Minimally invasive coronary artery bypass grafting via a lower ministernotomy for left anterior descending artery myocardial bridging: mid-term results.

OBJECTIVES: Coronary artery bypass grafting or supra-arterial myotomy is now suggested as a better therapeutic option in myocardial bridging (MB) when medical treatment fails to control symptoms. For left anterior descending (LAD) MB, minimally invasive coronary artery bypass via a lower ministernotomy can be offered. METHODS: Forty-four consecutive patients who underwent elective minimally invasive coronary artery bypass surgery from 2005 to 2014 via an inferior sternotomy using the left internal mammary artery as a bypass graft for LAD MB were evaluated retrospectively. RESULTS: The mean age was 59.1 ± 13.1 years with 26 (59%) men and 18 (41%) women. The mean body mass index was 27.2 ± 3.9 and the mean EuroSCORE II was 1.6 ± 1.8. Routine coronary multislice computed tomography angiography on the 6th postoperative day revealed 97.7% graft patency. During the initial hospital stay, 1 patient (2.3%) underwent a reoperation for early graft failure. Forty patients (91%) could be followed up for a mean period of 64.4 ± 24.5 months after the procedure, during which 2 patients (4.5%) died of non-cardiac causes and 9 patients (20.5%) underwent postoperative coronary angiography with confirmed graft occlusion in only 1 case (2.3%). The improvement in the distribution of patients in the Canadian Cardiovascular Society class 0 was from 4 patients (9%) preoperatively to 37 patients (84%) at the end of the follow-up period (P-value 0.001). CONCLUSIONS: Minimally invasive coronary artery bypass surgery via a lower ministernotomy may be safe and efficient for treating LAD artery MB with acceptable complication rates, cosmetic benefits and patency rates.

"Unlucky punch": unexpected annular rupture during TAVR and successful treatment.

Although rare, annular rupture in TAVR is a feared and often unpredictable complication with relevant impact on in-hospital prognosis. Severe annular calcification is a common risk factor for annular rupture. We report on a case of annular rupture during TAVR with a balloon-expanded prosthesis in the absence of any annular calcification in the planning CT scan and illustrate the proposed pathomechanism as well as its successful immediate surgical management.

Influence of an Early Application of Mammalian Target of Rapamycin Inhibitors Everolimus and Sirolimus on Acute Vascular Inflammatory Responses After Ischemia-Reperfusion Injury.

OBJECTIVES: Ischemia-reperfusion injury is correlated with a substantial inflammatory response. Inflammation triggers the migration of cells through vessel endothelium and leads to serious tissue injury. Our hypothesis was that an early application of mammalian target of rapamycin inhibitors has an impact on human vessels after ischemia-reperfusion injury. MATERIALS AND METHODS: After exposure to ischemia for 5 hours, human vessels (veins and arteries) from 20 patients were reperfused for 120 minutes in an in vitro bioreactor with heparinized human blood after oxygenation and warming to 37 °C. The vessels were treated with mammalian target of rapamycin inhibitor everolimus (5 ng/mL, n = 7) or sirolimus (10 ng/mL, n = 6). As a control group, untreated human vessels were reperfused (n = 7). During the reperfusion period, blood samples were collected continuously (after 0, 15, 30, 60, 120 minutes); vessel biopsies were performed at the end. Oxygen consumption was measured during reperfusion to determine vessel viability. Inflammatory markers (interleukin 6, tumor necrosis factor α, vascular endothelial growth factor) were analyzed in blood samples. To quantify vascular inflammation, we investigated the expression of CD11 and CD31. RESULTS: Physiological oxygen consumption and pH values verified vessel viability. After reperfusion, interleukin 6 and vascular endothelial growth factor levels were significantly increased in the control group over time, whereas everolimus and sirolimus showed no significant differences. Furthermore, tumor necrosis factor α level increased significantly in the sirolimus group, whereas the everolimus and control groups showed constant values. A significant decrease of expression of CD11b and CD31 in both mammalian target of rapamycin inhibitor cohorts compared with control cohort was investigated. CONCLUSIONS: Early use of mammalian target of rapamycin inhibitors may limit an inflammatory rise of interleukin 6 and vascular endothelial growth factor after ischemia-reperfusion injury and could be associated with a restriction in vascular cell transmigration.

