Optical coherence tomography in coronary atherosclerosis assessment and intervention.

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.

Baseline cardio-oncologic risk assessment in breast cancer women and occurrence of cardiovascular events: The HFA/ICOS risk tool in real-world practice.

BACKGROUND: the European Society of Cardiology Heart Failure Association (HFA) together with the International Cardio-Oncology Society (ICOS) proposed charts for baseline CV risk assessment of cancer patients scheduled to receive anthracyclines and anti-human epidermal growth factor receptor-2 (HER2) agents. METHODS: We investigated HFA/ICOS risk stratification, prescriptions of cardioactive drugs, and occurrence of CV events in a multicentric breast cancer (BC) cohort from 3 Italian Outpatient Cardio-Oncology Clinics. RESULTS: 373 BC patients who underwent a baseline Cardio-Oncologic evaluation were included, of whom 202 scheduled to receive anthracyclines and 171 anti-HER2. Mean age was 60 ± 12 years and 49% of BC patients had ≥2 CV risk factors. In the anthracyclines group, 51% were at low-risk, 43% at medium-risk and 6% at high-risk; while in the anti-HER2 group, 27% patients were at low-risk, 58% at medium-risk and 15% at high-risk. In both groups, a medium-to-high risk was associated with use of cardioactive therapies (p < 0.0001). There were no LVD events in anthracycline recipients, and 16 LVD among anti-HER2 patients. A medium-to-high risk was not associated with LVD occurrence (p = 0.17). CONCLUSIONS: Patients with medium-to-high HFA/ICOS risk were more likely to receive cardioactive therapies, possibly explaining the lack of association of risk categories with LVD occurrence.

[Use of intravascular ultrasound for the assessment and treatment of left main disease]. / Uso dell'ecografia intravascolare nella valutazione e nel trattamento percutaneo della malattia del tronco comune.

Left main coronary artery (LMCA) disease is a pathological condition of great clinical relevance due to its significant impact on both morbidity and mortality of patients with ischemic heart disease. Due to its bidimensional nature, angiography does not enable an accurate evaluation of the extension, distribution and morphology of LMCA disease. Intravascular ultrasound (IVUS) is the invasive imaging modality of choice for the evaluation of LMCA disease, due to its ability to accurately characterize atherosclerotic disease in all the segments of LMCA bifurcation (including LMCA ostium). IVUS is therefore useful in each step of LMCA procedures: (i) to assess stenosis severity and to evaluate the need for revascularization; (ii) to select the appropriate treatment strategy of LMCA bifurcation (e.g. single vs two stents); (iii) to guide all steps of percutaneous coronary intervention (PCI) (e.g. lesion preparation, decision of the landing zone, stent sizing, proximal optimization, side branch rewiring, kissing balloon); (iv) to optimize stent result (e.g. expansion, apposition, geographical miss, major dissections). Although data obtained from randomized clinical trials are limited, several meta-analyses and registry studies suggest the superiority of IVUS-guided LMCA PCI as compared with LMCA PCI guided by angiography alone in terms of mortality, non-fatal myocardial infarction, stent thrombosis, restenosis, and target lesion revascularization.

Invasive "in the cath-lab" assessment of myocardial ischemia in patients with coronary artery disease: When does the gold standard not apply?

International guidelines recommend that revascularization for coronary artery disease (CAD) should be guided by evidence of myocardial ischemia. Fractional flow reserve (FFR) and instantaneous free wave ratio (iFR) are the main invasive indices for assessing the ischemic potential of angiographically intermediate coronary stenosis as a large body of evidence supports their routine application. Both indices have been tested and validated in patients with isolated stable CAD, but notably their application outside this specific context is a matter of debate and investigation. In the present review we aim to look into the available evidence about the reliability and feasibility of FFR and iFR in clinical contexts different from stable angina where these techniques have been validated. We aim to shed light on which technique can be used to invasively assess ischemia when an angiographic moderate coronary stenosis is observed in a clinical setting other than isolated stable CAD.

Frequency-domain optical coherence tomography plaque morphology in stable coronary artery disease: sex differences.

