluting stent systems.

The purpose of this study was to evaluate the performance of biodegradable polymer sirolimus and ascorbic acid eluting stent systems with four commercially available drug-eluting stents (DES). We investigated the characterization of mechanical properties by dimension, foreshortening, recoil, radial force, crossing profile, folding shape, trackability, and dislodgement force. Additionally, we identify the safety and efficacy evaluation through registry experiments. Each foreshortening and recoil of D + Storm® DES is 1.3 and 3.70%, which has better performance than other products. A post-marketing clinical study to evaluate the performance and safety of D + Storm® DES is ongoing in real-world clinical settings. Two hundred one patients were enrolled in this study and have now completed follow-up for up to 1 month. No major adverse cardiovascular event (MACE) occurred in any subjects, confirming the safety of D + Storm® DES in the clinical setting. An additional approximately 100 subjects will be enrolled in the study and the final safety profile will be assessed in 300 patients. In conclusion, this study reported the objective evaluation of DES performance and compared the mechanical responses of four types of DES available in the market. There is little difference between the four cardiovascular stents in terms of mechanical features, and it can help choose the most suitable stent in a specific clinical situation if those features are understood. Graphical abstract.

Stent dislodgement force of drug-eluting coronary stents: a bench test.

Background: Coronary stent dislodgement can cause critical complications. The dislodgement force of coronary drug-eluting stents (DES) remains unknown. This study aimed to compare the dislodgement force and pattern of contemporary DES. Methods: Five DES designs which commonly used in clinical practice were tested. The force at which the stent dislodges relative to the balloon was measured. For the shim test, peak displacement force, defined as the first peak force that occurs during stent displacement and peak dislodgement force, defined as the peak force required to completely dislodge the stent from the delivery system, were measured. Three examples of each of the stents were tested using the shim test. Results: The peak displacement force of Orsiro (3.1±0.8 N) was lower than that of Xience Sierra (5.8±0.5 N) [Firehawk 3.8±0.2 N, Resolute Onyx 4.5±1.5 N, Synergy 4.8±0.5 N (P=0.024)]. The peak dislodgement force was lowest in Orsiro (3.2±0.8 N) when compared to the other stents (Firehawk 6.6±0.6 N, Resolute Onyx 7.4±0.3 N, Synergy 11.8±0.4 N, Xience Sierra 11.1±1.6 N) (P<0.001); this remained significant in the multiple comparison analysis. During pullback of the stents, most stents buckled without removal. However, the whole Orsiro stent was completely removed from the delivery system. Conclusions: The dislodgement force of DESs differed between stent designs. The Orsiro stent was lower than that of other DES; additionally, it easily removed the whole stent from the delivery system. During the coronary intervention, operators should consider stent design and be cautious when pulling DES back in lesions with calcifications or a previously implanted stent, which are at high risk for stent dislodgement.

Efficacy and Safety of 3 Versus 6 Months of Dual-Antiplatelet Therapy in Patients Implanted With a Coroflex ISAR Stents: A Prospective, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of dual-antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES), especially recently developed polymer-free DESs, is unknown. This study examined the efficacy and safety of 3- versus 6-month DAPT in patients implanted with Coroflex ISAR polymer-free DESs. METHODS: Between May 2015 and August 2020, 488 patients who underwent Coroflex ISAR stent implantation were enrolled in the study and randomly assigned to the 3-month (n=244) or 6-month (n=244) DAPT group. RESULTS: At 1 year, the primary endpoint (composite of cardiovascular death, myocardial infarction, target vessel revascularization, and Bleeding Academic Research Consortium [BARC] type 2-5 bleeding) occurred in 9 (3.7%) patients in the 3-month DAPT group and in 7 (2.9%) patients in the 6-month DAPT group (hazard ratio 1.31; P=.60). There was no difference between the 3- and 6-month DAPT groups in either BARC type 2-5 bleeding (1.6% vs 0.8%; hazard ratio 2.00; P=.42) or any bleeding (2.9% vs 3.3%; hazard ratio 0.87; P=.80). CONCLUSION: Compared with 6 months of DAPT, 3 months of DAPT did not increase the risk of primary endpoint 1 year after Coroflex ISAR stent implantation, although it should be noted that the trial has limited power to see differences due to low event rate and low recruitment rate.