Feasibility of a MPR-based 3DTEE guidance protocol for transcatheter direct mitral valve annuloplasty.

OBJECTIVES: Several interventional approaches have been established for the treatment of severe mitral regurgitation (MR) in patients at elevated risk for surgery. Direct annuloplasty is a relatively novel option in transcatheter mitral valve repair dedicated to reverse pathology in specific subsets of MR. With regard to echocardiographic guidance, this procedure presents with higher efforts in comparison with edge-to-edge therapy to enable safe and exact positioning of the device's anchors; evidence on optimal peri-interventional imaging is sparse. We tested a specific 3D-echo-guidance protocol implementing single-beat multiplanar reconstruction (MPR) and evaluated its feasibility. METHODS: Overall, 16 patients consecutively treated with transcatheter direct annuloplasty for severe MR (87.5% functional/6.3% degenerative/6.3% mixed pathology) were entered in this monocentric analysis. Of these, two patients received a combined procedure including edge-to-edge repair. For all implantations, a 3D-echo-guidance protocol inheriting MPR was employed. RESULTS: Periprocedural device time decreased continuously (overall mean 140 ± 55.1 minutes, 213 ± 38 minutes in the first 4 vs 108 ± 33 minutes in the last 4 procedures, P = .018) using the MPR-based echo protocol, going along with reduced fluoroscopy times and doses. Technical success rate was high (93.8%) without any serious cardiac-related adverse events. MR could be relevantly improved. CONCLUSION: Echocardiographic guidance of transcatheter direct annuloplasty using a real time MPR-based protocol is feasible and safe. Optimized imaging might enable reduced implantation times and potentially increases safety.

Echocardiography-guided subxiphoidal transapical TAVR in a challenging anatomy: a case report.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) via an antegrade transapical access (TA-TAVR) is largely reserved to cases not amenable to transfemoral TAVR. Challenges resulting from unusual thoracic anatomies may require special considerations in terms of the surgical access. CASE PRESENTATION: We present a case of TA-TAVR through a subxiphoidal approach in a patient who had undergone extensive thoracic surgery 8 years previously. CONCLUSION: Our case demonstrates that unusual anatomic features should not discourage from TA-TAVR but may require unusual approaches designed on a case-to-case basis following careful interdisciplinary preparation and planning including adequate pre-operative diagnostics and imaging.

T-shaped Transseptal Approach for Mitral Valve Surgery.

We present a T-shaped transseptal approach for mitral valve surgery that makes adequate exposure possible under challenging anatomic and surgical circumstances, hence eliminating the need for forceful retraction on potentially fragile tissues. Particularly suited for patients with complex mitral pathology, it also facilitates juxta-annular transseptal right atrial anchoring, especially in cases of endocarditic anterior mitral annular destruction.

Early LVAD Implantation in a Patient with Left Ventricular Failure after Aortic Dissection with Left Main Stem Involvement.

BACKGROUND: Coronary involvement in aortic dissection heralds a poor outcome. Involvement of the left main stem may lead to left ventricular (LV) failure requiring mechanical circulatory support. CASE REPORT: A staged approach was applied in a 24-year-old female who suffered extensive infarction due to aortic dissection with left main stem involvement. After replacement of the ascending aorta and grafting of the left internal thoracic artery to the left anterior descending artery following a failed attempt at reconstruction of the left coronary ostium, she failed to wean from cardiopulmonary bypass (CPB) and underwent implantation of an extracorporeal life support (ECLS) system as a bridge to decision. Subsequent implantation of a left ventricular assist device (LVAD) as a bridge to recovery/transplantation was followed by an uneventful further course. CONCLUSIONS: Our experience suggests that early implantation of a ventricular assist device (VAD) as bridge to recovery/transplantation is an alternative to prolonged ECLS in patients who suffered extensive myocardial infarction in the course of aortic dissection.

Giant right atrial myxoma: A rare cause of cardiovascular collapse.

We report the case of a patient with a giant right atrial myxoma that remained clinically silent until it almost completely obliterated the right atrium, prolapsed into the right ventricle and obstructed the tricuspid valve inflow. This case illustrates the importance of rapid surgical intervention in the setting of acute heart failure caused by tumor masses obliterating heart valves or cardiac chambers.

