One-year longitudinal changes of peripheral CD4+ T-lymphocyte counts, gut microbiome, and plaque vulnerability after an acute coronary syndrome.

Background: Longitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to characterize repeated profiles of gut microbiota and peripheral CD4+ T lymphocytes during the first year after an ACS, and to address their relationship with atherosclerotic plaque changes. Methods: Over one year we measured the microbiome, peripheral counts of CD4+ T populations and cytokines in 67 patients shortly after a first ACS. We compared baseline measurements to those of a matched population of 40 chronic patients. A subgroup of 20 ACS patients underwent repeated assessment of fibrous cap thickness (FCT) of a non-culprit lesion. Results: At admission, ACS patients showed gut dysbiosis compared with the chronic group, which was rapidly reduced and remained low at 1-year. Also, their Th1 and Th2 CD4+ T counts were increased but decreased over time. The CD4+ T counts were related to ongoing changes in gut microbiome. Unsupervised clustering of repeated CD4+ Th0, Th1, Th2, Th17 and Treg counts in ACS patients identified two different cell trajectory patterns, related to cytokines. The group of patients following a high-CD4+ T cell trajectory showed a one-year reduction in their FCT [net effect = -24.2 µm; p = 0.016]. Conclusions: Patients suffering an ACS show altered profiles of microbiome and systemic inflammation that tend to mimic values of chronic patients after 1-year. However, in one-third of patients, this inflammatory state remains particularly dysregulated. This persistent inflammation is likely related to plaque vulnerability as evident by fibrous cap thinning (Clinical Trial NCT03434483).

Non-atherosclerotic acute cardiac syndromes: spontaneous coronary artery dissection and Takotsubo syndrome. Comparison of long-term clinical outcomes.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two common causes of nonatherosclerotic acute cardiac syndrome particularly frequent in women. Currently, there is no information comparing long-term clinical outcomes in unselected patients with these conditions. METHODS: We compared the baseline characteristics, in-hospital outcomes, and the 12-month and long-term clinical outcomes of two large prospective registries on SCAD and TTS. RESULTS: A total of 289 SCAD and 150 TTS patients were included; 89% were women. TTS patients were older with a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS patients, while emotional triggers and depressive disorders were more common in the SCAD group. Left ventricular ejection fraction was lower in TTS patients, but SCAD patients showed higher cardiac biomarkers. In-hospital events (43.3% vs. 5.2%, P <0.01) occurred more frequently in TTS patients. TTS patients also presented more frequent major adverse events at 12-month (14.7% vs. 7.1%, HR 5.3, 95% CI: 2.4-11.7, P <0.01) and long-term (median 36 vs. 31 months, P =0.41) follow-up (25.8% vs. 9.6%, HR 4.5, 95% CI: 2.5-8.2, P <0.01). Atrial fibrillation was also more frequent in TTS patients. Moreover, TTS patients presented a higher 12-month and long-term mortality (5.6% vs. 0.7%, P =0.01; and 12.6% vs. 0.7%, P <0.01) mainly driven by noncardiovascular deaths. CONCLUSION: Compared to SCAD, TTS patients are older and present more cardiovascular risk factors but less frequent depressive disorder or emotional triggers. TTS patients have a worse in-hospital, mid-term, and long-term prognosis with higher noncardiac mortality than SCAD patients.

Increased Chamber Resting Tone Is a Key Determinant of Left Ventricular Diastolic Dysfunction.

