Pearls and Pitfalls of Epicardial Echocardiography for Implantation of Impella CP Devices in Ovine Models.

The Impella CP is a percutaneously inserted temporary left ventricular assist device used in clinical practice and in translational research into cardiogenic shock, perioperative cardiac surgery, acute cardiac failure and mechanical circulatory support. Fluoroscopic guidance is usually used for insertion of an Impella, thus limiting insertion to within catheterization laboratories. Transthoracic, transoesophageal and intracardiac echocardiography have been reported to guide Impella CP implantation with identified specific limitations stemming from the surgical, anatomical and equipment factors. We conducted translational prospective descriptive feasibility investigation as a part of two other hemodynamic Impella studies. It showed the successful application of epicardial echocardiographic scanning for implantation of Impella CP devices in ovine models, from which details of the technique and identified pitfalls are described with practical solutions for future investigators and clinicians. Many described findings are relevant to any other echocardiographic techniques when adequate imaging of the Impella and relevant anatomical structures is achievable.

Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias.

Preclinical data have confirmed that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can remuscularize the injured or diseased heart, with several clinical trials now in planning or recruitment stages. However, because ventricular arrhythmias represent a complication following engraftment of intramyocardially injected PSC-CMs, it is necessary to provide treatment strategies to control or prevent engraftment arrhythmias (EAs). Here, we show in a porcine model of myocardial infarction and PSC-CM transplantation that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. Two unique surface marker signatures, signal regulatory protein α (SIRPA)+CD90-CD200+ and SIRPA+CD90-CD200-, identify arrhythmogenic and non-arrhythmogenic cardiomyocytes, respectively. Our data suggest that modifications to current PSC-CM-production and/or PSC-CM-selection protocols could potentially prevent EAs. We further show that pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias.

Preventing Sheep Carotid Artery Spasm for Vascular Graft Surgery and Computed Tomography Angiography.

The development of small-diameter vascular grafts requires testing in large animal models before advancing to clinical trials. Vascular graft interposition implantation in sheep carotid arteries (CAs) is the most widely used model, but ovine CAs are prone to severe spasm following surgical manipulation, potentially impairing graft performance assessment. There is paucity in the literature on reducing sheep CA spasm using effective vasodilator therapeutic protocols. In this study, four healthy Merino cross White Suffolk wethers (1-2 years, 52.1 ± 0.8 kg) underwent CT angiography and CA graft surgery. CT angiography using iodinated contrast agent was performed with innominate artery access through the CA or ascending aortic arch access through the femoral artery. Sheep then underwent right CA sham surgery or left CA vascular graft implantation. A variety of vasodilators, including papaverine, sodium nitroprusside, verapamil, and their combination, were tested for preventing or treating CA spasms intraoperatively. Blood flow was reassessed immediately after CA surgery using CT angiography. The results showed that innominate artery access through the CA for CT angiography in sheep induced presurgical CA spasm with reduced arterial flow. Conversely, ascending aortic arch access through the femoral artery for CT angiography did not cause CA spasm and maintained arterial flow. During CA graft surgery, surgical trauma induced CA spasm, which was prevented by localized intra-arterial administration of vasodilators papaverine hydrochloride and verapamil before significant surgical manipulation.

Variation in colorectal cancer treatment and outcomes in Scotland: real world evidence from national linked administrative health data.

