Higher aldosterone levels were significantly associated with better survival in ATTR-CM patients, especially those not treated with MRA therapy (p=0.003).
Do circulating RAAS markers predict survival in patients with ATTR-CM?
In ATTR-CM, higher circulating aldosterone levels are associated with improved survival, particularly in patients not on MRA therapy, highlighting complex RAAS regulation in this disease.
Absolute Event Rate: 0% vs 0%
Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex condition caused by the accumulation of amyloid proteins in the heart, leading to heart failure. Despite recent advances in understanding the disease and the emergence of specific therapies, there is no evidence that commonly used heart failure medications, particularly renin-angiotensin-aldosterone system (RAAS) inhibitors, improve outcomes in ATTR-CM. The role of the RAAS in the disease's pathophysiology remains unclear. Purpose This study aims to elucidate the role of RAAS in ATTR-CM by 1) profiling RAAS activity in patients, 2) correlating angiotensin levels with clinical characteristics and 3) assessing the impact of RAAS profiles on mortality. Methods Consecutive ATTR-CM patients were enrolled in a prospective registry. Circulating levels of angiotensin peptides (Ang I, Ang II, Ang 1-7, Ang 1-5) and aldosterone were quantified using mass spectrometry. RAAS inhibitor use (ACEi, ARBs, MRAs) was recorded. Clinical and laboratory parameters were correlated with RAAS markers. The effect of RAAS markers on survival was assessed using Kaplan-Meier curves, stratified by median RAAS marker levels and MRA therapy use. Results A total of 61 ATTR-CM patients were analyzed (median age: 81 years IQR 75-86; 87% male, Table 1). RAAS inhibitor use included ACEi (20%), ARBs (39%) and MRAs (56%). Angiotensin levels varied significantly among patients, with Ang I levels at 141 pmol/L IQR 89–279, Ang II at 397 pmol/L IQR 221–709 and aldosterone at 166 pmol/L IQR 93–252. RAAS profiles were consistent with the expected effects of the respective RAAS inhibitors (Figure 1a). Significant correlations were observed between RAAS components and clinical markers: Notably, Ang I levels correlated with renal function (creatinine: r=0.31, p=0.016; BUN: r=0.36, p=0.004), while aldosterone levels were inversely linked to NT-proBNP (r=-0.29, p=0.023) and renal function (creatinine: r=-0.28, p=0.032; eGFR: r=0.30, p=0.018). During a median follow-up of 4.1 years IQR 2.2-5.2, 28 patients (46%) died. Higher aldosterone levels (above the median) were significantly associated with better survival, particularly in patients not receiving MRA therapy (p=0.003, Figure 1b). In contrast, Ang I and Ang II did not show a significant effect on survival (p=0.881 and p=0.137, respectively). Conclusion Distinct RAAS profiles in ATTR-CM suggest potential implications for disease progression and prognosis. While angiotensin levels correlated with various clinical parameters, they did not predict survival. In contrast, aldosterone emerged as a key prognostic marker, with higher levels linked to improved survival, particularly in patients not on MRA therapy. Our findings highlight the complexity of RAAS regulation in ATTR-CM and emphasize the need for further studies to understand why RAAS inhibitors do not improve outcomes in ATTR-CM, as they do in other forms of heart failure.
Kronberger et al. (Sat,) reported a other. Higher aldosterone levels were significantly associated with better survival in ATTR-CM patients, especially those not treated with MRA therapy (p=0.003).