Author + information
- Ning Jiang,
- Anyu Zhou,
- Guangbin Shi,
- Ruiping Ji,
- Peter Kennel,
- Paul Schulze and
- Samuel C. Dudley Jr.
Background: Heart failure and hypoxia downregulate cardiac sodium channel (SCN5A) mRNA and upregulate its mRNA splicing variant D (VD), which correlates with arrhythmic events in a heart failure population. In addition, heart failure is known to be associated with a reduction in L-type calcium channel (L-Ca) levels. Ventricular assist device (VAD) can restore cardiac output in patients with advanced heart failure and significantly improves both survival and quality of life. Nevertheless, the mechanisms are unclear. We tested whether VAD altered full-length SCN5A mRNA, SCN5A VD or L-Ca expression in the myocardium and further investigate its molecular modulation.
Methods: Cardiac tissue was obtained from advanced heart failure patients before VAD implantation and at the time of heart transplantation. L-Ca, SCN5A, VD and hypoxia-inducible factor (HIF) (1α, 2α, 3α) levels from left ventricle were compared at VAD implantation and at heart transplantation using the ratio of L-Ca to β-actin, HIF to β-actin or VD to total SCN5A transcripts.
Results: A total of 16 samples from heart failure patients were collected. The average duration of VAD was 289 days (range from 138 to 655 days). Compared with the mRNA level before VAD, SCN5A VD levels were significantly reduced from 1.52±0.47 to 1.06± 0.31 (P<0.05). HIF1α, released in response to tissue hypoxia, was markedly reduced (1.03±0.60 vs. 0.69±0.54, P<0.05) over the same period in patients receiving VAD. There was a significant correlation between the mRNA expression of HIF1α and VD (r=0.584, p<0.05). Nevertheless, there was no significant changes in HIF 2α or HIF 3α levels. After VAD implantation, patients had higher L-Ca mRNA (1.09±0.81 vs. 0.39±0.46, P<0.05) which might reflect the improvement of excitation/contraction coupling in the heart.
Conclusions: VAD results in molecular changes including a decreased proportion of nonfunctional sodium channels and improved L-Ca mRNA expression. These changes may help explain reductions in arrhythmias and improved contractility with VAD.
Poster Hall, Hall C
Sunday, March 19, 2017, 9:45 a.m.-10:30 a.m.
Session Title: The Evolving World of LVADs, Transplant and Other Novel Discoveries
Abstract Category: 13. Heart Failure and Cardiomyopathies: Clinical
Presentation Number: 1294-267
- 2017 American College of Cardiology Foundation