Circulating tumour cells in patients with lung cancer undergoing endobronchial cryotherapy.

Early diagnosis of lung cancer still poses a major issue, with a large proportion of patients diagnosed at late stages. Therapeutic options and treatment remain limited in these patients. In most cases only palliative therapies are available to alleviate any severe symptoms. Endobronchial cryotherapy (EC) is one form of palliative treatment offered to patients with obstructive airway tumours. Although successful, the impact on circulating tumour cell (CTCs) spread has not been investigated in detail. This study recruited 20 patients awaiting EC treatment. Baseline and post EC blood samples were analysed for presence of CTCs. Results showed an increase in CTCs following EC in 75% of patients. Significant increases were noticeable in some cases. Although EC is a well-accepted modality of treatment to alleviate symptoms, it may lead to an increase in CTCs, which in turn may have implications for tumour dissemination and metastatic spread.

Heterotopic abdominal heart transplantation in rats for functional studies of ventricular unloading.

INTRODUCTION: Chronic changes in mechanical load regulate long-term cardiac function. Chronic overload of the ventricle results in myocardial failure. Clinical use of ventricular assist devices shows that chronic reduction in load has a number of different consequences on the myocardium, including beneficial reverse remodeling as well as undesired remodeling (e.g., myocardial atrophy and fibrosis, both of which could have negative functional implications). The complex response to mechanical unloading necessitates reproducible animal models of mechanical unloading for use in the laboratory. This article aims to describe the operative technique of two animal models of mechanical unloading in detail, to enable the reproducible use of these animal models. METHODS: In 1964, Abbott et al first described the heterotopic abdominal heart transplantation technique as a means to study the biology of transplanted cardiac grafts. This involves an aorto-aortic anastomosis and a pulmonary artery to inferior vena cava anastomosis. In this model, the left ventricle is virtually completely volume unloaded, receiving only thebesian venous return, and substantially but not entirely pressure unloaded. In this report we describe two refined techniques for mechanical unloading of healthy or failing hearts based on experience with over 500 operations. RESULTS: We describe an operative technique, including cardioprotective strategies, that provides a model of mechanical unloading with no immunological rejection and allows measurements of parameters of myocardial structure and function for many months. We describe a refined technique that achieves a lesser degree of left ventricular volume unloading, involving transplantation of both heart and lungs via a single aorto-aortic anastomosis. CONCLUSIONS: This article is the first to describe these two techniques in sufficient detail to enable novices to attempt and understand these operations and the differences between them. The technique we describe provides an effective and reproducible model of complete and partial mechanical unloading.

Robotic mitral valve surgery.

Totally endoscopic robotic mitral valve repair is the least invasive surgical therapy for mitral valve disease. Robotic mitral valve surgery demonstrates faster recovery with shorter hospital stays, less morbidity, and equivalent mortality and mid-term durability compared to sternotomy. In this review, we will explore the advantages and disadvantages of robotic mitral valve surgery and consider important technical details of both operative set-up and mitral valve repair techniques. The number of robotic cardiac surgical procedures being performed globally is expected to continue to rise as experience grows with robotic techniques and increasing numbers of cardiac surgeons become proficient with this innovative technology. This will be facilitated by the introduction of newer robotic systems and increasing patient demand.

Prolonged mechanical unloading affects cardiomyocyte excitation-contraction coupling, transverse-tubule structure, and the cell surface.

