Brachial artery flow mediated assessment: A tool to predict the response to chronic PDE5 inhibition with tadalafil in patients with erectile dysfunction

Abstract

Subjects, n 26 11 15 Age, years 60.9±9.6 59.4±10.7 62.0±8.9 BMI 26,5±3,5 26±3,5 26,9±3,5 HB1c 6,8±1,7 5,6±0,3 7,6±1,9 Smoking history 11/26 2/11 9/15 Comorbidities Diabetes, % 6/26 0/11 6/15 Hypertension, % 3/26 0/11 3/15 Diabetes+hypertension 6/26 0/11 6/15 ⁎ Corresponding author. Andrology, San Paolo Hospital, University of Milano, Via A. di Rudini, 8 20142 Milano, Italy. E-mail address: mancinis178@msn.com (M. Mancini). Impairment of cavernosal arteries responsiveness is the most common cause of erectile dysfunction (ED) whose pathogenesis primarily depends on vascular endothelial dysfunction [1]. Atherosclerotic risk factors increase the rate of ED and most male patients with angiographically documented coronary artery disease (CAD) exhibit ED [2]. Endothelial injury is a basic step in the development of artheriosclerosis and its in-vivo evaluation by brachial artery flow mediated dilatation (BAD) technique provides relevant clinical and prognostic information [3]. Phosphodiesterase 5 inhibition (PDE5i) is an effective strategy for ED improvement which improves BAD response in both ED and non-ED patients [4,5]. It is undefined whether different pretreatment endothelial BAD patterns may predict the ED response to chronic PDE5i therapy. 26 impotent patients with no previous cardiovascular events diagnosed by IIEF questionnaire (questions 1, 2, 3, 4, 5, and 15) were enrolled and grouped according to absence (group A; n=11) or coexistence of hypertension and diabetes comorbidities (group B; n=15, n=6 with diabetes n=3 with hypertension, n=6 with diabetes and hypertension). All underwent brachial artery flowmediated evaluation (high resolution ultrasound Philips 11 MHz linear-array transducer) with measures of BAD and hyperemic (HYP) response [6], penile Duplex Ultrasound (DS) cavernosal peak systolic velocity (PSV) measure [7], and IIEF questionnaire evaluation before and after PDE5i treatment with tadalafil 10 mg on alternate days for 30 days. Differenceswithin group A and between group A and Bwere tested by ANOVA analysis and paired and unpaired Student t-test when appropriate. Linear regression analysis with least square method was used to correlate delta PSV with delta BAD and HYP. Populations were similar in terms of age, BMI, HB1c, and smoking history (Table 1). In all patients, a trend but not statistically significant increase in PSV (p=0.08) after tadalafil was observed while IIEF increased significantly (pb0.01) (Table 2). Significant differences in the BAD response were observed between group A and group B before and after treatment, even though tadalafil did not cause significant BAD improvement in both populations. Conversely, group A exhibited a significantly greater HYP response both at preand post-tadalafil treatment (Table 3). Post-tadalafil HYP response was significantly increased just in group A. After disease distribution a significant correlation between delta PSV and delta HYP was found in group A unless group B (Fig. 1A and B, r=0.677; p=0.022 and r=0.24; p=NS). The major finding of our study is that BAD may be a helpful screening technique in the identification of impotent patients that very likely may or may not get a hemodynamic advantage from midterm PDE5i treatment with tadalafil at current doses. Our observation provides a rationale for systematically using PSV evaluation in combination with BAD in the management of ED patients. In populations with variable degrees of cardiovascular risk, brachial ultrasound assessment has emerged as a strong and independent predictor of cardiovascular morbidity and mortality [3]. In this regard, changes in arterial diameter are considered more reliable than changes in flow. This because variations in flow reflect those in forearm microcirculation and brachial artery occlusion may still induce some degree of responsiveness to post-ischemic reperfusion stimuli even when the lumen of brachial conduit artery does not change significantly. In the present study no correlation was observed between changes in BAD and PSV. Conversely, brachial artery HYP response correlated with changes in PSV, at least in ED patients without hypertension and/ or diabetes. Remarkably, this seems to reflect a behavior similar to that observed at penile microcirculatory level and support the idea that in the initial stages of a penile arterial disease, a reduced PSVmay arise from an impaired microcirculation reactivity rather than from a real atherosclerotic process. Major study limitations are the small number of patients investigated, especially when considering the subset with comorbid conditions such as diabetes or hypertension and the lack of a followup period with PDE5i drug withdrawal. In conclusion, a preserved reactivity at brachial artery level in the absence of comorbid conditions predicts a favorable response at penile microcirculatory level to standard doses of PDE5i treatment. This study was supported by funds provided by the Monzino Foundation, Milano-Italy. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [8].