BACKGROUND:The clinical impact of different types of angiographic complications during elective PCIs remains largely unexplored. AIMS:To explore the incidence, management, and outcomes of angiographic complications by type and severity during non-urgent, non-CTO PCIs. METHODS:Clinical and procedural characteristics were prospectively collected and entered in a catheterization laboratory database, including a section dedicated to PCI complications, from 2015 to 2024. Angiographic complications were classified in eight categories: dissections, perforations, device entrapment/fracture, side branch flow impairment, vessel thrombosis, distal embolization, and any temporary or persistent slow-flow or total occlusion. 30-days and 1-year all-cause mortality were compared between two cohorts with or without angiographic complications, after a propensity score matching for demographic, clinical, procedural and anatomical characteristics. RESULTS:Out of 8401 non-urgent PCIs, 420 (5.0%) presented ≥ 1 angiographic complication (417 patients), with the following incidences: 2.2% iatrogenic dissections, 1.2% side branch flow impairment, 1.2% slow flow, 1.0% vessel occlusion, 0.4% distal embolization, 0.4% vessel thrombosis, 0.4% perforations, 0.1% device entrapment/fracture. Patients with angiographic complications showed a significantly higher risk of 30-days mortality compared to the propensity score-matched cohort without angiographic complications (4.1% vs. 1.6%, p = 0.045). Age, a previous hospitalization for decompensated heart failure, and a procedure on severely calcified lesions were independently associated with 1-year mortality in patients with angiographic complications. CONCLUSION:Angiographic complications during elective PCI significantly increase 30-day mortality compared with uncomplicated PCI. A history of decompensated heart failure warrants particular caution in the event of angiographic complications, as it is associated with an increased risk of mortality within the first year after the procedure.

Coronary artery disease (CAD) is a major health concern that also affects younger individuals, yet data on this population remain limited. We aimed to analyze trends, clinical features, and risk factors in patients aged ≤ 40 years undergoing invasive coronary angiography (ICA) at a high-volume Italian center. We retrospectively analyzed all patients aged ≤ 40 years who underwent ICA from January 2010 to March 2024, assessing demographics, cardiovascular risk factors (CVRFs), and clinical presentations. We compared patients with significant CAD requiring revascularization and those without, exploring gender and ethnic differences. Of 38,304 ICA procedures, 441 (1.2

Bicuspid aortic valve (BAV) is the most common congenital valvular anomaly, affecting roughly 1–2% of the population and predisposing to premature aortic stenosis and thoracic aortopathy. Surgical aortic valve replacement (SAVR) remains the standard therapy, while transcatheter aortic valve implantation (TAVI) is increasingly adopted across a broader range of risk profiles due to accumulating evidence and advancements in device technology. Observational registries and early trial data indicate that TAVI is technically feasible in selected BAV anatomies, with device-success rates exceeding 90%. Nonetheless, bicuspid morphology is still technically demanding, with several possible pitfalls during transcatheter procedure and pre-procedural planning compared with tricuspid valve. The rates of moderate-to-severe paravalvular leak (PVL), permanent pacemaker implantation (PPI), and annular complications remain high, especially in the presence of extensive calcifications with raphe or tapered roots, underscoring the importance of meticulous multimodality imaging, dedicated sizing algorithms, and device-specific strategies. Long-term durability signals are encouraging but remain limited, underlining the need for prospective trials with extended follow-up. This review summarizes current knowledge on BAV anatomy and its management, exploring the available evidence supporting the role of transcatheter approach in this challenging and unique scenario.

Background Stepwise provisional stenting is the most adopted approach for percutaneous coronary interventions (PCIs) in bifurcation lesions. During these procedures, the side branch (SB) may deserve treatment, but the best ballooning technique is still undetermined. Objectives The study sought to compare the stent configurations obtained by 2 SB ballooning sequences after main vessel (MV) stent implantation: the proximal optimization technique + kissing balloon inflation + final proximal optimization technique (PKP) vs the proximal optimization technique + isolated side branch dilation + final proximal optimization technique (PSP). Methods We conducted a 1:1 prospective, randomized, single-center trial to compare bifurcation PCI performed with either PKP or PSP in left main or large (SB diameter >2.75 mm) coronary bifurcations (NCT05559424). The achieved stent configurations (in terms of expansion, apposition, and eccentricity at 5 different bifurcation segments) were evaluated using optical coherence tomography in the MV. The predefined primary study endpoint was minimum stent expansion at the distal MV segment. Results A total of 60 patients undergoing bifurcation PCI according to stepwise provisional stenting were enrolled (30 randomized to PKP and 30 to PSP). At postintervention optical coherence tomography, minimum stent expansion at the distal MV segment was significantly higher with PKP as compared with PSP (99.3% ± 12.7% vs 83.8% ± 19.5%; P < 0.001). Additional relevant findings included a higher rate of malapposition in the bifurcation core and distal MV with PSP and improved SB scaffolding with PKP. No significant differences in terms of stent eccentricity were noted between PSP and PKP in all the segments analyzed. Conclusions The results of the present randomized trial show that during stepwise provisional stenting in left main or large bifurcations, the PKP ballooning sequence is associated with better stent configuration compared with the PSP.