BACKGROUND: The cause for discrepancy in the clinical presentation and outcome of coronary artery disease (CAD) between men and women is not established. Different prevalences of risk factors or specific sex-related atherosclerotic aspects have been advocated as possible explanations. We investigated coronary plaque morphology looking at possible differences in plaque vulnerability between men and women with stable CAD. PATIENTS AND METHODS: We retrospectively collected and analyzed clinical data and coronary plaque morphology by frequency-domain optical coherence tomography in men and women with stable CAD. RESULTS: A total of 181 (139 were in men and 42 in women) plaques from 138 patients were analyzed. The mean age was similar between men and women. Besides an overall absence of significant differences in the vast majority of risk factors and comorbidities, men had a higher prevalence of active smoking (19 vs. 2%, P=0.006), previous myocardial infarction (17 vs. 2%, P=0.01), and previous percutaneous coronary interventions (42 vs. 17%, P=0.003). Frequency-domain optical coherence tomography in women showed significantly more plaque-vulnerability features as testified by higher percent of lipid-rich plaques (55 vs. 36%, P=0.03), macrophages (21 vs. 5%, P=0.003), and microvessels (24 vs. 8%, P=0.01). Multivariate analysis showed that female sex was associated independently with lipid-rich plaques (P=0.034) and macrophages (P=0.001). In the analysis restricted to the more severe lesions that were revascularized, women continued to be characterized by more adverse morphological features, such as macrophages (30 vs. 7%, P=0.004) and lipid-rich plaques (63 vs. 39%, P=0.045). CONCLUSION: Women with stable CAD may be characterized by plaques that have increased prevalence of vulnerability compared with men. These findings support the hypothesis of sex-specific differences in the development of atherosclerosis.

Optical coherence tomography assessment and quantification of intracoronary thrombus: Status and perspectives.

Coronary angiography is the "golden standard" imaging technique in interventional cardiology and it is still widely used to guide interventions. A major drawback of this technique, however, is that it is inaccurate in the evaluation and quantification of intracoronary thrombus burden, a critical prognosticator and predictor of intraprocedural complications in acute coronary syndromes. The introduction of optical coherence tomography (OCT) holds the promise of overcoming this important limitation, as near-infrared light is uniquely sensitive to hemoglobin, the pigment of red blood cells trapped in the thrombus. This narrative review will focus on the use of OCT for the assessment, evaluation and quantification of intracoronary thrombosis.

No-reflow reversibility: a study based on serial assessment of multiple biomarkers.

No-reflow after primary percutaneous coronary intervention (pPCI) may be reversible. 40 patients undergoing pPCI were evaluated by assessing either improvement or lack of changes regarding angiographic and electrocardiographic indexes of no-reflow between admission and pre-discharge. Myeloperoxidase (MPO; in nanograms per milliliter), C-reactive protein (CRP; in milligrams per liter), endothelin-1 (ET-1; in nanograms per milliliter), angiopoietin-2 (Ang-2, in picograms per milliliter), and their pre-discharge/basal values variations (Δ) were related to no-reflow evolution. ΔMPO and ΔCRP were greater in patients with sustained no-reflow or lack of ST-segment resolution (STR) as compared with those with reversible no-reflow or lack of STR (p = 0.033, p = 0.04, p < 0.001, and p = 0.001, respectively), whereas ΔET-1 was similar in the two groups. ΔAng-2 was greater in patients with sustained no-reflow or lack of STR as compared with those with reversible no-reflow or lack of STR (p = 0.01 and 0.044, respectively). Bigger ΔMPO, ΔCRP (increasing levels), and ΔAng-2 (decreasing levels) are associated with sustained no-reflow, thus they might have a role in no-reflow evolution.

Angiographic assessment of myocardial perfusion in Tako-Tsubo syndrome.