Juxta-annular right atrial anchoring of prosthetic mitral valves in endocarditis with anterior annulus destruction†.

Destruction of the mitral annulus is associated with poor outcomes. We present the treatment of endocarditis using a technique that enables secure anchoring of prosthetic valves where the anterior part of the mitral annulus is severely disrupted. It was used in 5 patients. Follow-up at 10 ± 4 months showed the valves intact without recurrence of endocarditis. Mortality was limited to 1 patient who died of non-cardiac causes. We conclude that partial right atrial anchoring is a useful bail-out and enables favourable outcomes in patients with extensive loss of the (peri)annular tissue due to endocarditis.

A low threshold to ECG-gated repeat CTA reduces the risk of false-positive diagnosis of type A dissection in interhospital referrals: a case series study.

BACKGROUND: False-positive diagnosis of acute Stanford type A aortic dissection (AAD) on computed tomography angiography (CTA) is still an issue and may lead to substantial consequences. Given that electrocardiography (ECG)-gated CTA provides greater diagnostic safety, it may be assumed that interhospital referrals with a diagnosis of AAD based on non-ECG-gated pre-referral CTA carry an elevated risk of false-positive diagnosis. PATIENTS AND METHODS: We reviewed a series of patients in whom a diagnosis of AAD based on non-ECG-gated pre-referral CTA was subsequently proven false by ECG-gated CTA. The artifacts that gave rise to the misdiagnosis, as well as the diagnostic pathways followed and the consequences of false-positive diagnosis were investigated. RESULTS: In 5 patients, ECG-gated repeat CTA revealed artifacts in the pre-referral scans that had led to false-positive diagnosis and referral for emergent surgery. In the first case, the patient proceeded to surgery. In 4 subsequent cases, ECG-gated CTA was ordered because a false-positive diagnosis was suspected. We found that ECG-gated CTA rather than echocardiography provided sufficient information to rule out AAD in each of these cases. Comparison between pre-referral non-ECG-gated scans and ECG-gated repeat CTA demonstrated the wide range of artifacts that may give rise to a diagnosis of AAD. CONCLUSION: Patient condition permitting, the threshold to ECG-gated repeat CTA should be low when doubt arises with regard to a diagnosis of AAD based on non-ECG-gated CTA in interhospital referrals.

Repair of TEVAR-Associated Type A Dissection in the Elderly Is Possible With Reasonable Morbidity and Mortality.

BACKGROUND: Type A aortic dissection (AAD) is a devastating complication of thoracic endovascular repair (TEVAR). In elderly patients, surgery for AAD carries considerable morbidity and mortality. Repair of AAD after previous TEVAR is an even greater challenge as it usually requires the arch to be addressed and a preexisting stent graft to be included into the aortic repair. METHODS: A case series of 5 elderly patients who presented with acute AAD after previous TEVAR was reviewed. In 4 cases, there was retrograde AAD with involvement of the arch and stent graft. In 1 patient, intraoperative inspection showed no involvement of the arch. Three underwent ascending and subtotal arch replacement in moderate hypothermic circulatory arrest with selective cerebral perfusion. In 1 case, concomitant tricuspid valve repair was performed. The patient without involvement of the arch underwent emergent replacement of the ascending aorta in deep hypothermic circulatory arrest, and in the oldest, aged 88 years, surgery was limited to wrapping of the ascending aorta as an on-pump beating salvage procedure. RESULTS: Four (80%) of 5 patients survived and were discharged after an intensive care unit stay of 17.45 ± 15.98 days and a hospital stay of 26.0 ± 10.98 days. Mortality was 20%. All survivors were discharged with appropriate rehabilitation potential and without lasting neurological disabilities.

Impact of T-cell-mediated immune response on xenogeneic heart valve transplantation: short-term success and mid-term failure.

