Suchergebnisse

Narratives about overcoming illness based on actual patients at the Clinica Universidad de Navarra. Each year beginning in 2007 one author was selected by the Clinica and comissioned to narrate a particular patient's story. This volume collects the stories written during the first decade of the project.

Cardiovascular disease (CVD) is now the leading cause of mortality worldwide. Particularly in Low and Middle Income Countries, rapid urbanization and secondary factors such as increasing obesity, poor diet and lack of exercise have combined to propel CVD into this position. Given the enormous scope of this problem and the complex cultural, societal and political issues that are involved, and equally sophisticated and multipronged approach is required to combat CVD at the global level. In this review we outline the basic, clinical and population level challenges that we face in defending ourselves against this disease.

Background Data are limited on use patterns of low-dose aspirin and its role for primary prevention of cardiovascular disease (CVD) in different racial and ethnic groups. Methods and Results Overall, 65 231 non-Hispanic black and white people aged 40 to 79 years with no history of CVD enrolled from 2002 through 2009 in the SCCS (Southern Community Cohort Study). At cohort entry, the simplified Framingham 10-year CVD risk was calculated, and data related to low-dose aspirin use and clinical and socioeconomic covariates were collected. Race- and ethnicity-specific adjusted odds ratios for characteristics of low-dose aspirin users and hazard ratios for ischemic cardiac death according to aspirin use were calculated using multivariate logistic and Cox regression models. Black participants were less likely to take low-dose aspirin compared with white participants, regardless of CVD risk and covariates (adjusted odds ratio: 0.79; 95% CI, 0.75-0.82). Over a median follow-up of 11.3 years, low-dose aspirin use was associated with a trend toward decreased risk of ischemic cardiac death in white participants (adjusted hazard ratio: 0.86; 95% CI, 0.68-1.10), especially in women (adjusted hazard ratio: 0.72; 95% CI, 0.51-1.02), but not in black participants (adjusted hazard ratio: 1.18; 95% CI, 0.98-1.40). Similar trends were observed when the analysis was restricted to high-risk individuals aged 50 to 69 or 50 to 59 years, ages for which guidelines consider aspirin for CVD primary prevention. Conclusions Low-dose aspirin use for primary prevention of CVD is lower among black than white patients. Its use might be associated with a disparate impact on ischemic cardiac death according to race and ethnicity. Although additional studies are required, these findings provide no evidence of a beneficial effect of aspirin among black patients for CVD primary prevention. ; The SCCS (Southern Community Cohort Study) is funded by grants R01 CA092447 and U01 CA202979 from the National Cancer Institute, including American Recovery and Reinvestment Act funding (3R01 CA029447-08 51). Data collection was performed by the Survey and Biospecimen Shared Resource, which is supported in part by the VanderbiltIngram Cancer Center (P30 CA68485). This analysis forms part of a project that has received funding from the American Heart Association under grant no. 14SFRN20490315. Fernandez-Jimenez is a recipient of funding from the European Union Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie grant agreement no. 707642. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos Ill; the Ministerio de Ciencia, Innovacion y Universidades; and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).

Background: Cardiovascular disease (CVD) is a major cause of disability and premature death. Despite European guidelines advocating the use of medical therapies in CVD, many patients still do not achieve the guideline-recommended treatment, which highlights the need for change and innovations in this field. This requirement has been widely recognised by the national ministries of health, several European cardiology societies, and the European Parliament, who support the initiation of strategies to improve and promote cardiovascular health. Discussion: One of the key risk factors to recurrent cardiovascular events is the lack of adherence to medication and this has been added to the agenda of the European Commission. With the intention to improve treatment adherence in CVD, polypills have been investigated and numerous studies demonstrate that they significantly improve medication adherence, which contributes to the improvement of health outcomes. In Europe, the first cardiovascular polypill, developed by a public-private partnership (CNIC-Ferrer), recently became available for general prescription as a therapy for CVD prevention. This polypill significantly improves adherence, preventing fatal and non-fatal cardiovascular events, and appears to be a cost-effective strategy to improve sustainability of the health care systems in CVD. Conclusions: Given the importance of urgent and simple solutions to restraining the pandemic nature of CVD, the polypill approach should therefore be considered by physicians and public health systems as an available and innovative option to improve cardiovascular health. ; Financial support for the creation of this paper was provided by Ferrer Internacional. All content and opinions expressed in the article reflect those of the authors and were not influenced by Ferrer. ; Sí