OBJECTIVES: To angiographically assess myocardial perfusion in patients with Tako-Tsubo syndrome (TTS) in comparison with control individuals and patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Coronary microvascular dysfunction has been proposed as the pathophysiological mechanism underlying TTS. METHODS: We retrospectively selected consecutive TTS patients showing typical left ventricular (LV) apical dysfunction admitted to our Department in the period 2007-2011 (n=25). We also enrolled an age and gender-matched control group showing normal coronary arteries (CTR, n=25), patients with STEMI undergoing primary percutaneous intervention with myocardial reperfusion (SR, n=25) or microvascular obstruction (SMVO, n=25). TIMI flow, TIMI frame count (TFC) and both qualitative and quantitative myocardial blush grade in LV apex were assessed. Specifically, myocardial perfusion was quantitatively evaluated using 'Quantitative Blush Evaluator' (QuBE), an open source software previously validated in the setting of STEMI. RESULTS: In TTS, TIMI flow on the LAD was significantly lower and TFC significantly higher compared to CTR and SR (p=0.008 for both), while it did not significantly differ compared to SMVO (p=0.06). In TTS, MBG was significantly lower than that in CTR and SR (p=0.001 for both), while it was significantly higher than that in SMVO (p<0.001). In TTS, QuBE score was significantly lower than that in CTR and SR (p=0.001 for both) and higher than in SMVO (p=0.02). CONCLUSIONS: Our data indicate that myocardial perfusion assessed during angiography is more impaired in patients with TTS than in patients with STEMI exhibiting myocardial reperfusion, while it is less impaired than in patients with STEMI exhibiting MVO.

Maximal hyperemia in the assessment of fractional flow reserve: intracoronary adenosine versus intracoronary sodium nitroprusside versus intravenous adenosine: the NASCI (Nitroprussiato versus Adenosina nelle Stenosi Coronariche Intermedie) study.

OBJECTIVES: This study sought to compare increasing doses of intracoronary (i.c.) adenosine or i.c. sodium nitroprusside versus intravenous (i.v.) adenosine for fractional flow reserve (FFR) assessment. BACKGROUND: Maximal hyperemia is the critical prerequisite for FFR assessment. Despite i.v. adenosine currently representing the recommended approach, i.c. administration of adenosine or other coronary vasodilators constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which i.c. strategy allows the achievement of FFR values comparable to i.v. adenosine. METHODS: Fifty intermediate coronary stenoses (n = 45) undergoing FFR measurement were prospectively and consecutively enrolled. Hyperemia was sequentially induced by incremental boli of i.c. adenosine (ADN) (60 µg ADN60, 300 µg ADN300, 600 µg ADN600), by i.c. sodium nitroprusside (NTP) (0.6 µg/kg bolus) and by i.v. adenosine infusion (IVADN) (140 µg/kg/min). FFR values, symptoms, and development of atrioventricular block were recorded. RESULTS: Incremental doses of i.c. adenosine and NTP were well tolerated and associated with fewer symptoms than IVADN. Intracoronary adenosine doses (0.881 ± 0.067, 0.871 ± 0.068, and 0.868 ± 0.070 with ADN60, ADN300, and ADN600, respectively) and NTP (0.892 ± 0.072) induced a significant decrease of FFR compared with baseline levels (p < 0.001). Notably, ADN600 only was associated with FFR values similar to IVADN (0.867 ± 0.072, p = 0.28). Among the 10 patients with FFR values ≤0.80 with IVADN, 5 were correctly identified also by ADN60, 6 by ADN300, 7 by ADN600, and 6 by NTP. CONCLUSIONS: Intracoronary adenosine, at doses higher than currently suggested, allows obtaining FFR values similar to i.v. adenosine. Intravenous adenosine, which remains the gold standard, might thus be reserved for those lesions with equivocal FFR values after high (up to 600 µg) i.c. adenosine doses.

Comparison of two- and three-dimensional quantitative coronary angiography to intravascular ultrasound in the assessment of intermediate left main stenosis.

