Ansar Hassan

Minimally invasive mitral valve surgery: a systematic review and meta-analysis

The mitral valve has been traditionally approached through a median sternotomy. However, significant advances in surgical optics, instrumentation, tissue telemanipulation, and perfusion technology have allowed for mitral valve surgery to be performed using progressively smaller incisions including the minithoracotomy and hemisternotomy. Due to reports of excellent results, minimally invasive mitral valve surgery has become a standard of care at certain specialized centers worldwide. This meta-analysis quantifies the effects of minimally invasive mitral valve surgery on morbidity and mortality compared with conventional mitral surgery and demonstrates equivalent perioperative mortality (1641 patients, odds ratio (OR) 0.46, 95% confidence interval 0.15-1.42, p=0.18), reduced need for reoperation for bleeding (1553 patients, OR 0.56, 95% CI 0.35-0.90, p=0.02) and a trend towards shorter hospital stays (350 patients, weighted mean difference (WMD) -0.73, 95% CI -1.52 to 0.05, p=0.07). These benefits were evident despite longer cardiopulmonary bypass (WMD 25.81, 95% CI 13.13-38.50, p<0.0001) and cross-clamp times (WMD 20.91, 95% CI 8.79-33.04, p=0.0007) in the minimally invasive group. Case-control studies show consistently less pain and faster recovery compared to those having a conventional approach. Data for minimally invasive mitral valve surgery after previous cardiac surgery are limited but consistently demonstrate reduced blood loss, fewer transfusions and faster recovery compared to reoperative sternotomy. Long-term follow-up data from multiple cohort studies are also examined revealing equivalent survival and freedom from reoperation. Thus, current clinical data suggest that minimally invasive mitral valve surgery is a safe and a durable alternative to a conventional approach and is associated with less morbidity.

The impact of frailty on outcomes after cardiac surgery: A systematic review

OBJECTIVE Current preoperative assessments for cardiac surgery, such as the European System for Cardiac Operative Risk Evaluation II and the Society of Thoracic Surgeons risk score, are limited in their ability to predict postoperative outcomes. This is thought to be due to the reliance on chronological age as a predictor of health. In geriatrics, frailty assessments have been developed as a tool in determining physiologic functioning capacity. Whether or not frailty predicts postoperative outcomes independent of existing cardiac preoperative risk scores remains unknown. METHODS We performed a systematic review to determine the association of frailty with negative postoperative outcomes such as major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing cardiac surgery. We searched PubMed, EMBASE, the Cochrane library, and Ageline from inception until July 2013 and screened 5913 abstracts for potential inclusion. Of these, 6 studies examined the relationship between objective frailty assessments and postoperative outcomes. Our included studies evaluated 4756 patients undergoing cardiac surgery. RESULTS Frailty, defined using multiple criteria, had a strong positive relationship with the risk of MACCE (odds ratio, 4.89; 95% confidence interval, 1.64-14.60). Relationships were stronger in older patients undergoing transcatheter aortic valve replacement (TAVR) than younger patients undergoing coronary artery bypass grafting and valvular surgery (hazard ratio for frailty in TAVR, 3.31-4.89 vs hazard ratio for non-TAVR, 1.10-3.16). CONCLUSIONS Patients deemed frail, determined using an objective assessment tool, have a higher likelihood of experiencing mortality, morbidity, functional decline, and MACCE following cardiac surgery, regardless of definition. Further study is needed to determine which components of frailty are most predictive of negative postoperative outcomes before integration in risk prediction scores.