Prolonged mechanical unloading (UN) of the heart is associated with detrimental changes to the structure and function of cardiomyocytes. The mechanisms underlying these changes are unknown. In this study, we report the influence of UN on excitation-contraction coupling, Ca(2+)-induced Ca(2+) release (CICR) in particular, and transverse (t)-tubule structure. UN was induced in male Lewis rat hearts by heterotopic abdominal heart transplantation. Left ventricular cardiomyocytes were isolated from the transplanted hearts after 4 wk and studied using whole-cell patch clamping, confocal microscopy, and scanning ion conductance microscopy (SICM). Recipient hearts were used as control (C). UN reduced the volume of cardiomyocytes by 56.5% compared with C (UN, n=90; C, n=59; P<0.001). The variance of time-to-peak of the Ca(2+) transients was significantly increased in unloaded cardiomyocytes (UN 227.4+/-24.9 ms(2), n=42 vs. C 157.8+/-18.0 ms(2), n=40; P<0.05). UN did not alter the action potential morphology or whole-cell L-type Ca(2+) current compared with C, but caused a significantly higher Ca(2+) spark frequency (UN 3.718+/-0.85 events/100 mum/s, n=47 vs. C 0.908+/-0.186 events/100 microm/s, n=45; P<0.05). Confocal studies showed irregular distribution of the t tubules (power of the normal t-tubule frequency: UN 8.13+/-1.12x10(5), n=57 vs. C 20.60+/- 3.174x10(5), n=56; P<0.001) and SICM studies revealed a profound disruption to the openings of the t tubules and the cell surface in unloaded cardiomyocytes. We show that UN leads to a functional uncoupling of the CICR process and identify disruption of the t-tubule-sarcoplasmic reticulum interaction as a possible mechanism.

Cytoskeletal protein 4.1R affects repolarization and regulates calcium handling in the heart.

The 4.1 proteins are a family of multifunctional adaptor proteins. They promote the mechanical stability of plasma membranes by interaction with the cytoskeletal proteins spectrin and actin and are required for the cell surface expression of a number of transmembrane proteins. Protein 4.1R is expressed in heart and upregulated in deteriorating human heart failure, but its functional role in myocardium is unknown. To investigate the role of protein 4.1R on myocardial contractility and electrophysiology, we studied 4.1R-deficient (knockout) mice (4.1R KO). ECG analysis revealed reduced heart rate with prolonged Q-T interval in 4.1R KO. No changes in ejection fraction and fractional shortening, assessed by echocardiography, were found. The action potential duration in isolated ventricular myocytes was prolonged in 4.1R KO. Ca(2+) transients were larger and slower to decay in 4.1R KO. The sarcoplasmic reticulum Ca(2+) content and Ca(2+) sparks frequency were increased. The Na(+)/Ca(2+) exchanger current density was reduced in 4.1R KO. The transient inward current inactivation was faster and the persistent Na(+) current density was increased in the 4.1R KO group, with possible effects on action potential duration. Although no major morphological changes were noted, 4.1R KO hearts showed reduced expression of NaV1.5alpha and increased expression of protein 4.1G. Our data indicate an unexpected and novel role for the cytoskeletal protein 4.1R in modulating the functional properties of several cardiac ion transporters with consequences on cardiac electrophysiology and with possible significant roles during normal cardiac function and disease.

A combined approach to correct posterior left ventricular aneurysm, aortic stenosis and coronary artery disease.

Ischaemic heart disease and aortic stenosis are potentially life-threatening conditions. A post-infarct left ventricular aneurysm, when combined with the above, is particularly hazardous. We present a case where all three conditions occurred simultaneously and describe the surgical approach undertaken to attempt correction. The patient underwent aneurysmectomy together with aortic valve replacement and two-vessel coronary artery bypass grafting. The aneurysm was excised with direct linear closure of the walls using a Teflon-buttressed interrupted mattress suture technique. Post-operatively, ventricular systolic function was good (LVEF 40%) together with a well-seated aortic valve showing no paravalvular leaks. This case highlights the importance of meticulous removal of thrombus from the aneurysm and everting the edges thereby eliminating a thrombogenic surface and the risk of embolic stroke. The restorative procedure itself serves to underline the importance of ventricular shape in the effective functioning of the myocardium for sustaining an adequate stroke volume with normalized physiology.

Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure.

