An evidence review and gap analysis for obstructive hypertrophic cardiomyopathy.

BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy (oHCM) have a substantial humanistic, clinical, and economic burden due to the array of symptoms and complications associated with the disease. The objective of this review was to identify key evidence gaps related to oHCM, specifically in Europe, North America, and Japan. METHODS: A targeted literature review was conducted using PubMed to identify English-language studies published between 2012 and 2022 assessing patients with HCM/oHCM in France, Germany, Italy, Spain, the United Kingdom (UK), the United States (US), Canada, and Japan. Outcomes of interest were epidemiology, natural history, pathophysiology, management, and clinical, economic, and humanistic burden. Identified studies were assessed qualitatively to characterize evidence gaps. RESULTS: Among 2,262 abstracts and 531 full-text articles screened, 178 articles were included from PubMed searches. An additional 16 unique studies were identified via a supplemental Google Scholar search initially conducted in January 2023 and updated in July 2024. Disease natural history, pathophysiology, and management were well documented globally. Significant evidence gaps were noted for the epidemiology, treatment, and burden of oHCM. Although multiple US studies were identified on the clinical, economic, and humanistic burden of oHCM, and one clinical burden study was found for Japan, there was a lack of evidence for France, Germany, Italy, Spain, the UK, and Canada. CONCLUSIONS: Major evidentiary gaps exist for the epidemiology, treatment, and burden of oHCM. Future research should address these gaps, with a specific focus on generating real-world evidence for Canada and European countries that will support the evaluation of emerging therapies in these regions.

Development of parvalbumin neurons and perineuronal nets in the visual cortex of normal and dark-exposed cats.

During development, the visual system maintains a high capacity for modification by expressing characteristics permissive for plasticity, enabling neural circuits to be refined by visual experience to achieve their mature form. This period is followed by the emergence of characteristics that stabilize the brain to consolidate for lifetime connections that were informed by experience. Attenuation of plasticity potential is thought to derive from an accumulation of plasticity-inhibiting characteristics that appear at ages beyond the peak of plasticity. Perineuronal nets (PNNs) are molecular aggregations that primarily surround fast-spiking inhibitory neurons called parvalbumin (PV) cells, which exhibit properties congruent with a plasticity inhibitor. In this study, we examined the development of PNNs and PV cells in the primary visual cortex of a highly visual mammal, and assessed the impact that 10 days of darkness had on both characteristics. Here, we show that labeling for PV expression emerges earlier and reaches adult levels sooner than PNNs. We also demonstrate that darkness, a condition known to enhance plasticity, significantly reduces the density of PNNs and the size of PV cell somata but does not alter the number of PV cells in the visual cortex. The darkness-induced reduction of PV cell size occurred irrespective of whether neurons were surrounded by a PNN, suggesting that PNNs have a restricted capacity to inhibit plasticity. Finally, we show that PV cells surrounded by a PNN were significantly larger than those without one, supporting the view that PNNs may mediate trophic support to the cells they surround.

Fast Recovery of the Amblyopic Eye Acuity of Kittens following Brief Exposure to Total Darkness Depends on the Fellow Eye.

Recent studies conducted on kittens have revealed that the reduced visual acuity of the deprived eye following a short period of monocular deprivation imposed in early life is reversed quickly following a 10-day period spent in total darkness. This study explored the contribution of the fellow eye to the darkness-induced recovery of the acuity of the deprived eye. Upon emergence of kittens from darkness, the fellow eye was occluded for different lengths of time in order to investigate its effects on either the speed or the extent of the recovery of acuity of the deprived eye. Occlusion of the fellow eye for even a day immediately following the period spent in darkness blocked any recovery of the acuity of the deprived eye. Moreover, occlusion of the fellow eye two days after the period of darkness blocked any further visual recovery beyond that achieved in the short period when both eyes were open. The results imply that the darkness-induced recovery of the acuity of the deprived eye depends upon, and is guided by, neural activity in the mature neural connections previously established by the fellow eye.