Hemodynamic gain index and risk of ventricular arrhythmias: a prospective cohort study.

Objectives: Hemodynamic gain index (HGI), a novel hemodynamic index obtained from cardiopulmonary exercise testing (CPX), is associated with adverse cardiovascular outcomes. However, its specific relationship with ventricular arrhythmias (VAs) is unknown. We aimed to assess the association of HGI with risk of VAs in a prospective study. Design: Hemodynamic gain index was estimated using heart rate and systolic blood pressure (SBP) responses ascertained in 1945 men aged 42-61 years during CPX from rest to maximum exercise, using the formula: [(Heart ratemax x SBPmax) - (Heart raterest x SBPrest)]/(Heart raterest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for VAs. Results: Over a median follow-up duration of 28.2 years, 75 cases of VA were recorded. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of VA (HR 0.72, 95% CI: 0.55-0.95). The results remained consistent on adjustment for lifestyle factors and comorbidities (HR 0.72, 95% CI: 0.55-0.93). Comparing the top versus bottom tertiles of HGI, the corresponding adjusted HRs (95% CIs) were 0.51 (0.27-0.96) and 0.52 (0.28-0.94), respectively. The associations were attenuated on addition of CRF to the model. HGI improved risk discrimination beyond established risk factors but not CRF. Conclusions: Higher HGI is associated with a reduced risk of VAs in middle-aged and older Caucasian men, but dependent on CRF levels. Furthermore, HGI improves the prediction of the long-term risk for VAs beyond established risk factors but not CRF.

Clinical significance of the hemodynamic gain index in patients undergoing exercise stress testing and coronary computed tomography angiography.

BACKGROUND: Many hemodynamic parameters provide limited information regarding obstructive coronary artery disease (CAD) during exercise stress testing particularly when exercise is suboptimal. Hemodynamic gain index (HGI) is a recent sensitive indicator of ischemia and has been associated with increased mortality. This study evaluated the clinical impact of HGI in patients who underwent concomitant exercise stress testing and coronary computed tomography angiography (CCTA). METHODS: A total of 284 consecutive patients from the executive health program between 2010 and 2018 were identified. Resting and peak heart rate (HR) as well as systolic blood pressure (SBP) measurements were recorded. Framingham risk score (FRS), Duke treadmill score (DTS) and HGI [Formula: see text] were calculated. The latter was divided into quartiles. CCTA was used as a reference test to detect any CAD. Multivariate analysis and artificial neural network were used to determine the independent predictors of obstructive CAD. RESULTS: Mean age was 53 ± 12 years with 83% male. Mean HGI was 1.74 ± 0.67, with cut-off value of severely blunted HGI ≤ 1.25 (Quartile 4). Patients with severely blunted HGI were older, had higher FRS, and worse DTS. Patients with obstructive CAD had lower HGI when compared to those with normal CCTA/non-obstructive CAD (1.36 ± 0.53 vs. 1.77 ± 0.67, P = 0.005), and showed a higher prevalence of severely blunted HGI (44% vs. 22%, P = 0.019). After adjusting for traditional risk factors, HGI remained an independent predictor of obstructive CAD while severely blunted HGI was associated with threefold increased odds of having obstructive CAD (P = 0.05). Using artificial intelligence analysis, severely blunted HGI independently predicted obstructive CAD with an area under the curve of 0.83 and 0.96, and normalized importance of HGI of 100% and 63%, respectively for different models. CONCLUSIONS: Among patients who underwent concomitant exercise stress testing and CCTA, severely blunted HGI independently predicted obstructive CAD after multivariate adjustment for traditional risk factors.

Hemodynamic gain index and risk of chronic kidney disease: A prospective cohort study of middle-aged and older men.

