Impact of renal denervation on patients with coronary microvascular dysfunction: study rationale and design.

AIMS: Long-standing hypertension may cause an impairment in microvascular coronary circulation, which is involved in many different cardiac conditions. Renal sympathetic denervation (RDN) has been successfully proven as a valuable therapeutic choice for patients with resistant hypertension; moreover, the procedure looks promising in other settings, such as heart failure and atrial fibrillation, given its ability to downregulate the sympathetic nervous system, which is a recognized driver in these conditions as well as in microvascular dysfunction progression. The aim of this study is to explore the effect of RDN on coronary physiology in patients with ascertained coronary microvascular dysfunction and resistant hypertension. METHODS: This is a multicenter, prospective, nonrandomized, open-label, interventional study. Consecutive patients with resistant hypertension, nonobstructive coronary artery disease (NOCAD) and documented microvascular dysfunction will be enrolled. Patients will undergo RDN by Spyral Symplicity 3 (Medtronic Inc, Minneapolis, Minnesota, USA) and reassessment of coronary microvascular function 6 months after the procedure. Primary endpoint will be the difference in the index of microcirculatory resistance. CONCLUSION: The IMPRESSION study seeks to evaluate if there is any pleiotropic effect of the RDN procedure that results in modulation of microvascular function; if observed, this would be the first evidence showing RDN as a valuable therapy to revert hypertension-related microvascular dysfunction.

Prognostic value of combined fractional flow reserve and pressure-bounded coronary flow reserve: outcomes in FFR and Pb-CFR assessment.

BACKGROUND: Coronary flow reserve (CFR) has an emerging role to predict outcome in patients with and without flow-limiting stenoses. However, the role of its surrogate pressure bounded-CFR (Pb-CFR) is controversial. We investigated the usefulness of combined use of fractional flow reserve (FFR) and Pb-CFR to predict outcomes. METHODS: This is a sub-study of the PROPHET-FFR Trial, including patients with chronic coronary syndrome and functionally tested coronary lesions. Patients were divided into four groups based on positive or negative FFR (cut-off 0.80) and preserved (lower boundary ≥2) or reduced (upper boundary <2) Pb-CFR: Group1 FFR≤0.80/ Pb-CFR <2; Group 2 FFR≤0.80/Pb-CFR≥2; Group 3 FFR >0.80/Pb-CFR<2; Group 4 FFR>0.80/Pb-CFR≥2. Lesions with positive FFR were treated with PCI. Primary endpoint was the rate of major adverse cardiac events (MACEs), defined as a composite of death from any cause, myocardial infarction, target vessel revascularization, unplanned cardiac hospitalization at 36-months. RESULTS: A total of 609 patients and 816 lesions were available for the analysis. At Kaplan-Meier analysis MACEs rate was significantly different between groups (36.7% Group 1, 27.4% Group 2, 19.2% Group 3, 22.6% Group 4, P=0.019) and more prevalent in groups with FFR≤0.80 irrespective of Pb-CFR. In case of discrepancy, no difference in MACEs were observed between groups stratified by Pb-CFR. FFR≤0.80 was associated with an increased MACEs rate (30.2% vs. 21.5%, P<0.01) while Pb-CFR<2 was not (24.5% vs. 24.2% Pb-CFR≥2 P=0.67). CONCLUSIONS: FFR confirms its ability to predict outcomes in patients with intermediate coronary stenoses. Pb-CFR does not add any relevant prognostic information.

Ticagrelor Enhances the Cardioprotective Effects of Ischemic Preconditioning in Stable Patients Undergoing Percutaneous Coronary Intervention: the TAPER-S Randomized Study.

BACKGROUND: Ticagrelor improves clinical outcomes in patients with acute coronary syndrome compared with clopidogrel. Ticagrelor also inhibits cell uptake of adenosine and has been associated with cardioprotective effects in animal models. We sought to investigate the potential cardioprotective effects of ticagrelor, as compared with clopidogrel, in stable patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a Prospective Randomized Open Blinded End-points (PROBE) trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve (FFR)-guided PCI of intermediate epicardial coronary lesions. ST-segment elevation at intracoronary (IC)-ECG during a two-step sequential coronary balloon inflations in the reference vessel during PCI was used as an indirect marker of cardioprotection induced by ischemic preconditioning. The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by intracoronary-ECG during two-step sequential coronary balloon inflations. RESULTS: Fifty-three patients were randomized to either clopidogrel or ticagrelor. The study was stopped earlier because the primary endpoint was met at a pre-specified interim analysis. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel arms (p<0.0001). Ticagrelor was associated with lower angina score during coronary balloon inflations. There was no difference in coronary microvascular resistance between groups. Adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel. CONCLUSIONS: Ticagrelor enhances the cardioprotective effects of ischemic preconditioning compared with clopidogrel in stable patients with CAD undergoing PCI. Further studies are warranted to fully elucidate the mechanisms through which ticagrelor may exert cardioprotective effects in humans. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique Identifier: NCT02701140.

