Haemodynamic Gain Index Is Associated with Risk of Sudden Cardiac Death and Improves Risk Prediction: A Cohort Study

Abstract

Introduction: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study. Methods: HGI was calculated using heart rate and systolic blood pressure (SBP) responses measured in 1897 men aged 42–61 years during CPX from rest to peak exercise, using the formula: <inline-formula><mml:math id="m1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mrow><mml:mfenced close=")" open="("><mml:mrow><mml:mrow><mml:mfenced close=")" open="("><mml:mrow><mml:mi mathvariant="normal">H</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">t</mml:mi><mml:mspace width="0.25em" /><mml:msub><mml:mrow><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">t</mml:mi><mml:mi mathvariant="normal">e</mml:mi></mml:mrow><mml:mi>max</mml:mi></mml:msub><mml:mspace width="0.25em" /><mml:mo mathvariant="normal">×</mml:mo><mml:mspace width="0.25em" /><mml:msub><mml:mrow><mml:mi mathvariant="normal">S</mml:mi><mml:mi mathvariant="normal">B</mml:mi><mml:mi mathvariant="normal">P</mml:mi></mml:mrow><mml:mi>max</mml:mi></mml:msub></mml:mrow></mml:mfenced></mml:mrow><mml:mo>−</mml:mo><mml:mrow><mml:mfenced close=")" open="("><mml:mrow><mml:mi mathvariant="normal">H</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">t</mml:mi><mml:mspace width="0.25em" /><mml:msub><mml:mrow><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">t</mml:mi><mml:mi mathvariant="normal">e</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">s</mml:mi><mml:mi mathvariant="normal">t</mml:mi></mml:mrow></mml:msub><mml:mspace width="0.25em" /><mml:mo mathvariant="normal">×</mml:mo><mml:mspace width="0.25em" /><mml:msub><mml:mrow><mml:mi mathvariant="normal">S</mml:mi><mml:mi mathvariant="normal">B</mml:mi><mml:mi mathvariant="normal">P</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">s</mml:mi><mml:mi mathvariant="normal">t</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:mfenced></mml:mrow></mml:mrow></mml:mfenced></mml:mrow><mml:mo>/</mml:mo><mml:mrow><mml:mfenced close=")" open="("><mml:mrow><mml:mi mathvariant="normal">H</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">t</mml:mi><mml:mspace width="0.25em" /><mml:msub><mml:mrow><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">t</mml:mi><mml:mi mathvariant="normal">e</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">s</mml:mi><mml:mi mathvariant="normal">t</mml:mi></mml:mrow></mml:msub><mml:mspace width="0.25em" /><mml:mo mathvariant="normal">×</mml:mo><mml:mspace width="0.25em" /><mml:msub><mml:mrow><mml:mi mathvariant="normal">S</mml:mi><mml:mi mathvariant="normal">B</mml:mi><mml:mi mathvariant="normal">P</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="normal">r</mml:mi><mml:mi mathvariant="normal">e</mml:mi><mml:mi mathvariant="normal">s</mml:mi><mml:mi mathvariant="normal">t</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:mfenced></mml:mrow></mml:mrow></mml:math></inline-formula>. Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) were estimated for SCD. Results: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p value for non-linearity = 0.63). A unit (bpm/mm Hg) higher HGI was associated with a decreased risk of SCD (HR: 0.84; 95% CI: 0.71–0.99), which was attenuated following adjustment for CRF. CRF was inversely associated with SCD, which remained after further adjustment for HGI (HR: 0.85; 95% CI: 0.77–0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change = 0.0096; p = 0.017) and reclassification (net reclassification improvement [NRI] = 39.40%, p = 0.001). The corresponding values for CRF were (C-index change = 0.0178; p = 0.007) and (NRI = 43.79%, p = 0.001). Conclusion: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI.