Dilated Cardiomyopathy (DCM): Practice Essentials, Background, Pathophysiology

Dear Doctor: What Is High-output Heart Failure, And How Is It Treated?

DEAR DR. ROACH: My husband is 73 and was diagnosed with heart failure and a severely dilated left ventricle. At the time, he was pumping 10 liters per minute. He had a proBNP natriuretic peptide level over 10,000 and an ejection fraction of 39%. Later, he was found to have an abdominal arteriovenous malformation (AVM). He underwent three radiological procedures to reduce the size of the AVM.

One year post-procedure, his cardiac output was 5.7 liters per minute; his proBNP level was 1,300; and his ejection fraction was 54%. Clearly, the AVM was the source of the high-output congestive heart failure, and the three embolization procedures were effective. All his symptoms disappeared after the procedures, and he feels stronger and more vital than he has in years. He hikes several miles daily, bikes occasionally, and is able to climb a sand dune without getting winded.

My question is: Does he still have a high-output diagnosis if his heart is pumping at 5.7 liters per minute? If so, what is the proper treatment for someone with this condition? He is currently being treated with minimal doses of lisinopril and Coreg. He would like to know if the dilation to his left ventricle is permanent or will diminish over time. -- K.B.

ANSWER: Heart failure is simply when the heart is unable to pump all the blood it needs to meet the body's demands. Heart failure is broken down into big two categories based on the ejection fraction (EF) of the heart, which is the percentage of blood that the left ventricle squeezes out during each beat.

The EF is normally 50% to 75%, so heart failure with an EF of less than 50% is heart failure with reduced ejection fraction (HFrEF). Meanwhile, if a person has heart failure symptoms and an ejection fraction of 50% or greater, it's heart failure with preserved ejection fraction (HFpEF).

Most cases of heart failure are due to heart disease from longstanding high blood pressure levels, repeated heart attacks, or a condition called idiopathic dilated cardiomyopathy. Your husband has a less-common cause called high-output heart failure. In his case, he has an AVM. This is a direct connection of the arteries and veins that usually occurs in the colon but can be found in other places within the gastrointestinal tract.

You can think of it as a short-circuit of the blood supply; all the oxygenated blood going through the AVM does no good at all, and the heart has to work extra hard to provide the blood that the rest of the body needs. Closing the AVM by blocking it up stops the short-circuit so the heart doesn't have to work as hard.

The best news for your husband is that his symptoms are better. But it's also great that his ejection fraction is now in the normal range and that his BNP is better. Of course, 1,300 is still very abnormal, but it's much better than 10,000.

It takes time for the heart to recover from high-output heart failure. I don't know if there still is some blood going through his AVM, but based on his symptoms, I am optimistic that most, if not all, of the underlying cause is gone. Lisinopril and carvidolol (Coreg) are very standard treatments for heart failure and help to protect the heart.

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Dr. Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers may email questions to ToYourGoodHealth@med.Cornell.Edu or send mail to 628 Virginia Dr., Orlando, FL 32803.

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This Heart Failure Gene Therapy May Be On It's Way To Clinical Trials

(HealthDay News) — Failing hearts nearly returned to full function in laboratory pigs after they received an experimental gene therapy.

New research shows the gene therapy didn't just prevent heart failure, a condition disproportionately affecting Black Americans, from worsening in four lab pigs, but actually prompted hearts to repair and grow stronger.

"Even though the animals are still facing stress on the heart to induce heart failure, we saw recovery of heart function and that the heart also stabilizes or shrinks," said co-senior researcher Dr. TingTing Hong, an associate professor of pharmacology and toxicology at the University of Utah.

"We call this reverse remodeling," Hong added in a university news release. "It's going back to what the normal heart should look like."

The gene therapy focuses on a critical heart protein called cardiac bridging integrator 1 (cBIN1). Reduced levels of cBIN1 impair the heart muscle's ability to contract.

Previous studies have shown that heart failure patients have lower levels of cBIN1, and that the lower a person's levels are, the greater their risk for severe heart problems, researchers said.

"When cBIN1 is down, we know patients are not going to do well," said co-senior researcher Dr. Robin Shaw, director of the Nora Eccles Harrison Cardiovascular Research and Training Institute at the University of Utah.  "It doesn't take a rocket scientist to say, 'What happens when we give it back?'"

For the gene therapy, researchers placed an extra copy of the cBIN1 gene into a hollowed-out virus, then injected the virus into the four pigs. The virus moved through the bloodstream to the heart, delivering the gene to heart cells.

Pigs often are used in studies of diseases that affect human organs, because their organs are similar in shape and size to those of humans.

