Vector Field Heterogeneity for the Assessment of Locally Disorganised Cardiac Electrical Propagation Wavefronts From High-Density Multielectrodes.

High-density multielectrode catheters are becoming increasingly popular in cardiac electrophysiology for advanced characterisation of the cardiac tissue, due to their potential to identify impaired sites. These are often characterised by abnormal electrical conduction, which may cause locally disorganised propagation wavefronts. To quantify it, a novel heterogeneity parameter based on vector field analysis is proposed, utilising finite differences to measure direction changes between adjacent cliques. The proposed Vector Field Heterogeneity metric has been evaluated on a set of simulations with controlled levels of organisation in vector maps, and a variety of grid sizes. Furthermore, it has been tested on animal experimental models of isolated Langendorff-perfused rabbit hearts. The proposed parameter exhibited superior capturing ability of heterogeneous propagation wavefronts compared to the classical Spatial Inhomogeneity Index, and simulations proved that the metric effectively captures gradual increments in disorganisation in propagation patterns. Notably, it yielded robust and consistent outcomes for [Formula: see text] grid sizes, underscoring its suitability for the latest generation of orientation-independent cardiac catheters.

Morbimortalidad no cardiovascular en función de la fracción de eyección del ventrículo izquierdo tras una hospitalización por insuficiencia cardiaca / Noncardiovascular morbidity and mortality across left ventricular ejection fraction categories following hospitalization for heart failure

Introducción y objetivos Los eventos no cardiovasculares son una importante causa de morbimortalidad en pacientes con insuficiencia cardiaca (IC), pero parece que su riesgo difiere en función de la fracción de eyección del ventrículo izquierdo (FEVI). Nuestro objetivo es evaluar el riesgo de mortalidad y hospitalizaciones no cardiovasculares totales en función de la FEVI tras una hospitalización por IC. Métodos Se evaluó en retrospectiva a una cohorte multicéntrica de 4.595 pacientes tras una hospitalización por IC. Se evaluó la FEVI como variable continua y estratificada en 4 categorías (FEVI ≤ 40%, 41%-49%, 50-59% y ≥ 60%). Los objetivos fueron los riesgos de muerte no cardiovascular y de hospitalizaciones recurrentes por causas no cardiovasculares según la FEVI. Resultados Tras una mediana de seguimiento de 2,2 [intervalo intercuartílico, 0,76-4,8] años, se registraron 646 muertes y 4.014 episodios de rehospitalización por causas no cardiovasculares. En el análisis multivariante, que incluía el riesgo de evento cardiovascular como evento adverso competitivo, se halló relación directa entre la FEVI y el riesgo de muerte o rehospitalización no cardiovascular (p<0,001). En comparación con la FEVI ≤ 40%, la FEVI del 51-59% y especialmente la ≥ 60% se asociaron de manera significativa con un mayor riesgo de muerte no cardiovascular (respectivamente, HR=1,31; IC95%, 1,02-1,68; p=0,032; y HR=1,47; IC95%, 1,15-1,86; p=0,002) y de rehospitalizaciones no cardiovasculares (IRR=1,17; IC95%, 1,02-1,35; p=0,024; IRR=1,26; IC95%, 1,11-1,45; p=0,001). Conclusiones Tras una hospitalización por IC, la FEVI tiene relación directa con el riesgo de morbimortalidad no cardiovascular. Los pacientes con FEVI conservada tienen un riesgo significativamente mayor de muerte y hospitalizaciones por causas no cardiovasculares, fundamentalmente si la FEVI es ≥ 60%. (AU)

Introduction and objectives Noncardiovascular events represent a significant proportion of the morbidity and mortality burden in patients with heart failure (HF). However, the risk of these events appears to differ by left ventricular ejection fraction (LVEF) status. In this study, we sought to evaluate the risk of noncardiovascular death and recurrent noncardiovascular readmission by LVEF status following an admission for acute HF. Methods We retrospectively assessed a cohort of 4595 patients discharged after acute HF in a multicenter registry. We evaluated LVEF as a continuum, stratified in 4 categories (LVEF ≤ 40%, 41%-49%, 50%-59%, and ≥ 60%). Study endpoints were the risks of noncardiovascular mortality and recurrent noncardiovascular admissions during follow-up. Results At a median follow-up of 2.2 [interquartile range, 0.76-4.8] years, we registered 646 noncardiovascular deaths and 4014 noncardiovascular readmissions. After multivariable adjustment including cardiovascular events as a competing event, LVEF status was associated with the risk of noncardiovascular mortality and recurrent noncardiovascular admissions. When compared with patients with LVEF ≤ 40%, those with LVEF 51%-59%, and especially those with LVEF ≥ 60%, were at higher risk of noncardiovascular mortality (HR, 1.31; 95%CI, 1.02-1,68; P=.032; and HR, 1.47; 95%CI, 1.15-1.86; P=.002; respectively), and at higher risk of recurrent noncardiovascular admissions (IRR, 1.17; 95%CI, 1.02-1.35; P=.024; and IRR, 1.26; 95%CI, 1.11-1.45; P=.001; respectively). Conclusions Following an admission for HF, LVEF status was directly associated with the risk of noncardiovascular morbidity and mortality. Patients with HFpEF were at higher risk of noncardiovascular death and total noncardiovascular readmissions, especially those with LVEF ≥ 60%. (AU)

