Predominant Use of Bilateral Internal Mammary Arteries in Off-Pump Coronary Artery Bypass Surgery.

Bilateral internal mammary artery (BIMA) in coronary artery bypass grafting (CABG) has been shown to provide long-term clinical benefits over single internal mammary artery (SIMA) grafting. Nevertheless, the perceived technical complexity of the procedure and concerns about potential early postoperative complications, particularly sternal wound infections have led to a utilization rate of BIMA grafting of less than 5% in the United States. We systematically compared early (30-day) post-operative outcomes between the BIMA and SIMA cohorts in patients with similar baseline characteristics. A retrospective single center study was conducted on matched patients, using stabilized inverse probability treatment weighting to mitigate bias between the two study cohorts. From 546 off-pump CABG patients initially identified, we examined 328 BIMA and 213 SIMA grafts from the matched samples. Despite utilizing 60.4% BIMA grafts, we observed similar rates of 30-day overall and cardiac mortality between the BIMA and SIMA groups. Rates of 30-day postoperative complications, including superficial and deep sternal wound infections, stroke, sepsis, acute kidney injury, and cardiac arrest, were similar between the two groups. Rates of 30-day overall and cardiac readmission were also similar. Additionally, median length of hospital stays, intensive care unit stay, and ventilation times were similar between the two groups. In conclusion, our data suggest that a BIMA utilization rate of 60.4% in off-pump CABG procedure is achievable without causing any significant increment in early post-operative complications, including deep sternal wound infection.

Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives - Imidazoline Receptor Agonists.

Introduction: The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of these substances were studied, their structure was proved, and some components were found to have sugar-reducing activity on the model of alloxan diabetes in rats. Methods: The study used molecular modeling methods such as docking based on the evolutionary model (igemdock), RP_HPLC method to monitor the synthesis reaction, and 1H NMR and 13C NMR, and other methods of organic chemistry to confirm the structures of synthesized substances. Results & Discussion: The docking showed that the ursodeoxycholic acid benzimidazole derivatives have high tropics to all imidazoline receptor carriers (PDB ID: 2XCG, 2bk3, 3p0c, 1QH4). The ursodeoxycholic acid benzimidazole derivative and arginine and histidine benzimidazole derivatives showed the highest sugar-lowering activity in the experiment on alloxan-diabetic rats. For these derivatives, the difference in glucose levels of treated rats was significant against untreated control. Therefore, the new derivatives of benzimidazole and labile natural organic acids can be used to create new classes of imidazoline receptor inhibitors for the treatment of diabetes mellitus and hypertension.

Effect of F11 Receptor/Junctional Adhesion Molecule-A-derived Peptide on Neointimal Hyperplasia in a Murine Model.

PURPOSE: To determine whether inhibition of the F11 receptor/JAM-A (F11R) using F11R-specific antagonist peptide 4D results in inhibition of smooth muscle cell (SMC) proliferation and migration in vivo, known as neointimal hyperplasia (NIH), using a mouse focal carotid artery stenosis model (FCASM). MATERIALS AND METHODS: The mouse FCASM was chosen to test the hypothesis because the dominant cell type at the site of stenosis is SMC, similar to that in vascular access stenosis. Fourteen C57BL/6 mice underwent left carotid artery (LCA) partial ligation to induce stenosis, followed by daily injection of peptide 4D in 7 mice and saline in the remaining 7 mice, and these mice were observed for 21 days and then euthanized. Bilateral carotid arteries were excised for histologic analysis of the intima and media areas. RESULTS: The mean intimal area was significantly larger in control mice compared with peptide 4D-treated mice (0.031 mm2 [SD ± 0.024] vs 0.0082 mm2 [SD ± 0.0103]; P = .011). The mean intima-to-intima + media area ratio was significantly larger in control mice compared with peptide 4D-treated mice (0.27 [SD ± 0.13] vs 0.089 [SD ± 0.081]; P = .0079). NIH was not observed in the right carotid arteries in both groups. CONCLUSIONS: Peptide 4D, an F11R antagonist, significantly inhibited NIH in C57BL/6 mice in a FCASM.

Redo surgical aortic valve replacement for prosthetic valve valve-in-valve dysfunction.

