Predictive value of noninvasive evaluation by exercise echocardiography and BNP measurement for early identification of pulmonary arterial hypertension in patients affected by systemic sclerosis: 5 years follow-up

Background. Systemic Sclerosis (SSc) is a chronic multisystem disease characterized by fibrosis of the skin and internal organs, microangiopathy and autoimmune disturbance. Pulmonary arterial hypertension (PAH) is one of the most severe complications of the disease, carrying a poor prognosis. Because of the aspecificity of the symptoms, diagnosis is often made when the disease is in an advanced stage and the pulmonary vascular bed involvement is already severe. For this reason it is essential to develop suitable screening tools to early detect the pathology, providing an appropriate therapy, that could improve the prognosis. Aim of the study. To evaluate the pulmonary arterial systolic pressure (PAsP) during exercise echocardiography in a group of asymptomatic or mildly symptomatic patients affected to SSc. Patients were then submitted to a medium-long term follow-up performing a resting echocardiogram to evaluate the development of pulmonary hypertension, defining the predictive value of the exercise echocardiography to early identify such complication. Material and methods. 40 patients affected by SSc (33 females and 7 males) with NYHA functional class I and II and with normal PAsP at rest, underwent exercise echocardiography. Resting and exercise PAsP values were estimated through measurement of tricuspidal regurgitant jet velocity by Doppler, considering values of exercise PAsP ≥ 48 mmHg to be pathological. We also analysed resting and exercise hemodynamic parameters, clinical characteristics of the patients and of the underlying rheumatic disease as well as measurement of resting and exercise BNP values. A medium-long term follow-up was done (5,1 ± 0,4 years), performing a clinical and resting echocardiographic evaluation to detect the development of pulmonary hypertension. Results. Resting PAsP values were 26,5 ± 4,6 mmHg, reaching values of 45,1 ± 14,2 mmHg during exercise (p 0,00), with a mean increase of 18,7 ± 11,9 mmHg. 25 patients (62,5%) had normal values of exercise PAsP (group A), whereas 15 patients (37,5%), all women, had exercise-induced altered pulmonary vasoreactivity (group B). Comparing group A and B, we found significant differences regarding both resting and exercise PAsP values (respectively p 0,007 and p 0,00), but also regarding exercise BNP values and the variation between resting and exercise BNP (respectively p 0,02 and p 0,001). Out of 40 initial patients, 2 patients died because of extracardiac causes, and 2 patients were lost; therefore 36 patients were followed for a mean time of 5,1 ± 0,4 years. Data from follow-up showed mean resting PAsP of 29,67 ± 7,4 mmHg. 5 patients, belonging to group B, presented pathological resting PAsP values: 3 of these patients had PAsP values suggestive for the diagnosis of possible pulmonary arterial hypertension (PAsP > 37 mmHg), 2 patients had PAsP values suggestive for the diagnosis of probable PAH (PAsP > 50 mmHg). None of the group A patients developed pathological PAsP values at follow-up.   Conclusions. Prevalence of exercise-induced altered pulmonary vasoreactivity, detected by exercise echocardiography, is high in patients affected by SSc. Such patients had a higher risk for developing pulmonary hypertension at medium- to long- term follow-up. Exercise echocardiography, associated with BNP testing, has been demonstrated to be useful to identify SSc patients presenting an abnormal increase of PAsP during exercise that could, far away, develop PAH

Predictive value of noninvasive evaluation by exercise echocardiography and BNP measurement for early identification of pulmonary arterial hypertension in patients affected by systemic sclerosis: 5 years follow-up

