Diabetic HFpEF patients have worse outcomes than non-diabetics

Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients with Heart Failure and Preserved Ejection Fraction. A Report from the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial (I-Preserve)

Literature - Kristensen SL, Mogensen UM, Jhund PS et al. - Circulation. 2017;CIRCULATIONAHA.116.024593


Diabetes (DM) may play an important role in the development of Heart Failure with Preserved Ejection Fraction (HFpEF) and is associated with worse outcomes in HFpEF patients [1,2]. Moreover, while some anti-diabetes drugs may increase the risk of heart failure (HF), others may decrease it [3-5]. The pathophysiological mechanisms underlying these findings are unclear.

In this analysis, the risk of adverse CV outcomes according to DM status was investigated in 4128 patients with HFpEF included in the I-Preserve study (Irbesartan in Heart Failure with Preserved Ejection Fraction trial). In this trial, patients received the angiotensin II receptor antagonist irbesartan and 27% of these patients had DM.

Main results

Echocardiographic measurements (745 patients) showed that compared with patients without DM, DM patients had:

  • larger end systolic dimension (3.3±0.7 vs. 3.2±0.7 cm; P=0.02) • larger end-diastolic dimension (4.9 ±0.6 vs 4.8±0.6 cm; P=0.044) • greater left ventricular mass (173±48 vs. 161±48 grams; P=0.004) • similar relative wall thickness (0.40±0.08 vs. 0.40±0.08; P=0.40) • lower fractional shortening (33±10% vs.35±10%; P=0.09) • significantly higher early diastolic mitral inflow velocity, E (86±32 vs 76±27 cm/sec; P<0.0001) • higher ratio of E/e' (11.7 vs 10.4; P=0.001), in which e’ is the average of lateral and septal annular velocities • higher E/A (early/late) ratio (1.18±0.97 vs 1.00±0.65; P=0.01) • greater left atrial area (24±6 vs. 23±6 cm2; P=0.003) • more enlarged left atrium (75 vs. 66%; P=0.02)
  • Over a median of 4.1 years of follow-up, the unadjusted rates of the composite endpoint of CV death and HF hospitalisation and all-cause mortality were higher in patients with diabetes (34 vs. 22%), with event rates per 100 person years of 10.2 and 5.7, respectively (adjusted HR: 1.75; 95% CI: 1.49-2.05)
  • DM was associated with higher rates of all-cause death, CV death and non-CV death
  • 22% of DM patients were hospitalised due to HF compared to 14% of non-DM patients, with event rates per 100 person-years of 6.6 and 3.5 (DM/no DM adjusted HR: 1.77; 95% CI: 1.45-2.16)
  • When repeat HF hospitalisations were included, the event rates per 100 person-years were 9.3 and 5.7, respectively • The highest risk was in insulin-treated DM patients.

DM patients had higher NT-proBNP levels and a significantly worse quality of life as measured by the Minnesota Living with Heart Failure score.


HFpEF patients with DM have more signs of congestion, worse quality of life, higher NT-proBNP levels, greater structural and functional echocardiographic abnormalities and worse clinical outcomes compared with those without diabetes. These findings support the hypothesis that more intensive diuretic medication may be necessary for these patients.


1. Aguilar D, Deswal A, Ramasubbu K, et al. Comparison of patients with heart failure and preserved left ventricular ejection fraction among those with versus without diabetes mellitus. Am J Cardiol. 2010;105:373-7.

2. MacDonald MR, Petrie MC, Varyani F, et al. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J. 2008;29:1377-85.

3. Mosenzon O, Im K, Umez-Eronini AA, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130:1579-88.

4. Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG

OUTCOME(R) trial. Eur Heart J. 2016;37:1526-34.

5. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med. 2015;373:2247-57.

Find this article online at Circulation

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