Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model.

Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups. For the apex removal groups, each piglet was subjected to a partial wall thickness resection (~30% of the ventricular wall thickness). Heart muscle function was assessed via transthoracic echocardiograms; the seven-day surgery group experienced a decrease in ejection fraction and fractional shortening. Upon gross necropsy, for piglets euthanized four weeks post-surgery, all 0-day-old hearts showed no signs of scarring or any indication of the induced injury. Histological analysis confirmed that piglets in the 0-day surgery group exhibited various degrees of regeneration, with half of the piglets showing full regeneration and the other half showing partial regeneration. However, each piglet in the seven-day surgery group demonstrated epicardial fibrosis along with moderate to severe dissecting interstitial fibrosis, which was accompanied by an abundant collagenous extracellular matrix as the result of a scar formation in the resection site. Histology of one 0-day apex resection piglet (briefly lain on and accidentally killed by the mother sow three days post-surgery) revealed dense, proliferative mesenchymal cells bordering the fibrin and hemorrhage zone and differentiating toward immature cardiomyocytes. We further examined the heart explants at 5-days post-surgery (5D PO) and 1-week post-surgery (1W PO) to assess the repair progression. For the 0-day surgery piglets euthanized at 5D PO and 1W PO, half had abundant proliferating mesenchymal cells, suggesting active regeneration, while the other half showed increased extracellular collagen. The seven-day surgery piglets euthanized at 5D PO, and 1W PO showed evidence of greatly increased extracellular collagen, while some piglets had proliferating mesenchymal cells, suggesting a regenerative effort is ongoing while scar formation seems to predominate. In short, our qualitative findings suggest that the piglets lose the full myocardial regenerative potential by 7 days after birth, but greatly preserve the regenerative potential within 1 day post-partum.

The first 200 septal myectomies: Ensuring gold standard outcomes.

OBJECTIVES: Septal myectomy remains the gold standard treatment for symptomatic left ventricular outflow tract obstruction refractory to medical treatment. It is recommended that this operation be performed in dedicated hypertrophic obstructive cardiomyopathy centres by experienced surgeons. The septal myectomy option remains unavailable to many patients based solely on geography, including those who would clearly benefit more substantially from surgery than other therapeutic options. Here, we share our experience in starting new hypertrophic cardiomyopathy programmes. METHODS: We retrospectively reviewed initial septal myectomy experiences at two hypertrophic cardiomyopathy programmes starting in 2014. RESULTS: Two-hundred septal myectomies were performed. Mean age was 58.8 years and 51% were females. Advanced heart failure symptoms were present in 95.5% of patients and 23.5% had experienced syncope. Mean maximal intraventricular gradient was 89 mmHg and 48.5% underwent concomitant procedures at the time of septal myectomy. There was no perioperative (in-hospital or 30 days) mortality. Ninety-two per cent had provoked left ventricular gradients of ≤ 15 mmHg and 97% had none/mild mitral regurgitation at post-operative assessment. In our contemporary cohort, there were 2 (1%) intraoperative ventricular septal defects and 5% required a permanent pacemaker. CONCLUSIONS: Our early septal myectomy experience targeted a complex population, frequently in need of concomitant procedures. Abolition of left ventricular obstruction and resolution of systolic anterior motion mediated mitral regurgitation can be expected. The safety and efficacy of septal myectomy carried at hypertrophic cardiomyopathy centres by properly trained surgeons achieved the desired outcomes established by recent hypertrophic cardiomyopathy guidelines.

Effects of COVID-19 pandemic on cardiac surgery practice in 61 Hospitals worldwide: results of a survey.