Transcatheter aortic valve replacement (TAVR) has become the preferred intervention for patients with severe aortic stenosis and significant comorbidities. This technique can also be used for failed bioprosthetic valves and is known as the valve-in-valve (ViV) procedure. Placing TAVR in a small bioprosthesis (<23 mm) can lead to delayed dysfunction of the prosthetic valve. We present a case of a late explanted ViV 8 years post-initial aortic valve replacement and coronary artery bypass grafting, and 3 years post-ViV procedure in a 76-year-old female. A video of the surgical procedure is provided.

Use of a novel bicarbonate-based Impella 5.5 purge solution in a coagulopathic patient.

The Impella 5.5 with Smart Assist (Abiomed) is a life-saving treatment option in acute heart failure which utilizes a continuous heparin purge solution to prevent thrombosis. In patients with contraindications to heparin, alternative anticoagulation strategies are required. We describe the stepwise management of anticoagulation in a coagulopathic patient with persistent cardiogenic shock following a coronary artery bypass procedure who underwent Impella 5.5 placement. A direct thrombin inhibitor-based purge solution was utilized while evaluating for heparin-induced thrombocytopenia. The use of a novel bicarbonate-based purge solution (BBPS) was successfully used due to severe coagulopathy. There were no episodes of pump thrombosis or episodes of severe bleeding on the BBPS and systemic effects of alkalosis and hypernatremia were minimal.

Off-pump myocardial revascularization with Impella 5.5-assisted for cardiogenic shock.

We report a case of Impella 5.5-assisted off-pump coronary artery bypass grafting for acute myocardial infarction with cardiogenic shock. The Impella 5.5 was placed in the left ventricle during the emergent procedure, and an off-pump coronary artery bypass grafting was successfully performed with exposure of all three walls of the heart. Our findings demonstrated the feasibility of off-pump coronary revascularization in three-vessel disease in a patient assisted with an Impella 5.5 percutaneous left ventricular assist device without displacement of the device during the entire perioperative period.

Three-dimensional echocardiography assessment of carcinoid valvular heart disease: Images of each and all.

A 54-year-old male was found to have neuroendocrine carcinoma with hepatic metastasis. Two-dimensional (2D) transthoracic echocardiography (TTE) demonstrated dilated right ventricle and right atrium, and severe tricuspid and pulmonary regurgitation. Three-dimensional (3D) TTE en-face views showed thickened, retracted, and fixed tricuspid valve and pulmonic valve which remained widely open throughout the cardiac cycle. 3D TTE, particularly en-face views, demonstrates incremental value over 2D TTE by providing precise valvular anatomic details comparable to surgical findings. 3D TTE also offers a unique opportunity to assess all four valves simultaneously with en-face views to delineate their relationships with surrounding structures.

A Large Mitral Valve Vegetation Not Visualized on Transthoracic Echocardiography: A Case Report.

BACKGROUND Immediate evaluation, diagnosis, and treatment of a patient with infective endocarditis, an infection of the endocardium and/or integral structures found within the heart, is essential to patient survival. CASE REPORT We present the case of a 41-year-old man who was brought to the Emergency Department for altered mental status and fever. He was found to have methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia complicated with severe respiratory failure and metabolic encephalopathy, necessitating intubation and mechanical ventilation. As part of the workup for persistent Staphylococcal bacteremia, 2 transthoracic echocardiograms (TTE) failed to reveal any valvular abnormalities. However, a transesophageal echocardiogram (TEE) detected a 30×30 mm large vegetation on the anterior mitral valve leaflet. Due to the overall size and risk of systemic embolization, and the fact that the patient developed new-onset heart failure, the mitral valve was replaced using an open approach. The patient tolerated the procedure well and was discharged after an extended period of hospitalization. CONCLUSIONS Although the literature emphasizes that the sensitivity of TTE significantly increases when the vegetation size is above 1 cm, it is of utmost importance for clinicians to keep in mind that this is not always true, and clinicians should consider performing a TEE to rule out infective endocarditis whenever a TTE is unable to detect any vegetation in a patient with persistent Staphylococcal bacteremia. This is clearly demonstrated by the present case, in which two TTEs failed to detect a 30×30 mm vegetation.

Purulent Pericarditis in Sickle Cell Disease Due to Streptococcus agalactiae; a Unique Case Report and Literature Review.