BACKGROUND: Twitch-independent tension has been demonstrated in cardiomyocytes, but its role in heart failure (HF) is unclear. We aimed to address twitch-independent tension as a source of diastolic dysfunction by isolating the effects of chamber resting tone (RT) from impaired relaxation and stiffness. METHODS: We invasively monitored pressure-volume data during cardiopulmonary exercise in 20 patients with hypertrophic cardiomyopathy, 17 control subjects, and 35 patients with HF with preserved ejection fraction. To measure RT, we developed a new method to fit continuous pressure-volume measurements, and first validated it in a computational model of loss of cMyBP-C (myosin binding protein-C). RESULTS: In hypertrophic cardiomyopathy, RT (estimated marginal mean [95% CI]) was 3.4 (0.4-6.4) mm Hg, increasing to 18.5 (15.5-21.5) mm Hg with exercise (P<0.001). At peak exercise, RT was responsible for 64% (53%-76%) of end-diastolic pressure, whereas incomplete relaxation and stiffness accounted for the rest. RT correlated with the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide; R=0.57; P=0.02) and with pulmonary wedge pressure but following different slopes at rest and during exercise (R2=0.49; P<0.001). In controls, RT was 0.0 mm Hg and 1.2 (0.3-2.8) mm Hg in HF with preserved ejection fraction patients and was also exacerbated by exercise. In silico, RT increased in parallel to the loss of cMyBP-C function and correlated with twitch-independent myofilament tension (R=0.997). CONCLUSIONS: Augmented RT is the major cause of LV diastolic chamber dysfunction in hypertrophic cardiomyopathy and HF with preserved ejection fraction. RT transients determine diastolic pressures, pulmonary pressures, and functional capacity to a greater extent than relaxation and stiffness abnormalities. These findings support antimyosin agents for treating HF.

Prognostic implications of left ventricular systolic dysfunction in patients with spontaneous coronary artery dissection.

AIMS: Spontaneous coronary artery dissection (SCAD) is a relatively infrequent cause of acute coronary syndrome. Clinical features, angiographic findings, management, and outcomes of SCAD patients who present reduced left ventricular ejection fraction (LVEF) remain unknown. METHODS AND RESULTS: The Spanish multicentre prospective SCAD registry (NCT03607981), included 389 consecutive patients with SCAD. In 348 of these patients, LVEF could be assessed by echocardiography during the index admission. Characteristics and outcomes of patients with preserved LVEF (LVEF ≥50%, n = 295, 85%) were compared with those with reduced LVEF (LVEF <50%, n = 53, 15%). Mean age was 54 years and 90% of patients in both groups were women. The most frequent clinical presentation in patients with reduced LVEF was ST-segment elevation myocardial infarction (STEMI) (62% vs. 36%, P < 0.001), especially anterior STEMI. Proximal coronary segment and multi-segment involvement were also significantly more frequent in these patients. No differences were found on initial revascularization between groups. Patients with reduced LVEF significantly received more often neurohormonal antagonist therapy, and less frequently aspirin. In-hospital events were more frequent in these patients (13% vs. 5%, P = 0.01), with higher rates of death, cardiogenic shock, ventricular arrhythmia, and stroke. During a median follow-up of 28 months, the occurrence of a combined adverse event did not statistically differ between the two groups (19% vs. 12%, P = 0.13). However, patients with reduced LVEF had higher mortality (9% vs. 0.7%, P < 0.001) and readmission rates for heart failure (HF) (4% vs. 0.3%, P = 0.01). CONCLUSION: Patients with SCAD and reduced LVEF show differences in clinical characteristics and angiographic findings compared with SCAD patients with preserved LVEF. Although these patients receive specific medications at discharge, they had higher mortality and readmission rates for HF during follow-up.

Off-Hours versus Regular-Hours Implantation of Peripheral Venoarterial Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock.

BACKGROUND: The "weekend effect" has been associated with worse clinical outcomes. Our aim was to compare off-hours vs. regular-hours peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) in cardiogenic shock patients. METHODS: We analyzed in-hospital and 90-day mortality among 147 consecutive patients treated with percutaneous VA-ECMO for medical reasons between July 1, 2013, and September 30, 2022, during regular-hours (weekdays 8:00 a.m.-10:00 p.m.) and off-hours (weekdays 10:01 p.m.-7:59 a.m., weekends, and holidays). RESULTS: The median patient age was 56 years (interquartile range [IQR] 49-64 years) and 112 (72.6%) were men. The median lactate level was 9.6 mmol/L (IQR 6.2-14.8 mmol/L) and 136 patients (92.5%) had a Society for Cardiovascular Angiography and Interventions (SCAI) stage D or E. Cannulation was performed off-hours in 67 patients (45.6%). In-hospital mortality was similar in off-hours and regular hours (55.2% vs. 56.3%, p = 0.901), as was the 90-day mortality (58.2% vs. 57.5%, p = 0.963), length of hospital stay (31 days [IQR 16-65.8 days] vs. 32 days [IQR 18-63 days], p = 0.979), and VA-ECMO related complications (77.6% vs. 70.0%, p = 0.305). CONCLUSIONS: Off-hours and regular-hours percutaneous VA-ECMO implantation in cardiogenic shock of medical cause have similar results. Our results support well-designed 24/7 VA-ECMO implantation programs for cardiogenic shock patients.

