Tricuspid Regurgitation After AF Diagnosis Is Common, Worsens Outcomes

Among patients with new-onset atrial fibrillation (AF), almost one in three go on to develop subsequent moderate or greater tricuspid regurgitation (TR), according to new population data. This TR, in turn, is associated with an almost threefold increase in mortality risk.

The findings stress the importance of appropriately managing patients diagnosed with AF and how serious a condition it can be, the researchers say.

While the data cannot yet confirm that AF definitively causes TR, lead author Sri Harsha Patlolla, MBBS (Mayo Clinic, Rochester, MN), told TCTMD that “we have given a very clean data set and a very clear idea that atrial fibrillation can lead to tricuspid valve regurgitation, either directly into, as is reflected by the isolated group, or indirectly in collaboration with other heart diseases through the secondary TR that developed.”

Commenting on the study for TCTMD, Roy Chung, MD (Cleveland Clinic, OH), said the link warrants attention: “Certainly we have to pay closer attention to patients with atrial fibrillation and isolated TR in the beginning. And certainly earlier rhythm control intervention is much better than later.”

Further, he said, the findings confirm what his team conclude in the STOP AF First trial, where an initial strategy of cryoablation was superior to drug therapy for the prevention of AF recurrence over 1 year.

“We have always proposed that AF ablation as a therapy for rhythm control earlier than later can prevent earlier remodeling or left atrial remodeling because A-fib begets A-fib,” Chung explained. “The longer you have A-fib, [the more likely] it can cause atrial fibrosis, loss of atrial compliance and atrial dilatation. When the atrium dilates, it causes the chambers to dilate and the tricuspid automatic microannulus dilates and that causes worsening regurgitation, and perhaps that there is a mechanism in why these patients have worse outcomes.”

The findings were published online ahead of the December 13, 2022, issue of the Journal of the American College of Cardiology.

Population Data

For the study, Patlolla and colleagues followed 691 patients with new-onset AF (mean age 68 years; 38.9% women) from the Rochester Epidemiology Project registry after excluding those with evidence of moderate or greater tricuspid valve disease, left-sided valve disease, pulmonary hypertension, prior cardiac surgery, or impaired left ventricular systolic/diastolic function at baseline. About two-thirds (64%) were subsequently diagnosed with permanent or persistent AF, while the remainder had paroxysmal episodes. The vast majority (73.7%) were treated with rate control, with a rhythm control strategy only used in 26.3%.

Of the 232 (33.6%) who went on to develop moderate or greater TR (3.9 cases per 100 person-years) over a median of 13.3 years, 73 (10.6%) had isolated TR without significant underlying structural heart disease (1.3 cases per 100 person-years). Independent predictors of incident moderate or severe TR were older age (HR 1.96); female sex (HR 1.83); history of heart failure, cancer, chronic lung disease, and nonparoxysmal AF (HR 2.96). Use of an early rhythm control strategy was associated with a lower risk of TR (HR 0.71; 95% CI 0.51-0.99).

Overall, 313 patients died during follow-up, translating into a mortality incidence of 2.8 deaths per 100 person-years. This rose to 6.1 deaths per 100 person-years for those who developed incident significant TR, which was associated with an almost threefold heightened mortality risk even after adjustment for age, sex, comorbidities, baseline LVEF, and AF management strategy (HR 2.92; 95% CI 2.29-3.73). Isolated significant TR was also associated with an adjusted heightened risk of mortality (HR 1.51; 95% CI 1.03-2.22) while rhythm control reduced this risk (HR 0.69; 95% CI 0.51-0.93).

When a new atrial fibrillation patient comes and we manage them for atrial fibrillation, we will never really pay attention to the fact that these patients can develop tricuspid valve regurgitation and we have to manage that. Sri Harsha Patlolla

Patlolla said most of their findings were expected, but he was surprised to see how many patients who developed TR were female given how male-heavy the initial population was. “We have seen that a lot of female patients come to the hospitals for a tricuspid valve surgery or tricuspid valve repair replacement through transcatheter procedures, and we have always suspected this, but we did not expect to see this in this particular study,” he said. “And it was a very clear trend that was evident.”

The authors advocate for “a more-aggressive rhythm control strategy when possible” for many of these patients in order to improve outcomes, as was demonstrated in the EAST-AFNET 4 study of heart failure patients.

Also, while AF has long been known to have an effect on mortality, Patlolla said these findings clearly show that TR adds to this burden. “That is a very important point for clinicians to understand, because a lot of what we have done to date is when a new atrial fibrillation patient comes and we manage them for atrial fibrillation, we will never really pay attention to the fact that these patients can develop tricuspid valve regurgitation and we have to manage that,” he said, specifying that these patients deserve more-frequent echocardiography.

And once TR or mitral regurgitation is identified in this population, Patlolla advocates for intervention. In the past, operators have avoided intervening on isolated TR given the associated high operative mortality seen in the literature, he explained, “so people have largely refrained from doing that unless the patient also has some other condition that needs to be addressed.”

However, it’s likely that the AF patients with TR looked at in this study “do not have the poor functional status that the other tricuspid valve regurgitation patients have,” he continued. “[This] is why if you can actually correct the tricuspid valve regurgitation in these patients, [they] will probably have the greatest benefit.”

This is a topic Patlolla would like future research to explore, especially with more contemporary data sets. “I would really like to see somebody do that where they start out with atrial fibrillation patients and show gradual dilatation of the right atrium and the tricuspid valve annulus resulting in tricuspid valve regurgitation, so we can once and for all settle debate about the egg and the chicken and say: okay, atrial fibrillation is actually causing TR here,” he said.

Which Comes First?

Indeed, in an accompanying editorial, Tobias Friedrich Ruf, MD, Theresa Ann Maria Gößler, MD, and Ralph Stephan von Bardeleben, MD (all University Medical Center Mainz, Germany), question which condition is causing the other.

“By defining the cohort through new-onset AF, a causal relationship between AF and incident isolated TR cannot be proven,” they write. “However, the excessive incidence of 31.5% of isolated TR in a cohort of new-onset AF demonstrates the close association between the two, as does the observation that early rhythm control reduces this risk.”

Mitral regurgitation following an AF diagnosis is already called secondary mitral regurgitation (SMR) by some, the editorialists point out. “One wonders if ‘isolated TR’ might be renamed ‘atrial STR’ in the future, which could spawn a new generation of scientific chickens and eggs: Is there a coincidence of atrial SMR and atrial STR? Which one comes first? And does one cause the other?”

Chung called this an exercise in “semantics” that could further confuse the field. He argued that the TR in this case is not primary, but rather secondary to chronic AF or worsening AF burden. “It is reasonable, I suppose, to rename this if there is a paradigm shift for all of this and call it atrial STR,” he allowed, “but a lot of cardiologists will be thrown off, though.”

Patlolla agreed that he’d like to see future research in this space, regardless of how the conditions are named. It’s possible that in some patients SMR might be the initial presentation, but in others STR could make an appearance first. “We have seen both,” he said.