Cardiovascular health of patients with cancer: Challenges abound.

Patients with cancer have elevated cardiovascular risks compared to those without cancer. As cancer incidence increases and cancer-related mortality decreases, cardiovascular diseases in patients with a history of cancer will become increasingly important. This in turn is reflected by the exponentially increasing amount of cardio-oncology research in recent years.

Location, Location, Location: A Pilot Study to Compare Electrical with Echocardiographic-Guided Targeting of Left Ventricular Lead Placement in Cardiac Resynchronisation Therapy.

Cardiac resynchronisation therapy is ineffective in 30-40% of patients with heart failure with reduced ejection fraction. Targeting non-scarred myocardium by selecting the site of latest mechanical activation using echocardiography has been suggested to improve outcomes but at the cost of increased resource utilisation. The interval between the beginning of the QRS complex and the local LV lead electrogram (QLV) might represent an alternative electrical marker.

Comparison of Stress-Rest and Stress-LGE Analysis Strategy in Patients Undergoing Stress Perfusion Cardiovascular Magnetic Resonance.

Background: Stress perfusion cardiovascular magnetic resonance can be performed without rest perfusion for the quantification of ischemia burden. However, the optimal method of analysis is uncertain.

Methods: We identified 666 patients from CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) with complete stress perfusion, rest perfusion, late gadolinium enhancement (LGE), and quantitative coronary angiography data.

Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/-) hearts.

Reductions in cardiac action potential wavelength, and the consequent wavebreak, have been implicated in arrhythmogenesis. Tachyarrhythmias are more common in the Brugada syndrome, particularly following pharmacological challenge, previously modelled using Scn5a(+/-) murine hearts. Propagation latencies and action potential durations (APDs) from monophasic action potential recordings were used to assess wavelength changes with heart rate in Langendorff-perfused wild-type (WT) and Scn5a(+/-) hearts.

Abnormal Ca(2+) homeostasis, atrial arrhythmogenesis, and sinus node dysfunction in murine hearts modeling RyR2 modification.

Ryanodine receptor type 2 (RyR2) mutations are implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT) thought to result from altered myocyte Ca(2+) homeostasis reflecting inappropriate "leakiness" of RyR2-Ca(2+) release channels arising from increases in their basal activity, alterations in their phosphorylation, or defective interactions with other molecules or ions. The latter include calstabin, calsequestrin-2, Mg(2+), and extraluminal or intraluminal Ca(2+). Recent clinical studies additionally associate RyR2 abnormalities with atrial arrhythmias including atrial tachycardia (AT), fibrillation (AF), and standstill, and sinus node dysfunction (SND).

The role of ion channelopathies in sudden cardiac death: implications for clinical practice.

Sudden cardiac death (SCD) following ventricular tachyarrhythmias constitutes an important clinical cause of mortality; 4% of cases may involve ion channel-mediated cellular excitation in structurally normal hearts. Alterations in such processes could disturb action potential conduction, depolarization/ repolarization gradients, or Ca(2+) homeostasis with potential arrhythmogenic consequences. Although SCD may be the first presentation of arrhythmic syndromes, patients may present to the general physician with symptoms of palpitations or hemodynamic compromise, including dizziness, seizure, or syncope, particularly following exertion.

Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice.

Atrial fibrillation, the commonest cardiac arrhythmia, predisposes to thrombus formation and consequently increases risk of ischaemic stroke. Recent years have seen approval of a number of novel oral anticoagulants. Nevertheless, warfarin and aspirin remain the mainstays of therapy.

Pathophysiological Mechanisms of Sino-Atrial Dysfunction and Ventricular Conduction Disease Associated with SCN5A Deficiency: Insights from Mouse Models.

Genetically modified mice provide a number of models for studying cardiac channelopathies related to cardiac Na(+) channel (SCN5A) abnormalities. We review key pathophysiological features in these murine models that may underlie clinical features observed in sinus node dysfunction and progressive cardiac conduction disease, thereby providing insights into their pathophysiological mechanisms. We describe loss of Na(+) channel function and fibrotic changes associated with both loss and gain-of-function Na(+) channel mutations.

Nonlinearity between action potential alternans and restitution, which both predict ventricular arrhythmic properties in Scn5a+/- and wild-type murine hearts.

Electrocardiographic QT- and T-wave alternans, presaging ventricular arrhythmia, reflects compromised adaptation of action potential (AP) duration (APD) to altered heart rate, classically attributed to incomplete Na(v)1.5 channel recovery prior to subsequent stimulation. The restitution hypothesis suggests a function whose slope directly relates to APD alternans magnitude, predicting a critical instability condition, potentially generating arrhythmia.

Sudden cardiac death and inherited channelopathy: the basic electrophysiology of the myocyte and myocardium in ion channel disease.

Mutations involving cardiac ion channels result in abnormal action potential formation or propagation, leading to cardiac arrhythmias. Despite the large impact on society of sudden cardiac death resulting from such arrhythmias, understanding of the underlying cellular mechanism is poor and clinical risk stratification and treatment consequently limited. Basic research using molecular techniques, as well as animal models, has proved extremely useful in improving our knowledge of inherited arrhythmogenic syndromes.

Translational musculoskeletal science: is sarcopenia the next clinical target after osteoporosis?

Translational medicine must increasingly turn its attention to the aging population and the musculoskeletal deterioration that it entails. The latter involves the integrated function of both muscle and bone. Musculoskeletal science has an established interest in such problems in relationship to osteoporosis of bone.

Recent developments in the management of patients at risk for sudden cardiac death.

Sudden cardiac death (SCD) due to ventricular tachyarrhythmias is an important cause of mortality in the United States, 4% of which occurs in patients with structurally normal hearts. At least some arrhythmias are caused by ≥ 1 mutation in 1 of the genes that control electrical conduction through the heart by altering calcium homeostasis or depolarization or repolarization gradients in the ventricle. Although SCD may be the first presentation, patients may often present with symptoms of palpitations or hemodynamic compromise, such as dizziness, seizure, or syncope, particularly following exertion.