Giampaolo Cerisano1, Piergiovanni Buonamici2, Anna Maria Gori3, Renato Valenti2, Roberto Sciagrà4, Betti Giusti5, Alice Sereni5, Silvia Raspanti4, Paolo Colonna6, Gian Franco Gensini7, Rosanna Abbate5, Richard Schulz8, David Antoniucci2. 1. Department of Heart and Vessels, Careggi Hospital, Florence, Italy. Electronic address: giampaolo.cerisano@gmail.com. 2. Department of Heart and Vessels, Careggi Hospital, Florence, Italy. 3. Department of Experimental and Clinical Medicine, University of Florence, Italy; Don Carlo Gnocchi Foundation IRCCS, Florence, Italy. 4. Nuclear Medicine Unit, Department of Clinical Physiopathology - University of Florence, Careggi Hospital, Florence, Italy. 5. Department of Experimental and Clinical Medicine, University of Florence, Italy. 6. Division of Cardiology, Hospital Policlinico of Bari, Bari, Italy. 7. Department of Heart and Vessels, Careggi Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Italy; Don Carlo Gnocchi Foundation IRCCS, Florence, Italy. 8. Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Abstract
BACKGROUND: The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). METHODS:In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6months. A (99m)Tc-SPECT was performed to evaluate the 6-month infarct size and severity. RESULTS:Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (p<0.05). Plasma TIMP-2 levels above the median value at day 7 were correlated with the 6-month smaller infarct size (3% [0%-16%] vs. 12% [0%-30%], p=0.002) and severity (0.55 [0.44-0.64] vs. 0.45 [0.29-0.60], p=0.002), and LV dilation (-1ml/m(2) [from -7ml/m(2) to 9ml/m(2)] vs. 3ml/m(2) [from -2ml/m(2) to 19ml/m(2)], p=0.04), compared to their counterpart. CONCLUSIONS: In this clinical setting, doxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6month infarct size and severity as well as LV dilation.
RCT Entities:
BACKGROUND: The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). METHODS: In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6months. A (99m)Tc-SPECT was performed to evaluate the 6-month infarct size and severity. RESULTS:Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (p<0.05). Plasma TIMP-2 levels above the median value at day 7 were correlated with the 6-month smaller infarct size (3% [0%-16%] vs. 12% [0%-30%], p=0.002) and severity (0.55 [0.44-0.64] vs. 0.45 [0.29-0.60], p=0.002), and LV dilation (-1ml/m(2) [from -7ml/m(2) to 9ml/m(2)] vs. 3ml/m(2) [from -2ml/m(2) to 19ml/m(2)], p=0.04), compared to their counterpart. CONCLUSIONS: In this clinical setting, doxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6month infarct size and severity as well as LV dilation.
Authors: Stephanie L Thorn; Shayne C Barlow; Attila Feher; Mitchel R Stacy; Heather Doviak; Julia Jacobs; Kia Zellars; Jennifer M Renaud; Ran Klein; Robert A deKemp; Aarif Y Khakoo; TaeWeon Lee; Francis G Spinale; Albert J Sinusas Journal: Circ Cardiovasc Imaging Date: 2019-11-11 Impact factor: 7.792
Authors: Mari Merentie; Riina Rissanen; Line Lottonen-Raikaslehto; Jenni Huusko; Erika Gurzeler; Mikko P Turunen; Lari Holappa; Petri Mäkinen; Seppo Ylä-Herttuala Journal: PLoS One Date: 2018-01-19 Impact factor: 3.240