Pulmonary arterial hypertension (PAH) is a rare disease characterized by a narrowing of the small arteries and arterioles, which cause an elevation of pulmonary vascular resistance and lead to the development of right ventricular failure and death, if untreated. Despite advances in drug development, life expectancy remains poor and similar to that of many advanced cancers.
Currently, little is known about modality of death in these patients. In a recent prospective, monocentric study by Tonelli et al, PAH acted as the substratum, but not as the direct cause of death in a significant amount of deceased patients. In fact, progressive right ventricular failure or sudden death were the sole cause of death in half of patients. Several precipitants (mainly respiratory, infective and renal diseases) were therefore often crucial in determining clinical worsening and then triggering death. Furthermore, the main risk scores that have been found predictive of one-year mortality in patients with PAH have never systematically investigated the modality of death of patients with PAH nor it is clear whether specific risk factors may relate to specific modalities of death, in particular those triggered by extra-cardiac causes.
In left heart failure, different cofactors, such as pneumonia, ischemia, arrhythmia, nonadherence to diet or medications, hypertension, worsening of renal function, have a well-established role in triggering recrudescence of the pathology and increasing mortality. This knowledge allowed to adopt specific management strategies to prevent clinical worsening and death.
Similarly, understanding precipitants that contribute to exacerbations of Pulmonary Hypertension and lead to hospitalization and death, particularly those that are avoidable as triggered by preventable causes, is of great importance to clinicians and could favorably influence Pulmonary Hypertension disease management.
Despite advances in drug development, Pulmonary Arterial Hypertension (PAH) remains a fatal disease. Two-year morbi-mortality is around 50%. Five-year survival in absence of treatment is only about 50%.(1)
According to registries(2) and a small monocentric study by Tonelli et al.(3), half of deaths in patients with PAH is to be ascribed to decompensated right heart failure or sudden death. More than 40% of death, indeed, are imputed to one or more precipitating factors, that play a crucial role in determining the clinical outcome of patients and trigger death. Furthermore, the main risk scores available have shown to be predictive of one-year all-cause mortality, without assessing indeed the way patients actually die.(4-5)
In left heart failure, different cofactors, such as pneumonia, ischemia, arrhythmia, nonadherence to diet or medications, hypertension, worsening of renal function, have a well-established role in triggering recrudescence of the pathology and increasing mortality.(6-8) This knowledge allowed to adopt specific management strategies to prevent clinical worsening and death.(9-10) Similarly, understanding precipitants that contribute to exacerbations of Pulmonary Hypertension and lead to hospitalization and death, particularly those that are avoidable as triggered by extra-cardiac causes, is of great importance to clinicians and could favorably influence Pulmonary Hypertension disease management. Indeed, it would allow to dispose prevention strategies and to undertake a more aggressive treatment approach for patients at higher risk for death triggered by one or more precipitants. In a pathology with a poor life expectancy like PAH and which affect relatively young people, it is then critical to identify more tools to manage and possibly improve mortality rate.
In PAH the paucity of data available on this topic stems from several limitations including, first of all, rarity of disease, short-term or monocentric clinical studies and the absence of data regarding modality of death and its determinants in ongoing registries.
Therefore, being PAH a rare disease bearing a high mortality burden, a prospective, multicenter study, including the 43 most relevant referral centers in Italy, with a potential enrollment of 1000 patients focused on modality of death appears to be useful to improve our understanding. If this study manages to reach its goals, this would represent a step forward for patients management, allowing us to undertake earlier interventions and more aggressive and specific treatment strategies in patients at higher risk for specific modalities of deaths.
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