BACKGROUND. Amyloidosis is an infiltrative disease: protein misfolding lead to aggregation of monomers and formation of insoluble fibrils. These are deposited in tissues and can cause progressive organ damage with loss of function. Multiple proteins may be involved, and different protein precursors lead to forms of disease which differ in epidemiology, clinic, prognosis, and treatment. Cardiac involvement is the most prognostically relevant. Cardiac amyloidosis (CA) most frequently occurs with two precursors: immunoglobulin light chains for the AL form and wild type or mutated transthyretin for the ATTR form (ATTRwt and ATTRv, respectively). Echocardiography plays a role in diagnostic and prognostic suspicion. Very typical aspects are parietal hypertrophy, "granular sparkling" appearance, and "apical sparing" pattern on global longitudinal strain (GLS) analysis. Left ventricular diastolic dysfunction is characteristic of CA. In addition, the right ventricle is often involved: the free wall is thickened and the longitudinal excursion of the tricuspid anulus (TAPSE) is lower, revealing a right systolic dysfunction. AIMS. Other studies in literature report a right ventricular arterial coupling (RV-PAc) prognostic association in disease such as HFpEF or pulmonary hypertension. This study aims to investigate by echocardiographic parameters (TAPSE/PAPs and FAC/PAPs ratio), in the context of cardiac amyloidosis, the features of right ventricle and pulmonary circulation coupling and its prognostic significance. MATERIALS AND METHODS. This was a single-centre, observational, retrospective study with patients affected by ATTR-CA, AL-CA and evaluated at the Hospital of Padua until December 2022. We included who was in possession of a complete echocardiogram done one month from the diagnosis of CA. RESULTS. Of the patients observed (184), 59 (32%) had AL-CA and 125 (68%) had ATTR-CA. Regarding the AL population, the presence of dysfunctional RV-PAc had high prevalence but no prognostic value. Conversely, right atrium volume index (HR 1.03, 95% CI 1.01 - 1.06, p = 0.01) and left ventricular arterial coupling (LVAC) value (HR 2.34, 95% CI 1.03 - 5.3, p = 0.01) were independent predictors of mortality. By ROC curve analysis, a threshold value of LVAC of 0.783 was identified. Patients with a higher value were found to have a significantly lower probability of survival (p = 0.034) at 12 and 24 months than patients with a lower value (78% vs 90% and 62% vs 81%, respectively). Relative to the ATTR population, a high prevalence of dysfunctional RV-Pac was assessed by both parameters. Survival analysis revealed its prognostic significance as independent predictor of mortality (TAPSE/PAPs: HR 0.003, 95% CI 0.002 - 0.54, p = 0.02; FAC/PAPs: HR 0.2, 95% CI 0.04 - 0.87, p = 0.03). As reported in the literature, a threshold value of 0.31 was chosen for the first parameter. Patients with a lower value had a significantly lower probability of survival (p = 0.004) at 12 and 24 months (77% vs 97% and 38% vs 77%, respectively). For the latter, by spline curve analysis, a threshold value of 0.78 was identified. Patients with a lower value were found to have a significantly lower probability of survival (p = 0.001) at 12 and 24 months (83% vs 97% and 50% vs 85%, respectively). CONCLUSIONS. The study finds a high prevalence of left and right ventricular arterial uncoupling in patients with cardiac amyloidosis. In patients with the AL form, left uncoupling is an independent predictor of short- and long-term mortality. Among ATTR patients, right uncoupling was found to be an independent predictor of adverse events. Further studies, possibly with cardiac catheterization, are needed to elucidate the reasons for these differences between the AL form and the ATTR form.