Background: Colorectal cancer (CRC) is the fourth most common type of cancer in the United Kingdom and the second leading cause of cancer death. Despite improvements in CRC survival over time, Scotland lags behind its UK and European counterparts. In this study, we carry out an exploratory analysis which aims to provide contemporary, population level evidence on CRC treatment and survival in Scotland. Methods: We conducted a retrospective population-based analysis of adults with incident CRC registered on the Scottish Cancer Registry (Scottish Morbidity Record 06 (SMR06)) between January 2006 and December 2018. The CRC cohort was linked to hospital inpatient (SMR01) and National Records of Scotland (NRS) deaths records allowing a description of their demographic, diagnostic and treatment characteristics. Cox proportional hazards regression models were used to explore the demographic and clinical factors associated with all-cause mortality and CRC specific mortality after adjusting for patient and tumour characteristics among people identified as early-stage and treated with surgery. Results: Overall, 32,691 (73%) and 12,184 (27%) patients had a diagnosis of colon and rectal cancer respectively, of whom 55% and 53% were early-stage and treated with surgery. Five year overall survival (CRC specific survival) within this cohort was 72% (82%) and 76% (84%) for patients with colon and rectal cancer respectively. Cox proportional hazards models revealed significant variation in mortality by sex, area-based deprivation and geographic location. Conclusions: In a Scottish population of patients with early-stage CRC treated with surgery, there was significant variation in risk of death, even after accounting for clinical factors and patient characteristics.

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model.

Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or regenerative strategies. An essential component of drug development is determining how a novel therapeutic is to be administered. Physiologically relevant large animal models are of critical importance in assessing the feasibility and efficacy of various therapeutic delivery strategies. Due to their similarities to humans in cardiovascular physiology, coronary vascular anatomy, and heart weight to body weight ratio, swine is one of the preferred species in the preclinical evaluation of new therapies for myocardial infarction. The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. After percutaneously induced myocardial infarction, female landrace swine received treatment with novel agents through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump. The procedures employed for each technique are reproducible, resulting in reliable cardioactive drug delivery. These models can be easily adapted to suit individual study designs, and each of these delivery techniques can be used to investigate a variety of possible interventions. Therefore, these methods are a useful tool for translational scientists pursuing novel biological approaches in cardiac repair following myocardial infarction.

Splitting the anterior mitral leaflet impairs left ventricular function in an ovine model.

OBJECTIVES: During mitral valve replacement, the anterior mitral leaflet is usually resected or modified. Anterior leaflet splitting seems the least disruptive modification. Reattachment of the modified leaflet to the annulus reduces the annulopapillary distance. The goal of this study was to quantify the acute effects on left ventricular function of splitting the anterior mitral leaflet and shortening the annulopapillary distance. METHODS: In 6 adult sheep, a wire was placed around the anterior leaflet and exteriorized through the left ventricular wall to enable splitting the leaflet in the beating heart. Releasable snares to reduce annulopapillary distance were likewise positioned and exteriorized. A mechanical mitral prosthesis was inserted to prevent mitral incompetence during external manipulations of the native valve. Instantaneous changes in left ventricular function were recorded before and after shortening the annulopapillary distance, then before and after splitting the anterior leaflet. RESULTS: After splitting the anterior leaflet, preload recruitable stroke work, stroke work, stroke volume, cardiac output, left ventricular end systolic pressure and mean pressure were significantly decreased by 26%, 23%, 12%, 9%, 15% and 11%, respectively. Shortening the annulopapillary distance was associated with significant decreases in the end systolic pressure volume relationship, preload recruitable stroke work, stroke work and left ventricular end systolic pressure by 67%, 33%, 15% and 13%, respectively. Shortening the annulopapillary distance after splitting the leaflet had no significant effect. CONCLUSIONS: Splitting the anterior mitral leaflet acutely impaired left ventricular contractility and haemodynamics in an ovine model. Shortening the annulopapillary distance after leaflet splitting did not further impair left ventricular function.

Coronary Artery Bypass Surgery Without Saphenous Vein Grafting: JACC Review Topic of the Week.

Approximately 95% of patients of any age undergoing contemporary, coronary bypass surgery will receive at least 1 saphenous vein graft (SVG). It is recognized that SVG will develop progressive and accelerated atherosclerosis, resulting in a stenosis, and in occlusion that occurs in 50% by 10 years postoperatively. For arterial conduits, there is little evidence of progressive failure as for SVG. Could avoidance of SVG (total arterial revascularization [TAR]) lead to a different late (>5 year) survival? A literature review of 23 studies (N = 100,314 matched patients) at a mean 8.8 years postoperative found reduced all-cause mortality for TAR (HR: 0.77; 95% CI: 0.71-0.84; P < 0.001). An expanded analysis with a new unpublished data set (N = 63,288 matched patients) was combined with the literature review (N = 127,565). It found reduced all-cause mortality for TAR (HR: 0.78; 95% CI: 0.72-0.85; P < 0.001). Additional Bayesian analysis found a very high probability of a TAR-associated reduction all-cause mortality.

