Flow-limiting Lesions Research Articles

Diagnostic performance of fully automatic coronary CT angiography-based quantitative flow ratio

BackgroundMurray-law based quantitative flow ratio, namely μFR, was recently validated to compute fractional flow reserve (FFR) from coronary angiographic images in the cath lab. Recently, the μFR algorithm was applied to coronary computed tomography angiography (CCTA) and a semi-automated computed μFR (CT-μFR) showed good accuracy in identifying flow-limiting coronary lesions prior to referral of patients to the cath lab. We aimed to evaluate the diagnostic accuracy of an artificial intelligence-powered method for fully automatic CCTA reconstruction and CT-μFR computation, using cath lab physiology as reference standard. MethodsThis was a post-hoc blinded analysis of the prospective CAREER trial (NCT04665817). Patients who underwent CCTA, coronary angiography including FFR within 30 days were included. Cath lab physiology standard for determining hemodynamically significant coronary stenosis was defined as FFR≤0.80, or μFR≤0.80 when FFR was not available. ResultsAutomatic CCTA reconstruction and CT-μFR computation was successfully achieved in 657 vessels from 242 patients. CT-μFR showed good correlation (r ​= ​0.62, p ​< ​0.001) and agreement (mean difference ​= ​−0.01 ​± ​0.10, p ​< ​0.001) with cath lab physiology standard. Patient-level diagnostic accuracy for CT-μFR to identify patients with hemodynamically significant stenosis was 83.0 ​% (95%CI: 78.3%–87.8 ​%), with sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio of 84.2 ​%, 81.9 ​%, 82.1 ​%, 84.0 ​%, 4.7 and 0.2, respectively. Average analysis time for CT-μFR was 1.60 ​± ​0.34 ​min per patient. ConclusionThe fully automatic CT-μFR yielded high feasibility and good diagnostic performance in identifying patients with hemodynamically significant stenosis prior to referral of patients to the cath lab.

Commentary on “Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicenter, open-label, randomized controlled trial”

To address the potential risk of acute coronary syndrome, the current clinical guidelines on coronary artery diseases recommend revascularization in significant and flow-limiting lesions, but emerging data depict vulnerable atherosclerotic coronary plaques as possibly at risk of adverse cardiac events, compared to fibroatheromous or calcific plaques [...].

Exercise-based cardiac rehabilitation in stable angina pectoris: anarrative review on current evidence and underlying physiological mechanisms.

Stable angina pectoris (SAP) is aprevalent condition characterised by ahigh disease burden. Based on recent evidence, the need for revascularisation in addition to optimal medical treatment to reduce mortality and re-events is heavily debated. These observations may be explained by the fact that revascularisation is targeted at the local flow-limiting coronary artery lesion, while the aetiology of SAP relates to the systemic, inflammatory process of atherosclerosis, causing generalised vascular dysfunction throughout the entire vascular system. Moreover, cardiovascular events are not solely caused by obstructive plaques but are also associated with plaque burden and high-risk plaque features. Therefore, to reduce the risk of cardiovascular events and angina, and thereby improve quality of life, alternative therapeutic approaches to revascularisation should be considered, preferably targeting the cardiovascular system as awhole with aphysiological approach. Exercise-based cardiac rehabilitation fits this description and is apromising strategy as afirst-line treatment in addition to optimal medical treatment. In this review, we discuss the role of exercise-based cardiac rehabilitation in SAP in relation to the underlying physiological mechanisms, we summarise the existing evidence and highlight future directions.