Is it safe to train residents to perform cardiac surgery

BACKGROUND The impact of surgical training on patient outcomes in cardiac surgery is unknown. METHODS All cases performed by residents from 1998 to 2001 were compared to staff surgeon cases using prospectively collected data. Operative mortality and a composite morbidity of: reoperation for bleeding perioperative myocardial infarction, infection, stroke, or ventilation more than 24 hours were compared using multivariate analysis. RESULTS Four residents performed 584 cases. The cases were as follows: coronary artery bypass grafting (CABG), 366 cases; aortic valve replacement (AVR) with or without CABG (AVR +/- CABG), 86 cases; mitral valve replacement, 31 cases; mitral valve repair, 25 cases; thoracic aneurysm/dissection, 22 cases; aortic root, 20 cases; transplantations, 14 cases; and adult congenital defect repairs, 20 cases. There were 2,638 CABGs and 363 AVR +/- CABG performed by the staff during the same period. Crude operative mortality in CABG patients was 2.5% (resident) and 2.9% (staff) (p = 0.62). In multivariate analysis, resident was not associated with operative mortality odds ratio (OR) of 0.59 (p = 0.19). Resident cases had a higher incidence of the composite morbidity outcome for CABG cases (19.4% vs 13.6% for staff; p = 0.003). However, in multivariate analysis, resident was not associated with increased morbidity (OR = 1.23, p = 0.16). The AVR +/- CABG crude mortality was 3.6% (resident) and 2.8% (staff) (p = 0.69). Because of the small number of cases (n = 447), operative mortality was combined with the composite morbidity outcome for the AVR +/- CABG model. In all, 16.7% of resident cases and 19.8% of staff cases had the composite outcome or died (p = 0.51). In multivariate analysis resident was not associated with this outcome (OR = 0.74, p = 0.35). CONCLUSIONS In this analysis of our experience with residency training, the operative morbidity and mortality in CABG and AVR patients was similar for residents and staff. Training residents to perform cardiac surgery appears to be safe.

Increasing rates of angioplasty versus bypass surgery in Canada, 1994-2005.

BACKGROUND Percutaneous coronary intervention (PCI) is increasingly being offered to patients with coronary artery disease. The purpose of this study was to determine the impact of this change in coronary revascularization strategy on PCI and coronary artery bypass grafting (CABG) utilization across Canada. METHODS All cases of PCI and isolated CABG between years 1994 and 2005 were identified through the Canadian Institute for Health Information. Age- and sex-standardized rates of PCI and CABG per 100,000 population as well as PCI-to-CABG ratios were calculated by year and province and across age, sex, income, diabetes, and recent acute coronary syndrome subgroups. In addition, risk-adjusted rates of in-hospital mortality after PCI and CABG were reported by year. RESULTS Between 1994 and 2005, PCI rates increased from 85.6/100,000 to 186.7/100,000 (P < .001), whereas CABG rates remained stable (75.6/100,000-70.8/100,000; P = .43), resulting in an increase in PCI-to-CABG ratio (1.13-2.64; P < .001). Significant increases in PCI-to-CABG ratios were seen across all provinces (except Newfoundland and Alberta), as well as across all age, sex, income, diabetes, and recent acute coronary syndrome categories. Decline in risk-adjusted in-hospital mortality was seen after both CABG (3.9%-2.2%; P < .001) and PCI (1.6%-1.3%; P < .001) but appeared larger after CABG. CONCLUSIONS Since 1994, rates of PCI have increased significantly as compared to CABG. During the same period, greater declines in risk-adjusted rates of in-hospital mortality were seen among CABG versus PCI patients. Further study is needed to determine the appropriateness of PCI and CABG rates in terms of clinical outcomes and resource utilization.

Effect of marriage on duration of chest pain associated with acute myocardial infarction before seeking care

Background: Coronary artery disease is the most common cause of death in the Western world, and being married decreases the risk of death from cardiovascular causes. We aimed to determine whether marital status was a predictor of the duration of chest pain endured by patients with acute myocardial infarction before they sought care and whether the patient’s sex modified the effect. Methods: We conducted a retrospective, population-based cohort analysis of patients with acute myocardial infarction admitted to 96 acute care hospitals in Ontario, Canada, from April 2004 to March 2005. We excluded patients who did not experience chest pain. Using multivariable regression analyses, we assessed marital status in relation to delayed presentation to hospital (more than six hours from onset of pain), both overall and stratified by sex. In patients who reported the exact duration of chest pain, we assessed the effect of marital status on the delay in seeking care. Results: Among 4403 eligible patients with acute myocardial infarction, the mean age was 67.3 (standard deviation 13.6) years, and 1486 (33.7%) were women. Almost half (2037 or 46.3%) presented to a hospital within two hours, and 3240 (73.6%) presented within six hours. Overall, 75.3% (2317/3079) of married patients, 67.9% (188/277) of single patients, 68.5% (189/276) of divorced patients and 70.8% (546/771) of widowed patients presented within six hours of the onset of chest pain. Being married was associated with lower odds of delayed presentation (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.30–0.71, p < 0.001) relative to being single. Among men, the OR was 0.35 (95% CI 0.21–0.59, p < 0.001), whereas among women the effect of marital status was not significant (OR 1.36, 95% CI 0.49–3.73, p = 0.55). Interpretation: Among men experiencing acute myocardial infarction with chest pain, being married was associated with significantly earlier presentation for care, a benefit that was not observed for married women. Earlier presentation for medical care appears to be one reason for the observed lower risk of cardiovascular death among married men, relative to their single counterparts.

