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Pig’s Heart Took Longer to Generate a Beat in Transplant Patient

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A genetically modified pig heart transplanted into a severely ill person took longer to generate a heartbeat than those of typical pig or human hearts, research showed, another potential challenge for doctors aiming to conduct clinical trials of pig-organ transplants.

Doctors took daily electrocardiograms of

David Bennett,

a 57-year-old handyman and father of two who received a gene-edited pig heart in an experimental surgery at the University of Maryland Medical Center in Baltimore in January. Mr. Bennett died in March from heart failure, but doctors still aren’t sure why the pig heart thickened and lost its pumping ability.

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Doctors involved in the groundbreaking surgery have been studying data from Mr. Bennett’s case, which is being closely watched in the wider transplant community. Researchers reported in May that a common pig virus was detected in the pig heart transplanted into Mr. Bennett. They said there is no evidence the virus infected Mr. Bennett, but its presence in the pig heart could have caused inflammation that contributed to the cascade of events that led to his death from heart failure.

Researchers analyzed Mr. Bennett’s EKG data as part of efforts to understand his decline after the transplant, direct future research and determine a possible path toward opening clinical trials. Widely used tests that measure electrical signals that cause the heart to beat, EKGs can help diagnose heart attacks, irregular heart rhythms and other possible abnormalities.

Researchers reported unexpected findings in two aspects of Mr. Bennett’s EKG data: the time it takes electricity to travel from the top to the bottom chamber of the heart and across the bottom chambers, which pumps blood through the heart, and the time it takes the lower chambers of the heart to go through a full electrical cycle, which is associated with a heartbeat.



The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle.

Here’s one approach:

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells—including those in their organs— contain the edited genes.

Crispr acts like scissors cutting DNA at a specific place

scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

EASING ORGAN REJECTION

The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle. Here’s one approach:

Crispr acts like scissors cutting DNA at a specific place.

Scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells—including those in their organs—contain the edited genes.

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig

hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

EASING ORGAN REJECTION

The surfaces of pig cells contain a sugar molecule that triggers the human immune system to attack the organs. Scientists are using the gene editing tool Crispr to overcome this obstacle. Here’s one approach:

Crispr acts like scissors cutting DNA at a specific place.

Scientists edit troublesome genes in pig DNA…

…and sometimes add human genes…

…and then insert the edited DNA into a pig egg cell whose nucleus has been removed. The egg cell is then transferred to the uterus of a sow. The sow gives birth to pigs whose cells— including those in their organs—contain the edited genes.

ORGAN OPTIONS

Researchers are trying various techniques that might allow transplantation of gene-edited pig

hearts, kidneys and livers into humans. Recent studies on pig organ transplantation in baboons and people have focused mainly on hearts and kidneys.

HEART TO HEART

Pig and human hearts have similarities—but also some differences.

Pigs can be bred to have hearts of similar size as human hearts.

Pig and human hearts each have four pumping chambers—two small ones known as atria and two large ones known as ventricles.

The wall of tissue separating the ventricles is thicker in pig hearts than in human hearts.

Pig and human hearts each are attached to a large artery known as the aorta as well as to a large vein known as the vena cava.

A pig’s inferior (lower) vena cava joins a pig heart’s right atrium at an angle. The vein is longer in pigs than in humans.

The time intervals are typically shorter in pig hearts that are in pigs. But they took longer in the gene-modified pig heart inside a human. The time for the electricity to travel through the heart’s electrical system and generate a heartbeat also took longer than what is typical for human hearts, said

Timm Dickfeld,

a professor of medicine and director of electrophysiology research at the University of Maryland Medical Center, who was the leader of the EKG study.

What that might mean in the future for doctors caring for patients with gene-modified pig heart transplants is uncertain, said

Paul Wang,

director of the Stanford Cardiac Arrhythmia Service and a professor of medicine and bioengineering at Stanford University, who examined the data but wasn’t involved in the study.

“It has only been done once,” Dr. Wang said. “It needs to be done many more times for us to understand what these differences mean.”

The EKG data haven’t been published or undergone an outside vetting process. They are being presented by the Maryland team at an American Heart Association annual meeting starting Nov. 5. The Maryland team said they are studying the significance of the findings and hope to gather more data in future studies.

The fact that the electrical signals traveled through Mr. Bennett’s heart more slowly than expected “did not appear to be associated with a pathological outcome,” said

Bartley Griffith,

co-director of the cardiac xenotransplantation program at the University of Maryland School of Medicine, who performed Mr. Bennett’s transplant surgery.

Dr. Griffith added that if Mr. Bennett had survived longer and the time intervals became even slower, a pacemaker might eventually have become necessary.

