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Background While the overall acute myocardial infarction rates declined in women and men, premature acute myocardial infarction rates remained stable in men and increased in women. Objective The purpose of this study was to assess whether baseline apolipoprotein (apo) levels, clinical characteristics, and follow-up of patients with very premature coronary artery disease (CAD) could provide novel clues for the identification of high-risk individuals. Methods Apos were measured with a validated quantification liquid chromatography–mass spectrometry method in a well-defined cohort of 38 patients aged ≤45 years admitted with acute ST-segment elevation myocardial infarction. Results Mean age was 39.8 ± 4.6 years and 24% was female. Four of these patients (11%) had apoCII levels ≤5.0 mg/L. Compared with the very premature CAD group with apoCII > 5 mg/L, the patients with apoCII levels ≤5.0 mg/L were all females, tended to be younger (35.8 ± 8.4 years vs 40.3 ± 3.9 years, P = .063), had more often a family history of cardiovascular disease ≤65 years ( P = .034) and a significantly lower Framingham risk score ( P = .001). They presented with normal triglyceride levels, and had lower low-density lipoprotein cholesterol, apoB 100 , and apoE levels. Corrected for differences in risk profile, apoCII ≤ 5 mg/L was associated with increased risk of 10-years reinfarction or revascularization (hazard ratio 7.9 [95% confidence interval 1.5–41.6], P = .015). Conclusions In 38 patients with very premature CAD, 11% were found to have low apoCII levels (≤5.0 mg/L) with normal triglyceride levels. Despite their low a priori risk for CAD, these patients presented with ST-segment elevation myocardial infarction and had a high relative risk of 10-year reinfarction or revascularization. This particular phenotype of relatively young female patients with CAD is not recognized earlier and deserves further study.

The function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension. While much progress has been made in the treatment of pulmonary hypertension, therapies for the RV are less well established. In this review of treatment strategies for the RV, first we focus on ways to reduce wall stress since this is the main determinant of changes to the ventricle. Secondly, we discuss treatment strategies targeting the detrimental consequences of increased RV wall stress. To reduce wall stress, afterload reduction is the essential. Additionally, preload to the ventricle can be reduced by diuretics, by atrial septostomy, and potentially by mechanical ventricular support. Secondary to ventricular wall stress, left-to-right asynchrony, altered myocardial energy metabolism, and neurohumoral activation will occur. These may be targeted by optimising RV contraction with pacing, by iron supplement, by angiogenesis and improving mitochondrial function, and by neurohumoral modulation, respectively. We conclude that several treatment strategies for the right heart are available; however, evidence is still limited and further research is needed before clinical application can be recommended.

Introduction: Oxidation of catecholamines and serotonin by monoamine oxidase–A (MAO-A) may play a role in pulmonary hypertension (PH). MAO-A inhibition (MAOi) decreased proliferation in pulmonary artery intima, and was beneficial in several models of left heart failure. We hypothesized that MAOi will be beneficial in the setting of PH. Methods: Male Wistar rats underwent surgical banding of the pulmonary trunk (PTB) or sham surgery (sham, n=7). Two weeks later, echocardiography was performed and PTB rats were randomized to MAOi (PTB+MAOi, n=12) and treated with clorgyline (2 mg/kg i.p. 3x/week) or saline (PTB, n=12). Rats were treated for five weeks before evaluation echo and pressure-volume-loops (PV loop) were obtained. During echo and PV loops rats where anesthetized with sevoflurane (mix in 1.5L/min O2, 7% for induction, 3.5% for maintainance). Results: MAO-A activity increased almost 3-fold in PTB compared to sham, whereas MAOi completely reversed this. PTB increased total heart- and RV weight, which was partly reversed by MAOi. The ratio of RV weight to left ventricle + septum weight did not change after MAOi. MAOi did not improve RV function or reduce RV dilatation as analyzed by echocardiography or PV loops (Fig. 1). Conclusion: Despite normalization of MAO-A activity in PTB rats, no functional improvements or changes in cardiac size were observed. Histological analyses will further elucidate these findings.