Translesional Fractional Flow Reserve is Related to Plaque Components in Coronary Artery Disease: A Study Combining Pressure Wire and NIRS-IVUS Analysis.

OBJECTIVES: It remains unclear whether atherosclerotic plaque structure or composition is related to translesional biomechanical stresses in coronary artery disease. The aim of this study was to evaluate the association between translesional pressure parameters (using a pressure wire) and plaque characteristics (using a combined near-infrared spectroscopy [NIRS] and intravascular ultrasound [IVUS] imaging catheter). METHODS: Fractional flow reserve (FFR), delta (Δ) FFR, and Δ pressure were obtained during adenosine-induced maximum hyperemic status. Lipid core burden index (LCBI) and maximum LCBI within 2 mm (maxLCBI2mm) and tomographic anatomy were evaluated by NIRS-IVUS. RESULTS: Sixty-six lesions from 57 patients were analyzed (57 lesions for FFR, 45 lesions for ΔFFR). There was a negative correlation between FFR and maxLCBI2mm (r=-0.264; P=.049) and a positive correlation between ΔFFR and maxLCBI2mm (r=0.299; P=.049). ΔFFR of lesions with maxLCBI2mm ≥500 was significantly higher than maxLCBI2mm <500 (0.159 ± 0.085 vs 0.104 ± 0.075, respectively; P=.04). By receiver-operating characteristic curve analysis, ΔFFR ≥0.1 was a predictor for maxLCBI2mm ≥500 (area under curve, 0.707; 95% confidence interval, 0.552-0.862; P=.03). On multivariate analysis, ΔFFR was the only predictor of maxLCBI2mm (ß=0.347; P=.03). CONCLUSION: ΔFFR across a coronary artery lesion is related to lipid core burden assessed using NIRS-IVUS and might be a meaningful predictor of high-risk plaque (plaque with high lipid content).

Five-year clinical outcomes of the first Korean-made sirolimus-eluting coronary stent with abluminal biodegradable polymer.

ABSTRACT: This study evaluated the 5-year clinical outcomes of the Genoss DES, the first Korean-made sirolimus-eluting coronary stent with abluminal biodegradable polymer.We previously conducted the first-in-patient prospective, multicenter, randomized trial with a 1:1 ratio of patients using the Genoss DES and Promus Element stents; the angiographic and clinical outcomes of the Genoss DES stent were comparable to those of the Promus Element stent. The primary endpoint was major adverse cardiac events (MACE), which was a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR) at 5 years.We enrolled 38 patients in the Genoss DES group and 39 in the Promus Element group. Thirty-eight patients (100%) from the Genoss DES group and 38 (97.4%) from the Promus Element group were followed up at 5 years. The rates of MACE (5.3% vs 12.8%, P = .431), death (5.3% vs 10.3%, P = .675), TLR (2.6% vs 2.6%, P = 1.000), and target vessel revascularization (TVR) (7.9% vs 2.6%, P = .358) at 5 years did not differ significantly between the groups. No TLR or target vessel revascularization was reported from years 1 to 5 after the index procedure, and no MI or stent thrombosis occurred in either group during 5 years.The biodegradable polymer Genoss DES and durable polymer Promus Element stents showed comparable low rates of MACE at the 5-year clinical follow-up.

Managing Nonagenarians with Acute Myocardial Infarction: Invasive versus Conservative Treatment.