AIMS: Combined left ventricular assist device (LVAD) and pharmacological therapy has been proposed to favour myocardial recovery in patients with end-stage heart failure (HF). Clenbuterol (Clen), a beta(2)-adrenoceptor (beta(2)-AR) agonist, has been used as a part of this strategy. In this study, we investigated the direct effects of clenbuterol on unloaded myocardium in HF. METHODS AND RESULTS: Left coronary artery ligation or sham operation was performed in male Lewis rats. After 4-6 weeks, heterotopic abdominal transplantation of the failing hearts into normal recipients was performed to induce LV unloading (UN). Recipient rats were treated with saline (Sal) or clenbuterol (2 mg/kg/day) via osmotic minipumps (HF + UN + Sal or HF + UN + Clen) for 7 days. Non-transplanted HF animals were treated with Sal (Sham + Sal, HF + Sal) or clenbuterol (HF + Clen). LV myocytes were isolated and studied using optical, fluorescence, and electrophysiological techniques. Clenbuterol treatment improved in vivo LV function measured with echocardiography (LVEF (%): HF 35.9 +/- 2 [16], HF + Clen 52.1 +/- 1.4 [16]; P < 0.001; mean +/- SEM [n]). In combination with unloading, clenbuterol increased sarcomere shortening (amplitude (microm): HF + UN + Clen 0.1 +/- 0.01 [50], HF + UN + Sal 0.07 +/- 0.01 [38]; P < 0.001) by normalizing the depressed myofilament sensitivity to Ca(2+) (slope of the linear relationship between Ca(2+) transient and sarcomere shortening hysteresis loop during relaxation (microm/ratio unit): HF + UN + Clen 2.13 +/- 0.2 [52], HF + UN + Sal 1.42 +/- 0.13 [38]; P < 0.05). CONCLUSION: Clenbuterol treatment of failing rat hearts, alone or in combination with mechanical unloading, improves LV function at the whole-heart and cellular levels by affecting cell morphology, excitation-contraction coupling, and myofilament sensitivity to calcium. This study supports the use of this drug in the strategy to enhance recovery in HF patients treated with LVADs and also begins to elucidate some of the possible cellular mechanisms responsible for the improvement in LV function.

Novel Approach to Repairing a Traumatic Aortic Arch Pseudoaneurysm Following a Fall.

Traumatic pseudoaneurysms of the aortic arch are often treated with surgical repair regardless of the lesion size or age. The authors report a simple, less invasive surgical repair in a patient who sustained blunt aortic injury following a fall.

The influence of prolonged intensive care stay on quality of life, recovery, and clinical outcomes following cardiac surgery: A prospective cohort study.

OBJECTIVE: To examine the influence of prolonged intensive care unit (ICU) stay on quality of life and recovery following cardiac surgery. METHODS: Quality of life was assessed using the Short Form 36 Health Survey (SF36). The Postoperative Quality of Recovery Scale was used to assess quality of recovery, disability, and cognition after ICU discharge over 12 months' follow-up. Prolonged ICU stay was defined as ≥3 postoperative days. Mortality and major adverse cardiac and cerebrovascular events were recorded up to 12 months. RESULTS: For quality of life, the physical component improved over time in both groups (P < .01 for both groups), as did the mental component (P < .01 for both groups). The long ICU group had lower physical and mental components over time (both P values < .01), but by 12 months the values were similar. The overall quality of recovery was lower for the long ICU group (P < .01). Likewise, we found higher rates of recovery in the normal ICU group than in the long ICU group in terms of emotive recovery (P < .01), activities of daily living (P < .01), and cognitive recovery (P = .03) but no differences in terms of physiologic (P = .91), nociceptive (P = .89), and satisfaction with anesthetic care (P = .91). Major adverse cardiac and cerebrovascular events (P < .01), 30-day mortality (P < .01), and length of ward stay (P < .01) were all higher with prolonged ICU stay. CONCLUSIONS: Patients with prolonged ICU stay have lower quality of life scores; however, they achieve similar midterm quality of recovery, but with reduced survival, increased major adverse cardiac and cerebrovascular events, and longer hospital length of stay.

