Impact of type 2 diabetes mellitus in the utilization and in-hospital outcomes of surgical mitral valve replacement in Spain (2001–2015)

Surgical mitral valve replacement (SMVR) is the recommended treatment for irreparable valve pathologies, and mechanical or bioprosthetic valves have been the mainstream options. However, these preferences may change in the future with the emergence of transcatheter mitral valve replacement [1].

SMVR is more likely to be performed in patients with several comorbidities, including diabetes, [2, 3] and the overall prevalence of diabetes among patients undergoing SMVR has increased over time [4]. In the US, a retrospective study of 1757 patients who underwent SMVR, from 2000 to 2013, found that 19.8% had diabetes [5]. In Canada and in the US, in more than 20,000 patients with mitral valve pathologies, the prevalence of diabetes was double the prevalence in the general population after adjusting for age (10.9% vs. 5.5% in Canada and 13.4% vs. 7.9% in the USA) [6, 7]. Furthermore, the prevalence of diabetes is rising over time among SMVR patients [8].

Previous studies have found that those suffering from diabetes have a higher long-term mortality after SMVR than those not suffering from diabetes [9]. For other valve procedures, such as surgical aortic valve replacement, suffering from type 2 diabetes (T2MD) has been associated with significantly lower in-hospital mortality (IHM) than among those not suffering from type 2 diabetes [10].

The effect of diabetes on perioperative major adverse cardiovascular and cerebrovascular events (MACCE) and IHM after SMVR is not as well defined. Therefore, the aim of the present study was to examine nationwide trends, characteristics and in-hospital outcomes in mechanical and bioprosthetic SMVR among patients with or without T2DM. To accomplish this aim, we used Spanish National Hospital Discharge Database (SNHDD) data from 2001 to 2015. Also, we aimed to identify which factors are associated with suffering from MACCE among patients with or without T2DM after SMVR according to implanted valve type.

In our study, we identified a total of 42,937 hospitalizations of patients aged 40 years or older who underwent SMVR in Spain (2001–2015). We identified 35,904 (83.62%) hospitalized patients who underwent mechanical SMVR and 7033 (16.37%) who underwent bioprosthetic SMVR.

In the past 15 years, there has been an increase in the number of T2DM patients who underwent SMVR in Spain. In our investigation, the prevalence of T2DM among patients who underwent SMVR increased from 13.4 to 16.06% over the study period. Myllykangas et al. [8] described changes in the mitral valve surgery population over 18 years in the Finnish Cardiovascular Diseases Register. These authors found that the prevalence of diabetes in these patients rose from 12.30% in 1997–2002 to 20.9% in 2009–2014 (p < 0.001).

We found that, from 2001 to 2015, the incidence rates of hospitalization to undergo a SMVR were higher among the Spanish population suffering T2DM than the incidence rates for this procedure among the non-T2DM population. These higher incidence rates of hospitalizations were observed for either mechanical or bioprosthetic SMVR. This finding could be due to several factors, such as advanced age and a high index of comorbidities, leading to an increased risk of hospitalization for patients with T2DM and SMVR [9]. In addition, improvements in treatment in terms of short-term and long-term complications have broadened the indication for surgery over the years [13].

Among T2DM patients, we found an increase in the rate of implanted bioprosthetic valves from 2001 to 2015 meanwhile the trend in the use of mechanical valves remained stable. These findings are similar to those reported by the Society of Thoracic Surgeons Adult Cardiac Surgery Database, where the election of mechanical valves has decreased from 68 to 37% during the last decade [2]. Furthermore, a large study based on the Netherlands’ national registry showed that mechanical prostheses are less often implanted, and this occurrence has led to a decrease from 43.4% in 1995 to 13.8% in 2010 [14]. This trend has also been reported in other studies, and these results suggest improved durability of biological prostheses and fewer neurological and functional complications [15]. Although this approach may be reasonable in high-risk and elderly patients, and often occurs in T2DM patients, it is not supported by scientific evidence in younger patients, especially in those without comorbidities or contraindications for anticoagulation [16]. In any case, the selection of the valve type is a decision that should be made by the physician and patient in conjunction and must be individualized. For this decision, the risks for reoperation and for chronic anticoagulation and their consequences, in addition to characteristics of the patient, lifestyle, comorbidities and life expectancy, should be considered in order to increase quality of life and survival [17].