BACKGROUND: The aim of this study was to investigate the impact of COVID-19 infection on cardiac surgery community and practice. METHODS: A 43-question survey was sent to cardiac surgery centers worldwide. The survey analyzed the prepandemic organization of the center, the center's response to Covid-19 in terms of re-organization pathways, surveillance methods, personal-protective equipment (PPE), and allowed surgical practice with results. RESULTS: Sixty-one out of 64 centers (95.3%) fulfilled the survey. One third of ICUs were transformed into COVID-19 dedicated-ICUs and one-third moved to another location inside the hospital. Negative-pressure rooms were available in 60.6% centers. Informative measures from hospital administration were received after the first COVID-19 admitted case in 36.1% and during the spread of the infection inside the hospital in 19.6%. Inadequate supply of PPE was common, with no COVID-surveillance of the medical personnel in 4.9% of centers. COVID-19 infected 7.4% of staff surgeons, 8.3% of residents and 9.5% of anesthetists. Cardiac surgery caseload declined in 93.4% centers. COVID-19 infection in patients receiving cardiac surgery resulted in 41-50% mortality in 9.5% centers, and 91-100% mortality in 4.7% centers. Successful weaning with survival from veno-venous extra corporeal membrane oxygenation (ECMO) and veno-arterial ECMO was <50% in 79.2% and 80.0% centers respectively. COVID-19 infection in transplanted patients was rare, with a reported mortality of 0.5% and 1% in one center each. CONCLUSIONS: There is room for improvement in hospital surveillance, informative measures and PPE to the personnel. These measurements will reduce current spread of COVID-19 infection among medical personnel and patients, helping the rump up of cardiac surgical practice.

Incidence and variables associated with 30-day mortality after lung transplantation.

BACKGROUND: With the introduction of the lung allocation score (LAS), sicker patients are prioritized for lung transplantation (LT). There is a lack of data regarding variables independently associated with 30-day mortality after LT. METHODS: We queried the UNOS database for adult patients undergoing LT between 1989 and 2014. Patients with dual organ or previous transplantation and those with missing survival data were excluded. Mortality during the first 30 days after LT was the primary outcome variable. RESULTS: The yearly trends indicate a statistically significant reduction in the 30-day mortality during the study period (P < 0.001, overall mortality: 5.5%) which has continued in the post-LAS era (P = 0. 014, overall mortality: 3.6%). Among patients with 30-day mortality, "primary non-function" (n = 118, 72.8%) was reported as the most common etiology. Transplant indication of vascular diseases, history of non-transplant cardiac or lung surgery, mean pulmonary pressures >35 mm Hg, disabled functional status, ECMO support, high LAS, ischemic time >6 hours, and blunt injury as the mechanism of donor death are independently associated with 30-day mortality. CONCLUSION: The incidence of early mortality after LT continues to decline in the post-LAS era. Apart from the mechanism of donor death and ischemic time, early mortality appears to be primarily driven by the recipient characteristics.

Robotic-assisted microvascular surgery: skill acquisition in a rat model.

Microsurgery is a technically demanding field with long learning curves. Robotic-assisted microsurgery has the ability to decrease these learning curves. We, therefore, sought to assess the feasibility of robotic-assisted microvascular surgery in a rat model, and whether this could be translated into a worthwhile skills acquisition exercise for residents. Twenty-eight rats underwent microvascular anastomosis. Procedures were performed by a trained microvascular surgeon with no robotic experience (n = 14), or a trained robotic surgeon with no microvascular experience (n = 14). Anesthetized rats were subjected to complete transection and end-to-end anastomosis of the abdominal aorta using 10-0 prolene. Manually (n = 6) and robotic-assisted (n = 8) procedures were performed by both surgeons. A successful procedure required a patent anastomosis and no bleeding. After approximately 35 days, angiography and histopathological studies of the anastomoses were performed. Median times for robotic-assisted anastomoses were 37.5 (34.2-42.7) min for the microsurgeon and 38.5 (32.7-52) min for robotic surgeon. In the manual group, it took 17 (13.5-23) min for microsurgeon and 44 (34.5-60) min for robotic surgeon. Within the robotic-assisted group, there was a trend toward improvement in both surgeons, but greater in the microsurgeon. Robotic-assisted microvascular anastomosis in a rat model is a feasible skill acquisition exercise. By eliminating the need for a skilled microsurgical assistant, as well as, improved microsurgical technology, the robotic system may prove to be a crucial player in future microsurgical skill training.

Implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: an updated systematic review and meta-analysis of outcomes and complications.