Selecting the optimal treatment for left main coronary disease: The importance of identifying subgroups of patients.

Randomized trials of stenting versus surgery for patients with unprotected left main (LM) coronary stenosis have largely shown similar survival between the two interventions. However, patients with LM stenosis represent a heterogeneous group in which subgroups likely to benefit from one therapy more than another are difficult to identify. Increasing coronary disease burden is the most accepted subgrouping for identifying optimal therapy but this can be defined in more detail allowing greater discrimination. Competitive flow reduces bypass graft patency in patients with isolated LM stenosis and complex bifurcation stenoses reduce the effectiveness of coronary stenting. The evidence for LM stenosis subgroupings is presented.

Analogue Mean Systemic Filling Pressure: a New Volume Management Approach During Percutaneous Left Ventricular Assist Device Therapy.

The absence of an accepted gold standard to estimate volume status is an obstacle for optimal management of left ventricular assist devices (LVADs). The applicability of the analogue mean systemic filling pressure (Pmsa) as a surrogate of the mean circulatory pressure to estimate volume status for patients with LVADs has not been investigated. Variability of flows generated by the Impella CP, a temporary LVAD, should have no physiological impact on fluid status. This translational interventional ovine study demonstrated that Pmsa did not change with variable circulatory flows induced by a continuous flow LVAD (the average dynamic increase in Pmsa of 0.20 ± 0.95 mmHg from zero to maximal Impella flow was not significant (p = 0.68)), confirming applicability of the human Pmsa equation for an ovine LVAD model. The study opens new directions for future translational and human investigations of fluid management using Pmsa for patients with temporary LVADs.

The ALLEGRO trial: a placebo controlled randomised trial of intravenous lidocaine in accelerating gastrointestinal recovery after colorectal surgery.

BACKGROUND: Return of gastrointestinal (GI) function is fundamental to patient recovery after colorectal surgery and is required before patients can be discharged from hospital safely. Up to 40% of patients suffer delayed return of GI function after colorectal surgery, causing nausea, vomiting and abdominal discomfort, resulting in longer hospital stay. Small, randomised studies have suggested perioperative intravenous (IV) lidocaine, which has analgesic and anti-inflammatory effects, may accelerate return of GI function after colorectal surgery. The ALLEGRO trial is a pragmatic effectiveness study to assess the benefit of perioperative IV lidocaine in improving return of GI function after elective minimally invasive (laparoscopic or robotic) colorectal surgery. METHODS: United Kingdom (UK) multi-centre double blind placebo-controlled randomised controlled trial in 562 patients undergoing elective minimally invasive colorectal resection. IV lidocaine or placebo will be infused for 6-12 h commencing at the start of surgery as an adjunct to usual analgesic/anaesthetic technique. The primary outcome will be return of GI function. DISCUSSION: A 6-12-h perioperative intravenous infusion of 2% lidocaine is a cheap addition to usual anaesthetic/analgesic practice in elective colorectal surgery with a low incidence of adverse side-effects. If successful in achieving quicker return of gut function for more patients, it would reduce the rate of postoperative ileus and reduce the duration of inpatient recovery, resulting in reduced pain and discomfort with faster recovery and discharge from hospital. Since colorectal surgery is a common procedure undertaken in every acute hospital in the UK, a reduced length of stay and reduced rate of postoperative ileus would accrue significant cost savings for the National Health Service (NHS). TRIAL REGISTRATION: EudraCT Number 2017-003835-12; REC Number 17/WS/0210 the trial was prospectively registered (ISRCTN Number: ISRCTN52352431 ); date of registration 13 June 2018; date of enrolment of first participant 14 August 2018.

Intracardiac Echocardiography for Point-of-Care Guided Left Ventricular Assist Device Implantation: Surgical Implications for COVID-19.