Angiographic evaluation of intermediate left main coronary artery stenosis (LMS) is often limited. Three-dimensional (3D) quantitative coronary angiography has recently developed to overcome 2-dimensional (2D) quantitative coronary angiographic (QCA) limitations. In patients with angiographically intermediate LMS, we investigated whether 3D quantitative coronary angiography was superior to 2D quantitative coronary angiography in predicting the presence of a significant LMS, defined as a minimum luminal area <6 mm(2) at intravascular ultrasound (IVUS). 2D and 3D quantitative coronary angiography were compared in their measurements of minimum luminal area, percent area stenosis, minimum luminal diameter, and percent diameter stenosis and in their prediction of an IVUS minimum luminal area <6 mm(2). In total 58 target lesions were interrogated, 25 (43%) of which had an IVUS minimum luminal area <6 mm(2). Correlation between 3D-QCA minimum luminal area and IVUS minimum luminal area was stronger than the correlation between 2D-QCA minimum luminal area (or minimum luminal diameter) and IVUS minimum luminal area (R = 0.67, p = 0.0001, and R = 0.40, p = 0.001, respectively, p = 0.04 for comparison). To predict IVUS minimum luminal area <6 mm(2), the most accurate 2D-QCA measurement was minimum luminal diameter (area under curve 0.81, cutoff 2.2 mm, p = 0.0001), and the most accurate 3D-QCA measurement was minimum luminal area (area under curve 0.86, cutoff 5.6 mm(2), p = 0.0001). 2D-QCA percent diameter stenosis did not significantly predict IVUS minimum luminal area <6 mm(2) (area under curve 0.56, cutoff 38%, p = 0.45). In conclusion, the accuracy of quantitative coronary angiography in predicting LM IVUS minimum luminal area <6 mm(2) is limited. When IVUS is not available or contraindicated, 3D quantitative coronary angiography may assist in the evaluation of intermediate LMS. Among 2D-QCA parameters, minimum luminal diameter is more accurate than percent diameter stenosis in predicting significant LMS.

CT angiography with cardiac MRI: non-invasive functional and anatomical assessment for the etiology in newly diagnosed heart failure.

Exclusion of ischemia is important in patients with newly diagnosed systolic heart failure (HF). We prospectively compared standard-of-care invasive catheter angiography (iCA) and echocardiography to a novel non-invasive strategy of both Coronary Computed Tomographic Angiography (CCTA) and Cardiovascular MRI (CMR) to determine the etiology of myocardial dysfunction Prospective data were collected from consecutive patients referred for iCA to investigate echocardiographically-confirmed new onset HF. CMR (1.5T GE) and dual source CCTA were performed within 2-7 days of iCA. Results were blinded and separately analyzed by expert readers. 426 coronary segments from 28 prospectively enrolled patients were analyzed by CCTA and quantitative iCA. The per-patient sensitivity and specificity of CCTA was 100% and 90%, respectively, negative predictive value (NPV) 100%, positive predictive value (PPV) 78%. Mean ejection fraction by CMR was 24%. Presence of ischemic-type LGE on CMR conferred a 67% sensitivity, 100% specificity, 90% NPV and 100% PPV. Combining CCTA with CMR conferred 100% specificity, 100% sensitivity, 100% PPV and 100% NPV for detection or exclusion of coronary disease. In patients with negative CCTA all invasive angiograms could have been avoided. In addition, two patients with no ischemic LGE by CMR had severe coronary disease on both CCTA and iCA, indicating global hibernation. This is a noteworthy finding in contrast to previous reports which suggested that absence of LGE rules out significant CAD. CCTA with CMR in newly-diagnosed HF enables non-invasive assessment of coronary artery disease, the severity and etiology of myocardial dysfunction and defines suitability for revascularization. Absence of ischemic-type LGE at CMR does not exclude CAD as a cause of LV dysfunction. A first-line strategy of functional and anatomic imaging with CMR and CCTA appears appropriate in newly diagnosed HF.

Comparative assessment of mammalian target of rapamycin inhibitor-eluting stents in the treatment of coronary artery bifurcation lesions: the CASTOR-Bifurcation registry.