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.

Abstract Coronary microvascular dysfunction (CMD) relates to a broad range of clinical settings in which cardiac microcirculation is morphologically and/or functionally affected, leading to myocardial ischemia and causing anginal symptoms (microvascular angina). Based on the pathogenetic mechanism, there are two possible endotypes of CMD: 1) coronary microvascular spasm and 2) reduced coronary flow reserve (CFR). The gold standard for CMD diagnosis is represented by the coronary angiography with functional tests: 1) the acetylcholine provocative test for the diagnosis of microvascular spasm (endothelium–dependent dysfunction); 2) the determination of CFR and of the index of microvascular resistance (IMR) thorough a flow guidewire after endothelium–independent vasodilation (usually obtained with intracoronary adenosine injection). We report an emblematic case of CMD due to microvascular spasm in a young woman with episodes of typical angina at rest, especially during the night, associated with tachycardia episodes. The patient was admitted to the cardiology unit and underwent coronary angiography, which revealed mild coronary atherosclerosis without any significant stenosis. Due to the very suggestive clinical presentation, provocative test by intracoronary acetylcholine infusion at increasing doses (20–50–100 micrograms) was also performed: from the beginning of the second dose (50 micrograms) the patient started suffering from her typical angor (symptomatology similar to that reported at home), and diffuse ST–T alterations (ST depression and T waves inversion in precordial leads) occurred. At the beginning of the third dose (100 micrograms) a lateral ST–segment elevation (mostly in aVL) was surprisingly observed. The ST–T modifications (including the elevation) were interestingly associated with only diffuse moderate vasoconstriction of the left anterior descending artery, not fulfilling the Covadis criteria for epicardial vasospasm, thus suggesting the presence of a vasospasm of the coronary microcirculation. Symptoms and ECG changes both regressed after intracoronary nitrates administration. As a consequence of the diagnosis of microvascular angina with microvascular vasospasm, medical therapy with calcium antagonists was administered (withdrawing beta–blockers).

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.

Abstract Aims The guide extension catheter (GEC) is a helpful tool to increase catheter support when facing complex percutaneous coronary intervention (PCI) in unfavorable coronary anatomies. The aim of this study was to describe indication, efficacy, and safety of the GEC in a high-volume center. Methods and results From 2014 to 2021, we retrospectively identified and analyzed 351 interventional cases in which GEC was used to complete the procedure. The endpoints of the study were PCI success, procedural success and device failure. GEC use increased over the years and was more frequently used by radial approach (92.1%) in elective setting (90.6%) and using the 6F size (95.3%). The GEC was mostly implemented as bail-out strategy (75.9%) with the aim to improve back-up (89.6%), less frequently to optimize catheter alignment or obtain selective coronary cannulation (10.4%). Intracoronary advancement was performed using the guidewire in 1.3% of cases, after positioning of a second “buddy” wire in 23.2%, with support of a deflated balloon at the distal tip in 12.2%, or with anchoring technique in 63.3%. Mean coronary deep intubation depth was 38.8±23.9mm. Vessel and lesion characteristics are reported in Table I. Overall, PCI success rate was 92.5%, while procedural success (PCI success without in hospital adverse event) was 88.6%. GEC was successfully used in 92.7% of patients with no device-dependent severe adverse events; in particular, failures were related to inability to cross the target lesion in 4.5% or to device–related complication in 2.85% of cases. Conclusions This large real-world registry on GEC use in complex PCI confirms the GEC as a valid and safe tool to increase backup support and overcome the limits of conventional technique during complex PCI.

BACKGROUND: In the acute management of ST-elevation myocardial infarction (STEMI), glycoprotein IIb/IIIa inhibi-tors (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 oc-curred 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

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.