Efecto del suero aislado de pacientes con infarto agudo de miocardio con elevación del segmento ST en las células endoteliales / Effect of serum from patients with ST-segment elevation myocardial infarction on endothelial cells

Introducción y objetivos La reperfusión coronaria produce un daño en la microcirculación y, en concreto, las células endoteliales. Este estudio evalúa el efecto del suero aislado tras la revascularización de pacientes con un infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en la viabilidad celular, el grado de permeabilidad endotelial in vitro y la asociación de estos parámetros con una mayor extensión de los índices de resonancia magnética cardiaca (RMC) relacionados con el daño por reperfusión (edema, hemorragia y obstrucción microvascular). Métodos Se incubaron células endoteliales de arteria coronaria humana con suero aislado 24 h tras la revascularización de 43 pacientes con IAMCEST evaluados mediante RMC y 14 sujetos de control. Se testó el efecto del suero de pacientes con IAMCEST en la pérdida de viabilidad celular por activación de la apoptosis y la necrosis, así como en la permeabilidad y la estructura de la monocapa endotelial. Resultados El suero de pacientes con IAMCEST aumentó la apoptosis (p <0,01) y la necrosis (p <0,05) de células endoteliales de arteria coronaria humana y causó un incremento de la permeabilidad de la monocapa endotelial in vitro (p <0,01) debido a mayores espacios intercelulares (p <0,05 frente a los controles). Una mayor necrosis inducida por suero se asoció con más permeabilidad endotelial in vitro (p <0,05) y con una mayor extensión de los principales índices de daño tras reperfusión y mayor tamaño de infarto. Conclusiones El suero tras la reperfusión de pacientes con IAMCEST induce la apoptosis y la necrosis in vitro de las células endoteliales y la permeabilidad endotelial. Cuanto más potente sea el efecto inductor de necrosis, más deletéreas son las consecuencias en cuanto al daño estructural resultante. (AU)

Introduction and objectives Clinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction). Methods Human coronary artery endothelial cells were incubated with serum isolated 24hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer. Results Serum from STEMI patients increased apoptosis (P <.01) and necrosis (P <.05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P <.01), due to enlarged intercellular spaces (P <.05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P <.05) and with more extensive CMR-derived indices of reperfusion injury and infarct size. Conclusions Postreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure. (AU)

Impact of Epicardial Adipose Tissue on Infarct Size and Left Ventricular Systolic Function in Patients with Anterior ST-Segment Elevation Myocardial Infarction.

We aimed to assess the correlation of cardiovascular magnetic resonance (CMR)-derived epicardial adipose tissue (EAT) with infarct size (IS) and residual systolic function in ST-segment elevation myocardial infarction (STEMI). We enrolled patients discharged for a first anterior reperfused STEMI submitted to undergo CMR. EAT, left ventricular (LV) ejection fraction (LVEF), and IS were quantified at the 1-week (n = 221) and at 6-month CMR (n = 167). At 1-week CMR, mean EAT was 31 ± 13 mL/m2. Patients with high EAT volume (n = 72) showed larger 1-week IS. After adjustment, EAT extent was independently related to 1-week IS. In patients with large IS at 1 week (>30% of LV mass, n = 88), those with high EAT showed more preserved 6-month LVEF. This association persisted after adjustment and in a 1:1 propensity score-matched patient subset. Overall, EAT decreased at 6 months. In patients with large IS, a greater reduction of EAT was associated with more preserved 6-month LVEF. In STEMI, a higher presence of EAT was associated with a larger IS. Nevertheless, in patients with large infarctions, high EAT and greater subsequent EAT reduction were linked to more preserved LVEF in the chronic phase. This dual and paradoxical effect of EAT fuels the need for further research in this field.

