Modified mRNA-Mediated CCN5 Gene Transfer Ameliorates Cardiac Dysfunction and Fibrosis without Adverse Structural Remodeling.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure.

Post myocardial infarction left ventricular intramural dissecting hematoma: a case report describing a very rare complication.

BACKGROUND: Dissecting intramural hematoma is a rare complication of acute myocardial infarction (AMI) and has been associated with increased mortality. There has been paucity of literature to establish protocols and guidelines for management in such cases. CASE PRESENTATION: We hereby report the case of a 45-year-old male patient with left ventricular intramural dissecting hematoma (LV-IDH) who presented with chest pain and breathlessness and diagnosed as non-ST-elevation myocardial infarction (NSTEMI). Transthoracic echocardiography (TTE) was performed showing LV-IDH, confirmed with cardiac magnetic resonant imaging (cMRI). Selective coronary arteriography (CAG) was performed showing significant obstructive coronary artery disease (CAD). Further management with conservative approach involved discussion with patient, cardiothoracic surgeon and cardiology team including heart failure specialist and interventional cardiology. CONCLUSIONS: This case describes a rare complication of AMI and also focuses on utility of TTE and cMRI in the diagnosis of this rare complication. Both diagnosis and management are challenging and have to be individualized in similar cases. Multidisciplinary care coordination is important in management of patients with this diagnosis.

Sufficient cardiac unloading by Impella 5.0 in left ventricular rupture following mitral valve replacement: a case report.

A 72-year-old woman presented with exertional dyspnea. Echocardiography revealed severe mitral valve stenosis; therefore, mitral valve replacement was performed using a bioprosthetic valve. However, left ventricular wall rupture occurred following mitral valve replacement. Under re-cardiac arrest, we found a left ventricular tear under the posterior annulus of the mitral valve. We repaired the left ventricular muscle using a bovine pericardial patch and implanted a bioprosthetic valve again. Postoperatively, we implanted an Impella 5.0 heart pump through the right axillary artery to ensure left ventricular wall unloading. Systemic blood flow depended almost completely on mechanical circulatory assistance until postoperative day 3. After the fourth postoperative day, we started weaning the patient from Impella 5.0. Finally, it was completely discontinued on the sixth postoperative day. After that, the patient's condition was stable, and she was discharged 44 days postoperatively. Impella 5.0 is a potentially beneficial device for left ventricular unloading in patients with left ventricular wall rupture following mitral valve replacement.

Left ventricular rupture after embolic myocardial infarction due to mitral valve endocarditis.

We report a very rare case of a 43-year-old patient with fatal left ventricular subepicardial aneurysm rupture complicating embolic myocardial infarction due to mitral valve infective endocarditis.

Sutureless repair with Hydrofit® and bovine pericardial patch for oozing-type postinfarction cardiac rupture.

Left ventricular free wall rupture is a fatal complication of myocardial infarction for which infarctectomy and reconstruction of the left ventricle using a prosthetic patch under cardiopulmonary bypass are performed. However, these surgical treatments remain challenging. Left ventricular free wall rupture secondary to acute myocardial infarction was diagnosed in an 86-year-old man. We performed sutureless repair of the left ventricular free wall rupture without cardiopulmonary bypass. During the operation, a pre-gluing bovine pericardial patch with Hydrofit® was placed twice on the ruptured site and manually pressed to provide complete hemostasis. The postoperative course was uneventful. This sutureless technique has the benefit of avoiding sutures in the fragile infarcted myocardium and might be effective for left ventricular free wall rupture treatment.

Left ventricular free wall rupture caused by myocardial ischemia without treatable atherosclerotic coronary disease: a case series.

BACKGROUND: The clinical presentation of left ventricular free wall rupture (LVFWR) varies ranging from uneventful condition to congestive heart failure. Here we report two cases of LVFWR with different clinical presentation and notable outcome. A 53-year-old male presenting emergently with signs of myocardial infarction received immediate coronary angiography and thoracic CT-scan showing occlusion of the first marginal coronary branch without possibility of revascularization and minimal pericardial extravasation. Under ICU surveillance, LVFWR occurred 24 h later and was treated by pericardiocentesis and ECMO support followed by immediate uncomplicated surgical repair. Postoperative therapy-refractory vasoplegia and electromechanical dissociation caused fulminant deterioration and the early death of the patient. The second case is a 76-year old male brought to the emergency room after sudden syncope, clinical sings of pericardial tamponade and suspicion of a type A acute aortic dissection. Immediate CT-angiography excluded aortic dissection and revealed massive pericardial effusion and a hypoperfused myocardial area on the territory of the first marginal branch. Immediate sternotomy under mechanical resuscitation enabled removal of the massive intrapericardial clot and revealed LVFWR. After an uncomplicated surgical repair, an uneventful postoperative course, the patient was discharged with sinus rhythm and good biventricular function. One year after the operation, he is living at home, symptom free. DISCUSSION: Whereas the younger patient, who was clinically stable at hospital admission received delayed surgery and did not survive treatment, the older patient, clinically unstable at presentation, went into immediate surgery and had a flawless postoperative course. Thus, early surgical repair of LVFWR leads to best outcome and treating LVFWR as a high emergency regardless of the symptoms improve survival.

