Clinical and prognostic significance of central and obstructive apnoeas in patients with transthyretin cardiac amyloidosis

Aims: Central (CA) and obstructive apneas (OA) are highly prevalent in patients with chronic heart failure (HF) and transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized HF etiology. This study aimed to investigate the prevalence and impact of CA and OA in patients with ATTR-CA. Methods: Consecutive patients with ATTR-CA underwent a 24-hour ambulatory cardiorespiratory monitoring to evaluate the prevalence and severity of breathing disorders. The severity of these disorders was quantified using the apnea-hypopnea index (AHI). Accordingly, patients were categorized as having normal breathing (NB, AHI <5 events/hour), obstructive apnea (OA, AHI ≥5 events/hour with >50% being obstructive), or central apnea (CA, AHI >5 events/hour with ≥50% being central). The primary endpoint at follow-up was all-cause mortality. Results: Out of 142 patients enrolled (n=142, aged 77±7 years, 91% males, 96% wild-type ATTR-CA), considering the 24 hours, 20% had NB (39% at daytime, 8% at nighttime), while 35% had CA (45% at daytime, 39% at nighttime) and 45% had OA (25% at daytime, 54% at nighttime). After a median 2.3 (1.4-3.3) years follow-up, 24-hour, daytime, and nighttime AHI were higher in non-survivors vs. survivors (all p<0.05), independently of the prevalent apnea type (p=0.64). At multivariable regression analysis (adjusted for the possible clinical, echocardiographic, and biohumoral confounders), nighttime AHI ≥30 events/hour (hazard ratio 2.37 [95%CI 1.07-5.23], p=0.033) and hs-troponin T (hazard ratio 2.43 [95%CI 1.42-4.17], p=0.001) were predictors of mortality. Conclusion: CA and OA are highly prevalent both at daytime and nighttime in patients with ATTR-CA and are associated with higher mortality.