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 Ca(2+) 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 Ca(2+) 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) Ca(2+) release in response to caffeine (p < 0.0001), suggesting improved SR Ca(2+) 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.

The internal thoracic artery is the most effective conduit for coronary artery bypass surgery; however, most patients have multivessel disease and require additional saphenous vein or radial artery grafts. In this systematic review of the literature and meta-analysis, we aim to compare reported patency rates for these conduits and explore if differences are homogeneous across follow-up intervals. A literature search was performed using Embase, Medline, Cochrane Library, Google Scholar and randomised controlled trial databases to identify studies published between 1965 and October 2009. All studies reporting angiographic comparison of saphenous vein and radial artery conduit patency were included, irrespective of language. The end point was angiographic graft patency stratified over different follow-up intervals. Meta-analysis was performed according to recommendations from the Cochrane Collaboration and Meta-analysis Of Observational Studies in Epidemiology guidelines. We used a random-effect model and the odds ratio as the summary statistic. A total of 35 studies were identified. They reported early patency (≤ 1 year, 6795 grafts), medium-term patency (1-5 years, 3232 grafts) and long-term patency (>5 years, 1157 grafts). Significant variation of comparative patency existed across different follow-up intervals. Early saphenous vein patency was similar to radial artery patency with odds ratio of 1.04 (95% confidence interval 0.68-1.61). Medium-term saphenous vein patency, however, deteriorated significantly (odds ratio 2.06, 95% confidence interval 1.29-3.29). Similarly, long-term patency was better for radial artery conduits (odds ratio 2.28, 95% confidence interval 1.32-3.94). Heterogeneity was due to angiographic patency characteristics and related to risk of bias. In conclusion, the findings of this systematic review of the published literature and meta-analysis support the use of radial artery in preference to saphenous vein conduits for coronary artery bypass surgery.

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.

Objective: To assess early outcomes in the elderly population undergoing coronary revascularisation with and without cardiopulmonary bypass (CPB). Methods: Meta-analysis of all retrospective, non-randomised studies comparing off-pump coronary artery bypass (OPCAB) versus CPB techniques in the elderly (> 70 years) between 1999 and 2005. Age-related early outcomes of interest were death, stroke, atrial fibrillation (AF), renal failure and length of stay in hospital. The random effects model was used. Sensitivity and heterogeneity were analysed. Results: Analysis of 14 non-randomised studies comprising 4921 patients (OPCAB, 1533 (31.1%) and CPB, 3388 (68.9%)) showed a significantly lower incidence of death in the OPCAB group (odds ratio (OR) 0.48, 95% CI 0.28 to 0.84). This effect was greater in OPCAB octogenarians (OR 0.26, 95% CI 0.12 to 0.57). The pattern of incidence of stroke among the OPCAB octogenarians (OR 0.19, 95% CI 0.07 to 0.56) was similar. The incidence of AF was lower in the OPCAB group (OR 0.77, 95% CI 0.61 to 0.97). The incidence of renal failure did not differ. Length of hospital stay was shorter in the OPCAB group, although with significant heterogeneity. Conclusions: OPCAB may be associated with lower incidence of death, stroke and AF in the elderly, which may result in shorter length of hospital stay. A large randomised trial would confirm whether the elderly would benefit more from OPCAB surgery.

BACKGROUND: In elderly and comorbid patients with rectal cancer, radical surgery is associated with significant perioperative mortality. Data suggest that a watch-and-wait approach where a complete clinical response is obtained after neoadjuvant chemoradiotherapy might be oncologically safe. OBJECTIVE: This study aimed to determine whether patient age and comorbidity should influence surgeon and patient decision making where a complete clinical response is obtained. DESIGN: Decision-analytic modeling consisting of a decision tree and Markov chain simulation was used. Modeled outcome parameters were elicited both from comprehensive literature review and from a national patient outcomes database. SETTINGS: Outcomes for 3 patient cohorts treated with neoadjuvant therapy were modeled after either surgery or watch and wait. PATIENTS: Patients included 60-year-old and 80-year-old men with mild comorbidities (Charlson score 3). MAIN OUTCOME MEASURES: Absolute survival, disease-free survival, and quality-adjusted life years were measured. RESULTS: The model found that absolute survival was similar in 60-year-old patients but was significantly improved in fit and comorbid 80-year-old patients at 1 year after treatment where watch and wait was implemented instead of radical surgery, with a survival advantage of 10.1% (95% CI, 7.9–12.6) and 13.5% (95% CI, 10.2–16.9). At all of the other time points, absolute survival was equivalent for both techniques. There were no short- or long-term differences among any patient groups managed either by radical surgery or watch and wait in terms of either disease-free survival or quality-adjusted life years. LIMITATIONS: Oncologic data for the watch-and-wait approach used for this study is derived from only a small number of studies pertaining to a highly selected group of patients. The 90-day postoperative mortality rate derived from the United Kingdom population-based study might be lower in other countries or individual institutions. CONCLUSIONS: This study suggests competing effects of oncologic and surgical risk when using watch-and-wait management and that elderly and comorbid patients have the most to gain from this approach.