We investigated left ventricular diastolic dysfunction (LVDD) and its relationship with circulatory function and prognosis in cirrhosis with portal hypertension and normal creatinine. Conventional and tissue Doppler (TDI) echocardiography, systemic and hepatic hemodynamics, and the activity of endogenous vasoactive systems (AEVS) were measured prospectively in 80 patients. Plasma renin activity (PRA; >4 ng/mL/hour) was used as a surrogate of effective arterial blood volume. Patients were followed up for 12 months. Thirty-seven patients had LVDD (19 with grade 1 and 18 with grade 2). Left ventricular hypertrophy, left atrial volume, AEVS, and natriuretic peptide levels were significantly greater in patients with LVDD than without LVDD. Patients with grade 2 LVDD, compared to grade 1 LVDD and without LVDD, had significantly lower mean arterial pressure and higher Model for End-Stage Liver Disease (MELD) score, E-wave transmitral/early diastolic mitral annular velocity (E/e' ratio), cardiopulmonary pressures, PRA, and natriuretic peptide levels. Systolic and cardiac chronotropic function were significantly lower in patients with grade 2 LVDD than without LVDD. LVDD was more frequent in patients with ascites and increased PRA than patients without ascites or with ascites but normal PRA. Fourteen patients with LVDD developed hepatorenal syndrome (HRS) type 1 on follow-up. Survival was different according to degree of LVDD (without LVDD: 95%; grade 1 LVDD: 79%; grade 2 LVDD: 39%; P < 0.001). Independent predictive factors of mortality were MELD score and E/e' ratio. Conclusion: LVDD occurs simultaneously with other changes in cardiac structure and function and is associated with an impairment of effective arterial blood volume. LVDD is a sensitive marker of advanced cirrhosis, type 1 HRS development, and mortality. (HEPATOLOGY 2013;58:1732-1741 C irrhosis is associated with a specific subclinical cardiomyopathy 1-4 characterized by diminished systolic responsiveness to stress stimuli, 5,6 impaired diastolic relaxation, 7,8 electrophysiological abnormalities, 9 and enlargement and hypertrophy of cardiac chambers, 10,11 all in the absence of known cardiac disease. However, evidence suggests that patients with cirrhosis display primarily left ventricular diastolic dysfunction (LVDD) with normal systolic function at rest. 7Abbreviations: 2D, two-dimensional; A, atrial wave-filling peak; ALDO, plasma concentrations of aldosterone; ANF, atrial natriuretic factor; ASE, the American Society of Echocardiography; AUC, area under the curve; BNP, brain natriuretic peptide; CI, confidence interval; CO, cardiac output; DT, deceleration time; E, E-wave transmitral peak early filling; e 0 , early diastolic mitral annular velocity; E/A, early diastolic mitral inflow velocity/late diastolic; E/e 0 ratio, E-wave transmitral/early diastolic mitral annular velocity; FHVP, free hepatic venous

Entecavir and tenofovir achieved high biochemical and virological response. Renal function remained stable with both drugs. A Page-B cut-off ≥10 selected all patients at risk of HCC development.

Introduction Erectile dysfunction (ED) is highly associated to cardiovascular disease, especially arterial hypertension. Phosphodiesterase type 5 (PDE5) inhibitors and angiotensin II receptor blockers (ARB) are both common and efficient therapy in patients with ED and arterial hypertension, respectively. Aim To evaluate the effect of PDE5 inhibitor, sildenafil (S), and of ARB Losartan (L) in a continuous combined therapy for a long term on penile structures in a hypertensive rat model. Methods During 6 months, four groups of male spontaneously hypertensive rats (SHR) and one of Wistar-Kyoto (WKY) rats, as control group, were studied: no-treatment SHR, SHR with L, SHR with S, SHR with S+L, and no-treatment WKY. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, collagen type III (COL-III), and endothelial nitric oxide synthase (eNOS) expression in cavernous space were evaluated. Main Outcome Measure Functional and morphological differences between S and L in a continuous combined therapy vs. either drug as monotherapy on penile structures. Results After 6 months, SHR that received L, S, or combined therapy showed a similar reduction in blood pressure compared with untreated SHR. Nevertheless, SHR+L+S and control WKY showed significantly lower values of (i) CSM (P  &lt; 0.01), (ii) VSM (P  &lt; 0.01), and (iii) COL-III (P  &lt; 0.01) when compared with the untreated SHR and also with the SHR with monotherapy. Additionally, SHR+L+S, presented a higher eNOS expression in sinusoidal endothelium in comparison with the untreated SHR and the SHR with monotherapy (P  &lt; 0.01). In vitro studies revealed that SHR+L+S displayed a better relaxation response to acetylcholine than the untreated SHR and the SHR with monotherapy (P  &lt; 0.01). Conclusions These results suggest that a long-term combined therapy using L and S is a useful tool for functional and structural modification in cavernous tissue from SHR.

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