The effect of place of residence on access to invasive cardiac services following acute myocardial infarction.

BACKGROUND The Canadian health care system is mandated to provide reasonable access to health care for all Canadians regardless of age, sex, race, socioeconomic status or place of residence. In the present study, the impact of place of residence in Nova Scotia on access to cardiac catheterization and long-term outcomes following an acute myocardial infarction (MI) were examined. METHODS All patients with an acute MI who were hospitalized between April 1998 and December 2001 were identified. Place of residence was defined by postal code and separated into three categories: metropolitan area (MA); nonmetropolitan urban area (UA); and rural area (RA). Rates of and waiting times for cardiac catheterization were determined, as were risk-adjusted long-term rates of mortality and readmission to the hospital. RESULTS A total of 7351 patients were hospitalized with an acute MI during the study period. Rates of cardiac catheterization differed across the three groups (MA 45.6%, UA 37.3%, RA 37.3%; P<0.0001), as did mean waiting times (MA 15.0 days, UA 32.1 days, RA 28.7 days) (P<0.0001). After adjusting for differences among patients, residence in either UA or RA emerged as an independent predictor of lower rates of cardiac catheterization (UA: hazard ratio [HR] 0.77, P<0.0001; RA: HR 0.75, P<0.0001), greater waiting times (UA: an additional 14.1 days, P<0.0001; RA: an additional 10.8 days, P<0.0001) and increased long-term rates of readmission (UA: HR 1.24, P=0.0001; RA: HR 1.12, P=0.04). CONCLUSION In patients admitted with an acute MI, residence outside of an MA was associated with diminished rates of cardiac catheterization, longer waiting times and increased rates of readmission. Despite universal health care coverage, Canadians are subject to significant geographical barriers to cardiac catheterization with associated poorer outcomes.

State-of-the-Art Surgical Management of Acute Type A Aortic Dissection

Acute type A aortic dissections still present a major challenge to cardiac surgeons. Although surgical management remains the gold standard, operative mortality remains high, including in experienced centres. Nevertheless, recent advances in the understanding and management of various aspects of these complex operations are expected to improve overall patient outcomes. The Canadian Thoracic Aortic Collaborative (CTAC) represents a group of surgeons with interest and expertise in the management of patients with aortic diseases. The purpose of this state-of-the-art review is to detail our approach to the contemporary surgical management of acute type A aortic dissections. We focus specifically on cannulation strategies, cerebral protection, and extent of proximal and distal resection. In addition, specific clinical scenarios-including malperfusion, intramural hematomas, and surgery in octogenarians-are explored.

Glucolipotoxicity diminishes cardiomyocyte TFEB and inhibits lysosomal autophagy during obesity and diabetes

Impaired cardiac metabolism in the obese and diabetic heart leads to glucolipotoxicity and ensuing cardiomyopathy. Glucolipotoxicity causes cardiomyocyte injury by increasing energy insufficiency, impairing proteasomal-mediated protein degradation and inducing apoptosis. Proteasome-evading proteins are degraded by autophagy in the lysosome, whose metabolism and function are regulated by master regulator transcription factor EB (TFEB). Limited studies have examined the impact of glucolipotoxicity on intra-lysosomal signaling proteins and their regulators. By utilizing a mouse model of diet-induced obesity, type-1 diabetes (Akita) and ex-vivo model of glucolipotoxicity (H9C2 cells and NRCM, neonatal rat cardiomyocyte), we examined whether glucolipotoxicity negatively targets TFEB and lysosomal proteins to dysregulate autophagy and cause cardiac injury. Despite differential effects of obesity and diabetes on LC3B-II, expression of proteins facilitating autophagosomal clearance such as TFEB, LAMP-2A, Hsc70 and Hsp90 were decreased in the obese and diabetic heart. In-vivo data was recapitulated in H9C2 and NRCM cells, which exhibited impaired autophagic flux and reduced TFEB content when exposed to a glucolipotoxic milieu. Notably, overloading myocytes with a saturated fatty acid (palmitate) but not an unsaturated fatty acid (oleate) depleted cellular TFEB and suppressed autophagy, suggesting a fatty acid specific regulation of TFEB and autophagy in the cardiomyocyte. The effect of glucolipotoxicity to reduce TFEB content was also confirmed in heart tissue from patients with Class-I obesity. Therefore, during glucolipotoxicity, suppression of lysosomal autophagy was associated with reduced lysosomal content, decreased cathepsin-B activity and diminished cellular TFEB content likely rendering myocytes susceptible to cardiac injury.

The impact of sequential grafting on clinical outcomes following coronary artery bypass grafting

OBJECTIVES Sequential anastomoses in coronary artery bypass grafting (CABG) offer theoretical advantages including increased graft flow and more complete revascularisation. However, published studies concerning the safety and efficacy of this technique are not definitive. The objective of this study was to assess the effect of sequential anastomoses on outcomes following CABG. METHODS Perioperative data were prospectively collected on all patients with triple-vessel disease who underwent first-time, isolated, on-pump CABG between 1995 and 2005 at a single centre. Patients with a left internal mammary artery graft to the anterior wall and saphenous vein grafts to the lateral and posterior walls were included. RESULTS Compared to patients without sequential anastomoses (n=1108), patients with sequential anastomoses (n=1246) were more likely to have an ejection fraction (EF)<40% (14.9% vs 10.8%, p=0.004), a recent myocardial infarction (19.3% vs 14.3%, p=0.001) and an urgent/emergent operative status (19.6% vs 14.4%, p=0.0008). Median follow-up was 78 months. After adjusting for clinical covariates, sequential grafting was not an independent predictor of in-hospital adverse events (odds ratio (OR) 1.15, 95% confidence interval (CI) 0.88-1.50, p=0.31) or long-term mortality and/or readmission to hospital (hazard ratio (HR) 0.98, 95% CI 0.86-1.12, p=0.74). Sequential grafting was an independent predictor of receiving greater than three distal anastomoses (OR 9.26, 95% CI; 6.27-13.67, p<0.0001). CONCLUSIONS Patients undergoing sequential grafting presented with greater acuity and worse systolic function. After adjusting for baseline differences, sequential grafting was not found to be an independent predictor of adverse events. These results support the safety of sequential anastomoses in patients undergoing CABG.

Validation of optimal reference genes for quantitative real time PCR in muscle and adipose tissue for obesity and diabetes research

The global incidence of obesity has led to an increasing need for understanding the molecular mechanisms that drive this epidemic and its comorbidities. Quantitative real-time RT-PCR (RT-qPCR) is the most reliable and widely used method for gene expression analysis. The selection of suitable reference genes (RGs) is critical for obtaining accurate gene expression information. The current study aimed to identify optimal RGs to perform quantitative transcriptomic analysis based on RT-qPCR for obesity and diabetes research, employing in vitro and mouse models, and human tissue samples. Using the ReFinder program we evaluated the stability of a total of 15 RGs. The impact of choosing the most suitable RGs versus less suitable RGs on RT-qPCR results was assessed. Optimal RGs differed between tissue and cell type, species, and experimental conditions. By employing different sets of RGs to normalize the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), we show that sub-optimal RGs can markedly alter the PGC1α gene expression profile. Our study demonstrates the importance of validating RGs prior to normalizing transcriptional expression levels of target genes and identifies optimal RG pairs for reliable RT-qPCR normalization in cells and in human and murine muscle and adipose tissue for obesity/diabetes research.