SESSION TITLE: Late-Breaking Abstracts
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Tuesday, October 29, 2013 at 04:30 PM - 05:30 PM
PURPOSE: The finding of an elevated pulmonary arterial pressure (PAP) on echocardiography is common; when further evaluated, a large and rapidly growing proportion of these individuals will have pulmonary venous hypertension, increasingly from left ventricular (LV) diastolic dysfunction (heart failure with preserved ejection fraction; HFpEF). Among these patients, pulmonary hypertension (PH) is a poor prognostic indicator. Although there are extensive data for treating WHO Group 1 PH (PAH), there exist little data on treatment of WHO Group 2 PH. Ranolazine has been shown to improve LV wall stiffness and diastolic function in animals; however, there is currently no information about its use in patients with PH associated with diastolic dysfunction.
METHODS: In this 6 month, open-label pilot study of 10 patients with PH associated with HFpEF we evaluated the effect of ranolazine in this entity. Subject eligibility for inclusion included: age 21-75; NYHA/WHO FC II-III; 6MWD >150m and <450m; LVEF>50% and no significant valvular disease by echocardiography; mPAP>25mmHg, PCWP >18mmHg and <30mmHg, and pulmonary artery diastolic pressure (PADP)-PCWP gradient <10 by RHC. Evaluations during the trial included: FC, 6MWD, Borg dyspnea index (BDI), BNP, troponin, echocardiography, cardiac MRI (CMRI) and invasive hemodynamics at baseline and after 6mo of ranolazine (1000mg bid).
RESULTS: 80% of the participants were female; average age was 63 and average BMI 41.6; 100% were hypertensive; 80% were diabetic; 80% were dyslipidemic. After 6mo of ranolazine, there were significant improvements in FC (50% improved from III to II), 6MWD (+33m; 286m to 319m), mPAP (39mmHg to 23mmHg), and PCWP (22mmHg to 13mmHg). BDI, echocardiographic parameters, BNP and troponin did not change. Changes in CMRI were subtle and their significance is not clear. One patient discontinued the study due to symptomatic bradyarrhythmia. Four subjects have continued ranolazine for 1y; improvements in FC and 6MW have been maintained.
CONCLUSIONS: These observations suggest that ranolazine may be a promising treatment for PH associated with HFpEF
CLINICAL IMPLICATIONS: Further study of ranolazine in PH associated with PH associated with HFpEF is warranted.
DISCLOSURE: Harrison Farber: Grant monies (from industry related sources): Grant from Gilead for this project Kimberly Finch: Grant monies (from industry related sources): Salary in aprt supported by a grant from Gilead for this project Eric Stratton: Grant monies (from industry related sources): salary support in part from ta Gilead grant for this project
Off-label (investigational) use of ranolazine for pulmonary hypertension associated with LV diastolic dysfunction (HFpEF)