BACKGROUND: Since the introduction of the implantable cardioverter-defibrillator (ICD) in patients with hypertrophic cardiomyopathy (HCM), the incidence of sudden cardiac death (SCD) has been significantly reduced. Given its widespread use, it is important to identify the outcomes associated with ICD use in patients with HCM. The present paper is a systematic review and meta-analysis of the rates of appropriate and inappropriate interventions, mortality, and device complications in HCM patients with an ICD. METHODS: We conducted a systematic review and meta-analysis on 27 studies reporting outcomes and complications after ICD implantation in patients with HCM. ICD interventions, device complications, and mortality were extracted for analysis. RESULTS: A total of 3,797 patients with HCM and ICD implantation were included (mean age, 44.5 years; 63% male), of which 83% of patients had an ICD for primary prevention of SCD. The cardiac mortality was 0.9% (95% CI: 0.7-1.3) per year and non-cardiac mortality was 0.8% (95% CI: 0.6-1.2) per year. Annualized appropriate intervention rate was 4.8% and annualized inappropriate intervention was 4.9%. The annual incidence of lead malfunction, lead displacement and infection was 1.4%, 1.3%, and 1.1%, respectively. CONCLUSIONS: ICD use in patients with HCM produces low rates of cardiac and non-cardiac mortality, and an appropriate intervention rate of 4.8% per year. However, moderate rates of inappropriate intervention and device complications warrant careful patient selection in order to optimize the risk to benefit ratio in this select group of patients.

Septal myectomy after failed septal alcohol ablation.

Despite septal myectomy remaining the gold standard septal reduction therapy for hypertrophic obstructive cardiomyopathy (HOCM), there has been a disproportionate use of alcohol septal ablation (ASA) worldwide. Absolute resolution of left ventricular outflow tract (LVOT) obstruction with ASA is not achieved in a substantial proportion of patients. The mechanisms of failure from ASA are partially understood and described. Residual obstruction in hypertrophic cardiomyopathy is associated with worse clinical outcomes and mortality. There is a growing number of patients who present with significant residual gradients after ASA and require a rescue septal myectomy operation, which then carries an increased risk of perioperative complications and life-long sequelae. This contrasts with the excellent outcomes achieved by septal myectomy without previous percutaneous intervention. Despite complete resolution of obstruction in rescue myectomy, the outcomes remain compromised by the prior ASA.

Transaortic septal myectomy: techniques and pitfalls.

Hypertrophic cardiomyopathy (HCM) is the most common congenital cardiac disease, affecting up to 1 in 200 individuals. When it causes left ventricular outflow tract (LVOT) obstruction, treatment is indicated to reduce symptoms and the risk of sudden cardiac death. Pharmacologic therapy is the first line treatment, however if it fails, surgical myectomy or percutaneous ablation of the hypertrophic myocardium are the standard therapies to eliminate subaortic obstruction. Both surgical myectomy and percutaneous ablation have been demonstrated as safe and effective treatments; however, myectomy is the gold standard with a significantly lower complication rate and more complete and longstanding reduction of LVOT obstruction.

Open Aortic Arch Reconstruction After Coronary Artery Bypass Surgery: Worth the Effort?

Open aortic arch surgery after coronary artery bypass grafting (CABG) is considered a high-risk operation. We reviewed our surgical approach and outcomes to establish the risk profile for this patient population. In methods, from 2000-2014, 650 patients underwent aortic arch surgery with circulatory arrest. Of these, 45 (7%) had previous CABG. Complete medical record was available for review including all preoperative coronary angiograms and detailed management of myocardial protection. In results, the mean interval from previous CABG to aortic arch surgery was 6.8 ± 7.1 years. At reoperation, 33 (73%) patients had hemiarch replacement and 12 (27%) had a total arch replacement. The following were the indications for surgery: fusiform aneurysm in 20 (44%), pseudoaneurysm in 6 (13%), endocarditis in 4 (9%), valvular disease in 5 (11%), and acute aortic dissection in 10 (22%). There were 6 perioperative deaths (13%) and 1 stroke (2.2%). Selective antegrade cerebral perfusion was used in 13 patients (28.9%) and retrograde perfusion in 6 (13.3%). Survival was 74%, 65%, and 52% at 1, 3, and 5-year follow-up, respectively. Only predictors of early mortality were age (odds ratio = 1.20, CI: 1.01-1.44; P = 0.04) and nonuse of retrograde cardioplegia for myocardial protection (odds ratio = 6.80, CI: 1.06-43.48; P = 0.04). Intermediate survival of these patients was significantly lower than those of a sex-matched and age-matched population (P < 0.001). In conclusion, aortic arch surgery after previous CABG can be performed with acceptable early and midterm results and low risk of stroke. Perfusion strategies and myocardial protection contribute to successful outcomes.