In our opinion factors such as the greater use of bioprosthetic SMVR, increased number of patients who undergo mitral valve plasty/repair (as will be commented in the limitations section) and lastly, technological advances, like the transcatheter mitral valve procedure (TMVP), that have provided new alternatives to surgery in selected patients, could explain the stable trend in the use of mechanical valves from 2001 to 2015 among T2DM patients in our country.

As in patients who underwent SAVR, age in SMVR plays an important role in valve type selection for patients with T2DM [8, 18], with most patients aged > 73 years receiving bioprosthetic valves and patients with a younger age receiving mechanical valves.

IHM following mitral valve replacement is high [3]. We found that the IHM and MACCE for mechanical SMVR have decreased significantly over the last 15 years in both patients with T2DM and without T2DM. However, no significant changes in the IHM and the MACCE have been observed in those patients with diabetes who underwent bioprosthetic SMVR. Berginzi et al. [3] found that IHM of isolated bioprosthetic SMVR improved over time (7.8% in 2003 to 4.7% in 2014, p trend = 0.016), but surgery remained associated with significant morbidity, lengthy hospitalizations and high cost of care. They concluded that these findings highlight the importance of the evolving TMVP field in addressing the critical need to find alternatives with lower morbidity for these patients [3].

The IHM after SMVR found in our investigation is high when compared to studies from other countries [2, 3, 5, 8, 15, 19]. Possible explanations for this higher mortality could include that surgeries are conducted in Spain in patients with higher age and worse baseline conditions. Previous studies have found that the most important determinants of survival after mitral valve replacement are age and comorbidity [2, 3, 5, 8, 15, 19]. Other reasons that may be suggested are differences in the use of concomitant heart procedures and in the health care system characteristics and organization. If we compare our results with those described in Finland, European country with a similar health system to ours, we see that for the period 2009–2014 their 28-day mortality after mitral valve replacement was 8.1% in line with our result for the period 2011–2015 (10.39%) [8]. When we analyze the characteristic of patients who undergo surgery we observe that the mean age is similar in both countries (around 68 years) but the Spanish population has higher prevalence of comorbid conditions and undergo concomitant heart procedures in a greater proportion than the Finnish population (e.g. CABG > 12% in Spain vs. 7.5% in Finland) [8]. Beside these previous comments, the comparison in the mortality rates between countries is complicated due to the differences in data sources, study designs and the study variables collected among others possible reasons.

Our results showed that T2DM patients have rates of mortality and MACCE after mechanical and bioprosthetic SMVR which are not significantly different to those found among non-diabetic patients. This conclusion was confirmed after sensitivity analysis using PSM. One explanation may be that patients who undergo SMVR in the current era have high-risk features, including a significant prevalence of comorbid conditions (e.g., hypertension, anemia, atrial fibrillation, prior sternotomy, coronary artery disease, coagulopathy and chronic renal insufficiency) [3] and not only diabetes.

In our study, SMVR in T2DM patients with a mechanical valve, compared to those with a bioprosthetic valve, was associated with lower IHM and MACCE. In the general population, the choice of biologic or mechanical prosthesis does not significantly affect long-term patient survival after mitral valve replacement [19]. However, a study of 3433 patients (aged 50–69 years) who underwent SMVR in New York state hospitals from 1997 to 2007 found that mechanical prosthetic valves were associated with a lower risk for reoperation but greater risk for bleeding and stroke. The authors concluded that bioprosthetic valves are commonly used in patients judged to have shorter life expectancies based on characteristics such as frailty [20]. This finding could be a possible explanation for our results.