Effect of serum from patients with ST-segment elevation myocardial infarction on endothelial cells.

INTRODUCTION AND OBJECTIVES: Clinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction). METHODS: Human coronary artery endothelial cells were incubated with serum isolated 24hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer. RESULTS: Serum from STEMI patients increased apoptosis (P <.01) and necrosis (P <.05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P <.01), due to enlarged intercellular spaces (P <.05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P <.05) and with more extensive CMR-derived indices of reperfusion injury and infarct size. CONCLUSIONS: Postreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure.

Noncardiovascular morbidity and mortality across left ventricular ejection fraction categories following hospitalization for heart failure.

INTRODUCTION AND OBJECTIVES: Noncardiovascular events represent a significant proportion of the morbidity and mortality burden in patients with heart failure (HF). However, the risk of these events appears to differ by left ventricular ejection fraction (LVEF) status. In this study, we sought to evaluate the risk of noncardiovascular death and recurrent noncardiovascular readmission by LVEF status following an admission for acute HF. METHODS: We retrospectively assessed a cohort of 4595 patients discharged after acute HF in a multicenter registry. We evaluated LVEF as a continuum, stratified in 4 categories (LVEF ≤ 40%, 41%-49%, 50%-59%, and ≥ 60%). Study endpoints were the risks of noncardiovascular mortality and recurrent noncardiovascular admissions during follow-up. RESULTS: At a median follow-up of 2.2 [interquartile range, 0.76-4.8] years, we registered 646 noncardiovascular deaths and 4014 noncardiovascular readmissions. After multivariable adjustment including cardiovascular events as a competing event, LVEF status was associated with the risk of noncardiovascular mortality and recurrent noncardiovascular admissions. When compared with patients with LVEF ≤ 40%, those with LVEF 51%-59%, and especially those with LVEF ≥ 60%, were at higher risk of noncardiovascular mortality (HR, 1.31; 95%CI, 1.02-1,68; P=.032; and HR, 1.47; 95%CI, 1.15-1.86; P=.002; respectively), and at higher risk of recurrent noncardiovascular admissions (IRR, 1.17; 95%CI, 1.02-1.35; P=.024; and IRR, 1.26; 95%CI, 1.11-1.45; P=.001; respectively). CONCLUSIONS: Following an admission for HF, LVEF status was directly associated with the risk of noncardiovascular morbidity and mortality. Patients with HFpEF were at higher risk of noncardiovascular death and total noncardiovascular readmissions, especially those with LVEF ≥ 60%.

Mini Peltier Cell Array System for the Generation of Controlled Local Epicardial Heterogeneities.

The present study aims to design and fabricate a system capable of generating heterogeneities on the epicardial surface of an isolated rabbit heart perfused in a Langendorff system. The system consists of thermoelectric modules that can be independently controlled by the developed hardware, thereby allowing for the generation of temperature gradients on the epicardial surface, resulting in conduction slowing akin to heterogeneities of pathological origin. A comprehensive analysis of the system's viability was performed through modeling and thermal simulation, and its practicality was validated through preliminary tests conducted at the experimental cardiac electrophysiology laboratory of the University of Valencia. The design process involved the use of Fusion 360 for 3D designs, MATLAB/Simulink for algorithms and block diagrams, LTSpice and Altium Designer for schematic captures and PCB design, and the integration of specialized equipment for animal experimentation. The objective of the study was to efficiently capture epicardial recordings under varying conditions.Clinical relevance- The proposed system aims to induce local epicardial heterogeneities to generate labeled correct signals that can serve as a golden standard for improving algorithms that identify and characterize fibrotic substrates. This improvement will enhance the efficacy of ablation processes and potentially reduce the ablated surface area.

Novel Targets Regulating the Role of Endothelial Cells and Angiogenesis after Infarction: A RNA Sequencing Analysis.

