IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF-κB signaling pathway in a mouse model of acute myocardial infarction.

Cardiac rupture and ventricular remodeling are recognized as the severe complications and major risk factors of acute myocardial infarction (AMI). This study aims to evaluate the regulatory roles of interleukin-1 receptor-associated kinase 3 (IRAK3) and nuclear factor-κB (NF-κB) signaling pathway in cardiac rupture and ventricular remodeling. Microarray analysis was performed to screen AMI-related differentially expressed genes and IRAK3 was identified. The models of AMI were established in male C57BL/6 mice to investigate the functional role of IRAK3. Afterwards, lentivirus recombinant plasmid si-IRAK3 was constructed for IRAK3 silencing. Next, cardiac function parameters were measured in response to IRAK3 silencing. The regulatory effects that IRAK3 had on myocardial infarct size and the content of myocardial interstitial collagen were analyzed. The regulation of IRAK3 silencing on the NF-κB signaling pathway was further assayed. The obtained results indicated that highly expressed IRAK3 and activated NF-κB signaling pathway were observed in myocardial tissues of mouse models of AMI, accompanied by increased expression of matrix metalloproteinase (MMP)-2/9 and tissue inhibitor of metalloproteinase 2 (TIMP-2). Notably, IRAK3 gene silencing inhibited the activation of NF-κB signaling pathway. Furthermore, IRAK3 gene silencing led to the decreased thickness of infarct area and collagen content of myocardial interstitium, alleviated diastolic, and systolic dysfunctions, as well as, facilitated cardiac functions in mice with AMI, corresponding to decreased expression of MMP-2/9 expression and increased expression of TIMP-2. Taken together, silencing of IRAK3 inactivates the NF-κB signaling pathway, and thereby impeding the cardiac rupture and ventricular remodeling, which eventually prevents AMI progression.

Mitral Chordae Rupture as a Possible First-Time Presentation for Graves’ Disease.

Graves' disease is a common cause of hyperthyroidism that can lead to multiple cardiovascular complications. Herein is described the case of a 44-year-old male who presented with new-onset atrial fibrillation and mitral regurgitation secondary to flail anterior mitral leaflet with chordae tendineae rupture. This is a rare complication for Graves' disease, and has been reported only twice previously. It was hypothesized that this complication is secondary to Graves'-associated myxomatous degeneration of the mitral valve in the presence of a hyperdynamic circulation.

Post-Coital Acute Rupture of a Fenestrated Aortic Valve.

Fenestrated aortic valve is a frequent condition which is, for most of the time, asymptomatic and generally has no influence on aortic valve competence. However, aortic valve regurgitation could occur, especially in the case of fibrous strand rupture. In this situation, acute aortic regurgitation is poorly tolerated and requires urgent surgical correction. Herein is presented the case of a 70-year-old patient who was admitted as an emergency for acute heart failure after coital exertion. Echocardiography revealed severe acute aortic regurgitation due to leaflet prolapse. Intraoperative inspection of the valve showed a strand rupture of the isolated fenestration.

[Papillary Muscle Rupture after Repair of Ischemic Left Ventricular Free Wall Rupture; Report of a Case].

A 67-year-old man experienced acute inferior myocardial infarction. Echocardiography and computed tomography showed massive pericardial effusion. He underwent emergency operation for ischemic ventricular free wall rupture. During the operation, an oozing type rupture was found on the inferior wall and the bleeding was completely controlled by applying fibrin glue sheets. On the 5th day after the operation, ventricular tachycardia appeared with hemodynamic deterioration. Echocardiography showed a ruptured posteromedial papillary muscle with massive mitral regurgitation. Intra-aortic balloon pumping was introduced and emergency repair operation was performed. The mitral valve was replaced with a bioprosthetic valve. The postoperative course was uneventful.

Left main occlusion secondary to aortic root rupture following transcatheter aortic valve replacement managed by left main stenting.

Acute left main coronary occlusion secondary to a periaortic root hematoma secondary to annular rupture during transcatheter heart valve deployment is reported.

Lack of haptoglobin results in unbalanced VEGFα/angiopoietin-1 expression, intramural hemorrhage and impaired wound healing after myocardial infarction.