OBJECTIVES: Allogeneic frozen cryopreserved heart valves (allografts or homografts) are commonly used in clinical practice. A major obstacle for their application is the limited availability in particular for paediatrics. Allogeneic large animal studies revealed that alternative ice-free cryopreservation (IFC) results in better matrix preservation and reduced immunogenicity. The objective of this study was to evaluate xenogeneic (porcine) compared with allogeneic (ovine) IFC heart valves in a large animal study. METHODS: IFC xenografts and allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks. Immunohistochemistry, ex vivo computed tomography scans and transforming growth factor-ß release profiles were analysed to evaluate postimplantation immunopathology. In addition, near-infrared multiphoton imaging and Raman spectroscopy were employed to evaluate matrix integrity of the leaflets. RESULTS: Acellular leaflets were observed in both groups 1 week after implantation. Allogeneic leaflets remained acellular throughout the entire study. In contrast, xenogeneic valves were infiltrated with abundant T-cells and severely thickened over time. No collagen or elastin changes could be detected in either group using multiphoton imaging. Raman spectroscopy with principal component analysis focusing on matrix-specific peaks confirmed no significant differences for explanted allografts. However, xenografts demonstrated clear matrix changes, enabling detection of distinct inflammatory-driven changes but without variations in the level of transforming growth factor-ß. CONCLUSIONS: Despite short-term success, mid-term failure of xenogeneic IFC grafts due to a T-cell-mediated extracellular matrix-triggered immune response was shown.

Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation.

RATIONALE: Human cardiac mesenchymal cells (CMSCs) are a therapeutically relevant primary cell population. Diabetes mellitus compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. OBJECTIVE: To investigate the role of α-ketoglutarate (αKG) in the epimetabolic control of DNA demethylation in CMSCs. METHODS AND RESULTS: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing, and gene-specific GC methylation detection revealed an accumulation of 5-methylcytosine, 5-hydroxymethylcytosine, and 5-formylcytosine in the genomic DNA of human CMSCs isolated from diabetic donors. Whole heart genomic DNA analysis revealed iterative oxidative cytosine modification accumulation in mice exposed to high-fat diet (HFD), injected with streptozotocin, or both in combination (streptozotocin/HFD). In this context, untargeted and targeted metabolomics indicated an intracellular reduction of αKG synthesis in diabetic CMSCs and in the whole heart of HFD mice. This observation was paralleled by a compromised TDG (thymine DNA glycosylase) and TET1 (ten-eleven translocation protein 1) association and function with TET1 relocating out of the nucleus. Molecular dynamics and mutational analyses showed that αKG binds TDG on Arg275 providing an enzymatic allosteric activation. As a consequence, the enzyme significantly increased its capacity to remove G/T nucleotide mismatches or 5-formylcytosine. Accordingly, an exogenous source of αKG restored the DNA demethylation cycle by promoting TDG function, TET1 nuclear localization, and TET/TDG association. TDG inactivation by CRISPR/Cas9 knockout or TET/TDG siRNA knockdown induced 5-formylcytosine accumulation, thus partially mimicking the diabetic epigenetic landscape in cells of nondiabetic origin. The novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of αKG dehydrogenase, increased the αKG level in diabetic CMSCs and in the heart of HFD and streptozotocin mice eliciting, in HFD, DNA demethylation, glucose uptake, and insulin response. CONCLUSIONS: Restoring the epimetabolic control of DNA demethylation cycle promises beneficial effects on cells compromised by environmental metabolic changes.

Restrictive surgical approach to palliate angina in a patient with coronary three vessel disease and biventricular metastatic hepatocellular carcinoma.

BACKGROUND: Metastatic cardiac tumors may cause different symptoms including angina, symptoms of heart failure and/or arrhythmia. In patients with concomitant coronary artery disease, it may be difficult to distinguish between angina caused by metastases to the heart, for example, by stealing perfusion from the coronary arteries, and angina caused by coronary stenosis. Identifying the origin of the symptoms is, however, essential for designing appropriate surgical strategies. CASE PRESENTATION: A 69-year-old male with multifocal recurrence of a hepatocellular carcinoma (HCC) presented with increasing ventricular arrhythmia and angina several weeks after posterior myocardial infarction and PCI of the RCA culprit lesion during which two further lesions present in the distal RCX and a posterolateral branch, and a chronically occluded LAD had not been addressed. MRI showed a large metastatic tumor infiltrating the walls of both ventricles as well as the interventricular septum. His debilitating symptoms were attributed to steal phenomena and/or perivascular compression caused by the metastatic tumor rather than the remaining coronary lesions, and he was offered a restrictive surgical approach consisting of debulking of the metastasis with an option for subsequent coronary intervention. The palliative surgical procedure resulted in a reduction of the tumor mass by half and sufficiently reduced the patient's symptoms so that further coronary intervention was not required. CONCLUSIONS: Palliative surgery for metastases to the heart may benefit patients, provided that the origin of symptoms is identified correctly. It goes without saying that in a palliative setting, surgery should be limited to treating symptoms rather than performing extensive procedures addressing, for example, coronary artery or valve disease. Interventional cardiac procedures addressing not only CAD but also valve disease may supplement palliative tumor surgery.

