Graham R. McClure

Surgical ablation of atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials

Aims The aim of this review was to assess the effect of concomitant surgical atrial fibrillation (AF) ablation on postoperative freedom from AF and patient-important outcomes. Methods and results We searched Cochrane CENTRAL, MEDLINE, and EMBASE databases from inception to May 2016 for randomized controlled trials (RCTs) evaluating surgical AF ablation using any lesion set vs. no surgical AF ablation in adults with AF undergoing cardiac surgery. We performed screening, risk-of-bias evaluation, and data collection independently and in duplicate. We evaluated risk of bias with the modified Cochrane tool, quality of evidence using GRADE framework, and pooled data with a random-effects model. Of the 23 included studies, only one was considered at low risk of bias. Surgical AF ablation was associated with more freedom from AF at 12 months [relative risk (RR) = 2.32, 95% confidence interval (CI) 1.92-2.80; P < 0.001, low quality]. However, no significant difference was seen in mortality (RR = 1.07, 95% CI 0.72-1.52; P = 0.41, moderate quality), stroke (RR = 1.19, 95% CI 0.59-2.39; P = 0.63, moderate quality), or pacemaker implantation (RR = 1.28, 95% CI 0.85-1.95; P = 0.24, high quality). Comparing biatrial and left-sided lesion sets showed no difference in mortality (P-interaction = 0.60) or stroke (P-interaction = 0.12). At 12 months, biatrial procedures led to more freedom from AF (RR = 2.80, 95% CI 2.13-3.68; P < 0.0001) when compared with left-sided ablation (RR = 2.00, 95% CI 1.68-2.39; P < 0.0001) (P-interaction = 0.04) Biatrial procedures appear to increase the risk for pacemaker (RR = 2.68, 95% CI 1.41-5.11; P = 0.002) compared with no ablation while left-sided ablation does not (RR = 1.08, 95% CI 0.67-1.74; P = 0.76) (P-interaction = 0.03). Conclusion Surgical AF ablation during cardiac surgery improves freedom from AF. However, impact on patient-important outcomes including mortality and stroke has not shown statistical significance in current RCT evidence. Biatrial compared with left-sided lesion sets showed no difference in mortality or stroke but were associated with significantly increased freedom from AF and risk for pacemaker requirement.

International Normalized Ratio Targets for Left-Sided Mechanical Valve Replacement

BACKGROUND Guidelines recommend higher international normalized ratio (INR) targets for patients with mechanical valves believed to be at higher risk for thromboembolism. Higher INR targets are associated with increased bleeding risk. We performed a systematic review and meta-analysis assessing effects of lower and higher INR targets on thromboembolic and bleeding risk in patients with mechanical heart valves. METHODS We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized controlled trials (RCTs) evaluating lower versus higher INR targets for adults with bileaflet mechanical valves. We performed title and abstract screening, full-text review, risk of bias evaluation and data collection independently and in duplicate. We pooled data using a random effects model and used the Grading of Recommendations Assessment, Development and Evaluation framework to evaluate overall quality of evidence. RESULTS We identified six RCTs (n = 5,497). Lower INR targets were associated with significantly less bleeding-22% versus 40% (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.31, 0.93, p = 0.03, very low quality). There was no difference in thromboembolism-2% in both groups (RR: 1.28, 95% CI: 0.88, 1.85, p = 0.20, very low quality) or mortality-5.5% with lower INR targets versus 8.5% (RR: 1.00, 95% CI: 0.82, 1.21, p = 0.47, moderate quality). CONCLUSION In patients with mechanical valves, higher INR targets are not supported by current evidence, which is of very low quality. In fact, our systematic review suggests that lower INR targets offer significantly lower bleeding risks with no significant difference in thromboembolic risk.

