This retrospective study showed that the rates of renal dysfunction and pulmonary complications after hepatic resection are higher in patients with LVDD than in those with normal LV diastolic function.
LVDD as the most common cardiac abnormality in patients with liver cirrhosis is characterized by abnormal myocardial relaxation related to the development of myocardial fibrosis, hypertrophy, and subendothelial edema (Fouad YM et al., 2014). It occurs when the passive elastic properties of the myocardium are reduced because of increased myocardial mass and changes in extracellular collagen (Aurigemma GP et al., 2004). LVDD is prevalent in 25.7–81.4% of cirrhosis patients; it is also more prevalent in decompensated cirrhosis patients than in compensated cirrhosis patients (Farouk H et al., 2017). Liver cirrhosis, old age, hypertension, diabetes, and LV hypertrophy are major risk factors of LVDD (Jeong EM et al., 2015). In the current study, 37/190 patients (19.5%) had LVDD, and these patients were older and had a higher prevalence of hypertension than those with normal LV diastolic function.
Maintaining a CVP during hepatic resection and compensative administration of large amounts of fluid after its completion is a widely used effective strategy to minimize intraoperative blood loss. A previous study showed that clinically relevant renal dysfunction is highly uncommon in patients with a low CVP who undergo hepatic resection (Correa-Gallego C et al., 2015). However, patients with LVDD are vulnerable to the changes in fluid status. Lowering preload during the operation could decrease cardiac output, and it might lead to hypoperfusion of abdominal organs, making it a risk factor for postoperative renal dysfunction. Analysis for intraoperative changes of cardiac stroke volume would be helpful to reveal its influence on clinical outcomes, but this study was a retrospective nature and it might be a limitation. On the other hand, patients with LVDD are also at risk of fluid overload that fluid challenge after completion of hepatic resection can conversely cause postoperative renal dysfunction. Fluid overload is associated with a high risk of AKI and delayed recovery because tissue edema of the kidneys leads to hypoperfusion-induced organ injury (de Oliveira FS et al., 2015). Previous studies have shown that patients with LVDD often have elevated CVP; this in turn has a negative correlation with estimated glomerular filtration rate and increases the risk of postoperative AKI (Damman K et al., 2009; Palomba H et al., 2007). In the current study, CVP at the end of surgery with fluid challenge after hepatic parenchymal transection was higher in patients with LVDD. The incidence of postoperative AKI was also significantly higher in these patients than in those with normal LV diastolic function despite a similar fluid balance between them. In addition, we used CVP to assess the volume status although it has limited accuracy (De Backer D et al., 2018). Further studies to confirm this results are required using more reliable indicators reflecting fluid status and responsiveness, such as inferior vena cava size.
The current study showed that patients with LVDD had significantly lower daily urine outputs in the early postoperative period than those with normal LV diastolic function. Fluid therapy in this period would be important to avoid fluid overload, which is associated with the development of AKI. We adjusted the amounts of postoperative fluid administration in accordance with urine outputs so that there were no significant differences in daily fluid balances between the two groups. This might have influenced the result of no significant difference in postoperative hospital stay between patients with and without LVDD. All cases of postoperative AKIs were resolved at discharge without requiring renal replacement therapy. However, AKI was associated with prolonged postoperative hospital stay (22.0 ± 14.3 days vs. 12.3 ± 6.3 days, P = 0.001). Thus, usage of nephrotoxic medications, particularly those that cause either glomerular or interstitial damage, should be avoided in patients with LVDD, especially in the early postoperative period.
LVDD is associated with adverse postoperative cardiovascular events (Fayad A et al., 2016). Previous studies showed that LVDD is an independent risk factor for postoperative pulmonary edema in patients undergoing non-cardiac surgery owing to the increase in LV filling pressure concomitant with pulmonary venous pressure (Shigematsu K et al., 2019). The current study also found that pleural effusion or pulmonary edema was significantly higher in patients with LVDD than in those with normal diastolic function. Although most cases of pleural effusion or pulmonary edema were spontaneously improved with or without diuretics, two patients with LVDD (5.1%) required percutaneous drainage because of increasing oxygen requirement. LVDD can also impair coronary flow reserve, increasing LV wall stress in patients with normal diastolic function and leading to increased myocardial blood flow (Galderisi Met al., 2002). Patients with LVDD are at risk of coronary flow reduction after volume adjustment, and this would result in myocardial ischemia and adverse cardiovascular events. In the current study, one patient with LVDD had myocardial infarction requiring a stent placement at postoperative day 1.
There are some limitations to this study. The retrospective study design required us to rely on the integrity of completed medical records for our analysis. In addition, the study population was relatively small, and thus, we only compared the clinical outcomes between patients with and without LVDD. However, the outcomes differ by grade of LVDD, and thus, further large-scale studies with subgroup analysis by grade of LVD are needed. Finally, additional prospective studies are needed to confirm that fluid therapy for preventing fluid overload in the perioperative period would improve the clinical outcomes of patients with LVDD.