Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.

Age-Stratified Outcome in Treatment of Left Main Coronary Artery Stenosis: A NOBLE Trial Substudy.

BACKGROUND: In the treatment of left main coronary artery (LMCA) disease, patients' age may affect the clinical outcome after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study stratified the clinical outcome according to the age of patients treated for LMCA stenosis with PCI or CABG in the Nordic-Baltic-British Left Main Revascularization (NOBLE) study. METHODS: Patients with LMCA disease were enrolled in 36 centers in northern Europe and randomized 1:1 to treatment by PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST elevation myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCEs), a composite of all-cause mortality, nonprocedural myocardial infarction, any repeat coronary revascularization, and stroke. Age-stratified analysis was performed for the groups younger and older than 67 years and for patients older than 80 years. RESULTS: For patients ≥67 years, the 5-year MACCEs were 35.7 versus 22.3% (hazard ratio [HR] 1.72 [95% confidence interval [CI] 1.27-2.33], p = 0.0004) for PCI versus CABG. The difference in MACCEs was driven by more myocardial infarctions (10.8 vs. 3.8% HR 3.01 [95% CI 1.52-5.96], p = 0.0009) and more repeat revascularizations (19.5 vs. 10.0% HR 2.01 [95% CI 1.29-3.12], p = 0.002). In patients younger than 67 years, MACCE was 20.5 versus 15.3% (HR 1.38 [95% CI 0.93-2.06], p = 0.11 for PCI versus CABG. All-cause mortality was similar after PCI and CABG in both age-groups. On multivariate analysis, age was a predictor of MACCE, along with PCI, diabetes, and SYNTAX score. CONCLUSIONS: As the overall NOBLE results show revascularization of LMCA disease, age of 67 years or older was associated with lower 5-year MACCE after CABG compared to PCI. Clinical outcomes were not significantly different in the subgroup younger than 67 years, although no significant interaction was present between age and treatment. Mortality was similar for all subgroups (ClinicalTrials.gov identifier: NCT01496651).

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial.

BACKGROUND: Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. METHODS: In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke. INTERPRETATION: The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease. FUNDING: Biosensors, Aarhus University Hospital, and participating sites.

Examining the forgotten valve: outcomes of tricuspid valve surgery, a 15-year experience.

BACKGROUND: We have entered an era of renewed interest in novel approaches to surgical intervention and minimally invasive and transcatheter technique. With an aging population, isolated tricuspid valve regurgitation incidence is rising; however, referral for surgical intervention remains low. AIMS: We undertook this retrospective review to assess outcomes and challenges associated with tricuspid valve intervention. METHODS: A comprehensive retrospective review of all patients undergoing tricuspid valve intervention in our institution between 2004 and 2018 was carried out. RESULTS: A total of 259 patients who underwent a tricuspid intervention between 2004 and 2018 were identified. Of those, 229 underwent a repair and 30 underwent a replacement. Median survival for repair was 3124 days, and replacement was 2294 days. In-patient mortality was 12% for those undergoing repair and 7% for the replacement patients. Of those undergoing redo tricuspid valve intervention, eight patients (61.5%) were alive at most recent follow-up. Eight patients required intraoperative pacemakers, 2 required postoperative pacemakers. Of those who had intraoperative epicardial pacing systems placed, 5 of the 8 remained pacing dependent on most recent follow up. CONCLUSION: Beyond technical challenges, decision making regarding pacemaker requirement requires further exploration. Redo tricuspid valve surgery carries a significant mortality risk and consideration should be given to earlier intervention in this context.

Sex-Specific Clinical Outcomes After Treatment of Left Main Coronary Artery Disease. A NOBLE Substudy.

Background: While female sex has been associated with worse outcomes following coronary revascularization, previous analyses in left main coronary artery (LMCA) disease have been conflicting. In addition, a signal that increased mortality may be specific to women treated with percutaneous coronary intervention (PCI) requires further investigation. Methods: Nordic-Baltic-British left main revascularization study (NOBLE) was a randomized trial comparing PCI to coronary artery bypass surgery (CABG) in patients with LMCA disease. The primary endpoint was a composite of all-cause mortality, nonprocedural myocardial infarction, repeat revascularization, and stroke (major adverse cardiovascular and cerebrovascular events [MACCE]). We report the 5-year sex-specific outcomes. Results: Of 1184 patients analyzed, 256 (22%) were female and 928 (78%) were male. There were no significant within-sex differences in baseline characteristics, disease location, or complexity between those treated with PCI and those with CABG. The 5-year MACCE rates were 29% and 15% in females and 28% and 20% in males treated with PCI and CABG, respectively. Within both sexes, there was an increased risk of MACCE with PCI compared with CABG, but no difference in all-cause mortality. On multivariate analysis, female sex was not an independent predictor of MACCE. Conclusions: Following the treatment of LMCA disease, long-term outcomes favored CABG over PCI in both sexes. Importantly, there was no difference in all-cause mortality in females or males at 5 â€‹years.