Abstract 14679: Microcirculatory Flow and Resistance at Rest and Hyperemia in Relation to Major Adverse Cardiovascular Events in Chronic Coronary Syndrome

Background: The prognostic implications of coronary microvascular dysfunction in an all-comer cohort with chronic coronary syndrome (CCS) are not known. Aim: To investigate the association of baseline resistance index (BRI), index of microcirculatory resistance (IMR), and thermodilution-derived resting- and hyperemic flow velocities (RFV and HFV) with the primary composite endpoint consisting of all-cause mortality, incident myocardial infarction (MI) or hospitalization due to congestive heart failure (CHF) in CCS. Methods: CCS patients undergoing elective coronary angiography (CA) were included. Measurements of corrected IMR, BRI and mean transit time at baseline (Tmn base ) and during hyperemia (Tmn hyp ) were obtained in the LAD. RFV and HFV were calculated as 1/Tmn base and 1/Tmn hyp , respectively. Cox-regression was performed and Kaplan-Meier plots were constructed. Results: We included 503 patients before the coronary anatomy was known and thermodilution measurements in the LAD were obtained in 413 patients. Median age was 68 (IQR 61-74), 127 (25%) were women and 151 (37%) had a flow-limiting epicardial lesion in the LAD. Median follow-up was 5.3 years (IQR 3.0-6.6) and there were 57 events. Log 10 BRI was inversely associated with the primary endpoint before and after fractional flow reserve (FFR) adjustments (HR 0.64 [95% CI 0.42 - 0.97]; Figure 1A). Log 10 IMR was not associated with the primary endpoint (HR 0.94 [95% CI 0.61 - 1.5]; Figure 1B). Log 10 RFV was associated with the primary endpoint before and after FFR- adjustment (HR 1.8 [95% CI 1.2 - 2.7]) whereas log 10 HFV was not (HR 1.2 [95% CI 0.75-1.8]). Conclusion: Low microcirculatory resting resistance and high coronary resting flow velocity in the LAD, indicating impaired autoregulation, were associated with all-cause death, MI and/or CHF in CCS whereas hyperemic microcirculatory resistance and flow were not. Resting flow indices can be used for risk evaluation in patients with CCS undergoing CA. .

Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions: A Systematic Review and Meta-Analysis

BackgroundThe clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non–flow-limiting lesions remains uncertain. ObjectivesThe authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE). MethodsThirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling. ResultsCPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the MACE rate was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes. ConclusionsCharacterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810)

Functional (Re)Development of SYNTAX Score II 2020: Predictive Performance and Risk Assessment.

The present study investigates the prognostic value of the Syntax Score II 2020 corrected for flow-limiting lesions and its ability to better address treatment by benefit prediction among patients with left main or multivessel disease. We analyzed 1274 patients from the HALE-BOPP cohort and integrated the Syntax Score II 2020 with the result of the fractional flow reserve (FFR) evaluation. Absolute risk difference (ARD) between surgical and percutaneous revascularization was calculated for anatomic and functional Syntax Score II 2020 predicted mortality. The ARD allowed to stratify the population into two large categories: "coronary artery bypass graft (CABG) better" with ARD ≥ 4.5% and "CABG-percutaneous coronary intervention (PCI) equipoise" with ARD < 4.5%. The mean global anatomical Syntax Score was 15.5 ± 9.2, whereas the functional one was 9.5 ± 10 (p < 0.01). Using the anatomic Syntax Score II 2020, 881 patients had a CABG-PCI equipoise. This number increased to 1041 after considering only flow-limiting lesions by FFR (p < 0.001); therefore, 40% of CABG better patients were reclassified within the CABG-PCI equipoise category. Kaplan-Maier curves showed similar actual survival rates for patients originally with CABG-PCI equipoise and those reclassified, in both cases higher than those from CABG better patients (p < 0.01). The integration between Syntax Score II 2020 and physiology is feasible, and merging clinical, anatomic and functional data allows for better risk prediction and therapeutic guidance.

Incremental diagnostic value of perivascular fat attenuation index for identifying hemodynamically significant ischemia with severe calcification.

