Background-Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region-and type-specific distribution of MMPs occurs within the post-MI myocardium remained unknown. Methods and Results-Ten sheep were instrumented with a sonomicrometry array to measure dimensions in 7 distinct regions corresponding to the remote, transition, and MI regions. Eight sheep served as reference controls. The relative abundance of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was quantified by immunoblotting. Segment length increased from baseline in the remote (24.9Ϯ5.4%), transition (18.0Ϯ2.9%), and MI (53.8Ϯ11.0%) regions at 8 weeks after MI (PϽ0.05) and was greatest in the MI region (PϽ0.05). Region-and type-specific changes in MMPs occurred after MI. For example, MMP-1 and MMP-9 abundance was unchanged in the remote, fell to 3Ϯ2% in the transition, and was undetectable in the MI region (PϽ0.05). MMP-13, MMP-8, and MT1-MMP increased by Ͼ300% in the transition and MI regions (PϽ0.05). TIMP abundance decreased significantly in the transition region after MI and fell to undetectable levels within the MI region. Conclusions-The unique findings of this study were 2-fold. First, changes in regional geometry after MI were associated with changes in MMP levels. Second, a region-specific portfolio of MMPs was induced after MI and was accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory control. Targeting the regional imbalance between specific MMPs and TIMPs within the post-MI myocardium holds therapeutic potential.

This study tests the hypothesis that hypocontractile, borderzone myocardium adjacent to an expanding infarct becomes progressively larger and more hypocontractile as remodeling continues. Early infarct expansion following anteroapical myocardial infarction (MI) is associated with progressive ventricular dilation and heart failure. The contribution of perfused, hypocontractile, borderzone myocardium to this process is unknown. Using a sheep model of anteroapical infarction, sonomicrometry array localization and serial microsphere injections were used to track changes in regional myocardial contractility, geometry, and perfusion. Eight sheep were studied before and after infarction and two, five, and eight weeks later. Thirty intertransducer chord lengths were analyzed to measure regional contractility and serial changes in regional geometry at end systole. Beginning as a narrow band of fully perfused hypocontractile myocardium adjacent to the infarction, borderzone myocardium extends to involve additional contiguous myocardium that progressively loses contractile function as the heart remodels. Three distinct myocardial zones develop as a result of transmural MI: infarct, borderzone (perfused but hypocontractile), and remote (perfused and normally functioning).This study demonstrates that hypocontractile, fully perfused borderzone myocardium extends to involve contiguous normal myocardium during postinfarction remodeling. This borderzone myocardium is a unique type of perfused, hypocontractile myocardium, which is distinct from hibernating or stunned myocardium. Preventing extension of borderzone myocardium by medical or surgical means offers the prospect of preventing late-onset heart failure following transmural expanding MIs.

Background: Open surgical closure and small-bore suture-based preclosure devices have limitations when used for transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or percutaneous thoracic endovascular aortic aneurysm repair. The MANTA vascular closure device is a novel collagen-based technology designed to close large bore arteriotomies created by devices with an outer diameter ranging from 12F to 25F. In this study, we determined the safety and effectiveness of the MANTA vascular closure device. Methods and Results: A prospective, single arm, multicenter investigation in patients undergoing transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or thoracic endovascular aortic aneurysm repair at 20 sites in North America. The primary outcome was time to hemostasis. The primary safety outcomes were accessed site-related vascular injury or bleeding complications. A total of 341 patients, 78 roll-in, and 263 in the primary analysis cohort, were entered in the study between November 2016 and September 2017. For the primary analysis cohort, transcatheter aortic valve replacement was performed in 210 (79.8%), and percutaneous endovascular abdominal aortic aneurysm repair or thoracic endovascular aortic aneurysm repair was performed in 53 (20.2%). The 14F MANTA was used in 42 cases (16%), and the 18F was used in 221 cases(84%). The mean effective sheath outer diameter was 22F (7.3 mm). The mean time to hemostasis was 65±157 seconds with a median time to hemostasis of 24 seconds. Technical success was achieved in 257 (97.7%) patients, and a single device was deployed in 262 (99.6%) of cases. Valve Academic Research Consortium-2 major vascular complications occurred in 11 (4.2%) cases: 4 received a covered stent (1.5%), 3 had access site bleeding (1.1%), 2 underwent surgical repair (0.8%), and 2 underwent balloon inflation (0.8%). Conclusions: In a selected population, this study demonstrated that the MANTA percutaneous vascular closure device can safely and effectively close large bore arteriotomies created by current generation transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, and thoracic endovascular aortic aneurysm repair devices. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02908880.

After myocardial infarction (MI), the border zone expands chronically, causing ventricular dilatation and congestive heart failure (CHF). In an ovine model (n = 4) of anteroapical MI that results in CHF, contrast echocardiography was used to image short-axis left ventricular (LV) cross sections and identify border zone myocardium before and after coronary artery ligation. In the border zone at end systole, the LV endocardial curvature (K) decreased from 0.86 +/- 0.33 cm(-1) at baseline to 0.35 +/- 0.19 cm(-1) at 1 h (P < 0.05), corresponding to a mean decrease of 55%. Also in the border zone, the wall thickness (h) decreased from 1.14 +/- 0.26 cm at baseline to 1.01 +/- 0.25 cm at 1 h (P < 0.05), corresponding to a mean decrease of 11%. By Laplace's law, wall stress is inversely proportional to the product K. h. Therefore, a 55% decrease in K results in a 122% increase in circumferential stress; a 11% decrease in h results in a 12% increase in circumferential stress. These findings indicate that after MI, geometric changes cause increased dynamic wall stress, which likely contributes to border zone expansion and remodeling.