Pre-stenting residual thrombotic volume assessed by dual quantitative coronary angiography predicts microvascular obstruction in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Microvascular obstruction (MVO) is a frequent occurrence after primary percutaneous coronary intervention (pPCI), and is associated with adverse left ventricular remodeling and worse clinical outcome. Distal embolization of thrombotic material is one of the most important underlying mechanisms. The aim of this study was to investigate the relation between the thrombotic volume evaluated by dual quantitative coronary angiography (QCA) prior to stenting and the occurrence of MVO as assessed by cardiac magnetic resonance (CMR). METHODS: Forty-eight patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI and receiving CMR within 7 days from admission were included. Pre-stenting residual thrombus volume at the site of the culprit lesion was measured by applying automated edge detection and video-assisted densitometry techniques (i.e., dual-QCA), and patients were categorized into tertiles of thrombus volume. The presence of delayed-enhancement MVO, as well as its extent (MVO mass), were assessed by CMR. RESULTS: Pre-stenting dual-QCA thrombus volume was significantly greater in patients with MVO than in those without (5.85 mm3 [2.05-16.71] vs. 1.88 mm3 [1.03-6.92], P=0.009). Patients in the highest tertile showed greater MVO mass compared to those in the mid and lowest tertiles (113.3 gr [0.0-203.8] vs. 58.5 g [0.00-144.4] vs. 0.0 g [0.0-60.225], respectively; P=0.031). The best cut-off value of dual-QCA thrombus volume for prediction of MVO was 2.07 mm3 (AUC: 0.720). The addition of dual-QCA thrombus volume to the traditional angiographic indices of no-reflow enhanced the prediction of MVO by CMR (R=0.752). CONCLUSIONS: Pre-stenting dual-QCA thrombus volume is associated with the presence and extent of MVO detected by CMR in patients with STEMI. This methodology may aid the identification of patients at higher risk of MVO and guide adoption of preventive strategies.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

Safety and effectiveness of post percutaneous coronary intervention physiological assessment: Retrospective data from the post-revascularization optimization and physiological evaluation of intermediate lesions using fractional flow reserve registry.

Background: While the importance of invasive physiological assessment (IPA) to choose coronary lesions to be treated is ascertained, its role after PCI is less established. We evaluated feasibility and efficacy of Physiology-guided PCI in the everyday practice in a retrospective registry performed in a single high-volume and "physiology-believer" center. Materials and methods: The PROPHET-FFR study (NCT05056662) patients undergoing an IPA in 2015-2020 were retrospectively enrolled in three groups: Control group comprising patients for whom PCI was deferred based on a IPA; Angiography-Guided PCI group comprising patients undergoing PCI based on an IPA but without a post-PCI IPA; Physiology-guided PCI group comprising patients undergoing PCI based on an IPA and an IPA after PCI, followed by a physiology-guided optimization, if indicated. Optimal result was defined by an FFR value ≥ 0.90. Results: A total of 1,322 patients with 1,591 lesions were available for the analysis. 893 patients (67.5%) in Control Group, 249 patients (18.8%) in Angiography-guided PCI Group and 180 patients (13.6%) in Physiology-guided PCI group. In 89 patients a suboptimal functional result was achieved that was optimized in 22 cases leading to a "Final FFR" value of 0.90 ± 0.04 in Angiography-Guided PCI group. Procedural time, costs, and rate of complications were similar. At follow up the rate of MACEs for the Physiology-guided PCI group was similar to the Control Group (7.2% vs. 8.2%, p = 0.765) and significantly lower than the Angiography-guided PCI Group (14.9%, p < 0.001), mainly driven by a reduction in TVRs. Conclusion: "Physiology-guided PCI" is a feasible strategy with a favorable impact on mid-term prognosis. Prospective studies using a standardized IPA are warrant to confirm these data.