Data from animal models is now available to initiate assessment of human safety and feasibility of wide-angle three-dimensional intracardiac echocardiography (3D ICE) to guide point-of-care implantation of percutaneous left ventricular assist devices in critical care settings. Assessment of these combined new technologies could be best achieved within a surgical institution with pre-existing expertise in separate utilization of ICE and Impella.

Implementation of the Versius robotic surgical system for colorectal cancer surgery: First clinical experience.

BACKGROUND: The Versius surgical system, from CMR Surgical, is the first UK-based robotic platform to become commercially available. This is a prospective series in accordance with the IDEAL development framework for surgical innovation reporting the clinical implementation and initial experience using this robotic platform. METHODS: Patients with colorectal cancer were included. Exclusion criteria included T4 tumours, ultra-low rectal cancer and severe comorbidity (American Society of Anesthesiologists grade ≥ 3). Institutional ethical approval was obtained, and patients were counselled preoperatively with informed consent. Patients underwent colorectal resection using the Versius surgical system. Procedures were anticipated as hybrid operations (laparoscopic/robotic) consistent with a proof of concept/technical feasibility study. RESULTS: Main outcome measures included operative time, complication rates and pathological results. Thirty-two patients (15 men) underwent colorectal cancer resections. The mean age was 68 years (27-85 years). Estimated blood loss was 150 ml; range <100 to <500 ml. For right hemicolectomy, the average operative time was 221 min (183-323 min). The average console time was 111 min (64-213 min). For robotic anterior resection, the total operative time was on average 319 min (222-408 min) with an average console time of 204 min (85-242 min). Eight patients experienced Grade II morbidities (22%) with no serious morbidities and no mortalities. Mean return to bowel function was 2.9 days (1-6 days). The average length of stay was 5.3 days with a median of 4 days (2-20 days). All resections were R0 with an average lymph node yield of 20 nodes (8-46 nodes). CONCLUSION: Our initial experience with Versius demonstrates its safe adoption and implementation for colorectal resections.

Incorporating the anterior mitral leaflet to the annulus impairs left ventricular function in an ovine model.

Objectives: Transcatheter mitral valve prostheses are designed to capture the anterior leaflet and surgical techniques designed to fully preserve the subvalvular apparatus at prosthetic valve insertion both serve to shorten the anterior mitral leaflet height, thus effectively incorporating it into the anterior annulus. This study quantifies the acute effects of incorporating the anterior mitral leaflet into the annulus on left ventricular function. Methods: Fourteen adult sheep (weight, 48.7 ± 6.2 kg) underwent a mechanical mitral valve insertion on normothermic beating-heart cardiopulmonary bypass, with full retention of the native mitral valve but with placement of exteriorized releasable snares around the anterior mitral leaflet. Continuous measurements of left ventricular mechano-energetics were recorded throughout, alternating incorporating and releasing of the anterior mitral leaflet to the mitral annulus. Echocardiography confirmed the incorporation into the annulus and release. Results: The independent indices of left ventricular contractility (ie, end systolic pressure volume relationship and preload recruitable stroke work) were both significantly impaired when the anterior mitral leaflet was incorporated to the annulus and restored after release, as were the hemodynamic parameters: cardiac output, stroke volume, stroke work, and left ventricular pressure decreased by 15%, 17%, 23%, and 11%, respectively. Echocardiography demonstrated increased sphericity of the left ventricle during anterior mitral leaflet incorporation. Conclusions: Incorporating the anterior mitral leaflet to the anterior annulus adversely affected left ventricular contractility, caused distortion of the left ventricle in the form of increased sphericity, and impaired hemodynamic parameters in normal ovine hearts.

Bioprosthetic interstrut distance subtending the preserved anterior mitral leaflet mitigates left ventricular outflow tract obstruction.

