Efficacy of Sacubitril/Valsartan in a Patient With Heart Failure and Impaired Secretion of Atrial Natriuretic Peptide Due to Long-Standing Persistent Atrial Fibrillation

Abstract

Atrial natriuretic peptide (ANP) is a circulating hormone released from the atria in response to wall stretch and volume overload in the setting of heart failure. When atrial fibrillation (AF) becomes long-standing persistent, ANP secretion in response to volume overload is impaired due to degenerative changes of the atria. Here, we report a case of heart failure with preserved ejection fraction and impaired ANP secretion due to long-standing AF. N-terminal pro-brain natriuretic peptide (NT-proBNP) level was elevated (269 pg/mL), whereas the increase in ANP level was marginal (46.1 pg/mL), suggesting impaired ANP secretion due to long-standing AF. Valsartan (80 mg/day) was replaced with sacubitril/valsartan (100 mg/day) without changing other medications. Administration of sacubitril/valsartan was effective in improving the patient's symptoms, such as dyspnea and edema, and reducing NT-proBNP level by increasing endogenous ANP level from 46.1 pg/mL to 117 pg/mL in the first four weeks. This case highlights the possibility of impaired ANP secretion in response to volume overload as a predictor of the diuretic effect of sacubitril/valsartan in heart failure. This may lead to individualized treatment for each patient with heart failure based on natriuretic peptide profiles.

Keywords: echocardiography; electrocardiogram; mitral regurgitation; neprilysin; volume overload.

Figure 1. Electrocardiogram.

An electrocardiogram revealed AF with fibrillatory wave amplitudes <0.1 mV, the so-called fine AF. AF: atrial fibrillation

Figure 2. Initial and follow-up chest radiographs.

Initial chest radiograph showed a significantly enlarged cardiac silhouette with a cardiothoracic ratio of 85%, mainly depending on right atrial and ventricular dilatations (A, arrows). The follow-up chest radiograph revealed a slight decrease in the cardiothoracic ratio to 80% (B).

Figure 3. Transthoracic echocardiographic images.

A transthoracic echocardiogram showed normal LV systolic function with an ejection fraction of 76% (A). The tricuspid regurgitation pressure gradient was 52 mmHg (B). The LA was markedly enlarged (C). The enlarged LA displaced the posterior annulus onto the crest of the LV free wall. The hamstrung posterior mitral leaflet was tethered (D-E, arrows) and moderate mitral regurgitation with an eccentric jet was seen (F, arrows). Taken together, it was considered to be atrial functional mitral regurgitation related to long-standing persistent AF. The right atrium was also markedly enlarged with moderate tricuspid regurgitation (C-F). LV: left ventricular; LA: left atrial; AF: atrial fibrillation

Figure 4. Clinical course during hospitalization.

The patient’s weight decreased from 64 kg to 61 kg in the first two days. On hospital day five, her weight further decreased to 60 kg and edema in both lower extremities disappeared. The dose of azosemide was reduced to 30 mg and hydrochlorothiazide was discontinued.

Figure 5. Changes in natriuretic peptide levels during the follow-up period.

ANP level significantly increased, more than two-fold, from 46.1 pg/mL to 117 pg/mL in the first four weeks and then remained above 100 pg/mL until the 19th week. It eventually returned to 69.8 pg/mL in the 26th week. NT-proBNP level decreased from 269 pg/mL to 232 pg/mL in the first nine weeks and then remained around 200 pg/mL until the 19th week. It eventually returned to 176 pg/mL in the 26th week. BNP level decreased from 43.3 pg/mL to 26.2 pg/mL in the first nine weeks in parallel with NT-proBNP level. The dotted lines indicate the upper reference limits for natriuretic peptides. ANP: atrial natriuretic peptide; NT-proBNP: N-terminal pro-brain natriuretic peptide; BNP: brain natriuretic peptide