Pulmonary Sarcoidosis

GLP-1 Agonists May Reduce Risk Of AF Recurrence Postablation In Patients With Type 2 DM

Glucagon-like peptide-1 receptor (GLP-1) agonist use is associated with a decreased risk for atrial fibrillation (AF) recurrence after ablation among patients with type 2 diabetes mellitus (DM), according to study results presented at the Heart Rhythm Society 2024 conference, held from May 16 to 19, 2024, in Boston, Massachusetts.

Researchers analyzed data from the TriNetX research network of patients aged 18 years and older with DM who had AF ablation from January 1, 2015, to December 1, 2022.

The participants were stratified into 2 groups according to whether they were using a GLP-1 agonist at baseline. Propensity score matching was used to assign 2894 patients to each group.

The primary outcome was a composite of cardioversion, new antiarrhythmic drug therapy initiation, or re-do AF ablation. Secondary outcomes were AF readmissions, heart failure (HF) readmissions, readmissions due to ischemic stroke, and mortality.

After a follow-up of 12 months, GLP-1 agonist use was associated with a significantly lower composite risk for postprocedure cardioversion, new antiarrhythmic drug therapy, and re-do AF ablation in patients with DM who were receiving AF ablation (adjusted odds ratio [aOR], 0.75; 95% CI, 0.70-0.80; P <.0001).

Participants using GLP-1 agonists had overall lower mortality (aOR, 0.63; 95% CI, 0.47-0.84; P =.001), AF readmissions (aOR, 0.87; 95% CI, 0.78-0.97; P <.0001), and HF readmissions (aOR, 0.73; 95% CI, 0.62-0.86; P <.004) at 12 months. No difference was found for ischemic stroke between the 2 patient groups (aOR, 0.85; 95% CI, 0.45-1.58; P =.924).

This article originally appeared on The Cardiology Advisor

References:

Sheth A, Patel H, DeSimone CV, et al. Impact of GLP-1 agonists in patients with atrial fibrillation ablation. Abstract presented at: Heart Rhythm 2024; May 16-19, 2024; Boston, MA. Abstract CE-482907-002.

Long-term Digoxin Use Linked To VT/VF Risk In HF Patients

In patients with heart failure with reduced ejection fraction (HFrEF) who have an implantable cardioverter-defibrillator (ICD), the use of digoxin may increase the risk of ventricular tachyarrhythmia and death, new research cautions.

In a study of thousands of HF patients enrolled in four different trials involving automatic cardioverter-defibrillator implantation, those on digoxin had a 48% increased risk of device-detected ventricular tachycardia/ventricular fibrillation (VT/VF) and a 37% increased risk of all-cause death over 4 years compared with patients not taking digoxin, researchers report in the Journal of the American College of Cardiology: Clinical Electrophysiology.

To TCTMD, lead author Amole Ojo, MD (University of Rochester Medical Center, NY), said he and his colleagues became interested in the topic after one of their HFrEF patients developed a ventricular arrhythmia while on digoxin and they could find only limited data on an association between digoxin use and increased risk of tachyarrhythmias in HF patients.

While a link between digoxin use and increased risk of death in these HFrEF patients was not surprising and is within range of what others have reported, Ojo said what did surprise the investigators was the magnitude of the increased risk of VT/VF that they saw in their study.

"I was not expecting it to be as high as that," he said. "Based on these findings, I would not use digoxin in the long term."

Based on these findings, I would not use digoxin in the long term. Amole Ojo

In an accompanying editorial, Pattara Rattanawong, MD, and E. Kevin Heist, MD, PhD (both Massachusetts General Hospital/Harvard Medical School, Boston, MA), say despite the nostalgia that some clinicians still have for digoxin—one of the oldest drugs in continuous clinical use—the findings from this study and others that have shown a association between digoxin and mortality in patients with atrial fibrillation (AF) call for a reassessment of routine use of digoxin in HF management.

"The precise mechanism behind the observed association between digoxin use and heightened risk of ventricular arrhythmias and mortality remains uncertain," they write. "Potential factors include subclinical digoxin toxicity, which may induce ventricular arrhythmias through mechanisms, such as reentry or triggered membrane activity, including delayed afterdepolarizations."

One caveat they point to, however, is that the patients included in the study were enrolled between 1997 and 2011, which raises questions about the generalizability of findings to contemporary practice, noting that the "landscape of HF management has evolved significantly since then," with newer agents such as sacubitril/valsartan (Entresto; Novartis) and the sodium-glucose cotransporter 2 (SGLT2) inhibitors.

Ojo agreed, adding that digoxin has become mostly outdated in favor of newer drugs, although it is still a reasonable consideration in some situations, such as for short-term use in a patient in the ICU with AF and low BP.

