How to Achieve Left Ventricular Reverse Remodeling and Improve Outcomes in Heart Failure? Summary from HFA ESC Webinar
The current treatment algorithm for chronic heart failure with reduced ejection fraction (HFrEF) is well-known to clinicians. But how was its current form developed, and does it have the potential to change in the future? Experts discussed this and more at a web symposium on reverse remodeling sponsored by Novartis during the Heart Failure Association of the European Society of Cardiology (HFA ESC) congress. Notable presenters included HFA ESC President Professor Petar Seferovic and Professor Carolyn Lam from the National Heart Centre in Singapore.
The Vicious Cycle of Remodeling in Heart Failure
Cardiac remodeling represents changes in the volume, mass, shape, and structure of the left ventricle, which occur in response to mechanical and neurohormonal alterations associated with heart failure. These changes are triggered by an initiating factor (such as ischemia, conduction disorders, high blood pressure, etc.), leading to the progressive development of remodeling, decreased functional capacity of patients, and increased risk of cardiac events and sudden cardiac death. With each subsequent acute event, the patient's situation deteriorates dramatically, creating a vicious cycle of cardiac remodeling with a devastating impact on the quality of life and prognosis. Patients with a high degree of cardiac remodeling, including those treated on an outpatient basis, are at high risk for hospitalization and death.
Fortunately, we have therapeutic approaches that can prevent, halt, or even reverse cardiac remodeling. These include neurohormonal blockade through renin-angiotensin-aldosterone system blockers and beta-blockers, which are the first choice and gold standard for patients with HFrEF. Cardiac resynchronization therapy (CRT) achieves this effect in patients with a wide QRS complex.
Reverse Remodeling with ARNI Therapy: Impact on Prognosis and the Importance of Early Initiation
The ability to induce reverse remodeling of the left ventricle has also been demonstrated by the only representative of the angiotensin receptor-neprilysin inhibitor (ARNI) group, sacubitril/valsartan, even in patients who have not responded adequately to established ACEi/ARBs and MRA treatments at recommended doses. Studies such as PROVE-HF, EVALUATE-HF, PRIME, and others have shown positive improvements in remodeling parameters, including increases in left ventricular ejection fraction (LVEF), reductions in LV end-systolic and end-diastolic volumes, and decreases in functional mitral regurgitation, as well as reductions in biomarkers of cardiac fibrosis and improvements in patient prognosis following the initiation of sacubitril/valsartan therapy. Furthermore, outcomes were shown to be dose-dependent. The PIONEER-HF and TRANSITION studies shed more light on the optimal timing of ARNI therapy initiation, which should ideally begin as early as possible, even during hospitalization for acute HFrEF exacerbation, to achieve the best results.
Room for Development in Clinical Guidelines
These findings have been reflected in the latest clinical practice guidelines issued by the HFA ESC in 2019, which mention the possibility of considering ARNI therapy initiation in indicated cases, even for patients not previously treated with ACEi/ARBs/MRA.
Conversely, a stepwise approach to therapy is embedded in the latest ESC guidelines from 2016 (currently the basis for drug reimbursement). As Professor Lam emphasized, the design of these guidelines was solely based on clinical trial results, with new drugs always being additions to standard therapy. However, this does not mean that earlier initiation cannot benefit patients. On the contrary, a number of studies published since the initial findings of the PARADIGM trial in 2016 support the significant benefits of earlier ARNI initiation, not only for reverse remodeling but also for impacts on glycemia, renal function, congestion, etc., ultimately reducing mortality associated with HFrEF.
The presenters also outlined a potential future treatment algorithm, in which first-choice therapy would be positioned on a horizontal line alongside MRA, ARNI, and dapagliflozin. Although the lack of corresponding clinical trials currently makes this a vision for the future, it remains crucial to strive for the prescription of sacubitril/valsartan in indicated cases, as it is still underprescribed.
(luko)
Source: Lam C. S., Seferovic P., Mullens W., Guazzi M. Reversing cardiac remodeling and improving outcomes in heart failure: what are our first-choice treatments? Novartis Symposium. ESC-HFA Discoveries 2020 Jun 5.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.