Synergistic prognostic values of cardiac sympathetic innervation with left ventricular hypertrophy and left atrial size in heart failure patients without reduced left ventricular ejection fraction: a cohort study

Abstract

ObjectivesThis study tested whether cardiac sympathetic innervation assessed by metaiodobenzylguanidine (MIBG) activity has long-term prognostic value in combination with left ventricular hypertrophy (LVH) and left atrial size in heart failure (HF) patients without reduced left ventricular ejection fraction (LVEF).DesignA single-centre prospective cohort study.Setting/participantsWith primary endpoints of cardiac death and rehospitalisation due to HF progression, 178 consecutive symptomatic HF patients with 74% men, mean age of 56 years and mean LVEF of 64.5% were followed up for 80 months. The entry criteria consisted of LVEF more than 50%, completion of predischarge clinical evaluations including cardiac MIBG and echocardiographic studies and at least more than 1-year follow-up when survived.ResultsThirty-four patients with cardiac evens had larger left atrial dimension (LAD), increased LV mass index, reduced MIBG activity quantified as heart-to-mediastinum ratio (HMR) than did the others. Multivariable Cox analysis showed that LAD and HMR were significant predictors (HR of 1.080 (95% CI 1.00 to 1.16, p=0.044) and 0.107 (95% CI 0.01 to 0.61, p=0.012, respectively). Thresholds of HMR (1.65) and LAD (37 mm) were closely related to identification of high-risk patients. In particular, HMR was a significant determinant of cardiac events in both patients with and without LV hypertrophy. Reduced HMR with enlarged LAD or LV hypertrophy identified patients at most increased risk; overall log-rank value, 11.5, p=0.0032 for LAD and 17.5, p=0.0002, respectively.ConclusionsIn HF patients without reduced LV ejection fraction, impairment of cardiac sympathetic innervation is related to cardiac outcomes independently and synergistically with LA size and LV hypertrophy. Cardiac sympathetic innervation assessment can contribute to better risk-stratification in combination with evaluation of LA size and LV mass but is needed to be evaluated for establishing aetiology-based risk assessment in HF patients at increased risk.

A prediction model for 5-year cardiac mortality in patients with chronic heart failure using 123I-metaiodobenzylguanidine imaging

“…Inclusion of HMR reduced the prognostic contribution of LVEF to the model, consistent with the results for all-cause death in the full population, where MIBG showed better discrimination between high-risk and low-risk CHF patients than LVEF [ 13 ]. This result may correspond to previous findings that there is a non-negligible fraction of high-risk heart failure patients with preserved LVEF and that cardiac MIBG assessment can identify these high-risk patients with preserved LVEF [ 21 ].…”

Synergistic prognostication of left ventricular hypertrophy and three‐dimensional mechanical dyssynchrony in heart failure

“…The precise mechanisms underlying cardiac mortality have not been determined. Together with the results of our previous studies, however, it has been shown that impairment of cardiac sympathetic nerve function may exacerbate LV hypertrophy and increase LVMD in association with cardio‐renal anaemia syndrome, leading to lethal cardiac events in HF patients.…”

“…These findings strongly suggest that their clinical outcomes can be improved by prevention or amelioration of LV hypertrophy and kidney dysfunction together with treatment of their underlying diseases responsible for these conditions and LVMD. Impaired kidney function or chronic kidney disease and anaemia are known to be closely correlated with cardiac outcomes in HF patients, independently of LV systolic function . The precise mechanisms underlying cardiac mortality have not been determined.…”

“…Impaired kidney function or chronic kidney disease and anaemia are known to be closely correlated with cardiac outcomes in HF patients, independently of LV systolic function. 3,4,21,22 The precise mechanisms underlying cardiac mortality have not been determined. Together with the results of our previous studies, [21][22][23][24] however, it has been shown that impairment of cardiac sympathetic nerve function may exacerbate LV hypertrophy and increase LVMD in association with cardio-renal anaemia syndrome, 25 leading to lethal cardiac events in HF patients.…”

Impaired Cardiac Sympathetic Innervation Increases the Risk of Cardiac Events in Heart Failure Patients with Left Ventricular Hypertrophy and Mechanical Dyssynchrony

“…Furthermore, our recent study shows that this standardization method can be applied in cardiac event prediction models [ 23 ]. Prognostic values of cardiac autonomic innervation assessed by standardized HMR are also shown in HF patients with preserved or mid-range LVEF, as well as in HF patients with reduced LVEF [ 24 ]. Thus, the standardization technique in cardiac MIBG imaging can contribute to facilitating the wide-spread use of the neuroimaging in a clinical setting and in a multicenter study for precise identification and monitoring of life-threatening cardiac conditions.…”