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Cardiovascular disease is the leading cause of death globally. While pharmacological advancements have improved the morbidity and mortality associated with cardiovascular disease, non-adherence to prescribed treatment remains a significant barrier to improved patient outcomes. A variety of strategies to improve medication adherence have been tested in clinical trials, and include the following categories: improving patient education, implementing medication reminders, testing cognitive behavioral interventions, reducing medication costs, utilizing healthcare team members, and streamlining medication dosing regimens. In this review, we describe specific trials within each of these categories and highlight the impact of each on medication adherence. We also examine ongoing trials and future lines of inquiry for improving medication adherence in patients with cardiovascular diseases.

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Normal atrial conduction requires similar abundances and homogeneous/overlapping distributions of two connexins (Cx40 and Cx43). The remodeling of myocyte connections and altered electrical conduction associated with atrial fibrillation (AF) likely involves perturbations of these connexins. We conducted a comprehensive series of experiments to examine the abundances and distributions of Cx40 and Cx43 in the atria of AF patients. Atrial appendage tissues were obtained from patients with lone AF (paroxysmal or chronic) or normal controls. Connexins were localized by double label immunofluorescence confocal microscopy, and their overlap was quantified. Connexin proteins and mRNAs were quantified by immunoblotting and qRT-PCR. PCR amplified genomic DNA was sequenced to screen for connexin gene mutations or polymorphisms. Immunoblotting showed reductions of Cx40 protein (to 77% or 49% of control values in samples from patients with paroxysmal and chronic AF, respectively), but no significant changes of Cx43 protein levels in samples from AF patients. The extent of Cx43 immunostaining and its distribution relative to N-cadherin were preserved in the AF patient samples. Although there was variability of Cx40 staining among paroxysmal AF patients, all had some fields with substantial Cx40 heterogeneity and reduced overlap with Cx43. Cx40 immunostaining was severely reduced in all chronic AF patients. qRT-PCR showed no change in Cx43 mRNA levels, but reductions in total Cx40 mRNA (to <50%) and Cx40 transcripts A (to ~50%) and B (to <25%) as compared to controls. No Cx40 coding region mutations were identified. The frequency of promoter polymorphisms did not differ between AF patient samples and controls. Our data suggest that reduced Cx40 levels and heterogeneity of its distribution (relative to Cx43) are common in AF. Multiple mechanisms likely lead to reductions of functional Cx40 in atrial gap junctions and contribute to the pathogenesis of AF in different patients.

We have investigated the role of circulating glucocorticoids in the suppression of the hypothalamic-pituitary-thyroid (HPT) axis following lipopolysaccharide (LPS) injection in rats. Intraperitoneal injection of LPS (2.5 mg/kg) suppressed paraventricular nucleus thyrotropin-releasing hormone (TRH) mRNA, pituitary thyroid-stimulating hormone (TSH) mRNA and plasma triiodothyronine. In these animals LPS also increased paraventricular nucleus corticotropin-releasing hormone (CRH) mRNA, pituitary proopiomelanocortin (POMC) mRNA and plasma corticosterone levels. To investigate the role of plasma corticosterone in the suppression of the HPT axis, we clamped the plasma corticosterone level at morning baseline level by bilateral adrenalectomy and corticosterone pellet implantation. Ten days after surgery, LPS injection evoked a dramatic increase in CRH mRNA and POMC mRNA. Despite the lack of change in plasma corticosterone in the corticosterone-clamped rats, LPS was still able to suppress TRH and TSH mRNA levels in both corticosterone-clamped and sham-operated rats. These data indicate that in response to LPS, suppression of the HPT axis occurs and is independent of the LPS-induced increase in plasma corticosterone.

ObjectiveDespite the similar phenotypes, comparison between short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic features (SUNA) has hitherto not been possible due to the dearth of studies validating the phenotype of SUNA. Therefore, these 2 syndromes have been kept separate in the International Classification of Headache Disorders. The aim of this study is to characterize and compare the clinical phenotypes of large clinic-based cohorts of patients with SUNA and SUNCT.MethodsThe clinical phenotype of consecutive patients with SUNA identified from a single specialist headache center in the United Kingdom between 2007 and 2012 was studied and compared to that of patients with SUNCT.ResultsSixty-three patients with SUNA (18 male, 28.6%) and 70 patients with SUNCT (32 male, 35.7%) were included. The demographic and clinical characteristics of patients with SUNA were similar to those of patients with SUNCT. Ptosis and rhinorrhea were predictors of SUNCT. The corresponding odds ratios (ORs) (95% confidence interval) were 3.79 (1.64–8.77, p = 0.002) and 2.46 (1.09–5.59, p = 0.031), respectively. The presence of spontaneous only attacks was a predictor for SUNA (OR 2.58 [1.10–6.05], p = 0.029).ConclusionNo major clinical differences have emerged between SUNCT and SUNA, bar the fact that SUNCT is characterized by more prominent cranial autonomic features and triggerability. We propose that the 2 disorders be placed together in a single diagnostic category for which new diagnostic criteria are proposed.

Implantation of a continuous-flow LVAD is associated with changes in the performance of preexisting ICDs. ICD-related adverse events were encountered following LVAD implantation in this cohort, and at times resulted in invasive and noninvasive ICD system modification. Reductions in ICD sensing threshold after LVAD implantation may adversely affect ICD function. Formal ICD interrogation in addition to the regular follow-up testing is warranted post-LVAD.