What does this research mean for the field?

Chronotropic incompetence during exercise or pharmacological stress is associated with a 10-year mortality of 39% in patients with chronic coronary syndromes, compared to 21% in those without it. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

What question did this study set out to answer?

The aim is to evaluate how chronotropic incompetence during stress testing relates to survival in patients with chronic coronary syndromes.

February 8, 2026

Chronotropic incompetence during exercise or pharmacological stress is associated with survival in patients with chronic coronary syndromes

Key Result

Chronotropic incompetence was observed in 38% of patients with chronic coronary syndromes and was associated with a 60% increased risk of 10-year mortality (HR 1.60).

Key Points

The aim is to evaluate how chronotropic incompetence during stress testing relates to survival in patients with chronic coronary syndromes.
Prospective, multicenter observational study
Enrolled 13,445 patients from 19 sites across 10 countries
Utilized exercise, dobutamine, or dipyridamole for stress echocardiography
Measured heart rate using 1-lead ECG to define CI
Monitored all-cause mortality over a median follow-up of 3.5 years
CI observed in 5,045 patients (38%)
10-year mortality of 39% in patients with CI vs 21% without CI (p<0.0001)
CI is a significant predictor of mortality across all age groups
Cox analysis indicated hazard ratio of 1.60 for CI as a mortality predictor (p<0.0001)

Structured PICO

Does chronotropic incompetence during stress echocardiography predict all-cause mortality in patients with chronic coronary syndromes?

Population

13,445 patients with known or suspected chronic coronary syndromes who underwent stress echocardiography

Intervention

Presence of chronotropic incompetence (CI) during physical or pharmacological stress echocardiography

Comparator

Absence of chronotropic incompetence during stress echocardiography

Outcome

All-cause deathhard clinical

Chronotropic incompetence during stress echocardiography is a strong, independent predictor of long-term all-cause mortality in patients with chronic coronary syndromes.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Background Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. Aim To assess the risk stratification value of CI during physical or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods In a prospective, multicenter, international, observational study design, we enrolled 13,445 patients with known or suspected chronic coronary syndromes who underwent stress echo in 19 sites from 10 countries using either exercise (n=2,594), dobutamine (n=2,440), or dipyridamole (n=8,411). Heart rate was automatically measured from the 1-lead ECG in the echo monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) 1.22 (1.17 in permanent atrial fibrillation) for dipyridamole. All-cause death was the outcome measure. Results Heart rate reserve was available in all patients; there was no extra imaging or analysis time, and no intra- and inter-observer variability. CI was observed in 5,045 patients (38%); abnormal regional wall motion abnormality in 1,648 (13%). Over a median follow-up time of 3.5 years, there were 2,426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (p0.0001). CI was associated with a significant (p0.0001) increase in 10-year mortality in all age groups ranging from 54 years to 75 years. In addition, it was associated with increased mortality (p0.0001) irrespective of β-blocker use (Figure). Cox multivariable analysis revealed that CI was a significant predictor of mortality (HR 1.60, 95% confidence interval 1.47-1.74; p0.0001) together with age, male sex, diabetes mellitus, ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during physical or pharmacological stress is a simple, inexpensive, quantitative, and objective predictor of survival.

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