Cardiovascular disease is the leading cause of death and disability in the world, largely because of risk factors modifiable by changes in behavior. There is evolving evidence that our behavior as adults has its roots in the environment that we live in from early childhood. Early sustained multicomponent educational programs focused on health promotion in children may represent a window of opportunity to potentially prevent disease in adulthood. The integration of school-based, family-based, and community-based strategies, along with the support of public policies, are likely necessary for the success of these programs. In this review, the authors describe the future of promoting health. Specifically: 1) reasons why children should be a focus for health promotion (alarming trends of risk factors, association between unhealthy factors and subclinical disease, and cost-effectiveness); 2) strategies for health promotion in children (school-based, family-based, and community-based approaches) along with legislative efforts; and 3) research gaps are discussed. ; The FAMILIA (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health) study is funded by the American Heart Association under grant No 14SFRN20490315. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Fernandez-Jimenez has received funding from the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707642 ; Sí

European Union's FP7 (CardioNext ITN-608027, HEALTH. 2011-278967), European Union's Horizon 2020 (GA633765, RIA73152, AC16/00021, and AC16/00091), the Spanish Ministerio de Economia, Industria y Competitividad (MEIC) with cofunding from the Fondo Europeo de Desarrollo Regional (FEDER; SAF2015-65722-R, SAF2016-79490-R, SAF2013-49663-EXP, RTC-2015-4398-1, and RTC-2016-4911-1), the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PI16/02110, PI16/00123, DTS17/00136, and DTS15/00095), Fundacion BBVA, Mutua Madrilena Foundation, Spanish Society of Cardiology, the Fundacio Marato TV3 (122/C/2015), and the Progeria Research Foundation (Established Investigator Award 2014-52). The CNIC is supported by the MEIC and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). ; Sí

To propose and validate a novel imaging sequence that uses a single breath-hold whole-heart 3D T1 saturation recovery compressed SENSE rapid acquisition (SACORA) at 3T. The proposed sequence combines flexible saturation time sampling, compressed SENSE, and sharing of saturation pulses between two readouts acquired at different RR intervals. The sequence was compared with a 3D saturation recovery single-shot acquisition (SASHA) implementation with phantom and in vivo experiments (pre and post contrast; 7 pigs) and was validated against the reference inversion recovery spin echo (IR-SE) sequence in phantom experiments. Phantom experiments showed that the T1 maps acquired by 3D SACORA and 3D SASHA agree well with IR-SE. In vivo experiments showed that the pre-contrast and post-contrast T1 maps acquired by 3D SACORA are comparable to the corresponding 3D SASHA maps, despite the shorter acquisition time (15s vs. 188s, for a heart rate of 60 bpm). Mean septal pre-contrast T1 was 1453 ± 44 ms with 3D SACORA and 1460 ± 60 ms with 3D SASHA. Mean septal post-contrast T1 was 824 ± 66 ms and 824 ± 60 ms. 3D SACORA acquires 3D T1 maps in 15 heart beats (heart rate, 60 bpm) at 3T. In addition to its short acquisition time, the sequence achieves good T1 estimation precision and accuracy. ; TFdS has received funding from the European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement N722427. CGA is a P-FIS fellow (Instituto deSalud Carlos III). This study was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). ; Sí

<p><strong>Background: </strong>Hypertension is the leading global risk for mortality. Poor treatment and control of hypertension in low- and middle-income countries is due to several reasons, including insufficient human resources. Nurse management of hypertension is a novel approach to address the human resource challenge. However, specific barriers and facilitators to this strategy are not known. </p><p><strong>Objective: </strong>To evaluate barriers and facilitators to nurse management of hypertensive patients in rural western Kenya, using a qualitative research approach. </p><p><strong>Methods: </strong>Six key informant interviews (five men, one woman) and seven focus group discussions (24 men, 33 women) were conducted among physicians, clinical officers, nurses, support staff, patients, and community leaders. Content analysis was performed using Atlas.ti 7.0, using deductive and inductive codes that were then grouped into themes representing barriers and facilitators. Ranking of barriers and facilitators was performed using triangulation of density of participant responses from the focus group discussions and key informant interviews, as well as investigator assessments using a two-round Delphi exercise. <strong></strong></p><p><strong>Results: </strong>We identified a total of 23 barriers and nine facilitators to nurse management of hypertension, spanning the following categories of factors: health systems, environmental, nurse-specific, patient-specific, emotional, and community. The Delphi resultswere generally consistent with the findings from the content analysis. <strong></strong></p><p><strong>Conclusion: </strong>Nurse management of hypertension is a potentially feasible strategy to address the human resource challenge of hypertension control in low-resource settings. However, successful implementation will be contingent upon addressing barriers such as access to medications, quality of care, training of nurses, health education, and stigma. <em>Ethn Dis. </em>2016;26(3):315-322; doi:10.18865/ed.26.3.315. </p>

