November 2023 - Theresa-Marie Dachs

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Dr. Theresa-Marie Dachs

MedUni Wien RESEARCHER OF THE MONTH November 2023

The majority of patients suffering from heart failure with preserved ejection fraction (HFpEF) develop pulmonary hypertension (PH), which has been associated with worse outcome. To date, no targeted treatment exists for patients suffering from PH-HFpEF. Diseases of the heart failure and PH spectrum typically display endothelial dysfunction and nitric oxide (NO) deficiency which result in enhanced vasoconstriction, inflammation, proliferatory and fibrotic effects. Riociguat, an oral soluble guanylate cyclase (sGC) stimulator, counteracts these pathologic processes via direct stimulation of sGC and sensitization of sGC to circulating NO.

The phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicenter DYNAMIC trial investigated the efficacy of chronic treatment with riociguat in patients with PH-HFpEF. After completion of the 26-week study period, cardiac output (CO) at rest as the primary endpoint and further secondary haemodynamic endpoints increased significantly in response to riociguat. Dropout rates varied in favor of placebo due to mild and moderate adverse events, however no riociguat-related serious adverse events occurred.

Overall, the DYNAMIC trial yielded important insights regarding the potential benefit of riociguat for the treatment of patients suffering from PH-HFpEF, aiding in the search for targeted treatment.

Selected Literature

1. Dachs TM, Duca F, Rettl R, Binder-Rodriguez C, Dalos D, Camuz Ligios L, Kammerlander A Grünig E, Pretsch I, Steringer-Mascherbauer R, Ablasser K, Wargenau M, Mascherbauer J, Lang IM, Hengstenberg C, Badr-Eslam R, Kastner J, Bonderman D. Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial. European Heart Journal. 2022 Jul (IF: 35.855).

2. Badr Eslam R, Öztürk B, Rettl R, Capelle C, Qin H, Binder C, Dachs TM, Camuz Ligios L, Duca F, Dalos D, Schrutka L, Alasti F, Kastner J, Vila G, and Bonderman D. Impact of tafamidis and optimal background treatment on physical performance in patients with transthyretin amyloid cardiomyopathy. Circulation: Heart failure. 2022 Jul (IF: 8.790).

3. Schrutka L, Seirer B, Rettl R, Dachs TM, Binder-Rodriguez C, Duca F, Dalos D, Badr-Eslam R, Kastner J, Hengstenberg C, Frommlet F, Bonderman D. Heart failure with preserved ejection fraction: Calculating the risk of future heart failure events and death. Front. Cardiovasc. Med. 2022 Oct (IF: 6.050).

4. Hauck SR, Kern M, Dachs TM, Haider L, Stelzmüller ME, Ehrlich M, Loewe C, Funovics MA. Applicability of endovascular branched and fenestrated aortic arch repair devices to treat residual type A dissection after ascending replacement. Journal of Vascular Surgery. 2022 Aug (IF: 4.268)

5. Dachs TM, Hauck SR, Kern M, Klausenitz C, Funovics M. Fenestrierte und verzweigte endovaskuläre Aortenprothesen – ein Update. Der Radiologe. 2022 Jun (IF: 0.635).