Intracoronary bolus of glycoprotein IIb/IIIa inhibitor as bridging or adjunctive strategy to oral P2Y12 inhibitor load in the modern setting of ST-elevation myocardial infarction.

BACKGROUND: In the acute management of ST-elevation myocardial infarction (STEMI), glycoprotein IIb/IIIa inhibitors (GPIs) bolus not followed by intravenous infusion is potentially advantageous given their fast onset and offset of action, but clinical evidence in a contemporary setting is limited. METHODS: We collected data from consecutive STEMI patients admitted to the cardiac catheterization laboratory of the IRCCS A. Gemelli University Polyclinic Foundation from October 2017 to September 2019. RESULTS: Out of 423 consecutive STEMI patients, 297 met the inclusion and exclusion criteria and were included in the study. Of them, 107/297 (36%) received an intracoronary GPI bolus-only during primary percutaneous coronary intervention (PPCI) not followed by intravenous infusion and 190/297 (64%) received standard antithrombotic therapy. Of the 107 GPI-treated, 22/107 (21%) had P2Y12 inhibitor pretreatment (adjunctive strategy) and 85/107 (79%) did not (bridging strategy). During hospital staying, there was no difference in the primary safety endpoint of TIMI major+minor bleeding (P=0.283), TIMI major (P=0.267) or TIMI minor (P=0.685) bleeding between groups. No stroke event occurred in the GPI group. Despite patients receiving GPI having a significantly higher intraprocedural ischemic burden, no significant differences were found in the efficacy outcomes between groups. Consistent findings were observed for patients receiving GPIs bolus before (bridging strategy) or after (adjunctive strategy) P2Y12 inhibitors, compared to those receiving standard therapy. Multivariate logistic regression analyses did not find any independent predictors significantly associated to the primary and secondary composite endpoints. CONCLUSIONS: In a contemporary real-world population of STEMI patients undergoing PPCI, the use of intracoronary GPIs bolus-only in selected patients at high ischemic risk is safe and could represent a useful antithrombotic strategy both in those pretreated and in those naïve to P2Y12 inhibitors.

Physiological assessment after percutaneous coronary intervention: the hard truth.

Physiologically guided revascularization, using fractional flow reserve (FFR) or instantaneous wave free ratio (iFR) has been demonstrated to be associated with better long-term outcomes compared to an angiographically-guided strategy, mainly avoiding inappropriate coronary stenting and its associated adverse events. On the contrary, the role of invasive physiological assessment after percutaneous coronary intervention (PCI) is much less well established. However, a large body of evidence suggests that a relevant proportion of patients undergoing PCI with a satisfying angiographic result show instead a suboptimal functional product with a potentially negative prognostic impact. For this reason, many efforts have been focused to identify interventional strategies to physiologically optimize PCI. Measuring the functional result after as PCI, especially when performed after a physiological assessment, implies that the operator is ready to accept the hard truth of an unsatisfactory physiological result despite angiographically optimal and, consequently, to optimize the product with some additional effort. The aim of this review was to bridge this gap in knowledge by better defining the paradigm shift of invasive physiological assessment, from a simple tool for deciding whether an epicardial stenosis must be treated, to a thoroughly physiological approach to PCI with the suggestion of a practical flow chart.

Colchicine in ischemic heart disease: the good, the bad and the ugly.

Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.

Prognostic impact of FFR/contrast FFR discordance.