The hemodynamic gain index (HGI), a novel non-invasive hemodynamic marker, represents a promising advancement in cardiovascular risk assessment. Cardiovascular disease and chronic kidney disease (CKD) are closely intertwined and share bidirectional relationships. We aimed to assess the association of HGI with CKD risk in a prospective study. Hemodynamic gain index was calculated using heart rate and systolic blood pressure (SBP) responses measured in 1765 men aged 42-61 years with normal kidney function during exercise testing using the formula: [(Heart ratemax x SBPmax)-(Heart raterest x SBPrest)]/(Heart raterest x SBPrest). Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for CKD. Over a median follow-up duration of 25.9 years, 175 CKD cases occurred. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of CKD (HR 0.78, 95% CI 0.65-0.95). Comparing extreme tertiles of HGI, the corresponding adjusted HR (95% CI) for CKD was 0.53 (0.33-0.85). Addition of HGI to a CKD risk prediction model containing established risk factors improved risk discrimination and reclassification (p-value for difference in -2 log likelihood = .011; net-reclassification-improvement = 59.37%, p = .018; integrated-discrimination-improvement = 0.0064, p = .008). Higher HGI is associated with a lower CKD risk and improves the prediction and classification of CKD beyond common established risk factors.

Prognostic Value of Hemodynamic Gain Index in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Assessment of functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) is essential for risk stratification, and it traditionally relied on cardiopulmonary exercise testing (CPET)-derived peak oxygen consumption (peak Vo2). OBJECTIVES: This study sought to investigate the prognostic value of alternative nonmetabolic exercise testing parameters in a contemporary cohort with HFrEF. METHODS: Medical records of 1,067 consecutive patients with chronic HFrEF who underwent CPET from December 2012 to September 2020 were reviewed for a primary outcome that was a composite of all-cause mortality, left ventricular assist device implantation, and/or heart transplantation. Multivariable Cox regression and log-rank testing were used to determine prognostic values of various exercise testing variables. RESULTS: The primary outcome was identified in 331 of 954 patients (34.7%) of the HFrEF cohort (median follow-up time, 946 days). After adjustment for demographics, cardiac parameters, and comorbidities, higher hemodynamic gain index (HGI) and peak rate-pressure product (RPP) were associated with greater event-free survival (adjusted HR per doubling: 0.76 and 0.36; 95% CI: 0.67-0.87 and 0.28-0.47; all P < 0.001, respectively). Moreover, HGI (area under the curve [AUC]: 0.69; 95% CI: 0.65-0.72) and peak RPP (AUC: 0.71; 95% CI: 0.68-0.74) were comparable to the standard peak Vo2 (AUC: 0.70; 95% CI: 0.66-0.73; P for comparison = 0.607 and 0.393, respectively) for primary outcome discrimination. CONCLUSIONS: HGI and peak RPP show good correlation with peak Vo2 in terms of prognostication and outcome discrimination in patients with HFrEF and may serve as suitable alternatives to CPET-derived prognostic variables.

Validation of prognostic value of the hemodynamic gain index in different groups of patients undergoing exercise stress testing.

Background: Recently, the hemodynamic gain index (HGI) has shown to be a strong independent predictor of all-cause mortality and associated with metabolic equivalents (METs) in a cohort of male patients. However, the prognostic implications of the HGI have never been externally validated with subgroup analyses based on gender, body mass index (BMI) of 35 kg/m2, history of heart failure (HF), coronary artery disease (CAD) and beta-blocker use. Methods: We identified 126,356 consecutive patients undergoing treadmill exercise testing between January 1st, 1991 and February 27th, 2015. HGI was calculated using the formula: [(SBPpeak × HRpeak) - (SBPrest × HRrest)] / (SBPrest × HRrest). Cox regression models were used to determine the associations between HGI quartiles and all-cause mortality with adjustment for cardiovascular risk factors and exercise testing parameters. Results: Mean age was 53.5 ± 12.6 years. There were 74,724 (59.1 %) male, 5940 (4.7 %) HF, 21,123 (16.7 %) CAD, and 30,568 (24.2 %) beta-blocker-using patients. During the median follow up of 7.1 years, 9929 (7.9 %) died. Median HGI was 1.93 (interquartile range [IQR] 1.40-2.54) bpm/mmHg. After adjustment for the covariates, lower HGI was independently associated with all-cause mortality in the entire cohort (quartile 1 vs 4, adjusted hazard ratio [95 % confidence interval] 1.33 [IQR 1.21-1.45], p < 0.001), and subgroups of men, women, patients with body mass index <35 kg/m2, with and without HF, CAD, and beta-blocker use. The HGI also correlates well with METs in every subgroup. Conclusions: The HGI is a strong predictor of long-term mortality independently of traditional cardiovascular risk factors, and exercise performance across patient subgroups.