BACKGROUND: Limited data are available to support an invasive treatment strategy in nonagenarians with acute myocardial infarction (AMI). We aimed to investigate whether percutaneous coronary intervention (PCI) is beneficial in this frail population. METHODS: We retrospectively analyzed 41 nonagenarians with AMI (both ST-segment-elevation and non-ST-segment-elevation MI) between 2006 and 2015 in a single center. We assessed 30-day and one-year mortality rates according to the treatment strategy. RESULTS: Among study subjects, 24 (59%) were treated with PCI (PCI group) and 17 (41%) were treated with conservative management (medical treatment group) per the clinician's discretion. The median follow-up duration was 30 months (0-74 months). Thirty-day mortality was lower in the PCI group than in the medical treatment group (17% vs. 65%; P < 0.001). One-year mortality was also lower in the PCI group than in the medical treatment group (21% vs. 76%; P < 0.001). The PCI group presented a 73% decreased risk of death (adjusted hazard ratio: 0.269; 95% confidence interval: 0.126-0.571; P < 0.001). In the Killip class 1 through 3 subgroups (n = 36), 30-day and one-year mortality were still higher among those in the medical treatment group (13% vs. 54% at 30 days; P < 0.001 and 17% vs. 69% at one year; P < 0.001). Landmark analysis after 30 days revealed no significant difference in the cumulative mortality rate between the two groups, indicating that the mortality difference was mainly determined within the first 30 days after AMI. CONCLUSION: Mortality after AMI was decreased in correlation with the invasive strategy relative to the conservative strategy, even in nonagenarians. Regardless of age, PCI should be considered in AMI patients. However, large-scale randomized controlled trials are needed to support our conclusion.

Comparison of three-dimensional quantitative coronary angiography and intravascular ultrasound for detecting functionally significant coronary lesions.

BACKGROUND: Three-dimensional quantitative coronary angiography (3D-QCA) can provide more accurate measurement of true vessel size and may be comparable to intravascular ultrasound (IVUS) in identifying functionally significant coronary stenosis, as determined by fractional flow reserve (FFR). This study aimed to evaluate the diagnostic accuracy of 3D-QCA for predicting FFR <0.8. METHODS: We assessed 175 lesions in 175 patients by FFR, IVUS, and 3D-QCA. Correlations between 3D-QCA values, IVUS values, and FFR values were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy of 3D-QCA for predicting FFR <0.8 and to determine the appropriate cut-off value. RESULTS: Upon evaluating 3D-QCA values, minimum lumen area (MLA) correlated with FFR value (r=0.48, P<0.001). Considering IVUS values, MLA correlated with FFR value (r=0.43, P<0.001). Also, 3D-QCA MLA was well correlated with IVUS MLA (r=0.61, P<0.001). The area under the ROC curve (AUC) for 3D-QCA MLA was 0.77, and the best cut-off value was 2.37 (sensitivity: 73%, specificity: 71%). The AUC for IVUS MLA was 0.73, and the best cut-off value was 3.01 (sensitivity: 71%, specificity: 65%). There was no significant difference in AUC for 3D-MLA and IVUS-MLA (P=0.27). CONCLUSIONS: 3D-QCA is not inferior to IVUS for functional assessment of intermediate coronary lesions. We can consider 3D-QCA as a suitable substitute for IVUS or FFR in determining coronary intervention.

Usefulness of the trans-stent fractional flow reserve gradient for predicting clinical outcomes.

OBJECTIVES: We evaluated the usefulness of a fractional flow reserve (FFR) gradient across the stent (ΔFFRstent ) for long-term clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). BACKGROUND: The clinical meaning of a trans-stent pressure gradient after DES implantation has not been estimated adequately. METHODS: FFR pull-back and intravascular ultrasound (IVUS) were performed after successful PCI in 135 left anterior descending artery lesions. ΔFFRstent was defined as the FFR gradient across the stent. The ΔFFRstent/length was defined as the ΔFFRstent value divided by the total stent length multiplied by 10. Major adverse cardiac events (MACEs) were the composite of all-cause death, target vessel-related myocardial infarction, and target lesion revascularization. RESULTS: Despite successful PCI, ΔFFRstent > 0 was observed in 98.5% of cases. ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 predicted suboptimal stenting defined as final minimal stent area < 5.5 mm2 . During 2,183 ± 898 days, the MACE-free survival rate was significantly lower in patients with ΔFFRstent ≥ 0.04 and ΔFFRstent/length ≥ 0.009 compared to those with lower values (69.6 vs. 93.4%, log-rank p = .031; 72.1 vs. 97.7%, log-rank p = .003, respectively). ΔFFRstent/length ≥ 0.009 (hazard ratio 10.1, p = .032) was an independent predictor of MACE. CONCLUSION: A trans-stent FFR gradient was frequently observed. ΔFFRstent and ΔFFRstent/length are related to long-term outcomes in DES-treated patients.

