Imaging Targets to Visualize the Cardiac Immune Landscape in Heart Failure.

Heart failure involves a complex interplay between diverse populations of immune cells that dynamically shift across the natural history of disease. Within this context, the character of the immune response is a key determinant of clinical outcomes. Recent technological advances in single-cell transcriptomic, spatial, and proteomic technologies have fueled an explosion of new and clinically relevant insights into distinct immune cell populations that reside within the diseased heart including potential targets for molecular imaging and therapy. In this review, we will discuss the immune cell types and their respective functions with respect to myocardial infarction remodeling, dilated cardiomyopathy, and heart failure with preserved ejection fraction. In addition, we give a brief overview regarding myocarditis and cardiac sarcoidosis as inflammatory heart failure etiologies. We will highlight markers and cell populations as targets for molecular imaging to visualize inflammation and tissue healing and discuss clinical implications including the development and implementation of precision medicine approaches.

Circulating microRNAs predispose to takotsubo syndrome following high-dose adrenaline exposure.

AIMS: Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and in the absence of culprit coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. METHODS AND RESULTS: miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal), cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavß subunit), RGS4 (regulator of G-protein signalling 4), and G-protein subunit Gß (GNB1) as underlying these effects. CONCLUSION: miR-16 and miR-26a sensitize the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future.

Immunity and inflammation: the neglected key players in congenital heart disease?

Although more than 90% of children born with congenital heart disease (CHD) survive into adulthood, patients face significantly higher and premature morbidity and mortality. Heart failure as well as non-cardiac comorbidities represent a striking and life-limiting problem with need for new treatment options. Systemic chronic inflammation and immune activation have been identified as crucial drivers of disease causes and progression in various cardiovascular disorders and are promising therapeutic targets. Accumulating evidence indicates an inflammatory state and immune alterations in children and adults with CHD. In this review, we highlight the implications of chronic inflammation, immunity, and immune senescence in CHD. In this context, we summarize the impact of infant open-heart surgery with subsequent thymectomy on the immune system later in life and discuss the potential role of comorbidities and underlying genetic alterations. How an altered immunity and chronic inflammation in CHD influence patient outcomes facing SARS-CoV-2 infection is unclear, but requires special attention, as CHD could represent a population particularly at risk during the COVID-19 pandemic. Concluding remarks address possible clinical implications of immune changes in CHD and consider future immunomodulatory therapies.