Improved early screening for heart failure with preserved ejection fraction using pulse wave-derived measures of arterial stiffness

J. Gronwald (Göttingen)¹, C. Becker (Göttingen)¹, L. Regent (Göttingen)¹, M. Lange (Göttingen)¹, S. Gersch (Göttingen)¹, T. Lange (Göttingen)¹, A. Schuster (Rosdorf)², M. Koziolek (Göttingen)³, M. Wallbach (Göttingen)³, K. Toischer (Göttingen)¹, A. Schulz (Göttingen)^1
1Universitätsmedizin Göttingen Herzzentrum, Klinik für Kardiologie und Pneumologie Göttingen, Deutschland; ²Forum Medizin GbR Kardiologie Rosdorf, Deutschland; ³Universitätsmedizin Göttingen Nephrologie und Rheumatologie Göttingen, Deutschland

Background
Heart failure with preserved ejection fraction (HFpEF) represents a major public health problem while early diagnosis remains challenging. Established screening models, such as the HFpEF-ABA score, incorporate conventional cardiovascular risk factors to detect HFpEF in patients who already present with shortness of breath. As arterial stiffness was recently suggested as a very early phenomenon in the pathogenesis of HFpEF, we set out to investigate whether arterial stiffness, as measured by non-invasive pulse wave analysis, may improve early screening for HFpEF in patients at risk of the disease.

Methods
Between February and October 2024, 192 patients referred to internal medicine outpatient departments for consultations unrelated to heart failure were prospectively enrolled. Inclusion criteria comprised presence of at least one risk factor for HFpEF (age>60 years, arterial hypertension (RR≥140/90mmHg or ≥2 antihypertensive drugs), diabetes, chronic kidney disease (CKD, eGFR <60ml/min/1,73m2 or albumin creatinine ratio ≥30mg/g), obesity (BMI≥30kg/m2). Patients with established diagnosis of HFpEF, left ventricular ejection fraction <50%, known cardiomyopathy, severe lung disease, prior cardiotoxic chemotherapy or severe heart valve disease were excluded from further evaluation. Systematic data collection included anamnesis, laboratory testing and transthoracic echocardiography. Pulse wave velocity (PWV) and aortic augmentation index (AIXao) as measures for arterial stiffness were derived from oscillometric pulse wave analysis. HFpEF was diagnosed in patients with ≥5 points in the HFA-PEFF score. The HFpEF-ABA score was used as a reference standard for risk-screening and calculated according to the original publication.

Results
After exclusion of patients with incidental findings during diagnostic assessments, 184 patients (55±17 years, 38% female) were included for final analysis. Of the patients evaluated, 30 (16%) received a first diagnosis of HFpEF. Patients diagnosed with HFpEF were older (54 vs. 67 years, p=0.001) and had CKD more frequently (71(46%) vs. 21(70%), p=0.025). No differences were found regarding sex, BMI, presence of arterial hypertension, diabetes and history of atrial fibrillation compared to patients without HFpEF. NT-proBNP levels were elevated in the HFpEF group (78 (42-167)ng/l vs. 326 (224-602)ng/l, p<0.001). Patients with HFpEF had increased arterial stiffness as indicated by higher AIXao (25.4(15.5-26.9)% vs. 37.1(31.7-49.5)%, p<0.001) and higher pulse wave velocity (9.6(8.5-10.5)m/s vs. 10.3(9.0-12.0)m/s, p=0.048). Both, increased PWV and AIXao were associated with HFpEF and both parameters remained associated with HFpEF after adjustment for age, sex, BMI and eGFR (PWV: OR 1.335, 95% CI 1.038-1.717, p=0.025; AIXao: OR 1.075, 95% CI 1.031-1.121, p<0.001). Receiver operating characteristic (ROC) curve analyses for detection of HFpEF revealed an area under the curve (AUC) of 0.670 (95 % CI 0.581-0.759, p<0.001) using HFpEF-ABA score while age-adjusted PWV and age-adjusted AIXao had superior diagnostic accuracy for detecting HFpEF (PWV: AUC 0.794, 95% CI 0.713-0.875, p<0.001; AIX: AUC 0.826, 95% CI 0.752-0.900, p<0.001; Fig. 1).

Conclusion
In a population at risk for HFpEF, pulse wave-derived measures of arterial stiffness enhance screening for HFpEF, outperforming the HFpEF-ABA score. Systematic assessments of arterial stiffness beyond conventional risk factors may improve early diagnosis of HFpEF.