Abstract
Routine use of diuretics and neurohumoral activation make hypokalemia (serum K+ < 3. 5 mM) a prevalent electrolyte disorder among heart failure patients, contributing to the increased risk of ventricular arrhythmias and sudden cardiac death in heart failure. Recent experimental studies have suggested that hypokalemia-induced arrhythmias are initiated by the reduced activity of the Na+/K+-ATPase (NKA), subsequently leading to Ca2+ overload, Ca2+/Calmodulin-dependent kinase II (CaMKII) activation, and development of afterdepolarizations. In this article, we review the current mechanistic evidence of hypokalemia-induced triggered arrhythmias and discuss how molecular changes in heart failure might lower the threshold for these arrhythmias. Finally, we discuss how recent insights into hypokalemia-induced arrhythmias could have potential implications for future antiarrhythmic treatment strategies.
Highlights
Despite continuous improvements in therapies, long-term prognosis in heart failure (HF) remains poor, with overall 5-year mortality reaching 50% (Yancy et al, 2013), and even higher in more advanced stages (NYHA III-IV) (Arnold et al, 2013)
We review the current evidence for mechanisms of triggered hypokalemia-induced arrhythmias, how cardiac remodeling in HF might lower the threshold for these arrhythmias, and use this to propose future antiarrhythmic drug targets
Ventricular tachyarrhythmias are highly prevalent in HF, with 50–80% of patients having nonsustained ventricular tachyarrhythmias (VTs) on ambulatory cardiac monitoring (Singh et al, 1997; Teerlink et al, 2000)
Summary
Despite continuous improvements in therapies, long-term prognosis in heart failure (HF) remains poor, with overall 5-year mortality reaching 50% (Yancy et al, 2013), and even higher in more advanced stages (NYHA III-IV) (Arnold et al, 2013). In patients with left ventricular dysfunction there was 30– 40% increased risk of arrhythmic death among patients who used diuretics (Cooper et al, 1999) These results collectively suggest that, even though diuretics are important drugs for blood pressure reduction and prevention of volume overload in HF, being aware of the risk of hypokalemia and cardiac arrhythmias, in particular in the setting of heart disease, is important. The combination of hyperkalemia and subsequent hypokalemia with increased catecholamines during physical exercise could potentially contribute to the increased risk of cardiac arrhythmias and SCD observed during exercise in patients with structural or ischemic heart diseases (Siscovick et al, 1984; Thompson et al, 2007). Low serum-[K+] might be a cause of arrhythmias in patients even without clinically recognized hypokalemia
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