Therapeutic Strategies Targeting Inherited Cardiomyopathies

Abstract

Purpose of Review

Cardiomyopathies due to genetic mutations are a heterogeneous group of disorders that comprise diseases of contractility, myocardial relaxation, and arrhythmias. Our goal here is to discuss a limited list of genetically inherited cardiomyopathies and the specific therapeutic strategies used to treat them.

Recent Findings

Research into the molecular pathophysiology of the development of these cardiomyopathies is leading to the development of novel treatment approaches. Therapies targeting these specific mutations with gene therapy vectors are on the horizon, while other therapies which indirectly affect the physiologic derangements of the mutations are currently being studied and used clinically. Many of these therapies are older medications being given new roles such as mexiletine for Brugada syndrome and diflunisal for transthyretin amyloid cardiomyopathy. A newer targeted therapy, the inhibitor of myosin ATPase MYK-461, has been shown to suppress the development of ventricular hypertrophy, fibrosis, and myocyte disarray and is being studied as a potential therapy in patients with hypertrophic cardiomyopathy.

Summary

While this field is too large to be completely contained in a single review, we present a large cross section of recent developments in the field of therapeutics for inherited cardiomyopathies. New therapies are on the horizon, and their development will likely result in improved outcomes for patients inflicted by these conditions.

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Publisher’s Note

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Video similarity detection using fixed-length Statistical Dominant Colour Profile (SDCP) signatures

Abstract

This paper presents a fast and effective technique for videos' visual similarity detection and measurement using compact fixed-length signatures. The proposed technique facilitates for building real-time and scalable video matching/retrieval systems through generating a representative signature for a given video shot. The generated signature (Statistical Dominant Colour Profile, SDCP) effectively encodes the colours' spatio-temporal patterns in a given shot, towards a robust real-time matching. Furthermore, the SDCP signature is engineered to better address the visual similarity problem, through its relaxed representation of shot contents. The compact fixed-length aspect of the proposed signature is the key to its high matching speed (>1000 fps) compared to the current techniques that relies on exhaustive processing, such as dense trajectories. The SDCP signature encodes a given video shot with only 294 values, regardless of the shot length, which facilitates for speedy signature extraction and matching. To maximize the benefit of the proposed technique, compressed-domain videos are utilized as a case study following their wide availability. However, the proposed technique avoids full video decompression and operates on tiny frames, rather than full-size decompressed frames. This is achievable through using the tiny DC-images sequence of the MPEG compressed stream. The experiments on various standard and challenging datasets (e.g. UCF101 13k videos) shows the technique's robust performance, in terms of both, retrieval ability and computational performances.

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Chemotherapy-induced cardiomyopathy caused by Pemetrexed

Summary

Chemotherapy-related cardiac toxicity is a rare but serious adverse event in patients with cancer. Thus far, no case of serious cardiac toxicity of pemetrexed has been reported. We describe the case of a patient with advanced lung cancer and cardiomyopathy due to pemetrexed. A 59-year-old woman visited our hospital, and we found abnormal findings on a chest radiograph. She was diagnosed as having stage IV lung adenocarcinoma. Chemotherapy with cisplatin and pemetrexed every 3 weeks was initiated. After four cycles of chemotherapy, maintenance chemotherapy with pemetrexed was administered every 3 weeks. During the seventeenth cycle of pemetrexed, she had shortness of breath in her daily life. A chest radiograph showed an enlarged cardiothoracic ratio (66%), and the transthoracic echocardiogram demonstrated expansion of the left ventricle (diastolic diameter, 67 mm), severe global hypokinesis, and reduced left ventricular ejection fraction (28%). The coronary angiogram showed no coronary constriction. There was no delayed accumulation on the contrast-enhanced cardiac magnetic resonance imaging scan. After right heart catheterization, pathological results of a myocardial biopsy from the ventricular septum indicated no cardiac muscle hypertrophy, cardiac fibrosis, inflammatory cell infiltration, or myocyte disarray. Eventually, she was diagnosed as having pemetrexed-induced cardiomyopathy. Pemetrexed was discontinued, and furosemide, enalapril, and carvedilol were started. Then her symptoms and cardiac function improved. Early detection and discontinuation of causative agents are the most important treatment strategies in similar patients. Diuretics, angiotensin-conversion enzyme inhibitors, and beta-blockers may be effective for treating heart failure.

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Deficiency of NALP3 Signaling Impairs Liver Regeneration After Partial Hepatectomy

Abstract

Inflammatory response is required to proceed the optimal liver regeneration after liver injury. Recent reports demonstrated that inflammasomes are involved in the innate immune response. Several NOD-Like receptors (NLRs) participated in the formation of the inflammasomes. NACHT, LRR, and PYD domain-containing protein 3 (NALP3) belongs to the NLR families and recognizes adenosine triphosphate (ATP), crystals, and reactive oxygen species. The present study examined the effect of inflammasomes on the process of liver regeneration using NALP3 knockout (KO) mice. The activation of inflammasomes in the liver was induced after 70% partial hepatectomy (PHx). The liver-to-body weight ratio was significantly decreased in NALP3-KO mice compared to that in WT mice after PHx. The number of Ki67-positive cells and the expression of Cyclin D1 and E1 after PHx were reduced in NALP3-KO mice compared to WT mice. The expression of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) were decreased in the remnant liver of NALP3-KO mice compared to WT mice. Flow cytometric analysis revealed that the expression of chemokines was decreased and the accumulation of CD11b-positive cells was suppressed in NALP3-KO mice after PHx. The treatment with ATP, which is a ligand to NALP3, increased the liver-to-body weight ratio in WT mice. These results indicate that NALP3 signaling is required for the induction of inflammatory response and the development of liver regeneration after PHx.

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VSD with severe aortic regurgitation with an anomalous coronary artery: a rare case

Abstract

Coronary anomalies are found in less than 1% of diagnostic coronary angiograms. The clinical relevance of these anomalies varies from insignificant to potentially lethal. Here, we present a rare case of a 46-year-old male who was previously diagnosed with severe aortic regurgitation with sub-aortic ventricular septal defect with coronary cameral fistula. Coronary angiography and 2-D echocardiography were showing that this fistula was connecting from the left circumflex artery to the left atrium (LA). Intra-operatively, there was no coronary cameral fistula; it was just an anomalous coronary artery arising from the left circumflex artery and ending upon the left atrial wall. This rare entity should be discussed; as in the literature, anomalous coronary in a case of ventricular septal defect with aortic regurgitation has not been reported yet.

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Performance improvement of ERP-based brain–computer interface via varied geometric patterns

Abstract

Recently, many studies have been focusing on optimizing the stimulus of an event-related potential (ERP)-based brain–computer interface (BCI). However, little is known about the effectiveness when increasing the stimulus unpredictability. We investigated a new stimulus type of varied geometric pattern where both complexity and unpredictability of the stimulus are increased. The proposed and classical paradigms were compared in within-subject experiments with 16 healthy participants. Results showed that the BCI performance was significantly improved for the proposed paradigm, with an average online written symbol rate increasing by 138% comparing with that of the classical paradigm. Amplitudes of primary ERP components, such as N1, P2a, P2b, N2, were also found to be significantly enhanced with the proposed paradigm. In this paper, a novel ERP BCI paradigm with a new stimulus type of varied geometric pattern is proposed. By jointly increasing the complexity and unpredictability of the stimulus, the performance of an ERP BCI could be considerably improved.

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