BACKGROUND: Contrast fractional flow reserve (cFFR) is a relatively new tool for the assessment of intermediate coronary artery stenosis and represents a reliable surrogate of FFR with the advantage of potentially simplifying functional evaluation. We aimed to compare the incidence of major adverse cardiac events (MACE) in patients undergoing functional evaluation with both FFR and cFFR based on the results of the two indexes. METHOD AND RESULT: We retrospectively analyzed outcomes in 488 patients who underwent functional evaluation with FFR and cFFR. Patients were divided into four groups using the cutoff values of 0.80 for FFR and 0.85 for cFFR: -/- (n = 298), +/+ (n = 134), -/+(n = 31) and +/- (n = 25). All patients were treated according to FFR value. MACE rate was assessed in each group, including death, myocardial infarction and urgent target vessel revascularization (TVR). Mean follow-up time was 22 ± 15 months. Incidence of MACE at follow-up was 8.3% in FFR-/cFFR-, 14.0% in FFR+/cFFR+, 16.0% in FFR-/cFFR+ and 8.0% in FFR+/cFFR- without a significant difference amongst the 4 groups (p = 0.2). Nevertheless, a significant difference in the rate of TVR comparing FFR-/cFFR- (n = 17) and FFR-/cFFR+ (n = 5) was found at 24 months (5.7% vs 16.0%; p = 0.027). CONCLUSION: cFFR is accurate in predicting FFR and consequently reliable in guiding coronary revascularization. In the rare case of discordance, while FFR+/cFFR- patients show a prognosis similar to FFR-/cFFR- patients, FFR-/cFFR+ patients show a prognosis similar to FFR+/cFFR+ patients.

Sex-Related Differences in Dilated Cardiomyopathy with a Focus on Cardiac Dysfunction in Oncology.

PURPOSE OF REVIEW: The aim of this report is to describe the main aspects of sex-related differences in non-ischemic dilated cardiomyopathies (DCM), focusing on chemotherapy-induced heart failure (HF) and investigating the possible therapeutic implications and clinical management applications in the era of personalized medicine. RECENT FINDINGS: In cardio-oncology, molecular and multimodality imaging studies confirm that sex differences do exist, affecting the therapeutic cardioprotective strategies and, therefore, the long-term outcomes. Interestingly, compelling evidences suggest that sex-specific characteristics in drug toxicity might predict differences in the therapeutic response, most likely due to the tangled interplay between cancer and HF, which probably share common underlying mechanisms. Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestations, from sex-determined differential gene expression to sex hormone interaction with their receptors in the heart. Non-ischemic DCM is an umbrella definition that incorporates several etiologies, including chemotherapy-induced cardiomyopathies. The role of sex as a risk factor for cardiotoxicity is poorly explored. However, understanding the various features of disease manifestation and outcomes is of paramount importance for a prompt and tailored evaluation.

Telemedicine, Artificial Intelligence and Humanisation of Clinical Pathways in Heart Failure Management: Back to the Future and Beyond.

New technologies have been recently introduced to improve the monitoring of patients with chronic syndromes such as heart failure. Devices can now be employed to gather large amounts of data and data processing through artificial intelligence techniques may improve heart failure management and reduce costs. The analysis of large datasets using an artificial intelligence technique is leading to a paradigm shift in the era of precision medicine. However, the assessment of clinical safety and the evaluation of the potential benefits is still a matter of debate. In this article, the authors aim to focus on the development of these new tools and to draw the attention to their transition in daily clinical practice.

Antithrombotic therapy in the early phase of non-ST-elevation acute coronary syndromes: a systematic review and meta-analysis.

AIMS: Despite the increasing use of early invasive strategies in non-ST-elevation acute coronary syndromes (NSTE-ACS), optimal initial antithrombotic therapy (ATT) based on the safety/efficacy profile of all guideline-recommended combinations remains crucial for the early management of both medically and invasively treated NSTE-ACS patients. METHODS AND RESULTS: Randomized controlled trials on ATT in NSTE-ACS/unstable angina reporting early (within 14 days) major adverse cardiovascular events (MACE) and major bleeding were selected. Overall, 3799 studies were screened, 117 clinical trials were assessed as potentially eligible, 20 trials were included in the study. According to treatment and type of intervention, nine different meta-analyses were performed including a total of 88 748 patients. A significant reduction of trial-defined MACE was found for aspirin vs. placebo [odds ratio (OR), 0.57; 95% confidence interval (CI), 0.34-0.96], heparin vs. placebo (OR, 0.38; 95% CI, 0.15-0.97), aspirin + heparin vs. placebo (OR, 0.32; 95% CI, 0.18-0.59), aspirin + heparin vs. aspirin (OR, 0.57; 95% CI, 0.42-0.79), aspirin + low molecular weight heparin (LMWH) vs. aspirin + unfractionated heparin (UFH; OR, 0.81; 95% CI, 0.69-0.95) and aspirin + ticagrelor/prasugrel + heparins vs. aspirin + clopidogrel + heparins (OR, 0.76; 95% CI, 0.62-0.94). A significant decrease in major bleeding was found only for fondaparinux vs. LMWH on the background of aspirin + clopidogrel (OR, 0.52; 95% CI, 0.44-0.62) despite a clear trend towards increased bleeding for heparin compared to aspirin, aspirin + heparin compared to placebo, aspirin + heparin compared to aspirin, aspirin + P2Y12inhibitors + UFH/LMWH compared to aspirin + UFH/LMWH, and aspirin + ticagrelor/prasugrel + heparins compared to aspirin + clopidogrel + heparins. CONCLUSION: To our knowledge, these findings are the first to report the safety and efficacy of all the various combinations of currently recommended ATT for the early management of NSTE-ACS, providing a comprehensive evidence-base to guide decisions depending on the patients' bleeding risk and treatment strategy.

Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly different from heart failure with reduced EF in terms of etiology and natural history (Graziani et al., 2018). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (Crea et al., 2017). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (Paulus and Tschope, 2013). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (Ohanyan et al., 2018). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-ß) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (Graziani et al., 2018;Lam et al., 2018). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart.

Dual quantitative coronary angiography accurately quantifies intracoronary thrombotic burden in patients with acute coronary syndrome: Comparison with optical coherence tomography imaging.

BACKGROUND: Dual quantitative coronary angiography (QCA) has been recently tested for assessment of intracoronary thrombus volume in experimental models. The present study aimed to validate dual QCA in vivo for the assessment of thrombus burden by exploring the correlations between dual QCA-thrombus volume and optical coherence tomography (OCT)-derived indices of thrombotic burden. METHODS AND RESULTS: Fifty-one patients with ACS and angiographic evidence of thrombus undergoing OCT of the culprit lesion before stenting were included. Dual QCA-thrombus volume was calculated as difference between edge-detection and video-densitometry area functions along the target segment. Culprit lesion was categorized using the Ambrose's and AHA/ACC angiographic classifications. Thrombus volume (mean thrombus area × thrombus length), thrombus burden [(mean thrombus area/mean lumen area) x100] and Prati thrombus score (number of quadrants with thrombus) were measured by OCT, and the presence of plaque rupture (PR) or intact fibrous cap (IFC) was assessed. Dual QCA-thrombus volume correlated significantly with OCT-thrombus volume (R = 0.791), thrombus burden (R = 0.767) and Prati thrombus score (R = 0.600) (all p < 0.001). Dual-QCA thrombus volume was significantly higher in patients with PR compared with those with IFC (3.48 mm3 [1.45-11.26] vs. 1.69 mm3 [0.09-5.02], p = 0.013). Compared with IFC, PR showed higher prevalence of eccentric type II Ambrose lesion (41.7% vs. 7.4%, p = 0.004), complex B2/C lesion (87.5% vs. 55.6%, p = 0.012), and heavy calcification (29.2% vs. 3.7%, p = 0.013). CONCLUSIONS: Dual QCA analysis appears to be a promising tool for quantification of intracoronary thrombus in vivo. This novel methodology may be useful to guide intracoronary thrombus removal during percutaneous coronary intervention and to aid prognostic stratification in patients with ACS.

Coronary Atherosclerotic Phenotype and Plaque Healing in Patients With Recurrent Acute Coronary Syndromes Compared With Patients With Long-term Clinical Stability: An In Vivo Optical Coherence Tomography Study.

Importance: At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. Objective: To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. Design, Setting, and Participants: This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. Exposures: Intracoronary OCT imaging of nonculprit coronary segments. Main Outcomes and Measures: Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. Results: Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). Conclusions and Relevance: Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.

Electronic Cigarettes and Cardiovascular Risk: Caution Waiting for Evidence.

Electronic cigarettes use is a growing trend in contemporary societies, with the propensity to compete with traditional tobacco smoking. Some preclinical studies demonstrated the toxic and detrimental effects of electronic cigarettes liquid components. Its impact on human health remains unknown and insufficiently studied. While some studies suggest that electronic cigarettes use might be associated with endothelial dysfunction, impaired platelet function and increased risk of adverse clinical events, other studies did not confirm these findings and epidemiological data mostly suggest that the use of electronic cigarettes appears to be safer than that of traditional tobacco cigarettes. This article provides an up-to-date overview of the current state of knowledge regarding electronic cigarettes and their impact on human health, with special emphasis on their effect on cardiovascular diseases.