Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial.

BACKGROUND: Thin-cap fibroatheroma (TCFA) lesions are associated with a high risk of future major adverse cardiovascular events. However, the impact of other optical coherence tomography-detected vulnerability features (OCT-VFs) and their interplay with TCFA in predicting adverse events remains unknown. AIMS: We aimed to evaluate the individual as well as the combined prognostic impact of OCT-VFs in predicting the incidence of the lesion-oriented composite endpoint (LOCE) in non-ischaemic lesions in patients with diabetes mellitus (DM). METHODS: COMBINE OCT-FFR (ClinicalTrials.gov: NCT02989740) was a prospective, double-blind, international, natural history study that included DM patients with ≥1 non-culprit lesions with a fractional flow reserve>0.80 undergoing systematic OCT assessment. OCT-VFs included the following: TCFA, reduced minimal lumen area (r-MLA), healed plaque (HP), and complicated plaque (CP). The primary endpoint, LOCE - a composite of cardiac mortality, target vessel myocardial infarction, or clinically driven target lesion revascularisation up to 5 years - was analysed according to the presence of these OCT-VFs, both individually and in combination. RESULTS: TCFA, r-MLA, HP and CP were identified in 98 (25.3%), 190 (49.0%), 87 (22.4%), and 116 (29.9%) patients, respectively. The primary endpoint rate increased progressively from 6.3% to 55.6% (hazard ratio 15.2, 95% confidence interval: 4.53-51.0; p<0.001) in patients without OCT-VFs as compared to patients with concomitant HP, r-MLA, CP, and TCFA. The coexistence of TCFA with other OCT-VFs resulted in an increased risk of the LOCE at 5 years. CONCLUSIONS: In DM patients with non-ischaemic lesions, TCFA was the strongest predictor of future LOCE events. However, lesions that present additional OCT-VFs are associated with a higher risk of adverse events than OCT-detected TCFA alone. Further randomised studies are warranted to confirm these findings and their potential clinical implications.

OCT-Guided versus Angiography-Guided Coronary Stent Implantation in Complex Lesions: An ILUMIEN IV Substudy.

BACKGROUND: ILUMIEN IV was the first large-scale, multicenter, randomized trial comparing optical coherence tomography (OCT)-guided versus angiography-guided stent implantation in patients with high-risk clinical characteristics and/or complex angiographic lesions. OBJECTIVE: Here, we aimed to specifically examine outcomes in the complex angiographic lesions subgroup. METHODS: From the original trial population (n=2487), high-risk patients without complex angiographic lesions were excluded (n=514). Complex angiographic lesion characteristics included 1) long or multiple lesions with intended total stent length ≥28 mm; 2) bifurcation lesion with intended two-stent strategy; 3) severely calcified lesion; 4) chronic total occlusion; or 5) in-stent restenosis. The study endpoints were 1) final minimal stent area (MSA); 2) 2-year composite of serious major adverse cardiovascular events (MACE; cardiac death, target-vessel myocardial infarction (MI), or stent thrombosis); and 3) 2-year effectiveness, defined as target-vessel failure (TVF), a composite of cardiac death, target-vessel MI, or ischemia-driven target-vessel revascularization. RESULTS: The post-PCI MSA was larger in the OCT- (n=992) versus angiography-guided (n=981) group (5.56±1.95 versus 5.26±1.81mm2; difference, 0.30; 95% confidence interval [CI], 0.14-0.47; P<0.001). Compared with angiography-guided PCI, OCT-guided PCI resulted in a lower risk of serious MACE (3.1% versus 4.9%; hazard ratio [HR], 0.63; 95% CI, 0.40-0.99; P=0.04). TVF was not significantly different between groups (7.3% versus 8.8%; HR, 0.82; 95% CI, 0.59-1.12; P=0.20). CONCLUSIONS: In complex angiographic lesions, OCT-guided PCI led to a larger MSA and reduced the serious MACE composite of cardiac death, target-vessel MI, or stent thrombosis compared with angiography-guided PCI at 2 years, but did not significantly improve TVF.

Impact of coronary calcium morphology on intravascular lithotripsy.

BACKGROUND: Coronary calcification negatively impacts optimal stenting. Intravascular lithotripsy (IVL) is a new calcium modification technique. AIMS: We aimed to assess the impact of different calcium morphologies on IVL efficacy. METHODS: This was a prospective, multicentre study (13 tertiary referral centres). Optical coherence tomography (OCT) was performed before and after IVL, and after stenting. OCT-defined calcium morphologies were concentric (mean calcium arc >180°) and eccentric (mean calcium arc ≤180°). The primary outcomes were angiographic success (residual stenosis <20%) and the presence of fracture by OCT in concentric versus eccentric lesions. RESULTS: Ninety patients were included with a total of 95 lesions: 47 concentric and 48 eccentric. The median number of pulses was 60 (p=1.00). Following IVL, the presence of fracture was not statistically different between groups (79.0% vs 66.0% for concentric vs eccentric; p=0.165). The number of fractures/lesion (4.2±4.4 vs 2.3±2.8; p=0.018) and ≥3 fractures/lesion (57.1% vs 34.0%; p=0.029) were more common in concentric lesions. Angiographic success was numerically but not statistically higher in the concentric group (87.0% vs 76.6%; p=0.196). By OCT, no differences were noted in final minimum lumen area (5.9±2.2 mm2 vs 6.2±2.1 mm2; p=0.570), minimum stent area (5.9±2.2 mm² vs 6.25±2.4 mm2; p=0.483), minimum stent expansion (80.9±16.7% vs 78.2±19.8%), or stent expansion at the maximum calcium site (100.6±24.2% vs 95.8±27.3%) (p>0.05 for all comparisons of concentric vs eccentric, respectively). Calcified nodules were found in 29.5% of lesions; these were predominantly non-eruptive (57%). At the nodule site, dissection was more common than fracture with stent expansion of 103.6±27.2%. CONCLUSIONS: In this prospective, multicentre study, the effectiveness of IVL followed by stenting was not significantly affected by coronary calcium morphology.

Development and Clinical Application of Left Ventricular-Arterial Coupling Non-Invasive Assessment Methods.

The constant and dynamic interaction between ventricular function and arterial afterload, known as ventricular-arterial coupling, is key to understanding cardiovascular pathophysiology. Ventricular-arterial coupling has traditionally been assessed invasively as the ratio of effective arterial elastance over end-systolic elastance (Ea/Ees), calculated from information derived from pressure-volume loops. Over the past few decades, numerous invasive and non-invasive simplified methods to estimate the elastance ratio have been developed and applied in clinical investigation and practice. The echocardiographic assessment of left ventricular Ea/Ees, as proposed by Chen and colleagues, is the most widely used method, but novel echocardiographic approaches for ventricular-arterial evaluation such as left ventricle outflow acceleration, pulse-wave velocity, and the global longitudinal strain or global work index have arisen since the former was first published. Moreover, multimodal imaging or artificial intelligence also seems to be useful in this matter. This review depicts the progressive development of these methods along with their academic and clinical application. The left ventricular-arterial coupling assessment may help both identify patients at risk and tailor specific pharmacological or interventional treatments.

Angiographic patterns in spontaneous coronary artery dissection: novel diagnostic insights.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a rare but well-recognized cause of acute coronary syndrome, especially important in women. Invasive coronary angiography (ICA) is the fundamental diagnostic technique for the confirmation of SCAD. Knowing the angiographic patterns suggestive of SCAD is essential for the correct identification of patients with this entity. AREAS COVERED: In this narrative review, the main angiographic characteristics of SCAD lesions as detected by ICA are presented and discussed. EXPERT OPINION: In addition to the specific angiographic classification of SCAD, several authors have described complementary angiographic patterns suggestive of SCAD. Knowledge and correct identification of these angiographic patterns is essential for the correct diagnosis of patients with clinical suspicion of SCAD.

Intravascular Imaging-Guided Versus Coronary Angiography-Guided Complex PCI: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Trials evaluating the role of intravascular imaging in percutaneous coronary intervention (PCI) for complex coronary artery disease have yielded mixed results. This study aimed to compare the outcomes of intravascular imaging specifically intravascular ultrasound (IVUS) with those from conventional coronary angiography in complex PCI. METHODS: Comprehensive electronic search of MEDLINE, EMBASE, and Cochrane databases was performed until March 2023 for randomized clinical trials (RCTs) comparing intravascular imaging with coronary angiography in patients undergoing complex PCI. Complex PCI was defined per each study, and included PCI for American College of Cardiology/American Heart Association (ACC/AHA) type B2/C lesions, unprotected left main coronary artery disease, or multivessel stenting. The primary study outcome was major adverse clinical events (MACE). RESULTS: The meta-analysis included 10 RCTs with a total of 6615 patients (3576 in the intravascular imaging group and 3039 in the coronary angiography group). The weighted mean-follow up was 28.9 months. Compared with coronary angiography, intravascular imaging reduced MACE (8% vs. 13.3%; relative risk [RR] 0.63; 95% confidence interval [CI] 0.54-0.73), cardiac death (RR 0.47; 95% CI 0.31-0.73), definite/probable stent thrombosis (RR 0.48; 95% CI 0.24-0.97), target vessel revascularization (RR 0.62; 95% CI 0.46-0.83), and target lesion revascularization (RR 0.61; 95% CI 0.47-0.79). There was no difference between both groups in all-cause death (RR 0.79; 95% CI 0.53-1.18) and myocardial infarction (RR 0.80; 95% CI 0.61-1.04). CONCLUSION: In patients undergoing complex PCI, intravascular imaging-specifically IVUS-reduced MACE by decreasing the incidence of cardiac death, stent thrombosis, and target vessel and target lesion revascularization.

