Impaired retinal micro-vascular function in patients with atrial fibrillation.

BACKGROUND: Cardiovascular (CV) risk factors and CV diseases, in particular heart failure, are strongly associated with impaired microvascular retinal endothelial function. Whether atrial fibrillation (AF) contributes to vascular dysfunction is not clear. Therefore, the aim of this study was to investigate the impact of AF on retinal microvascular function. METHODS: In this study, vascular function was measured non-invasively with flicker-light induced vasodilatation of retinal arterioles (FIDart%). Patients with a history of AF and risk factors for heart failure (HF) or heart failure (n = 69; age 67.9 ± 9.2 years, 71% male, 35% HFrEF, 56% paroxysmal, 25% persistent, 19% permanent AF), as well as age, sex and ejection fraction matched patients with absent history of AF (n = 66; age 63.4 ± 10.6 years, 67% male, 47% HFrEF) were included. Patients with AF were further divided into those with paroxysmal AF (in sinus rhythm - AFSR: n = 38, age 71.4 ± 9.2, 73% male), and those with AF at the time of the study visit. RESULTS: Retinal microvascular function was impaired in patients with AF compared to patients without AF (FIDart% 1.1% [0.3-2.8] vs. 2.7% [1.3-5.1], p < 0.001). Patients currently in AF have poorer retinal microvascular function (FIDart% 0.8% [0.1-1.9) compared to patients with a history of AF but currently in SR at the time of retinal function measurement (1.5% [0.6-4.9] p = 0.017). In patients with AF, impaired retinal vascular function was independently associated with larger left atrial volume (mean 49.8 ± 18.4), even after correction for confounding factors in different models (SCR = -0. 251 to -0.256, p = 0.035-0.01). CONCLUSIONS: AF in patients with heart failure is associated with impaired vascular function, even if currently in sinus rhythm. The association of retinal microvascular dysfunction with left atrial volume, a surrogate for elevated cardiac filling pressures, may further highlight the important interplay between the vasculature and elevated filling pressures in the development of AF.

Vascular function in patients with advanced heart failure and continuous-flow or pulsatile ventricular assist devices.

BACKGROUND: A significant proportion of patients with heart failure (HF) progress to an advanced stage, which is associated with a substantial increase in morbidity and mortality. These patients may be eligible for advanced treatment strategies such as mechanical circulatory support with ventricular assist devices (VAD). Vascular dysfunction is a hallmark of heart failure pathophysiology and prognosis. However, whether and to what degree the hemodynamic benefits of VADs influence vascular function remain unknown. METHODS AND RESULTS: In this study, we evaluated endothelial vascular function with flow-mediated vasodilatation (FMD) and with flicker-light induced retinal vasodilatation (FID). 34 patients with a VAD (age 58 ± 10 years, 85% male, 74% ischemic heart disease, 26 continuous-flow (CF)-LVAD, and 8 pulsatile biventricular (bi)-VAD) were compared to 34 propensity-matched patients (mean age 62 ± 9 years, 68% male, 59% ischemic heart disease) with advanced HF (AdvHF). Endothelial function of larger arteries (FMD) was significantly better in patients after VAD implantation compared to matched AdvHF patients (7.2 ± 4.6% vs. 5.0 ± 3.2%, p = 0.03), whereas microvascular arteriolar function (FIDart) did not differ (0.99 ± 1.43% vs. 1.1 ± 1.7%, p = 0.78). The arterio-venous ratio (AVR) was higher in the VAD group (0.90 ± 0.06 vs 0.85 ± 0.09, p = 0.01), reflecting wider retinal arteriolar and narrower venular diameters. There was no difference in vascular function between patients with CF-LVAD and pulsatile Bi-VAD. CONCLUSION: In patients with advanced heart failure, VAD implantation was associated with better endothelial function at the level of large arteries, but not in the microcirculation.

Diverging role of epicardial adipose tissue across the entire heart failure spectrum.

AIMS: Epicardial adipose tissue (EAT) is a metabolically highly active tissue modulating numerous pathophysiological processes. The aim of this study was to investigate the association between EAT thickness and endothelial function in patients with heart failure (HF) across the entire ejection fraction spectrum. METHODS AND RESULTS: A total of 258 patients with HF with an ejection fraction across the entire spectrum [HF with reduced ejection fraction (HFrEF), n = 168, age 60.6 ± 11.2 years; HF with preserved ejection fraction (HFpEF), n = 50, mean age 65.1 ± 11.9 years; HF with mildly reduced ejection fraction (HFmrEF), n = 32, mean age 65 ± 12] were included. EAT was measured with transthoracic echocardiography. Vascular function was assessed with flicker-light-induced vasodilation of retinal arterioles (FIDart%) and flow-mediated dilatation (FMD%) in conduit arteries. Patients with HFrEF have less EAT compared with patients with HFpEF (4.2 ± 2 vs. 5.3 ± 2 mm, respectively, P < 0.001). Interestingly, EAT was significantly associated with impaired microvascular function (FIDart%; r = -0.213, P = 0.012) and FMD% (r = -0.186, P = 0.022), even after multivariate correction for confounding factors (age, body mass index, hypertension, and diabetes; standardized regression coefficient (SRC) = -0.184, P = 0.049 for FIDart% and SRC = -0.178, P = 0.043 for FMD%) in HFrEF but not in HFpEF. CONCLUSIONS: Although less EAT is present in HFrEF than in HFpEF, only in HFrEF EAT is associated with vascular dysfunction. The diverging role of EAT in HF and its switch to a functionally deleterious tissue promoting HF progression provide the rationale to specifically target EAT, in particular in patients with reduced ejection fraction.

Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross-sectional study.

Background and Aims: Sustained neurohormonal activation plays a central role in the progression of heart failure (HF). Other endocrine axes may also be affected. It was the aim of this study to examine the endocrine profile (thyroid, parathyroid, glucocorticoid, and sex hormones) in a contemporary sample of patients with HF and reduced ejection fraction (EF) on established disease-modifying therapy. Methods: This study prospectively measured morning fasting hormones in 52 ambulatory and stable HF patients with EF < 50% on disease-modifying therapy (mean age 63 ± 11 years, 29% female, mean LVEF 32 ± 9.6%) and compared them to 54 patients at elevated risk for HF (61 ± 12 years, 28% female) and 62 healthy controls (HC; 61 ± 13 years, 27% female). Main comparisons were performed using one-way analysis of variance. Associations with biomarkers were studied with linear regression. Results: HF patients showed a reduced free triiodothyronine (fT3)/free thyroxine (fT4) ratio compared to HC (0.30 ± 0.06 vs. 0.33 ± 0.05, p = 0.046). Parathyroid hormone (PTH) and cortisol were increased in HF compared to both HC (median [IQR] 59 [50-84] vs. 46 [37-52] ng/L, p < 0.001 and 497 ± 150 vs. 436 ± 108 nmol/L, p = 0.03, respectively) and patients at risk (both p < 0.001). Total testosterone was reduced in male HF compared to HC (14.4 ± 6.6 vs. 18.6 ± 5.3 nmol/L; p = 0.01). No differences in TSH, estradiol, progesterone, and prolactin were found. Lower fT3 levels were found in HF with EF < 40% versus EF 40%-49% (4.6 ± 0.3 vs. 5.2 ± 0.7 pmol/L, p = 0.009). In HF patients, fT3 was an independent predictor of NT-proBNP and high-sensitivity troponin T in multiple regression analysis. PTH was positively associated with NT-proBNP. Conclusion: There is evidence of endocrine hormonal imbalance in HF with reduced EF beyond principal neurohormones and despite the use of disease-modifying therapy.

Eyes on amyloidosis: microvascular retinal dysfunction in cardiac amyloidosis.

AIMS: Cardiac involvement in systemic amyloidosis is a marker of particularly poor prognosis. Cardiac amyloidosis (CA) is characterized by extracellular amyloid deposits inducing heart failure and symptoms of cardiac microvascular disease. While amyloid deposition is most common in the myocardium but also seen in pericardium and endocardium, atria, and vasculature, the role of (micro-)vascular dysfunction in CA pathophysiology remains still elusive. Because vascular function is associated with cardiovascular risk and severity of heart failure and represents a potential therapeutic target in CA, the present study investigated retinal vascular function, flow-mediated dilatation (FMD), and pulse-wave analysis and velocity (PWA/PWV) in patients with CA. METHODS AND RESULTS: Flicker-induced arterial dilatation (FIDa) was measured using dynamic retinal vessel analysis additionally to FMD and PWA/PWV. Thirty-three patients with CA [age 67 years [interquartile range, IQR, 62, 74], 14 with amyloid light-chain (AL) and 19 with transthyretin (ATTR) amyloidosis] were prospectively included in this cross-sectional, observational study and 70 healthy individuals (age 53 years [IQR 39, 67]) served as control. Potential confounders were balanced using entropy balancing propensity score analysis [inverse probability weighting (IPW)]. FIDa was reduced in CA patients (1.52 ± 1.73% vs. 3.09 ± 1.96%, P < 0.001, after IPW). While PWV was increased (8.74 ± 2.34 m/s vs. 7.49 ± 1.65 m/s, P = 0.018, after IPW), no difference in FMD was observed. FIDa was significantly associated with prognostic biomarkers of CA [estimated glomerular filtration rate (r = 0.33; P < 0.001), log-scaled troponin T (r = -0.49; P < 0.001), and N-terminal pro-B-type natriuretic peptide (r = -0.51; P < 0.001)]. CONCLUSIONS: Retinal vascular function is impaired, associated with cardiac and renal biomarkers of CA severity, and may represent a potential therapeutic target in patients with amyloidosis.