To explore the incremental value of perivascular fat attenuation index (FAI) to identify hemodynamically significant ischemia in severe calcified vessels. Patients who underwent coronary computed tomographic angiography (CCTA) examination at Chinese PLA General Hospital from 2017 to 2020 and subsequently underwent fractional flow reserve (FFR) examination within 1 month were consecutively included. Several CCTA-derived indices were measured, including the coronary artery calcification score (CACS), lesion length, ≥CAD-RADS 4 proportion, perivascular FAI and CT-FFR. The included vessels were divided into a nonsevere calcification group and a severe calcification group according to the quartile of CACS. FFR ≤ 0.80 represents the presence of hemodynamically significant ischemia. A total of 124 patients with 152 vessels were included (age: 61.1 ± 9.2 years; male 64.5%). Significant differences in lesion length (28.4 ± 14.2 vs. 23.1 ± 12.3mm, P = 0.021), perivascular FAI (-73.0 ± 7.5 vs. -79.0 ± 7.4 HU, P < 0.001) and CT-FFR (0.78 ± 0.06 vs. 0.86 ± 0.04, P < 0.001) were noted between the FFR ≤ 0.80 group (47 vessels) and the FFR > 0.80 group (105 vessels). Furthermore, the perivascular FAI in the FFR ≤ 0.80 group was significantly greater than that in the FFR > 0.80 group (nonsevere calcification: -73.2 ± 7.5 vs. -78.2 ± 7.4 HU, P = 0.002; severe calcification: -72.8 ± 7.7 vs. -82.7 ± 6.3 HU, P < 0.001). In discriminating hemodynamically significant ischemia, the specificity and accuracy of CT-FFR were significantly affected by severe calcification, which demonstrated a significantly declining trend (P = 0.033 and P = 0.010, respectively). The diagnostic performance of CT-FFR in the severe calcification group was lower than that in the nonsevere calcified group. However, perivascular FAI showed good discriminative performance in the severe calcification group. In combination with perivascular FAI, the predictive value of CT-FFR in identifying hemodynamically significant ischemia with severe calcification increased from an AUC of 0.740 to 0.919. For coronary artery with severe calcification, the diagnostic performance of CT-FFR in discriminating flow-limiting lesions could be greatly impaired. Perivascular FAI represents a potential reliable imaging marker to provide incremental diagnostic value over CT-FFR for identifying hemodynamically significant ischemia with severe calcification.

Absent Right Coronary Artery in an Active Young Female

Absent Right Coronary Artery in an Active Young Female

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

Role of Quantitative Flow Ratio in Predicting Future Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

Coronary angiography is the gold standard for cardiac allograft vasculopathy (CAV) diagnosis, but it usually detects the disease at an advanced stage. We investigated the role of quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, in predicting CAV development in heart transplant recipients. Consecutive heart transplant recipients with no evidence of angiographic CAV at baseline coronary angiography were retrospectively included between January 2010 and December 2015, and QFR computation was performed. The relationship between vessel QFR and the occurrence of angiographic vessel-related CAV (≥50% stenosis) was assessed. One hundred forty-three patients were included and QFR computation was feasible in 241 vessels. The median value of QFR at baseline coronary angiography was 0.98 (interquartile range, 0.94-1.00). During a median follow-up of 6.0 years (interquartile range, 4.6-7.8 years), vessel-related CAV occurred in 25 (10.4%) vessels. Receiver-operating characteristic curve analysis identified a QFR best cutoff of ≤0.95 (area under the curve, 0.81 [95% CI, 0.71-0.90]; P<0.001). QFR≤0.95 was associated with an increased risk of vessel-related CAV (adjusted hazard ratio, 20.87 [95% CI, 5.35-81.43]; P<0.001). In an exploratory analysis, QFR≤0.95 in at least 2 vessels was associated with higher incidence of cardiovascular death or late graft dysfunction (71.4% in recipients with 2-3 vessels affected versus 5.1% in recipients with 0-1 vessels affected, P<0.001). In a cohort of heart transplant recipients, QFR computation at baseline coronary angiography may be a safe and reliable tool to predict vessel-related CAV and clinical outcomes at long-term follow-up.