Purulent pericarditis is a localized infection with a thick, fibrinous hypercellular exudate and is historically associated with a high mortality. We describe a case of purulent pericarditis due to Streptococcus agalactiae (S. agalactiae) in a 30-year-old woman with sickle cell disease who presented with fever, dyspnea, and S. agalactiae septicemia. Despite timely initiation of antibiotics, she developed a large purulent pericardial effusion requiring surgical pericardiocentesis followed by a pericardial window. At 14 months follow-up, she has remained asymptomatic without sequelae. A review of the literature contained only four patients with purulent pericarditis in sickle cell patients. We discuss the unique aspects of this case in the context of purulent pericarditis in the age of modern antibiotics and hypothesize on the pathogenesis of delayed pericardial effusion after pericarditis.

Simple technique to preserve the LSVC during reoperative orthotopic heart transplant.

Increasingly, patients undergo heart transplant after previous heart surgery. In patients with a persistent left superior vena cava (LSVC), the preferred technique, preservation of drainage via the native coronary sinus, can be difficult in reoperative cases due to adhesions. We report a technique simplifying this operation in such a patient.

Anomalous right coronary artery from the left sinus: a minimally invasive approach.

OBJECTIVE: Anomalous right coronary artery arising from the left sinus (ARCA) is a known cause of sudden cardiac death, particularly in young athletes. Surgery is recommended for all adult patients who are symptomatic or who have evidence of exercise-induced myocardial ischemia. Surgical options include coronary artery bypass grafting (CABG) and anatomic correction by unroofing the ostium or by reimplanting the ostium into the right sinus of Valsalva. We describe the rationale and technique of a minimally invasive right thoracotomy approach for correction of ARCA. METHODS: We reviewed all patients with coronary artery disease operated upon at Mount Sinai Medical Center. Between March 2008 and September 2010, 17 patients underwent surgery for anomalous coronary origin from the opposite sinus of Valsalva. Nine of these patients had ARCA. We describe four adult patients with ARCA who were operated upon using a small right anterior thoracotomy incision to perform a right internal mammary artery (RIMA) to right coronary artery (RCA) bypass with ligation of the proximal RCA. This was performed under direct vision and without cardiopulmonary bypass. RESULTS: There were two male and two female patients. Mean age was 55.3 ± 4.8 years (range 50-61 years). Three of the patients manifested chest pain and one each syncope, dyspnea, and palpitations. Two patients had preoperative stress testing that was positive for ischemia. Postoperative follow-up (mean 14 months and range 5-37 months) is complete. All patients are alive and asymptomatic. CONCLUSIONS: ARCA can be managed with good early and midterm results using a minimally invasive right thoracotomy approach.

Transplantation of high panel-reactive antibody left ventricular assist device patients without crossmatch using on-bypass pheresis and alemtuzumab.

BACKGROUND: Highly sensitized (HS) left ventricular assist device (LVAD) patients with high panel-reactive antibody (PRA) levels present a challenge. Alemtuzumab, a potent depleting agent for T and B lymphocytes (months to years), and plasmapheresis, offer an opportunity for heart transplantation to these patients who might die of VAD complications on the transplant waiting list. This study compared rates of acute rejection and survival of a HS LVAD cohort with a contemporaneous control group after heart transplant. METHODS: Clinical courses of 31 consecutive patients who underwent transplantation between January 2006 and January 2011 were reviewed. Eight patients with a T or B PRA of 70 or more (HS+) received non-crossmatched, ABO-compatible hearts using intraoperative plasmapheresis and alemtuzumab induction. Controls (HS-) received basiliximab induction. Acute rejection was defined as International Society for Heart and Lung Transplantation grades 2R or higher, or antibody-mediated rejection. RESULTS: The difference in survival between HS+ and HS- groups at 1 year (100% vs 94%) or at a mean follow-up of 2.3 and 2.4 years (75% vs 70%) was not significant. Retrospective lymphocytotoxic crossmatches were positive in 7 of 8 HS+ patients (6 T+ and B+, 1 B+) vs none in the HS- group (p < 0.001). There was a trend toward increased risk of cellular rejection per 100 patient-days beyond 1 year in the HS+ group (p = 0.07). Risk of humoral rejection was significantly increased in the HS+ group (38% vs 4%; p = 0.04). CONCLUSIONS: Heart transplantation with plasmapheresis and alemtuzumab in HS LVAD patients, most with a positive crossmatch, does not compromise midterm survival. The expected higher rates of rejection, especially beyond the first postoperative year, demand adjustments in surveillance strategies and immunosuppressive management.

Thoracoscopic management of empyema thoracis.

Appropriate management of empyema thoracis is dependent upon a secure diagnosis of the etiology of empyema and the phase of development. Minimal access surgery using video-assisted thoracoscopy (VATS) is one of many useful techniques in treating empyema. Complex empyema requires adjunctive treatment in addition to VATS.