Background: The anterior mitral leaflet (AML) contributes to left ventricular (LV) function but is normally excised at the time of a bioprosthetic valve insertion. This study aimed to investigate methods of safely retaining the AML at the time of mitral valve replacement. Methods: Five adult sheep (57 ± 3.8 kg) each underwent 3 insertions of a bioprosthetic mitral valve (asymmetric interstrut sectors) alternating the wide and narrow interstrut distance under the AML. Each insertion was performed on normothermic beating-heart cardiopulmonary bypass, with full retention of the native valve. After each valve insertion, continuous measurements of LV and aortic pressures were recorded with echocardiographic assessment of mitral valve function. If LV outflow tract obstruction (LVOTO) was not seen on the resumption of normal cardiac output, a bolus of adrenaline was given to precipitate it. Results: Thirteen of 15 valve insertions resulted in LVOTO caused by systolic anterior motion (SAM), independent of valve orientation. The wide interstrut distance subtending the AML was associated with a greater requirement for inotropic stress to precipitate an obstruction and was associated with late systolic rather than holosystolic obstruction. Conclusions: The predisposition to and nature of LVOTO due to SAM were associated with the bioprosthetic valve interstrut distance subtending the fully retained AML and may explain the survival differences in such patients. This model represents an effective method for research into prevention of LVOTO following mitral valve replacement with preservation of the native valve.

Radial Artery vs Bilateral Mammary Composite Y Coronary Artery Grafting: 15-Year Outcomes.

BACKGROUND: Total arterial coronary revascularization for three coronary territory disease can be achieved with a second arterial conduit joined to the left internal mammary artery as a Y graft, by using either a radial artery (RAY) or a second mammary artery (BIMAY). METHODS: Patients undergoing total arterial revascularization for three coronary territory disease were identified from two cardiac surgical databases (in Sydney and Melbourne, Australia) using Society of Thoracic Surgeons-based definitions. BIMAY-treated patients underwent surgery between 1994 and 2009, mostly using an age-limited protocol, whereas RAY-treated patients underwent surgery between 1996 and 2003 without age limits. All-cause mortality data were acquired from the national death registry, and survival was estimated by the Kaplan-Meier method. Propensity score matching was performed using 13 variables. Given the age imbalance between the groups, the primary comparison was performed for age 66 years or younger. RESULTS: Overall, 1896 patients underwent RAY procedures, and 720 patients underwent BIMAY operations. Older age at surgery was the strongest independent predictor of mortality, with a hazard ratio of 2.06, and a 95% confidence interval of 1.93, 2.22 (P < .001). After propensity score matching, we identified 299 pairs of patients 66 years of age or younger with no preoperative or operative differences and similar ages at surgery: RAY 56.4 ± 7.0 years of age vs BIMAY 56.4 ± 6.8 years of age (P = .96). The RAY group had 4.0 ± 0.9 grafts, and the BIMAY group had 3.9 ± 0.9 grafts (P = .814). All-cause mortality was not different, with the proportion surviving at 15 years at 74.9% for the RAY group vs 76.2% for the BIMAY group (P = .211). CONCLUSIONS: Survival was not different between the RAY and BIMAY groups for total arterial revascularization of three coronary territory bypass grafting.

Implantation of Impella CP left ventricular assist device under the guidance of three-dimensional intracardiac echocardiography.

Impella CP is a percutaneously inserted left ventricular assist device indicated for temporary mechanical cardiac support during high risk percutaneous coronary interventions and for cardiogenic shock. The potential application of Impella has become particularly relevant during the current COVID-19 pandemic, for patients with acute severe heart failure complicating viral illness. Standard implantation of the Impella CP is performed under fluoroscopic guidance. Positioning of the Impella CP can be confirmed with transthoracic or transoesophageal echocardiography. We describe an alternative approach to guide intracardiac implantation of the Impella CP using two-dimensional and three-dimensional intracardiac echocardiography. This new technique can be useful in selected groups of patients when fluoroscopy, transthoracic and transoesophageal echocardiography is deemed inapplicable or limited for epidemiological or clinical reasons. Intracardiac three-dimensional echocardiography is a feasible alternative to the traditional techniques for implantation of an Impella CP device but careful consideration must be given to the potential limitations and complications of this technique.