Exercise SPECT Study: Hemodynamic Gain Index(HGI) Separates Risk When Perfusion Deficits Are Below 5%

In a two-center retrospective study published online July 18, 2026, in the Journal of Nuclear Cardiology, first author S. Yang and 10 co-authors reported that the hemodynamic gain index was independently associated with major adverse cardiac events (MACE) in 1,254 patients who had symptom-limited cycle-ergometer single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The index is built from heart rate and blood pressure readings that exercise stress labs already record. Adding it significantly improved discrimination among patients with stress total perfusion deficits below 5%, while no statistically significant improvement was detected among those with larger deficits.

Over a median follow-up of 63 months (interquartile range 53 to 69), 187 patients (14.9%) had MACE. Crude event rates fell across tertiles of the index, from 21.3% in the lowest to 14.8% in the intermediate and 8.6% in the highest (p < 0.001).

The stakes sit in the low-deficit group. Of the 1,254 patients, 1,152 had a stress total perfusion deficit (TPD) below 5%, and that group still produced 120 of the 187 events. Among those patients, five-year MACE-free survival was 92.1% with high HGI and 80.1% with low HGI, a gap of 12 percentage points between patients whose stress perfusion deficits fell in the same range.

How the hemodynamic gain index is calculated

The hemodynamic gain index (HGI) is the relative rise in rate-pressure product from rest to peak exercise. As a formula, HGI = (peak heart rate × peak systolic pressure) / (resting heart rate × resting systolic pressure) − 1. In this cohort, one standard deviation equaled 0.563 HGI units. Patients with prior myocardial infarction, prior percutaneous coronary intervention or coronary artery bypass grafting, significant valvular or congenital disease, or an implanted device were excluded, so the population had no history of infarction or revascularization.

Imaging was conventional. Patients received 740 to 925 MBq of 99mTc-sestamibi, the perfusion tracer, at peak exercise, and were scanned on either a Siemens Symbia T16 (sodium iodide detector) or a GE Healthcare Discovery NM 530c (cadmium zinc telluride detector) with gated SPECT and no attenuation or scatter correction. Stress TPD and post-stress left ventricular ejection fraction were quantified with Cedars-Sinai Quantitative Perfusion SPECT and Quantitative Gated SPECT software and Emory Cardiac Toolbox v3.2.

The authors describe HGI as drawn from routinely recorded exercise data and say it could serve as a practical complementary marker. The idea that it adds no cost is an inference from that, not a finding of the study, and the calculation still depends on a peak exercise blood pressure being recorded.

What HGI added to stress TPD

HGI and stress TPD were essentially uncorrelated (ρ = 0.012, p = 0.675). In the full cohort, the concordance index (C-index) went from 0.806 for the base clinical and functional model to 0.848 with stress TPD and 0.854 with HGI added (ΔC 0.006, p = 0.046). The net reclassification improvement (NRI) was 0.310 and the integrated discrimination improvement 0.009. A ΔC of 0.006 is statistically significant but small.

After adjustment, each one-standard-deviation increase in HGI carried a hazard ratio (HR) for MACE of 0.748 (95% confidence interval 0.623 to 0.898; p = 0.002). Low versus high HGI, split at a cutoff of 0.94, had an adjusted HR of 1.738 (1.239 to 2.438; p = 0.001). That cutoff was derived from the outcomes in this same dataset, and the authors say it shouldn’t be treated as a generalizable clinical threshold without external validation.

The time course is telling. Adding HGI to TPD raised the time-dependent area under the curve (AUC) by 0.025 at 12 months, which wasn’t significant, then by 0.060 at 24 months, 0.058 at 36 months and 0.081 at 60 months (p < 0.001), when the AUC stood at 0.775 versus 0.694. In this cohort, the index’s added discrimination grew at longer horizons.

HGI also added to resting heart rate plus resting systolic pressure (ΔC 0.0068, p = 0.028), suggesting its information isn’t captured by the starting values alone.

