Prognostic value of heart rate reserve in patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging
Authors: Nappi C , Petretta M , Cantoni V , Green R , Assante R , Zampella E , Gaudieri V , Mannarino T , D"antonio A , Manganelli M , Piscopo L , Ponsiglione A , Acampa W , Cuocolo A 
Published: July 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background. The prognostic value of stress myocardial perfusion single-photon emission computed tomography (MPS) has been widely demonstrated. Also, chronotropic incompetence, evaluated by heart rate reserve (HRR) is associated with increased risk of adverse events. Yet, the incremental prognostic value of HRR over stress MPS data has not been fully investigated.
Purpose. To assess the incremental prognostic value of HRR over stress MPS finding in patients with suspected coronary artery disease (CAD) undergoing exercise stress MPS.
Methods. The study population consisted of 866 consecutive patients with suspected CAD undergoing exercise stress-MPS at University of Naples Federico II, between May 2002 and January 2014 as part of their diagnostic program. The primary study endpoint was all-cause mortality. All patients were followed for at least 60 months. HRR was calculated as the difference between peak exercise and resting HR, divided by the difference of age-predicted maximal and resting HR and expressed as percent. The summed difference score (SDS) was considered an index of ischemic burden. Patients were considered to have mild ischemia with a SDS of 2 to 6, and moderate-severe ischemia with a SDS ≥6. During follow-up, the occurrence of all-cause of deaths was noted and considered as event. Follow-up was censored at 84 months.
Results. During follow-up, 61 deaths occurred, with a 7% cumulative event rate. Patients experiencing death were older (56.2 ± 10.7 years vs. 66.4 ± 8.6 years), with a higher prevalence of male gender (56% vs. 87 %, P &lt; 0.05) and diabetes mellitus (23% vs. 36%, P &lt; 0.05). At stress-MPS, patients with event had lower mean values of HRR (53.2 ± 21.3% vs. 61.5 ± 16.4%, P &lt; 0.0001) and higher prevalence of moderate-severe ischemia (24% vs. 8%, P &lt; 0.0001). The best trade-off between sensitivity and specificity for identifying chronotropic incompetence was a HRR &lt;67% with an area under the receiver operating characteristic curve of 0.62. The event free survival was lower in patients with HRR &lt;67% compared to those with HRR ≥67% (log-rank 9.75, P &lt; 0.005). Accordingly, the annualized event rate was 0.006 in patients with HRR &lt;67% and 0.014 in those with HRR ≥67% (P &lt; 0.001). At Cox regression analysis, univariable predictors of all-cause mortality were age, male gender, diabetes mellitus, HRR and moderate-severe ischemia (all P &lt; 0.05). At multivariable analysis age, male gender, HRR and moderate-severe ischemia were independent predictors of all-cause mortality (all P &lt; 0.05). HRR improved the prognostic power of a model including clinical data and MPS findings for the prediction of all-cause mortality, increasing the global chi-square from 76.16 to 82.68 (P &lt; 0.005).
Conclusion. Chronotropic incompetence assessed by HRR evaluation, has independent and incremental prognostic value in predicting all cause of death in patients with suspected CAD undergoing exercise stress-MPS.