Impact of new-onset diabetes on clinical outcomes after ST segment-elevated myocardial infarction.

Objective. Patients with diabetes have higher mortality rate than patients without diabetes after ST-segment elevated myocardial infarction (STEMI). Prognosis of patients with new onset diabetes (NOD) after STEMI remains unclear. The aim of this study was to evaluate the prognosis of patients with NOD compared to that of patients without NOD after STEMI. Design. This study was a retrospective observational study. We enrolled 901 STEMI patients. Patients were divided into diabetic and non-diabetic groups at index admission. Non-diabetic group was divided into NOD and non-NOD groups. Kaplan-Meier analysis and Cox's proportional hazard regression models were used to compare major adverse cardiac events (MACE) free survival rate and hazard ratio for MACE between NOD and non-NOD groups. Results. Mean follow-up period was 59 ± 28 months. Diabetes group had higher MACE than non-diabetes group (p = .038). However, MACE was not different between NOD and non-NOD groups (p = 1.000). After 1:2 propensity score matching, incidence of MACE was not different between the two groups. In Kaplan-Meier survival curves, MACE-free survival rates were not statistically different between NOD and non-NOD groups either (p = .244). Adjusted hazard ratios of NOD for MACE, all-cause of death, recurrent myocardial infarction, and target vessel revascularization were 0.697 (95% confidence interval [CI]: 0.362-1.345, p = .282), 0.625 (95% CI: 0.179-2.183, p = .461), 0.794 (95% CI: 0.223-2.835, p = .723), and 0.506 (95% CI: 0.196-1.303, p = .158), respectively. Conclusion. This retrospective observational study with a limited statistical power did not show a different prognosis in patients with and without NOD.

Lipid-Core Plaque Assessed by Near-Infrared Spectroscopy and Procedure Related Microvascular Injury.

BACKGROUND AND OBJECTIVES: Microvascular damage due to distal embolization during percutaneous coronary intervention (PCI) is an important cause of periprocedural myocardial infarction. We assessed the lipid-core plaque using near-infrared spectroscopy (NIRS) and microvascular dysfunction invasively with the index of microcirculatory resistance (IMR) and evaluated their relationship. METHODS: This study is pilot retrospective observational study. We analyzed 39 patients who performed NIRS before and after PCI, while fractional flow reserve, thermo-dilution coronary flow reserve (CFR) and IMR were measured after PCI. The maximum value of lipid core burden index (LCBI) for any of the 4-mm segments at the culprit lesion (culprit LCBI4mm) was calculated at the culprit lesion. We divided the patients into 2 groups using a cutoff of culprit LCBI4mm ≥500. RESULTS: Mean pre-PCI LCBI was 333±196 and mean post-PCI IMR was 20±14 U. Post-PCI IMR was higher (15.6±7.3 vs. 42.6±17.6 U, p<0.001) and post-PCI CFR was lower (3.7±2.2 vs. 2.1±1.0, p=0.029) in the high LCBI group. Pre-PCI LCBI was positively correlated with post-PCI IMR (ρ=0.358, p=0.025) and negatively correlated with post-PCI CFR (ρ=-0.494, p=0.001). The incidence of microvascular dysfunction (IMR ≥25 U) was higher in the high LCBI group (9.4% vs. 85.7%, p<0.001). However, there were no significant differences in the incidences of creatine Kinase-MB (9.4% vs. 14.3%, p=0.563) and troponin-I elevation (12.5% vs. 14.3%, p=1.000). CONCLUSIONS: A large lipid-core plaque at the 'culprit' lesion is observed higher incidence of post-PCI microvascular dysfunction after PCI. Prospective study with adequate subject numbers will be needed.