Low perfusion deficits, unequal risk

A significant discrimination gain was detected in the low-TPD subgroup, but not in the much smaller higher-TPD subgroup; this does not establish that the incremental value differs between groups. In the TPD below 5% group, adding HGI gave a ΔC of 0.011 (p = 0.046) and an NRI of 0.353 (p = 0.022). In the group with TPD of 5% or more (n = 102, 67 events), no statistically significant improvement was detected (ΔC −0.002, p = 0.873).

The event mix matters for how to read the 12-percentage-point gap in five-year MACE-free survival. More than half of first MACE events (102, or 54.5%) were hospitalizations for unstable angina, and all-cause death was the first event in 18 patients (9.6%). MACE in this study wasn’t mainly hard events. HGI also remained significantly associated with the secondary endpoint, which excluded unstable angina and occurred in 85 patients (6.8%).

HGI and heart-rate recovery overlap

The strongest case for restraint comes from the paper itself. Heart-rate recovery at one minute (HRR1) rose across HGI tertiles, with medians of 22, 25 and 29 beats per minute, and correlated with HGI at ρ = 0.280. HRR1, peak heart rate and HGI were each associated with lower MACE risk when added separately.

Once HRR1 was in the model, HGI still improved model fit (Δχ² 3.94, p = 0.047) but didn’t significantly improve the C-index. The same pattern held after adjusting for peak heart rate (Δχ² 6.21, p = 0.013). The authors call HRR1 a strong prognostic marker and say HGI isn’t uniformly superior to it. That leaves HGI as one exercise hemodynamic marker to consider alongside HRR1, not a replacement for it.

Exploratory medication analyses found HGI significantly associated with MACE in patients not taking beta-blockers, non-dihydropyridine calcium channel blockers, or angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, but not in users. The interaction p values were 0.422, 0.321 and 0.867, so the study doesn’t show that the effect actually differs by medication.

For a related look at stress hemodynamics in cardiac imaging, see The Heart-Rate Response Hiding in a Cardiac PET Stress Test.

Related evidence on exercise hemodynamics

A separate cohort in the International Journal of Cardiovascular Imaging offers related background, not confirmation. It followed 1,020 patients with normal rest and exercise-stress SPECT, with normal perfusion defined partly by the absence of transient ischemic dilation, and recorded 44 primary events over 55 ± 22 months. Failing to reach 85% of age-predicted maximum heart rate wasn’t linked to higher risk, but a stress rate-pressure product below 25,000 was (HR 2.03, 1.08 to 3.83; p = 0.028). That’s an absolute product in a cohort built differently, with normal-perfusion patients only and a mixed history of coronary disease, not the relative rise HGI measures.

What the Yang study can’t answer

The findings are associations and better model performance, not causation, and the authors state the study doesn’t show that HGI-guided management improves outcomes. This study did not test HGI with treadmill protocols, in other populations, with attenuation-corrected imaging, or with pharmacologic stress, so its generalizability to those settings remains uncertain. For now, HGI belongs alongside HRR1 as a complementary exercise marker, not a validated management threshold; the next test is external validation of the outcome-derived 0.94 cutoff.

About the sources: Figures for the Yang study come from its full text, “Incremental prognostic value of the hemodynamic gain index in patients undergoing exercise stress myocardial perfusion imaging” (J Nucl Cardiol 2026;63:102822, September 2026 issue), which was funded by Chinese public grants from the National Natural Science Foundation of China and Shanxi province; the authors declare no competing interests. The International Journal of Cardiovascular Imaging study is described from published summaries of the paper. The Journal of Nuclear Cardiology’s September 2026 issue also carries a related article by A. Brar, E. A. Hulten and colleagues, “Unmasking residual risk: The incremental value of the hemodynamic gain index in exercise single-photon emission computed tomography myocardial perfusion imaging.”