ASIAN-HF: T2D affects heart structure, hospitalization, mortality risk in patients with HF

The presence of type 2 diabetes mellitus (T2DM) in patients with heart failure (HF) is associated with structural abnormalities in the heart, reduced quality of life (QoL), and an elevated risk of hospitalization for heart failure (HHF) and death, according to a recent study.

The study population comprised 5,028 patients with HF and reduced ejection fraction (HFrEF; EF <40 percent; mean age 60 years, 78.2 percent male) and 1,139 patients with HF and preserved ejection fraction (HFpEF; EF ≥50 percent; mean age 68.7 years, 50.3 percent male) enrolled in the ASIAN-HF* registry.

T2DM prevalence was higher and the duration longer in patients with HFpEF than HFrEF (45.0 percent vs 40.2 percent; p=0.003 and mean 12.0 vs 9.8 years; p<0.001, respectively). Singapore and Hong Kong clocked the highest prevalence of T2DM at 58.2 and 56.9 percent, respectively, while the prevalence was lowest in China (22.8 percent).

Patients with HFrEF and T2DM had smaller indexed left ventricular (LV) end-diastolic and end-systolic volumes and a higher mitral E/e’ ratio than those without T2DM (p<0.001 for all). Patients with HFpEF and T2DM had smaller indexed LV end-diastolic volumes (p=0.017) and higher mitral E/e’ ratio (p=0.029) but smaller indexed left atrial volumes (p=0.002) compared with HFpEF patients without T2DM. LV wall thickness did not differ with T2DM status in HFrEF patients but was thicker in HFpEF patients with T2DM (p=0.037). [J Am Heart Assoc 2019;8:e013114]

There was a predominance of eccentric hypertrophy in patients with HFrEF and concentric hypertrophy in HFpEF. These findings could be put down to a variation in how T2DM affects cardiac structure in the different HF phenotypes, said the researchers.

“In HFrEF, [T2DM] causes increased cardiac cell death with its attendant fibrosis. Cell death occurs as a result of several pathways, including lipotoxicity and deposition of advanced glycation end products … In HFpEF, cardiac cell hypertrophy and stiffness may occur because of hyperinsulinemia as well as endothelial dysfunction resulting from coronary microvascular disease seen in [T2DM] with downstream lack of cGMP in the myocardium,” they said.

Health-related QoL, determined using the Kansas City Cardiomyopathy Questionnaire, was reduced in both HFrEF and HFpEF patients with T2DM (vs without T2DM), with a more prominent difference in patients with HFpEF. The impact of T2DM on individual QoL domains differed between HFrEF and HFpEF, such as physical limitation score (p_interaction=0.002), clinical summary score (p_interaction=0.006), and QoL score, overall summary score, and social limitation (p_interaction=0.001 for all).

At 1 year, HF patients with T2DM had a higher rate of a composite of all-cause mortality and HHF vs those without T2DM (adjusted hazard ratio [adjHR], 1.22, 95 percent confidence interval [CI], 1.05–1.41; p=0.011). This was driven by a higher rate of HF hospitalization at 1 year among patients with T2DM compared with those without (adjHR, 1.27, 95 percent CI, 1.05–1.54; p=0.014). These outcomes were not affected by HF phenotype (p_interaction>0.05).

“These increased hospitalizations result in increased morbidity and costs, lending further evidence to the deleterious effects of [T2DM] in this fragile HF population and the need for adequate prevention, screening, and management of [T2DM],” said the researchers.

“Primary prevention strategies and tailored treatment options are needed to tackle this twin scourge of diseases,” said study co-author Dr Jonathan Yap from the Department of Cardiology, National Heart Centre Singapore. “Our findings emphasize the need for preventative public health measures at the community and primary care level. For HF patients who have diabetes, physicians should closely monitor and optimize their management.”

The researchers acknowledged that patients with T2DM in this study were undertreated with low use of ACE inhibitors, ARBs**, and metformin. Furthermore, enrolment for this study was conducted prior to the widespread use of SGLT-2*** inhibitors in Asia. Future research could look into these outcomes following “more recent trends in antidiabetic therapy,” they said.

The majority of studies on the effects of concomitant T2DM and HF have centred on Western populations. This has reduced the generalizability of their findings, “particularly in light of recent studies showing distinct differences between Asians and white populations,” they said, on the importance of these findings.