Kommerell's diverticulum, risk factor for aortic dissection.

A 54-year-old man presented with sharp chest pain and hypertension. He was treated with intravenous antihypertensive with good control of the blood pressure. Chest X-ray showed widened mediastinum, and subsequent computed tomography scan of the chest demonstrated dissection of the descending thoracic aorta. It also showed an aberrant right subclavian artery with retrograde extension of dissection and Kommerell's diverticulum, which is dilatation at the origin of the aberrant subclavian artery.

Incidence and outcome of re-entry injury in redo cardiac surgery: benefits of preoperative planning.

OBJECTIVES: Repeat sternotomy for redo cardiac surgery may be associated with catastrophic injuries to mediastinal structures. The purpose of this study was to determine the frequency of these injuries, associated outcome and if a preoperative computerized tomography (CT) scan reduces the risk of re-entry injury. METHODS: Five hundred and forty-four patients who underwent redo cardiac surgery between 2001 and 2011 were identified by review of our unit's prospectively maintained cardiac surgery database. Demographic details, surgical strategy, re-entry injuries, hospital stay, in-hospital mortality and long-term survival were analysed. RESULTS: The mean age was 61 years; 326 were male, 218 were female. Four hundred and eighty six patients underwent first time redo surgery, while 58 patients had multiple previous operations. The median logistic EuroSCORE was 11, in-hospital mortality rate was 9.5% and observed to expected mortality rate was 0.8. Re-entry complications occurred in 15 cases (2.7%). These included injuries to the aorta (n = 2), right atrium (n = 1), innominate vein (n = 2), internal mammary artery (n = 2), pulmonary artery (n = 2), lung parenchyma (n = 1), saphenous vein graft (n = 2), right ventricle (n = 2) and ventricular fibrillation (n = 1). The mortality rate in patients with re-entry injury was 26% (n = 4) compared with 9% (n = 48) in those without re-entry complications. Preoperative planning by CT scan was performed in 162 cases and adherence of vital structures to the sternum was found in 60 cases; the right ventricle, innominate vein and bypass grafts in 41, 11 and 8, respectively. The incidence rate of re-entry injury was 0.6% in these patients vs 3.6% in those who did not have a preoperative CT scan (P = 0.046). Peripheral arterial cannulation was carried out in 35 patients (6.4%) to establish cardiopulmonary bypass (CPB) prior to sternotomy, and there were no mediastinal injuries observed in these cases. Multivariate logistic regression analysis revealed re-entry injury as one of the independent predictors of in-hospital mortality (P = 0.039). CONCLUSIONS: The incidence of re-entry injury during repeat sternotomy is low; however, it is associated with a significant increase in the risk of in-hospital mortality. Preoperative planning using CT scan reduces the risk by identifying adherent structures, and, in selected patients, establishing CPB prior to sternotomy is a safe strategy in redo cardiac surgery.

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Endoscopic vein harvest: advantages and limitations.

BACKGROUND: Although long saphenous vein remains the most commonly used conduit in coronary revascularization, traditional open vein harvest (OVH) may lead to significantly impaired wound healing and postoperative pain. Endoscopic vein harvest (EVH) attempts to reduce this morbidity and improve patient satisfaction with no compromise in outcome. METHODS: From September 2000 to November 2001, 108 saphenous vein harvests were prospectively randomly assigned to EVH (n = 52) or OVH (n = 56); EVH was performed with the Clearglide endoscopic vein harvest system (Cardiovations) by a single surgeon. Endpoints included impaired wound healing (ASEPSIS score), operative and harvest time, vein quality (including histology), outcome and postoperative pain (Visual Analog Scale). Follow-up was as long as 3 years. RESULTS: The groups were well matched demographically. Endoscopic vein harvest was quicker to perform if sufficient vein for two grafts was needed (p < 0.01). Wound healing was significantly impaired (ASEPSIS score) in the OVH group compared with the EVH group (p < 0.01). The new procedure did not prolong the overall operative time (p = 0.77). Postoperative pain was less (p < 0.01) in the EVH group. Stepwise multiple regression showed age, diabetes, peripheral vascular disease, total operative time, type of procedure, length of incision, and number of vein grafts to be predictive of impaired wound healing. More late interventions were needed in the OVH group for wound-related morbidity. CONCLUSIONS: These data demonstrate that endoscopic vein harvest results in fewer cases of impaired wound healing and reduced postoperative pain, and it does not prolong the operative time significantly nor compromise the vein quality. Furthermore, it is quicker to perform if two grafts are needed, and it reduces late interventions.

