‘Lemon-on-sticks’ phenotype indicates poor prognosis in heart failure, finds study

Analyses identified a high-risk subgroup of patients – described as the ‘lemon-on-sticks’ phenotype – who had a high disease burden and poor outcomes, according to results presented today at Heart Failure 2026, the annual congress of the Heart Failure Association of the European Society of Cardiology.

Over recent years, advancements in medical and device therapies have substantially improved outcomes for patients with heart failure. However, the disease state is complex and heterogeneous, and there is a need to personalise therapy to maximise benefits.

Explaining the rationale for the presented analysis, Doctor Camilla van der Hoef from University Medical Centre Groningen, Netherlands, said: “Obesity is a risk factor for cardiovascular disease, yet paradoxically, in patients with established heart failure, a higher body mass index (BMI) is associated with better survival. BMI does not distinguish between different components of body composition, including fat, fluid and muscle mass. There is also evidence that a higher waist-to-hip ratio (WHR), an indicator of abdominal fat, is associated with worse outcomes in patients with heart failure. We therefore investigated the clinical phenotypes associated with BMI and WHR, and all-cause mortality in patients with heart failure.”

Data from 1,467 patients were analysed from the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort. The data were categorised into high and low BMI and WHR using the median cutoffs (BMI 28.1 kg/m²; WHR 0.97). Four phenotypic quadrants were analysed. Based on body shape, the low BMI/high WHR subgroup was described as the ‘lemon-on-sticks’ phenotype, while the high BMI/low WHR subgroup was described as the ‘general adiposity’ phenotype. The other two subgroups were the concordant BMI/WHR phenotypes: low BMI/low WHR and high BMI/high WHR. Clinical characteristics, blood biomarkers and all-cause mortality were compared across the phenotypes.

Patients with the ‘lemon-on-sticks’ phenotype (low BMI/high WHR) showed the strongest signs of congestion, had the highest concentrations of the heart strain biomarker, N-terminal pro-B-type natriuretic peptide, and presented with a predominantly inflammatory profile.

Of note, patients with the ‘lemon-on-sticks’ phenotype had double the risk of all-cause mortality compared with the ‘general adiposity’ phenotype (age- and sex-adjusted hazard ratio [HR] 2.20; 95% confidence interval [CI] 1.59 to 3.03; p<0.001). All-cause mortality was significantly higher in the high BMI/high WHR phenotype than the ‘general adiposity’ phenotype (HR 1.50; 95% CI 1.09 to 2.07; p=0.013) but was not significantly different in the low BMI/low WHR phenotype (HR 1.28; 95% CI 0.92 to 1.76; p=0.138).

Doctor van der Hoef concluded: “Our analyses suggest that in heart failure, BMI and WHR capture distinct biological and clinical phenotypes. Integrating these measures identified the high-risk ‘lemon-on-sticks’ phenotype where patients have relatively low overall body mass together with disproportionate central distribution of fat and a high burden of adverse disease indicators. Further longitudinal studies of changes in body composition over time are warranted, with the ultimate aim of enabling more precise risk assessment and individualised management of patients with heart failure.”