While stuck in a starship trash compactor and muttering, “I have a bad feeling about
this,” Han Solo1 likely feared a worse prognosis compared with that of heart disease
patients with first‐degree atrioventricular block (AVB). However, while P‐R interval
prolongation is often considered a benign finding, the evidence linking it with a
variety of adverse cardiovascular outcomes continues to accumulate.
Prolongation of the P‐R interval to >200 ms typically does not warrant therapy absent
the rare scenario where severe elongation leads to symptoms arising from atrial contraction
immediately after ventricular systole. The infrequent need for therapy has led to
a general impression of first‐degree AVB to represent a benign finding. Among healthy
adults, the data remain mixed as to its prognostic significance. Some large cohort
studies show no association with adverse outcomes,2, 3 whereas others report an association
with increased risk of atrial fibrillation.4 However, among patients with coronary
artery disease and/or heart failure, significant associations are reported between
P‐R interval prolongation and a variety of end points, including mortality and hospitalization
for heart failure.5, 6 A comprehensive review of population and heart disease studies
relating to first‐degree AVB and clinical outcomes has been reported by Nikolaidou
and colleagues.7
In this issue of the Journal of the American Heart Association (JAHA), Higuchi and
colleagues8 report the association between first‐degree AVB and outcomes in a cohort
of 414 patients with hypertrophic cardiomyopathy (HCM). Although such associations
have been described in heart failure cohorts, this report is the first to focus on
HCM. Approximately one quarter of the cohort demonstrated P‐R prolongation ≥200 ms,
which associated in multivariable analyses with HCM‐related death (adjusted hazard
ratio, 2.41; 95% CI, 1.27–4.58) as well as a secondary end point of sudden death or
potentially lethal arrhythmic events (adjusted hazard ratio, 2.60; 95% CI, 1.28–5.27).8
Variables used in the risk adjustment included risk factors associated with sudden
death in HCM, as well as known modifiers of the P‐R interval. Of note, given limited
numbers of events, the multiple variables informing the European Society of Cardiology
HCM risk calculator9 were combined to create a single risk variable to be used in
the multivariable modeling.
Specific strengths of this report include its robust adjudication of outcomes as well
as an approximate similarity in event rates to other HCM observational studies.10,
11, 12 Over a median follow‐up of 8.8 years, 56 patients (13.5%) experienced HCM‐related
deaths: 47 patients (11.4%) had sudden death or potentially lethal arrhythmic events
(17 patients [4.1%] with sudden death, 10 [2.4%] with successfully resuscitated cardiac
arrest, and 20 [4.8%] with appropriate implantable cardioverter defibrillator shocks);
the remaining 9 patients included 6 (1.4%) with heart failure–related death and 3
(0.7%) with stroke‐related death. The annualized HCM death rate was 1.53%, and the
aborted cardiac event rate was 0.9%. Although higher than the estimates of a recent
study,13 the event rates in the current study are still consistent with the overall
trend of declining morbidity and mortality over the past several decades.
A key limitation of the current report is the lack of robust phenotyping of cardiac
structure and function. Parameters of interest include myocardial strain imaging,
as well as direct assessment of focal and diffuse myocardial fibrosis,14, 15 which
have been associated with P‐R interval and outcomes in other conditions.16 Specific
to HCM, left atrial remodeling, diastolic dysfunction, and myocardial fibrosis are
prevalent14 and likely to influence conduction parameters. The authors do describe
a lack of association between echocardiography septal peak velocity of early diastolic
transmitral flow/peak velocity of early diastolic mitral annular motion (E/e’) and
first‐degree AVB, although this observation in isolation provides limited insight
into the health of the myocardium, given the wide variety of structural derangements
known to occur in HCM. In addition, longitudinal study of such parameters as they
relate to P‐R interval in patients with HCM would be of great interest. Such data
may inform the mechanism by which P‐R interval prolongation associates with outcomes:
is it merely reflective of underlying structural heart disease, or might there be
a direct deleterious effect on cardiac function leading to adverse remodeling and
outcomes?
In summary, the current report by Higuchi and colleagues8 demonstrates an intriguing
association between first‐degree AVB and cardiac outcomes among patients with HCM,
even after moderate risk adjustment for common risk factors. Clinical application
of this potential risk marker is not yet warranted. Further investigation is required
to characterize this prognostic association in relation to comprehensive cardiac imaging
parameters, as well as to delineate its ability for risk reclassification in the context
of current guideline‐recommended algorithms.9, 17 Nonetheless, this report reminds
the clinician that the ECG will likely remain a fundamental part of the evaluation
of the patient with HCM, whether on Earth or in galaxies far, far away.
Disclosures
None.