Heart Xenotransplantation: Historical Background, Experimental Progress, and Clinical Prospects.

If pig hearts could be transplanted successfully into patients with end-stage cardiac failure, the critical shortage of hearts from deceased human donors would be overcome. The several attempts at cardiac xenotransplantation carried out in the 20th century, usually with hearts from nonhuman primates (NHPs), are reviewed, as are the surgical techniques used in experimental heart transplantation in animals. For a number of reasons, the pig has been selected as the potential source of organs for clinical transplantation. The major pathobiological barriers that the pig presents, and progress in overcoming these barriers either by genetic engineering of the pig or by the administration of novel immunosuppressive agents, are described. Currently, non-life-supporting pig heterotopic heart transplantation in NHPs has extended to more than 2 years in 1 case, with life-supporting orthotopic heart transplantation of almost 2 months. Future approaches to resolve the remaining problems and the selection of patients for the initial clinical trials are briefly discussed.

Intraoperative Epiaortic Ultrasound for Traumatic Pseudoaneurysm of the Ascending Aorta.

Epiaortic ultrasound is an imaging modality that is commonly used to evaluate the ascending aorta for atheroma and other mural lesions during elective cardiac surgery. Its use in contained aortic rupture has not been established. We present a case of thoracic trauma with contained pseudoaneurysm of the ascending aorta. At operation, the precise location of the aortic tear could not be identified by visual inspection, manual palpation, or transesophageal echocardiography. Epiaortic ultrasound was employed and the aortic defect was identified and successfully repaired. This intraoperative imaging modality may play an increasing role in the identification of aortic pathology when visual inspection and other intraoperative imaging is insufficient.

Aortic arch surgery after previous type A dissection repair: results up to 5 years.

OBJECTIVES: Open aortic arch surgery after type A dissection repair is challenging. We sought to review our surgical experience to analyse the causes and timing, establish the risk profile for this patient population, and better define outcomes. METHODS: From 2000 to 2014, we identified 55 patients who required aortic arch surgery after a previous type A dissection repair. Medical records were available for review including computerized tomographic angiograms, cerebral protection strategies and follow-up. RESULTS: The mean interval from previous type A dissection repair to aortic arch surgery was 5.7 ± 5.4 years. At reoperation 36 patients (65%) had total arch replacement and 19 (35%) had hemiarch replacement. Indications for reoperations were: enlarging aneurysm in 27 (49%), impending rupture in 12 (22%), chronic dissection in 10 (18%) and aneurysms in 6 (11%). Arterial peripheral cannulation was used in 80% of patients. Selective antegrade cerebral perfusion was used in 35 patients (64%) and retrograde perfusion in 2 (4%). There were 3 perioperative deaths (5%) and 4 cases of permanent stroke (7%). Survival rates were 90, 85 and 77% at the 1-, 3- and 5-year follow-up, respectively. The 5-year survival rate was 10% lower than that of an age- and sex-matched population (P < 0.001). The only predictor of the follow-up mortality was older age (odds ratio: 1.07, 95% confidence interval: 1.02-1.13, P = 0.007). CONCLUSIONS: Aortic arch surgery after previous type A dissection repair can be performed with satisfactory early and mid-term results and acceptable risk of stroke. Cerebral perfusion strategies likely contribute to positive outcomes. Favourable mid-term survival justifies performing such difficult reoperations.