Aortic valve replacement in younger patients

Population Health Research Institute, Hamilton, Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Division of Cardiac Surgery, McMaster University, Hamilton, Ontario, Canada; Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; and Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Surgical ablation of atrial fibrillation: a protocol for a systematic review and meta-analysis of randomised controlled trials

Introduction Atrial fibrillation (AF) affects 10% of patients undergoing cardiac surgery and is an independent risk factor for all-cause mortality, ischaemic stroke and heart failure. Surgical AF ablation has been shown to significantly improve maintenance of sinus rhythm, however, small to medium size trials conducted to date lack the power required to assess patient-important outcomes such as mortality, stroke, heart failure and health-related quality of life. Moreover, a recent randomised trial (RCT) suggested harm by surgical AF ablation with an almost threefold increase in the requirement for permanent pacemaker postablation. We aim to perform a systematic review and meta-analysis to evaluate efficacy and safety of surgical AF ablation compared to no surgical ablation. Methods and analysis We will search Cochrane CENTRAL, MEDLINE and EMBASE for RCTs evaluating the use of surgical AF ablation, including any lesion set, versus no surgical AF ablation in adults with AF undergoing any type of cardiac surgery. Outcomes of interest include mortality, embolic events, quality of life, rehospitalisation, freedom from AF and adverse events, including need for pacemaker and worsening heart failure. Independently and in duplicate, reviewers will screen references, assess eligibility of potentially relevant studies using predefined eligibility criteria and collect data using prepiloted forms. We will pool data using a random effects model and present results as relative risk with 95% CIs for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. We will assess risk of bias using the Cochrane Collaboration tool, and quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ethics and dissemination Our results will help guide clinical practice by providing the most comprehensive analysis of risks and benefits associated with the procedure. Our results will be disseminated through publication in peer-reviewed journals and conference presentations. Trial registration number CRD42015025988.

The Deferred Consent Model in a Prospective Observational Study Evaluating Myocardial Injury in the Intensive Care Unit

Background: Informed consent is a hallmark of ethical clinical research. An inherent challenge in critical care research is obtaining consent when patients lack decision-making capacity. One solution is deferred consent, which is often used for studies that are low risk or involve emergency interventions. Our objective was to describe a deferred consent model in a low-risk critical care study. Methods: Prognostic Value of Elevated Troponins in Critical Illness Study was a prospective, pilot observational study of critically ill patients in 3 intensive care units, involving serial electrocardiograms and cardiac biomarkers. Newly admitted patients were enrolled over 1 month. When possible, informed consent was obtained a priori from the patient or substitute decision maker (SDM); otherwise, consent was deferred until the patient regained consent capacity or until their SDM was available. Logistic regression analysis was used to determine the association between patient’s sex, Acute Physiology and Chronic Health Evaluation II score, study center, person providing consent (patient vs SDM), method of consent (telephone vs in person), and the provision or not of informed consent. Results: The overall consent rate was 80.1% (213 of 266 persons approached). Of the 53 persons declining consent, 37 (69.8%) agreed to the use of data collected up until that point. Over half of all consent encounters were with patients rather than SDMs. Median interval delay between enrollment and the consent encounter was 1 day. On multivariate analysis, the only variable associated with consent was male sex of the patient (odds ratio for males 2.59, confidence interval: 1.19-5.63). Conclusion: Deferred consent facilitates implementation of time-sensitive research protocols until a consent encounter is possible. As a feasible alternative to exclusive a priori consent, the deferred consent model can be useful in low-risk studies in critically ill patients.