"In that situation where you cannot use all of the medications we normally use, maybe you use digoxin temporarily at that point," he said. "But once things improve, they should be switched to other medications. If rate is still not controlled, [you can] put in a pacemaker and do AV node ablation . . . And people do well with that."

More Events and Death Seen

For the study, Ojo and colleagues looked at patients enrolled in the four landmark Multicenter Automatic Defibrillator Implantation Trials (MADIT). Of the 4,499 patients, 26% were on digoxin (mean age 64 years; 26% female; 14% Black).

Compared with patients not on digoxin, more of those on the drug had history of atrial arrhythmias and LVEF of 25% or lower.

In addition to greater risks of VT/VF, the digoxin group also had increased risks of severe life-threatening arrhythmic events including fast VT/VF (HR 1.58; 95% CI 1.31-1.92) and recurrent VT/VF (HR 1.46; 95% CI 1.17-1.82) compared with the group not on digoxin. The digoxin group had an average of 1.5 VT/VF events per patient over the 4-year follow-up period, versus an average of 1.1 per patient in the nondigoxin group (P < 0.001).

The investigators also looked at appropriate and inappropriate ICD shocks, finding that the digoxin group had a higher incidence of appropriate shocks over the follow-up period than the nondigoxin group (25% vs 12%; P < 0.001), with no differences seen between the groups in terms of inappropriate ICD shocks.

The cumulative probability of death was 20% in those on digoxin and 14% in those not on digoxin (P < 0.001). Looking at the cumulative probability of the composite endpoint of VT/VF or death over the follow-up period, the digoxin group had a 48% probability versus 31% for those not taking digoxin (P < 0.001).

Ojo and colleagues note that while it is possible that digoxin dosing impacted outcomes, that information was not available to them.

According to Rattanawong and Heist, another limitation of this research is the heterogeneous nature of HF patient populations, which complicates data interpretation, particularly in a nonrandomized study like this one.

"Baseline differences between digoxin users and nonusers, despite attempts at propensity adjustment, may introduce residual biases," they write. "Factors such as disease severity, comorbidities, and concomitant medications could confound the observed associations between digoxin use and clinical outcomes."

Bariatric Surgery Reduces Hard Events In Obese Patients With Sleep Apnea

Patients with moderate-to-severe obstructive sleep apnea (OSA) and obesity who undergo bariatric surgery have significantly reduced risks of major adverse cardiovascular events and all-cause mortality when compared with those treated without surgery, the MOSAIC study shows.

The findings, which were published today in the Journal of the American College of Cardiology, suggest that intentional weight loss with bariatric surgery should be strongly considered for those with moderate-to-severe OSA, say investigators.

"Everything starts with obesity," lead investigator Ali Aminian, MD (Cleveland Clinic, OH), told TCTMD. "Obesity is the driver of disease in the first place, and we showed that if we help them lose weight, people who have moderate-to-severe sleep apnea can significantly decrease their risk of dying, and significantly decrease their risk of cardiovascular events."

Clinical guidelines for OSA recommend treatments that include positive airway pressure (PAP), oral devices, changing sleep positions, lifestyle modification with an emphasis on diet and physical activity, or surgery that involves removing tissue in the neck or jaw. While weight loss is advised for all obese patients with OSA, Aminian said there is less consideration given to bariatric surgery. In 2021, a scientific statement from the American Heart Association stated that bariatric surgery could be a treatment option for those with OSA-related comorbidity.

"In the future, the guidelines need to focus more on effective therapies for weight loss such as anti-obesity medications or bariatric surgery, not just lifestyle modification, to help people lose more weight," he said. "Lifestyle modification is needed, but it's not enough because the more weight lost, the greater the benefit."

Nishant Shah, MD (Duke University Medical Center, Durham, NC), a preventive cardiologist who wasn't involved in the study, said the results further support the urgency to aggressively battle obesity in the United States. There is accumulating evidence that cardiovascular events can be reduced when people are treated with the new anti-obesity medications, such as GLP-1 receptor agonists, and now these data supporting treatment with metabolic surgery. Recently, top-line findings from the SURMOUNT-OSA trials suggested that tirzepatide (Zepbound and Mounjaro; Eli Lily) may have significant benefits for patients with moderate-to-severe OSA.

"These results support the treatment of obesity in various settings," Shah told TCTMD. "The results of the current study also shed light into the importance metabolic surgery may have on the improving not only OSA, but also cardiometabolic risk factors, MACE, and all-cause death in obese patients. Metabolic surgery referrals are often underutilized and earlier referrals for high-risk obese patients is critical."

MOSAIC Results

OSA occurs with the complete or partial collapse of the upper airway and results in fragmented, disrupted sleep. It's a common condition, affecting nearly 1 billion individuals worldwide, and moderate-to-severe OSA is strongly linked to excess weight and obesity, said Aminian. Bulky, fatty tissue in the neck can compress the airway while a person is laying down, and those with OSA usually wake up tired and have a poorer quality of life.

