Heart Failure 1st edition by Johann Bauersachs, Javed Butler, Peter Sandner ISBN 3319866737 978-3319866734

1. Introduction

This section would set the stage for understanding heart failure (HF), its importance in cardiovascular health, and the need for better therapies.

2. Epidemiology

The epidemiology of heart failure highlights the prevalence, incidence, and impact of HF on populations worldwide, with particular attention to factors such as age, comorbidities, and risk factors that contribute to its growing burden.

3. Clinical Trial Design, Endpoints, and Regulatory Requirements

Discusses the design of clinical trials for heart failure treatments, focusing on important endpoints (e.g., mortality, hospitalizations, quality of life) and regulatory challenges in developing new therapies. It would also touch on regulatory frameworks used by agencies like the FDA and EMA.

4. Biomarkers in HFpEF/HFrEF

• HFpEF (Heart Failure with Preserved Ejection Fraction) and HFrEF (Heart Failure with Reduced Ejection Fraction) are two forms of heart failure with distinct pathophysiology and biomarkers.

• This section explores the biomarkers used to diagnose, monitor, and prognosticate both conditions, such as B-type natriuretic peptide (BNP), galectin-3, and others.

5. Imaging Technologies / MRI and Echo

Imaging technologies like Magnetic Resonance Imaging (MRI) and Echocardiography (Echo) play crucial roles in diagnosing heart failure, assessing cardiac function, and evaluating treatment response.

6. Comorbidities in HF

Heart failure often occurs alongside other diseases such as hypertension, diabetes, chronic kidney disease, and atrial fibrillation. This section highlights the impact of these comorbidities on disease progression and treatment.

7. Current Guideline-Based Therapy for HFrEF and HFpEF

• HFrEF: Standard treatments include ACE inhibitors, beta-blockers, aldosterone antagonists, and ARNIs (angiotensin receptor-neprilysin inhibitors).

• HFpEF: Management typically focuses on controlling comorbidities like hypertension and diabetes, though effective therapies are less well-defined compared to HFrEF.

8. New and Emerging Therapies and Targets

Focuses on novel treatments and biological targets in heart failure, such as:

• Ivabradine: A drug that reduces heart rate, useful in HFrEF.

• Beta-3 Agonists: Involved in regulating cardiac function and energy metabolism.

• Novel MRAs (Mineralocorticoid Receptor Antagonists): These may offer better efficacy and safety profiles compared to current MRAs.

• pGCs (particulate Guanylate Cyclase) and Natriuretic Peptides: Agents that help regulate vasodilation and natriuresis.

• sGC Stimulators: Drugs that enhance cyclic GMP production to improve cardiac function.

• PDE Inhibitors: Target phosphodiesterase to improve cardiac performance.

• Adenosine A1 Agonists: Modulating adenosine receptors to reduce myocardial oxygen demand.

• Myosin Heavy Chain/Troponin Activation: Approaches aimed at improving myocardial contraction.

• Stem Cells: Explores regenerative therapies using stem cells to repair damaged heart tissue.

9. Diuretics and Vasopressin

• Diuretics: Still the mainstay for fluid management in heart failure, addressing volume overload.

• Vasopressin: A hormone that could be targeted to manage fluid balance more effectively.

10. Gene Therapy

Gene-based therapies are emerging as potential treatments for heart failure, aimed at correcting underlying genetic defects or enhancing heart regeneration.

11. RNA-Based Therapies and MicroRNAs

• Investigates the role of RNA-based therapies, including antisense oligonucleotides and microRNAs, to modulate gene expression in heart failure.

12. Cardiac Myosin Activation Using Gene Therapy

Gene therapy to activate cardiac myosin, potentially improving myocardial contractility and efficiency, holds promise for treating heart failure.

13. Bendavia – Mitochondrial Therapies

Bendavia and other mitochondrial-targeting therapies aim to improve mitochondrial function and energy production in heart cells, which can be crucial in heart failure management.

14. WNT Signaling

WNT signaling pathways are involved in cardiac regeneration and repair. Modulating these pathways could offer new approaches to heart failure therapy, particularly for reversing fibrosis and promoting tissue repair.

15. Anticoagulation Therapy and NOACs in HF

• Anticoagulation: Used in heart failure patients with atrial fibrillation to reduce the risk of stroke.

• NOACs (Non-Vitamin K Oral Anticoagulants): These newer anticoagulants offer advantages over traditional therapies like warfarin in managing stroke risk in heart failure patients.

16. Potassium Binders

These agents are used to manage hyperkalemia, a common side effect of medications such as MRAs and ACE inhibitors.

17. Iron in Heart Failure

Iron deficiency is common in heart failure and can worsen symptoms. Iron supplementation, including intravenous iron, is an emerging treatment to improve outcomes in heart failure patients with iron deficiency.