European Society of Cardiology

European Society of Cardiology

Source:

Ho C, et al. Late-Breaking Science in Heart Failure. Presented at: European Society of Cardiology Congress; Aug. 27-30, 2021 (virtual meeting).

Disclosures: The study drug was donated by Novartis. The authors report no relevant financial disclosures.
September 01, 2021
2 min read
Save

Valsartan stunts disease progression in early-stage sarcomeric hypertrophic cardiomyopathy

Source:

Ho C, et al. Late-Breaking Science in Heart Failure. Presented at: European Society of Cardiology Congress; Aug. 27-30, 2021 (virtual meeting).

Disclosures: The study drug was donated by Novartis. The authors report no relevant financial disclosures.
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

In patients with early-stage sarcomeric hypertrophic cardiomyopathy, valsartan improved certain parameters of disease progression compared with placebo, researchers reported at the European Society of Cardiology Congress.

Carolyn Y. Ho

“In many individuals, [hypertrophic cardiomyopathy] is oftentimes genetic, caused by pathogenic variants in sarcomeric genes. These variants account for at least 65% of familial [hypertrophic cardiomyopathy] and are most commonly involving variants in myosin-binding protein C and myosin heavy chain,” Carolyn Y. Ho, MD, medical director of the Cardiovascular Genetics Center at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, said during a presentation.

Heart
Source: Adobe Stock

Studies in mouse models of HCM showed that activation of transforming growth factor (TGF)-beta played a major role in upregulation of profibrotic genetic pathways leading to clinically overt disease, and that losartan, an angiotensin receptor blocker which has some ability to inhibit TGF-beta activation, reduced the development of left ventricular hypertrophy and myocardial fibrosis; moreover, treatment was most beneficial when started early before onset of LV hypertrophy, Ho said.

For the VANISH trial, the researchers randomly assigned 178 asymptomatic patients with pathogenic variants in sarcomeric genes (mean age, 23.5 years; 39% female) to valsartan, an angiotensin receptor blocker, 320 mg per day or placebo for 2 years.

Ho said a standard analysis plan was unlikely to be successful due to low likelihood of CV events in a short follow-up time, so the primary outcome was change in a composite z score between baseline and year 2; the z score included a composite of nine metrics of cardiac structure or function. An increase (positive change) in the composite z score indicates improvement, whereas a decrease indicates worsening. 

For the composite z score, the adjusted mean change at 2 years was –0.095 in the placebo group vs. 0.136 in the valsartan group (between-group difference, 0.231; 95% CI, 0.098-0.364; P = .001), Ho said during the presentation.

The following components of the composite favored the valsartan group at 2 years:

  • N-terminal pro-B-type natriuretic peptide (between-group difference, –0.25 pg/mL; 95% CI, –0.47 to –0.03; P = .025);
  • LV end-diastolic volume index (between-group difference, 4.1 mL/m2; 95% CI, 0.06-8.14; P = .047); and
  • E’ velocity (between-group difference, 0.35 cm/sec; 95% CI, 0.06-0.63; P = .017).

The results did not vary by sex, age or disease-causing gene, but the treatment effect of valsartan was greater in those who had baseline z score of LV wall thickness of 7.3 or below than in those who did not (P for interaction = .04), she said.

She said the difference in treatment effect by LV wall thickness “supports the hypothesis that disease-modifying therapy may be most effective if given early in the disease to individuals with less cardiac remodeling.”

Serious adverse events were similar between the groups, and there were no cases of hypotension, hyperkalemia or renal insufficiency, Ho said.

“Disease progression stabilized or potentially improved” in the valsartan group, Ho said during the presentation. “The VANISH trial suggests there is an opportunity to attenuate disease progression in sarcomeric HCM with a widely available and well-tolerated medication.”