Kinetics of circulating endothelial progenitor cells in patients undergoing carotid artery surgery.

AIM: Endothelial progenitor cells (EPCs) are primitive cells found in the bone marrow and peripheral blood (PB). In particular, the potential of EPCs to differentiate into mature endothelial cells remains of high interest for clinical applications such as bio-functionalized patches for autologous seeding after implantation. The objective of this study was to determine EPCs' kinetics in patients undergoing carotid artery thromboendarterectomy (CTEA) and patch angioplasty. METHODS: Twenty CTEA patients were included (15 male, mean age 76 years). PB samples were taken at 1 day preoperatively, and at 1, 3, and 5 days postoperatively. Flow cytometric analysis was performed for CD34, CD133, KDR, and CD45. Expression of KDR, SDF-1α, and G-CSF was analyzed by means of enzyme-linked immunosorbent assay. RESULTS: Fluorescence-activated cell sorting analysis revealed 0.031%±0.016% (% of PB mononuclear cells) KDR+ cells and 0.052%±0.022% CD45-/CD34+/CD133+ cells, preoperatively. A 33% decrease of CD45-/CD34+/CD133+ cells was observed at day 1 after surgery. However, a relative number (compared to initial preoperative values) of CD45-/CD34+/CD133+ cells was found on day 3 (82%) and on day 5 (94%) postoperatively. More profound upregulated levels of CD45-CD34+/CD133+ cells were observed for diabetic (+47% compared to nondiabetic) and male (+38% compared to female) patients. No significant postoperative time-dependent differences were found in numbers of KDR+ cells and the concentrations of the cytokines KDR and G-CSF. However, the SDF-1α levels decreased significantly on day 1 postoperatively but returned to preoperative levels by day 3. CONCLUSION: CTEA results in short-term downregulation of circulating EPCs and SDF-1α levels. Rapid return to baseline levels might indicate participation of EPCs in repair mechanisms following vascular injury.

Influence of hypothermia and subsequent rewarming upon leukocyte-endothelial interactions and expression of Junctional-Adhesion-Molecules A and B.

Patients with risks of ischemic injury, e.g. during circulatory arrest in cardiac surgery, or after resuscitation are subjected to therapeutic hypothermia. For aortic surgery, the body is traditionally cooled down to 18 °C and then rewarmed to body temperature. The role of hypothermia and the subsequent rewarming process on leukocyte-endothelial interactions and expression of junctional-adhesion-molecules is not clarified yet. Thus, we investigated in an in-vitro model the influence of temperature modulation during activation and transendothelial migration of leukocytes through human endothelial cells. Additionally, we investigated the expression of JAMs in the rewarming phase. Exposure to low temperatures alone during transmigration scarcely affects leukocyte extravasation, whereas hypothermia during treatment and transendothelial migration improves leukocyte-endothelial interactions. Rewarming causes a significant up-regulation of transmigration with falling temperatures. JAM-A is significantly modulated during rewarming. Our data suggest that transendothelial migration of leukocytes is not only modulated by cell-activation itself. Activation temperatures and the rewarming process are essential. Continued hypothermia significantly inhibits transendothelial migration, whereas the rewarming process enhances transmigration strongly. The expression of JAMs, especially JAM-A, is strongly modulated during the rewarming process. Endothelial protection prior to warm reperfusion and mild hypothermic conditions reducing the difference between hypothermia and rewarming temperatures should be considered.

