Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF

Aims Impact of type 2 diabetes mellitus (T2DM) on non‐thromboembolic outcomes in atrial fibrillation (AF) is insufficiently explored. This prospective cohort study of AF patients aimed (i) to analyse the association between T2DM and heart failure (HF) events (including new‐onset HF), and all‐cause and cardiovascular mortality, (ii) to assess the impact of baseline T2DM treatment on outcomes, and (iii) to explore characteristics of new‐onset HF phenotypes in relation to T2DM status. Methods and results Of 1803 AF patients (515/1288, with/without prior HF), 389 (22%) had T2DM at baseline. After 5 years of median follow‐up, T2DM patients had an 85% greater risk of HF events [adjusted hazard ratio (aHR) 1.85; 95% confidence interval (CI) 1.51–2.28; P < 0.001], including a 45% increased risk for new‐onset HF (1.45; 1.17–2.28; P = 0.015). T2DM conferred a 56% higher all‐cause (1.56, 1.22–2.01; P = 0.003) and a 48% higher cardiovascular mortality (1.48; 1.34–1.93; P = 0.007). Fine–Gray analysis, with mortality as a competing risk, confirmed greater HF risk among T2DM patients. All risks were highest among insulin‐treated patients. The prevalence of new‐onset HF phenotypes was as follows: 67% preserved ejection fraction (HFpEF), 20% mid‐range ejection fraction (HFmrEF) and 13% reduced ejection fraction (HFrEF). On time‐dependent Cox regression, adjusted for baseline characteristics and an interim acute coronary event, T2DM increased aHRs for new‐onset HFpEF (2.38; 1.30–4.58; P <0.001) and the combined HFmrEF/HFrEF (1.77; 1.11–3.62; P = 0.017). Conclusions Atrial fibrillation patients with T2DM have independently increased risk of new‐onset/recurrent HF events, cardiovascular and all‐cause mortality, particularly when insulin‐treated. The prevailing phenotype of new‐onset HF was HFpEF; T2DM conferred higher risk of both HFpEF and HFmrEF/HFrEF.

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Type 2 diabetes increases the long‐term risk of heart failure and mortality in patients with atrial fibrillation

Polovina

Lund

Đikić³

et al. 2019

“…While clinical cardiology originally focused on diseases of the large epicardial conduit arteries, myocardial perfusion is importantly determined by structure and function of the coronary microvasculature and capillaries . An increasing number of studies have shown that coronary microvascular dysfunction (CMD) plays an important role in many cardiovascular diseases, including heart failure with preserved ejection fraction (HFpEF) . In this patient cohort, CMD has been demonstrated histologically, via imaging techniques, and invasively .…”

Section: Introductionmentioning

confidence: 96%

Endothelium‐dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction

Yang

Obokata

Reddy

et al. 2019

100

Background Coronary microvascular inflammation is hypothesized to play a fundamental role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). No study has directly evaluated both endothelium‐dependent and independent coronary microvascular function in HFpEF. Methods and results Consecutive patients with HFpEF undergoing invasive coronary physiologic testing and echocardiography were examined. Endothelial function was quantified by the increase in coronary blood flow in response to intracoronary infusion of acetylcholine (10−6–10−4 mol/L) using a Doppler flow wire with quantitative angiography. Endothelium‐independent coronary microvascular function was assessed by the hyperaemic increase in coronary flow reserve in response to adenosine infusion. Among 162 HFpEF patients (67% women), coronary microvascular function was abnormal in 117 (72%). Isolated endothelium‐dependent microvascular dysfunction was present in 47 patients (29%), isolated endothelium‐independent microvascular dysfunction in 53 patients (33%), and combined microvascular dysfunction in 17 patients (10%). The presence of coronary microvascular dysfunction was not identifiable from medical co‐morbidities or other clinical characteristics. As compared to patients with normal endothelium‐independent function, HFpEF patients with endothelium‐independent coronary microvascular dysfunction displayed lower diastolic relaxation velocities (7.0 ± 1.8 vs. 8.4 ± 2.9 cm/s, P = 0.002) and higher estimated filling pressures (E/e' 13.1 ± 4.1 vs. 9.6 ± 3.4, P < 0.001). There were no relationships between left ventricular structure, function, or haemodynamics and endothelium‐dependent coronary vasodilatation. Endothelium‐independent microvascular dysfunction was associated with increased mortality. Conclusions Coronary microvascular dysfunction is common in patients with HFpEF and is caused equally by endothelium‐dependent and independent mechanisms, but the presence of microvascular dysfunction cannot be identified from clinical markers and co‐morbidities alone. Patients with HFpEF and endothelium‐independent microvascular dysfunction display worse diastolic dysfunction and outcomes.

“…Epicardial adipose tissue is increased in patients with HFpEF and in those with AF, and is particularly prominent when HFpEF and AF coexist, particularly if patients have evidence of systemic inflammation or are at risk of adverse outcomes . Coronary microvascular dysfunction is exceptionally common in HFpEF and, when present, is associated with a two‐fold increase in the prevalence of AF . Cardiac magnetic resonance imaging (MRI) reveals meaningful myocardial fibrosis (in the LA and LV) in both patients with HFpEF and those with AF .…”

Section: Pathophysiological Mechanisms Leading To Hfpefmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.