Cardiac pheochromocytoma encasing the left main coronary artery

A 29-year-old previously healthy male presented with persistent anxiety, dyspnea, palpitations, and headaches. He had a heart rate of 119 beats/min, blood pressure of 176/108mmHg, a respiratory rate of 17, and an oxygen saturation of 97% on room air. A 12-lead electrocardiogram showed sinus tachycardia and a chest xray showed some airspace disease with pulmonary edema. An echocardiogram showed global hypokinesis with an ejection fraction of 33% and moderate pulmonary hypertension (right ventricular systolic pressure 57mmHg). Urinary metanephrines (39.0 μmol/dL; normal <11) and normetanephrine levels (11.9 μmol/day; normal<3.4)wereelevated, as were 24-h collections of norepinephrine, epinephrine, and dopamine. A cardiac magnetic resonance image showed a well circumscribed abnormal signal intensity in the mediastinum between the main pulmonary artery (PA) and the ascending aorta. A computed tomography (CT) scan showed a 4.6 × 3.6-cm mediastinal mass between the aortic root and the PA. A MIBG scan confirmed the presence of the mass seenon theCT scan (Figure1). A coronary angiogramshowed that the mass received a blood supply from both the proximal left and right coronary arteries (Figure 2). The patient was started on an alphablocking agent (doxazosin 2mg po daily started 1 month preoperatively) and referred for surgery. At the time of surgery, cardiopulmonary bypass (CPB) was initiated through a mediansternotomy with ascending aortic and bicaval cannulation. Following cardioplegic arrest with antegrade/ retrograde blood cardioplegia, the mass was noted to invade parts of the right ventricular outflow tract (RVOT); the left coronary sinus; the left main coronary artery; and parts of the left anterior descending (LAD), circumflex (LCX), and first diagonal branches (Figure 3). The mass was excised, the left coronary sinus was resected and repaired with a bovine patch and the RVOT was repaired with a #29 Freestyle root prosthesis (Xenosure biologic patch and Medtronic freestyle bioprosthesis 29mm, Medtronic, Minneapolis, MN). The left internal mammary artery (LIMA) was used to bypass the LAD, and a radial artery graft was used to bypass the diagonal and LCX branches, and anastomosed proximally to the LIMA (CPB time: 233min, cross-clamp time: 196min). The patient tolerated the procedure well and had an uncomplicated postoperative course. The histology was consistent with a cardiac pheochromocytoma with no evidence of lymphovascular involvement. The patient is now 5 months postop, all his symptoms have resolved, and his blood pressure and plasma metanephrine levels have returned to normal.

The Ross procedure versus prosthetic and homograft aortic valve replacement: a systematic review and meta-analysis

OBJECTIVES Young adults undergoing aortic valve replacement (AVR) have decreased life expectancy compared to matched controls. The Ross procedure aims to improve valve lifespan while avoiding anticoagulation. We prepared a systematic review and meta-analysis to assess the Ross procedure compared to conventional AVR. METHODS We searched MEDLINE, EMBASE and Cochrane CENTRAL for studies evaluating the Ross procedure versus any conventional AVR in adult patients. We performed screening, full-text assessment, risk of bias evaluation and data collection independently and in duplicate. We evaluated the risk of bias with the ROBINS-I and Cochrane tools and quality of evidence with the GRADE framework. We pooled data using the random- and fixed-effects models. RESULTS Thirteen observational studies and 2 randomized controlled trials (RCTs) were identified (n = 5346). No observational study was rated as having low risk of bias. The Ross procedure was associated with decreased late mortality in observational and RCT data [mean length of follow-up 2.6 years, relative risk (RR) 0.56, 95% confidence interval (CI) 0.38-0.84, I2 = 58%, very low quality]. The RCT estimate of effect was similar (mean length of follow-up 8.8 years, RR 0.33, 95% CI 0.11-0.96, I2 = 66%, very low quality). No difference was observed in mortality <30 days after surgery. All-site reintervention was similar between groups in cohorts and significantly reduced by the Ross procedure in RCTs (RR 1.41, 95% CI 0.89-2.24, I2 = 55%, very low quality and RR 0.41, 95% CI 0.22-0.78, I2 = 68%, high quality, respectively). CONCLUSIONS Observational data, with residual confounding, and RCT data suggest a late survival benefit with the Ross procedure with no increased risk of reintervention when compared to conventional AVR. Considering the quality of available evidence and limited follow-up, additional high-quality randomized studies are required to strengthen these findings. Systematic review PROSPERO registration CRD42016052512.