Intended for healthcare professionals


Ann Robinson’s research reviews—19 January 2023

BMJ 2023; 380 doi: (Published 19 January 2023) Cite this as: BMJ 2023;380:p112
  1. Ann Robinson, NHS GP and health writer and broadcaster

Happy Zappy: ablating atrial fibrillation

If you had persistent atrial fibrillation lasting longer than a week, would you try drugs first or opt for ablation? This three year follow-up of 303 patients in the EARLY-AF trial, found that initial ablation was associated with fewer episodes of persistent atrial fibrillation compared with antiarrhythmic drug therapy (1.9% v 7.4%), less recurrent atrial tachyarrhythmia (56.5% v 77.2%), and reduced atrial fibrillation burden, which is the percentage of monitored time spent in atrial fibrillation (0 v 0.12%). Implantable devices improved reliability of the findings, but drug therapy may not have been optimal in all cases, which would limit the reliability of the results. Overall, ablation was safe compared with antiarrhythmic drugs, with serious adverse events of 4.5% versus 10.1%. But even if you opt for ablation, you can’t throw away all your pills; anticoagulants are still recommended if you’re at increased risk of stroke.

N Engl J Med doi:10.1056/NEJMoa2212540

Happy Zappy: the sequel

Ablation of the pulmonary veins (pulmonary vein isolation), where most ectopic beats originate in persistent atrial fibrillation, works well. The question is whether zapping the left atrial posterior wall, which may also be a source of ectopic beats (posterior wall isolation), in addition to pulmonary vein isolation produces even better results?

This first ever randomised trial comparing pulmonary vein isolation plus posterior wall isolation with pulmonary vein isolation alone, in 338 patients with persistent atrial fibrillation, found no significant difference in the number who remained free of recurrent atrial arrhythmias without medication for a year after their first catheter ablation procedure (52.4% v 53.6%). I was surprised that ablation only works in half of cases and intrigued that adding posterior wall isolation didn’t improve the outcome, when theoretically it should. Multiple ablation procedures pushed up the success rate but still failed to show any benefit from adding posterior wall isolation (58.2 v 60.1%). It took significantly longer to zap the posterior wall as well as the pulmonary vein (ablation time 24 v 28 minutes) with no discernible benefit. Side effects were few, and there were no deaths, strokes, or oesophageal fistulae. If money were no object, post-ablation rhythm monitoring would always use implantable cardiac devices for accuracy. Future studies are likely to use atrial fibrillation burden as a more clinically meaningful primary outcome.

JAMA doi:10.1001/jama.2022.23722

Do healthy diets work?

This is perfect January fodder. A huge US cohort study asked whether there’s any association between recommended national dietary guidelines and total and cause-specific mortality. Follow-up of over 75 000 women from the Nurses’ Health Study and over 44 000 men from the Health Professionals Follow-up Study between 1984-6 and 2020 showed that greater adherence to several healthy eating patterns laid out in US dietary guidelines was associated with a lower risk of death across different racial and ethnic groups (comparing highest with lowest quintiles, pooled multivariable adjusted hazard ratio of total mortality was 0.8), and all dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease.

Participants in these studies were mostly health professionals so findings may not be generalisable to the population at large. Sceptics who are rightly concerned about the vagaries of self reporting and potential for confounding in observational studies may take comfort from the fact that Food Frequency Questionnaires used in this study were well validated against diet records and biomarkers. Diets are a mix of multiple components, so these types of studies can only examine combinations of foods rather than individual foods; who knows whether it’s blueberries alone or the whole fruit salad that make you live longer? Unhealthy diet is now a leading preventable cause of death globally, and providing realistic and reliable advice is arguably one of our most important tasks as doctors.

JAMA Intern Med doi:10.1001/jamainternmed.2022.6117

Positive news for HER2

Women with HER2-positive metastatic breast cancer that has persisted or recurred after first line treatment with trastuzumab and a taxane (with or without pertuzumab) need effective and safe second line treatment options. In this multicentre trial of 524 women, trastuzumab deruxtecan (which delivers the toxic substance deruxtecan into cancer cells) showed a statistically significant improvement in overall survival versus trastuzumab emtansine (which contains the cytotoxic agent DM1.)

Trastuzumab deruxtecan resulted in better median progression-free survival (28.8 months v 6.8 months), higher overall survival at 12 months (94% v 86%), and greater objective response rates (79% v 35%). The safety profiles were similar, with serious adverse events including interstitial lung disease of 25% versus 22%. Better antiemetic treatment may improve the acceptability of the treatment. Trastuzumab deruxtecan is likely to become standard second line treatment for HER2-positive metastatic breast cancer, and studies are under way to see whether it’s also safe and effective as first line treatment.

Lancet doi:10.1016/S0140-6736(22)02420-5

High stakes for kidneys

What can we offer patients with chronic kidney disease (CKD) to keep their kidneys functioning for as long as possible without needing dialysis or a transplant? This multicentre, two year study of 6609 people with an eGFR of 20-45 mL/min/1.73 m2 (or 45-90 and albuminuria) found that there was less progression of CKD and fewer deaths from cardiovascular causes in patients treated with empagliflozin, usually used to treat diabetes, than placebo, regardless of whether they had diabetes and how severe their CKD was (13.1% v 16.9%). There was no difference in the number of serious adverse events. There were fewer cardiovascular events than expected which limited the statistical robustness of the findings although other studies have shown that SGLT2 inhibitors like empagliflozin lower the risk of cardiovascular events and deaths. Disappointingly, there was no significant difference in overall death rates (4.5% v 5.1%), but this EMPA-KIDNEY trial adds to two other large, well conducted trials (CREDENCE and DAPA-CKD) which showed similarly encouraging results in terms of disease progression and cardiovascular deaths.

Ann Intern Med doi:10.7326/M22-2904


  • Competing interests: None declared

  • Provenance and peer review: Not commissioned; not peer reviewed