DISCUSSION
The main findings of study can be summarized as follow:
a) Individuals with MetS, according to the WHO definition, had significant greater burdens of clinical comorbidities;
b) post-operative complications, including prolonged post-operative LOS, were more frequent in the surgical strata MetS group; mortality rate was significant higher in the MVS MetS group;
c) however, in the TAVR cohort, post-operative complications and mortality rate did not differ between patients with and without MetS; overall LOS was longer in the MetS group.
MetS may cause a number of effects on the myocardium and the circulatory system, including myocardial fibrosis, activation on inflammatory and proatherogenic pathways (macrophage infiltration and cytokine gene expression), endothelial dysfunction and heart failure with either preserved or reduced ejection function(13).
To the best of our knowledge, this is the first study that specifically investigated the effect of MetS on post-operative complications after isolated valve intervention.
It is important to notice that MetS in our study was a significant independent predictor for post-operative mortality, however this was largely driven by the mitral cohort. Notably, when controlling for other confounders, systemic hypertension, atherogenic dyslipidaemia and insulin resistance were not significantly associated to mortality. On the contrary, BMI was inversely correlated with mortality. This latter concept is known as ‘obesity paradox’ and has been described already by others(13, 14).
Nevertheless, there are two important considerations to be made for ‘obesity’: the first is that not always obesity is synonymous of MetS since there are so-called metabolically healthy obese (MHO) individuals with high level of insulin sensitivity without systemic hypertension and atherogenic dyslipidaemia and other features of MetS(12, 15). A survey analysis, suggested that MHO may account for a significant percentage of obese population(15). The second consideration is that waist circumference rather than BMI is a more sensitive index for the definition of obesity(16). An epidemiological study showed that, when BMI and waist circumference were included in the same regression model, the latter remained a positive predictor of risk of death while the former was unrelated or inversely related to the risk of death(17). Waist circumference is a more precise index for visceral adiposity / central obesity(16). Visceral obesity causes a decrease in insulin-mediated glucose uptake, insulin resistance and ultimately endothelial dysfunction (3, 5). Nonetheless, waist circumference is seldom measured in the cardiac surgery context, and most studies that investigated the obesity paradox have considered the BMI as measure of obesity, rather than waist circumference(14).
In our study cohort, individuals with MetS had significant greater burdens of comorbidities that included COPD, peripheral vascular and previously treated coronary disease, advanced age, reduced LVEF, renal failure and prevalent female sex. The latter is a proven ‘condition of risk’ associated to worst outcome in cardiac surgery(18). The association of MetS with those comorbidities can explain the excess mortality and complication rate in this group.
Post-operative LOS was significantly prolonged in the MetS group. The presence of MetS was also independent predictor for increased LOS; also, sensitivity analysis showed diabetes, systemic hypertension but not BMI nor obesity (defined as BMI>30kg/m2) to be independently associated to LOS.
Evaluating the feasibility and performance of the minimally invasive surgical approach (both mitral and aortic) in individual with MetS is beyond the scope of this research. However, there was no difference in terms of number of patients approached with minimally invasive techniques (mitral and aortic) among MetS and no-MetS.
With the advent of TAVR, many high-risk patients with symptomatic aortic valve stenosis have been treated worldwide. Some studies investigated the effect of specific risk factors (i.e., diabetes / obesity)(19) in patients undergoing TAVR, but none focused on MetS. Two studies found BMI as inversely associated to mortality, while visceral adiposity as independent risk factor for post-operative mortality(20, 21). Those findings confirm the suboptimal accuracy of BMI as trait for MetS. Opposite to the surgical group, in our series we found that MetS was not associated with worst post-operative outcomes in the TAVR subgroup.