Giant Coronary Artery Aneurysm: A Successful Diagnosis

Coronary artery aneurysms (CAAs) are rare, with giant CAAs being even rarer. The precise pathophysiology of this phenomenon is still unknown. CAAs are seldom reported life-threatening abnormalities of the cardiovascular system. We herein present a case of a 74-year-old man who presented at the hospital complaining of chest pain. An adenosine thallium scan revealed a small, reversible defect in the inferior wall of the left ventricle extending into the apex, consistent with ischemia. Echocardiography uncovered a large right coronary artery (RCA) aneurysm, measuring 5.6 × 7.5 cm. Diagnostic coronary angiography confirmed the presence of a large RCA aneurysm and aneurysmal dilation of the left anterior descending and circumflex arteries with no flow-limiting lesions. A reversed saphenous vein interposition graft was placed from the ascending aorta to the right posterior descending artery. The RCA aneurysmal sac was resected and sent to pathology, which uncovered myxoid degeneration of the media as well as thrombus formation. No complications were encountered during the procedure. Early diagnosis is vital to avoid fatal complications of CAAs, and therapeutic approaches are currently individualized in view of absence of evidence-based management strategies.

448 Comparison of quantitative flow ratio, Pd/Pa, and diastolic hyperaemia-free ratio vs. fractional flow reserve in non-culprit lesion of patients with non-ST-segment elevation myocardial infarction

Abstract Aims To investigate the correlation between quantitative flow ratio (QFR), Pd/Pa, diastolic hyperaemia-free ratio (DFR), and fractional flow reserve (FFR, gold standard) in non-culprit lesion (NCL) of patients with non ST-segment elevation myocardial infarction (NSTEMI). The non-hyperemic pressure ratio (NHPR) and the angiography-based indexes have been developed to overcome the limitation of the use of the FFR. Methods and results Between January and December 2019, 184 NCL from 116 NSTEMI patients underwent physiologic assessment and were included in the study. NCLs were investigated with QFR, Pd/Pa, DFR, and FFR. Mean values of QFR, Pd/Pa, DFR, and FFR were 0.85 ± 0.10, 0.92 ± 0.07, 0.93 ± 0.05, and 0.84 ± 0.07, respectively. DFR and FFR showed a good correlation (r = 0.76). Bland and Altman plot showed a mean difference of 0.080. DFR diagnostic accuracy was 88%. The area under the ROC curve (AUC) for DFR was 0.946 (95% CI: 0.90–0.97, P = 0.0001). Similar findings were reported for Pd/Pa [r = 0.73; mean difference 0.095, diagnostic accuracy 84%, AUC 0.909 (95% CI: 0.85–0.94, P = 0.0001)] and QFR [r = 0.68; mean difference: 0.01; diagnostic accuracy: 88%, AUC: 0.964 (95% CI: 0.91–0.98, P = 0.0001)]. FFR, QFR, Pd/Pa, and DFR identified 31%, 32%, 30%, and 32% potentially flow-limiting lesions, respectively. Conclusions In NSTEMI patients, QFR, Pd/Pa, and DFR showed equivalence as compared to gold standard FFR in the discrimination of non-culprit lesions requiring revascularization.

The Role of Coronary Artery Disease in Demand Mediated Myocardial Infarction: A Retrospective Study from a Community Hospital

