Endothelial dysfunction in heart failure identifies responders to cardiac resynchronization therapy

Wrigley

et al. 2011

Circ: Heart Failure

Background— Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited. Methods and Results— In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF (“disease controls”) and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine ( P =0.001) and reduced FMD ( P <0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P <0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P <0.001) and ACs (4.55±3.56%, P =0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels ( P =0.003). There were no differences in numbers of endothelial microparticles. Conclusions— The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.

Section: Discussionsupporting

confidence: 87%

Ethnic Differences in Macrovascular and Microvascular Function in Systolic Heart Failure

Wrigley

et al. 2011

Circ: Heart Failure

“…Two small studies have shown consistent improvement in microvascular cutaneous reactive hyperaemia post‐CRT insertion,5, 6 while studies of the effects of CRT on large conduit vessels utilizing flow‐mediated [i.e. nitric oxide (NO)‐dependent] dilatation (FMD) have shown conflicting results 7, 8, 9. In this present study, we sought to evaluate the effect of CRT on peripheral vascular function and associated markers of inflammation, as well as vascular and platelet NO signalling, we also examined the effects of CRT on parameters of inflammatory and neurohumoral activation.…”

Section: Introductionmentioning

confidence: 99%

Does cardiac resynchronization therapy restore peripheral circulatory homeostasis?

et al. 2017

AimsTo evaluate whether peripheral circulatory ‘remodelling’ as measured by changes in vascular compliance and in markers of nitric oxide signalling contributes to patient response to cardiac resynchronization therapy (CRT).Methods and resultsEffects of CRT were evaluated in 33 patients pre‐procedure and 6 months post‐procedure. Peak oxygen consumption, 6 min walk distance, New York Heart Association class, and quality of life score were evaluated. Augmentation index and its interactions with nitric oxide (NO) were evaluated by applanation tonometry. Platelet NO responsiveness and content of thioredoxin‐interacting protein were assessed. Plasma concentrations of N‐terminal proBNP, asymmetric and symmetric dimethylarginine (SDMA), high sensitivity C‐reactive protein, catecholamines, and matrix metalloproteinases‐2 and ‐9 were assessed. Despite significant improvement in 6 min walk distance (P = 0.005), New York Heart Association class (P < 0.001), quality of life (P = 0.001), and all echocardiographic parameters post‐CRT, there were no significant changes in augmentation index measurements, thioredoxin‐interacting protein content, and platelet NO response. Significant falls in N‐terminal proBNP (P = 0.008) and SDMA (P = 0.013; independent of renal function) occurred. Falls in SDMA predicted reduction in high‐sensitivity C‐reactive protein (P = 0.04) and increases in peak oxygen consumption (P = 0.04). There were no correlations between changes in echocardiographic parameters and those in vascular function.ConclusionsThese data suggest that the beneficial effects of CRT over 6 months are independent of any change in peripheral NO‐related signalling. However, there is evidence that suppression of inflammation occurs, and its magnitude predicts extent of clinical improvement.

“…Despite clinical response, several studies demonstrated, as well, left ventricular reverse remodeling benefit, with left ventricular ejection fraction increase and systolic left ventricular volume decrease [8,9]. It has been reported that 3-months after the cardiac implant, responders have significant left ventricular end-systolic volume (LVESV) decrease and LV ejection fraction (LVEF) increase, endothelial function increase, 6-min walk test (6MWT), NYHA class and quality of life (QOL) improvement [11][12][13], compared to non-responders. Major trials have shown that 30-40% of patients who undergo CRT are non-responders with no clinical or echocardiographic improvement [10].…”

Section: Introductionmentioning

confidence: 99%

Imaging predictive factors and exercise training in CRT patients

Abreu

Santa-Clara

2016

Monaldi Arch Chest Dis

Cardiac resynchronization therapy (CRT) is an established treatment for patients with moderate-to-severe chronic heart failure (CHF) and intraventricular conduction delay, which is identified by a QRS interval of 120 msec or more on a 12-lead electrocardiogram (ECG). CRT improves functional capacity, reduced hospitalizations for worsening CHF and increased survival, however, about 30-40% of patients who undergo CRT are non-responders with no clinical or echocardiographic improvement. Imaging parameters for prediction of CRT response have been reviewed. Cardiac magnetic resonance (CMR), recognized as the gold standard to assess viability, has shown to obtain good results regarding quantification of scar burden. CMR-derived measures of mechanical dyssynchrony appear to predict the outcome of CRT, however these have not been externally validated. Nuclear imaging techniques, namely single-photon emission cardiac tomography (SPECT) provide data on scar burden and location, left ventricular (LV) function, LV contraction and mechanical dyssynchrony from a single scan. The presence, location and burden of myocardial scar have been shown to affect response to CRT. However, compared to CMR, the low spatial resolution of scintigraphy might overestimate the scar extent. This problem can be overcome by positron emission tomography (PET). SPECT has also been used to quantify dyssynchrony, using phase analysis. Imaging investigation is ongoing, trying to better identify CRT non-responders. The combination of ExT in CRT has not been well investigated, however some data show that different aerobic exercise modes and intensities can further improve CRT benefits. Data available on the effects of ExT in patients with CRT have been reviewed.