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Mechanical dyssynchrony alters left ventricular flow energetics in failing hearts with LBBB: a 4D flow CMR pilot study.

ABSTRACT: The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB. CMR data were acquired at 3 T in 22 heart failure patients; 11 with LBBB and 11 without LBBB matched according to several demographic and clinical parameters. An established 4D flow analysis method was used to separate the LV end-diastolic (ED) volume into functional flow components based on the blood's timing and route through the heart cavities. While the Direct Flow volume was not different between the groups, the KE possessed at ED was lower in LBBB patients (P?=?0.018). Direct Flow entering the LV during early diastolic filling possessed less KE at ED in LBBB patients compared to non-LBBB patients, whereas no intergroup difference was observed during late filling. Pre-systolic KE of LV Direct Flow was reduced in patients with LBBB compared to matched patients with normal conduction. These intriguing findings propose that 4D flow specific measures can serve as markers of LV mechanical dyssynchrony in heart failure patients, and could possibly be investigated as predictors of response to cardiac resynchronization therapy.

SUBMITTER: Zajac J

PROVIDER: S-EPMC5859696 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Mechanical dyssynchrony alters left ventricular flow energetics in failing hearts with LBBB: a 4D flow CMR pilot study.

Zajac Jakub J Eriksson Jonatan J Alehagen Urban U Ebbers Tino T Bolger Ann F AF Carlhäll Carl-Johan CJ

The international journal of cardiovascular imaging 20171102 4

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic functio ...[more]

PMID: 29098524

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Project description:BackgroundThe beating heart is the generator of blood flow through the cardiovascular system. Within the heart's own chambers, normal complex blood flow patterns can be disturbed by diseases. Methods for the quantification of intra-cardiac blood flow, with its 4D (3D+time) nature, are lacking. We sought to develop and validate a novel semi-automatic analysis approach that integrates flow and morphological data.MethodIn six healthy subjects and three patients with dilated cardiomyopathy, three-directional, three-dimensional cine phase-contrast cardiovascular magnetic resonance (CMR) velocity data and balanced steady-state free-precession long- and short-axis images were acquired. The LV endocardium was segmented from the short-axis images at the times of isovolumetric contraction (IVC) and isovolumetric relaxation (IVR). At the time of IVC, pathlines were emitted from the IVC LV blood volume and traced forwards and backwards in time until IVR, thus including the entire cardiac cycle. The IVR volume was used to determine if and where the pathlines left the LV. This information was used to automatically separate the pathlines into four different components of flow: Direct Flow, Retained Inflow, Delayed Ejection Flow and Residual Volume. Blood volumes were calculated for every component by multiplying the number of pathlines with the blood volume represented by each pathline. The accuracy and inter- and intra-observer reproducibility of the approach were evaluated by analyzing volumes of LV inflow and outflow, the four flow components, and the end-diastolic volume.ResultsThe volume and distribution of the LV flow components were determined in all subjects. The calculated LV outflow volumes [ml] (67 +/- 13) appeared to fall in between those obtained by through-plane phase-contrast CMR (77 +/- 16) and Doppler ultrasound (58 +/- 10), respectively. Calculated volumes of LV inflow (68 +/- 11) and outflow (67 +/- 13) were well matched (NS). Low inter- and intra-observer variability for the assessment of the volumes of the flow components was obtained.ConclusionsThis semi-automatic analysis approach for the quantification of 4D blood flow resulted in accurate LV inflow and outflow volumes and a high reproducibility for the assessment of LV flow components.

Project description:Cardiac mechanical function is supported by ATP hydrolysis, which provides the chemical-free energy to drive the molecular processes underlying cardiac pumping. Physiological rates of myocardial ATP consumption require the heart to resynthesize its entire ATP pool several times per minute. In the failing heart, cardiomyocyte metabolic dysfunction leads to a reduction in the capacity for ATP synthesis and associated free energy to drive cellular processes. Yet it remains unclear if and how metabolic/energetic dysfunction that occurs during heart failure affects mechanical function of the heart. We hypothesize that changes in phosphate metabolite concentrations (ATP, ADP, inorganic phosphate) that are associated with decompensation and failure have direct roles in impeding contractile function of the myocardium in heart failure, contributing to the whole-body phenotype. To test this hypothesis, a transverse aortic constriction (TAC) rat model of pressure overload, hypertrophy, and decompensation was used to assess relationships between metrics of whole-organ pump function and myocardial energetic state. A multiscale computational model of cardiac mechanoenergetic coupling was used to identify and quantify the contribution of metabolic dysfunction to observed mechanical dysfunction. Results show an overall reduction in capacity for oxidative ATP synthesis fueled by either fatty acid or carbohydrate substrates as well as a reduction in total levels of adenine nucleotides and creatine in myocardium from TAC animals compared to sham-operated controls. Changes in phosphate metabolite levels in the TAC rats are correlated with impaired mechanical function, consistent with the overall hypothesis. Furthermore, computational analysis of myocardial metabolism and contractile dynamics predicts that increased levels of inorganic phosphate in TAC compared to control animals kinetically impair the myosin ATPase crossbridge cycle in decompensated hypertrophy/heart failure.

Project description:BackgroundMyocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment.MethodsForty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups.ResultsLV KEiEDV was higher in controls than in MI patients (8.5 ± 3 μJ/ml versus 6.5 ± 3 μJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P < 0.05). In logistic-regression analysis, systolic KEiEDV (Beta = - 0.24, P < 0.01) demonstrated the strongest association with the presence of MI. In multiple-regression analysis, infarct size was most strongly associated with in-plane KE (r = 0.5, Beta = 1.1, P < 0.01). In patients with preserved LV ejection fraction (EF), minimal and in-plane KEiEDV were reduced (P < 0.05) and time difference to peak E-wave KE propagation during diastole increased (P < 0.05) when compared to controls with normal EF.ConclusionsReduction in LV systolic function results in reduction in systolic flow KEiEDV. Infarct size is independently associated with the proportion of in-plane LV KE. Degree of LV impairment is associated with TD of peak E-wave KE. In patient with preserved EF post MI, LV blood flow KE mapping demonstrated significant changes in the in-plane KE, the minimal KEiEDV and the TD. These three blood flow KE parameters may offer novel methods to identify and describe this patient population.

Dataset Information

Mechanical dyssynchrony alters left ventricular flow energetics in failing hearts with LBBB: a 4D flow CMR pilot study.

Publications

Mechanical dyssynchrony alters left ventricular flow energetics in failing hearts with LBBB: a 4D flow CMR pilot study.

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