Pediatric takotsubo cardiomyopathy: A review and insights from a National Multicentric Registry.

Takotsubo syndrome (TTS) in the pediatric population is an infrequent but relevant cause of morbidity and mortality, with limited studies addressing its clinical course and prognosis. We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. We included a total of 54 patients from 4 different hospitals in Spain, as well as pediatric TTS patients from the published literature. Comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between pediatric and adult population features. Patients with pediatric TTS are more commonly male and exhibit a higher prevalence of physical triggers. The left ventricular ejection fraction (LVEF) was significantly lower in the pediatric population (30.5 + 10.4 vs 36.9 + 16.9, p < 0.05), resulting in more than fivefold rates of cardiogenic shock on admission compared to the general adult TTS population (Killip IV 74.1% vs 10.5%, p < 0.001) with similar rates of death and recurrence between groups. TTS in the pediatric population presents a distinctive clinical profile, with higher prevalence of atypical symptoms and physical triggers, as well as higher rates of cardiogenic shock on admission and similar mortality and recurrence rates than those of the adult population. This study provides valuable insights into understanding pediatric TTS and underscores the necessity for further research in this age group.

Timing of Complete Multivessel Revascularization in Patients Presenting With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Complete revascularization of the culprit and all significant nonculprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD) reduces major adverse cardiac events, but optimal timing of revascularization remains unclear. OBJECTIVES: This study aims to compare immediate complete revascularization (ICR) and staged complete revascularization (SCR) in patients presenting with NSTE-ACS and MVD. METHODS: This prespecified substudy of the BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease) trial included patients with NSTE-ACS and MVD. Risk differences of the primary composite outcome of all-cause mortality, myocardial infarction (MI), unplanned ischemia-driven revascularization (UIDR), or cerebrovascular events and its individual components were compared between ICR and SCR at 1 year. RESULTS: The BIOVASC trial enrolled 1,525 patients; 917 patients presented with NSTE-ACS, of whom 459 were allocated to ICR and 458 to SCR. Incidences of the primary composite outcome were similar in the 2 groups (7.9% vs 10.1%; risk difference 2.2%; 95% CI: -1.5 to 6.0; P = 0.15). ICR was associated with a significant reduction of MIs (2.0% vs 5.3%; risk difference 3.3%; 95% CI: 0.9 to 5.7; P = 0.006), which was maintained after exclusion of procedure-related MIs occurring during the index or staged procedure (2.0% vs 4.4%; risk difference 2.4%; 95% CI: 0.1 to 4.7; P = 0.032). UIDRs were also reduced in the ICR group (4.2% vs 7.8%; risk difference 3.5%; 95% CI: 0.4 to 6.6; P = 0.018). CONCLUSIONS: ICR is safe in patients with NSTE-ACS and MVD and was associated with a reduction in MIs and UIDRs at 1 year.

Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. Design, Setting, and Participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. Conclusions and Relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. Trial registration: ClinicalTrials.gov Identifier: NCT03208153.

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study.

BACKGROUND: Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES: The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS: The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS: A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS: Coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307).

Transcatheter aortic valve replacement in the treatment of bicuspid aortic stenosis with "down-size" interventional valves: procedural and mid-term follow-up.

