BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.

• MeSH
• Adult MeSH
• Muscle, Skeletal * diagnostic imaging   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Spectroscopy * methods   MeSH
• Tomography, X-Ray Computed * methods   MeSH
• Prognosis MeSH
• Prospective Studies MeSH
• Sarcopenia etiology   metabolism   MeSH
• Aged MeSH
• Liver Transplantation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

AIMS: The determinants and relevance of right ventricular (RV) mechanical dyssynchrony in heart failure with reduced ejection fraction (HFrEF) are poorly understood. We hypothesized that increased afterload may adversely affect the synchrony of RV contraction. METHODS AND RESULTS: A total of 148 patients with HFrEF and 36 controls underwent echocardiography, right heart catheterization, and gated single-photon emission computed tomography to measure RV chamber volumes and mechanical dyssynchrony (phase standard deviation of systolic displacement timing). Exams were repeated after preload (N = 135) and afterload (N = 15) modulation. Patients with HFrEF showed higher RV dyssynchrony compared with controls (40.6 ± 17.5° vs. 27.8 ± 9.1°, P < 0.001). The magnitude of RV dyssynchrony in HFrEF correlated with larger RV and left ventricular (LV) volumes, lower RV ejection fraction (RVEF) and LV ejection fraction, reduced intrinsic contractility, increased heart rate, higher pulmonary artery (PA) load, and impaired RV-PA coupling (all P ≤ 0.01). Low RVEF was the strongest predictor of RV dyssynchrony. Left bundle branch block (BBB) was associated with greater RV dyssynchrony than right BBB, regardless of QRS duration. RV afterload reduction by sildenafil improved RV dyssynchrony (P = 0.004), whereas preload change with passive leg raise had modest effect. Patients in the highest tertiles of RV dyssynchrony had an increased risk of adverse clinical events compared with those in the lower tertile [T2/T3 vs. T1: hazard ratio 1.98 (95% confidence interval 1.20-3.24), P = 0.007]. CONCLUSIONS: RV dyssynchrony is associated with RV remodelling, dysfunction, adverse haemodynamics, and greater risk for adverse clinical events. RV dyssynchrony is mitigated by acute RV afterload reduction and could be a potential therapeutic target to improve RV performance in HFrEF.

• MeSH
• Ventricular Dysfunction, Left * MeSH
• Echocardiography methods   MeSH
• Ventricular Function, Left MeSH
• Humans MeSH
• Heart Ventricles diagnostic imaging   MeSH
• Heart Failure * MeSH
• Stroke Volume MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Right ventricular (RV) function is currently being evaluated solely according to the properties of RV myocardium. We have tested a concept that in patients with heart failure with reduced ejection fraction (HFrEF), RV assessment should integrate the information about both RV function as well as size. METHODS: A total of 836 stable patients with HFrEF (LVEF 23.6 ± 5.8%, 82.8% males, 68% NYHA III/IV) underwent echocardiographic evaluation and were prospectively followed for a median of 3.07 (IQRs 1.11; 4.89) years for the occurrence of death, urgent heart transplantation or implantation of mechanical circulatory support. RESULTS: RV size (measured as RV-basal diameter, RVD1) was significantly associated with an adverse outcome independent of RV dysfunction grade (p = 0.0002). The prognostic power of RVD1 was further improved by indexing to body surface area (RVD1i, p < 0.05 compared to non-indexed value). A novel parameter named RV global dysfunction score (RVGDs) was calculated as a product of RVD1i and the degree of RV dysfunction (1-4 for preserved RV function, mild, moderate and severe dysfunction, respectively). RVGDs showed a superior prognostic role compared to RV dysfunction grade alone (ΔAUC >0.03, p < 0.0001). In every subgroup of RVGDs (<20, 20-40, 40-60, >60), patients with milder degree of RV dysfunction but more dilated RV had similar outcome as those with more severe degree of RV dysfunction but smaller RV size (all p > 0.50), independent of tricuspid regurgitation severity and degree of pulmonary hypertension. CONCLUSION: RV dilatation is a manifestation of RV dysfunction. The evaluation of RV performance should integrate the information about both RV size and function.