Decreased haptoglobin (Hp) functionality due to allelic variations is associated with worsened outcome in patients after myocardial infarction (MI). However, mechanisms through which haptoglobin deficiency impairs cardiac repair remain to be elucidated. In the present study, we identified novel molecular alterations mediated by Hp involved in early and late cardiac repair responses after left coronary artery ligation in Hp(-/-) and wild-type (WT) mice. We observed a higher mortality rate in Hp(-/-) mice despite similar infarct size between groups. Deaths were commonly caused by cardiac rupture in Hp(-/-) animals. Histological analysis of 3 and 7days old non-ruptured infarcted hearts revealed more frequent and more severe intramural hemorrhage and increased leukocyte infiltration in Hp(-/-) mice. Analyses of non-ruptured hearts revealed increased oxidative stress, reduced PAI-1 activity and enhanced VEGFα transcription in Hp(-/-) mice. In line with these observations, we found increased microvascular permeability in Hp(-/-) hearts 3days after infarction. In vitro, haptoglobin prevented hemoglobin-induced oxidative stress and restored VEGF/Ang-1 balance in endothelial cell cultures. During long-term follow-up of the surviving animals, we observed altered matrix turnover, impaired scar formation and worsened cardiac function and geometry in Hp(-/-)mice. In conclusion, haptoglobin deficiency severely deteriorates tissue repair and cardiac performance after experimental MI. Haptoglobin plays a crucial role in both short- and long-term cardiac repair responses by reducing oxidative stress, maintaining microvascular integrity, myocardial architecture and proper scar formation.

Potential mechanism of annulus rupture during transcatheter aortic valve implantation.

Although annulus rupture is one of the most severe complications of transcatheter aortic valve implantation (TAVI), the incidence and mechanism of this complication remain unclear. Out of 387 consecutive TAVI cases in our institution, the incidence of annulus rupture was 1.0% (4/387). The first two patients died because of hemodynamic collapse due to tamponade on day 0. Both surviving patients had undergone preprocedural multidetector computed tomography which revealed large calcifications in the epicardial fat part of the aortic annulus. In both cases, annulus rupture occurred after deployment of a balloon expandable valve suggesting that mechanical compression of this "vulnerable area" by calcification may cause annulus rupture.

Animal models of mitral regurgitation induced by mitral valve chordae tendineae rupture.

BACKGROUND AND AIM OF THE STUDY: Mitral regurgitation (MR) is a common valvular disease throughout the world. Various diagnostic techniques have been developed to assess the causes and severity of MR, and the therapeutic approaches to this disease have been widely documented. However, treatments for chronic MR remain controversial, and various animal models of chronic MR (including chordae tendineae rupture, rapid pacing and ischemia) have been developed to study the pathophysiology and therapeutic approaches to this condition. The study aim was to review the animal MR models that have been developed using a mitral valve chordae tendineae rupture technique. METHODS AND RESULTS: Among the animals used for these investigations, dogs and sheep have been most commonly used as models of MR induced by mitral valve chordae tendineae rupture, mainly due to considerations of cardiac size. Chordae tendineae cutting is performed using either closed- or open-chest techniques. In the closed-chest model, long flexible grasping forceps are positioned percutaneously in order to tear the mitral valve chordae. In the open-chest model, cardiopulmonary bypass is performed, and either selected chordae are cut under direct visualization or a non-specified number of chordae are cut, using a metal device inserted through the left ventricular apex. Whichever model is used, MR has been found to become chronic at three to six months after the induction of MR by chordae rupture. The reported mortality and complication rates of these models are high. CONCLUSION: In the long term, the experimental evolution of chronic MR is similar to the evolution occurring naturally in patients suffering from the condition. Hence, these models could be useful in understanding the disease better, and in testing new therapeutic modalities. The present review summarizes the physiological effects of each of these techniques, and compares the advantages and disadvantages of each procedure.

Haemodynamic effects of negative pressure wound therapy when using a rigid barrier to prevent heart rupture.

Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier has been suggested to offer protection against this lethal complication by preventing the heart from being drawn up and damaged by the sharp sternum bone edges. The aim of this study was to investigate the haemodynamic effects of placing a rigid barrier over the heart to protect it from rupture during NPWT. Eight pigs underwent median sternotomy followed by NPWT at --70 and --120 mmHg, using foam, with or without a rigid plastic disc between the heart and the sternal edges. The heart frequency, cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, central venous pressure and left atrial pressure were recorded. Cardiac output was not affected by NPWT, regardless of whether a rigid barrier was used. Heart frequency decreased during NPWT without a disc, and showed a tendency towards a decrease when using a rigid disc. The blood pressure decreased during NPWT without a disc, and showed only a tendency towards a decrease when a disc was inserted between the heart and the sternum. In conclusion, the results of this haemodynamic study show that a rigid disc can safely be placed over the heart during NPWT, to prevent heart rupture. The haemodynamic effects of NPWT in sternotomy wounds are slightly reduced by the presence of the rigid disc.