Abstract Aims Atherosclerotic plaque healing is a dynamic process developing after plaque rupture or erosion, which aims to prevent lasting occlusive thrombus formation and to promote plaque repair. We hypothesized that diabetes mellitus, one of the major conventional cardiovascular risk factors, may influence the healing capacity after plaque destabilization. Methods and results In this single-centre observational cohort study, patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) who underwent optical coherence tomography (OCT) imaging at Fondazione Policlinico A. Gemelli–IRCCS, Rome, were included. Patients were divided into two groups (i.e. diabetes vs. no diabetes), and stratified based on diabetes medications (i.e. insulin, vs. oral antidiabetic drugs). OCT analysis of non-culprit coronary segments was performed. 105 patients were included (44 diabetes, 61 no diabetes). Prevalence of HCPs was not significantly different between patients with and without diabetes (3.6% vs. 3.8%, P = 0.854). However, patients with diabetes on insulin showed a lower prevalence of HCPs both at patient-based (7.1% vs. 26.4%, P = 0.116) and at segment-based analysis (1.2% vs. 4.2%, P = 0.020). When comparing HbA1c levels based on the presence or absence of healed plaque at the non-culprit lesions, patients with healed plaque showed significantly lower levels of HbA1c compared to patients without healed plaques (43.5 ± 12.1% vs. 61.2 ± 10.4%, P < 0.001). At segment-based analysis, normal vessel structure, pathological intimal thickening (PIT), and spotty calcifications were significantly less prevalent in diabetic patients (2.1% vs. 5.1%, P = 0.001; 7.2% vs. 9.5%, P = 0.05; 9.9% vs. 13.6%, P = 0.02, respectively), whereas neovascularization was significantly higher (19.2% vs. 15.6%, P = 0.035). Conclusions Patients with diabetes have a distinct coronary non-culprit plaque phenotype. Healing capacity may be impaired in patients with advanced diabetes on insulin therapy and in those with a suboptimal control of the disease. Further prospective, larger scale studies are warranted to confirm these findings.

Background Myocardial bridging (MB) may represent a cause of myocardial ischemia in patients with non‐obstructive coronary artery disease (NOCAD). Herein, we assessed the interplay between MB and coronary vasomotor disorders, also evaluating their prognostic relevance in patients with myocardial infarction and non‐obstructive coronary arteries (MINOCA) or stable NOCAD. Methods and Results We prospectively enrolled patients with NOCAD undergoing intracoronary acetylcholine provocative test. The incidence of major adverse cardiac events, defined as the composite of cardiac death, non‐fatal myocardial infarction, and rehospitalization for unstable angina, was assessed at follow‐up. We also assessed angina status using Seattle Angina Questionnaires summary score. We enrolled 310 patients (mean age, 60.6±11.9; 136 [43.9%] men; 169 [54.5%] stable NOCAD and 141 [45.5%] MINOCA). MB was found in 53 (17.1%) patients. MB and a positive acetylcholine test coexisted more frequently in patients with MINOCA versus stable NOCAD. MB was an independent predictor of positive acetylcholine test and MINOCA. At follow‐up (median, 22 months; interquartile range, 13–32), patients with MB had a higher rate of major adverse cardiac events, mainly driven by a higher rate of hospitalization attributable to angina, and a lower Seattle Angina Questionnaires summary score (all P<0.001) compared with patients without MB. In particular, the group of patients with MB and a positive acetylcholine test had the worst prognosis. Conclusions Among patients with NOCAD, coronary spasm associated with MB may predict a worse clinical presentation with MINOCA and a higher rate of hospitalization attributable to angina at long‐term follow‐up with a low rate of hard events.

Introduction: The relationship between culprit plaque morphology, healed culprit plaques prevalence and clinical presentation of acute myocardial infarction (AMI) remains largely unexplored. Hypothesis: We hypothesized that pre-infarction angina (PIA) may reflect a distinct morphologic phenotype of culprit plaques and a different healing capacity. Methods: We conducted a retrospective observational study in patients with AMI who underwent intracoronary optical coherence tomography (OCT) imaging of the culprit lesion before PCI at the Fondazione Policlinico Gemelli-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome. Based on the clinical history, patients were classified into 2 groups: i) PIA group, defined as either intermittent chest pain within 6 hours preceding the final episode of chest pain, or unstable angina (or both) in the week preceding AMI; or ii) no-PIA group, defined as a single episode of chest pain without prodromal symptoms in the preceding week. Culprit plaques were classified as plaque rupture (PR) or intact fibrous cap (IFC), and presence of layered appearance (healed plaque, HP) was assessed. Thrombus burden (TB) was estimated, and prevalence of diffuse calcification, neovascularization, and OCT-defined macrophage accumulation were evaluated. Results: A total of 102 patients with AMI were included (50 PIA, 52 no-PIA). Patients with PIA showed a higher prevalence of IFC than PR (58% vs 42%, p=0.030). PR in patients with PIA were more frequently associated with macrophage accumulation (71.4% vs 28.6% p=0.001), and TB tended to be lower [22.0 (15.8-30.3) vs. 38.5 (12.8-67.5), p=0.145]. Diffuse calcifications were significantly less frequent in patients with PIA (22.0% vs. 40.4%, p=0.045), while neovascularization tended to be more frequent (58.0% vs. 42.3%, p=0.113). HPs prevalence was significantly higher in the PIA than in the no-PIA group (66.0% vs 25.0%, p<0.001). Conclusions: Patients with PIA have a distinct culprit plaque phenotype, more frequently characterized by IFC and a relatively lower TB, with a significantly higher prevalence of plaque healing.

