Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).
Background Vasodilator stress cardiac magnetic resonance (stressCMR) has shown robust diagnostic and prognostic value in patients with known or suspected chronic coronary syndrome (CCS). However, it is unknown whether integration of several prognostic stressCMR parameters, such as the ischemic burden (number of segments with first-pass stress-induced perfusion defects -PD-) and left ventricular ejection fraction (LVEF), with clinical variables can improve risk prediction in this population. Purpose We aim to explore the usefulness of a clinical-stressCMR score to predict the risk of all-cause mortality in patients with known or suspected CCS submitted to undergo a stressCMR. Methods We included 6187 patients in a large prospective multicenter registry (mean age 65.18±11.51 years, 37.3% female) which underwent stressCMR for known or suspected CCS. Several clinical and stressCMR variables were collected, such as LVEF, end-diastolic and end-systolic volume indices, ischemic burden and segments with necrosis (with late gadolinium enhancement imaging). Results During a mean and median follow-up of 5.85±3.82 years we registered 682 (11%) all-cause deaths. Several clinical and all stressCMR variables were associated with all-cause mortality in univariate analysis. However, the only independent predictors of all-cause mortality in multivariate analysis were age (HR 1.07 [1.06–1.08] per year, p<0.001), male sex (HR 1.36 [1.15–1.61], p<0.001), diabetes mellitus (HR 1.6 [1.37–1.87], p<0.001), LVEF (0.98 [0.97–0.98] per %, p<0.001) and ischemic burden (HR 1.04 [1.02–1.06] per segment with stress-induced PD, p=0.001). By means of the chi-square increase at each step of the stepwise multiparametric Cox regression we created a clinical-stressCMR score that included these variables (age, male sex, diabetes mellitus, LVEF and ischemic burden) kept in their continuous state if possible. This score showed a good performance to predict all-cause mortality (area under the curve = 0.716 [0.697–0.735], p<0.001). Dividing the population into quintiles according to the clinical-stressCMR score allowed for a stratification of the annualized risk of all-cause mortality (0.39%/year, 0.94%/year, 1.62%/year, 2.63%/year and 3.83%/year, respectively; log-rank 420.33 and p<0.001 for Kaplan-meier curves). Conclusions A novel clinical-stressCMR, which includes clinical (age, male sex, and diabetes mellitus) and stressCMR (LVEF and ischemic burden) variables, can provide robust prediction and stratification of the risk of all-cause mortality in a population of patients with know or suspected CCS. Figure 1. Clinical-stress CMR score Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (PIE15/00013, PI17/01836, and CIBERCV16/11/00486 grants) and by Generalitat Valenciana (GV/2018/116).
Background The prognostic value of both exercise ECG testing (ExECG) and vasodilator stress cardiac magnetic resonance (VS-CMR) is well-known in patients with chest pain of unknown coronary origin. However, it is unknown whether performing both techniques can improve the risk stratification of these patients. Purpose We aim to confirm the additive prognostic value of ExECG and VS-CMR in a real-world cohort of patients with chest pain of unknown coronary origin. Methods We retrospectively included 288 patients in which ExECG and VS-CMR had been subsequently performed within one year. Clinical, ExECG and VS-CMR variables were registered. We performed univariate and multivariate analysis to check for the association of variables with the risk of MACE, defined as a combined endpoint of acute coronary syndrome (ACS), admission for heart failure (aHF) or all-cause death. Results During a mean follow-up of 4.2±2.15 years, we registered 27 MACE (15 ACS, 8 aHF and 8 all-cause deaths). The history of hypertension, previous coronary artery disease and/or coronary artery bypass grafting, lower maximal heart rate during ExECG (maxHR) and more extensive ischemic burden (segments with perfusion defects -PD- on stress first-pass perfusion) and myocardial necrosis (number of segments with necrosis at late gadolinium enhancement imaging) associated with the MACE endpoint. However, the only independent predictors of MACE were maxHR during ExECG (HR 0.98 [0.96–0.99], p=0.01) and more extensive segments with PD in the VS-CMR (HR 1.2 [1.07–1.34], p=0.002). We identified the best cut-off using the Youden index derived from receiver operating characteristics (ROC) analysis to predict MACE - it was ≤130bpm for maxHR during ExECG and ≥2 segments with PD on VS-CMR. These cathegories allowed us to stratify the annualized rate of MACE, which was very low (0.97%/year) in patients with normal maxHR and no PD on VS-CMR, intermediate in patients with only abnormal maxHR (1.98%/year) or PD on VS-CMR (3.24%/year) and high in patients with both abnormal maxHR and segments with PD (6.26%/year). Adding maxHR to the multivariable model including stress-induced PD by VS-CMR significantly improved the predictive power of MACE as derived from the continuous reclassification improvement index (0.47 [0.10–0.81], p<0.05). Conclusions ExECG and VS-CMR can have an additive prognostic value to predict the long-term risk of MACE in patients with chest pain of unknown coronary origin. Patients with maxHR during ExECG ≤130bpm and ≥2 segments with PD on VS-CMR are at the highest risk of MACE. Figure 1. MACE risk stratification. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (PIE15/00013, PI17/01836, and CIBERCV16/11/00486 grants) and by Generalitat Valenciana (GV/2018/116).
Background Left ventricular thrombus (LVTh) is an uncommon yet serious complication after ST-segment elevation myocardial infarction (STEMI). Late gadolinium enhancement (LGE) sequences in cardiac magnetic resonance (CMR) imaging allows for accurate detection of LVTh. However, the implications of CMR to predict and characterize LVTh occurrence is this population is unclear. Purpose We aim to characterize the incidence, outcomes, and predictors of LVTh after STEMI by CMR imaging. Methods Our registry comprised 455 patients admitted for a first reperfused STEMI in our university hospital. Baseline characteristics were recorded. All patients underwent early (1-week) and late (6-month) CMR. Left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments) were measured. LGE sequences were used to analyze the presence of LVTh. Patients with LVTh at 6-month CMR underwent an additional CMR 1 year after admission. Univariate and multivariate comparisons were performed to study the ocurrence of LVTh in the first 6 months after STEMI. Results Mean age was 58.24±11.69 years, most patients were male (82.6%) and anterior infarction occurred in more than half of the cohort (52.7%). LVTh was detected in 36 (7.9%) patients in the first 6 months after STEMI. Anticoagulation was initiated in all cases. Of these, 27 patients had LVTh at early (1-week) CMR, but 9 had LVTh at late (6-month) CMR with no prior evidence of LVTh at early CMR. A total of 6 patients had persisting LVTh at 1-year CMR (37.5% of patients with 6-month LVTh). In multivariable analysis, anterior infarction (HR 6.6 [1.91–22.83], p<0.001) and 1-week CMR-LVEF (HR 0.97 [0.93–0.99], p=0.04) and MVO (HR 1.19 [1.02–1.39], p=0.03) independently predicted the occurrence of LVTh in the first 6 months after STEMI. We computed a risk score of LVTh assigning 1 point to each of these variables (anterior infarction, CMR-LVEF <50% and MVO >3.5 segments), which allowed us to stratify the risk of LVTh in the first 6 months after STEMI (0.6% if 0 points, 3.8% if 1 point, 14.4% if 2 points, and 31.2% if 3 points). Conclusions CMR imaging soon after STEMI can contribute relevant prognostic value regarding LVTh occurrence after the acute event. Patients with anterior infarction, LVEF <50% and MVO in >3.5 segments at early (1-week) CMR have the highest risk of LVTh in the first 6 months after STEMI. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Instituto de Salud Carlos III and “Fondos Europeos de Desarrollo Regional FEDER” and Conselleria de Educaciόn – Generalitat Valenciana.
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