Researchers have tried for decades to develop the transplantation of organs between different species, or xenotransplantation, to address a chronic shortage of organs. More than 3,500 people are on the waiting list in the U.S. for a heart transplant, according to a 2022 update from the American Heart Association.

Megan Sykes,

director of the Columbia Center for Translational Immunology in New York, said that although pigs are similar to humans in organ size and physiology, the EKG data illustrate that there are differences that may only emerge after doing transplants into humans.

“We have reached the point where we need human studies as well as animal studies,” Dr. Sykes said.

The Maryland team and other groups have met with the Food and Drug Administration recently to discuss how to start small clinical trials of genetically modified pig organs. The FDA has requested additional data from the Maryland team in baboons, said

Muhammad Mohiuddin,

the scientific program director of cardiac xenotransplantation at the University of Maryland School of Medicine. Dr. Mohiuddin said they plan to gather additional EKG data as part of the research.

Write to Amy Dockser Marcus at amy.marcus@wsj.com

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Health

Study finds Paxlovid can interact badly with some heart medications, and White House renews COVID emergency through Jan. 11

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A new study has found that the COVID antiviral Paxlovid can interact badly with certain heart medications, raising concerns for patients with cardiovascular risk who test positive.

The study was published in the Journal of the American College of Cardiology and found the reaction involved such medications as blood thinners and statins. As patients who are hospitalized with COVID are at elevated risk of heart problems, they are likely to be described Paxlovid, which was developed by Pfizer
PFE,
-0.28%.

 “Co-administration of NMVr (Paxlovid) with medications commonly used to manage cardiovascular conditions can potentially cause significant drug-drug interactions and may lead to severe adverse effects,” the authors wrote. “It is crucial to be aware of such interactions and take appropriate measures to avoid them.”

The news comes just days after the White House made a renewed push to encourage Americans above the age of 50 to take Paxlovid or use monoclonal antibodies if they test positive and are at risk of developing severe disease.

White House coordinator Dr. Ashish Jha told the New York Times that greater use of the medicine could reduce the average daily death count to about 50 a day from close to 400 currently.

“I think almost everybody benefits from Paxlovid,” Jha said. “For some people, the benefit is tiny. For others, the benefit is massive.” 

Yet a smaller share of 80-year-olds with COVID in the U.S. is taking it than 45-year-olds, Jha said, citing data said he has seen.

On Thursday, the White House extended its COVID pubic health emergency through Jan. 11 as it prepares for an expected rise in cases in the colder months, the Associated Press reported.

The public health emergency, first declared in January 2020 and renewed every 90 days since, has dramatically changed how health services are delivered.

The declaration enabled the emergency authorization of COVID vaccines, as well as free testing and treatments. It expanded Medicaid coverage to millions of people, many of whom will risk losing that coverage once the emergency ends. It temporarily opened up telehealth access for Medicare recipients, enabling doctors to collect the same rates for those visits and encouraging health networks to adopt telehealth technology.

Since the beginning of this year, Republicans have pressed the administration to end the public health emergency.

President Joe Biden, meanwhile, has urged Congress to provide billions more in aid to pay for vaccines and testing. Amid Republican opposition to that request, the federal government ceased sending free COVID tests in the mail last month, saying it had run out of funds for that effort.

Separately, the head of the World Health Organization urged countries to continue to surveil, monitor and track COVID and to ensure poorer countries get access to vaccines, diagnostics and treatments, reiterating that the pandemic is not yet over.

Tedros Adhanom Ghebreyesus said most countries no longer have measures in place to limit the spread of the virus, even though cases are rising again in places including Europe.

“Most countries have reduced surveillance drastically, while testing and sequencing rates are also much lower,” Tedros said in opening remarks at the IHR Emergency Committee on COVID-19 Pandemic on Thursday.

“This,” said the WHO leader, “is blinding us to the evolution of the virus and the impact of current and future variants.”

U.S. known cases of COVID are continuing to ease and now stand at their lowest level since late April, although the true tally is likely higher given how many people overall are testing at home, where the data are not being collected.

The daily average for new cases stood at 38,530 on Thursday, according to a New York Times tracker, down 19% from two weeks ago. Cases are rising in six states, namely Nevada, New Mexico, Kansas, Maine, Wisconsin and Vermont, and are flat in Wyoming. They are falling everywhere else.

The daily average for hospitalizations was down 7% at 26,665, while the daily average for deaths is down 7% to 377. 