Drug-eluting stents (DES) have revolutionized the treatment of coronary bifurcation lesions. Among different DES types, sirolimus-eluting stents (SES) showed better outcomes than paclitaxel-eluting stents. Because novel sirolimus analogues have been implemented in DES, a prospective observational comparison was undertaken to compare major mammalian target of rapamycin inhibitor-eluting stents in the treatment of bifurcation lesions according to the provisional T-stenting and small protrusion (TAP) technique. Overall, 187 patients (165 men, 65 ± 10 years) were enrolled in the study: 80 patients received a SES, whereas zotarolimus-eluting stents (ZES) were implanted in 53 patients and everolimus-eluting stents (EvES) in 62 patients. Primary end-point of the study was the 12-month incidence of target bifurcation failure (TBF) defined as occurrence of cardiovascular death, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR) or angiographic documentation of > 50% restenosis on the main vessel or TIMI flow < 3 on the side branch. Groups were homogeneous according to main clinical and angiographic characteristics. Overall, 17 (9.1%) patients had TBF: 4 (2.1%) patients had nonfatal non-ST-segment elevation MI, 9 (4.8%) patients underwent TVR, and 6 (3.2%) patients had an angiographic restenosis. The rate of TBF was statistically different among the three groups (7.9% in SES group, 18% in ZES group, and 3.3% in EvES group, P = 0.024). Previous MI was associated with a worse outcome (P = 0.025), whereas final kissing balloon was associated with a better outcome (P = 0.045). In conclusion, in this prospective registry, significant differences between DES were found in the outcome of patients treated for coronary bifurcation lesions according to provisional TAP technique. Thus, prospective randomized trials in this field are needed.

Angiographic assessment of microvascular perfusion--myocardial blush in clinical practice.

Assessment of myocardial "blush" by either Myocardial Blush Grade or TIMI Myocardial Perfusion Grade, is the angiographic method currently preferred to confirm myocardial tissue-level perfusion after primary percutaneous intervention. This review focuses on the utility of angiographic "blush" as a simple, widely available, and virtually costless technique for the immediate diagnosis of microvascular impairment at the time of acute catheterization. We comprehensively outline the available evidence behind the "blush," its use in clinical practice, and draw comparisons with other new technologies for assessment of microvascular integrity.

Resting myocardial blood flow is impaired in hibernating myocardium: a magnetic resonance study of quantitative perfusion assessment.

BACKGROUND: Although impairment in perfusion reserve is well recognized in hibernating myocardium, there is substantial controversy as to whether resting myocardial blood flow (MBF) is reduced in such circumstances. Quantitative first-pass cardiovascular magnetic resonance (CMR) perfusion imaging allows absolute quantification of MBF. We hypothesized that MBF assessed at rest by quantitative CMR perfusion imaging is reduced in hibernating myocardium. METHODS AND RESULTS: Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1 dysfunctional myocardial segment undergoing PCI were studied with preprocedure, early (24 hours), and late (9 months) postprocedure CMR imaging. First-pass perfusion images at rest were acquired in 3 short-axis planes by use of a T1-weighted turboFLASH sequence. In each slice, MBF was determined for 8 myocardial segments in mL . min(-1) . g(-1) by deconvolution of signal intensity curves with an arterial input function measured in the left ventricular blood pool. Cine MRI for assessment of global and segmental function and delayed enhancement MRI for detection of viability were also obtained. All coronary lesions were 80% to 95% stenosis in severity. Over all segments, mean MBF normalized by rate-pressure product ("corrected MBF") was 1.2+/-0.3 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments without significant coronary stenosis and 0.7+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments with coronary stenosis before PCI (mixed model controlling for slice and segment z=-23.9, P<0.001). Early after the procedure, the MBF was 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in revascularized segments and 1.3+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in nondiseased segments (z=-6.1, P<0.001). Late after PCI, the systolic wall thickening and end-diastolic wall thickness both increased significantly more (both P<0.001) in the myocardial segments subtended by severe coronary stenosis (8+/-17% to 40+/-19% and 6.5+/-1.1 to 9.3+/-2 mm, respectively) than in the myocardial segments supplied by nondiseased vessels. Mean MBF in dysfunctional segments with significantly improved contraction after revascularization was 0.8+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) before PCI and 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) after PCI (z=2.0, P=0.04). CONCLUSIONS: CMR perfusion imaging detects impaired resting MBF in hibernating myocardial segments.