Citations 2
A Roadmap for Therapeutic Discovery in Pulmonary Hypertension Associated with Left Heart Failure. A Scientific Statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function
Pollesello, Piero , Anker, Markus S. , Backs, Johannes , Bayés‐Genís, Antoni , González, Aránzazu , Maack, Cristoph, Madden, Brendan , Redfield, Margaret M. , Rich, Stuart , Schiattarella, Gabriele G. , Skaara, Hall, Stellos, Konstantinos , Vachiéry, Jean Luc, Meer, Peter van der, Linthout, Sophie Van , Pruszczyk, Piotr , Seferović, Petar , Metra, Marco , Rosano, Giuseppe, Tocchetti, Carlo G. , Schiattarella, Gabriele G. , Stellos, Konstantinos , Metra, Marco , Tocchetti, Carlo Gabriele , Ameri, Pietro , Mercurio, Valentina , Borlaug, Barry A. , Burkhoff, Daniel , Caravita, Sergio , Chan, Stephen Y. , Man, Frances S. de , Giannakoulas, George , Guazzi, Marco , Hassoun, Paul M. , Hemnes, Anna R. , Melenovský, Vojtěch , Müller, Oliver Josef , Papp, Zoltán , Pullamsetti, Soni Savai , Rainer, Peter P. , Tedford, Ryan J. , Thum, Thomas , Vachiéry, Jean‐Luc , Meer, Peter van der , Coats, Andrew J.S. , Rosenkranz, Stephan
European Journal of Heart Failure | April 19, 2024 | Volume: 26 | Issue: 4 | Pages: 707-729
Abstract Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF.
Complex electrophysiological remodeling in postinfarction ischemic heart failure
Hegyi, Bence , Bossuyt, Julie , Griffiths, Leigh G. , Shimkunas, Rafael, Coulibaly, Zana, Jian, Zhong , Grimsrud, Kristin, Søndergaard, Claus S., Ginsburg, Kenneth S., Chiamvimonvat, Nipavan , Belardinelli, Luiz, Varró, András , Papp, Julius Gy., Pollesello, Piero , Levijoki, Jouko , Izu, Leighton T. , Boyd, W. Douglas, Bers, Donald M. , Chen‐Izu, Ye , Griffiths, Leigh G , Bányász, Tamás
Proceedings of the National Academy of Sciences | March 12, 2018 | Volume: 115 | Issue: 13 | Pages: No page available
Significance Cardiac arrhythmias often occur in heart failure (HF) patients, but drug therapies using selective ion channel blockers have failed clinical trials and effective drug therapies remain elusive. Here we systematically study the major ionic currents during the cardiac action potential (AP) and arrhythmogenic Ca 2+ release in postinfarction HF. We found that changes in any individual current are relatively small, and alone could mislead as to consequences. However, differential changes in multiple currents integrate to shorten AP in the infarct border zone but prolong AP in the remote zone, increasing AP repolarization inhomogeneity. Our findings help explain why single channel-blocker therapy may fail, and highlight the need to understand the integrated changes of ionic currents in treating arrhythmias in HF.