"With the hypoxia they have during the night, this increases the release of hormones and increases sympathetic tone, and that can increase blood pressure," said Aminian. "It can also increase inflammation in the body. All of these—hypoxia, autonomic dysfunction, increase in blood pressure—are risk factors for cardiovascular disease."

While OSA is typically treated with PAP to decrease symptoms, it doesn't cure it and several trials have failed to show that PAP decreases the risk of MACE or mortality. Despite the strong association with obesity, it has been uncertain if intentional weight loss in patients with OSA can decrease the risk of cardiovascular outcomes. There have been no randomized trials to date.

MOSAIC was a retrospective cohort study of patients with obesity and moderate-to-severe OSA treated at the Cleveland Clinic Health System between 2004 and 2018. All patients were referred to clinic for bariatric surgery for weight loss. Moderate-to-severe OSA was defined as 15 or more events per hour based on polysomnography or a home sleep apnea test within 1 year of surgery. In total, 13,657 adults (mean age 52.0 years; 54.9% male) with obesity were included in the analysis, of whom 970 underwent bariatric surgery (either Roux-en-Y bypass or sleeve gastrectomy).

The researchers analyzed outcomes using overlap weighting and regression analysis, the latter a propensity-score method that attempts to mimic a randomized trial. With overlap weighting, patients are assigned weights proportional to the probability they would belong to the opposite treatment group, a method that ensures patient characteristics are balanced between two groups.

The cumulative incidence of MACE—a composite of coronary and cerebrovascular events, as well as heart failure (HF), atrial fibrillation (AF), and all-cause mortality—at 10 years was 27.0% in the surgical group versus 35.6% in the nonsurgical arm (adjusted HR 0.58; 95% CI 0.48-0.71). The results were consistent across various subgroups, with no heterogeneity seen for the primary endpoint based on sex, age, body mass index, race, smoking status, and other factors.

All-cause mortality at 10 years also was lower in the surgical group: 9.1% versus 12.5% (adjusted HR 0.63; 95% CI 0.45-0.89). Regarding other secondary endpoints, the risks of HF and coronary events were significantly lower in the surgical arm, but the incidence of cerebrovascular events and AF did not differ between groups.

At 10 years, patients treated with bariatric surgery lost approximately 33.2 kg compared with 6.6 kg for the control group. A decade after surgery, those treated with surgery had maintained a loss of 24.0% of their body weight versus 4.7% for those in the nonsurgical group.

Shah was impressed by the findings, calling it "as strong of an observational study as you can find," but pointed out it is a single center study, which limits generalizability to other communities, countries, or health systems. "There also is residual confounding, even though the authors did an amazing job to limit it, in any observational study," he said. "Thus, it is still important to have supporting data with randomized clinical trials that are multicentered with adjudicated hard endpoints."

Weight Loss or Less Sleep Apnea?

To TCTMD, Aminian said this is the first study showing that bariatric surgery can lower the risk of cardiovascular events and improve survival in patients with obesity and OSA.

In a prior study, the researchers showed that Roux-en-Y bypass surgery was associated with greater weight loss, better diabetes control, and a lower risk of MACE in patients with obesity and type 2 diabetes. In 2020, a Swedish observational study found that bariatric surgery was associated with longer life expectancy when compared with usual care in patients with obesity. Cardiovascular and cancer mortality were also lower in those treated surgery.

The reductions in MACE and all-cause mortality with bariatric surgery seen in MOSAIC are likely attributable both to weight loss and treatment of OSA, said Aminian.

"It's hard to differentiate," he said. "Losing weight, all those cardiometabolic risk factors—blood pressure, cholesterol, hyperglycemia, diabetes, inflammation—are going to improve. So, there's systemic effects, but at the same time, when fat goes away, including from around the neck area, the severity of sleep apnea is going to improve." He noted that a small subset of patients had a repeat sleep study performed a few years after bariatric surgery. In this group, 58% had severe OSA at baseline, but this number declined to 13% after surgery.

When compared with the surgical patients, the 10-year incidence of MACE was higher in the subset of nonsurgical patients who lost less than 10% of their body weight (adjusted HR 0.45; 95% CI 0.36-0.57). There was no difference in MACE outcomes between the control group who lost more than 10% of their body weight and the bariatric surgery group.

"This supports the hypothesis that the amount weight loss maybe the biggest driver of benefit, independent of how it is lost," said Shah. "However, multicentered randomized data will certainly make the hypothesis clearer if there remains any debate."

With the introduction of GLP-1 receptor agonists for weight loss, Aminian suspects the results would be comparable. "It's the weight loss itself that's important," he said. "It doesn't matter how they get to that weight loss, or how they lose weight, they're going to see the benefits."  

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