Spontaneous coronary artery dissection and ST-segment elevation myocardial infarction: Does clinical presentation matter?

BACKGROUND: Some patients with spontaneous coronary artery dissection (SCAD) present as ST-segment-elevation myocardial infarction (STEMI). This study evaluates the characteristics, management and outcomes of SCAD patients presenting as STEMI compared to non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We analysed data from consecutive patients included in the prospective Spanish Registry on SCAD. All coronary angiograms were centrally reviewed. All adverse events were adjudicated by an independent Clinical Events Committee. RESULTS: Between June 2015 to December 2020, 389 patients were included. Forty-two percent presented with STEMI and 56% with NSTEMI. STEMI patients showed a worse distal flow (TIMI flow 0-1 38% vs 19%, p < 0.001) and more severe (% diameter stenosis 85 ± 18 vs 75 ± 21, p < 0.001) and longer (42 ± 23 mm vs 35 ± 24 mm, p = 0.006) lesions. Patients with STEMI were more frequently treated with percutaneous coronary intervention (PCI) (31% vs 16%, p < 0.001) and developed more frequently left ventricular systolic dysfunction (21% vs 8%, p < 0.001). No differences were found in combined major adverse events during admission (7% vs 5%, p = 0.463), but in-hospital reinfarctions (5% vs 1.4%, p = 0.039) and cardiogenic shock (2.6% vs 0%, p = 0.019) were more frequently seen in the STEMI group. At late follow-up (median 29 months) no differences were found in the incidence of major adverse cardiac and cerebrovascular events (13% vs 13%, p-value = 0.882) between groups. CONCLUSIONS: Patients with SCAD and STEMI had a worse angiographic profile and were more frequently referred to PCI compared to NSTEMI patients. Despite these disparities, both short and long-term prognosis were similar in STEMI and NSTEMI SCAD patients.

Endothelial dysfunction in patients with angina and non-obstructed coronary arteries is associated with an increased risk of mayor cardiovascular events. Results of the Spanish ENDOCOR registry.

BACKGROUND: Coronary endothelial dysfunction and vasospasm are potential causes of ischemia in patients without obstructive coronary stenoses (INOCA). OBJECTIVE: To evaluate the prevalence of endothelial dysfunction and the clinical profile of patients with INOCA in Spain, as well as to identify the predictors and the prognostic impact of endothelial dysfunction in this scenario. METHODS: A total of 438 consecutive patients with INOCA in whom the acetylcholine test was performed were prospectively enrolled. Patients were followed up at 1 and 2 years. RESULTS: Mean age was 62 ± 11 years with 60% female. Clinical presentation comprised 52.6% angina at rest, 61.2% exertional angina, and 31.7% dyspnea. There were no major complications of the acetylcholine test. Endothelial dysfunction was observed in 198 (45%) of patients, with severe vasoconstriction (defined as over 70% constriction), being observed in 101 (23%). Multivariable regression analysis showed that endothelial dysfunction was predicted by the presence of exertional angina (OR 2.2; CI95%1.01-2.55; p = 0.02), prior coronary disease (OR 2.46; CI95% 1.57-3.89; p < 0.01), and coronary intramyocardial bridging (2.35; CI95% 1.02-5.60; p = 0.04). Patients with endothelial dysfunction presented with worsening angina compared to those without endothelial dysfunction (25.6% vs. 12.8%) and also presented with increased levels of minimal effort angina (40% vs. 26,7%, p = 0.03) more frequently during the follow up than those without endothelial dysfunction. Endothelial dysfunction was also an independent predictor of the occurrence of myocardial infarction or unstable angina at one year (OR 2.85, CI 95% 1.01-9.25; p = 0.03). CONCLUSIONS: Endothelial dysfunction is present in almost half of patients with INOCA and is associated with worsening symptoms, as well as with a higher rate of adverse events.

