Correction to: Reference ranges of left ventricular structure and function assessed by contrast-enhanced cardiac MR and changes related to ageing and hypertension in a population-based study.

The original version of this article, published on 14 March 2018, unfortunately contained a mistake.

Reference ranges of left ventricular structure and function assessed by contrast-enhanced cardiac MR and changes related to ageing and hypertension in a population-based study.

OBJECTIVES: Reference ranges of left ventricular (LV) parameters from cardiac magnetic resonance (CMR) were established to investigate the impact of ageing and hypertension as important determinants of cardiac structure and function. METHODS: One thousand five hundred twenty-five contrast-enhanced CMRs were conducted in the Study of Health in Pomerania. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), ejection fraction (LVEF), and myocardial mass (LVMM) were determined using long- and short-axis steady-state free-precession sequences. The reference population was defined as participants without late enhancement, hypertension, and prior cardiovascular diseases. Reference ranges were established by quantile regression (5th and 95th percentile) and compared with an additional sample of treated and untreated hypertensives. RESULTS: LV volumes in the reference population (n = 634, 300 males, 334 females, 52.1 ± 13.3 years) aged between 20-69 years were lower with higher age (p = 0.001), whereas LVEFs were higher (p ≤ 0.020). LVMM was lower only in males (p = 0.002). Compared with the reference population, hypertension was associated with lower LVEDV in males (n = 258, p ≤ 0.032). Antihypertensive therapy was associated with higher LVEF in males (n = 258, +2.5%, p = 0.002) and females (n = 180, +2.1%, p = 0.001). CONCLUSIONS: Population-based LV reference ranges were derived from contrast-enhanced CMR. Hypertension-related changes were identified by comparing these values with those of hypertensives, and they might be used to monitor cardiac function in these patients. KEY POINTS: • Left ventricular function changed slightly but significantly between 20-69 years. • Reference values of BSA-indexed myocardial mass decreased with age in males. • Hypertension was associated with lower LV end-diastolic volume only in males. • CMR may allow assessing remodelling related to hypertension or antihypertensive treatment.

Dynamic adaptation of myocardial proteome during heart failure development.

Heart failure (HF) development is characterized by huge structural changes that are crucial for disease progression. Analysis of time dependent global proteomic adaptations during HF progression offers the potential to gain deeper insights in the disease development and identify new biomarker candidates. Therefore, hearts of TAC (transverse aortic constriction) and sham mice were examined by cardiac MRI on either day 4, 14, 21, 28, 42, and 56 after surgery (n = 6 per group/time point). At each time point, proteomes of the left (LV) and right ventricles (RV) of TAC and sham mice were analyzed by mass spectrometry (MS). In TAC mice, systolic LV heart function worsened from day 4 to day 14, remained on a stable level from day 14 to day 42, and showed a further pronounced decline at day 56. MS analysis identified in the LV 330 and in RV 246 proteins with altered abundance over time (TAC vs. sham, fc≥±2). Functional categorization of proteins disclosed the time-dependent alteration of different pathways. Heat shock protein beta-7 (HSPB7) displayed differences in abundance in tissue and serum at an early stage of HF. This study not only provides an overview of the time dependent molecular alterations during transition to HF, but also identified HSPB7 as a novel blood biomarker candidate for the onset of cardiac remodeling.

Protective effects of endothelin receptor A and B inhibitors against doxorubicin-induced cardiomyopathy.

The clinical efficiency of the highly potent antitumor agent doxorubicin is limited by cardiotoxic effects. In a murine doxorubicin cardiotoxicity model, increased endothelin-1 (ET-1) expression and cardioprotective effects of the dual ET-1 blocker bosentan were demonstrated. To date it is unclear if combined blocking of endothelin A/B receptors is necessary or whether selective inhibition of one of the ET-1 receptors is sufficient for the observed cardioprotection. Therefore, we investigated the impact of dual (bosentan) and single endothelin receptor antagonism through sitaxentan (receptor A blocker) or BQ788 (receptor B blocker) in a murine doxorubicin cardiotoxicity model (C57BL/6N). Simultaneous administration of each endothelin receptor antagonist (ERA) with doxorubicin resulted in a significantly improved hemodynamic performance in comparison to the impaired cardiac function in control mice with bosentan being most effective but closely followed by sitaxentan and also BQ788. This cardioprotection was not caused by diminished doxorubicin levels in heart since the doxorubicin content in cardiac tissue was not altered by ERAs significantly. However, whole transcript expression profiling showed partly different effects of the ERAs on doxorubicin-modulated cardiac gene expression of genes involved in signal transduction (e.g. Stat3, Pim1, Akt1, Plcb2), fibrosis (e.g. Myl4), energy production (e.g. Ant1) or oxidative stress (e.g. Aox1). Furthermore, doxorubicin-mediated gene regulations were verified in the murine cardiomyocyte model HL-1 showing partly reversed expression patterns after co-administration of the ERAs. In summary, our results demonstrate strong cardioprotective effects of blocking ET-1 receptors against the doxorubicin-related cardiomyopathy and provide evidence to potential underlying signaling pathways.