Endothelial cells (ECs) are a key target for cardioprotection due to their role in preserving cardiac microvasculature and homeostasis after myocardial infarction (MI). Our goal is to identify the genes involved in post-MI EC proliferation, EC apoptosis, and angiogenesis regulation via RNA-sequencing transcriptomic datasets. Using eight studies from the Gene Expression Omnibus, RNA-sequencing data from 92 mice submitted to different times of coronary ischemia or sham were chosen. Functional enrichment analysis was performed based on gene ontology biological processes (BPs). Apoptosis-related BPs are activated up to day 3 after ischemia onset, whereas endothelial proliferation occurs from day 3 onwards, including an overrepresentation of up to 37 genes. Endothelial apoptosis post-MI is triggered via both the extrinsic and intrinsic signaling pathways, as reflected by the overrepresentation of 13 and 2 specific genes, respectively. BPs implicated in new vessel formation are upregulated soon after ischemia onset, whilst the mechanisms aiming at angiogenesis repression can be detected at day 3. Overall, 51 pro-angiogenic and 29 anti-angiogenic factors displayed altered transcriptomic expression post-MI. This is the first study using RNA sequencing datasets to evaluate the genes participating in post-MI endothelium physiology and angiogenesis regulation. These novel data could lay the groundwork to advance understanding of the implication of ECs after MI.

Short-Term Heart Rate Variability in Metabolic Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Our aim was to determine the differences in short-term heart rate variability (HRV) between patients with metabolic syndrome (MS) and healthy controls. METHODS: We searched electronic databases for primary works with short-term HRV recordings (≤30 min) that made comparisons between individuals with MS versus healthy controls. This systematic review and meta-analysis (MA) was performed according to PRISMA guidelines and registered at PROSPERO (CRD42022358975). RESULTS: Twenty-eight articles were included in the qualitative synthesis and nineteen met the criteria for the MA. Patients with MS showed decreased SDNN (-0.36 [-0.44, -0.28], p < 0.001), rMSSD (-7.59 [-9.98, -5.19], p < 0.001), HF (-0.36 [-0.51, -0.20], p < 0.00001) and LF (-0.24 [-0.38, -0.1], p = 0.001). In subsequent subanalyses, we found a decrease in SDNN (-0.99 (-1.45, -0.52], p < 0.001), rMSSD (-10.18 [-16.85, -3.52], p < 0.01) and HF (-1.04 [-1.97, -0.1] p < 0.05) in women. In men, only LF showed a significant lower value (-0.26 [-0.5, -0.02], p < 0.05). We could not perform MA for non-linear variables. CONCLUSIONS: Patients with MS showed changes in time-domain analyses, with lower values in SDNN and rMSSD. Regarding frequency-domain analyses, MS patients showed a decrease in HF and LF When sex was used as a grouping variable, the MA was only possible in one of both sexes (men or women) in rMSSD and LF/HF. Lastly, when data for both men and women were available, subanalyses showed a different behavior compared to mixed analyses for SDNN, HF and LF, which might point towards a different impact of MS in men and women.

Changes in the extracellular matrix at microvascular obstruction area after reperfused myocardial infarction: A morphometric study.

BACKGROUND: Extracellular matrix (ECM) suffers substantial alterations after myocardial infarction (MI), including the invasion of leukocyte subtypes. Despite a complete reopening at epicardial level, hypoperfusion within the infarcted myocardium, known as microvascular obstruction (MVO), occurs and exerts a negative impact on ventricular remodeling. In this study, ECM composition at MVO regions was described using a morphometric analysis. METHODS: MI was induced in female swine (n = 10) by transitory 90-minute coronary occlusion followed by seven days of reperfusion. Prior to euthanasia, intracoronary thioflavin-S was infused. Within the infarcted myocardium, regions displaying MVO (thioflavin-S-) or no MVO (thioflavin-S+) were isolated and stained to morphometrically compare ECM composition. RESULTS: As reflected by cell invasion through ECM, areas with MVO displayed an enlarged presence of neutrophils and lymphocytes, whilst no differences in the amount of macrophages and myofibroblasts were detected compared to infarcted myocardium without MVO. Indeed, those regions with macroscopic MVO showed lower capillary density than areas without MVO. Lastly, a significant reduction in the extension of total collagen, type I, but not type III, collagen, laminin, and fibronectin together with an augmentation of polysaccharides were noted in areas showing MVO compared to those without microvascular injury. CONCLUSIONS: ECM composition in infarcted regions with MVO isolated from female swine displays a higher presence of inflammatory infiltrate and polysaccharides as well as reduced number of microvessels and collagen content compared to those areas without microvascular hypoperfusion. These characteristics might underlie the development of adverse ventricular remodeling in MI patients with extensive MVO.

Evaluation and assessment of clique arrangements for the estimation of omnipolar electrograms in high density electrode arrays: an experimental animal model study.

