Recently published data suggest that the use of selective beta blockers, such as atenolol, bisoprolol, or metoprolol, is associated with very high treatment failure rates.Flecainide is a class 1c antiarrhythmic drug that is recommended for those with CPVT who experience abnormal heart rhythms despite taking a beta blocker. Flecainide reduces the risk of arrhythmias in those with CPVT, but it remains uncertain how Flecainide achieves this. Some have suggested that Flecainide directly interacts with the cardiac ryanodine receptor, which is frequently abnormal in those with CPVT, while other suggest that the anti-arrhythmic effects of Flecainide rely entirely on its sodium channel blocking effects.Verapamil is a calcium channel antagonist that, when combined with a beta blocker, may reduce the risk of arrhythmias in patients with CPVT. Propafenone is another antiarrhythmic that may reduce the risk of arrhythmias, potentially through direct effects on the ryanodine receptor. Sympathetic denervation
Some persons with CPVT continue to experience life-threatening arrhythmias despite pharmaceutical therapy. In this case a surgical procedure can be used to affect nerves supplying the heart that communicate using catecholamines. A collection of nerves known as the sympathetic nervous system supply the heart as well as other organs. These nerves, when activated, encourage the heart to beat harder and faster. The sympathetic nervous system uses noradrenaline, a catecholamine, as a chemical messenger or neurotransmitter, which can promote arrhythmias in those with CPVT.To prevent this, a region of the sympathetic nervous system can be intentionally damaged in an operation known as cardiac sympathetic denervation or sympathectomy.
The higher peaks in free calcium have greater potential to cause store-overload induced calcium release from the sarcoplasmic reticulum, leading to afterdepolarisations.In addition to its role as a calcium buffer, calsequestrin also regulates the release of calcium from the sarcoplasmic reticulum by directly modulating ryanodine receptors. When the concentration of calcium is low, calsequestrin monomers form a complex with the proteins triadin and junctin, which inhibit ryanodine receptors. However, at high calcium concentrations, calsequestrin forms polymers that dissociate from the ryanodine receptor channel complex, removing the inhibitory response and increasing the sensitivity of the ryanodine receptor to spontaneously releasing calcium.Decreased CASQ2 is also associated with high levels of calreticulin, a protein which among other roles regulates the reuptake of calcium into the sarcoplasmic reticulum by SERCA. In the absence of CASQ2, calreticulin levels increase and provide some compensatory calcium binding within the sarcoplasmic reticulum. It is possible that calreticulin may contribute to the generation of arrhythmias seen in association with CASQ2 mutations. Diagnosis
CPVT may be challenging to diagnose as the structure of the heart appears normal in those affected by the condition when assessed using an echocardiogram, cardiac MRI scan or cardiac CT scan, while the electrical function of the heart also appears normal at rest when assessed using a standard 12-lead ECG. However, in response to exercise or catecholamines such as adrenaline, abnormal heart rhythms such as bidirectional ventricular tachycardia or frequent polymorphic ventricular ectopic beats may be seen.