Early detection of heart failure through exercise testing

This editorial refers to ‘Haemodynamic gain index and heart failure incidence- Prognostic and preventive value’, by B. Vainshelboim and J. Myers, https://doi.org/10.1093/eurjpc/zwad236. Heart failure (HF) is a clinical syndrome associated with significant morbidity and mortality, poor functional capacity and quality of life, and high healthcare costs.1 While incidence of ischaemic heart disease is declining in developed countries, prevalence of HF is increasing globally due to an ageing population and higher prevalence of HF with preserved ejection fraction (HFpEF).2 Treatment of HF at a late stage is associated with less prognostic benefit; thus, early detection and prevention of HF have been named as a major healthcare priority worldwide.3 Exercise intolerance and dyspnoea are key HF symptoms, but unfortunately, history and physical examination alone are not sensitive and specific to detect incident HF.4 Especially in patients with HFpEF, a long pre-symptomatic phase exists, and limitations of physical activity are often manifested at a late stage in an elderly, co-morbid population.5 At an early stage, resting examinations can be normal, and exercise stress may be used to elicit symptoms, demonstrate physical limitation, and stratify risk of future cardiovascular (CV) events.5,6 Several diagnostic tests are available to enable early detection of HF: blood natriuretic peptide sampling, echocardiography, and multi-variable risk scores.7 These tests are unfortunately not universally available, and depending on the healthcare setting, they can be associated with significant costs or delays, even in developed countries.8 Active screening for HF is recommended in patients at high risk of HF (e.g. patients with hypertension, atherosclerotic CV disease, diabetes, metabolic syndrome and obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or positive family history of cardiomyopathy) in the 2022 American College of Cardiology/American Heart Association HF guidelines.7 Thus, an unmet need for easy, widely applicable screening tests for HF remains. In this issue of the journal, Vainshelboim et al.9 demonstrated that the haemodynamic gain index (HGI), a simple metric calculated from heart rate (HR) and systolic blood pressure (SBP) during exercise, predicted future development of HF with high accuracy. Haemodynamic gain index is calculated as [(HRpeak ∗ SBPpeak) − (HRrest ∗ SBPrest)]/(HRrest ∗ SBPrest) and can thus be easily implemented in every standard incremental exercise test. The authors calculated the HGI in a large cohort of 5539 men free from HF at baseline and are to be commended for the long-term follow-up of this population. The predictive value of HGI was independent of traditional risk factors, including cardiorespiratory fitness. While the HGI had previously been demonstrated to predict all-cause mortality in different populations, the association with HF is novel and might even explain the relation between HGI and mortality.10–12 Of note, the population characteristics precluded the inclusion of women in the current study, but the HGI has previously been validated in a general female population.10 Several studies have demonstrated the usefulness of other parameters obtained during exercise testing to predict incident HF (Table 1). The HGI can be added to this list; whether it may provide incremental benefit over existing parameters remains to be assessed. Exercise test parameters predictive of incident heart failure CI, confidence interval; CO, cardiac output; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HR, heart rate; ICD, International Classification of Diseases; NR, not reported; PAWP, pulmonary artery wedge pressure; PP, pulse pressure; Q1–Q4, Quartile 1–4; SBP, systolic blood pressure; SD, standard deviation. Exercise test parameters predictive of incident heart failure CI, confidence interval; CO, cardiac output; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HR, heart rate; ICD, International Classification of Diseases; NR, not reported; PAWP, pulmonary artery wedge pressure; PP, pulse pressure; Q1–Q4, Quartile 1–4; SBP, systolic blood pressure; SD, standard deviation. Considering the practical use of HGI in daily routine, an HGI below median (<1.05, associated with a more than two-fold increased incidence of HF) could trigger further in-depth CV investigations. The HGI might serve as a ‘gatekeeper’ for further HF testing as well as ‘red flag’ in pre-symptomatic individuals. Thus, the study by Vainshelboim et al. adds to existing evidence confirming exercise stress testing as CV screening tool: (i) exercise intolerance is a key manifestation of HF regardless of left ventricular ejection fraction, (ii) exercise may unmask physical limitation in a pre-symptomatic stage, (iii) it is a widely available test that can be performed without specialist supervision, and (iv) several exercise parameters, including the HGI, accurately predict incident HF. This may provide opportunities for prevention or early intervention, which has been associated with better outcomes.6 Exercise testing may thus serve as the crystal ball that offers not foretellings of doom but an alternate ending, a rewrite towards a healthier prognosis. This work was supported by the Research Foundation Flanders (FWO; Brussels, Belgium) (senior clinical investigator grant to EMVC). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. No new data were generated or analysed in support of this research.