The new bivalent vaccine might be the first step in developing annual Covid shots, which could follow a similar process to the one used to update flu vaccines every year. Here’s what that process looks like, and why applying it to Covid could be challenging. Illustration: Ryan Trefes

Coronavirus Update: MarketWatch’s daily roundup has been curating and reporting all the latest developments every weekday since the coronavirus pandemic began

Other COVID-19 news you should know about:

• Federal Health Minister Karl Lauterbach has urged German states to reintroduce face-mask requirements for indoor spaces due to high COVID cases numbers, the Local.de reported. Lauterbach was launching his ministry’s new COVID campaign on Friday. “The direction we are heading in is not a good one,” he said at a press conference in Berlin, adding it’s better to take smaller measures now than be forced into drastic ones later.

• Health officials in Washington and Oregon said Thursday that a fall and winter COVID surge is likely headed to the Pacific Northwest after months of relatively low case levels, the AP reported. King County (Wash.) Health Officer Dr. Jeff Duchin said during a news briefing that virus trends in Europe show a concerning picture of what the U.S. could soon see, the Seattle Times reported.

Two banners unfurled from a highway overpass in Beijing condemned Chinese President Xi Jinping and his strict Covid policies, in a rare display of defiance. The protest took place days before the expected extension of the leader’s tenure.

• Kevin Spacey’s trial on sexual-misconduct allegations will continue without a lawyer who tested positive for COVID on Thursday, Yahoo News reported. The “American Beauty” and “House of Cards” star is on trial in Manhattan federal court facing allegations in a $40 million civil lawsuit that he preyed upon actor Anthony Rapp in 1986 when Rapp was 14 and Spacey was 26. Jennifer Keller’s diagnosis comes after she spent about five hours cross-examining Rapp on the witness stand over two days — a few feet away from the jury box without wearing a mask.

• A man who presents himself as an Orthodox Christian monk and an attorney with whom he lived fraudulently obtained $3.5 million in federal pandemic relief funds for nonprofit religious organizations and related businesses they controlled, and spent some of it to fund a “lavish lifestyle,” federal prosecutors said Thursday. Brian Andrew Bushell, 47, and Tracey M.A. Stockton, 64, are charged with conspiracy to commit wire fraud and unlawful monetary transactions, the U.S. attorney’s office in Boston said in a statement, as reported by the AP.

Here’s what the numbers say:

The global tally of confirmed cases of COVID-19 topped 623.9 million on Monday, while the death toll rose above 6.56 million, according to data aggregated by Johns Hopkins University.

The U.S. leads the world with 96.9 million cases and 1,064,821 fatalities.

The Centers for Disease Control and Prevention’s tracker shows that 226.2 million people living in the U.S., equal to 68.1% of the total population, are fully vaccinated, meaning they have had their primary shots. Just 110.8 million have had a booster, equal to 49% of the vaccinated population, and 25.6 million of those who are eligible for a second booster have had one, equal to 39% of those who received a first booster.

Some 14.8 million people have had a shot of the new bivalent booster that targets the new omicron subvariants.

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Health

Covid-19 Vaccines Carry Low Risk of Heart Conditions, Studies Find

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The risk of developing inflammatory heart conditions after Covid-19 vaccination is relatively low, two large studies found, especially when compared with the heart-related risks from Covid-19 disease itself and from vaccines against other diseases.

One study, an analysis of 22 previous studies, found that the risk of the conditions including myocarditis in people who received a Covid-19 vaccine wasn’t significantly different from that for non-Covid-19 vaccines such as those against flu, polio and measles. And the heart risk associated with Covid-19 shots was lower than the risk after smallpox vaccination. The results of the analysis, which included data on the effects of more than 400 million doses of various vaccines, were published online Monday by The Lancet Respiratory Medicine.

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Health

Exercise Is Good for You, Even if You Have a Mild Case of Covid

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To exercise with Covid or not—that’s the question some fitness buffs are asking. The American College of Sports Medicine has suggested people under 50 who experience mild or no symptoms to rest for at least seven to 10 days after testing positive. Their recommendation appears to be motivated by the concern that even a mild Covid-19 infection may damage the heart and potentially cause sudden death during physical exertion.

There’s little evidence to support this recommendation. Because exercise boosts the immune system, it may even help people bounce back faster from Covid.

Viral infections, including those that cause the flu and the common cold, are a major cause of myocarditis, the inflammation of the heart muscle. The condition can cause chest pain and irregular heartbeat, though it is often asymptomatic. This makes its prevalence hard to measure. According to some estimates, 1% to 5% of all people with acute viral infections may develop myocarditis.

Yet sudden death from myocarditis during physical activity appears to be rare. A study from 1980 to 2006 documented 41 sudden deaths in young athletes (under 40) linked to myocarditis—one-tenth as many as from blunt trauma.