Pig-to-baboon heterotopic heart transplantation--exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens.

BACKGROUND: Three costimulation blockade-based regimens have been explored after transplantation of hearts from pigs of varying genetic backgrounds to determine whether CTLA4-Ig (abatacept) or anti-CD40mAb+CTLA4-Ig (belatacept) can successfully replace anti-CD154mAb. METHODS: All pigs were on an α1,3-galactosyltransferase gene-knockout/CD46 transgenic (GTKO.CD46) background. Hearts transplanted into Group A baboons (n=4) expressed additional CD55, and those into Group B (n=3) expressed human thrombomodulin (TBM). Immunosuppression included anti-thymocyte globulin with anti-CD154mAb (Regimen 1: n=2) or abatacept (Regimen 2: n=2) or anti-CD40mAb+belatacept (Regimen 3: n=2). Regimens 1 and 2 included induction anti-CD20mAb and continuous heparin. One further baboon in Group B (B16311) received a modified Regimen 1. Baboons were followed by clinical/laboratory monitoring of immune/coagulation parameters. At biopsy, graft failure, or euthanasia, the graft was examined by microscopy. RESULTS: Group A baboons survived 15 to 33 days, whereas Group B survived 52, 99, and 130 days, respectively. Thrombocytopenia and reduction in fibrinogen occurred within 21 days in Group A, suggesting thrombotic microangiopathy (TM), confirmed by histopathology. In Group B, with follow-up for >4 m, areas of myofiber degeneration and scarring were seen in two hearts at necropsy. A T-cell response was documented only in baboons receiving Regimen 2. CONCLUSIONS: The combination of anti-CD40mAb+belatacept proved effective in preventing a T-cell response. The expression of TBM prevented thrombocytopenia and may possibly delay the development of TM and/or consumptive coagulopathy.

Short and medium term outcomes of surgery for patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: We report one surgeon's experience of corrective surgery for hypertrophic obstructive cardiomyopathy (HOCM) over a 10-year span and comment on factors that influence longer term outcomes. Septal myectomy (SM) and adjunctive procedures, including shortening of the aorta, a novel technique in HOCM patients, are described. METHODS: Perioperative data were obtained by retrospective review of institutional surgical databases between 2001 and 2011. Review of most recent echocardiogram and clinical status by telephone interview was performed. RESULTS: A total of 211 patients underwent SM for HOCM. There was a bimodal age distribution related to sex; mean age for males and females was 46 ± 13 and 54 ± 14 years, respectively (p < 0.001). Functional New York Heart Association (NYHA) class improved significantly after surgery; 79% were in class III-IV preoperatively and 84% were in class I-II at follow-up (p < 0.001). Sixty percent had angina of Canadian Cardiovascular Society (CCS) grade III-IV preoperatively and 89% were in CCS I-II at follow-up (p < 0.001). There were significant improvements in resting left ventricular outflow tract gradient (64 ± 36 to 5 ± 5 mm Hg, p < 0.001), right ventricular systolic pressure (36 ± 7.3 to 32 ± 8 mm Hg, p < 0.001), left atrial size (4.6 ± 0.7 to 4.3 ± 0.6 cm, p < 0.001), and grade of mitral regurgitation (moderate to severe mitral regurgitation 28% to 3.5%, p < 0.001). In-hospital mortality was 0.5%, 1 year survival 98.6%, and 5-year survival 98.1%. Predictors of worse clinical outcomes were preoperative NYHA and CCS class III-IV (p < 0.001, p = 0.05), new onset atrial fibrillation (p < 0.001), and female sex (p = 0.03). CONCLUSIONS: Septal myectomy in patients with obstructive HOCM offers excellent symptom relief and minimal operative risk.

"The balloon plug concept" for tricuspid valve repair: ex vivo proof of concept.

