A Systematic Review Concerning the Relation between the Sympathetic Nervous System and Heart Failure with Preserved Left Ventricular Ejection Fraction

BackgroundHeart failure with preserved left ventricular ejection fraction (HFPEF) affects about half of all patients diagnosed with heart failure. The pathophysiological aspect of this complex disease state has been extensively explored, yet it is still not fully understood. Since the sympathetic nervous system is related to the development of systolic HF, we hypothesized that an increased sympathetic nerve activation (SNA) is also related to the development of HFPEF. This review summarizes the available literature regarding the relation between HFPEF and SNA.ConclusionCurrent literature confirms a relation between increased SNA and HFPEF. However, current literature is not able to distinguish whether enhanced SNA results in HFPEF, or HFPEF results in enhanced SNA. The most likely setting is a vicious circle in which HFPEF and SNA sustain each other.     

Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium

Although paracrine effects of mesenchymal stem cells (MSCs) have been suggested previously, cardioprotection by human MSC secretions has never been demonstrated. Human MSC-conditioned medium (CM) was collected by following a clinically compliant protocol. In a porcine model of ischemia and reperfusion injury, intravenous and intracoronary MSC-CM treatment significantly reduced myocardial nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2′-deoxyguanosine. In addition, expression levels of phospho-SMAD2 and active caspase 3 were diminished following CM treatment, suggesting that TGF-β signaling and apoptosis were reduced. This was associated with a 60% reduction in infarct size and marked improvement of systolic and diastolic cardiac performance as assessed with echocardiography and pressure volume loops. Fractionation studies revealed that only the fraction of the CM containing products > 1000 kDa (100–220 nm) provided cardioprotection in a mouse model of ischemia and reperfusion injury. This indicates that the responsible paracrine factor of human MSCs is likely a large complex rather than a single small molecule. These data identify human MSC-CM as a promising therapeutic option to reduce myocardial infarct size in patients with acute MI and suggest that the use of stem cell secretions could extend the applicability of stem cells for therapeutic purposes.     

Cardiomyogenic differentiation-independent improvement of cardiac function by human cardiomyocyte progenitor cell injection in ischaemic mouse hearts

We previously showed that human cardiomyocyte progenitor cells (hCMPCs) injected after myocardial infarction (MI) had differentiated into cardiomyocytes in vivo 3 months after MI. Here, we investigated the short-term (2 weeks) effects of hCMPCs on the infarcted mouse myocardium. MI was induced in immunocompromised (NOD/scid) mice, immediately followed by intramyocardial injection of hCMPCs labelled with enhanced green fluorescent protein (hCMPC group) or vehicle only (control group). Sham-operated mice served as reference. Cardiac performance was measured 2 and 14 days after MI by magnetic resonance imaging at 9.4 T. Left ventricular (LV) pressure-volume measurements were performed at day 15 followed by extensive immunohistological analysis. Animals injected with hCMPCs demonstrated a higher LV ejection fraction, lower LV end-systolic volume and smaller relaxation time constant than control animals 14 days after MI. hCMPCs engrafted in the infarcted myocardium, did not differentiate into cardiomyocytes, but increased vascular density and proliferation rate in the infarcted and border zone area of the hCMPC group. Injected hCMPCs engraft into murine infarcted myocardium where they improve LV systolic function and attenuate the ventricular remodelling process 2 weeks after MI. Since no cardiac differentiation of hCMPCs was evident after 2 weeks, the observed beneficial effects were most likely mediated by paracrine factors, targeting amongst others vascular homeostasis. These results demonstrate that hCMPCs can be applied to repair infarcted myocardium without the need to undergo differentiation into cardiomyocytes.     

Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement after transplantation

Although mesenchymal stromal cells (MSCs) have been applied clinically to treat cardiac diseases, it is unclear how and to which extent transplanted MSCs exert their beneficial effects. To address these questions, pre-clinical MSC administrations are needed for which pigs appear to be the species of choice. This requires the use of porcine cells to prevent immune rejection. However, it is currently unknown to what extent porcine MSCs (pMSCs) resemble human MSCs (hMSCs). Aim of this study was to compare MSC from porcine bone marrow (BM) with human cells for phenotype, multi-lineage differentiation potential, immune-modulatory capacity and the effect on cardiac function after transplantation in a mouse model of myocardial infarction. Flow cytometric analysis revealed that pMSC expressed surface antigens also found on hMSC, including CD90, MSCA-1 (TNAP/W8B2 antigen), CD44, CD29 and SLA class I. Clonogenic outgrowth was significantly enriched following selection of CD271+ cells from BM of human and pig (129 ± 29 and 1961 ± 485 fold, respectively). hMSC and pMSC differentiated comparably into the adipogenic, osteogenic or chondrogenic lineages, although pMSC formed fat much faster than hMSC. Immuno-modulation, an important feature of hMSC, was clearly demonstrated for pMSC when co-cultured with porcine peripheral blood cells stimulated with PMA and pIL-2. Finally, pMSC transplantation after myocardial infarction attenuated adverse remodelling to a similar extent as hMSC when compared to control saline injection. These findings demonstrate that pMSCs have comparable characteristics and functionality with hMSCs, making reliable extrapolation of pre-clinical pMSC studies into a clinical setting very well possible.     

Direct comparison of predictive performance of PRECISE-DAPT versus PARIS versus CREDO-Kyoto: a subanalysis of the ReCre8 trial

BackgroundMultiple scores have been proposed to guide risk stratification after percutaneous coronary intervention. This study assessed the performance of the PRECISE-DAPT, PARIS and CREDO-Kyoto risk scores to predict post-discharge ischaemic or bleeding events.MethodsA total of 1491 patients treated with latest-generation drug-eluting stent implantation were evaluated. Risk scores for post-discharge ischaemic or bleeding events were calculated and directly compared. Prognostic performance of both risk scores was assessed with calibration, Harrell’s c‑statistics net reclassification index and decision curve analyses.ResultsPost-discharge ischaemic events occurred in 56 patients (3.8%) and post-discharge bleeding events in 34 patients (2.3%) within the first year after the invasive procedure. C‑statistics for the PARIS ischaemic risk score was marginal (0.59, 95% confidence interval (CI) 0.51–0.68), whereas the CREDO-Kyoto ischaemic risk score was moderate (0.68, 95% CI 0.60–0.75). With regard to post-discharge bleeding events, CREDO-Kyoto displayed moderate discrimination (c-statistic 0.67, 95% CI 0.56–0.77), whereas PRECISE-DAPT (0.59, 95% CI 0.48–0.69) and PARIS (0.55, 95% CI 0.44–0.65) had a marginal discriminative capacity. Net reclassification index and decision curve analysis favoured CREDO-Kyoto-derived bleeding risk assessment.ConclusionIn this contemporary all-comer population, PARIS and PRECISE-DAPT risk scores were not resilient to independent testing for post-discharge bleeding events. CREDO-Kyoto-derived risk stratification was associated with a moderate predictive capability for post-discharge ischaemic or bleeding events. Future studies are warranted to improve risk stratification with more focus on robustness and rigorous testing.Electronic supplementary materialThe online version of this article (10.1007/s12471-020-01486-y) contains supplementary material, which is available to authorized users.     

ONCOR: design of the Dutch cardio-oncology registry

Netherlands Heart Journal - The relative new subspecialty ‘cardio-oncology’ was established to meet the growing demand for an interdisciplinary approach to the management of cancer...