Background
Right Ventricular failure (RVF) complicates 9–44% of LVAD implants postoperatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. We aimed to study chemokine receptor regulation in LVAD recipients who develop RVF.
Methods
Expression of chemokine receptor genes 3–8 was examined in the peripheral blood of 111 LVAD patients, collected 24 hours prior to implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold and normalized to the average of 3 control genes- GAPDH, HPRT1 and B2M. Secondary outcomes studied were 1 year mortality and long-term RV failure (RVF-LT).
Results
Chemokine receptors CCR3, CCR4, CCR6, CCR7 and CCR8 were down regulated in LVAD recipients who had RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further down regulated in those that required mechanical support of their RV. Additionally, under-expression of CCR3–8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. Chemokine receptor expression did not predict RVF-LT in our patient cohort.
Conclusions
Pre-LVAD chemokine receptor down regulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play an important role in prognostication in this patient population.
This study aimed to demonstrate feasibility of statistical shape analysis techniques to identify distinguishing features of right ventricle (RV) shape as related to hemodynamic variables and outcome data in pulmonary hypertension (PH).Cardiovascular magnetic resonance images were acquired from 50 patients (33 PH, 17 Non-PH). Contemporaneous right heart catheterization data was collected for all individuals. Outcome was defined by all-cause mortality and hospitalization for heart failure. RV endocardial borders were manually segmented, and 3D surfaces reconstructed at end-diastole and end-systole. Registration and harmonic mapping were then used to create a quantitative correspondence between all RV surfaces. Proper orthogonal decomposition was performed to generate modes describing RV shape features. The first 15 modes captured over 98 % of the total modal energy. Two shape modes, 8 (free wall expansion) and 13 (septal flattening), stood out as relating to PH state (Mode 13: r=0.424, p=0.002. Mode 8: r=0.429, p=0.002). Mode 13 was significantly correlated with outcome (r = 0.438, p = 0.001), more so than any hemodynamic variable. Shape analysis techniques can derive unique RV shape descriptors corresponding to specific, anatomically meaningful features. The modes quantify shape features that had been previously only qualitatively related to PH progression. Modes describing relevant RV features are shown to correlate with clinical measures of RV status, as well as outcomes. These new shape descriptors lay the groundwork for a non-invasive strategy for identification of failing RVs, beyond what is currently available to clinicians.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.