Diabetes in Left Ventricular Assist Device Therapy　― Harmful or Harmless? ―

Diabetes is a major public health concern and is increasing worldwide. Generally, diabetes plays a role in the development and progression of heart failure, contributing to an increased rate of all-cause mortality. A left ventricular assist device (LVAD) is essential for treating advanced heart failure, and the number of LVAD recipients has been increasing in Japan.¹ However, it is still unclear whether diabetes is harmful or harmless for the outcomes of LVAD recipients. Several studies have addressed this question in the past decade (Table). Vest et al and Mohamedali et al suggested that diabetes does not affect all-cause mortality.^2,3 In contrast, Asleh et al and Usoh et al reported that diabetes is associated with an increased rate of all-cause mortality.^4,5 Although recent meta-analyses, including these reports, concluded that diabetes is not a risk factor for LVAD recipients, the impact of diabetes is still under debate.⁶ Importantly, these results are based on studies conducted in the US and cannot be directly applied to Japan, where LVAD implantation was, until recently, performed only as a bridge to transplantation.

Table. Impact of Diabetes on Outcomes and Study/Patient Characteristics in Each Study

	Yoshioka et al7	Vest et al2	Mohamedali et al3	Asleh et al4	Usoh et al5
Effect of diabetes on
All-cause mortality	No	No	No	Yes	Yes
MACE, except death	Driveline infection	No	Hemolysis	Devise infection, thromboembolic events	No
Study characteristics
Country	Japan	US	US	US	US
Study period	2013–2019	2006–2013	2006–2013	2007–2016	2008–2014
Follow-up duration	Median 2.3 years	Median 268 days (DM)/ 266 days (non-DM)	Mean 1,132 days (DM)/ 1,143 days (non-DM)	Median 16.1 months	Mean 1.8 years
Destination therapy	0	37% (DM)/ 39% (non-DM)	NR	70% (DM)/ 59% (non-DM)	38% (DM)/ 36% (non-DM)
Patient characteristics (DM/non-DM)
No. patients	116/429	129/171	122/166	131/210	96/95
Age (years)	54 [47–60]/ 44 [34–55]	59 [52–65]/ 56 [40–64]	62±11/ 59±14	62 [56–69]/ 62 [50–69]	57±11/ 56±12
BMI (kg/m2)	21.7 [19.6–23.9]/ 20.1 [18.4–22.6]	28.7 [25.6–32.6]/ 26.0 [22.7–30.5]	29.8±6/ 26.6±6	30.6±5.6/ 28.1±5.5	31±6/ 29±5
Albumin (g/dL)	3.7 [3.3–4.0]/ 3.8 [3.4–4.1]	3.5 [3.2–4.0]/ 3.5 [3.1–3.9]	3±0.46/ 3±0.47	3.7±0.7/ 3.8±0.5	NR
Creatinine (mg/dL)	0.98 [0.80–1.22]/ 0.90 [0.70–1.13]	1.4 [1.1–1.7]/ 1.2 [1.0–1.5]	1.50±0.46/ 1.34±0.45	1.5±0.6/ 1.4±0.6	1.31±0.50/ 1.22±0.40

Unless indicated otherwise, data are given as the mean±SD or median [interquartile range]. BMI, body mass index; DM, diabetes; MACE, major cardiovascular events; NR, not reported.

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In this issue of the Journal, Yoshioka et al highlight the impact of diabetes on outcomes in patients supported with LVAD from the Japanese National Database (see also Table).⁷ Yoshioka et al clearly demonstrated that overall survival under LVAD support was comparable between patients with and without diabetes.⁷ This report is of great value because it contains data from Japan obtained through a prospective registry, and the authors’ work is commendable. However, it should be noted that the patient characteristics differ from those of other US studies presented in the Table. For example, Cowger et al reported that older age, hypoalbuminemia, and renal dysfunction are associated with mortality in US patients supported with LVAD.⁸ The Japanese study population of Yoshioka et al is characterized by younger age and relatively better patient background, especially renal function, compared with other US studies. These could be reasons for the better prognosis after LVAD implantation in Japanese patients compared with the INTERMACS database in the US.^9,10 Thus, the impact of diabetes during LVAD support is limited to responses from populations with these characteristics. Conversely, there is an important message here, because it may present an ideal indication for LVAD in patients with diabetes.

Analysis in the age- and body mass index-adjusted cohort in the study of Yoshioka et al revealed that diabetes was a risk factor for driveline infection.⁷ During LVAD support, driveline infection is a serious concern that can lead to death. Interestingly, this infection did not increase the mortality rate, which may be because the primary cause of death is a neurologic event. Although infection is the second leading cause of death, it accounts for less than half of all neurologic events.⁹ However, Kirklin et al reported in the Seventh INTERMACS Annual Report that, over time, infection increases as a cause of death and is closely related to late mortality.¹⁰ Therefore, longer-term observations are required to determine the impact of diabetes during LVAD support in terms of infection.

In Japan, the waiting period for heart transplant in patients supported with LVAD is getting longer. Moreover, because destination therapy (DT) was recently approved in Japan, more long-term LVAD management data are needed, not only for diabetes. In addition, in the DT era, the age of eligible patients is expected to be higher, and patient backgrounds will become more complex and worse. Once again, we want to congratulate Yoshioka et al on their work. However, further verification is needed to conclude that diabetes is not a risk factor for increased mortality during LVAD support. Specifically, longer observational studies are required in older diabetes populations with poorer renal function (Figure). Nevertheless, if we make a “deep dive” into the unresolved issues, we believe this report can be the signpost of the DT era in Japan.

Figure.

What have we learned, and do not yet know, from this study? Yoshioka et al revealed that diabetes is not a risk factor for death during left ventricular assist device support in a relatively young Japanese diabetic population with preserved renal function.⁷ However, there are still unresolved issues that require further cohort studies of the Japanese population.

Acknowledgments

None.

Disclosures

The authors declare that there are no conflicts of interest.

References

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