Factors associated with physician decision making on withholding cardiopulmonary resuscitation in prehospital medicine.

This study seeks to identify factors that are associated with decisions of prehospital physicians to start (continue, if ongoing) or withhold (terminate, if ongoing) CPR in patients with OHCA. We conducted a retrospective study using anonymised data from a prehospital physician response system. Data on patients attended for cardiac arrest between January 1st, 2010 and December 31st, 2018 except babies at birth were included. Logistic regression analysis with start of CPR by physicians as the dependent variable and possible associated factors as independent variables adjusted for anonymised physician identifiers was conducted. 1525 patient data sets were analysed. Obvious signs of death were present in 278 cases; in the remaining 1247, resuscitation was attempted in 920 (74%) and were withheld in 327 (26%). Factors significantly associated with higher likelihood of CPR by physicians (OR 95% CI) were resuscitation efforts by EMS before physician arrival (60.45, 19.89-184.29), first monitored heart rhythm (3.07, 1.21-7.79 for PEA; 29.25, 1.93-442. 51 for VF / pVT compared to asystole); advanced patient age (modelled using cubic splines), physician response time (0.92, 0.87-0.97 per minute) and malignancy (0.22, 0.05-0.92) were significantly associated with lower odds of CPR. We thus conclude that prehospital physicians make decisions to start or withhold resuscitation routinely and base those mostly on situational information and immediately available patient information known to impact outcomes.

Outcomes of emergency or urgent mitral valve repair in patients with papillary muscle rupture and active infective endocarditis.

BACKGROUND: Emergency or urgent surgery is often required in patients with papillary muscle rupture and active mitral valve infective endocarditis. The aim of this study was to analyze the outcomes of patients with active endocarditis who underwent emergency or urgent mitral valve repair. METHODS: From 2005 to 2014, 154 ischemic mitral regurgitation patients and 41 infective endocarditis patients underwent mitral valve repair in our institution; 23 had emergency operations due to papillary muscle rupture, and 18 with active infective endocarditis underwent urgent surgery. RESULTS: Cardiopulmonary bypass time (141.4 ± 43.3 versus 145.3 ± 46.5 min) and crossclamp time (77.7 ± 34.1 versus 79.2 ± 33.0 min) were similar in the papillary muscle rupture and elective ischemic mitral regurgitation subgroups, and major postoperative complications were comparable. Hospital mortality was 17.4% in the papillary muscle rupture subgroup and 8.4% in the elective ischemic mitral regurgitation subgroup. Cardiopulmonary bypass time (103.6 ± 37.0 versus 75.5 ± 20.8 min) and crossclamp time (61.7 ± 21.2 versus 45.3 ± 18.0 min) were significantly longer in infective endocarditis patients. There were no major complications or hospital deaths. Eight years postoperatively, overall survival was 94.4% and 86.5% in the papillary muscle rupture and elective ischemic mitral regurgitation subgroups, respectively (p = 0.730). Overall survival was 100% in both infective endocarditis subgroups. CONCLUSION: The feasibility and effectiveness of emergency or urgent mitral valve repair in patients with papillary muscle rupture and active infective endocarditis are satisfactory. Early and mid-term outcomes are comparable to those of elective operations.

Changes in hospital mortality rates in 425 patients with acute ST-elevation myocardial infarction and cardiac rupture over a 30-year period.

BACKGROUND: Possible changes in the incidence and outcome of cardiac rupture in patients with ST-elevation myocardial infarction over a long period of time have not been investigated. METHODS AND RESULTS: The incidence of cardiac rupture in ST-elevation myocardial infarction patients and its mortality rate were investigated during a 30-year period divided into 5 intervals (1977 to 1982, 1983 to 1988, 1989 to 1994, 1995 to 2000, and 2001 to 2006). Of a total of 6678 consecutive patients, 425 experienced a free wall rupture (280 with cardiac tamponade: 227 with electromechanical dissociation and 53 with hypotension) or a septal rupture (145). After the exclusion of referrals from other centers (n=44), the incidence of definite cardiac rupture (septal rupture, anatomic evidence of free wall rupture, or electromechanical dissociation) declined progressively (6.2% in 1977 to 1982 to 3.2% in 2001 to 2006; P<0.001) in parallel with a progressive use of reperfusion therapy (0% to 75.1%; P<0.001). In addition, among patients with cardiac rupture, there was a progressive fall in the rate of death (94% to 75%; P<0.001) despite a trend toward increasing age (66+/-8 to 75+/-8 years; P<0.054) in conjunction with better control of systolic blood pressure at 24 hours (130+/-24 versus 110+/-18 mm Hg; P<0.001); an increased use of reperfusion therapy (0% to 59%; P<0.001), beta-blockers (0% to 45%; P<0.001), angiotensin-converting enzyme inhibitors (0% to 38%; P<0.001), and aspirin (0% to 96%; P<0.001); and a lower use of heparin (99% to 67%; P<0.001). CONCLUSIONS: The decline in the incidence in cardiac rupture and its rate of death over the last 30 years appears to be associated with the increasing use of reperfusion strategies and adjunct medical therapy.