Background. Systemic Sclerosis (SSc) is a chronic multisystem disease characterized by fibrosis of the skin and internal organs, microangiopathy and autoimmune disturbance. Pulmonary arterial hypertension (PAH) is one of the most severe complications of the disease, carrying a poor prognosis. Because of the aspecificity of the symptoms, diagnosis is often made when the disease is in an advanced stage and the pulmonary vascular bed involvement is already severe. For this reason it is essential to develop suitable screening tools to early detect the pathology, providing an appropriate therapy, that could improve the prognosis. Aim of the study. To evaluate the pulmonary arterial systolic pressure (PAsP) during exercise echocardiography in a group of asymptomatic or mildly symptomatic patients affected to SSc. Patients were then submitted to a medium-long term follow-up performing a resting echocardiogram to evaluate the development of pulmonary hypertension, defining the predictive value of the exercise echocardiography to early identify such complication. Material and methods. 40 patients affected by SSc (33 females and 7 males) with NYHA functional class I and II and with normal PAsP at rest, underwent exercise echocardiography. Resting and exercise PAsP values were estimated through measurement of tricuspidal regurgitant jet velocity by Doppler, considering values of exercise PAsP ≥ 48 mmHg to be pathological. We also analysed resting and exercise hemodynamic parameters, clinical characteristics of the patients and of the underlying rheumatic disease as well as measurement of resting and exercise BNP values. A medium-long term follow-up was done (5,1 ± 0,4 years), performing a clinical and resting echocardiographic evaluation to detect the development of pulmonary hypertension. Results. Resting PAsP values were 26,5 ± 4,6 mmHg, reaching values of 45,1 ± 14,2 mmHg during exercise (p 0,00), with a mean increase of 18,7 ± 11,9 mmHg. 25 patients (62,5%) had normal values of exercise PAsP (group A), whereas 15 patients (37,5%), all women, had exercise-induced altered pulmonary vasoreactivity (group B). Comparing group A and B, we found significant differences regarding both resting and exercise PAsP values (respectively p 0,007 and p 0,00), but also regarding exercise BNP values and the variation between resting and exercise BNP (respectively p 0,02 and p 0,001). Out of 40 initial patients, 2 patients died because of extracardiac causes, and 2 patients were lost; therefore 36 patients were followed for a mean time of 5,1 ± 0,4 years. Data from follow-up showed mean resting PAsP of 29,67 ± 7,4 mmHg. 5 patients, belonging to group B, presented pathological resting PAsP values: 3 of these patients had PAsP values suggestive for the diagnosis of possible pulmonary arterial hypertension (PAsP > 37 mmHg), 2 patients had PAsP values suggestive for the diagnosis of probable PAH (PAsP > 50 mmHg). None of the group A patients developed pathological PAsP values at follow-up.   Conclusions. Prevalence of exercise-induced altered pulmonary vasoreactivity, detected by exercise echocardiography, is high in patients affected by SSc. Such patients had a higher risk for developing pulmonary hypertension at medium- to long- term follow-up. Exercise echocardiography, associated with BNP testing, has been demonstrated to be useful to identify SSc patients presenting an abnormal increase of PAsP during exercise that could, far away, develop PAH.Background. La sclerosi sistemica (SSc) è una complessa patologia caratterizzata da una eccessiva produzione di tessuto connettivo, una vasculopatia del microcircolo e disturbi dell'autoimmunità. L'ipertensione arteriosa polmonare (IAP) rappresenta una delle complicanze più severe di questa patologia, gravata da una prognosi piuttosto infausta. La diagnosi, data l’aspecificità dei sintomi, viene solitamente posta in uno stadio avanzato della malattia, quando l’interessamento del letto vascolare polmonare è già severo. Proprio per questo è fondamentale lo sviluppo di adeguate metodiche di screening per individuare la patologia in uno stadio precoce, che potrebbe permettere l'instaurazione di una appropriata terapia e migliorare la prognosi. Scopo dello studio. Valutare il comportamento della pressione arteriosa sistolica polmonare in un gruppo di pazienti affetti da SSc, asintomatici o paucisintomatici, sottoposti ad ecocardiografia da sforzo. I pazienti sono stati poi seguiti con un follow-up a medio-lungo ripetendo un ecocardiogramma di base per valutare l'eventuale sviluppo di ipertensione polmonare, definendo così il valore predittivo dell'ecocardiografia da sforzo nell'identificare precocemente l'ipertensione polmonare. Materiali e Metodi. 40 pazienti affetti da SSc (33 femmine e 7 maschi), in classe funzionale NYHA I e II, e con normali valori di pressione arteriosa polmonare sistolica (PAPs) a riposo sono stati sottoposti ad ecocardiogramma da sforzo. Sono stati valutati i valori di PAPs a riposo e da sforzo, mediante la misurazione del jet di rigurgito tricuspidale considerando patologica una PAPs da sforzo ≥ 48 mmHg. Sono stati analizzati inoltre alcuni parametri emodinamici basali e da sforzo, le caratteristiche cliniche dei pazienti e della patologia reumatologica di base, oltre che i valori di BNP basali e dopo sforzo. E' stato eseguito un follow-up a medio-lungo termine (5,1 ± 0,4 anni) sottoponendo i pazienti ad una valutazione clinica e ad un ecocardiogramma di base per valutare lo sviluppo di ipertensione polmonare. Risultati. I valori di PAPs a riposo sono stati di 26,5±4,6 mmHg, raggiungendo valori di 45,1±14,2 mmHg durante esercizio (p 0,00), con un incremento medio di 18,7±11,9 mmHg. In 25 (62,5%) pazienti la PAPs da sforzo è risultata normale (Gruppo A), mentre in 15 pazienti (37,5%), tutti di sesso femminile, abbiamo riscontrato un’alterata vasoreattività polmonare da sforzo (Gruppo B). I due gruppi differivano significativamente sia per i valori di PAPs a riposo (p 0,007) che da sforzo (p 0,00) ma anche per i valori di BNP da sforzo e la variazione del BNP con l’esercizio (rispettivamente p 0,02 e p 0,001). Dei 40 pazienti iniziali, 2 sono deceduti per cause extracardiache e 2 pazienti sono stati persi; abbiamo pertanto valutato 36 pazienti al follow-up di 5,1 ± 0,4 anni. La PAPs media a riposo è risultata di 29,67 ± 7,4 mmHg. 5 pazienti, tutti appartenenti al gruppo B, hanno presentato valori di PAPs a riposo patologici. Tra questi, in 3 pazienti i valori di PAPs erano suggestivi per la diagnosi di possibile IAP (PAPs >37 mmHg), in 2 erano invece indicativi di probabile IAP (PAPs >50 mmHg). Nessuno dei pazienti del gruppo A ha invece presentato nel follow-up valori di PAPs patologici.  Conclusioni. La prevalenza di alterata vasoreattività polmonare indotta dall'esercizio, valutata tramite l'ecocardiografia da sforzo, è elevata nei pazienti affetti da SSc. Questi pazienti hanno un rischio più elevato di sviluppare ipertensione polmonare ad un follow-up a medio-lungo termine. L’ecocardiografia da sforzo, associata al dosaggio del BNP, si è quindi dimostrata utile nell’identificare i pazienti con Ssc, asintomatici o paucisintomatici, che, presentando un’anomalo incremento della PAPs con l’esercizio, possono sviluppare ipertensione polmonare a medio-lungo termine