Type 2 Myocardial Infarction (T2MI) is an increasingly recognized clinical entity due to the availability of highly sensitive troponin assays for patients admitted due to common medical diagnoses. However, there is little epidemiological data on the significance and long-term prognosis of T2MI, which occurs secondary to an increase in myocardial oxygen demand and/or a decrease in myocardial blood flow. Arrhythmia, hypoxia, and sepsis are the major etiologies for T2MI. Therefore, sepsis was the identified area of interest for the study giving how common it is in a community hospital. We studied the cardiac workup of patients with elevated troponin in the context of sepsis due to acute medical illness to find out the prevalence of obstructive coronary artery disease (CAD) in this population. In this two-year retrospective, descriptive study, electronic medical records (EMR) were reviewed for all patients aged 18 years and older admitted to a single community teaching hospital with a diagnosis of sepsis and elevated troponin I (> 0.07 ug/L). The primary outcome was the presence of obstructive CAD. The secondary outcome was time to peak serum troponin. Of 222 patients, 40 patients underwent invasive or/and noninvasive cardiac testing for CAD. The study revealed 30% of patients admitted with T2MI due to sepsis have underlying obstructive coronary artery lesions. Troponin rose slower in patients with T2MI with underlying obstructive CAD. Pneumonia was the most common underlying cause of sepsis in both groups. Given the considerable prevalence of underlying flow-limiting coronary artery lesions, it may be advisable to evaluate for obstructive CAD sooner than later, during the index hospitalization, when patients developed elevated troponin secondary to sepsis.

Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial

Compared with visual angiographic assessment, pressure wire-based physiological measurement more accurately identifies flow-limiting lesions in patients with coronary artery disease. Nonetheless, angiography remains the most widely used method to guide percutaneous coronary intervention (PCI). In FAVOR III China, we aimed to establish whether clinical outcomes might be improved by lesion selection for PCI using the quantitative flow ratio (QFR), a novel angiography-based approach to estimate the fractional flow reserve. FAVOR III China is a multicentre, blinded, randomised, sham-controlled trial done at 26 hospitals in China. Patients aged 18 years or older, with stable or unstable angina pectoris or patients who had a myocardial infarction at least 72 h before screening, who had at least one lesion with a diameter stenosis of 50-90% in a coronary artery with a reference vessel of at least 2·5 mm diameter by visual assessment were eligible. Patients were randomly assigned to a QFR-guided strategy (PCI performed only if QFR ≤0·80) or an angiography-guided strategy (PCI based on standard visual angiographic assessment). Participants and clinical assessors were masked to treatment allocation. The primary endpoint was the 1-year rate of major adverse cardiac events, a composite of death from any cause, myocardial infarction, or ischaemia-driven revascularisation. The primary analysis was done in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03656848). Between Dec 25, 2018, and Jan 19, 2020, 3847 patients were enrolled. After exclusion of 22 patients who elected not to undergo PCI or who were withdrawn by their physicians, 3825 participants were included in the intention-to-treat population (1913 in the QFR-guided group and 1912 in the angiography-guided group). The mean age was 62·7 years (SD 10·1), 2699 (70·6%) were men and 1126 (29·4%) were women, 1295 (33·9%) had diabetes, and 2428 (63·5%) presented with an acute coronary syndrome. The 1-year primary endpoint occurred in 110 (Kaplan-Meier estimated rate 5·8%) participants in the QFR-guided group and in 167 (8·8%) participants in the angiography-guided group (difference, -3·0% [95% CI -4·7 to -1·4]; hazard ratio 0·65 [95% CI 0·51 to 0·83]; p=0·0004), driven by fewer myocardial infarctions and ischaemia-driven revascularisations in the QFR-guided group than in the angiography-guided group. In FAVOR III China, among patients undergoing PCI, a QFR-guided strategy of lesion selection improved 1-year clinical outcomes compared with standard angiography guidance. Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Centre for Cardiovascular Diseases, Fuwai Hospital.

Coronary artery bypass grafting or percutaneous coronary intervention in patients with severe three vessel disease

Recent randomized controlled trials confirmed the beneficial outcomes with coronary artery bypass grafting (CABG) compared with percutaneous coronary intervention (PCI) in patients with severe three-vessel coronary artery and left main disease. An increased long-term survival after CABG is associated with a reduction in spontaneous myocardial infarction and repeat revascularization rates. While PCI treats only flow-limiting lesions, CABG treats the whole coronary artery, preventing events in the future. Due to different clinical and anatomic factors affecting the outcomes, the heart team should formulate treatment assignment recommendations.

Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study

Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3·7 (IQR 3·0-4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0-15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2-10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25-4·13) and non-culprit lesion-specific MACEs (7·83, 4·12-14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0-10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4-17·6). Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Abbott Vascular, Infraredx, and The Medicines Company.

Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque

BackgroundAcute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild. ObjectivesThis study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non–flow-limiting vulnerable plaques. MethodsThree-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel–related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion–related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up. ResultsA total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy–IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm2, and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm2 compared with 3.0 ± 1.0 mm2 in GDMT alone–treated lesions (least square means difference: 3.9 mm2; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone–treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion–related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone–treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12). ConclusionsPCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065)

Vessel-specific quantification of absolute myocardial blood flow, myocardial flow reserve and relative flow reserve by means of fused dynamic 13NH3 PET and CCTA: Ranges in a low-risk population and abnormality criteria

ObjectivesThe goal of the present work is to present a novel methodology for the extraction of MBF, MFR and RFR along coronary arteries by means of multimodality image fusion of dynamic PET and CCTA images. BackgroundFFR is the reference standard to identify flow-limiting lesions, but its invasiveness limits broad application. New noninvasive methodologies are warranted to stratify patients and guide treatment. MethodsA group of 16 low-risk CAD subjects who underwent both 13NH3 PET and CCTA were analyzed. Image fusion techniques were employed to align the studies and CCTA-derived anatomy used to identify coronaries trajectories. MBF was calculated by means of a 1-tissue compartmental model for the standard vascular territories and along patient-specific vessel paths from the base to the apex of the heart. ResultsLow-risk ranges for MBF. MFR and RFR for LAD, LCX and rPDA were computed for the entire cohort and separated by gender. Computed low-risk ranges were used to assess a prospective patient with suspected CAD. ConclusionsOur vessel-specific functional indexes and 3D displays offer promise to more closely replicate what is commonly performed during a catheterization session and have the potential of providing effective noninvasive tools for the identification of flow-limiting lesions and image-guided therapy.

Skeletal muscle expression of adipose-specific phospholipase in peripheral artery disease.

Flow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case-control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) was PLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR; PLA2G16 was downregulated by 68% in patients with PAD (p < 0.001). Expression of Pla2g16 was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression of Pla2g16 in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.

Early Outcomes of Transconal Repair of Transseptal Anomalous Left Coronary Artery From Right Sinus

Anomalous aortic origin of the left coronary artery (AAOCLA) with an extended transseptal course behind the right ventricular outflow tract (RVOT) is a rare variant that poses challenges not addressed by current surgical techniques. We utilized a novel transconal approach in 7 consecutive patients. A retrospective review was made of a prospectively collected database for consecutive patients undergoing transconal unroofing of transseptal AAOLCA. Surgical repair entails transection of the RVOT, unroofing the septal course of the AAOLCA, followed by RVOT extension with a rectangular strip of autologous pericardium. Preoperative characteristics, operative details, and postoperative course were abstracted. All 7 patients identified were symptomatic. Median age was 48 years (range, 12 to 62). The AAOLCA with transseptal course was confirmed by computed tomography angiography. Three patients had provocative testing demonstrating anterolateral ischemia. Four patients underwent cardiac catheterization with intravascular ultrasound and indexed fractional flow reserve, confirming flow-limiting lesion. Importantly, 3 patients had negative provocative noninvasive testing for ischemia. Median postoperative hospital length of stay was 6 days (range, 4 to 12). No mortality or major complications occurred during a median follow-up of 0.75 years. Postoperative evaluation demonstrated anatomically patent unroofed AAOLCA with improved indexed fractional flow reserve compared with preoperative (0.59 ± 0.16 vs 0.90 ± 0.03, P= .05). Complete unroofing of AAOLCA with transseptal course repaired with posterior extension of RVOT is an effective technique with excellent early outcome. Multimodality provocative testing is critical to evaluate these lesions as individual studies may be misleading. Intravascular ultrasound with indexed fractional flow reserve is clinically useful to confirm the hemodynamic significance of specific lesions.