Background: Due to the influence of anatomical structure, replacing the bicuspid valve using transcatheter aortic valve replacement (TAVR) would increase the risk of perivalvular leakage and conduction block, affecting the hemodynamic effect of the interventional valve. In this study, for bicuspid and tricuspid valves, we implemented different valve selection strategies to explore the safety and effectiveness of TAVR in the treatment of bicuspid aortic stenosis with "down-size" interventional valves using the VenusA-valve system. Methods: The operation was performed with the VenusA-valve via transfemoral approach. The selected valves were appropriately sized based on the results of transthoracic echocardiography (TTE), contrast-enhanced computed tomography (CT), and the morphology of intraoperative pre-dilation balloons. For tricuspid valve cases, the VenusA valve is usually larger than the annulus diameter, whereas the "down-size" approach was adopted for bicuspid aortic valve (BAV) cases. The shape of the pre-dilation balloon allowed further sizing of the annulus diameter by the degree of lumbar constriction of the balloon, aiding in intervention valve size selection, particularly in cases of BAVs. Results: A total of 65 patients underwent TAVR for aortic stenosis with VenusA-valve systems. Of these, 29 cases had a BAV and 36 cases had a tricuspid aortic valve (TAV). The distribution of VenusA-valve sizes differed between TAV and BAV cases (P=0.007). Furthermore, there was a significant decrease in the average mean gradient in TAV patients from 54.7 to 12.2 mmHg (P<0.001), and in BAV patients from 61.6 to 14.3 mmHg (P<0.001). The percentage of paravalvular leakage greater than mild was 6.90% in the BAVs and 5.56% in the TAVs at procedural outcomes (P=0.955). The mean follow-up period was 22.23 months (range, 12 to 39 months). The proportion of New York Heart Association (NYHA) class III/IV decreased from 78.5% preoperatively to 11.3% at the last follow-up (P<0.001). A total of 27 patients with TAV and 19 patients with BAV underwent TTE at 1-year follow-up after operation. There was no significant contrast in the average pressure difference between TAVs and BAVs at 1-year follow-up (11.9 vs. 14.3 mmHg, P=0.18). Conclusions: The VenusA-valve for TAVR produced positive clinical outcomes and valve functionality in both BAVs and TAVs. In the case of BAVs, selecting a smaller interventional valve size was deemed viable.

Impact of age on the outcomes of Takotsubo syndrome.

BACKGROUND: The impact on age on the short-term and long-term prognosis in patients with Takotsubo syndrome (TTS) is unclear. We aimed to evaluate whether age has prognostic implications during hospital stay and long-term follow-up of TTS patients. METHODS: 688 consecutive patients were admitted for TTS in 7 tertiary centers from January-2008 to June-2021. We divided our cohort into two groups (patients <75 years and ≥75 years). Clinical, analytical, and hemodynamic variables as well as in-hospital management were registered and compared between groups. Mortality rates during hospital stay and follow-up were assessed. Adverse cardiovascular events (ACE) were defined as the composite of cardiovascular death, heart failure event, acute myocardial infarction, stroke and symptomatic arrhythmia. RESULTS: Median age was 74.7 years and 49.4 % were ≥75 years. 86.9 % were women and 22.3 % were secondary forms of TTS. In-hospital mortality was 3.6 % (1.5 % cardiovascular). Median clinical follow-up was 4.3 years. Mortality during the follow-up period was 23 % (5.0 % cardiovascular) while ACE were 22.5 %, mainly due to heart failure events. Kaplan-Meier curves showed both higher rates of mortality and ACE in ≥75 years group (30.2 % vs 15.8 %; p < 0.001 and 28.3 % vs 16.7 %; p < 0.001). Age was independently associated with higher rates of overall mortality and ACE in patients with TTS. Hypertension, absence of sinus rhythm, Killip class > I and a more impaired coronary microvascular resistance were also associated to ACE in TTS patients. CONCLUSIONS: Advanced age was associated with higher rate of overall mortality and ACE during long-term follow-up in TTS patients.

Left Atrial Strain Predicts Stroke Recurrence and Death in Patients With Cryptogenic Stroke.

Left atrial strain (LAS) has been widely studied as a predictor of atrial fibrillation (AF) after cryptogenic stroke (CS). However, the evidence about its prognostic role in terms of stroke recurrence and death in this setting remains scarce. A total of 92 consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography, including LAS was performed during admission. The primary outcome measure was the composite of stroke recurrence or death. The mean age was 77.5 ± 7.7, and 58% of patients were female. After a median follow up of 28 months, the primary outcome measure occurred in 15 patients (16%). The primary outcome was more frequent in patients with diabetes (53% vs 21%, p = 0.02), chronic kidney disease (33% vs 10%, p = 0.034), and a history of heart failure (13% vs 0%, p = 0.025). LAS reservoir (LASr) and LAS conduit (LAScd) were lower in patients developing the primary outcome (21% ± 7% vs 28.8% ± 11%, p = 0.017 and 7.7% ± 3.9% vs 13.7% ± 7%, p = 0.007, respectively). On multivariate analysis, LASr (hazard ratio 0.9, 95% confidence interval 0.85 to 0.99, p = 0.048) and diabetes (hazard ratio 3.3, 95% confidence interval 1.03 to 10.4, p = 0.045) were associated with stroke recurrence or all-cause death after CS. On the log-rank test (using the discriminatory cut-off value of LASr <23%), LASr (p = 0.009) was associated with higher risk of the primary outcome. In conclusion, lower values of the LAS reservoir were associated with a higher risk of stroke recurrence or death after CS. LAS may identify patients at higher risk of thromboembolism and stress conditions.