-L’amiloidosi è una patologia infiltrativa caratterizzata da un difetto di ripiegamento di proteine, a cui segue l’aggregazione dei monomeri e la formazione di fibrille insolubili. Esse si depositano nei tessuti e provocano un danno progressivo con perdita di funzionalità d’organo. Esistono molteplici precursori fibrillari che provocano diverse presentazioni di malattia, in quanto epidemiologia, clinica, prognosi e trattamento. Le fibrille amiloidee si possono depositare in diversi organi, ma coinvolgimento cardiaco è quello prognosticamente più rilevante. L’amiloidosi cardiaca (CA) si verifica più frequentemente con due precursori: le catene leggere delle immunoglobuline per la forma AL e la transtiretina wild type (ATTRwt) o mutata (ATTRv). L’ecocardiografia ha un ruolo di sospetto diagnostico e prognostico: aspetti caratteristici sono l’ipertrofia parietale, l’aspetto a “granular sparkling” e il pattern di “apical sparing”del GLS. Inoltre, la disfunzione diastolica ventricolare sinistra è tipica di questa malattia, come anche il coinvolgimento del ventricolo destro. Esso si presenta ispessito nella sua parete libera e con una riduzione precoce della TAPSE, tale alterazione indica una disfunzione sistolica destra. -In letteratura è nota un’associazione prognostica dell’accoppiamento ventricolo arterioso destro (RV-PAc) in altre patologie (HFpEF, PH). Questo studio si propone di indagare, nell’ambito dell’amiloidosi cardiaca e tramite parametri ecocardiografici (rapporto TAPSE/PAPs e FAC/PAPs), le caratteristiche dell’accoppiamento ventricolo destro-circolo polmonare ed il suo significato prognostico. -Si tratta di uno studio monocentrico, osservazionale e retrospettivo in cui sono stati inclusi pazienti malati di ATTR-CA e AL-CA valutati presso AOPD fino al 12/2022 e che disponessero di un’ecocardiografia completa ad un mese dalla diagnosi di amiloidosi cardiaca. -Dei pazienti osservati (184), 59 (32%) erano affetti da AL-CA e 125 (68%) erano affetti da ATTR-CA. Riguardo la popolazione AL, la presenza di RV-PAc disfunzionale è risultato avere alta prevalenza, in assenza però di valore prognostico. Viceversa, sono risultati predittori indipendenti di mortalità il volume indicizzato dell’atrio destro (HR 1.03, p=0.01) e il valore dell’accoppiamento ventricolo arterioso sinistro (LVAC) (HR 2.34, p=0.01). Mediante analisi della curva ROC si è individuato un valore soglia di LVAC pari a 0.783: i pazienti con un valore superiore hanno riportato una probabilità di sopravvivenza significativamente ridotta (p=0.034) a 24 mesi rispetto ai pazienti con valore inferiore (62% vs 81%). Relativamente alla popolazione ATTR, è stata rilevata un’alta prevalenza di disaccoppiamento destro valutato con entrambi i parametri precedentemente citati. L’analisi di sopravvivenza ha inoltre riscontrato un significativo valore prognostico di TAPSE/PAPs (HR 0.003, p=0.02) e FAC/PAPs (HR 0.2, p=0.03). Per il primo parametro è stato scelto un valore soglia di 0.31, come riportato dalla letteratura: pazienti con valore inferiore sono risultati avere una probabilità di sopravvivenza significativamente bassa a 24 mesi (38 vs 77%). Per il secondo, è stato individuato un valore soglia pari a 0.78 mediante analisi della spline curve per l’hazard ratio: i pazienti con valori sottosoglia hanno evidenziato una probabilità di sopravvivenza significativamente inferiore a 24 mesi (50 vs 85%). -Lo studio rileva un’alta prevalenza di disaccoppiamento destro e sinistro nei pazienti affetti da amiloidosi cardiaca. Nei pazienti con la forma AL il disaccoppiamento sinistro è un predittore indipendente di mortalità a breve e lungo termine. Tra i pazienti ATTR il disaccoppiamento destro è risultato predittore indipendente di mortalità. Sono necessari ulteriori studi, possibilmente con cateterismo cardiaco, per delucidare i motivi di tali differenze tra le forme AL e ATTR.