High-density catheters combined with Orientation Independent Sensing (OIS) methods have emerged as a groundbreaking technology for cardiac substrate characterisation. In this study, we aim to assess the arrangements and constraints to reliably estimate the so-called omnipolar electrogram (oEGM). Performance was evaluated using an experimental animal model. Thirty-eight recordings from nine retrospective experiments on isolated perfused rabbit hearts with an epicardial HD multielectrode were used. We estimated oEGMs according to the classic triangular clique (4 possible orientations) and a novel cross-orientation clique arrangement. Furthermore, we tested the effects of interelectrode spacing from 1 to 4 mm. Performance was evaluated by means of several parameters that measured amplitude rejection ratios, electric field loop area, activation pulse width and morphology distortion. Most reliable oEGM estimations were obtained with cross-configurations and interelectrode spacings [Formula: see text] mm. Estimations from triangular cliques resulted in wider electric field loops and unreliable detection of the direction of the propagation wavefront. Moreover, increasing interelectrode distance resulted in increased pulse width and morphology distortion. The results prove that current oEGM estimation techniques are insufficiently accurate. This study opens a new standpoint for the design of new-generation HD catheters and mapping software.

Differences in Long-Term Heart Rate Variability between Subjects with and without Metabolic Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Our aim was to determine the impact that metabolic syndrome (MS) produces in long-term heart rate variability (HRV), quantitatively synthesizing the results of published studies to characterize the cardiac autonomic dysfunction in MS. METHODS: We searched electronic databases for original research works with long-term HRV recordings (24 h) that compared people with MS (MS+) versus healthy people as a control group (MS-). This systematic review and meta-analysis (MA) was performed according to PRISMA guidelines and registered at PROSPERO (CRD42022358975). RESULTS: A total of 13 articles were included in the qualitative synthesis, and 7 of them met the required criteria to be included in the MA. SDNN (-0.33 [-0.57, 0.09], p = 0.008), LF (-0.32 [-0.41, -0.23], p < 0.00001), VLF (-0.21 [-0.31, -0.10], p = 0.0001) and TP (-0.20 [-0.33, -0.07], p = 0.002) decreased in patients with MS. The rMSSD (p = 0.41), HF (p = 0.06) and LF/HF ratio (p = 0.64) were not modified. CONCLUSIONS: In long-term recordings (24 h), SDNN, LF, VLF and TP were consistently decreased in patients with MS. Other parameters that could be included in the quantitative analysis were not modified in MS+ patients (rMSSD, HF, ratio LF/HF). Regarding non-linear analyses, the results are not conclusive due to the low number of datasets found, which prevented us from conducting an MA.

Impact of Persistent Microvascular Obstruction Late After STEMI on Adverse LV Remodeling: A CMR Study.

BACKGROUND: Little is known about the occurrence and implications of persistent microvascular obstruction (MVO) after reperfused ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: The authors used cardiac magnetic resonance (CMR) to characterize the impact of persistent MVO on adverse left ventricular remodeling (ALVR). METHODS: A prospective registry of 471 STEMI patients underwent CMR 7 (IQR: 5-10) days and 198 (IQR: 167-231) days after infarction. MVO (≥1 segment) and ALVR (relative increase >15% at follow-up CMR) of left ventricular end-diastolic index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were determined. RESULTS: One-week MVO occurred in 209 patients (44%) and persisted in 30 (6%). The extent of MVO (P = 0.026) and intramyocardial hemorrhage (P = 0.001) at 1 week were independently associated with the magnitude of MVO at follow-up CMR. Compared with patients without MVO (n = 262, 56%) or with MVO only at 1 week (n = 179, 38%), those with persistent MVO at follow-up (n = 30, 6%) showed higher rates of ALVR-LVEDVI (22%, 27%, and 50%; P = 0.003) and ALVR-LVESVI (20%, 21%, and 53%; P < 0.001). After adjustment, persistent MVO at follow-up (≥1 segment) was independently associated with ΔLVEDVI (relative increase, %) (P < 0.001) and ΔLVESVI (P < 0.001). Compared with a 1:1 propensity score-matched population on CMR variables made up of 30 patients with MVO only at 1 week, patients with persistent MVO more frequently displayed ALVR-LVEDVI (12% vs 50%; P = 0.003) and ALVR-LVESVI (12% vs 53%; P = 0.001). CONCLUSIONS: MVO persists in a small percentage of patients in chronic phase after STEMI and exerts deleterious effects in terms of LV remodeling. These findings fuel the need for further research on microvascular injury repair.

MRI Investigation of the Differential Impact of Left Ventricular Ejection Fraction After Myocardial Infarction in Elderly vs. Nonelderly Patients to Predict Readmission for Heart Failure.

BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI), especially elderly individuals, have an increased risk of readmission for acute heart failure (AHF). PURPOSE: To study the impact of left ventricular ejection fraction (LVEF) by MRI to predict AHF in elderly (>70 years) and nonelderly patients after STEMI. STUDY TYPE: Prospective. POPULATION: Multicenter registry of 759 reperfused STEMI patients (23.3% elderly). FIELD STRENGTH/SEQUENCE: 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. ASSESSMENT: One-week MRI-derived LVEF (%) was quantified. Sequential MRI data were recorded in 579 patients. Patients were categorized according to their MRI-derived LVEF as preserved (p-LVEF, ≥50%), mildly reduced (mr-LVEF, 41%-49%), or reduced (r-LVEF, ≤40%). Median follow-up was 5 [2.33-7.54] years. STATISTICAL TESTS: Univariable (Student's t, Mann-Whitney U, chi-square, and Fisher's exact tests) and multivariable (Cox proportional hazard regression) comparisons and continuous-time multistate Markov model to analyze transitions between LVEF categories and to AHF. Hazard ratios (HR) with 95% confidence intervals (CIs) were computed. P < 0.05 was considered statistically significant. RESULTS: Over the follow-up period, 79 (10.4%) patients presented AHF. MRI-LVEF was the most robust predictor in nonelderly (HR 0.94 [0.91-0.98]) and elderly patients (HR 0.94 [0.91-0.97]). Elderly patients had an increased AHF risk across the LVEF spectrum. An excess of risk (compared to p-LVEF) was noted in patients with r-LVEF both in nonelderly (HR 11.25 [5.67-22.32]) and elderly patients (HR 7.55 [3.29-17.34]). However, the mr-LVEF category was associated with increased AHF risk only in elderly patients (HR 3.66 [1.54-8.68]). Less transitions to higher LVEF states (n = 19, 30.2% vs. n = 98, 53%) and more transitions to AHF state (n = 34, 53.9% vs. n = 45, 24.3%) were observed in elderly than nonelderly patients. DATA CONCLUSION: MRI-derived p-LVEF confers a favorable prognosis and r-LVEF identifies individuals at the highest risk of AHF in both elderly and nonelderly patients. Nevertheless, an excess of risk was also found in the mr-LVEF category in the elderly group. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Cardiac magnetic resonance outperforms echocardiography to predict subsequent implantable cardioverter defibrillator therapies in ST-segment elevation myocardial infarction patients.

Background: Implantable cardioverter defibrillators (ICD) are effective as a primary prevention measure of ventricular tachyarrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) and depressed left ventricular ejection fraction (LVEF). The implications of using cardiac magnetic resonance (CMR) instead of echocardiography (Echo) to assess LVEF prior to the indication of ICD in this setting are unknown. Materials and methods: We evaluated 52 STEMI patients (56.6 ± 11 years, 88.5% male) treated with ICD in primary prevention who underwent echocardiography and CMR prior to ICD implantation. ICD implantation was indicated based on the presence of heart failure and depressed LVEF (≤ 35%) by echocardiography, CMR, or both. Prediction of ICD therapies (ICD-T) during follow-up by echocardiography and CMR before ICD implantation was assessed. Results: Compared to echocardiography, LVEF was lower by cardiac CMR (30.2 ± 9% vs. 37.4 ± 7.6%, p < 0.001). LVEF ≤ 35% was detected in 24 patients (46.2%) by Echo and in 42 (80.7%) by CMR. During a mean follow-up of 6.1 ± 4.2 years, 10 patients received appropriate ICD-T (3.16 ICD-T per 100 person-years): 5 direct shocks to treat very fast ventricular tachycardia or ventricular fibrillation, 3 effective antitachycardia pacing (ATP) for treatment of ventricular tachycardia, and 2 ineffective ATP followed by shock to treat ventricular tachycardia. Echo-LVEF ≤ 35% correctly predicted ICD-T in 4/10 (40%) patients and CMR-LVEF ≤ 35% in 10/10 (100%) patients. CMR-LVEF improved on Echo-LVEF for predicting ICD-T (area under the curve: 0.76 vs. 0.48, p = 0.04). Conclusion: In STEMI patients treated with ICD, assessment of LVEF by CMR outperforms Echo-LVEF to predict the subsequent use of appropriate ICD therapies.

Risk of death associated with incident heart failure in patients with known or suspected chronic coronary syndrome.