Visit-to-visit systolic blood pressure variability in patients with ST-elevation myocardial infarction predicts long-term cardiovascular outcomes.

Elevated visit-to-visit blood pressure variability (BPV), independent of mean BP, has been associated with cardiovascular events. However, its impact after ST-elevation myocardial infarction (STEMI) has not been established. This study aimed to investigate the prognostic impact of BPV on patients after STEMI. We analyzed the data and clinical outcomes of STEMI survivors who underwent successful primary coronary intervention from 2003 to 2009. BP was measured at discharge and at 1, 3, 6, 12, 24, and 36 months, and we calculated BPV as the intra-individual standard deviations (SDs) of systolic BP (SBP) across these measurements. We classified the patients as high and low-BPV group, and evaluated the outcomes: occurrence of major adverse cardiovascular events (MACEs), death, recurrent myocardial infarction, and target vessel revascularization within 60 months. We enrolled 343 patients, and mean follow-up duration was 68 ± 34 months (median: 76 months). Mean and median SBP SDs were 13.2 and 12.3 mmHg, and patients were divided into one of the two groups based on the median (high-BPV group = SD ≥ 12.3 mmHg; low-BPV group = SD < 12.3 mmHg). The MACE-free survival in the high-BPV group was significantly worse than that in low-BPV group (log-rank p = 0.035). For the high-BPV group, the risk of a MACE significantly increased by 57% (95% confidence interval: 1.03-2.39; p = 0.038). Visit-to-visit systolic BPV was associated with increased rates of adverse clinical outcomes in patients after STEMI. Careful assessment of BP and attempts to reduce BPV might be also important in STEMI survivors.

Intravascular ultrasound characteristics in patients with intermediate coronary lesions and borderline fractional flow reserve measurements.

Revascularization of borderline fractional flow reserve (FFR) is controversial and the morphologic characteristics of borderline FFR lesions are not well known. The objective of this study was to determine the intravascular ultrasound (IVUS) characteristics in intermediate coronary lesions with borderline FFR in patients with intermediate coronary artery stenosis (40%-70% diameter stenosis).Both IVUS and FFR were performed in a total of 228 left anterior descending arteries. We divided them into 3 groups by FFR value: ischemic (n = 46, FFR < 0.75), borderline (n = 71, FFR 0.75 to ≤0.80), and non-ischemic (n = 111, FFR > 0.80). We compared the IVUS parameters, including minimum lumen area, lesion length, plaque burden, and volumetric analysis among the 3 groups.In the IVUS analysis, the minimum lumen area was smaller (2.5 ±â€Š0.6 vs. 2.7 ±â€Š0.7 vs. 3.4 ±â€Š1.2 mm, P < .001); lesion length was longer (23.6 ±â€Š8.4 vs. 23.6 ±â€Š7.4 vs. 17.4 ±â€Š6.8 mm, P < .001); plaque burden was larger (76.1 ±â€Š9.6 vs. 73.9 ±â€Š7.5 vs. 69.8 ±â€Š9.5%, P < .001); plaque volume was larger (173.0 ±â€Š78.3 vs. 167.7 ±â€Š75.0 vs. 129.5 ±â€Š79.1 mm, P < .01); and percent atheroma volume was larger (57.9 ±â€Š7.5 vs. 57.6 ±â€Š6.6 vs. 53.9 ±â€Š8.0%, P < .01) in the ischemic and borderline groups compared with the non-ischemic group, respectively. However, post-hoc analyses showed there were no significant differences between the ischemic and borderline group for all IVUS parameters.There were no differences in IVUS characteristics between borderline and functionally significant FFR, but the amount of atheromatous plaque was more severe in these 2 groups than in the non-ischemic group.

Comparison of Fractional FLow Reserve And Intravascular ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate Stenosis (FLAVOUR): Rationale and design of a randomized clinical trial.