The incidence of cardiovascular (CV) risk factors is increasing globally, with a disproportionate burden in the low and low-middle income countries (L/LMICs). Peer support, as a low-cost lifestyle intervention, has succeeded in managing chronic illness. For global CV risk reduction, limited data exists in LMICs. Aim: The GHP-CHANGE was designed as a community-based randomized trial to test the effectiveness of peer support strategy for CV risk reduction in the island of Grenada, a LMIC. Methods: We recruited 402 adults from the Grenada Heart Project (GHP) Cohort Study of 2827 subjects with at least two CV risk factors. Subjects were randomized in a 1:1 fashion to a peer-group based intervention group (n = 206) or a self-management control group (n = 196) for 12 months. The primary outcome was the change from baseline in a composite score related to Blood pressure, Exercise, Weight, Alimentation and Tobacco (FBS, Fuster-BEWAT Score), ranging from 0 to 15 (ideal health = 15). Linear mixed-effects models were used to test for intervention effects. Results: Participants mean age was 51.4 years (SD 14.5) years, two-thirds were female, and baseline mean FBS was 8.9 (SD 2.6) and 8.5 (SD 2.6) in the intervention and control group, respectively (P = .152). At post intervention, the mean FBS was higher in the intervention group compared to the control group [9.1 (SD 2.7) vs 8.5 (SD 2.6), P = .028]. When balancing baseline health profile, the between-group difference (intervention vs. control) in the change of FBS was 0.31 points (95% CI: −0.12 to 0.75; P = .154). Conclusions: The GHP-CHANGE trial showed that a peer-support lifestyle intervention program was feasible; however, it did not demonstrate a significant improvement in the FBS as compared to the control group. Further studies should assess the effects of low-cost lifestyle interventions in LMICs ; This study was funded by the Louis B Mayer Foundation. VF is a recipient of funding from the American Heart Association under grant No 14SFRN20490315. R.F-J is a recipient of funding from the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707642. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

BACKGROUND: The incidence of cardiovascular (CV) risk factors is increasing globally, with a disproportionate burden in the low and low-middle income countries (L/LMICs). Peer support, as a low-cost lifestyle intervention, has succeeded in managing chronic illness. For global CV risk reduction, limited data exists in LMICs. AIM: The GHP-CHANGE was designed as a community-based randomized trial to test the effectiveness of peer support strategy for CV risk reduction in the island of Grenada, a LMIC. METHODS: We recruited 402 adults from the Grenada Heart Project (GHP) Cohort Study of 2827 subjects with at least two CV risk factors. Subjects were randomized in a 1:1 fashion to a peer-group based intervention group (n = 206) or a self-management control group (n = 196) for 12 months. The primary outcome was the change from baseline in a composite score related to Blood pressure, Exercise, Weight, Alimentation and Tobacco (FBS, Fuster-BEWAT Score), ranging from 0 to 15 (ideal health = 15). Linear mixed-effects models were used to test for intervention effects. RESULTS: Participants mean age was 51.4 years (SD 14.5) years, two-thirds were female, and baseline mean FBS was 8.9 (SD 2.6) and 8.5 (SD 2.6) in the intervention and control group, respectively (P = .152). At post intervention, the mean FBS was higher in the intervention group compared to the control group [9.1 (SD 2.7) vs 8.5 (SD 2.6), P = .028]. When balancing baseline health profile, the between-group difference (intervention vs. control) in the change of FBS was 0.31 points (95% CI: -0.12 to 0.75; P = .154). CONCLUSIONS: The GHP-CHANGE trial showed that a peer-support lifestyle intervention program was feasible; however, it did not demonstrate a significant improvement in the FBS as compared to the control group. Further studies should assess the effects of low-cost lifestyle interventions in LMICs. ; This study was funded by the Louis B Mayer Foundation. VF is a recipient offunding from the American Heart Association under grant No 14SFRN20490315. R.F-J isa recipient of funding from the European Union Horizon 2020 research and innovationprogramme under the Marie Skłodowska-Curie grant agreement No 707642. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación yUniversidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center ofExcellence (SEV-2015-0505). ; Sí

