Ventricular–arterial coupling in the clinical evolution of acute ischemic stroke

Cardiac function and its efficient coupling with the arterial system are of extreme importance not only in the maintenance of an adequate tissue perfusion, but also in determining the potentially adverse effects of several cardiovascular risk factors – in particular hypertension and atherosclerosis – on target organ damage [1]. In the setting of cerebrovascular disease, arterial damage caused by increased blood pressure (BP) may be exacerbated by higher vascular stiffness and by a concomitant reduced cardiac performance, leading to a decrease in cardiac output and in tissue perfusion. Moreover, left ventricular (LV) dysfunction may be ‘per se’ associated with an increased risk of ischemic stroke. Patients with heart failure not only display a high incidence of ischemic stroke, up to 10.4% per year [2], but also a more severe extent of the subsequent neurologic alterations, with very high cardiovascular morbidity and mortality [3–5]. A poorer neurological outcome after ischemic stroke was observed in elderly patients with overt heart failure and low (i.e. <35%) ejection fraction [6,7], who also display a worse response in the presence of hypertensive emergencies and urgencies [8]. Several aspects may contribute to these aspects, namely, the higher incidence of atrial fibrillation and of cerebral hypoperfusion, as well as the association with diffuse atherosclerosis and with other known cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes, smoking history, coronary artery disease and atherosclerosis of the extracranial and intracranial vessels. A very recent article by Di Tullio et al.[9] evaluated the relationship of LV ejection fraction with stroke and cardiovascular events in 2305 patients with systolic heart failure (defined as ejection fraction <35%) and sinus rhythm, who were enrolled in the heart failure Warfarin Versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. The authors concluded that in patients with systolic heart failure and sinus rhythm, ejection fraction is inversely associated with death and its components, whereas an association with stroke was only observed for very low ejection fraction values (i.e. <15%), with a 2.125 adjusted hazard ratio [95% confidence interval (CI) 1.182–3.818; P = 0.012] [9]. Obviously, the presence of atrial fibrillation exposes to a much higher risk of stroke, and both the CHADS2 and the CHA2DS2–VASC scores take into account the presence of heart failure, independent of any ejection fraction evaluation (in both acronyms, ‘C’ stands for ‘congestive heart failure’). Recently, Kondo et al.[10] showed that the CHADS2 score can also be predictive in chronic heart failure patients without atrial fibrillation. The well recognized relationship between atrial fibrillation and the risk of cerebrovascular events has been shown also in patients with heart failure and preserved ejection fraction [11]. Interestingly, the incidence of stroke in these patients was not different when compared with patients with heart failure and reduced ejection fraction (relative risk 0.85, 95% CI 0.70–1.03, P = 0.094; n = 33 773), despite a lower all-cause mortality [12]. In their attempt to clarify the relationship between ejection fraction and stroke risk in the presence of nonvalvular atrial fibrillation, Banerjee et al.[13] evaluated a cohort of 1276 patients. No difference was found in the rate of stroke between ejection fraction categories. In multivariate analyses, only previous stroke and vascular disease (but not decreased ejection fraction) independently increased the risk of stroke [13]. As to the vascular function, increased arterial stiffness is associated with higher cardiovascular risk, and carotid stiffness (as determined by ultrasonography) was shown to be a predictor of incident stroke, independent of other cardiovascular risk factors and of aortic stiffness as estimated by carotid–femoral pulse wave velocity [14]. Moreover, in the setting of ischemic stroke, arterial stiffening is associated with the acute hypertensive response, a marker of poor outcome [15]. Increased arterial stiffness may be one of the determinants of higher pulse pressure (PP), which has been shown to be associated with major adverse cardiovascular outcomes in the Reduction of Atherothrombosis for Continued Health registry [16]. Moreover, PP is higher in patients with metabolic syndrome, as shown in the Global Cardiometabolic Risk Profile in Patients with hypertension disease survey [17]. Therefore, it appears reasonable to evaluate the potential association between cardiac performance (as assessed by LV ejection fraction), arterial stiffness and acute ischemic stroke. In their article, published in the present issue of the Journal of Hypertension, Rojek et al.[18] investigated the impact of ejection fraction and arterial stiffness on the early neurological outcome after an acute cerebrovascular event. To this aim, they recruited 216 patients, in whom echocardiography and applanation tonometry were performed within 1 week after the onset of an ischemic stroke. At day 10, favorable outcome was defined as a 4 or more point improvement from baseline National Institutes of Health Stroke Scale (NIHSS) or final NIHSS of 0–1. When compared with patients with poorer prognosis, patients with a better outcome presented significantly higher ejection fraction (54.3 vs. 49.9%, P < 0.05), lower heart rate and higher pulse wave velocity at baseline. At multivariable analysis, ejection fraction at least 50% remained a significant predictor of outcome after full adjustment for potential confounders. As acknowledged by the authors, the study encompasses a number of limitations, namely the potential role of coronary artery disease, the lack of a serial evaluation of cardiac performance and of time-varying arterial BP during the hospital stay, the time delay between the onset of the acute event and the evaluation of cardiac and arterial function, the potential effect of acute stroke management strategies and the assessment of neurological outcome 10 days after stroke onset. Nonetheless, the study demonstrates that the combination of LV systolic dysfunction and increased aortic stiffness identifies patients with the poorest post-stroke prognosis. Moreover, even mild impairment of LV ejection fraction may be prognostically relevant. Because ejection fraction as a descriptor of LV performance presents major limitations, further studies are clearly needed to assess the potential interplay between cardiac function, arterial distensibility and the evolution of acute ischemic cerebrovascular events. The cross talk between the heart and the large vessels appears crucial not only in determining the risk of a vascular event, but also in modulating its short-term and long-term sequelae. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.