Pulmonary infarct cytologically mimicking adenocarcinoma of the lung.

We describe a patient who underwent a right lower lobectomy for a lung lesion with a preoperative diagnosis of adenocarcinoma made on sputum cytology. Pathologic assessment of the resected specimen revealed a pulmonary infarct with no evidence of malignancy. All thoracic surgeons should be aware of this diagnostic pitfall. A positive sputum specimen should not always be regarded as definitive evidence of malignancy. Instead a full assessment of all available information should be made if unnecessary surgery is to be avoided.

Right atrial myxoma arising from the Eustachian valve in a patient with colonic polyposis.

Right atrial myxoma arising from the Eustachian valve is rare, with only two reported cases; moreover, any association with colonic polyps is uncommon, with only one such case documented. A case is described of a 68-year-old male who presented with chronic anemia; an initial investigation revealed colonic polyps, but anemia persisted after polypectomy. Further investigation revealed a right atrial myxoma arising from the Eustachian valve and prolapsing into the right ventricle through the tricuspid valve. After successful removal of the lesion, hematological indices returned to normal. In cases of persisting anemia, other rare causes such as atrial myxoma should be sought.

Management of mild to moderate aortic valve disease during coronary artery bypass grafting.

OBJECTIVE: The long term survival of patients with mild to moderate aortic valve disease who do not have valve replacement at the time of coronary artery bypass grafting (CABG) is unknown. Therefore we have reviewed our experience with such patients. METHODS: We reviewed the medical records of consecutive patients between June 1978 and December 1996, and identified 40 patients with mild to moderate aortic valve disease, who underwent CABG, without valve replacement (study group). Mean preoperative aortic gradient was 34 mmHg and mean intraoperative gradient 20 mmHg. Eleven patients underwent valve inspection, and an equal number, underwent valve repair. The records of 61 other patients with severe aortic valve disease, who underwent concomitant aortic valve replacement (AVR) and CABG (control group), were also reviewed. RESULTS: Survival was significantly better in the control group. Eleven patients (27.5%) in the study group underwent reoperation for AVR, with no operative mortality. Multivariate analysis confirmed valve replacement at initial CABG to be the only predictor of survival (beta=0.586,P=0.038) Preoperative gradient <40 mmHg, intraoperative gradient <20 mmHg, age over 70, sex, aortic stenosis and valve pathology did not predict survival in the study group. CONCLUSION: Patients with mild to moderate aortic valve disease undergoing coronary artery bypass grafting may be best served by valve replacement, rather than repair, inspection or no procedure.

An unexpected mortality following cardiac surgery: a post-mortem diagnosis of cardiac amyloidosis.

Amyloidosis is a rare systemic disease that is notoriously difficult to diagnose early. Cardiac involvement is associated with a poor prognosis. We present the case of a 72-year-old gentleman who underwent elective coronary artery bypass grafting and mitral valve repair. While initially making a good post-operative recovery, a sudden deterioration on post-operative day 3 led to an unexpected mortality. Post-mortem examination demonstrated previously undiagnosed severe systemic amyloidosis, which particularly affected his heart, due to underlying multiple myeloma. It is important to emphasise that due to the absence of the typical findings on routine pre-operative investigations suggestive of cardiac amyloidosis in this patient, cardiac surgeons should be aware that symptoms inconsistent with angiography findings should prompt consideration of amyloidosis. Diagnostic tools including cardiac MRI and ultimately endomyocardial biopsy could then facilitate earlier recognition of this enigmatic disease process.

Ventricular assist device therapy in post-cardiotomy cardiogenic shock: historical outcomes and current trends.