BACKGROUND The ideal cardiovascular health score (ICHS) is recommended for use in primary prevention. Simpler tools not requiring laboratory tests, such as the Fuster-BEWAT (blood pressure [B], exercise [E], weight [W], alimentation [A], and tobacco [T]) score (FBS), are also available. OBJECTIVES The purpose of this study was to compare the effectiveness of ICHS and FBS in predicting the presence and extent of subclinical atherosclerosis. METHODS A total of 3,983 participants 40 to 54 years of age were enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) cohort. Subclinical atherosclerosis was measured in right and left carotids, abdominal aorta, right and left iliofemoral arteries, and coronary arteries. Subjects were classified as having poor, intermediate, or ideal cardiovascular health based on the number of favorable ICHS or FBS. RESULTS With poor ICHS and FBS as references, individuals with ideal ICHS and FBS showed lower adjusted odds of having atherosclerotic plaques (ICHS odds ratio [OR]: 0.41; 95\% confidence interval [CI]: 0.31 to 0.55 vs. FBS OR: 0.49; 95\% CI: 0.36 to 0.66), coronary artery calcium (CACS) >= 1 (CACS OR: 0.41; 95\% CI: 0.28 to 0.60 vs. CACS OR: 0.53; 95\% CI: 0.38 to 0.74), higher number of affected territories (OR: 0.32; 95\% CI: 0.26 to 0.41 vs. OR: 0.39; 95\% CI: 0.31 to 0.50), and higher CACS level (OR: 0.40; 95\% CI: 0.28 to 0.58 vs. OR: 0.52; 95\% CI: 0.38 to 0.72). Similar levels of significantly discriminating accuracy were found for ICHS and FBS with respect to the presence of plaques (C-statistic: 0.694; 95\% CI: 0.678 to 0.711 vs. 0.692; 95\% CI: 0.676 to 0.709, respectively) and for CACS >= 1 (C-statistic: 0.782; 95\% CI: 0.765 to 0.800 vs. 0.780; 95\% CI: 0.762 to 0.798, respectively). CONCLUSIONS Both scores predict the presence and extent of subclinical atherosclerosis with similar accuracy, highlighting the value of the FBS as a simpler and more affordable score for evaluating the risk of subclinical disease. (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. ; The PESA study was co-funded by Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Banco Santander. Funding was also provided by Institute of Health Carlos III (PI15/02019) and European Regional Development Fund. CNIC is supported by the Ministry of Economy, Industry and Competitiveness and Pro CNIC Foundation; and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work is part of a project that received funding from the European Union Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant 707642 and American Heart Association grant 14SFRN20490315. Dr. Bueno has received research funding from Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; is a consultant for Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speakers fees and travel and attendance support from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Ferrer, Novartis, Servier, and Medscape. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Matthew Budoff, MD, served as Guest Editor for this paper. ; Sí

Long-term evaluations of child health promotion programs are required to assess their sustainability and the need for reintervention. This study sought to explore the long-term impact of a preschool health promotion intervention delivered in an urban low-income area of Colombia (phase 1) and to assess the effect of a new community-based intervention (phase 2). In phase 1, a cross-sectional analysis of knowledge, attitudes, and habits (KAH) toward a healthy lifestyle and ideal cardiovascular health (ICH) scores of 1,216 children 9 to 13 years old was performed. Of the total, 596 had previously received a preschool health promotion intervention at 3 to 5 years old, whereas the remaining 620 were not previously intervened (intervention-naive group). In phase 2, all children were cluster randomized 1:1 to receive either a 4-month educational intervention (the SI! Program) to instill healthy behaviors in community centers (24 clusters, 616 children) or to control (24 clusters, 600 children). Previously intervened and intervention-naive children were not mixed in the same cluster. The primary outcomes were the change from baseline in KAH and ICH scores. Intervention effects were tested for with linear mixed-effects models. In phase 1, ∼85% of children had nonideal cardiovascular health, and those who previously received a preschool intervention showed a negligible residual effect compared with intervention-naive children. In phase 2, the between-group (control vs. intervention) differences in the change of the overall KAH and ICH scores were 0.92 points (95% confidence interval [CI]: -0.28 to 2.13; p = 0.133) and -0.20 points (95% CI: -0.43 to 0.03; p = 0.089), respectively. No booster effect was detected. However, a dose-response effect was observed, with maximal benefit in children attending >75% of the scheduled intervention; the difference in the change of KAH between the high- and low-adherence groups was 3.72 points (95% CI: 1.71 to 5.73; p < 0.001). Although overall significant differences between the intervention and control groups were not observed, high adherence rates to health promotion interventions may improve effectiveness and outcomes in children. Reintervention strategies may be required at multiple stages to induce sustained health promotion effects (Salud Integral Colombia [SI! Colombia II]; NCT03119792). ; This study was funded by the Santo Domingo Foundation. Dr. Fuster is the recipient of funding from the American Heart Association under grant no. 14SFRN20490315. Dr. Fernández-Jiménez is the recipient of funding from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PI19/01704) and has received funding from the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 707642. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). ; Sí

