Carvedilol Does Not Improve Exercise Performance in Fontan Patients: Results of a Crossover Trial

Effects of Carvedilol on Blood Pressure, Blood Sugar, and Blood Lipids in Elderly Patients with Refractory Hypertension

“…ET increases vascular responsiveness to other vasoconstrictors such as endogenous and exogenous norepinephrine substances [ 25 ]. ET promotes vascular smooth muscle cell proliferation and hypertrophy, resulting in narrowing of the lumen, thickening of the vessel wall, and increased peripheral resistance, and activation of phospholipase A2, which produces thromboxane A2, can further enhance vasoconstriction and increase blood pressure [ 26 ]. The increase in blood pressure increases the shear stress on the vessel wall and promotes the expression of ET-mRNA, and EH in turn can aggravate endothelial damage and increase endothelial dysfunction, with impaired production of diastolic substances such as nitric oxide (NO) and prostacyclin (PGL2) and increased release of thromboxane A2, along with massive secretion of ET [ 27 ].…”

Cardiac Drugs in ACHD Cardiovascular Medicine

“…Preload deprivation represents the Achilles' heel of Fontan physiology and can result from such treatments in asymptomatic patients. A recent crossover trial found that carvedilol did not improve exercise performance and was associated with a mildly increased N-terminal-proBNP level [41]. Finally, it is unknown whether the significant benefits of sacubitril/valsartan and SGLT2i in HF in the absence of CHD would have a similar impact on diuresis and prevention of adverse cardiac remodeling in patients with failing Fontan.…”

“…, not yet published) SGLT2i (ongoing studies: NCT05580510) Bosentan: conflictual effect on peakVO2 and NYHA, no effect on NTproBNP and QoL [35,42] Ambrisentan: improvement of peak VO2 [43] Macitentan (not yet published) Udenafil (FUEL): no improvement in peak VO2 [36] Sildenafil: conflictual results on peak VO2 [44,45]; no change in pressure-volume loop [46]; increase in cardiac index [47] Iloprost: improvement of peak VO2 [48] Meta-analysis [34]: significant improvements in hemodynamics, functional class, and 6 min walk distance but no changes in mortality or NT-proBNP Enalapril in asymptomatic patients: decrease in cardiac index [40] Carvedilol: no change in exercise performance and mild increase in NT-proBNP level [41] Open label trial No data No data Eplerenone: no effect on collagen biomarkers, 6MWD, or QoL [16] Bosentan: no changes in saturations of oxygen, exercise performance, and QoL [38]; improvement of 6MWD and MRI-derived resting cardiac output [49] Sildenafil: improvement of peak VO2 [50] Prospective observational studies Guideline-directed medical therapy would improve LVEF [3] B-blockers may improve NYHA, QoL, +/− sRVEF [12] ACEi or ARBs: no association with a reduced HF incidence or mortality […”