Accoppiamento ventricolo arterioso del cuore destro in amiloidosi cardiaca e valore prognostico: uno studio di ecocardiografia.
PORTALONE, LISA
2022/2023
Abstract
BACKGROUND. Amyloidosis is an infiltrative disease: protein misfolding lead to aggregation of monomers and formation of insoluble fibrils. These are deposited in tissues and can cause progressive organ damage with loss of function. Multiple proteins may be involved, and different protein precursors lead to forms of disease which differ in epidemiology, clinic, prognosis, and treatment. Cardiac involvement is the most prognostically relevant. Cardiac amyloidosis (CA) most frequently occurs with two precursors: immunoglobulin light chains for the AL form and wild type or mutated transthyretin for the ATTR form (ATTRwt and ATTRv, respectively). Echocardiography plays a role in diagnostic and prognostic suspicion. Very typical aspects are parietal hypertrophy, "granular sparkling" appearance, and "apical sparing" pattern on global longitudinal strain (GLS) analysis. Left ventricular diastolic dysfunction is characteristic of CA. In addition, the right ventricle is often involved: the free wall is thickened and the longitudinal excursion of the tricuspid anulus (TAPSE) is lower, revealing a right systolic dysfunction. AIMS. Other studies in literature report a right ventricular arterial coupling (RV-PAc) prognostic association in disease such as HFpEF or pulmonary hypertension. This study aims to investigate by echocardiographic parameters (TAPSE/PAPs and FAC/PAPs ratio), in the context of cardiac amyloidosis, the features of right ventricle and pulmonary circulation coupling and its prognostic significance. MATERIALS AND METHODS. This was a single-centre, observational, retrospective study with patients affected by ATTR-CA, AL-CA and evaluated at the Hospital of Padua until December 2022. We included who was in possession of a complete echocardiogram done one month from the diagnosis of CA. RESULTS. Of the patients observed (184), 59 (32%) had AL-CA and 125 (68%) had ATTR-CA. Regarding the AL population, the presence of dysfunctional RV-PAc had high prevalence but no prognostic value. Conversely, right atrium volume index (HR 1.03, 95% CI 1.01 - 1.06, p = 0.01) and left ventricular arterial coupling (LVAC) value (HR 2.34, 95% CI 1.03 - 5.3, p = 0.01) were independent predictors of mortality. By ROC curve analysis, a threshold value of LVAC of 0.783 was identified. Patients with a higher value were found to have a significantly lower probability of survival (p = 0.034) at 12 and 24 months than patients with a lower value (78% vs 90% and 62% vs 81%, respectively). Relative to the ATTR population, a high prevalence of dysfunctional RV-Pac was assessed by both parameters. Survival analysis revealed its prognostic significance as independent predictor of mortality (TAPSE/PAPs: HR 0.003, 95% CI 0.002 - 0.54, p = 0.02; FAC/PAPs: HR 0.2, 95% CI 0.04 - 0.87, p = 0.03). As reported in the literature, a threshold value of 0.31 was chosen for the first parameter. Patients with a lower value had a significantly lower probability of survival (p = 0.004) at 12 and 24 months (77% vs 97% and 38% vs 77%, respectively). For the latter, by spline curve analysis, a threshold value of 0.78 was identified. Patients with a lower value were found to have a significantly lower probability of survival (p = 0.001) at 12 and 24 months (83% vs 97% and 50% vs 85%, respectively). CONCLUSIONS. The study finds a high prevalence of left and right ventricular arterial uncoupling in patients with cardiac amyloidosis. In patients with the AL form, left uncoupling is an independent predictor of short- and long-term mortality. Among ATTR patients, right uncoupling was found to be an independent predictor of adverse events. Further studies, possibly with cardiac catheterization, are needed to elucidate the reasons for these differences between the AL form and the ATTR form.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/46990