Pulmonary arterial hypertension (PAH) is a deadly vascular disease, characterized
by increased pulmonary arterial pressures and right heart failure. Considering
prior non-US studies of atrial arrhythmias in PAH, this retrospective, regional
multi-center US study sought to define more completely the risk factors and
impact of paroxysmal and non-paroxysmal forms of atrial fibrillation and flutter
(AF/AFL) on mortality in this disease. We identified patients seen between 2010
and 2014 at UPMC (Pittsburgh) hospitals with hemodynamic and clinical criteria
for PAH or chronic thromboembolic pulmonary hypertension (CTEPH) and determined
those meeting electrocardiographic criteria for AF/AFL. We used Cox proportional
hazards regression with time-varying covariates to analyze the association
between AF/AFL occurrence and survival with adjustments for potential cofounders
and hemodynamic severity. Of 297 patients with PAH/CTEPH, 79 (26.5%) suffered
from AF/AFL at some point. AF/AFL was first identified after PAH diagnosis in 42
(53.2%), identified prior to PAH diagnosis in 27 (34.2%), and had unclear timing
in the remainder. AF/AFL patients were older, more often male, had lower left
ventricular ejection fractions, and greater left atrial volume indices and right
atrial areas than patients without AF/AFL. AF/AFL (whether diagnosed before or
after PAH) was associated with a 3.81-fold increase in the hazard of death (95%
CI 2.64–5.52, p < 0.001). This finding was consistent with
multivariable adjustment of hemodynamic, cardiac structural, and heart rate
indices as well as in sensitivity analyses of patients with paroxysmal versus
non-paroxysmal arrhythmias. In these PAH/CTEPH patients, presence of AF/AFL
significantly increased mortality risk. Mortality remained elevated in the
absence of a high burden of uncontrolled or persistent arrhythmias, thus
suggesting additional etiologies beyond rapid heart rate as an explanation.
Future studies are warranted to confirm this observation and interrogate whether
other therapies beyond rate and rhythm control are necessary to mitigate this
risk.
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