Analysis of aortic area/height ratio in patients with thoracic aortic aneurysm and Type A dissection.

OBJECTIVES: Significant proportions of aortic dissections occur at aortic diameters <5.5 cm. By indexing aortic area to height and correlating with absolute aortic diameter, we sought to identify those aneurysm patients with aortic diameters <5.5 cm who do not meet current size thresholds for surgery, yet with corresponding abnormal indexed aortic areas (IAAs) >10 cm2/m, are at increased risk of aortic complications. METHODS: IAAs were calculated at 3 aortic locations in 187 aneurysm and 66 dissection patients operated on between 2010 and 2016 at our tertiary aortic centre. Proportions of patients with IAA >10 cm2/m, mean IAAs corresponding to aortic diameters <4.0 cm, 4.0-4.5 cm, 4.5-5.0 cm, 5.0-5.5 cm and >5.5 cm, and mean aortic diameters corresponding to IAAs 10-12 cm2/m, 12-14 cm2/m and >14 cm2/m were determined. RESULTS: Proportions of patients with abnormal IAAs were similar in both groups. In all, 49.1% of aneurysm patients with aortic diameters 4.5-5.0 cm, and 98.5% with aortic diameters 5.0-5.5 cm had abnormal IAAs. Out of 200 separate aneurysms with IAAs >10 cm2/m between the mid-sinus and mid-ascending aorta, 139 (69.5%) would not warrant surgery according to existing guidelines. CONCLUSIONS: Using the IAA, we identified a significant proportion of patients with thoracic aortic aneurysms who are at increased risk of aortic complications, despite current aortic guidelines not endorsing surgical intervention in this group. Our data suggests the IAA may be useful in preoperative risk evaluation and as a criterion for surgery.

Fate of the Aortic Arch Following Surgery on the Aortic Root and Ascending Aorta in Bicuspid Aortic Valve.

BACKGROUND: Recent guidelines support more aggressive surgery for aneurysms of the ascending aorta and root in patients with bicuspid aortic valve. However, the fate of the arch after surgery of the root and ascending aorta is unknown. We set out to assess outcomes following root and ascending aortic surgery and subsequent growth of the arch. METHODS: Between 2005 and 2016, 536 consecutive patients underwent surgery for aneurysm of the root and ascending aorta; 168 had bicuspid aortic valve. Patients with dissection were excluded. Arch diameter was measured before and after surgery, at 6 months and then annually. RESULTS: Of 168 patients, 127 (75.6%) had aortic root replacement and 41 (24.4%) had ascending replacement. Mean age was 57 ± 12.8 years, 82.7% were men, and 5 operations were performed during pregnancy. There was 1 (0.6%) hospital death. One (0.6%) patient had a stroke and 1 (0.6%) had resternotomy for bleeding. Median intensive care unit and hospital stays were 1 and 6 days, respectively. Follow-up was complete for 94% at a median of 5.9 years (range, 1 to 139 months). Aortic arch diameter was 2.9 cm preoperatively and 3.0 cm at follow-up. There was 97% freedom from reoperation and none of the patients required surgery on the arch. CONCLUSIONS: Prophylactic arch replacement during aortic root and ascending aortic surgery in patients with bicuspid aortic valve is not supported. Our data do not support long-term surveillance of the rest of the aorta in this population.

The role of the cardiac Na+/Ca2+ exchanger in reverse remodeling: relevance for LVAD-recovery.