The left ventricular "lining" technique for repair of ischemic ventricular septal rupture.

We describe a technique to repair ischemic ventricular septal rupture via a left ventriculotomy. It employs a large endoventricular patch as a "lining" over the locally patched septal defect and the free wall defect which is going to be roofed with an external patch. Both defects are then closed in double layers, holding a single continuous patch. The technique enhances the advantage of the left ventriculotomy in the repair and minimizes ventriculotomy-related morbidity.

Successful sutureless repair of multiple left ventricular free wall ruptures due to Takotsubo cardiomyopathy: a case report.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is a temporary and reversible systolic abnormality of the left ventricular apical area resembling a myocardial infarction. Cardiac rupture due to TCM is a rare but fatal complication. Without cardiac surgery, 94% of patients with left ventricular free wall rupture (LVFWR) due to TCM die. Furthermore, successful surgical cases are rare. We report herein the successful treatment of multiple LVFWRs due to TCM using a sutureless repair. CASE PRESENTATION: An 80-year-old man quarreled with his daughter and had a sudden onset of chest pain. He was transferred to our hospital in shock. Electrocardiography showed ST elevation and contrast-enhanced computed tomography revealed a bloody pericardial effusion. Emergent coronary angiography showed no significant stenosis. Cardiac arrest ensued because of cardiac tamponade. Emergent surgery was undertaken and three oozing lacerations on the lateral and inferior walls were noted. A sutureless repair was performed using TachoSil® patches. We also applied Surgicel Nu-Knit® absorbable hemostat with Hydrofit® where TachoSil® failed to completely adhere because of hematoma formation and achieved complete hemostasis. We diagnosed the ruptures due to TCM according to the Mayo criteria. The patient was discharged on postoperative day 71. CONCLUSIONS: A sutureless repair using TachoSil® patches and Surgicel® with Hydrofit® is a minimally invasive and effective method for the treatment of multiple LVFWRs due to TCM.

Successful surgical repair of a huge left ventricular pseudoaneurysm after repair of left ventricular rupture during mitral valve replacement.

A 78-year-old man underwent pericardial patch repair for left ventricular (LV) rupture during mitral valve replacement. After the first operation, a huge (>10 cm) LV pseudoaneurysm was detected, necessitating reoperation. LV rupture is a rare but often fatal complication of mitral valve replacement. Although repair of LV rupture during mitral valve replacement has been reported, the development of pseudoaneurysm after such repair is exceedingly rare. In this case, we successfully treated a huge LV pseudoaneurysm using two pericardial patches to sandwich the rupture hole from the inside.

Acute Left Ventricle Free-Wall Rupture Post Primary PCI: In Vivo Imaging.

A 69-year-old male was referred to our cath lab for primary percutaneous coronary intervention due to acute anterior ST-segment elevation myocardial infarction. Left coronary angiography revealed acute occlusion of the proximal left anterior descending artery. After several additional diagnostic procedures and implantation of a drug-eluting stent, an abrupt clinical deterioration manifested with sudden hypotension. There was evidence of cardiac tamponade, and the constant supply of blood from the pericardium along with the development of cardiogenic shock state led us to suspect cardiac laceration. This imaging series illustrates a heart team operating in vivo on a rare acute myocardial infarction mechanical complication, which occurred soon after primary percutaneous coronary intervention.

A case report of rescue of a patient with a left ventricular free wall rupture associated with a small subtle ST-elevation myocardial infarction.

Background: Left ventricular (LV) free wall ruptures (LVFWRs) of myocardial infarctions (MIs) are still one of the most fatal mechanical complications after an acute MI (AMI). LVFWRs are estimated to occur in 0.01% to 0.52% of patients following an ST-elevation MI (STEMI) and are rarely reported in the setting of a non- or subtle-ST-elevation MI. Case summary: We herein present a report of a 92-year-old male rescue case with an LVFWR following a small subtle-STEMI. Contrast cardiac computed tomography was useful to diagnose the LVFWR. An emergent cardiac surgery was performed. Finally, the patient's life was saved. Discussion: This case demonstrates that even without clinical evidence of transmural infarction such as non- or subtle-STEMI, those patients may carry a risk of fatal complications including LVFWR, especially in older age and a first lateral wall AMI without collateral flow, as in this present case. Thus, the physicians should be aware of the possibility of LVFWRs even in the setting of an AMI without or with subtle-ST-elevation. High clinical suspicion and vigilance are the cornerstones of a timely and accurate diagnosis of LVFWR. This is the first report of a rescue case of a patient with an LVFWR associated with a subtle-STEMI.