Older age and more comorbidities are factors that increased MACCE in patients with T2DM regardless of the type of valve implanted. These findings are similar to those reported in other studies [14] and in the general population [21, 22].

Diabetes is a predictor of long-term mortality for patients undergoing SMVR [14] and in those with concomitant CABG [23]. In our study, we found significantly higher MACCE in T2DM patients with concomitant CABG and with intra-aortic balloon counter-pulsation independent of the type of valve used than in T2DM patients without these procedures. These data might be useful when interpreting the emerging literature on TMVP [3].

We found that factors associated with a lower risk of dying or suffering MACCE after SMVR included atrial fibrillation, pacemaker implantation, pulmonary hypertension and obesity. The protective effect of atrial fibrillation and pacemaker implantation has been previously found in T2DM patients undergoing surgical aortic valve replacement (SAVR) and atrial fibrillation among patients suffering COPD with SAVR [24, 25]. In our opinion this may be consequence of a selection bias, with patients with arrhythmia undergoing heart surgery having a better baseline comorbidity profile than those without these disorders. This explanation could also be applicable for pulmonary hypertension.

Regarding obesity, several but not all, authors have reported the existence of the “obesity paradox” after cardiac surgery, finding that overweight and obese patients had lower mortality and adverse perioperative outcomes compared with normal weight, underweight, and morbidly obese patients [26‐29].

There are some points that should be taken into consideration when interpreting the results of the present study.

In our investigation we analyzed the use of SMVR but not of those patients who underwent mitral valve plasty/repair that is nowadays a common operation in many centers. Therefore the influence of the use of valve plasty/repair in our results is not evaluated. As can be seen in Additional file 6: Table S4 the number of mitral valve plasty/repair has increased significantly over the study period in Spain, from 277 cases in 2001–2005 to 799 cases in 2011–2015 among T2DM patients, and from 1792 to 4010 cases among non-T2DM patients. As can be seen in Additional file 6: Table S4 even if the use of these procedures is increasing overtime, and possibly replacing SMVR, they still represent under 25% of all procedures conducted on mitral valves in Spain for those aged 40 years or over in the period 2011–2015. Further studies are needed in the future to assess the time trends in mitral valve plasty/repair in our country.

We used the SNHDD, an administrative database rather than a clinical database [11]. Therefore, it was subject to coding error. In addition, it is based on mandatory discharge data, and it lacks important clinical details that likely influence treatment selection and outcomes (e.g., ejection fraction, valve size, and medication history).

Unfortunately in the SNHDD among 35,151 patients who received mechanical SMVR only 11,038 (30.74%) had information regarding the etiology of the mitral valve disease and presentation (mitral stenosis, rheumatic mitral insufficiency or mitral stenosis with insufficiency). For those with bioprosthetic SMVR this proportion was even lower 17.86% (1256/7033). The lack of this information makes impossible to analyze these relevant variables and constitutes an important limitation of our investigation.

Despite these limitations, the quality and validity of our dataset has been assessed and has been found to be useful for health research [10]. Furthermore, this dataset reflects the outcome of a real-world population, which is different from that selected in randomized controlled trials. Thus, the results could be extrapolated to the general population.

In Spain from 2001 to 2015, the incidence rates of hospitalization to undergo mechanical or bioprosthetic SMVR were higher among the population suffering T2DM than among the non-T2DM population. In both groups of patients the use of bioprosthetic SMVR increased over time and the use of mechanical valves remained stable in T2DM. T2DM patients have IHM and MACCE after mechanical and bioprosthetic SMVR which are not significantly different to those found among non-diabetic patients. Among T2DM patients, the crude IHM was significantly higher in those who received a bioprosthetic SMVR than those with mechanical SMVR.