Can a heart failure drug help treat long COVID symptoms?

• Some people who have recovered from COVID-19 experience ongoing symptoms — such as brain fog, increased heart rate, and chronic fatigue — sometimes known as long COVID.
• There is an overlap between the symptoms of long COVID and postural orthostatic tachycardia syndrome (POTS), which has led some researchers to suggest they are related.
• A small clinical trial suggests that ivabradine, a drug approved for use in heart failure, may be an effective treatment for POTS, with fewer side effects than existing treatments.

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An estimated 1–3 million people in the United States have POTS, which causes tachycardia — a rapid heart rate of more than 100 beats per minute — when a person stands up.

Other common symptoms include:

• poor concentration, or brain fog
• lightheadedness, dizziness, or fainting
• blurred vision
• palpitations
• nausea
• tiredness

The condition predominantly affects females between the ages of 15 and 50, but males can develop it as well.

Patients are often fit and active before they develop POTS. At its worst, the condition can be debilitating and life changing.

POTS affects the body’s autonomic nervous system, which exerts involuntary control over bodily functions, such as heart rate, blood pressure, sweating, and temperature.

Its causes are poorly understood, but the condition often follows a viral infection, trauma, major surgery, or pregnancy.

There is a distinct overlap between the common symptoms of long COVID and POTS. This has led some researchers to propose that the new coronavirus, which can affect the central nervous system, may trigger POTS in some people.

Limitations of current treatment

While the Food and Drug Administration (FDA) have not approved any treatments for POTS, doctors often prescribe beta-blockers to patients with POTS to lower their heart rate.

The drugs reduce activity in the sympathetic nervous system, which is the wing of the autonomic nervous system that reacts to perceived threats with fight-or-flight responses, such as increased heart rate.

However, a drawback of beta-blockers is that they not only reduce heart rate but also lower blood pressure, which can exacerbate patients’ fatigue and lack of energy.

One promising alternative is ivabradine, a heart failure drug that slows the heart without reducing blood pressure.

In the first randomized controlled trial of ivabradine for POTS, researchers at the University of California (UC), San Diego, found that the drug significantly reduced heart rate and improved patients’ quality of life 1 month after treatment started.

They report that the drug was well tolerated and that there were no severe side effects.

The research appears in the Journal of the American College of Cardiology.

“Ivabradine is a novel agent that’s FDA-approved for heart failure, but based on its mechanism, we thought it could be helpful for patients with POTS, as it reduces heart rate without impacting blood pressure,” said first author Dr. Pam Taub, a cardiologist at UC San Diego Health and associate professor of medicine at UC San Diego School of Medicine.

“When we can lower the heart rate, we’re providing these patients with the ability to stand up, something they couldn’t do without difficulty before due to their POTS diagnosis,” she added.

How the study worked

The researchers recruited 22 patients, 21 of whom were female, with an average age of 34. The majority of patients — 86.4% — were white.

All of the patients had hyperadrenergic POTS, a subtype of the condition in which blood levels of norepinephrine, or noradrenaline, are raised. Norepinephrine is a key neurotransmitter in the sympathetic nervous system.

The researchers randomly assigned the patients to receive either ivabradine or a placebo for 1 month. After a washout period of 1 week, the patients who had taken the placebo then switched to the drug for 1 month, and the patients who had been given ivabradine started taking the placebo.

Over the course of the trial, the researchers measured the participants’ plasma norepinephrine levels and their heart rate while sitting, lying down, or standing up. The researchers also assessed the quality of life of the participants throughout the trial.

Compared with the patients taking the placebo, the patients taking ivabradine had significantly lower heart rates and an improved quality of life, as measured by a standard health questionnaire.

There were also reduced levels of norepinephrine in the bloodstream of the patients taking the drug when they stood up. However, this result was not statistically significant.

Summing up the study’s findings, Dr. Taub said:

“Before the study, these patients would be living with elevated heart rates ranging between 100 to 115 beats per minute when standing. After taking ivabradine twice per day for 1 month, the standing heart rate decreased significantly to around 77 beats per minute compared to the placebo group.”

However, it is worth noting that this was a small study. Larger clinical trials will be needed to investigate the drug’s safety and efficacy for treating the condition.

Also, ivabradine is not currently approved for use in either POTS or long COVID, so prescription for these conditions would be “off label.”

POTS and long COVID

Early reports suggest that one feature of long COVID is symptoms resembling POTS. In September 2020, for example, researchers at Stanford University in Palo Alto, CA, reported the case of a 26-year-old nurse who developed symptoms of POTS after recovering from COVID-19.

“In our contemporary practice, we are seeing patients who have previously been infected with COVID-19 present with symptoms consistent with POTS,” said Dr. Jonathan Hsu, a cardiologist at UC San Diego Health and one of the authors of the ivabradine study.

“Given the similarities, this study leads to the question whether therapy with ivabradine may help patients who experience similar symptoms after a COVID-19 infection, and provide an important area for future study as well.”

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