• Publication type
• Journal Article MeSH

BACKGROUND: Phosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced heart failure with reduced ejection fraction before heart transplant or left ventricular assist device implantation to decrease right ventricular (RV) afterload and mitigate the risk of right heart failure. Conflicting evidence exists regarding the impact of these drugs on RV contractility. The aim of this study was to explore the acute effects of PDE5i on ventricular-vascular coupling and load-independent RV contractility. METHODS: Twenty-two patients underwent right heart catheterization and gated equilibrium blood pool single photon emission computed tomography, before and after 20 mg intravenous sildenafil. Single photon emission computed tomography and right heart catheterization-derived data were used to calculate RV loading and contractility. RESULTS: PDE5i induced a decrease in the right atrial pressure (-43%), pulmonary artery (PA) mean pressure (-26%), and PA wedge pressure (PAWP; -23%), with favorable reductions in pulmonary vascular resistance (-41%) and PA elastance (-40%), and increased cardiac output (+13%) (all P < 0.01). The RV ejection fraction increased with sildenafil (+20%), with no change of RV contractility (P = 0.74), indicating that the improvement in the RV ejection fraction was related to enhanced RV-PA coupling (r = 0.59, P = 0.004) by a decrease in the ventricular load. RV diastolic compliance increased with sildenafil. The decrease in the PAWP correlated with RV end-diastolic volume decrease; no relationship was observed with the change in LV transmural pressure, suggesting decreased pericardial constraint. CONCLUSIONS: Acute PDE5i administration has profound RV afterload-reducing effects, improves the RVEF, decreases RV volumes, and decreases the PAWP, predominantly through relief of pericardial constraint, without effects on RV chamber contractility. These findings support further study of PDE5i in protection of RV function in advanced heart failure with reduced ejection fraction who are at risk of RV failure.

• MeSH
• Pulmonary Artery MeSH
• Ventricular Dysfunction, Right * diagnostic imaging   drug therapy   MeSH
• Ventricular Function, Right MeSH
• Humans MeSH
• Sildenafil Citrate MeSH
• Heart Failure * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Úvod: Sarkopenie (těžká svalová deplece) a myosteatóza (patologická akumulace tuku ve svalech) jsou časté svalové abnormality u pacientů s cirhózou spojené s nepříznivou prognózou. Cílem naší práce bylo posoudit význam sarkopenie a myosteatózy u kandidátů transplantace jater (LT) v našem centru na peritransplantační průběh a na přežívání pacientů a štěpů. Metodika: Tato prospektivní studie zahrnula dospělé kandidáty LT, u kterých bylo provedeno klinické a laboratorní vyšetření. Na CT byl na úrovni L3 zhodnocen index kosterního svalstva (SMI) a změřena radiodenzita musculus psoas major (PM-RA). Výsledky: Ze 103 pacientů byla předtransplantační sarkopenie nalezena u 49 (47,6 %) a myosteatóza u 53 (51,5 %) pacientů. Pacienti se sarkopenií měli nižší BMI, obvod pasu, výskyt hypertenze a metabolického syndromu a nižší hladiny triglyceridů a C-peptidu než pacienti bez sarkopenie. Pacienti s myosteatózou měli vyšší Child-Pugh skóre a nižší HDL cholesterol než pacienti bez myosteatózy. Předtransplantační SMI negativně koreloval s počtem erymas podaných během LT a výskytem biliárních komplikací. Pacienti s myosteatózou měli vyšší spotřebu erymas během i po LT a vyšší počet operačních revizí. Výskyt sarkopenie neměl významný vliv na přežívání pacientů a štěpů. Pacienti s myosteatózou měli horší dlouhodobé přežívání než pacienti bez myosteatózy, přežívání štěpů se nelišilo. Závěr: Sarkopenie a myosteatóza jsou časté svalové abnormality u kandidátů LT, které mají negativní vliv na peritransplantační průběh. Myosteatóza byla v našem souboru spojena s horším dlouhodobým přežíváním pacientů po LT.

Introduction: Sarcopenia (severe muscle depletion) and myosteaosis (pathological fat accumulation in muscle) are frequent muscle abnormalities in patients with cirrhosis associated with unfavorable prognosis. The aim of our study was to evaluate the impact of sarcopenia and myosteatosis in liver transplant (LT) candidates in our center on the peritransplant course and patient and graft survival. Methods: This prospective study included adult LT candidates who underwent clinical and laboratory examination. The skeletal muscle index (SMI) at L3 level and radiodensity of psoas major muscle (PM-RA) were evaluated by CT. Results: Pretransplant sarcopenia was found in 49 of 103 patients (47.6%) and myosteatosis in 53 (51.5%) patients. Patients with sarcopenia had lower BMI, waist circumference, occurrence of hypertension and metabolic syndrome and lower triglyceride and C-peptide levels than patients without sarcopenia. Patients with myosteatosis had higher Child-Pugh score and lower HDL-cholesterol levels than patients without myosteatosis. Pretransplant SMI negatively correlated with the amount of blood transfusions given during LT and occurrence of biliary complications. Patients with myosteatosis had higher need for blood transfusions during LT and after LT, and higher number of surgical revisions. Occurrence of sarcopenia had no significant effect on patient and graft survival. Patients with myosteatosis had worse long-term survival than patients without myosteatosis, the graft survival did not differ. Conclusion: Sarcopenia and myosteatosis are frequent muscle abnormalities in LT candidates with negative impact on peritransplant course. Myosteatosis was associated with a worse long-term survival in our study.

• Keywords
• myosteatóza,
• MeSH
• Survival Analysis MeSH
• Humans MeSH
• Postoperative Complications MeSH
• Prospective Studies MeSH
• Sarcopenia * diagnosis   MeSH
• Liver Transplantation * MeSH
• Check Tag
• Humans MeSH