AIMS: Traditional adverse events in chronic coronary syndrome (CCS) include atherothrombotic events but usually exclude heart failure (HF). Data are scarce about how new-onset HF modifies mortality risk. We aimed to determine the incidence of HF and compare its long-term mortality risk with myocardial infarction (MI) and stroke in patients with known or suspected CCS. METHODS: We prospectively evaluated 5811 consecutive HF-free patients submitted to vasodilator stress cardiac magnetic resonance (CMR) for known or suspected CCS. Ischaemic burden and left ventricular ejection fraction were assessed by CMR. HF included outpatient diagnosis or acute HF hospitalization. The mortality risk for the incident events and their cross-comparisons were evaluated using a Markov illness-death model with transition-specific survival models. RESULTS: The mean age was 55 ± 11 years, and 38.9% were female. At a median follow-up of 5.44 (IQR = 2.53-8.55) years, 591 deaths were registered (1.79 per 100 P-Y). The rates of new-onset HF were higher compared with MI and stroke [1.02, 0.62, and 0.51, respectively (P < 0.05)]. The adjusted association between new-onset HF, MI, and stroke, and subsequent mortality was time dependent. The risk increased almost linearly for HF and became significant by the third year. By Year 10, the mortality risk attributable to new-onset HF was more than 2.5-fold (HR: 2.68, 95% CI = 1.74-4.12). For MI, there was a significant increase in mortality risk up to the second year, followed by a monotonic decrease. For stroke, the mortality risk increased for the entire follow-up but became significant by the third year. A cross-comparison among incident endpoints HF outnumbers risk for those with MI by the sixth year (HRyear6.3 : 1.88, 95% CI = 1.03-3.43). There was no difference in mortality risk between incident HF and stroke. CONCLUSIONS: In patients with CCS, long-term rates of incident HF were higher than MI and stroke. Patients with new-onset HF showed a higher risk of long-term mortality.

Short-Course High-Intensity Statin Treatment during Admission for Myocardial Infarction and LDL-Cholesterol Reduction-Impact on Tailored Lipid-Lowering Therapy at Discharge.

We hypothesized that a short-course high-intensity statin treatment during admission for myocardial infarction (MI) could rapidly reduce LDL-C and thus impact the choice of lipid-lowering therapy (LLT) at discharge. Our cohort comprised 133 MI patients (62.71 ± 11.3 years, 82% male) treated with atorvastatin 80 mg o.d. during admission. Basal LDL-C levels before admission were analyzed. We compared lipid profile variables before and during admission, and LLT at discharge was registered. Achieved theoretical LDL-C levels were estimated using LDL-C during admission and basal LDL-C as references and compared to LDL-C on first blood sample 4-6 weeks after discharge. A significant reduction in cholesterol from basal levels was noted during admission, including total cholesterol, triglycerides, HDL-C, non-HDL-C, and LDL-C (-39.23 ± 34.89 mg/dL, p < 0.001). LDL-C levels were reduced by 30% in days 1-2 and 40-45% in subsequent days (R2 0.766, p < 0.001). Using LDL-C during admission as a reference, most patients (88.7%) would theoretically achieve an LDL-C < 55 mg/dL with discharge LLT. However, if basal LDL-C levels were considered as a reference, only a small proportion of patients (30.1%) would achieve this lipid target, aligned with the proportion of patients with LDL-C < 55 mg/dL 4-6 weeks after discharge (36.8%). We conclude that statin treatment during admission for MI can induce a significant reduction in LDL-C and LLT at discharge is usually prescribed using LDL-C during admission as the reference, which leads to insufficient LDL-C reduction after discharge. Basal LDL-C before admission should be considered as the reference value for tailored LLT prescription.

Residual ST-segment elevation to predict long-term clinical and CMR-derived outcomes in STEMI.

Residual ST-segment elevation after ST-segment elevation myocardial infarction (STEMI) has traditionally been considered a predictor of left ventricular (LV) dysfunction and ventricular aneurism. However, the implications in terms of long-term prognosis and cardiac magnetic resonance (CMR)-derived structural consequences are unclear. A total of 488 reperfused STEMI patients were prospectively included. The number of Q wave leads with residual ST-segment elevation > 1 mm (Q-STE) at pre-discharge ECG was assessed. LV ejection fraction (LVEF, %) and infarct size (IS, % of LV mass) were quantified in 319 patients at 6-month CMR. Major adverse cardiac events (MACE) were defined as all-cause death and/or re-admission for acute heart failure (HF), whichever occurred first. During a mean follow-up of 6.1 years, 92 MACE (18.9%), 39 deaths and 53 HF were recorded. After adjustment for baseline characteristics, Q-STE (per lead with > 1 mm) was independently associated with a higher risk of long-term MACE (HR 1.24 [1.07-1.44] per lead, p = 0.004), reduced (< 40%) LVEF (HR 1.36 [1.02-1.82] per lead, p = 0.04) and large (> 30% of LV mass) IS (HR 1.43 [1.11-1.85] per lead, p = 0.006) at 6-month CMR. Patients with Q-STE ≥ 2 leads (n = 172, 35.2%) displayed lower MACE-free survival, more depressed LVEF, and larger IS at 6-month CMR (p < 0.001 for all comparisons). Residual ST-segment elevation after STEMI represents a universally available tool that predicts worse long-term clinical and CMR-derived structural outcomes.