BACKGROUND: Coronary angiography has limitations in defining the ischemia-causing stenotic lesion, especially in cases with intermediate coronary stenosis. Fractional flow reserve (FFR) is a current standard method to define the presence of ischemia, and intravascular ultrasound (IVUS) is the most commonly used invasive imaging tool that can provide the lesion geometry and can provide the information on plaque vulnerability. The primary aim of this study is to compare the safety and efficacy of FFR-guided and IVUS-guided percutaneous coronary intervention (PCI) strategies in patients with intermediate coronary stenosis. TRIAL DESIGN: Comparison of Fractional FLow Reserve And Intravascular ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate Stenosis (FLAVOUR) trial is an international, multicenter, prospective, randomized clinical trial. A total of 1,700 consecutive patients with intermediate stenosis (40%-70% by visual estimation) in a major epicardial coronary artery will be randomized 1:1 to receive either FFR-guided or IVUS-guided PCI strategy. Patients will be treated with PCI according to the predefined criteria for revascularization; FFR ≤ 0.80 in the FFR-guided group and Minimal Lumen Area (MLA) ≤3 mm2 (or 3 mm270%) in the IVUS-guided group. The primary end point is the patient-oriented composite outcome, which is a composite of all-cause death, myocardial infarction, and any repeat revascularization at 24months after randomization. We will test noninferiority of current standard FFR-guided PCI strategy compared with IVUS-guided decision for PCI and stent optimization strategy. CONCLUSION: The FLAVOUR trial will compare the safety and efficacy of FFR- and IVUS-guided PCI strategies in patients with intermediate coronary stenosis. This study will provide an insight on optimal evaluation and treatment strategy for patients with intermediate coronary stenosis.

Impact of body fat distribution on long-term clinical outcomes after drug-eluting stent implantation.

BACKGROUND AND OBJECTIVE: The distribution of body fat is closely related to cardiovascular disease and outcomes, although its impact on patient prognosis after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) has not been evaluated. We investigated the impact of truncal fat distribution on long-term clinical outcomes after DES treatment. METHODS: In 441 DES-treated patients, dual energy X-ray absorptiometry was performed to assess total and regional body fat distribution after index PCI. The ratio of truncal fat to total body fat mass (%FMtrunk/FMtotal) was calculated as a representative parameter for truncal fat distribution. The primary endpoint was major adverse cardiac events (MACE), a composite of ischemia-driven target vessel revascularization (TVR), non-procedural myocardial infarction, cardiac death at 5 years. RESULTS: During the median follow-up duration of 1780 days, MACE occurred in 22.0% of patients, with the highest-quartile group of %FMtrunk/FMtotal having a higher rate than the lowest quartile group (27.8% vs. 15.3%; log rank p = 0.026). The difference was driven by a higher rate of ischemia-driven TVR (25.9% vs. 9.9%; log rank p = 0.008). In multivariable Cox regression analyses, %FMtrunk/FMtotal was independently associated with MACE (hazard ratio: 1.075; 95% CI: 1.022-1.131; p = 0.005), but body mass index (BMI) was not. CONCLUSIONS: In DES-treated patients, truncal fat distribution is associated with unfavorable clinical outcomes and is more clinically relevant than BMI.

Long-term prognostic value of invasive and non-invasive measures early after heart transplantation.

BACKGROUND: Invasively assessed coronary microvascular resistance early after heart transplantation predicts worse long-term outcome; however, little is known about the relationship between microvascular resistance, left ventricular function and outcomes in this setting. METHODS: A total of 100 cardiac transplant recipients had fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) measured in the left anterior descending artery and echocardiographic assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at 1 year after heart transplantation. The primary endpoint was the composite of death and retransplantation occurring beyond the first post-operative year. RESULTS: The mean FFR, IMR, LVEF, and GLS values at 1 year were 0.87 ±â€¯0.06, 21.3 ±â€¯17.3, 60.4 ±â€¯5.4%, and 14.2 ±â€¯2.4%, respectively. FFR and IMR had no significant correlation with LVEF and GLS. During a mean follow-up of 6.7 ±â€¯4.2 years, the primary endpoint occurred in 24 patients (24.0%). By ROC curve analysis, IMR = 19.3 and GLS = 13.3% were the best cutoff values for predicting death or retransplantation. Cumulative event-free survival was significantly lower in patients with higher IMR (log-rank p = 0.02) and lower GLS (log-rank p < 0.001). Cumulative event-free survival can be further stratified by the combination of IMR and GLS (long-rank p < 0.001). By multivariable Cox proportional hazards model, higher IMR and lower GLS were independently associated with long-term death or retransplantation (elevated IMR, hazard ratio = 2.50, p = 0.04 and reduced GLS, hazard ratio = 3.79, p = 0.003, respectively). CONCLUSION: Invasively assessed IMR does not correlate with GLS at 1 year after heart transplantation. IMR and GLS determined at 1 year may be used as independent predictors of late death or retransplantation.

