The Pump and the Pipes: Another Step towards the Non-Invasive Evaluation of Left Ventricular-Arterial Coupling in the Spectrum of Heart Failure

In patients with or at risk of heart failure (HF), especially in those falling into the ill-defined phenotype characterised by preserved left ventricular ejection fraction (LV EF, HFpEF), vascular remodelling and arterial dysfunction likely have an equally relevant impact as cardiac dysfunction on the development and progression of the disease [1‒4]. Noteworthy, a growing body of evidence demonstrates that focusing on the complex interactions between cardiac and systemic arterial function (i.e., ventricular-arterial coupling [VAC]), rather than considering the heart and vessels as two separate and independent entities, can significantly refine the pathophysiological characterisation and risk stratification of patients with HF and other cardiovascular conditions [5]. Historically, VAC has been usually derived from pressure-volume loops obtained during cardiac catheterisation, as the ratio of arterial elastance (EA) to LV end-systolic elastance (EES) [5]. While this is indubitably the most accurate index of the interaction between the heart and systemic arteries, its applicability is obviously limited due to high cost, specialised equipment, expertise requirement, and small but measurable risk. Standard non-invasive estimations based on transthoracic echocardiography, such as the single-beat method or the simplified LV end-systolic volume to stroke volume ratio, have the advantage of being much more easily available in clinical practice but are also less reliable [5]. In the last years, novel methods to evaluate VAC without the need for cardiac catheterisation have been introduced and validated, using pulse-wave velocity (PWV) and LV global longitudinal strain (GLS) as proxies for EA and EES, respectively [1, 6‒8].In the latest issue of this Journal, Wang and Lu [9] present interesting data on the pathophysiologic impact of VAC differences in healthy subjects and in patients at risk of or with established HF (stages A to D according to the American College of Cardiology/American Heart Association HF Staging System), irrespective of LV EF. They evaluate VAC as the ratio between estimated PWV (ePWV) and LV GLS. As shown by Greve and colleagues [7], ePWV calculated based solely on age and mean blood pressure has a similar prognostic value compared to tonometry-derived carotid-femoral PWV in patients with cardiovascular disease. It is worth noting that carotid-femoral PWV is the gold standard for measuring central arterial stiffness [10]. Still, it is relatively time-consuming, is prone to errors related to the measurement of the surface distance, and might be burdened by accuracy issues (e.g., in obese patients). Finally, carotid-femoral PWV reflects the stiffness of distal muscular arteries, ignoring the role of the elastic proximal aorta, which represents one of the most significant pathophysiological determinants of VAC [1]. In this regard, it has been previously demonstrated that the ratio of aortic arch PWV to GLS as a measure of VAC was more closely related to the cardiopulmonary response to exercise [11] and enabled more precise differentiation of patients at risk of or with established HF, compared to the ratio of carotid-femoral PWV to GLS [1]. Thus, evaluating the potential differences between the ePWV/GLS ratio and the aortic arch PWV/GLS ratio would have been exciting.In the present article, patients with HFrEF showed the highest ePWV/GLS values, followed by patients with HFpEF, who in turn had higher ePWV/GLS compared to controls and patients in stages A-B [9]. This is in partial discordance with the data from our research group, showing a higher aortic arch PWV/GLS ratio in patients with HFpEF compared to those with HFrEF, notwithstanding lower GLS in the latter group. However, the difference might be due to the low cardiac output and central blood pressure characterising the HFrEF subgroup, which might reduce the mechanical stimulation and pulsatile load on the aortic arch without influencing the stiffness of the distal muscular arteries. Furthermore, ePWV/GLS showed a moderate positive correlation with non-invasively estimated EA/EES, indeed highlighting its utility as a quickly available alternative non-invasive measure of VAC. ePWV/GLS also correlated with worsening abnormalities in cardiovascular structure and function, such as increased E/e’ ratio and LV mass index. While this may be due to the fact that the highest ePWV/GLS values were observed in patients with HFpEF and HFrEF, who also displayed the most advanced cardiac structural and functional abnormalities, it is conceivable that increased LV afterload and pulsatile load, caused by heightened arterial stiffness, would result in LV hypertrophy, fibrosis, and ultimately increase LV stiffness. Based on these results, the authors propose the use of the ePWV/GLS ratio to differentiate patients at risk of or with established HF from healthy subjects. While a strong correlation was found between the ePWV/GLS ratio and NT-proBNP, the approach proposed by the authors might be premature, as the paper does not demonstrate the superiority, or at least non-inferiority, of the ePWV/GLS ratio compared to the current criteria for the diagnosis of HF. Furthermore, it requires the measurement of GLS, which, while useful in many cases, is not strictly necessary for the echocardiographic evaluation of patients with suspected HF. Nonetheless, we agree with the authors that this novel indicator might be integrated into risk scores to aid in complex clinical tasks such as identifying and following patients in the early stages of the “slippery slope” of HF. It may also allow for refined characterisation of the pathophysiological impact of the abnormal interaction between the LV and systemic arteries in HF, paving the way for tailored therapeutic solutions that might reduce arterial stiffness and ameliorate VAC. This might prove particularly useful in patients falling into the complex spectrum of HFpEF. Interestingly, the latter condition seems to be not only characterised by impaired coupling between the LV and systemic arteries but also between the right ventricle and pulmonary arteries and between the left atrium and the LV [12]. In summary, the present research work has the merit of expanding the evidence on the utility of ePWV as a readily available and reliable index of arterial stiffness and on the importance of the non-invasive evaluation of VAC to refine the pathophysiological characterisation of patients across the cardiovascular continuum.The authors have no conflicts of interest to declare.The authors have not received any financial support.Conceptualisation and writing – original draft preparation: Nicolò De Biase and Nicola Riccardo Pugliese; supervision and writing – review and editing: Kristina Kopeva. All authors carefully read the manuscript and gave final approval.