OBJECTIVE: Functional tricuspid regurgitation (TR) is recognized as a significant cause of morbidity and mortality in cardiothoracic surgery. We hypothesized that a variably expandable, transvalvular balloon mounted on a catheter could be percutaneously inserted and fixed to the right ventricle apex. This novel approach could provide a minimally invasive way to eliminate clinically relevant TR caused by annular dilatation. This study was performed to test the ex vivo hemodynamic effects and the feasibility of the "balloon plug concept." METHODS: Twenty harvested calf tricuspid valves were placed in a mechanical simulator. Tricuspid regurgitation was created by annular stretching and displacement of the papillary muscles so as to create central TR. A flexible catheter with a 4-cm-long, soft, fusiform balloon was positioned across the valve so that the balloon was suspended centrally across the valve annular plane. After activating the mechanical ventricle, data were collected with balloon inflation volumes of saline from 5 to 20 mL. Transvalvular pressure gradients and leaflet mechanics were evaluated with incremental inflation. RESULTS: In all cases, 5-mL inflation did not significantly reduce TR and 20-mL inflation caused obstruction to antegrade flow (mean transvalvular gradient > 4 mm Hg). Inflation between 10 and 15 mL caused significant reduction in TR with acceptable transvalvular gradients (<3 mm Hg). CONCLUSIONS: The balloon plug concept showed promising ex vivo hemodynamic results. In vivo investigations are warranted to evaluate percutaneous techniques, thrombogenicity, and effects of repeated balloon-leaflet contact on valve integrity.

Open aortic arch reconstruction after previous cardiac surgery: outcomes of 168 consecutive operations.

OBJECTIVE: Open arch interventions after previous cardiac surgery are considered high risk. We reviewed our outcomes in patients requiring aortic arch reconstruction after previous cardiovascular surgery. METHODS: From March 2000 to March 2014, the data from 168 patients with previous sternotomy requiring aortic arch replacement were reviewed. The indications for surgery, perioperative data, and outcomes of reoperation were analyzed. RESULTS: The mean age was 61 ± 14 years, and 119 were men (70%). The indications for reoperation were aneurysm (57%), valvular disease (13%), impending rupture (12%), aortic dissection (9.0%), and endocarditis (7.7%). The median time from the previous operation to reoperation was 7 years. The mean aortic diameter was 55 mm. Total or partial arch replacement was performed in 38% and 62% of patients, respectively. Fifty-five patients (32.7%) had undergone previous ascending dissection repair and 45 (26.8%) had previous coronary bypass surgery. Deep hypothermic circulatory arrest was used in all. Selective cerebral perfusion was used in 39% and retrograde cerebral perfusion in 14%. The incidence of permanent stroke was 5.4%. Operative mortality (30-day) was 8.3%. Older age (odds ratio, 1.05; 95% confidence interval, 1.00-1.10; P = .04), New York Heart Association class III/IV (odds ratio, 3.15; 95% confidence interval, 1.01-9.86; P = .04), and extracorporeal circulation time (odds ratio, 1.01; 95% confidence interval, 1.00-1.02; P = .001) were predictors of perioperative death. The median follow-up was 3.0 years. Survival was 85%, 78%, and 68% at 1, 3, and 5 years, respectively. CONCLUSIONS: Reoperations to address the aortic arch have acceptable mortality and morbidity. Open repair under circulatory arrest is the benchmark to which endovascular therapies should be compared.

Outcomes of surgical aortic valve replacement: the benchmark for percutaneous therapies.

Historically, many patients with severe senile calcific aortic valve stenosis (AS) were not offered surgery, largely due to the perception that the risks of operation were prohibitive. Such patients have subsequently been formally designated as 'high risk' or 'inoperable' with respect to their suitability for surgical aortic valve replacement (SAVR) in the evolving lexicon of heart valve disease. The recent availability of transcatheter aortic valve replacement (TAVR) represents an alternative treatment option, and permits the opportunity to re-examine algorithms for assessing operative risk. As the experience with TAVR grows, expanded use in new patient populations can be anticipated. While TAVR in high risk AS patients has demonstrated benefits, the emerging indication in intermediate AS is less clear and conclusions will necessarily await the availability of results from ongoing clinical trials. This article will discuss current outcomes for SAVR among high- and intermediate-risk patients with AS as a barometer in assessing the results of nascent percutaneous therapies.