12-lead ECG
The resting 12-lead ECG is a useful test to differentiate CPVT from other electrical diseases of the heart that can cause similar abnormal heart rhythms. Unlike conditions such as long QT syndrome and Brugada syndrome, the resting 12-lead ECG in those with CPVT is generally normal. However, approximately 20% of those affected have a slow resting heart rate or sinus bradycardia. Exercise and other provocative testing
Exercise testing, commonly performed on a treadmill or stationary bicycle, can help to diagnose CPVT. During the test, those with CPVT often experience ectopic beats, which may progress to bidirectional and then polymorphic ventricular tachycardia as the intensity of exercise increases. Some of those suspected of having CPVT, such as young children, may not be able to perform an exercise tolerance test. In these cases, alternative forms of testing include adrenaline provocation testing, during which adrenaline is infused into a vein at gradually increasing doses under close supervision and ECG monitoring. Additionally, long term or Holter ECG monitoring can be performed, although this form of testing is less likely to detect an arrhythmia. Invasive electrophysiological studies do not provide useful information to help diagnose CPVT or to assess the risk of life-threatening arrhythmias. Genetic testing
CPVT can also be diagnosed by identifying a disease-causing mutation in a gene associated with CPVT using genetic testing. This technique may be the only way to identify the condition in someone suspected of having CPVT who has died, and in this case may be known as a molecular autopsy.
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.