Check out for genetic testing in cardiovascular diseases

The last decade has seen an explosion in cardiovascular diseases, with 60 percent of premature death attributable to cardiac causes. With high case fatality rate after cardiac events, fewer experts of advanced cardiac interventions and high cost of such interventions; disease prevention assumes a very promising and attractive solution.

Current prevention strategies revolve around lifestyle management like smoking, diet and exercise among others, which have yielded differential benefit to individuals. The gap in our understanding of this differential response might be answered by the genetic makeup of individuals. Genomic sequencing solves the dual purpose of confirming diagnosis and expanding treatment options in patients, at the same time creating a sneak peek of probable disease encoding defects in healthy individuals.

Due to rapid pace of genomic discovery, gaps in genetic literacy and paucity of big Indian trials, the genomic-based diagnostic and treatment approach is at best, overwhelming to the current cardiologists.

However at present genetic testing in India have moved beyond hematologic and cancer management and have become available for some cardiac conditions in the day to day practice as discussed, by Dr Deepesh Venkatraman, consultant interventional cardiologist, BGS Gleneagles Global Hospitals, Bangalore, below:

- Thrombotic Profile: Individuals with increased tendency for blood clotting causing disabling conditions like stroke, heart attacks and pulmonary embolism in young often remain under-diagnosed or empirically treated. A test for genetic defects in Factor V Leiden, Protein C, and MTHFR gene have proven to produce remarkable impact on preventing recurrence.

- Cardiomyopathies: Young individuals who develop reduced pumping capacity of heart or an abnormal increase in size, often have unknown etiology. Given their life threatening potential and knowing that it can result from a genetic defect, opens up a wide new set of options for prevention, early diagnosis, risk reduction (MYBC3 / MYH7 positive Hypertrophic cardiomyopathy) and sometimes curative treatment (LMNA positive Dilated cardiomyopathy).

- Channelopathies (Long QT, Brugada, CPVT etc.): Often young people who present with sudden loss of consciousness or disabling palpitation are deprived of a specific cause, as their base line ECG and Echocardiography is found to be normal. Research has unraveled a molecular defect at cell membrane level entailing these patients vulnerable to life threatening arrhythmias. Sequencing the genome in such patients, can not only confirm this defect but also give information of exact drug therapy needed and provides a tool for screening healthy family members.

- Pharmacogenomics: Some critical life-saving drugs have varied performance amongst individuals, mainly stemming from their genetic makeup. Blood thinners like Clopidogrel (CYP2C19) and Warfarin (VKORC1), which are very crucial to heart attack patients and in those with Prosthetic Valves/Deep vein thrombosis/Atrial Fibrillation, can have fatal complication upon unresponsiveness. Gene testing based dosing of these drugs are soon to be inducted in upcoming guidelines.

Genetic testing has also proven its confirmatory role in Marfans Syndrome and familial hypercholesterolemia.

Amongst the more commonly encountered clinical Cardiac conditions, Coronary artery disease and hypertension have the maximum morbidity and mortality. Their causation is multi-factorial, with an ever-increasing list of culprit genes. Societies have begun to address this complexity by devising genetic risk scores (GRS), which when incorporated with traditional risk factors have incremental prediction value. We are still far from the day when heart attacks can be prevented entirely, but genetic testing enables us to enhance our capability of identifying the people at higher risk. May be GRS based targeting of lifestyle and drug therapy in future; mitigate the menace better than ever.

Genetic testing is increasingly available in India, especially in metro cites, and all that is required is a painless cheek scrapping. The tests are becoming more affordable with time. A targeted study of specific gene requires only a few thousand rupees, and the more comprehensive complete genome sequencing with 100 GB of data, being available for just over a lakh. The future will see the tests being more readily available, with larger spectrum of options and at a more moderated price.

The flip side of the trajectory is the unpreparedness of the Patients, Doctors and the Genetists to precisely interpret the results, and has a potential to complicate management, increase anxiety in the asymptomatic individuals with mutations of unknown significance, and increase the price of health care in our cost constrained society.

"As things stand, Genetic testing has a role in a very narrow subset of rare cardiac disorders, and for the larger and more relevant entities, it is a scientific astrology at best, which risks burning the peace of mind and the pocket at the same time. Hence a self-testing is discouraged and a, informed cardiologist should only prescribe the right tests for proven indications," said Dr. Deepesh Venkatraman.