Inhibition of Jak2 phosphorylation attenuates pressure overload cardiac hypertrophy.

RATIONALE: We examined the role of Jak2 kinase phosphorylation in the development of pressure overload hypertrophy in mice subjected to transverse aortic constriction (TAC) and treated with tyrphostin AG490, a pharmacological inhibitor of Jak2. METHODS: Control mice (sham), subjected to TAC for 15 days (TAC) or to TAC and treated with 48 microg/kg/day i.p. of tyrphostin AG490 (TAC+AG490) were evaluated for morphological, physiological, and molecular changes associated with pressure overload hypertrophy. RESULTS: Mice subjected to TAC alone developed concentric hypertrophy that accompanied activation of the components of the Jak/STAT signaling pathway manifested by an increase in phosphorylation of Jak2 and STAT3. We also observed increased phosphorylation of MAPK p44/p42, p38 MAPK and JNK in the TAC group, as well as, an increase in expression of MKP-1 phosphatase which negatively regulates MAPK kinases. Treatment of aortic constricted mice with tyrphostin AG490 failed to develop hypertrophy and showed a marked reduction in phosphorylation of Jak2 and STAT3. There was, however, in TAC and AG490 treated mice, a notable increase in the phosphorylation state of the MAPK p44/42, whereas MKP-1 phosphatase was downregulated. CONCLUSION: These findings suggest that Jak2 kinase plays an important role in left ventricular remodeling during pressure overload hypertrophy. Pharmacological inhibition of Jak2 kinase during pressure overload blocks the development of concentric hypertrophy.

Janus kinase-2 signaling mediates apoptosis in rat cardiomyocytes.

We tested the hypothesis that activation Jak2, which is prominently involved in the up-regulation of the renin-angiotensin system (RAS), constitutes a focal point in relaying signals triggered by a Angiotensin II (Ang II) and hypoxia/reoxygenation separately to cause an enhanced susceptibility of cardiac myocyte to apoptotic cell death. Ang II-treated adult cardiomyocytes in culture exhibited an increased level of apoptosis that accompanied activation of pro-apoptotic as well as anti-apoptotic signaling pathways. We observed increased phosphorylation of Jak2 kinase, Stat1, JNK, with increased expression of Bax protein, followed by an increase in caspase-1 and caspase-3 activity. Activation of these pro-apoptotic pathways was blocked by the Jak2 pharmacological inhibitor, Tyrphostin AG490. We also observed an increase in phosphorylation of cardioprotective pathway components, namely S6 ribosomal protein, and heat shock protein 27 (HSP27). Likewise, the oxidative stress, via the hypoxia/reoxygenation treatment of rat adult cardiomyocytes, produced apoptosis that was dependent upon activation of Jak2. The apoptotic response was not only reduced by Losartan, an inverse agonist of the AT1, receptor, but by treatment with AG490 as well. Taken together, these observations provide clear evidence in favor of Jak2 signaling as mediator of the apoptotic response in cardiomyocytes. However, there was a concomitant induction of cytoprotective signaling that presumably provides a negative feed-back to the deleterious effects of the agonist.

Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts.

Reactive oxygen species play a central role in myocardial ischemic injury and are a target for therapeutic intervention. Vitamin C is an essential antioxidant yet difficult to deliver in pharmacologic concentration to the myocardium. We found that adult rat cardiomyocytes accumulate vitamin C by transporting dehydroascorbic acid (DHA), the oxidized form of vitamin C, but do not transport ascorbic acid. Loading cells with vitamin C by DHA treatment resulted in resistance to hypoxia- and hypoxia/reoxygenation-induced cell death associated with the quenching of reactive oxygen species. When rats were injected with DHA before coronary occlusion, the ascorbic acid content in the heart was six to eight times higher than in untreated controls and myocardial infarction was reduced by 62%. DHA also provided significant protection when administered intravenously 2 h after coronary occlusion. In cardiomyocytes subjected to hypoxia/reoxygenation, DHA treatment resulted in decreased apoptosis associated with inhibition of Bax expression, caspase-3 activation, and cytochrome c translocation into the cytoplasm. DHA treatment also inhibited Jak2, STAT1, and STAT5 phosphorylation, and increased STAT3 phosphorylation, in hypoxic cardiomyocytes and ischemic myocardial tissue. Our findings suggest that DHA may be useful as a cardioprotectant in ischemic heart disease.