Usually, large animals with the level of heart failure that the pigs had would die within a few months, researchers noted.

But all four pigs survived the full six-month period of the study.

What's more, some key measures of heart function improved, suggesting that the treatment prompted the damaged heart to repair itself.

The gene-treated hearts' ability to pump blood increased over time, never reaching fully healthy levels but becoming closer to normal, researchers said.

Previous heart failure treatments have improved heart function by 5% to 10%. This gene therapy caused a 30% improvement.

The hearts also regained much of the physical appearance of a healthy heart, researchers noted.

The new study was published Dec. 10 in the journal npj Regenerative Medicine.

This reversal of existing damage is highly unusual in heart failure, Shaw said.

"In the history of heart failure research, we have not seen efficacy like this," Shaw said. "It's night and day."

The gene therapy also appeared to improve heart function on a genetic level, causing heart cells and proteins to become better organized.

The research team is working with pharma company TikkunLev Therapeutics to prepare the gene therapy for use in humans. They intend to apply for FDA approval of a clinical trial by the fall of 2025.

"When you see large animal data that's really close to human physiology, it makes you think," Hong said. "This human disease, which affects more than six million Americans—maybe this is something we can cure."

Heart failure disproportionately impacts Black Americans, resulting in higher rates of hospitalization, complications, and mortality. This disparity arises from a complex interplay of factors, including socioeconomic limitations such as restricted access to quality healthcare, nutritious food, and safe living environments. Additionally, genetic predispositions, higher prevalence of comorbidities like high blood pressure, diabetes, and obesity, and disparities in lifestyle factors such as smoking rates, dietary habits, and physical activity levels contribute to this increased risk.

More information

The American Heart Association has more about heart failure.

SOURCE: University of Utah, news release, Dec. 10, 2024

Proton's Device Aims To Help Those With Kidney Disease And Cut Heart-failure Risks

People with chronic kidney disease or those at risk of heart failure are greatly affected by potassium imbalances in the body. These can even be life-threatening. While wearable glucose monitors are now commonplace and have transformed the lives of diabetes patients, potassium monitoring is in its infancy, as it's hard to do. Now startups are emerging to address the problem. 

Proton Intelligence is a Canada-based startup developing a continuous potassium monitoring product. It has now closed a $6.95 million seed round led by SOSV. Clinical trials are underway for the product, which is due to launch in 2025.

Proton is developing a small device that would be inserted just below the skin in order to monitor potassium levels. This would connect with a smartphone app so that patients can monitor their potassium levels and get notifications if their levels move out of a safe range, based on lifestyle choices like diet or medication.

A clinician dashboard will provide a view of a patient's potassium trends, and care teams will be able to use the data to fine-tune therapies.

The company was co-founded by CEO Sahan Ranamukhaarachchi (based in Vancouver, Canada) and CSO Victor Cadarso (based in Melbourne).

The two founded the startup after working on wearable biosensors as researchers in Switzerland 10 years ago. Ranamukhaarachchi went on to found a skin-based drug delivery startup (Microdermics), while Cadarso  became a professor in micro- and nano-sensors at Monash University in Melbourne. Proton has a commercial-focused HQ in Canada and a wholly owned R&D-focused subsidiary in Melbourne, Australia.

Ranamukhaarachchi told TechCrunch the team did over 100 in-depth interviews with care teams to research their product. "These highlighted the devastating consequences of 'flying blind' when managing potassium levels, because delays in monitoring often lead to preventable hospitalizations, stopping therapies, or even sudden cardiac death," he said.

He described how patients talked about "a constant fear of potassium imbalances, questioning if eating a single banana or missing a blood test" could affect their health or even put their lives at risk. 

The problem is real. Some 10% of the population worldwide is affected by chronic kidney disease, and thousands die each year because they do not have access to affordable treatment. 

Proton competes with a number of other emerging firms in the sector. 

AliveCor estimates potassium levels indirectly by detecting cardiac activity (it's raised $154.3 million to date). Alio does potassium monitoring in dialysis patients (it has raised $46 million). Renalyse out of Spain measures potassium via finger-prick blood samples (it has raised €1 million). There are, of course, several others.

That said, Proton's founders claim that its solution will be more scalable: "No other technology currently offers this level of usability, accuracy, and clinical impact," said Ranamukhaarachchi.

In a statement, Mohan S. Iyer, general partner at SOSV, said: "We are proud to be the first institutional investor in Proton Intelligence … and we are excited to continue to support them as they move into clinical validation."

The seed round also saw participation from We Venture Capital, Tenmile, LongeVC, 15th Rock, Exor, and Trampoline Venture Partners. 

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