Different strategies can, at least in certain conditions, prevent or reverse myocardial remodeling due to heart failure and induce myocardial functional improvement. Na+/Ca2+ exchanger (NCX) is considered a major player in the pathophysiology of heart failure but its role in reverse remodeling is unknown. A combination of mechanical unloading by left ventricular assist devices (LVADs) and pharmacological therapy has been shown to induce clinical recovery in a limited number of patients with end-stage heart failure. In myocytes isolated from these patients we found that, after LVAD treatment, NCX1/SERCA2a mRNA was 38% higher than at device implant. We studied the ability of NCX to extrude Ca2+ during caffeine-induced SR Ca2+ release in isolated ventricular myocytes from these patients. The time constant of decline was slower in heart failure. In myocytes from patients with clinical recovery following mechanical and pharmacological treatment, NCX1-mediated Ca2+ extrusion was faster compared with myocytes from patient who, despite identical treatment, did not recover. We propose that increased NCX function may be associated with reverse remodeling in patients and that factors that regulate NCX function (i.e., phosphorylation or intracellular [Na+]) other than NCX expression levels alone, may have detrimental consequences on cardiac function.

Aortic Root Surgery: Does High Surgical Volume and a Consistent Perioperative Approach Improve Outcome?

There is evidence that high surgical volume and team consistency improve outcomes. Mortality of 4%-12% for aortic root surgery has been reported in the United States and UK. We aim to assess outcomes of patients undergoing aortic root surgery by a consistent, high-volume team. Data on patients undergoing elective or urgent aortic root replacement (ARR) were collected prospectively. Patients undergoing emergency surgery were excluded. A standardized perioperative approach was maintained and was achieved by delivering training to team members, including surgical trainees, anesthetic, nursing, and perfusion staff, whenever there was a change of team. Between 2005 and 2014, 344 patients underwent ARR. Median age was 59 years (18-86) and 74% were men. Procedures included ARR (biological [186; 54%] or mechanical [101; 29.4%]) and valve sparing root replacement, remodeling technique (57; 16.6%). A total of 42 patients (12.2%) underwent concomitant procedures. There were 4 (1.2%) in-hospital deaths and no incidence of stroke. In total, 3 (0.9%) required resternotomy for bleeding and 8 (2.3%) required hemofiltration. Follow-up was complete for 94% of patients with median intensive care unit and hospital stays of 1 and 6 days, respectively. Follow-up was complete for 94% of patients at a median of 5.6 years with 98% freedom from reoperation and prosthetic valve dysfunction. There was 90% freedom from aortic insufficiency at 7 years in the valve sparing root replacement, remodeling technique cohort. We have demonstrated that high surgical volume and standardized care improves outcomes in aortic root surgery. Maintaining a consistent perioperative approach ensures team members are aware and well rehearsed in their roles, thereby improving outcomes.

A Survey of Cardiothoracic Surgical Training in the United Kingdom: Realities of a 6-Year Integrated Training Program.

BACKGROUND: In recent years, cardiothoracic (CT) surgical training has faced several challenges, including a reduction in working hours and trainees favoring shorter training programs. We carried out a national survey in the United Kingdom (UK) to assess the CT 6-year training program. METHODS: All CT trainees in the UK (n = 121) were sent an online survey. This was combined with a debate at the Society for CT Surgery of Great Britain and Ireland. RESULTS: Ninety-one (75.2%) of all trainees responded. Despite 56 (68.1%) being rostered for more than a 48-hour week, 31 (34.1%) of all trainees work an extra 10 hours. The majority (56, 61.5%) thought that on-calls and night duty are useful. Just over half of the trainees (47, 51.6%) spend at least 2 full days in the operating room, but 79 (86.8%) thought that this is too little and would spend voluntary time operating. Simulation of operations is thought to be useful; however, few thought that this should take more precedence in their training program. The majority of trainees thought that the current assessment of surgical training is suboptimal and does not examine surgical skill. Similarly, the majority thought that a defined number of operations is required before qualification. CONCLUSIONS: Trainees remain committed to their profession and are willing to dedicate more time perfecting their art. They believe that despite wanting extra operating experience, they will be ready for independent practice at the completion of their training. It rests with training bodies to find alternative assessments for surgical ability and to define experience at the exit point of training.