BACKGROUND: Socioeconomic status (SES)-education, income level, and occupation-is associated with cardiovascular risk. OBJECTIVES: This study aimed to investigate the association between SES and subclinical atherosclerosis and the potential mechanisms involved. METHODS: SES, lifestyle habits (smoking, dietary patterns, physical activity, and hours of sleep), traditional risk factors, and subclinical atherosclerosis extent were prospectively assessed in 4,025 individuals aged 40 to 54 years without known cardiovascular disease enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) study. After factors associated with atherosclerosis were identified, a multiple mediation model was created to quantify the effect of SES on subclinical atherosclerosis as explained by lifestyle behaviors. RESULTS: Although education level was significantly associated with the presence of atherosclerosis, no differences were found according to income level in this population. Participants with lower education presented with a higher risk of generalized atherosclerosis than those with higher education (odds ratio: 1.46; 95% confidence interval: 1.15 to 1.85; p = 0.002). Lifestyle behaviors associated with both education level and atherosclerosis extent were: smoking status, number of cigarettes/day, and dietary pattern, which explained 70.5% of the effect of SES on atherosclerosis. Of these, tobacco habit (smoking status 35% and number of cigarettes/day 32%) accounted for most of the explained differences between groups, whereas dietary pattern did not remain a significant mediator in the multiple mediation model. CONCLUSIONS: Despite the relative economic homogeneity of the cohort, lower education level is associated with increased subclinical atherosclerosis, mainly mediated by the higher and more frequent tobacco consumption. Smoking cessation programs are still needed, particularly in populations with lower education level. ; The PESA study is cofunded equally by the Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; and Banco Santander, Madrid, Spain. The study also receives funding from the Institute of Health Carlos III (PI15/02019) and the European Regional Development Fund. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No707642; and from the American Heart Association under grantnumber14SFRN20490315. Dr. Bueno has received research funding from the Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; has received consulting fees from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speaking fees or support for attending scientific meetings from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Ferrer, Novartis, Servier, and MEDSCAPE-the heart.org. ; Sí

The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment. Large-White male pigs (n = 40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure (0.45 mg/kg intracoronary (IC) doxorubicin per injection) and follow-up: Control (no doxorubicin); Single injection and sacrifice either at 48 hours (ExPr. 1) or 2 weeks (ExPr. 2); Three injections two weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; Five injections two weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls.A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (3 biweekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibers even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime. Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects. ; This study was supported by a European Research Council grant MATRIX (ERC-COG-2018- ID: 819775) to B.I.; the ERA-CVD Joint Translational Call 2016 (funded through the Instituto de Salud Carlos III (ISCIII), and the European Regional Development Fund (ERDF); ID: AC16/00021); a Health Research Project from the ISCIII-FIS (ID: PI16/02110); The BBVA foundation grant (ID: BIO CAR 0265). This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare. C.G. and R.V-G. are P-FIS fellows (Instituto de Salud Carlos III). E.O. is recipient of funds from the Programa de Atracción de Talento (2017-T1/BMD-5185) of the Comunidad de Madrid. This study was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European Union structural and investment funds. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU), and the Pro CNIC Foundation. ; Sí

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty. ; This study received funding from the Ministry of Science and Innovation ("RETOS 2019" Grant no. PID2019-107332RB-I00), from the Instituto de Salud Carlos III (ISCIII; PI16/02110) and the European Regional Development Fund (ERDF) "A way of making Europe" (# AC16/00021), and from the Spanish Society of Cardiology through a 2017 Translational Research grant. BI has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC-Consolidator Grant agreement no. 819775). M.L received support from a 2015 Severo Ochoa CNIC intramural grant. X.R. received support from the SEC-CNIC CARDIOJOVEN fellowship program. R.F-J is a recipient of funding from the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PI19/01704) and has received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 707642. EO is recipient of funds from Programa de Atracción de Talento (2017-T1/BMD-5185) of Comunidad de Madrid. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MICINN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). ; Sí