Early changes of left ventricular filling pattern after reperfused ST-elevation myocardial infarction and doxycycline therapy: Insights from the TIPTOP trial

• Published in: International journal of cardiology Vol. 240; pp. 43 - 48
• Main Authors: Cerisano, Giampaolo, Buonamici, Piergiovanni, Parodi, Guido, Santini, Alberto, Moschi, Guia, Valenti, Renato, Migliorini, Angela, Colonna, Paolo, Bellandi, Benedetta, Gori, Anna Maria, Antoniucci, David
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2017
• Subjects: Acute myocardial infarction; Aged; Cardiovascular; Diastolic function; Doxycycline - pharmacology; Doxycycline - therapeutic use; Doxycycline therapy; Echocardiography, Doppler - trends; Female; Humans; Left ventricular remodeling; Male; Matrix Metalloproteinase Inhibitors - therapeutic use; Middle Aged; Percutaneous Coronary Intervention - trends; Primary percutaneous coronary intervention; Prospective Studies; ST Elevation Myocardial Infarction - blood; ST Elevation Myocardial Infarction - diagnostic imaging; ST Elevation Myocardial Infarction - therapy; Ventricular Dysfunction, Left - blood; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - therapy; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology; ST-elevation myocardial infarction; E; LVESVi; LVEF; mealloproteinases; left ventricular ejection fraction; DT; left ventricular end diastolic volume index; percutaneous coronary intervention; HFP; left ventricular end systolic volume index; STEMI; transmitral late peak velocity; NFP; normal filling pressure; A-wave; transmitral early peak velocity; Vp; left ventricular remodeling; doxycycline therapy; MMPs; extracellular cardiac matrix; ECM; LVEDVi; E-wave; left ventricular flow propagation velocity during early filling; high filling pressure; PCI; early peak velocity on the septal side of the mitral annulus; deceleration time of transmitral early peak velocity; acute myocardial infarction; primary diastolic function; Primary percutaneous coronary intervention; Doxycycline therapy; Diastolic function; Acute myocardial infarction; Left ventricular remodeling
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2017.03.125

Abstract Aim Metalloproteinases inhibition by doxycycline reduces cardiac protein degradation at extracellular and intracellular level in the experimental model ischemia/reperfusion injury. Since both extracellular cardiac matrix and titin filaments inside the cardiomyocyte are responsible for the myocardial stiffness, we hypothesized that doxycycline could favorably act on left ventricular (LV) filling pressures in patients after reperfused acute ST-elevation myocardial infarction (STEMI). Methods and results Seventy-three of 110 patients of the TIPTOP trial underwent a 2D–Echo-Doppler on admission, and at pre-discharge and at 6-month after a primary PCI for STEMI and LV dysfunction. From admission to pre-discharge, LV filling changed from a high filling pressure (HFP) to a normal filling pressure (NFP) pattern in 91% of the doxycycline-group, and in 67% of the control-group. Conversely, 1% of the doxycycline-group, and 37% of the control-group changed the LV filling from NFP to HFP pattern. Overall, a pre-discharge HFP pattern was present in 4 patients (11%) of the doxycycline-group and in 13 patients (36%) of the control-group (p = 0.025). The evaluation of metalloproteinases and their tissue inhibitors plasma concentrations provide possible favorable action of doxycycline. On the multivariate analyses, troponine I peak (p = 0.026), doxycycline (p = 0.033), and on admission to pre-discharge LVEF changes (p = 0.044) were found to be associated with pre-discharge HFP pattern. Independently of their baseline LV filling behavior, the 6-month remodeling was less in patients with pre-discharge NFP pattern than in patients with HFP pattern. Conclusions In patients with STEMI and LV dysfunction doxycycline can favorably modulate the LV filling pattern early after primary PCI.