Infective calcified amorphous tumor on mitral valve and critical course of left ventricular rupture.

Calcified amorphous tumor is a rare intracavitary cardiac lesion and an accompanying infection is extremely rare. A 76-year-old woman was transferred to our hospital because of cerebral infarction. Echocardiography and chest computed tomography showed a calcified large mobile mass on the posterior mitral valve that was diagnosed with a calcified amorphous tumor. Moderate aortic regurgitation and severe mitral regurgitation were also confirmed. Her blood culture detected Gamella sp. We surgically dissected this infective calcified amorphous tumor. The border between this infective tumor and the mitral annulus was unclear because of severe infection and necrotic tissue. After careful complete resection, the healthy ventricular muscle was exposed and we performed annular reconstruction with bovine pericardial patches. And we replaced the aortic and mitral valves using bioprosthesis. While weaning from cardiopulmonary bypass, however, left ventricular rupture occurred twice. Despite successful repair of left ventricular rupture, which controlled bleeding, she died from multi-organ failure on postoperative day 6. An infective calcified amorphous tumor in such a critical case has not been reported previously. The calcified amorphous tumor probably become serious when the infection occurred. In this situation, the utmost caution should be paid to the patient. .

Left Ventricular Rupture as a Complication of Anterior Wall Myocardial Infarction on Computed Tomography Angiography and Ventriculography.

Rupture of the free wall of the left ventricle, rupture of the interventricular septum and acute mitral regurgitation are mechanical complications of myocardial infarction. They are rare; left ventricular rupture occurs in about 2-4% of patients with myocardial infarction. We present the case of an 85-year-old woman with an anterior wall infarction complicated by left ventricular rupture. We present diagnostic images of pathology visualized by computed tomography angiography, performed in order to exclude aortic dissection as the cause of the presence of fluid in the pericardial sac. Images from ventriculography are also presented. Summing up, during the diagnostic and therapeutic process of acute coronary syndrome, it is important to bear in mind the risk of possible complications, such as left ventricular rupture.

Cardiac autotransplantation for repair of left ventricular rupture after mitral valve replacement.

Left ventricular rupture is an infrequent but potentially fatal complication of mitral valve replacement. We report a case of large posterior mid-ventricular rupture following mitral valve replacement, which was successfully treated by a patch repair and autotransplantation.

Repair of left ventricular rupture in a patient with mitral annular calcification.

Left ventricular free wall rupture is a complication following acute myocardial infarction or mitral valve replacement. We report the case of a 56-year-old female patient with idiopathic left ventricular rupture confirmed by contrast-enhanced computed tomography (CT). CT also showed no coronary artery obstruction and severe mitral annular calcification. Left ventricular rupture was successfully repaired internally with bovine pericardium. Mitral valve replacement with annular decalcification was also performed.

Cardiac autotransplantation for repair of left ventricular rupture after mitral valve replacement.

Left ventricular rupture is an infrequent but potentially fatal complication of mitral valve replacement. Here, we report a case of large posterior mid-ventricular rupture following mitral valve replacement, which was successfully treated by a sandwich style repair and autotransplantation.

Off-pump sutureless repair for ischemic left ventricular free wall rupture: a systematic review.

BACKGROUND: Clinical results of ischemic left ventricular free-wall rupture show high mortality rates. METHODS: We reviewed studies published after 1993 on PubMed. RESULTS: A sutureless technique using fibrin glue sheets or patches with/without fibrin glue might contribute to improved clinical results. However, some technique limitations remain for blowout-type ruptures, and the possibility of a pseudoaneurysm formation at the repair site after surgery should be considered. CONCLUSIONS: The sutureless technique can be a promising strategy for the treatment of ischemic rupture, but serial echocardiographic studies should be mandatory for diagnosing a left ventricular pseudoaneurysm formation thereafter.

Left ventricular pseudoaneurysm after valve replacement.

We present a case of left ventricular pseudoaneurysm, which is a very rare and fatal complication of cardiac procedures such as mitral valve replacement. A 55-year-old woman presented to the Department of Thoracic and Cardiovascular Surgery at Hanyang University Seoul Hospital with chest pain. Ten years prior, the patient had undergone double valve replacement due to aortic regurgitation and mitral steno-insufficiency. Surgical repair was successfully performed using a prosthetic pericardial patch via a left lateral thoracotomy.