Myocardial Mass Contributes to the Discrepancy Between Anatomic Stenosis Severity Assessed by Intravascular Ultrasound and Fractional Flow Reserve in Intermediate Lesions of the Coronary Artery.

OBJECTIVES: The present study investigated the major contributors to the discrepancy between the minimal lumen area (MLA) and fractional flow reserve (FFR). BACKGROUND: There was considerable discrepancy between MLA or diameter stenosis (DS) and FFR. METHODS: We enrolled 744 patients with intermediate stenoses of the left anterior descending artery (LAD). Summed epicardial coronary artery length distal to the target stenosis was obtained from each longest view of the vessels on the coronary angiograms. Mismatching was defined as a lesion with FFR of >0.80 and MLA smaller than the best cut-off value (BCV) for predicting FFR of ≤0.80. Reverse mismatching was defined as a lesion with FFR of ≤0.80 and MLA larger than the BCV. RESULTS: Summed epicardial coronary artery length was longer at the lesions of proximal LAD than that of middle LAD (380 mm ± 82 mm vs. 341 mm ± 80 mm, P < 0.001). Reverse mismatching was found more frequently in the proximal than middle LAD (28.3% vs. 5.5%, P < 0.001). Independent predictors of FFR ≤ 0.80 were age, male, multi-vessel disease, proximal LAD lesion, MLA, DS, plaque burden at distal reference, lesion length and summed epicardial coronary artery length. Proximal LAD lesion was an independent predictor of reverse mismatching (hazard ratio 3.162, 1.858-5.382, P < 0.001). CONCLUSIONS: Myocardial mass subtended by a lesion is an important factor predicting FFR ≤0.80 and discrepancy between FFR and MLA. Myocardial mass subtended by a lesion should be considered when determining the revascularization therapy by intravascular ultrasound parameters. © 2017 Wiley Periodicals, Inc.

Ischemia-based Coronary Revascularization: Beyond Anatomy and Fractional Flow Reserve.

Treatment strategies for patients with coronary artery disease (CAD) should be based on objective evidence of inducible ischemia in the subtended myocardium to improve clinical outcomes, symptoms, and cost-effectiveness. Fractional flow reserve (FFR) is the most verified index to-date for invasively evaluating lesion-specific myocardial ischemia. Favorable results from large clinical trials that applied FFR-guided percutaneous coronary intervention (PCI) prompted changes in coronary revascularization guidelines to emphasize the importance of this ischemia-based strategy using invasive coronary physiology. However, the frequency of functional evaluations is lacking in daily practice, and visual assessment still dominates treatment decisions in CAD patients. Despite recent efforts to integrate functional and anatomical assessments for coronary stenosis, there is considerable discordance between the 2 modalities, and the diagnostic accuracy of simple parameters obtained from current imaging tools is not satisfactory to determine functional significance. Although evidence that supports or justifies anatomy-guided PCI is more limited, and FFR-guided PCI is currently recommended, it is important to be aware of conditions and factors that influence FFR for accurate interpretation and application. In this article, we review the limitations of the current anatomy-derived evaluation of the functional significance of coronary stenosis, detail considerations for the clinical utility of FFR, and discuss the importance of an integrated physiologic approach to determine treatment strategies for CAD patients.