As a greater proportion of patients survive their initial cardiac insult, medical systems worldwide are being faced with an ever-growing need to understand the mechanisms behind the pathogenesis of chronic heart failure (HF). There is a wealth of information about the role of inflammatory cells and pathways during acute injury and the reparative processes that are subsequently activated. We discuss the different causes that lead to chronic HF development and how the sum of initial inflammatory and reparative responses only sets the trajectory for disease progression. Unfortunately, comparatively little is known about the contribution of the immune system once the trajectory has been set, and chronic HF has been established—which clinically represents the majority of patients. It is known that chronic HF is associated with circulating inflammatory cytokines that can predict clinical outcomes, yet the causative role inflammation plays in disease progression is not well defined, and the majority of clinical trials that target aspects of inflammation in patients with chronic HF have largely been negative. This review will present what is currently known about inflammation in chronic HF in both humans and animal models as a means to highlight the gap in our knowledge base that requires further examination.

Chronic Heart Failure and Inflammation: What Do We Really Know?

Despite considerable advances in our understanding of myocarditis pathogenesis, the clinical management of myocarditis has changed relatively little in the last few years. This review aims to help bridge the widening gap between recent mechanistic insights, which are largely derived from animal models, and their potential impact on disease burden. We illustrate the pathogenetic mechanisms that are prime targets for novel therapeutic interventions. Pathway and pathogen-specific molecular diagnostic tests have expanded the role for endomyocardial biopsy. State of the art cardiac magnetic resonance imaging can now provide non-invasive tissue characterization and localize inflammatory infiltrates but imaging techniques are misleading if infectious agents are involved. We emphasize the gaps in our current clinical knowledge, particularly with respect to aetiology-based therapy, and suggest opportunities for high impact, translational investigations.

The management of myocarditis

Sex and Gender Differences in Myocarditis and Dilated Cardiomyopathy

The Quest for New Approaches in Myocarditis and Inflammatory Cardiomyopathy

Multiple roles of the coagulation protease cascade during virus infection.

Myocarditis and dilated cardiomyopathy (DCM) are often caused by viral infections and occur more frequently in men than in women, but the reasons for the sex difference remain unclear. The aim of t...

https://www.physiology.org/doi/pdf/10.1152/ajpheart.00783.2011

Testosterone and interleukin-1β increase cardiac remodeling during coxsackievirus B3 myocarditis via serpin A 3n.

Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR)3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3) myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL)-4-dominant T helper (Th)2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

/pdf/th2-regulation-of-viral-myocarditis-in-mice-different-roles-4d9a51q9d2.pdf

Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

We demonstrate two-dimensional imaging using illumination via a single-mode fiber with a multiply scattering tip and compressed sensing acquisition. We illuminate objects with randomly structured, but deterministic, speckle patterns produced by a coherent light source propagating through a TiO2-coated fiber tip. The coating thickness is optimized to produce speckle patterns that are highly sensitive to laser wavelength, yet repeatable. Images of the object are reconstructed from the characterized wavelength dependence of the speckle patterns and the wavelength dependence of the total light collected from the object using a single photodetector. Our imaging device is mechanically scan-free and insensitive to bending of the fiber, making it suitable for micro-endoscopy.

Single-pixel imaging using compressed sensing and wavelength-dependent scattering.

Ultra-miniaturized microendoscopes are vital for numerous biomedical applications. Such minimally invasive imagers allow for navigation into hard-to-reach regions and observation of deep brain activity in freely moving animals. Conventional solutions use distal microlenses. However, as lenses become smaller and less invasive, they develop greater aberrations and restricted fields of view. In addition, most of the imagers capable of variable focusing require mechanical actuation of the lens, increasing the distal complexity and weight. Here, we demonstrate a distal lens-free approach to microendoscopy enabled by computational image recovery. Our approach is entirely actuation free and uses a single pseudorandom spatial mask at the distal end of a multicore fiber. Experimentally, this lensless approach increases the space-bandwidth product, i.e., field of view divided by resolution, by threefold over a best-case lens-based system. In addition, the microendoscope demonstrates color resolved imaging and refocusing to 11 distinct depth planes from a single camera frame without any actuated parts.

A minimally invasive lens-free computational microendoscope

We demonstrate imaging using a multi-core fiber with a scattering distal tip and compressed sensing signal acquisition. We illuminate objects with randomly structured speckle patterns generated by a coherent light source separately coupled through each fiber core to a ground glass diffuser at the distal end. Using the characterized speckle patterns and the total light collected from the object, we computationally recover pixelation-free object images with up to a seven times higher space-bandwidth product than the number of cores. The proposed imaging system is insensitive to bending of the fiber and extremely compact, making it suitable for minimally invasive endomicroscopy.

Jaewook Shin

Papers

Testosterone and interleukin-1β increase cardiac remodeling during coxsackievirus B3 myocarditis via serpin A 3n.

Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

Single-pixel imaging using compressed sensing and wavelength-dependent scattering.

A minimally invasive lens-free computational microendoscope

Compressive fluorescence imaging using a multi-core fiber and spatially dependent scattering.