Multivessel spontaneous coronary artery dissection: Clinical features, angiographic findings, management, and outcomes.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. Multivessel (MV) SCAD is a challenging clinical presentation that might be associated to a worse prognosis compared with patients with single-vessel (SV) involvement. METHODS: The Spanish multicentre nationwide prospective SCAD registry included 389 consecutive patients. Patients were classified, according to the number of affected vessels, in SV or MV SCAD. Major adverse events (MAE) were analyzed during hospital stay and major cardiac or cerebrovascular adverse events (MACCE) at long-term clinical follow-up. RESULTS: A total of 41 patients (10.5%) presented MV SCAD. These patients had more frequently a previous history of hypothyroidism (22% vs 11%, p = 0.04) and anxiety disorder (32% vs 16%, p = 0.01). MV SCAD patients presented more often as non-ST segment elevation myocardial infarction (73% vs 52%, p = 0.01) and showed less frequently type 1 angiographic lesions (12% vs 21%, p = 0.04). An impaired initial Thrombolysis In Myocardial Infarction (TIMI) flow 0-1 was less frequent (14% vs 29%, p < 0.01) in MV SCAD. In both groups, most patients were treated conservatively (71% vs 79%, p = NS). No differences were found regarding in-hospital MAE or MACCE at late follow-up (median 29 ± 11 months). However, the rate of stroke was higher in MV SCAD patients, both in-hospital (2.4% vs 0%, p < 0.01) and at follow-up (5.1% vs 0.6%, p = 0.01). CONCLUSIONS: Patients with MV SCAD have some distinctive clinical and angiographic features. Although composite clinical outcomes, in-hospital and at long-term follow-up, were similar to those seen in patients with SV SCAD, stroke rate was significantly higher in patients with MV SCAD.

Effects of Cardiac Stem Cell on Postinfarction Arrhythmogenic Substrate.

Clinical data suggest that cardiosphere-derived cells (CDCs) could modify post-infarction scar and ventricular remodeling and reduce the incidence of ventricular tachycardia (VT). This paper assesses the effect of CDCs on VT substrate in a pig model of postinfarction monomorphic VT. We studied the effect of CDCs on the electrophysiological properties and histological structure of dense scar and heterogeneous tissue (HT). Optical mapping and histological evaluation were performed 16 weeks after the induction of a myocardial infarction by transient occlusion of the left anterior descending (LAD) artery in 21 pigs. Four weeks after LAD occlusion, pigs were randomized to receive intracoronary plus trans-myocardial CDCs (IC+TM group, n: 10) or to a control group. Optical mapping (OM) showed an action potential duration (APD) gradient between HT and normal tissue in both groups. CDCs increased conduction velocity (53 ± 5 vs. 45 ± 6 cm/s, p < 0.01), prolonged APD (280 ± 30 ms vs. 220 ± 40 ms, p < 0.01) and decreased APD dispersion in the HT. During OM, a VT was induced in one and seven of the IC+TM and control hearts (p = 0.03), respectively; five of these VTs had their critical isthmus located in intra-scar HT found adjacent to the coronary arteries. Histological evaluation of HT revealed less fibrosis (p < 0.01), lower density of myofibroblasts (p = 0.001), and higher density of connexin-43 in the IC+TM group. Scar and left ventricular volumes did not show differences between groups. Allogeneic CDCs early after myocardial infarction can modify the structure and electrophysiology of post-infarction scar. These findings pave the way for novel therapeutic properties of CDCs.

