Discussion
In this nationwide, register-based cohort study, we studied all patients with PS from birth to over the last half century in Sweden. To the best of our knowledge, this is the largest population-based study of patients with PS in this field.
The main finding of our study is that the mortality in patients with PS was almost five times higher than in matched controls without congenital heart disease, with over 90% deaths occurring in patients with PS who not have undergone any intervention. Furthermore, there was no change in risk of mortality over birth decades between men and women with PS. Diagnosis of PS within the first year of life appeared to be a specific high-risk group. However, when interpreting these data, there needs to be awareness that this study was designed to investigate patients with PS and no concomitant congenital heart lesions to avoid interference with analysis of mortality. This is in contrast to a recent study where more than 40% of the patients with repaired PS had concomitant lesions, which were predominantly atrial septal defects and persistent ductus arteriosus.10 Moreover, compared with other patient cohort studies, few (12.8%) patients underwent any valve intervention.
Isolated PS, if mild to moderate, is generally thought to have a good prognosis, even if intervention is sometimes needed.14 No prior study has followed a nationwide cohort of patients since birth and, an increased risk of mortality in patients with PS on a population level has not been previously reported. This finding should have an effect on decisions regarding follow-up and on information regarding the importance of life-time follow-up in accordance with the latest European Society of Cardiology Guidelines, 2020.12 Our study suggests that the condition of isolated PS should not be generally considered a benign lesion. Analysis of subgroups, such as an operation, the time period and sex, indicated that an increased risk of mortality appeared almost regardless of subgroup. An exception to this would appear to be those with a registered diagnosis after 1 year of age but as the majority of those were born before the coverage of the patient registry was complete, an unknown proportion of infants and children with isolated PS may have died before being registered, contributing to the seemingly benign prognosis in this group. By contrast, patients with an early diagnosis within the first year of life, accounted for four out of five of deaths in this study and appeared to be a high-risk group. Extra attention should be paid to these patients in follow-up. Diagnosis of PS early in life could indicate severe disease.
However, in our study, the mortality rate in patients with valve interventions appeared to be low. This finding suggests that these patients do not represent a higher risk population for mortality (eg, from postoperative progressive pulmonary valve regurgitation and its related complications and reinterventions), but further analysis on this possibility is beyond the scope of this study. The higher mortality rate in patients with no valve interventions compared with patients with valve interventions in our study raises some concern. High prevalence of severe congenital comorbidity among deaths is noteworthy and could reflect a less active treatment approach to PS related to this comorbidity.
In our study, there was no increased risk of mortality in women with PS compared with controls. Previous studies have shown that patients with stenotic vitiae and pulmonary regurgitation have an increased risk of mortality in pregnancy.19 20 This situation could increase risk in patients with unoperated PS and postsurgical pulmonary regurgitation. These studies suggested that an increased risk of PS in pregnancy had no effect on overall mortality in women.
Limitations
Patient-specific data reflecting the severity of PS were not available in this study, which meant that we were unable to classify the severity in patients with PS. Furthermore, the diagnosis of PS has not been validated. Under-reporting of surgery and interventions might have occurred because the patient registries were not uniformly complete from the beginning of the study period, and children dying from complications of PS between 1970 and 1986 but unrecognised in the death registry will not have been captured. Furthermore, general under-reporting of patients from the first part of the study period is possible for the same reason, with a proportion of children probably diagnosed early but not registered before being referred to specialist cardiology at a later stage.
This study has a national perspective and includes all types of clinics. Both tertiary centres with likely many severe cases as well as regional and local outpatient clinics, which may include many mild cases as well. Finally, even though we used data from an extended period from an entire nation, the absolute number of deaths in the PS group was low.