Verici...WHAAAT?

After reading the latest Heart Failure (HF) guidelines, I had to acknowledge the massive difference from those of just five years ago. Here are a few key points I want to highlight before diving into vericiguat:

HF is a syndrome. Mix everything

HF results from an impairment in the function AND/OR structure of the heart, leading to elevated intracardiac pressure AND/OR inadequate cardiac output at rest AND/OR during exercise. 

The number of times the guideline says "AND/OR" is truly impressive.

HF can have preserved cardiac output (>50% EF), mildly reduced (40–49%), or reduced (The classic <40%).

Then, of course, there are the stages:

Stage A: Just risk factors—nothing too dramatic.

Stage B (Pre-HF): Structural changes show up on echocardiography, but no symptoms yet.

Stage C: Et voilà —breathlessness, ankle swelling, fatigue, JVP elevation, pulmonary crackles, peripheral edema. Maybe you’ll even catch the point of maximal impulse shift or, for the experts, the elusive S3 (rare AND/OR specific, naturally).

Stage D: The grand finale—symptoms become refractory, second-line therapies enter the chat, and, in some cases, it’s time to consider replacing the whole heart.

The "Fantastic Four" of HF with Reduced EF: If they had characters, here’s how I’d cast them:

Mr. Fantastic – Beta-blockers

"Obviously, it’s SGLT2 inhibitors, they work for EVERYTHING!"

Nope⛔. It’s beta-blockers. They started it all and hold the team together.

Invisible Woman – ARNI

It’s not SGLT2 inhibitors (they’re very visible right now). Instead, it’s ARNI, a dual-action drug: angiotensin receptor inhibition + preventing natriuretic peptide degradation. Just like the character, it has two distinct yet similar superpowers.

Human Torch – SGLT2 inhibitors 🔥🔥🔥

Bursting onto the scene. They do not need presentation.

The Thing – MRA

Mineralocorticoid receptor antagonists. Why "The Thing"? Because minerals… like rocks. -Sorry, It made sense in my mind-.

Now we’re ready for Vericiguat...

A guanylate cyclase stimulator used in HF with reduced EF. It increases phosphokinase G levels, leading to cellular hyperpolarization and cardiac muscle relaxation.

And what does VICTORIA say? (Not the person—the clinical trial: Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction).

"Vericiguat has a beneficial effect with a hazard ratio of 0.90 (95% CI: 0.82 – 0.98; P=0.02) for cardiovascular death and first heart failure hospitalization."

 

The future of the "Fantastic Four"?

Meet Omecamtiv Mecarbil—a cardiac myosin activator that works independently of calcium levels. In the GALACTIC-HF trial (Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure), it showed an 8% reduction in first HF events or CV death.

Could it be our next superhero? Maybe. Will it ever be as famous as SGLT2 inhibitors? I highly doubt it.

😎Vyas A, Onteddu N. Vericiguat. [Updated 2023 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574528/

 
Image: Eur Heart J. 2021 Feb 7; 42(6): 681–683.