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Effects of IV Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and LV Remodeling in Patients with Anteri

Study evaluating the effects of IV Atrial Natriuretic Peptide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with first anterior acute myocardial infarction.

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Effects of IV Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and LV Remodeling in Patients with Anteri

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  1. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction Shu Kasama, MD; Takuji Toyama, MD; Takashi Hatori, MD; Hiroyuki Sumino, MD; Hisao Kumakura, MD; Yoshiaki Takayama, MD; Shuichi Ichikawa, MD; Tadashi Suzuki, MD; Masahiko Kurabayashi, MD Published in JACC February 13, 2007

  2. IV Atrial Natriuretic Peptide and Cardiac Sympathetic Nerve Activity and LV Remodeling in Anterior Acute MI: Background • Event-free survival after acute myocardial infarction (AMI) is influenced by the extent of residual myocardial ischemia and the global left ventricular (LV) ejection fraction. • In addition, because activation of the sympathetic nervous system is a chief indicator of a failing human heart, plasma norepinephrine concentrations also affect the morbidity and mortality in patients with AMI. Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  3. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Background (cont.) • Atrial natriuretic peptide (ANP) has a wide range of potent biologic effects, including natriuretic, diuretic, and vasodilatory properties and inhibition of the RAAS. • Intravenous administration of ANP has been shown to prevent LV dilation and remodeling after primary coronary angioplasty in patients with AMI. • This study sought to evaluate the effects of ANP on CSNA and LV remodeling in patients with first anterior AMI after primary coronary angioplasty. Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  4. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Study Design 50 patients with AMI (chest pain > 30 min, ST-segment elevation of >2 mm in 2 contiguous ECG leads and more than threefold increase in serum creatine phosphokinase activities Prospective. Randomized. Double-blind. Exclusion Criteria: cardiogenic shock or hypotension (SBP<80 mm Hg), prior MI, multivessel disease, and need for mechanical support (intra-aortic balloon pumping, mechanical ventilation, or both). R Atrial Natriuretic Peptide (ANP) > 48 h of 0.025 μg/kg/min n=25 Isosorbide Dinitrate (ISDN) > 48 h of 0.67 μg/kg/min n=25 • Primary Endpoint: Extent Score (ES) determined from 99mTc-pyrophosphate scintigraphy to evaluate the area of initial myocardial damage 3 to 5 days after initial angioplasty. • Secondary Endpoint: LV end-diastolic volume and LV ejection fraction determined by left ventriculography after 2 weeks. • Tertiary Endpoint: Delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) determined from 123I-MIBG scintigraphy after 3 weeks. Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  5. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Clinical Characteristics Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  6. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Clinical Characteristics (cont.) Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  7. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Primary Endpoint Total Defect Score of 201T1 Extent Score of 99mTc-PYP p=1.00 p<0.01 9 ± 3 9 ± 4 32 ± 6 27 ± 7 H/M ratio TDS n = 25 n = 25 n = 25 n = 25 Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  8. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Primary Endpoint (cont.) • The 201T1 and 99mTc-PYP dual single-photon emission computed tomography (SPECT) imaging were performed to evaluate the area of initial myocardial damage 3 to 5 days after primary angioplasty. • The extent score was similar in both groups; therefore the initial area at risk was probably similar for both groups. • However, defect scores were significantly lower in the ANP group than in the ISDN group (p<0.01). • Therefore, the intravenous administration of ANP may have increased the amount of salvaged myocardium after reperfusion therapy in patients with AMI.

  9. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Secondary Endpoint LV Parameters 2 weeks after treatment • LV end diastolic volume was significantly lower and LV ejection fraction was significantly higher in the ANP group than in the ISDN group. • However, LV end diastolic pressure was similar in both groups. Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  10. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Tertiary Endpoint 123I-MIGB scintigraphic findings 3 weeks after treatment Heart/Mediastinum count (H/M) ratio Washout Rate Total Defect Score p < 0.005 p < 0.05 p < 0.05 1.96 ± 0.18 44 ± 12% 1.74 ± 0.23 41± 8 35 ± 8% 34 ± 8 H/M ratio TDS WR n = 25 n = 25 n = 25 n = 25 n = 25 n = 25 Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  11. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Limitations • The study had a small number of patients with AMI (n=50). • This study used a fixed ANP dose, but future studies should assess the dose-response effects of ANP on 123I-MIBG scintigraphic findings and LV parameters. • Swan-Ganz catheterization was not performed to measure hemodynamic parameters after treatment; however, the LV end diastolic pressure was similar in the two groups. Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  12. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Summary • The TDS, H/M ratio, and WR as determined by cardiac 123I-MIGB scintigraphy were better in the ANP group than in the ISDN group. • The ES determined by 99mTc-PYP was similar in the two groups. • Two weeks after treatment, LV parameters were better in the ANP group than in the ISDN group. Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

  13. Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with First Anterior Acute Myocardial Infarction: Summary (cont.) • These findings demonstrate for the first time that intravenous administration of ANP could improve cardiac sympathetic nerve activity and prevent left ventricular remodeling to a larger extent compared with ISDN after reperfusion therapy in patients with first anterior AMI. Kasama et al. JACC. 2007 Feb 13; 49(6):667-74.

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