Some experts feared Covid-19 would increase cardiac risk in otherwise young and healthy people. A study early in the pandemic from Germany reported signs of myocarditis in 60% of Covid-19 patients, including some with relatively mild illness. But criticisms of the study’s design and data errors prompted more investigation, and recent studies have been mostly reassuring.

In one study, cardiac tests were performed on 789 professional athletes (soccer, baseball, basketball, football and hockey) with prior infections, most of whom had mild or no Covid symptoms. Only five (0.6%) had inflammation on cardiac imaging—in line with estimates for other viral infections—and all of them had symptoms that the researchers said “exceeded empirical definitions of mild COVID-19 illness” such as cough, fatigue or loss of taste.

In another study, only 0.7% of 3,018 college athletes who tested positive for Covid had abnormal cardiac test results that researchers believed were definitely, probably or possibly linked to the virus. (Extremely fit athletes are known to have “remodeled” hearts that can cause abnormal findings on cardiac tests. That makes it hard for cardiologists to tell if the abnormalities result from the virus.)

A third study, involving 3,597 college athletes who had tested positive with symptoms ranging from none to chest pain and shortness of breadth, found that only 1.2% experienced symptoms that persisted for more than three weeks. Only 4% experienced heart- or lung-related symptoms when they returned to exercise. Yet the vast majority of those who underwent more testing didn’t show evidence of cardiac damage from Covid-19, and it’s normal to experience fatigue or shortness of breath when returning to exercise after a flulike illness.

Studies on young competitive athletes are easier to perform than on the general population, and they may not be 100% applicable to recreational athletes. Still, they show that otherwise healthy and fit people who catch Covid are unlikely to suffer cardiac complications.

A recent study of U.K. healthcare workers found those who had mild or no Covid symptoms were no more likely to have cardiac abnormalities on tests six months after infection than those who hadn’t been infected. “This study demonstrates that in healthy people, measured cardiovascular abnormalities are common, but no more common in those who had had mild SARS-CoV-2 6 months previously compared with those who had not,” the researchers found.

The seven- to 10-day rest recommendation appears to be as arbitrary as the six-foot social distancing from early in the pandemic. Most people who don’t know they have Covid won’t follow it anyway.

“There is very little good quality data on exercise resumption post-Covid,”

Gabriel Vorobiof,

a cardiologist at UCLA, says in an email. “At one point there was a big controversy when a few cardiac MRI papers showed some potentially concerning cardiac findings post-Covid.” But since the studies didn’t include a control group for comparison—such as athletes or young people without Covid who get an MRI—he says the “findings were later dismissed as associations, not necessarily causative links.”

He adds: “I’ve seen quite a few young athletes requiring ‘cardiac clearance’ by their sporting club after having uncomplicated Covid prior to re-engaging in their respective sports, many of which were noncompetitive. The need to clear a young person following an asymptomatic viral illness, like many things during this pandemic, seems to be an overreaction based on little if any science.”

Doctors generally advise people with head colds that they may exercise, but should listen to their bodies. This seems like sensible advice for otherwise healthy people with mild Covid. “However, if symptoms of chest pain or discomfort, lightheadedness or palpitations arise, one should stop and seek medical attention,” Dr. Vorobiof says.

Exercise has been found to protect people from other viral infections, including flu, herpes, Epstein-Barr and the common cold, and improve the immune response to vaccinations. Each workout mobilizes billions of immune cells, especially the T-cells that circulate, identify and kill virus-infected cells. Exercise also reduces levels of the stress hormone cortisol, which impairs white blood cells and increases inflammation.

As people learn to live with Covid, there’s no reason they shouldn’t work out with it too.

Ms. Finley is a member of the Journal’s editorial board.

Wonder Land: The weaponization of ‘science’ began with climate policy and accelerated with Covid-19. Now many think it’s all misinformation. Images: AFP/Getty Images Composite: Mark Kelly

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Health

No ‘good’ vs. ‘bad’ foods: 10 eating ‘patterns’ to prevent heart disease, death

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Looks like we’ve been talking about healthy eating all wrong. 

The American Heart Association released a new scientific statement on Tuesday that encourages everyone to focus on their overall dietary “patterns” to take care of their tickers, rather than zeroing in on foods, ingredients and drinks that are “good” or “bad” for their hearts.

The full “2021 Dietary Guidance to Improve Cardiovascular Health” was published in the Association’s flagship journal Circulation on Tuesday. And this more modern approach to nutrition is intended to adapt more easily to different cultural traditions, individual likes and dislikes, as well as societal issues such as whether most meals are made and eaten at home, or picked up on-the-go while people are at work or school.

