Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study

Abstract

AimsWe sought to determine if heart failure (HF) care with a goal to lower N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations, compared with standard of care (SOC) management, is associated with improvement in echocardiographic parameters of cardiac structure and function. Methods and resultsOf 151 subjects with HF due to left ventricular systolic dysfunction (LVSD) prospectively randomized to NT-proBNP-guided vs. SOC HF care, 116 had serial echocardiographic data. Endpoints in this echocardiographic study included the relationship between change in NT-proBNP and LV reverse remodelling, as well as associations between biomarker-guided therapy and measures of diastolic function, right ventricular (RV) size and function, estimates of LV filling pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation (MR). After a mean of 10 months of study procedures, in adjusted analyses, final NT-proBNP concentrations predicted risk of remodelling [hazard ratio (HR) LV end-diastolic volume index ¼ 1.43, 95% confidence interval (CI) 1.10-1.86, P ¼ 0.007; HR LV end-systolic volume index ¼ 1.54, 95% CI 1.10-1.91, P ¼ 0.01; HR LV ejection fraction (LVEF) ¼ 1.53, 905% CI 1.12 -1.89, P ¼ 0.02]. In addition to greater improvement in LVEF and reductions in LV volume, compared with SOC, NT-proBNP-guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity (E/E'), pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity. ConclusionNT-proBNP concentrations may serve as a non-invasive indicator of the state of cardiac structure and function in HF due to LVSD. Multiple, prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT-proBNP-guided care vs. SOC.

Assessing the benefits of natriuretic peptides-guided therapy in chronic heart failure

“…Because of the deficiencies in care that are well documented, in present therapy of HF [5] by itself this is a desirable effect. Indeed in the PROTECT study [38], both arms received more intensified therapy than in other studies. Again, it must be remembered that most data came from two 'specialized' centers and from authors who have published modern Cardiac Guidelines on Diagnosis and Therapy of HF ( Table 1).…”

“…Also fluctuations in NPs levels are not associated with changed symptoms, clinical status or edema [10,11,14,15,25,33,[35][36][37][38].…”

“…Most published data, i.e. 19 publications [8,9,18,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] are from these cardiologists. The number of treated patients in these centers outweighs that of patients treated elsewhere and the results from the 'specialized' and 'normal' centers are different and sometimes opposed.…”

“…Nonetheless, in CHF, a change in BNP values of > 20% between monthly follow-ups indicates a clinically important change, greater than would be expected from spontaneous variations [7-9, 15, 42, 43]. Indeed, NPs plasma levels offer a risk prediction that is independent from other factors [38,43]. As shown in Table 2, persistently elevated or increasing levels of NPs are consistently associated with an increased risk of cardiac morbidity and hospitalization [37,43].…”

“…In CHF, NPs levels have been shown to fall in response to loop diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers and mineral receptor antagonists [29][30][31][32][33][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. The response to the beta-blocker metoprolol is complex, sometimes with a rise of BNP levels in the first 2-3 months followed by a fall [26].…”