## 4 Discussion  
Our prospective study shows that PDE5 inhibition with tadalafil for 6 months, in patients who underwent penile rehabilitation for erectile function secondary to radical prostatectomy, is associated with favorable effects on left ventricular diastolic function, improving the E/e' ratio and the tricuspid jet (TR). Although over 20 parameters have been suggested to noninvasively assess left ventricular diastolic function, not all these parameters are currently utilized in routine clinical practice [13]. In 2016, the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) proposed a simple algorithm for the noninvasive evaluation of left ventricular diastolic function based on the evaluation of the E/e' ratio and peak TR velocity [13]. The ESC 2021 guidelines on heart failure confirmed that both the E/e' ratio and peak TR velocity should be used as echocardiographic markers of left ventricular diastolic dysfunction/ raised left ventricular filling pressures [18]. It remains to be proven that the improvement in E/e' ratio and peak TR velocity observed in our patients after tadalafil therapy may have clinical importance. Indeed, the patients enrolled in our study showed no signs of left ventricular diastolic dysfunction. However, the finding that a drug can improve left ventricular diastolic function may be of interest, although additional investigations dedicated to this issue are needed. Pre-emptive intervention with drugs capable of improving left ventricular diastolic function could prevent the onset of left ventricular diastolic dysfunction in subjects at greater risk or attenuate its progression to heart failure. Data on the beneficial effect of drugs acting on the guanylate cyclase stimulator on patients with chronic HF with reduced ejection fraction have recently been published. Increased levels of cyclic GMP caused by inducing nitric oxide soluble guanylate cyclase (cGM) pathway appear to have a positive impact on hospitalization for heart failure and mortality [19]. Even if no data on nitric oxide pathways induction in patients with HF with preserved systolic function have been provided, a beneficial analogous effect could be supposed for both cGM and PDE drugs that act by increasing nitric oxide levels with a beneficial impact on cardiovascular function. It is known that asymptomatic left ventricular diastolic dysfunction can evolve into overt heart failure. In a randomly selected cohort of  
Figure 2: Clinical case of patient undergoing 6 months of tadalafil treatment. Patient’s diastolic function at baseline (**left**) panel and after 6 months of treatment (**right**) panel; from top to bottom: pulsed Doppler velocity on mitral valve, tissue Doppler velocity of the lateral mitral annulus, peak systolic tricuspid jet velocity. 2042 subjects \(\geq\)45 years old that were followed for 4 years, [PERSON] et al. demonstrated that diastolic dysfunction was an independent risk factor for heart failure in the elderly, even in apparently healthy subjects [20]. A subsequent meta-analysis of 13 reports based on 11 distinct studies assessing a total of 25,369 participants followed for 7.9 years on average, including asymptomatic subjects with diastolic dysfunction, revealed a 70% increased risk of progressing to heart failure in subjects with asymptomatic diastolic dysfunction in comparison with subjects without asymptomatic diastolic dysfunction [21]. To date, no treatment has been shown to convincingly reduce mortality and morbidity in a population of patients with heart failure with preserved ejection fraction [21]. Therefore, the development of new therapies remains a challenging and unresolved task. The observed improvements in diastolic function indices after 6 months of tadalafil therapy could be tested in a prospective and randomized trial to assess whether tadalafil provides clinical benefit in patients with heart failure and preserved ejection fraction.