Discussion
Based on our studies, we propose that QRS axis is an important factor
for risk stratification in population with PR prolongation. The extent
to which this population with PR prolongation and QRS axis ≤37° is at
higher risk of death compared with the population without PR
prolongation. These associations were independent of P-wave duration and
other known risk factors.
Our results were similar to previous studies, indicated that PR
prolongation is not an independent risk factor for poor prognosis among
adults without CVD2,12. Some studies of PR interval
examining general populations only reported prolongation of the PR
interval has been associated with increased risks of AF and HF compared
with a normal PR interval6,8,21. For all-cause death,
results are conflicting. But from the pathophysiological point of view,
diastolic mitral regurgitation (MR) was indeed observed in individuals
with PR prolongation22. Furthermore, normalized PR
interval may eliminate this hemodynamic change, leading to a decrease in
left atrial pressure and higher LV preload23. Thus,
accurate risk stratification on the potential significance of this
change in this population is warranted.
It is worth noting that PR prolongation is an important risk factor for
early death in some special population. In a recent study in patients
with HCM, PR interval ≥200ms was associated with HCM-related death,
including the combined end point of sudden death or lethal
arrhythmia10. In sub-analyses of two trials on cardiac
resynchronization therapy (CRT) in patients with HF, individuals with a
prolonged PR interval in the control group had a higher risk of
all-cause death than those with normal PR
interval24,25. Diastolic dysfunction (DD) is a
prominent clinical feature both in HCM or HF
patients26,27 and superposition of PR prolongation and
DD would probably produce greater damage28. One
possible mechanism would be mechanical LV dyssynchrony associated with
DD deteriorated this abnormality of atrioventricular
coupling29. Several studies investigated the value of
restored AV coupling for clinical benefit in patients with prolonged PR
interval. In these studies, CRT reduced the all-cause mortality risk of
HF patients, but this benefit was confined to individuals with PR
prolongation30,31. Our study may complement the
mechanism proposed above for the interaction between LV function and PR
interval.
QRS axis as a parameter directly obtained from ECG reports could be a
surrogate marker of LV diastolic20. But we found that
prolonged PR and QRS axis do not had the strong association with death
when considered separately. This result may show that neither abnormal
QRS axis nor prolonged PR interval can be used separately as a criterion
to assess prognosis of population without CVD. The previous study also
suggested that taking into account both abnormal QRS axis and prolonged
PR interval may be helpful in further identifying abnormal LV
function32. And we detected statistically significant
interaction between the two. With QRS axis left shift, population with
PR prolongation were at continuously increased risk of all-cause death.
Therefore, we proposed that QRS axis can be an important factor for risk
stratification in population with PR prolongation and compared the
prognostic difference across populations stratified by their
combination. This result is also in accordance with our conjecture.
People had worse outcomes when they suffer from both QRS less than
median and PR prolongation.
Previous studies have indicated that P-wave duration is a more sensitive
marker for assessing the cardiovascular risk than PR segment because
significant correlations between PR prolongation and death were observed
only in high P/PR ratio group15. Prolonged P-wave
duration indeed reflects both structural as well as electrophysiologic
abnormalities in the atria33. The clinical
implications of the two are partly overlapping yet not entirely
identical. Our sensitivity analyses highlight a still independent
prognostic value for the combination of both PR prolongation and QRS
≤37° in the low P/PR ratio population. Notably, MR associated with
prolongation PR segment also induces atrial chronic stretch and
conduction abnormalities and causes P-wave
prolongation34,35. Their causal relationship cannot be
determined due to the lack of some relevant studies. Our data provide a
new light that P-wave duration might serve as another factor for risk
stratification other than QRS axis in people with PR prolongation. The
ultimate goal of our study presented here is to improve risk assessment
for populations with PR prolongation by ECG. For those at high risk,
close follow-up and aggressive early intervention may be required.