No abstract

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have been widely proposed as in vitro models of myocardial physiology and disease. A significant obstacle, however, is their immature phenotype. We hypothesised that Ca2+ cycling of iPSC-CM is influenced by culture conditions and can be manipulated to obtain a more mature cellular behaviour. To test this hypothesis we seeded iPSC-CM onto fibronectin coated microgrooved polydimethylsiloxane (PDMS) scaffolds fabricated using photolithography, or onto unstructured PDMS membrane. After two weeks in culture, the structure and function of iPSC-CM were studied. PDMS microgrooved culture substrates brought about cellular alignment (p < 0.0001) and more organised sarcomere. The Ca2+ cycling properties of iPSC-CM cultured on these substrates were significantly altered with a shorter time to peak amplitude (p = 0.0002 at 1 Hz), and more organised sarcoplasmic reticulum (SR) Ca2+ release in response to caffeine (p < 0.0001), suggesting improved SR Ca2+ cycling. These changes were not associated with modifications in gene expression. Whilst structured tissue culture may make iPSC-CM more representative of adult myocardium, further construct development and characterisation is required to optimise iPSC-CM as a model of adult myocardium.

Systolic anterior motion (SAM) of the mitral valve (MV) can be a life-threatening condition. The SAM can result in severe left ventricular outflow tract obstruction and/or mitral regurgitation and is associated with an up to 20% risk of sudden death (which is substantially lower in hypertrophic cardiomyopathy (HCM)). The mechanisms of SAM are complex and depend on the functional status of the ventricle. The SAM can occur in the normal population, but is typically observed in patients with HCM or following MV repair. Echocardiography (2D, 3D and stress) has a central diagnostic role as the application of echocardiographic SAM predictors allows the incorporation of prevention techniques during surgery and post-operative SAM assessment. Cardiac magnetic resonance imaging has a special role in understanding the dynamic nature of SAM, especially in anatomically atypical hearts (including HCM). This article describes what the clinician needs to know about SAM ranging from pathophysiological mechanisms and imaging modalities to conservative (medical) and surgical approaches and their respective outcomes. A stepwise approach is advocated consisting of medical therapy, followed by aggressive volume loading and beta-adrenoceptor blockade. Surgery is the final option. The correct choice of surgical technique requires an understanding of the anatomical substrate of SAM.

Background Step-count monitors (pedometers, body-worn trackers and smartphone applications) can increase walking, helping to tackle physical inactivity. We aimed to assess the effect of step-count monitors on physical activity (PA) in randomised controlled trials (RCTs) amongst community-dwelling adults; including longer-term effects, differences between step-count monitors, and between intervention components. Methods Systematic literature searches in seven databases identified RCTs in healthy adults, or those at risk of disease, published between January 2000–April 2020. Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcome was mean differences (MD) with 95% confidence intervals (CI) in steps at follow-up between treatment and control groups. Our preferred outcome measure was from studies with follow-up steps adjusted for baseline steps (change studies); but we also included studies reporting follow-up differences only (end-point studies). Multivariate-meta-analysis used random-effect estimates at different time-points for change studies only. Meta-regression compared effects of different step-count monitors and intervention components amongst all studies at ≤4 months. Results Of 12,491 records identified, 70 RCTs (at generally low risk of bias) were included, with 57 trials (16,355 participants) included in meta-analyses: 32 provided change from baseline data; 25 provided end-point only. Multivariate meta-analysis of the 32 change studies demonstrated step-counts favoured intervention groups: MD of 1126 steps/day 95%CI [787, 1466] at ≤4 months, 1050 steps/day [602, 1498] at 6 months, 464 steps/day [301, 626] at 1 year, 121 steps/day [− 64, 306] at 2 years and 434 steps/day [191, 676] at 3–4 years. Meta-regression of the 57 trials at ≤4 months demonstrated in mutually-adjusted analyses that: end-point were similar to change studies (+ 257 steps/day [− 417, 931]); body-worn trackers/smartphone applications were less effective than pedometers (− 834 steps/day [− 1542, − 126]); and interventions providing additional counselling/incentives were not better than those without (− 812 steps/day [− 1503, − 122]). Conclusions Step-count monitoring leads to short and long-term step-count increases, with no evidence that either body-worn trackers/smartphone applications, or additional counselling/incentives offer further benefit over simpler pedometer-based interventions. Simple step-count monitoring interventions should be prioritised to address the public health physical inactivity challenge. Systematic review registration PROSPERO number CRD42017075810.

BH-ONCAB is a safe and comparable alternative to C-ONCAB in terms of early mortality and late survival. Furthermore, BH-ONCAB may confer a particular advantage in preventing perioperative myocardial infarction and reducing overall blood loss. Future work should focus on larger matched studies and multicenter randomized controlled trials that risk-stratify patients according to preoperative ventricular function and renal insufficiency to allow us to optimize our surgical revascularization strategy in these high-risk patients.