Introduction Hypercholesterolemia is a well-known risk factor for developing atherosclerosis and subsequently for the risk of a myocardial infarction (MI). Moreover, it might also be related to the extent of damaged myocardium in the event of a MI. The aim of this study was to evaluate the association of baseline low density lipoprotein-cholesterol (LDL-c) level with infarct size in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneously coronary intervention (pPCI). Methods Baseline blood samples were obtained from all patients admitted between 2004 and 2014 with STEMI who underwent pPCI. Patients were excluded in case of out of hospital cardiac arrest, treatment delay of at least 10 h or no complete reperfusion after pPCI in the culprit vessel. Peak creatine kinase (CK) level was used for infarct size estimation, defined as the maximal value during admission. Results A total of 2248 patients were included in this study (mean age 61.8 ± 12.2 years; 25.0% female). Mean LDL-c level was 3.6 ± 1.1 mmol/L and median peak CK level was 1275 U/L (IQR 564–2590 U/L). Baseline LDL-c level [β = 0.041; (95% CI 0.019–0.062); p

Introduction To investigate the additive prognostic value of growth differentiation factor (GDF-15) levels in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneously coronary intervention (pPCI) with 10-year mortality on top of clinical characteristics and known cardiac biomarkers. Methods Baseline serum GDF-15 levels were measured in 290 STEMI patients treated with pPCI in the MISSION! intervention trial conducted from February 1, 2004 through October 31, 2006. The incremental prognostic value of GDF-15 and NTproBNP levels was evaluated on top of clinical characteristics using Cox proportional hazards analysis, Chi-square models and C-index. Outcome was 10-year all-cause mortality. Results Mean age was 59.0 ± 11.5 years and 65 (22.4) patients were female. A total of 37 patients died during a follow-up of 9.4 (IQR 8.8–10.0) years. Multivariable Cox regression revealed GDF-15 and NTproBNP levels above median to be independently associated with 10-year all-cause mortality [HR GDF-15, 2.453 (95% CI 1.064–5.658), P = 0.04; HR NTproBNP, 2.413 (95% CI 1.043–5.564), P = 0.04] after correction for other clinical variables. Stratified by median GDF-15 (37.78 pmol/L) and NTproBNP (11.74 pmol/L) levels, Kaplan–Meier curves showed significant better survival for patients with GDF-15 and NTproBNP levels below the median versus above the median. The likelihood ratio test showed a significant incremental value of GDF-15 (P = 0.03) as compared with a model with clinically important variables and NTproBNP. The C-statistics for this model improved from 0.82 to 0.84 when adding GDF-15. Conclusion GDF-15 levels at admission in STEMI patients are independently associated with 10-year all-cause mortality rates and could improve risk stratification on top of clinical variables and other cardiac biomarkers. Electronic supplementary material The online version of this article (10.1007/s40119-019-0127-4) contains supplementary material, which is available to authorized users.

Introduction The current way to assess the risk of cardiovascular disease (CVD) is to measure conventional lipid and lipoprotein cholesterol fractions. Despite the success of statin treatment, residual cardiovascular risk remains high. Therefore, the value of extensive serum apolipoprotein (apo) profiling to assess the risk of ST-segment elevation myocardial infarction (STEMI) and of major adverse cardiac events (MACE) in patients with STEMI was investigated in a case–control design. Methods and results Serum apo levels were measured using liquid chromatography and mass spectrometry in 299 healthy individuals and 220 patients with STEMI. First, the association of apo profiles in baseline samples with risk of STEMI was examined, and second, the association of apo profiles at baseline with risk of recurrent MACE in patients with STEMI in a longitudinal study design was studied. High baseline (> 1.25 g/L) apoA1 levels were associated with a decreased risk of STEMI [odds ratio (OR) 0.17; 95% CI 0.11–0.26], whereas high apoB (> 1.00 g/L) levels (OR 2.17; 95% CI 1.40–3.36) and apoB/apoA1 ratio (OR per 1 SD (OR/SD): 2.16; 95% CI 1.76–2.65) were associated with an increased risk. Very-low-density-lipoprotein (VLDL)-associated apos gave conflicting results. Neither conventional lipid levels nor apo levels were associated with MACE in the STEMI group. Conclusion In conclusion, apoA1, apoB, and apoB/apoA1 were strongly associated with risk of STEMI. No clear relation between VLDL-associated apos and the risk of STEMI was found. Neither baseline serum apos nor lipids predicted MACE in statin-treated patients during long-term follow-up after a first STEMI.