New Percutaneous Approaches for the Treatment of Heavily Calcified Mitral Valve Stenosis.

Important breakthroughs have considerably improved the outcomes of the percutaneous treatment of valvular heart diseases during the last decades. However, calcium deposition and progressive calcification of the left-sided heart valves present a challenge with prognostic implications that have not been addressed until recently. In the case of native mitral stenosis with no surgical options, a compelling need for tackling heavily calcified valves has led to the development of novel debulking techniques and to the use of aortic balloon-expandable bioprosthesis in the mitral position. In this section of the special issue "Mitral Valve Disease: State of the Art", we will review standard approaches and indications for the treatment of native mitral stenosis; summarize these two innovative solutions and their evidence, describing both procedures in a "step-by-step" fashion; and briefly comment on future directions in this field.

Clinical Implications of the "Broken Line" Angiographic Pattern in Patients With Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute myocardial infarction. Coronary angiography remains the best diagnostic tool; however, clinical suspicion and experience is required to interpret angiographic findings. This study sought to assess the clinical implications of the "broken line" (BKL) angiographic pattern in a large, nationwide, cohort of patients with SCAD. The Spanish SCAD registry (NCT03607981) prospectively enrolled consecutive patients with SCAD. All angiograms were centrally analyzed and the BKL pattern was systematically assessed. The BKL angiographic pattern was found in 64 of 389 patients (16%). Patients with the BKL appearance were more frequently female (97 vs 87%, p <0.05), presented more often as intramural hematoma (83 vs 58%, p <0.001), had longer lesions (47 ± 29 vs 36 ± 22 mm, p <0.01), and had severe tortuosity (25 vs 10%, p <0.01) but showed better initial coronary flow (thrombolysis in myocardial infarction flow 2.6 ± 0.8 vs 2.1 ± 1.2, p <0.01). Patients with BKL received more frequently conservative medical management (91 vs 76%, p <0.01). At late clinical follow-up (median 29 months, interquartile range 17 to 38) predefined adverse events (death, myocardial infarction, revascularization, recurrent SCAD, or stroke) occurred less frequently (3.5 vs 15%, p <0.05) in patients with the BKL appearance. The better clinical outcomes of patients in the BKL group persisted after adjusting for potential confounders (adjusted hazard ratio 0.2, 95% confidence interval 0.1 to 0.9, p <0.05). In conclusion, patients with SCAD presenting the BKL angiographic pattern are more frequently female and present more often as intramural hematoma with longer lesions and severe vessel tortuosity but have better coronary flow. Patients with the BKL morphology have a favorable prognosis (NCT03607981).

Combined atrial fibrillation ablation and balloon mitral commissurotomy in patients with rheumatic mitral stenosis.

INTRODUCTION: Ablation of atrial fibrillation (AF) is usually not considered in patients with rheumatic mitral stenosis (RMS). We analyzed the results of a combined procedure of AF ablation and percutaneous balloon mitral commissurotomy (PBMC). METHODS: We prospectively included 22 patients with severe RMS to undergo a combined PBMC + AF ablation procedure. Noninvasive mapping of the atria was also performed. A historical sample of propensity-scored matched patients who underwent PBMC alone was used as controls. The primary endpoint was freedom from AF/AT at 1-year. Multivariate analysis evaluated sinus rhythm (SR) predictors. RESULTS: Successful pulmonary vein isolation and electrocardiographic imaging-based drivers ablation was performed in 20 patients following PBMC. At 1-year, 75% of the patients in the combined group were in SR compared to 40% in the propensity-score matched group (p = 0.004). The composite of AF recurrence, need for mitral surgery and all-cause mortality was also more frequent in the control group (65% vs. 30%; p = 0.005). Catheter ablation (odds ratio [OR] 1.58; 95% confidence interval [CI] [1.17-17.37]; p = 0.04) and AF type (OR 1.46; 95% CI [1.05-82.64]; p < 0.001) were the only independent predictors of SR at 1-year. Noninvasive mapping in the combined group showed that the number of simultaneous rotors (OR 2.10; 95% CI [1.41-10.2]; p = 0.04) was the only independent predictor of AF. CONCLUSION: A combined procedure of AF ablation and PBMC significantly increased the proportion of patients in sinus rhythm at 1-year. Noninvasive mapping may help to improve AF characterization and guide personalized AF treatment.