Background Ticagrelor is a reversibly binding, direct-acting, oral, P 2 Y 12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. Methods To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart. Discussion Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes. Trial registration EudraCT No. 2016–004746-28 . No. NCT02701140 . Trial status Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019. Trial sponsor Fondazione Policlinico Universitario A. Gemelli – Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.

BACKGROUND:Coronary vasomotor dysfunction represents an important mechanism responsible for myocardial ischaemia in patients with non-obstructive coronary artery disease (CAD). The use of invasive provocative tests allows identifying patients with epicardial or microvascular spasm. Of note, clinical characteristics associated with the occurrence of epicardial or microvascular spasm have still not completely clarified.METHODS AND RESULTS:We prospectively enrolled consecutive patients undergoing coronary angiography for suspected myocardial ischaemia/necrosis with evidence of non-obstructive CAD and undergoing intracoronary provocative test for suspected vasomotor dysfunction. Patients with a positive provocative test were enrolled. Clinical, echocardiographic and angiographic characteristics of patients were evaluated according to the pattern of vasomotor dysfunction (epicardial vs. microvascular spasm). We included 120 patients [68 patients with stable angina and 52 patients with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. In particular, 77 (64.2%) patients had a provocative test positive for epicardial spasm and 43 (35.8%) patients for microvascular spasm. Patients with epicardial spasm were more frequently males, smokers, had higher rates of diffuse coronary atherosclerosis at angiography and more frequently presented with MINOCA. On the other hand, patients with microvascular spasm presented more frequently diastolic dysfunction. At multivariate logistic regression analysis male sex, smoking, and diffuse coronary atherosclerosis were independent predictors for the occurrence of epicardial spasm.CONCLUSIONS:Our study showed that specific clinical features are associated with different responses to intracoronary provocative test. Epicardial spasm is more frequent in males and in MINOCA patients, whereas microvascular spasm is more frequent in patients with stable angina and is associated with diastolic dysfunction.

Lipid-lowering therapies have been shown to improve cardiovascular outcome in a wide range of patients. The current guidelines recommend a graded approach to reduction in low-density lipoprotein cholesterol (LDL-C) proportional to the patient's risk, with the goal of achieving either a certain magnitude of reduction or a specific threshold of final LDL-C. Recent findings from a meta-analysis of numerous randomized trials suggest that more attention should be given to the baseline LDL-C of an individual patient. In this review, we discuss how the baseline LDL-C level may provide a means to better understand the results of recent cardiovascular outcome trials and the expected benefits of lipid-lowering therapies. The exact quantification of the clinical benefit associate with an intensified lipid-lowering therapy depends on the baseline LDL-C. Mortality is reduced in a log-linear fashion only when LDL-C > 100 mg/dL.

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 inOCTRegistry of the Fondazione PoliclinicoA. 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 acutemyocardial infarctions (AMIs) or at least 4ACS 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 healingmay play a role in leading the natural history of patients with CAD.

Lipid-lowering therapies have been shown to improve cardiovascular outcome in a wide range of patients. The current guidelines recommend a graded approach to reduction in low-density lipoprotein cholesterol (LDL-C) proportional to the patient's risk, with the goal of achieving either a certain magnitude of reduction or a specific threshold of final LDL-C. Recent findings from a meta-analysis of numerous randomized trials suggest that more attention should be given to the baseline LDL-C of an individual patient. In this review, we discuss how the baseline LDL-C level may provide a means to better understand the results of recent cardiovascular outcome trials and the expected benefits of lipid-lowering therapies. The exact quantification of the clinical benefit associate with an intensified lipid-lowering therapy depends on the baseline LDL-C. Mortality is reduced in a log-linear fashion only when LDL-C > 100 mg/dL.