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It is now well recognized that many lifesaving oncology drugs may adversely affect the heart and cardiovascular system, including causing irreversible cardiac injury that can result in reduced quality of life. These effects, which may manifest in the short term or long term, are mechanistically not well understood. Research is hampered by the reliance on whole-animal models of cardiotoxicity that may fail to reflect the fundamental biology or cardiotoxic responses of the human myocardium. The emergence of human induced pluripotent stem cell-derived cardiomyocytes as an in vitro research tool holds great promise for understanding drug-induced cardiotoxicity of oncological drugs that may manifest as contractile and electrophysiological dysfunction, as well as structural abnormalities, making it possible to deliver novel drugs free from cardiac liabilities and guide personalized therapy. This article briefly reviews the challenges of cardio-oncology, the strengths and limitations of using human induced pluripotent stem cell-derived cardiomyocytes to represent clinical findings in the nonclinical research space, and future directions for their further use.

The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.

A major goal of basic research in cardiac electrophysiology is to understand the mechanisms responsible for ventricular fibrillation (VF). Here we review recent experimental and numerical results, from the ion channel to the organ level, which might lead to a better understanding of the cellular and molecular mechanisms of VF. The discussion centers on data derived from a model of stable VF in the Langendorff-perfused guinea pig heart that demonstrate distinct patterns of organization in the left (LV) and right (RV) ventricles. Analysis of optical mapping data reveals that VF excitation frequencies are distributed throughout the ventricles in clearly demarcated domains. The highest frequency domains are usually found on the anterior wall of the LV, demonstrating that a high frequency reentrant source (a rotor) that remains stationary in the LV is the mechanism that sustains VF in this model. Computer simulations predict that the inward rectifying potassium current (IK1) is an essential determinant of rotor stability and rotation frequency, and patch-clamp results strongly suggest that the outward component of the background current (presumably IK1) of cells in the LV is significantly larger in the LV than in the RV. These data have opened a new and potentially exciting avenue of research on the possible role played by inward rectifier channels in the mechanism of VF and may lead us toward an understanding of its molecular basis and hopefully lead to new preventative approaches.

There is general agreement that AF is most likely a reentrant rhythm disturbance. However, the precise pathophysiological bases for its initiation and maintenance have not been fully resolved. In the original description of the multiple wavelet hypothesis of atrial fibrillation, as put forward by Moe et al. and later substantiated by Allessie et al., the wavelets were thought to move randomly throughout the atria. However, more recent studies that have applied high resolution mapping of wave propagation and rigorous analyses in the time and frequency domains to long episodes of AF, have provided evidence that atrial fibrillation is not random, but is accompanied by a high degree of spatiotemporal periodicity. This has led to the hypothesis that maintenance of AF may depend on the uninterrupted periodic activity of a small number of discrete reentrant sites, established by the interaction of propagating waves with anatomical heterogeneities in the atria. It has been proposed also that the rapidly successive wave fronts emanating from these sources propagate through both atria and interact with anatomical and/or functional obstacles, leading to fragmentation and wavelet formation. In support of this idea, observations made during radiofrequency ablation of AF in humans suggest that, in some patients, a single, repetitive focal source of activity propagate impulses from an individual pulmonary vein to the remainder of the atrium as fibrillatory waves. These studies underscore the need for identification of continuing AF sources at localized sites, and of transient AF "triggers", which may involve normal or abnormal pacemaker mechanisms or even reentrant activity, and of the manner in which electrical activity initiated by such triggers interacts with the normally propagating electrical waves to initiate fibrillatory activity in the atria.