““It does not need to be complicated, time consuming, expensive or unappealing.””

“We can all benefit from a heart-healthy dietary pattern regardless of stage of life, and it is possible to design one that is consistent with personal preferences, lifestyles and cultural customs,” said Alice H. Lichtenstein, the chair of the scientific statement writing group, in a statement.

“It does not need to be complicated, time consuming, expensive or unappealing,” added Lichtenstein, who is the director of the Cardiovascular Nutrition Team at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston. 

She concedes that adopting heart-healthy eating habits such as choosing the fish entrée over the steak at a restaurant, or opting for brown rice instead of fried white rice from your favorite Chinese takeout joint, may feel strange at first. “It might take a little planning, however, after the first few times it can become routine,” she said.

Here’s the American Heart Association’s 10 steps for a dietary pattern to promote heart health:

  1. Balance food and calorie intake with physical activity to maintain a healthy weight.
  2. Choose a wide variety of fruits and vegetables, and eat plenty of produce, to get a full range of nutrients from food — rather than from supplements.
  3. Choose whole grains and other foods made up mostly of whole grains, such as whole wheat, oatmeal, brown rice and popcorn.
  4. Include healthy sources of lean and/or high-fiber protein such as plant proteins (nuts and legumes); fish or seafood; low fat or non-fat dairy; lean cuts of meat — and limit red and processed meats.
  5. Use liquid non-tropical plant oils such as olive or sunflower oils.
  6. Choose minimally-processed foods (such as a bag of salad or  roasted, unsalted nuts) rather than ultra-processed foods (such as sugary cereal, potato chips or smoked sausage) as much as possible.
  7. Minimize eating and drinking food and beverages with added sugars.
  8. Choose or prepare foods with little or no salt.
  9. Limit alcohol consumption. And if you don’t drink, do not start. 
  10. Apply this guidance no matter where food is prepared or consumed, such as whether you’re at home, dining out or ordering takeout.

These tips should sound familiar; much of this advice has been supported by scientific research for years. 

Read more: These 4 diet and lifestyle changes can lower your cancer risk by almost 20%

And that’s the point. The AHA’s new statement reflects the latest scientific evidence on the benefits of heart-healthy eating throughout life, and how poor diet quality is strongly associated with an increased risk of cardiovascular disease and death.

Weight Watchers took a similar step a few years ago. The company was founded to help people lose weight, and watching the scale was literally in its name. But in 2018, Weight Watchers International Inc. announced it was shifting its focus from weight loss to a wellness journey, and it changed its legal name to WW International Inc
WW,
-1.19%.
in September 2019. More people were joining Weight Watchers for “something more than getting into a size 8,” Chief Executive Mindy Grossman said in 2018. “Today, healthy is the new skinny.” And the brand has been customizing its lifestyle guides for individual users, and moving away from the old school “one size fits all” approach.

Related: ‘The Covid 15?’ If only — this is how much weight the average person actually gained during the pandemic

And now for the first time, the AHA is highlighting challenges such as societal factors that can make it tougher for people to learn or maintain healthy eating patterns. For example, about 2.3 million Americans live in food deserts more than one mile away from a supermarket and do not own a car, according to federal data, making it difficult to shop for more nutritious and less processed foods. The COVID-19 pandemic also saw more people ordering takeout from home — and, conversely, dining out spiked as bars and restaurants have reopened in some areas.

The AHA highlighted the following societal challenges that can make it harder to start or maintain a heart-healthy eating pattern:  

  • Widespread dietary misinformation from the internet.
  • A lack of nutrition education in grade schools and medical schools.
  • Food and nutrition insecurity — according to references cited in the statement, an estimated 37 million Americans had limited or unstable access to safe and nutritious foods in 2020.
  • Structural racism and neighborhood segregation, whereby many communities with a higher proportion of racial and ethnic diversity have few grocery stores but many fast-food outlets.
  • Targeted marketing of unhealthy foods and beverages to people from diverse racial and ethnic backgrounds through tailored advertising efforts and sponsorship of events and organizations in those communities.

The guidance recommends public health action and policy changes to address these barriers, calling it “a public imperative.” 

The AHA statement also notes that this heart-healthy eating pattern is good for the environment. Popular animal products, particularly red meat (beef, lamb, pork, veal, venison or goat), have the largest environmental impact in terms of water and land usage, and contribute significantly to greenhouse gas emissions, compared with plant-based foods. “It is important to recognize that the guidance is consistent not only with heart health but also sustainability — it is a win-win for individuals and our environment,” said Lichtenstein.

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