Ventricular assist device (VAD) therapy has been used successfully as a bridge to recovery, bridge to transplant and in the last decade as a destination therapy. The use of VAD for post-cardiotomy cardiogenic shock (PCCS) is not currently reported in national databases in the UK and Ireland. Data were collected through a telephone survey of chief perfusionists from all the cardiac surgery units in the UK and Ireland between October 2007 and October 2008. Approximately 28 000 adult cardiac surgical procedures were performed at 45 cardiac centres, of which 33 (73%) reported using VAD. The total number of patients supported was 66, of which 41% (n = 27) survived to be discharged home. About 42.5% (n = 28) died during VAD in place, and 16.5% died after successful weaning from VAD. Preferences for device types were Biomedicus (n = 25), Levitronix (n = 10), Sorin (n = 3), roller pump (n = 3) and Berlin heart (n = 2). Despite the reasonable survival rates after VAD use in post-cardiotomy heart failure, there are significant differences in their availability and individual's attitude towards their use. VAD use in PCCS should be prospectively documented in the audit returns of all the units, for further analysis and for generation of protocols.

Stroke due to a cardiac myxoma.

Cardioembolic stroke is an important cause of stroke in young people. Cardioembolism classically causes infarcts in multiple vascular territories. In the case described here a young woman developed cardioembolic stroke secondary to atrial myxoma. The presentation was atypical in that the woman had no systemic manifestations of her myxoma.

Erythropoietin receptor expression in non-small cell lung carcinoma: a question of antibody specificity.

Immunohistochemical studies on formalin-fixed, paraffin-embedded (FFPE) tissue utilizing polyclonal antibodies form the cornerstone of many reports claiming to demonstrate erythropoietin receptor (EPOR) expression in malignant tissue. Recently, Elliott et al. (Blood 2006;107:1892-1895) reported that the antibodies commonly used to detect EPOR expression also detect non-EPOR proteins, and that their binding to EPOR was severely abrogated by two synthetic peptides based on the sequence of heat shock protein (HSP) 70, HSP70-2, and HSP70-5. We have investigated the specificity of the C20 antibody for detecting EPOR expression in non-small cell lung carcinoma (NSCLC) utilizing tissue microarrays. A total of 34 cases were available for study. Antibody absorbed with peptide resulted in marked suppression of cytoplasmic staining compared with nonabsorbed antibody. Four tumors that initially showed a membranous pattern of staining retained this pattern with absorbed antibody. Positive membranous immunoreactivity was also observed in 6 of 30 tumors that originally showed a predominantly cytoplasmic pattern of staining. Using the C20 antibody for Western blots, we detected three main bands, at 100, 66, and 59 kDa. Preincubation with either peptide caused abolition of the 66-kDa band, which contains non-EPOR sequences including heat shock peptides. These results call into question the significance of previous immunohistochemical studies of EPOR expression in malignancy and emphasize the need for more specific anti-EPOR antibodies to define the true extent of EPOR expression in neoplastic tissue.

Diffuse coronary artery disease and dystrophic calcification of the radial artery--is there an association?

Arterial revascularization is an attractive surgical option in the management of coronary artery disease (CAD). In the recent years, the radial artery (RA) has enjoyed resurgence in popularity as the preferred arterial conduit of choice after the internal mammary artery. Despite renewed interest in RA conduits, little is known of the prevalence of preexisting disease in this vessel, and in particular which patient subgroups are most affected, hence implications for long-term graft patency remain uncertain. We present our experience of three patients with diffuse CAD, found to have dystrophic calcification of their radial arteries intraoperatively. In all cases, the radial arteries were used, and the patients remain well and symptom-free. Soft tissue X-rays of the contra lateral forearm taken postoperatively demonstrated obvious calcification in the radial arteries in all patients. Diffuse CAD may reflect calcific disease in the RA. Suitability of a calcified RA as a conduit for CABG depends on long-term patency, which requires further evaluation.

Off-pump coronary artery bypass grafting and left lower lobectomy simultaneously performed via a left postero-lateral thoracotomy.

A 75-year-old male with angina and a squamous carcinoma of the left lower lobe underwent a single-stage procedure for the treatment of these lesions. Through a left postero-lateral thoracotomy, a left lower lobectomy was performed with systematic nodal dissection including the subcarinal and paraaortic lymph nodes. A reversed saphenous vein segment was used to bypass the left anterior descending artery from the ascending aorta without cardiopulmonary bypass.