Cardiovascular Diseases in the Digital Health Era: A Translational Approach from the Lab to the Clinic.

Translational science has been introduced as the nexus among the scientific and the clinical field, which allows researchers to provide and demonstrate that the evidence-based research can connect the gaps present between basic and clinical levels. This type of research has played a major role in the field of cardiovascular diseases, where the main objective has been to identify and transfer potential treatments identified at preclinical stages into clinical practice. This transfer has been enhanced by the intromission of digital health solutions into both basic research and clinical scenarios. This review aimed to identify and summarize the most important translational advances in the last years in the cardiovascular field together with the potential challenges that still remain in basic research, clinical scenarios, and regulatory agencies.

Meta-Analysis of Percutaneous Endomyocardial Cell Therapy in Patients with Ischemic Heart Failure by Combination of Individual Patient Data (IPD) of ACCRUE and Publication-Based Aggregate Data.

Individual patient data (IPD)-based meta-analysis (ACCRUE, meta-analysis of cell-based cardiac studies, NCT01098591) revealed an insufficient effect of intracoronary cell-based therapy in acute myocardial infarction. Patients with ischemic heart failure (iHF) have been treated with reparative cells using percutaneous endocardial, surgical, transvenous or intracoronary cell delivery methods, with variable effects in small randomized or cohort studies. The objective of this meta-analysis was to investigate the safety and efficacy of percutaneous transendocardial cell therapy in patients with iHF. Two investigators extracted the data. Individual patient data (IPD) (n = 8 studies) and publication-based (n = 10 studies) aggregate data were combined for the meta-analysis, including patients (n = 1715) with chronic iHF. The data are reported in accordance with PRISMA guidelines. The primary safety and efficacy endpoints were all-cause mortality and changes in global ejection fraction. The secondary safety and efficacy endpoints were major adverse events, hospitalization and changes in end-diastolic and end-systolic volumes. Post hoc analyses were performed using the IPD of eight studies to find predictive factors for treatment safety and efficacy. Cell therapy was significantly (p < 0.001) in favor of survival, major adverse events and hospitalization during follow-up. A forest plot analysis showed that cell therapy presents a significant benefit of increasing ejection fraction with a mean change of 2.51% (95% CI: 0.48; 4.54) between groups and of significantly decreasing end-systolic volume. The analysis of IPD data showed an improvement in the NYHA and CCS classes. Cell therapy significantly decreased the end-systolic volume in male patients; in patients with diabetes mellitus, hypertension or hyperlipidemia; and in those with previous myocardial infarction and baseline ejection fraction ≤ 45%. The catheter-based transendocardial delivery of regenerative cells proved to be safe and effective for improving mortality and cardiac performance. The greatest benefit was observed in male patients with significant atherosclerotic co-morbidities.

Optimal surgical timing after post-infarction ventricular septal rupture.

BACKGROUND: Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) is a dangerous condition. Surgical VSR closure is the definitive therapy, but there is controversy regarding the surgical timing and the bridging therapy between diagnosis and intervention. The objective of this study is to analyze the ideal time of surgical repair and to establish the contribution of mechanical circulatory support (MCS) devices on the prognosis. METHODS: We designed an observational, retrospective, multicenter study, selecting all consecutive patients with post-AMI VSR between January 1, 2008 and December 31, 2018, with non-exclusion criteria. The main objective of this study was to analyze the optimal timing for surgical repair of post-AMI VSR. Secondary endpoints were to determine which factors could influence mortality in the patients of the surgical group. RESULTS: A total of 141 patients were included. We identified lower mortality rates with an odds ratio of 0.3 (0.1-0.9) in patients operated on from day 4 compared with the surgical mortality in the first 24 hours after VSR diagnosis. The use of MCS was more frequent in patients treated with surgery, particularly for intra-aortic balloon pump (IABP; 79.6% vs. 37.8%, p < 0.001), but also for veno-arterial extracorporeal membrane oxygenation (VA-ECMO; 18.2% vs. 6.4%, p = 0.134). Total mortality was 91.5% for conservative management and 52.3% with surgical repair (p < 0.001). CONCLUSIONS: In our study, we observed that the lowest mortality rates in patients with surgical repair of post-AMI VSR were observed in patients operated on from day 4 after diagnosis of VSR, compared to earlier interventions.