Prognostic value of cardiac magnetic resonance early after ST-segment elevation myocardial infarction in older patients.

BACKGROUND: older patients with ST-segment elevation myocardial infarction (STEMI) represent a very high-risk population. Data on the prognostic value of cardiac magnetic resonance (CMR) in this scenario are scarce. METHODS: the registry comprised 247 STEMI patients over 70 years of age treated with percutaneous intervention and included in a multicenter registry. Baseline characteristics, echocardiographic parameters and CMR-derived left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments) were prospectively collected. The additional prognostic power of CMR was assessed using adjusted C-statistic, net reclassification index (NRI) and integrated discrimination improvement index (IDI). RESULTS: during a 4.8-year mean follow-up, the number of first major adverse cardiac events (MACE) was 66 (26.7%): 27 all-cause deaths and 39 re-admissions for acute heart failure. Predictors of MACE were GRACE score (HR 1.03 [1.02-1.04], P < 0.001), CMR-LVEF (HR 0.97 [0.95-0.99] per percent increase, P = 0.006) and MVO (HR 1.24 [1.09-1.4] per segment, P = 0.001). Adding CMR data significantly improved MACE prediction compared to the model with baseline and echocardiographic characteristics (C-statistic 0.759 [0.694-0.824] vs. 0.685 [0.613-0.756], NRI = 0.6, IDI = 0.08, P < 0.001). The best cut-offs for independent variables were GRACE score > 155, LVEF < 40% and MVO ≥ 2 segments. A simple score (0, 1, 2, 3) based on the number of altered factors accurately predicted the MACE per 100 person-years: 0.78, 5.53, 11.51 and 78.79, respectively (P < 0.001). CONCLUSIONS: CMR data contribute valuable prognostic information in older patients submitted to undergo CMR soon after STEMI. The Older-STEMI-CMR score should be externally validated.

Fourier analysis of collagen bundle orientation in myocardial infarction scars.

Collagen bundle orientation (CBO) in myocardial infarct scars plays a major role in scar mechanics and complications after infarction. We aim to compare four histopathological methods for CBO measurement in myocardial scarring. Myocardial infarction was induced in 21 pigs by balloon coronary occlusion. Scar samples were obtained at 4 weeks, stained with Masson's trichrome, Picrosirius red, and Hematoxylin-Eosin (H&E), and photographed using light, polarized light microscopy, and confocal microscopy, respectively. Masson's trichrome images were also optimized to remove non-collagenous structures. Two observers measured CBO by means of a semi-automated, Fourier analysis protocol. Interrater reliability and comparability between techniques were studied by the intraclass correlation coefficient (ICC) and Bland-Altman (B&A) plots and limits of agreement. Fourier analysis showed an almost perfect interrater reliability for each technique (ICC ≥ 0.95, p < 0.001 in all cases). CBO showed more randomly oriented values in Masson's trichrome and worse comparability with other techniques (ICC vs. Picrosirius red: 0.79 [0.47-0.91], p = 0.001; vs. H&E-confocal: 0.70 [0.26-0.88], p = 0.005). However, optimized Masson's trichrome showed almost perfect agreement with Picrosirius red (ICC 0.84 [0.6-0.94], p < 0.001) and H&E-confocal (ICC 0.81 [0.54-0.92], p < 0.001), as well as these latter techniques between each other (ICC 0.84 [0.60-0.93], p < 0.001). In summary, a semi-automated, Fourier-based method can provide highly reproducible CBO measurements in four different histopathological techniques. Masson's trichrome tends to provide more randomly oriented CBO index values, probably due to non-specific visualization of non-collagenous structures. However, optimization of Masson's trichrome microphotographs to remove non-collagenous components provides an almost perfect comparability between this technique, Picrosirius red and H&E-confocal.