Targeted deletion of class A macrophage scavenger receptor increases the risk of cardiac rupture after experimental myocardial infarction.

BACKGROUND: Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A-deficient (SR-A(-/-)) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction. METHODS AND RESULTS: Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A(-/-) and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A(-/-) mice than in WT mice (P=0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A(-/-) mice and 12% (6 of 51 mice) in WT mice (P=0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Real-time reverse transcription-polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Furthermore, SR-A(-/-) mice showed augmented expression of tumor necrosis factor-alpha and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-alpha and decreased interleukin-10 expression in activated SR-A(-/-) macrophages. CONCLUSIONS: The present findings suggest that SR-A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor-alpha and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.

Percutaneous closure of left ventricular free wall rupture with associated false aneurysm to prevent cardioembolic stroke.

Left ventricular (LV) false aneurysm is an uncommon complication of myocardial infarction. Conventional treatment mandates surgical repair but is associated with significant perioperative risk. We present a case of successful percutaneous closure of a LV false aneurysm in a patient at high operative risk who suffered cardioembolic stroke related to thrombus within the aneurysm. The primary aim of treatment was to prevent recurrent embolic event.

[Ischemic mitral regurgitation]. / L'insuffisance mitrale ischémique.

Mitral regurgitation (MR) is a serious complication of coronary heart disease. The functional form is the most frequent, often presenting with a dynamic character. The presence, and in particular the severity of MR and its dynamic character have a major impact on the medium and long term prognosis. The mechanisms responsible for MR are complex and occur in a state of disequilibrium between traction forces and closing forces, for which the significance is partly affected by the presence of asynchrony in left ventricular contraction. The therapeutic management of these patients is difficult. In cases of proven asynchrony, implantation of a biventricular pacemaker is justified. A mitral surgical procedure may be envisaged in cases of severe MR where bypass surgery is planned. In cases of moderate MR at rest, an evaluation of its dynamic character on effort can assist with the decision to undertake combined surgery. Mitral regurgitation (MR) is a common and serious complication of ischemic heart disease. Three general forms are distinguished: MR related to acute rupture of the mitral pillar, ischemic MR and functional MR.

Association between hypertension and primary mitral chordae tendinae rupture.

BACKGROUND: Mitral regurgitation from chordae tendinae rupture (CTR) may cause severe clinical symptoms and is a progressive disease that eventually results in the need for mitral valve surgery. Early recognition of CTR and identification of risk factors are important because early intervention increases the chances of survival. Hypertension may increase mitral valve complex mechanical strain and cause the chordae tendinae to rupture. METHOD: Using a cross-sectional study of medical files in one medical center in Taiwan, we enrolled 98 patients with mitral CTR and classified them into two groups, comprising 68 subjects (69%) without obvious predisposing factors (primary group) and 30 subjects (31%) with known predisposing causes (secondary group). RESULT: Of the subjects, 63 (64%) were men with a mean age of 57.5 +/- 1.5 years. The posterior mitral leaflet was most commonly involved (64%). The known predisposing factors in secondary group include mitral valve prolapse, infective endocarditis, and rheumatic heart disease. The patients who had primary CTR were older (59.9 +/- 1.6 v 52.1 +/- 3.1 years, P = .029), had a higher prevalence of hypertension (56% v 30%, P = .018) and complained more often of dyspnea (82% v 53%, P = .003) than the patients in the secondary group. Using binary logistic regression analyses, the variation in primary group was found to be independently explained by age (P = .039, odds ratio = 1.039, 95% confidence interval = 1.002 to 1.077) and hypertension (P = .048, odds ratio = 2.717, 95% confidence interval = 1.008 to 7.326). CONCLUSION: We conclude that hypertension was an independent predictor for primary CTR in this study.