Heart failure with preserved ejection fraction disproportionately affects women. Dr Pankaj Garg, lead author of a recent study published in the European Heart Journal Open, discusses the necessity of sex-specific approaches in cardiovascular diagnostics and treatment to address this disparity, and summarises how this research paves the way for future studies and clinical guidelines to embrace personalised medicine.
Despite known differences in cardiac structure and function between the sexes, there are no validated sex-specific diagnostic tools for heart failure.
Specifically focusing on heart failure with preserved ejection fraction (HFpEF), which has a higher prevalence in women versus men, our recent research investigated whether sex influences the assessment of left ventricular filling pressure (LVFP) using cardiac magnetic resonance (CMR), which is crucial for diagnosing heart failure regardless of ejection fraction.
Our study’s motivation lay in enhancing diagnostic accuracy and enabling personalised treatment strategies by considering sex-specific physiological variations.
The heart failure study
In the derivation cohort of 835 patients (60% female), participants were suspected of having pulmonary hypertension and heart failure. Each patient underwent invasive right heart catheterisation and CMR within a 24-hour period.
We utilised multivariable regression to develop a sex-specific CMR model for estimating LVFP, measured by pulmonary capillary wedge pressure (PCWP). This model included left atrial volume (LAV) and left ventricular mass (LVM) to account for the structural differences between sexes.
The study further validated the model using a cohort of 454 patients with confirmed heart failure, of which 36% were female. This validation assessed primary endpoints, including heart failure hospitalisation and major adverse cardiovascular events (MACE).
The derivation cohort was meticulously selected, and the close timing between the invasive right heart catheterisation and CMR ensured accuracy in correlating the two measurements.
Multivariable regression allowed for incorporating relevant cardiac parameters that differ between sexes, such as LAV and LVM. These parameters are crucial as they reflect the anatomical and functional differences in the cardiac structure between men and women.
The validation cohort provided a robust testing ground for the model, ensuring its applicability in a real-world clinical setting. The primary endpoints of heart failure hospitalisation and MACE are clinically relevant, reflecting the model’s potential to predict significant adverse outcomes.
The findings that the sex-specific CMR-derived PCWP was significantly associated with these endpoints over a considerable follow-up period underline the model’s prognostic value.
Generic vs sex-specific results
The comparison between the generic and sex-specific CMR-derived PCWP models revealed significant differences in LVFP estimates between males and females when using the generic model (14.7 ± 4 vs. 13 ± 3.0 mmHg, P < 0.001). These differences were absent when using the sex-specific model (14.1 ± 3 vs. 13.8 mmHg, P = 0.3), underscoring the importance of a tailored approach.
Unlike the generic model, the sex-specific CMR-derived PCWP demonstrated a significant association with heart failure hospitalisation (hazard ratio (HR) 3.9, P = 0.0002) and MACE (HR 2.5, P = 0.001) over a mean follow-up period of 2.4 ± 1.2 years.
This indicates that accounting for sex improves the precision and prognostic performance of CMR biomarkers for heart failure.
The need for tailored diagnostics
Our study emphasises the substantial differences in cardiac structure and function between men and women. Women typically have smaller cardiac dimensions, higher heart rates and distinct patterns of cardiac remodelling compared with men.
These differences are crucial as they affect the interpretation of diagnostic tests and the effectiveness of subsequent treatments. HFpEF, which is more prevalent in women, is characterised by a stiffer left ventricle, leading to increased LVFP and LAV. In contrast, men are more prone to heart failure with reduced ejection fraction (HFrEF), which follows different pathophysiological mechanisms.
Using generic models for estimating LVFP often leads to misdiagnosis or underestimation of disease severity in women, resulting in inadequate treatment. The sex-specific models developed in this study offer a more accurate assessment of cardiac function, enhancing risk stratification and enabling personalised treatment plans.
Indeed, our study demonstrated that the sex-specific CMR model is more effective than traditional diagnostics in predicting heart failure hospitalisation and MACE, highlighting the necessity of tailored diagnostic tools. Improved diagnostic accuracy facilitates timely and appropriate interventions, ultimately enhancing clinical outcomes for both men and women.
A ‘paradigm shift’ in heart failure care
Recognising and addressing sex differences in cardiovascular diseases is essential for developing clinical guidelines that incorporate sex-specific diagnostic and treatment approaches.
Our research underscores the importance of considering sex differences in cardiovascular physiological models and the need for more studies focused on these differences to enhance the overall quality of care and reduce health disparities between men and women.
By developing and validating a sex-specific CMR model for assessing LVFP, we have shown that accounting for sex-specific factors significantly improves diagnostic accuracy and prognostic performance in heart failure patients.
Incorporating these factors into clinical practice can refine heart failure diagnosis and treatment, leading to better health outcomes and personalised patient care. The findings advocate for integrating sex-specific approaches in clinical guidelines and practices, ensuring that both men and women receive optimal and tailored cardiovascular care.
This approach enhances diagnostic precision and facilitates better management of heart failure, having profound implications for clinical practice and potentially reducing the burden of this condition globally.
Furthermore, our study highlights the necessity of personalised medicine and advocates for a paradigm shift in how heart failure is diagnosed and treated. The significant differences found in LVFP estimates between males and females using the generic but not the sex-specific model illustrate the potential for misdiagnosis and inappropriate management if sex differences are not accounted for.
Our findings are a call to action for the healthcare community to prioritise research on sex differences in cardiovascular diseases. This will lead to developing diagnostic tools and treatment protocols that reflect sex-specific physiological differences, ultimately improving patient outcomes.
Author
Dr Pankaj Garg MD MRCP PhD
Associate professor in cardiovascular medicine, University of East Anglia, and honorary consultant cardiologist, Norfolk and Norwich University Hospitals Foundation Trust, UK
