Matters Of The Heart
The words “heart failure” might bring to mind a chubby businessman clutching his chest and keeling over at the steakhouse. The reality is more nuanced. Medically, the phrase refers to a chronic condition that affects multitudes. Nearly 6 million people in the U.S. are affected, and over 23 million worldwide. Your lifetime risk of developing heart failure is an unnerving one in five.
This WEEKLY explores the diagnosis and symptoms of this painful, often deadly condition. Then we look at current treatments and promising new developments.
Term Of The Week: Heart Failure
Known also as chronic or congestive heart failure, the disease occurs when the heart can no longer pump and/or fill with blood normally. Its causes are complex and varied. Risk factors include high blood pressure, diabetes, coronary artery disease—the narrowing of blood vessels brought on by cholesterol-containing plaque—and previous heart attacks. Viral infections can also weaken heart muscle, making it more vulnerable. According to the Mayo Clinic, (Rochester, MN) symptoms include shortness of breath, fatigue and weakness, swelling in legs, ankles, and feet, and rapid or irregular heartbeat.
Three Flavors Of Heartache
Health care providers divide heart failure into three categories: left-sided, right-sided and congestive. As everyone no doubt remembers from tenth-grade biology, the heart’s left side pumps oxygen-filled blood into the body. The right side pumps blood from the body into the lungs for re-oxygenating.
- Left-sided: When this side fails to contract normally, it no longer exerts enough force to push blood into circulation. That weakness also means the muscle can no longer relax completely, so it also fails to replenish its blood supply.
- Right-sided: This usually results from left-side failure. When blood builds up on left side of heart, the resulting increase in pressure on right side inflicts damage.
- Congestive: As blood flow out of the heart slows, blood returning through the veins backs up. The back-up leads to congestion and swelling.
Doctors may suspect heart failure based on a combination of symptoms and risk factors. A variety of tests can confirm a diagnosis, including X-rays to check for enlarged heart or lung congestion, EKG to detect enlarged heart muscle and abnormal rhythms, or an exercise stress test to observe how a patient responds to physical activity.
The Biotech Twist
Diagnosis isn’t all monitors and treadmills though. Sometimes a single vial of blood uncovers elevated levels of one of the cardiac hormones—a B-type natriuretic peptide (BNP) in the blood. This protein is a hormone produced by heart muscle. During heart failure, muscle cells are stretched as the heart swells with blood that isn’t being pumped out efficiently. Stretching releases BNP into the blood.
A blood test provides only one of many ways to find heart failure. However, they’re especially helpful as a screening tool for early stage cases. Doctors also use them to rule out heart failure in emergencies and to monitor people already undergoing treatment. BNP tests on the market include Biosite’s (San Diego, CA) Triage BNP test, Bayer Healthcare Diagnostics’ (Tarrytown, NY) ADVIA Centaur assay, Abbott Diagnostic’s (Abbott Park, IL) AxSym BNP assay, Roche Diagnostic’s (Indianapolis, IN) Elecsys NT-proBNP assay, Dade Behring’s (Deerfield, IL) Dimension test and Stratus Acute Care NT-proBNP assay.
Mending Those Broken Hearts
A major breakthrough came in 2015, with Novartis’ (Basel, Switzerland) Entresto. The company made headlines when it became obvious that its new product treated heart failure so much more effectively than the existing standard of care that continuing the trial would be unethical. Entresto combines two drugs: Valsartan and Sacubitril. Together, they lower blood pressure. In turn, this reduces strain on the heart and how much fluid accumulates in the lungs and other tissues.
Valsartan is an angiotensin II receptor inhibitor. When this small hormone attaches to its receptor, it unleashes a chain of reactions. These ultimately cause blood vessels to constrict, raising blood pressure. It’s all about physics: it takes more pressure to move fluid through a narrow tube (or artery) than through a wide one. Angiotensin II also promotes the release of aldosterone. This hormone increases how much sodium our kidneys retain, further driving up blood pressure. By blocking its receptor, angiotensin II has nowhere to land. That prevents the cascade of doom—keeping blood vessels nice and open, lowering blood pressure.
Sacubitril inhibits neprilysin inhibitor. Neprilysin breaks down a hormone called natriuretic peptide. By stopping neprilysin, we increase levels of natriuretic peptide. Natriuretic peptide gets rid of sodium and dilates blood vessels; therefore, blood pressure is lowered. By combining an angiotensin II receptor inhibitor and a neprilysin inhibitor, the effect is enhanced.
More Steps In The Right Direction
There are currently a number of treatments in Phase III clinical studies:
- Vericiguat (Bayer; Leverkusen, Germany): activates soluble guanylyl receptor (sGC), the only known receptor for nitric oxide. This causes blood vessels to relax (vasodilation), increasing blood flow.
- Omecamtiv mecerbil (Amgen; Thousand Oaks, CA): switches on the protein myosin, which is vital for heart muscle contraction This mechanism results in prolonged contraction, revving up the heart’s ability to pump.
- RT-100 (Renova Therapeutics; San Diego): this gene therapy delivers the adenylyl cyclase type 6 (AC6) gene. The protein regulates heart function. It’s found at lower than normal levels in cardiac patients.
If any of these products make it to the finish line of FDA approval, heart failure patients and their doctors will have one more weapon in their arsenal.
Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.