Clinical outcomes in spontaneous coronary artery dissection.

OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute coronary syndrome. Our aim was to assess adverse events at follow-up from a nationwide prospective cohort. METHODS: The Spanish Registry on SCAD (SR-SCAD) included patients from 34 hospitals. All coronary angiograms were analysed by two experts. Those cases with doubts regarding the diagnosis of SCAD were excluded. The angiographic SCAD classification by Saw et al was followed. Major adverse cardiovascular and cerebrovascular event (MACCE) was predefined as composite of death, myocardial infarction, unplanned revascularisation, SCAD recurrence or stroke. All events were assigned by a Clinical Events Committee. RESULTS: After corelab evaluation, 389 patients were included. Most patients were women (88%); median age 53 years (IQR 47-60). Most patients presented as non-ST-segment-elevation myocardial infarction (54%). A type 2 intramural haematoma (IMH) was the most frequent angiographic pattern (61%). A conservative initial management was selected in 78% of patients. At a median time of follow-up of 29 months (IQR 17-38), 46 patients (13%) presented MACCE, mainly driven by reinfarctions (7.6%) and unplanned revascularisations (6.2%). Previous history of hypothyroidism (HR 3.79; p<0.001), proximal vessel involvement (HR 2.69; p=0.009), type 2 IMH (HR 2.12; p=0.037) and dual antiplatelet therapy (DAPT) at discharge (HR 2.18; p=0.042) were independent predictors of MACCE. CONCLUSIONS: In this large prospective cohort of patients with SCAD, prognosis was overall favourable, with events mainly driven by reinfarctions or unplanned revascularisations. History of hypothyroidism, proximal vessel involvement, type 2 IMH and DAPT at discharge were associated with MACCE. TRIAL REGISTRATION NUMBER: NCT03607981.

Microvascular dysfunction of the non-culprit circulation predicts poor prognosis in patients with ST-segment elevation myocardial infarction.

Background: Endothelial and microvascular dysfunction are frequently found in the non-culprit territory in patients with acute myocardial infarction (AMI). We aimed to determine whether an impaired coronary physiology of the non-culprit territory impacts long-term prognosis. Methods: FISIOIAM was an observational single-center study which included patients with AMI and another coronary artery lesion in a different territory. Intracoronary physiology of the non-culprit artery was analyzed early after primary percutaneous coronary intervention of the culprit artery, using fractional flow reserve (FFR), index of microcirculatory resistance (IMR), coronary flow reserve (CFR), endothelium-dependent CFR (eCFR) and macrovascular endothelial function . Patients were followed for a composite outcome of cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and hospitalization due to heart failure or unstable angina. Results: A total of 84 patients (mean age: 62 ± 10 years) were included and functional abnormalities were detected in 93% of them. During follow-up (median of 1422 days; interquartile range, 1287-1634), 13.1% of the patients experienced at least one adverse cardiovascular event. Kaplan-Meier analysis revealed that patients with a CFR < 2 had a higher risk of events (Hazard Ratio, HR: 4.97, 95% Confidence Interval, CI, 1.32-18.75), whereas other parameters such as FFR, IMR, eCFR, and macrovascular endothelial function had no effect. A low CFR was an independent predictor of cardiovascular events, even after adjustment for age and traditional cardiovascular risk factors (adjusted HR: 6.62, 95% CI, 1.30-33.70). Conclusions: The presence of abnormal coronary microvascular function as measured by a CFR < 2 in the non-culprit territory predicts future risk of adverse cardiovascular events.