Percutaneous SAPIEN S3 Transcatheter Valve Implantation for Post-Left Ventricular Assist Device Aortic Regurgitation.

Aortic regurgitation was found to develop in a considerable share of patients supported with continuous flow left ventricular assist devices (LVADs). The resulting circulatory loop renders LVAD operation inefficient so that symptoms of heart failure develop in spite of high LVAD flows. In patients with a high reoperative risk, transcatheter aortic valve implantation may be considered as an alternative to reoperative valve surgical procedures. We report a case of percutaneous transcatheter aortic valve implantation using the SAPIEN S3 (Edwards Lifesciences, Inc, Irvine, CA) valve for post-LVAD aortic regurgitation.

Associated risk of recombinant activated factor VIIa application.

BACKGROUND: The recombinant human coagulation FVIIa was approved for the treatment of bleeding in hemophilia patients. The reports of a good hemostatic effect were followed by studies and applications without a regulatory extension of the therapeutic indication (off-label use). The aim of this retrospective study is the evaluation of thromboembolic adverse events and side effects in a large cohort of patients with FVIIa therapy. METHODS: In the period from January 2009 to March 2011, a total of 143/2453 (5.8%) cardiac surgical patients (69% male; age 67 ± 11 years; 39% thoracic aorta) were treated with different doses (mean, 6.1 mg; range, 1 to 27.2 mg) of factor VIIa. The administration of FVIIa was seen as a last therapeutic option and administered at the end of the treatment algorithm for severe bleeding. RESULTS: Due to an acute bleeding situation in 143 patients, 7.9 ± 5.8 units of packed red blood cells, 9.5 ± 6.1 units of fresh frozen plasma, 1740 ± 1860 IU PPSB (Prothrombin-Proconvertin-Stuart Factor-Antihemophilic Factor B), 5.6 ± 4 g fibrinogen, and 7.9 ± 7.6 units of platelets were administered. A re-thoracotomy was necessary, despite maximal procoagulant therapy, in 55% of patients. The in-hospital mortality was 36% (51/2453 = 2%). Thrombotic complications occurred with a frequency of 16% (mesenteric infarction, n = 9; stroke/transient ischemic attack, n = 3; myocardial infarction, n = 3; other, n = 8). CONCLUSION: The proof of direct causality of the events in relation to the administration of FVIIa is difficult because the temporal and therapeutic relationships with concomitant vasoconstrictive and procoagulant therapies were not obvious. However, there remains a suspicion that a higher rate of mesenteric infarctions may be provoked by the administration of FVIIa.

Application of intravascular dissection devices for closed chest coronary sinus lead extraction: an interdisciplinary approach.

BACKGROUND: Increasing application of cardiac resynchronization therapy is accompanied by an increase in patients requiring removal of coronary sinus (CS) leads. The aim of this study was to determine outcomes of closed chest CS lead extraction using intravascular dissection devices. METHODS: Between 2000 and 2011, 41 patients (80.5% men; aged 64.2±13.8 years) underwent transvenous CS lead extraction procedures. Reasons for lead extraction were infection in 9, CS lead dislodgement in 15, lead malfunction, including manufacturer-initiated product recall in 6, phrenic nerve stimulation in 5, combinations of causes in 5, and elective extraction concomitant with generator replacement for battery depletion in 1. RESULTS: In addition to 24 isolated CS lead extractions, we performed 17 multiple lead extractions (2 to 4 leads) after a mean of 30.6±32.5 months. The time elapsed from implantation was 4.6±9.1 months for isolated CS and 42.6±32.4 months for multiple lead extractions. Extraction by direct manual traction was feasible in 13 patients by locking stylets in 6. Escalation to mechanical sheaths was required in 17 patients and to electrosurgical sheaths in 5. More aggressive methods were associated with longer implantation times and positive infection status. No deaths or major periprocedural complications occurred. Six minor postprocedural complications, of which three were surgically related, occurred in 5 patients. CONCLUSIONS: Closed chest CS lead extraction can be safely performed with excellent results. We recommend an escalating approach from isolated manual traction over locking stylets to mechanical sheaths and, eventually, electrosurgical dissection devices. The application in mainly high-risk patients demands an interdisciplinary approach to enhance safety and limit morbidity and death.