Researchers ID potential genetic marker for tachycardia-induced cardiomyopathy
Japanese researchers believe they’ve identified a genetic risk marker that could pinpoint which people with atrial fibrillation (AFib) are at risk of developing tachycardia-induced cardiomyopathy (TIC).
“[TIC] is a supraventricular or ventricular tachyarrhythmia that is reversible after control of the underlying arrhythmia,” explained lead author Yukiko Nakano, MD, PhD, of Hiroshima University, and colleagues in Circulation: Genomic and Precision Medicine.
“There are no established diagnostic criteria for TIC, but it should be suspected in patients with left ventricular (LV) dysfunction, tachycardia of less than 100 beats/min, and satisfying the following conditions: (1) no other identified cause of ischemic or nonischemic cardiomyopathy, (2) no enlargement of end-diastolic LV dimensions, and (3) recovery of LV function after control of tachycardia by rate control, cardioversion, or radiofrequency ablation.”
The researchers enrolled 930 patients with AFib and compared them to 1,635 patients without AFib.
They found rs7164883—a single-nucleotide polymorphism (SNP) of the HCN4 gene—in 26 percent of the patients with TIC and only 9.7 percent of patients without TIC. In a replication cohort of 350 patients—41 of whom were diagnosed with TIC—the minor allele was found in 28 percent of those with TIC and 9.9 percent of individuals without TIC.
Notably, patients with AFib but no TIC had almost exactly the same prevalence of the allele as the control group without AFib.
“We think that HCN4 SNPs are potential genetic risk markers for TIC in patients with (AFib),” the authors wrote. “Stratification of TIC risk is important because it can facilitate early therapeutic intervention (eg, stricter heart rate control or early rhythm control) to prevent heart failure in patients with an HCN4 minor allele.”
The researchers said distinguishing TIC from dilated cardiomyopathy is challenging but crucial for choosing the appropriate treatment strategy. They recommended ivabradine as a potentially effective medication for TIC.
“Mechanisms by which rs7164883 regulates HCN4 function or expression are not clear,” Nakano et al. wrote. “TIC accounted for ≈10% of the total subjects, so the total number of cases was small. We therefore must validate the association between TIC and HCN4 SNP rs7164883 in a larger sample of cases and controls. Nonetheless, HCN4 SNPs are promising genetic markers for TIC and may be useful for selecting the most appropriate therapeutic intervention.”
In a related editorial, Chi-Ti Tsai, MD, PhD, agreed additional research is needed before this genetic approach can be incorporated into clinical practice.
“This is basically a single-gene genetic association study,” Tsai wrote. “The most critical part of genetic association study is the definition of disease phenotype (case and control phenotypes) and its case number. An inappropriate definition of case or control phenotype or a small case number may lead to a spurious association.”
Tsai also questioned the researchers’ definition of TIC, which involved left ventricular ejection fraction (LVEF) improving from less than 40 percent within six months of an AFib attack.
“A better definition of TIC is those with persistence of decreased LVEF when the ventricular rate is normal,” Tsai noted. “Furthermore, patients in the TIC group might have a rapid ventricular rate simply because they are not well treated, or had poor compliance to rate-control drugs. … With the confounding of drug treatment, it is difficult to clearly define which patient is having a genetic susceptibility to TIC.”
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.