Dissonances of ethnic nationalism have in Western cultural policy long been concealed by the universalist discourses of the international treaties on material heritage protection, as framed by the expansive heritage conservation apparatuses of the European nation states. Originally inspired by the 19th century romantic spirit of conservation, they became in the 20th century part of the modern, state-apparatus. Yet parallel with the European enlargements and new kinds of memory debates on the Holocaust and postcolonialism, these authorized heritage regimes have received more and more competition from a transnational counter-discourse on intangible cultural heritage. Like the earlier transformative, internationalist notion of world heritage, this intangible perception of cultural heritage is embraced by the European Community and promoted on a global scale by the Paris headquarters of the 1946 founded UNESCO. And yet, at the same time, it neglects much of the deep-rooted symbolic identifications with Europe’s dissonant pasts and identity crusades, and fosters the assumption of an almost touristic kind of bottom-up heritagization as a more democratic road to Europeanization. Altogether, such contradictory statements on what is analysed as an "intangible heritage turn", thus ask for a critical observation in the context of the current authoritarian revolt and the related revival of Identitarian discourses in large parts of Europe, both from the Left and from the Right (in defense of, respectively, minority cultures and national cultures). Sketching the past and current state of affairs in intangible heritage policy, and using examples from the Dutch postcolonial case of Black Pete to the Russian-Ukrainian folklore war on Kolobok, it is argued how by highlighting cultural diversity, the Intangible Heritage Convention takes the risk of becoming a legitimizing instrument for groups and communities claimingexclusive rights and values in competition with others. The protection of cultural traditions and expressions might then lead to the result that what is safeguarded as intangible heritage may actually be a community’s nostalgic brand identity, whereas such community values might at the same time be framed by populist governments and movements as being threatened by precisely the kind of cultural diversity, or the “creolization of the world”,3 which the Convention should help to support.

Uncoupling of mitochondrial proton pumping and adenosine triphosphate (ATP) production lowers mitochondrial efficiency. Current methods to determine mitochondrial efficiency require substantial amounts of tissue and permeabilization or isolation procedures. A simple histochemical method has been described by Meijer and Vloedman (Histochemistry 69:217-232, 1980, https://doi.org/10.1007/BF00489769 ), but this was not quantitative. We found linear correlations between (1) absorbance and sections thickness and (2) absorbance and incubation time. Because the method obeys Lambert-Beer's law, we can estimate ATP/O2 ratios for healthy and overloaded right-sided rat myocardium. We related mitochondrial efficiency to the ratio between cardiolipin and its precursor phosphatidylglycerol. We found a non-linear relationship between mitochondrial efficiency and this ratio, indicating that lower mitochondrial efficiency as found in experimental pulmonary hypertension may be due to altered composition of the mitochondrial inner membrane. We conclude that the histochemical method of Meijer and Vloedman can be applied to quantify mitochondrial efficiency.

Summary The capacity to regenerate damaged tissues, such as the heart, various enormously amongst species. While heart regeneration is generally very low in mammals 1–3, it can regenerate efficiently in certain amphibian and fish species 4,5. Zebrafish has been used extensively to study heart regeneration, resulting in the identification of proliferating cardiomyocytes that drive this process 5–7. However, mechanisms that drive cardiomyocyte proliferation are largely unknown. Here, using a single-cell mRNA-sequencing approach, we find a transcriptionally distinct population of dedifferentiated and proliferating cardiomyocytes in regenerating zebrafish hearts. While adult cardiomyocytes are known to rely on mitochondrial oxidative phosphorylation (OXPHOS) for energy production, these proliferating cardiomyocytes show reduced mitochondrial gene expression and decreased OXPHOS activity. Strikingly, we find that genes encoding rate-limiting enzymes of the glycolysis pathway are induced in the proliferating cardiomyocytes, and inhibiting glycolysis impairs cardiomyocyte cell cycle reentry. Mechanistically, glycolytic gene expression is induced by Nrg1/Erbb2 signaling, and this is conserved in a mouse model of enhanced regeneration. Moreover, inhibiting glycolysis in murine cardiomyocytes abrogates the mitogenic effects of Nrg1/ErbB2 signaling. Together these results reveal a conserved mechanism in which cardiomyocytes undergo metabolic reprogramming by activating glycolysis, which is essential for cell cycle reentry and heart regeneration. This could ultimately help develop therapeutic interventions that promote the regenerative capacity of the mammalian heart.