Umar A.R. Chaudhry

The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have been widely proposed as in vitro models of myocardial physiology and disease. A significant obstacle, however, is their immature phenotype. We hypothesised that Ca2+ cycling of iPSC-CM is influenced by culture conditions and can be manipulated to obtain a more mature cellular behaviour. To test this hypothesis we seeded iPSC-CM onto fibronectin coated microgrooved polydimethylsiloxane (PDMS) scaffolds fabricated using photolithography, or onto unstructured PDMS membrane. After two weeks in culture, the structure and function of iPSC-CM were studied. PDMS microgrooved culture substrates brought about cellular alignment (p < 0.0001) and more organised sarcomere. The Ca2+ cycling properties of iPSC-CM cultured on these substrates were significantly altered with a shorter time to peak amplitude (p = 0.0002 at 1 Hz), and more organised sarcoplasmic reticulum (SR) Ca2+ release in response to caffeine (p < 0.0001), suggesting improved SR Ca2+ cycling. These changes were not associated with modifications in gene expression. Whilst structured tissue culture may make iPSC-CM more representative of adult myocardium, further construct development and characterisation is required to optimise iPSC-CM as a model of adult myocardium.

Modern management of systolic anterior motion of the mitral valve

Systolic anterior motion (SAM) of the mitral valve (MV) can be a life-threatening condition. The SAM can result in severe left ventricular outflow tract obstruction and/or mitral regurgitation and is associated with an up to 20% risk of sudden death (which is substantially lower in hypertrophic cardiomyopathy (HCM)). The mechanisms of SAM are complex and depend on the functional status of the ventricle. The SAM can occur in the normal population, but is typically observed in patients with HCM or following MV repair. Echocardiography (2D, 3D and stress) has a central diagnostic role as the application of echocardiographic SAM predictors allows the incorporation of prevention techniques during surgery and post-operative SAM assessment. Cardiac magnetic resonance imaging has a special role in understanding the dynamic nature of SAM, especially in anatomically atypical hearts (including HCM). This article describes what the clinician needs to know about SAM ranging from pathophysiological mechanisms and imaging modalities to conservative (medical) and surgical approaches and their respective outcomes. A stepwise approach is advocated consisting of medical therapy, followed by aggressive volume loading and beta-adrenoceptor blockade. Surgery is the final option. The correct choice of surgical technique requires an understanding of the anatomical substrate of SAM.

Off-Pump Versus On-Pump Coronary Revascularization: Meta-Analysis of Mid- and Long-Term Outcomes

BACKGROUND Early outcomes for off-pump coronary artery bypass grafting (OPCAB) have been extensively compared with on-pump coronary revascularization (ONCAB); however, the long-term effects of OPCAB continue to be debated. This study aims to compare the mid-term (>1year; ≤5 years) and long-term (>5 years) survival and major adverse cardiovascular and cerebrovascular events of OPCAB versus ONCAB. METHODS A systematic search identified 32 studies meeting our inclusion criteria. These were analyzed using random effects modeling, with subgroup evaluation according to study type. Primary outcomes were mid- and long-term survival over a follow-up period greater than 1 year. Secondary outcomes were mid- and long-term events including repeat revascularization, myocardial infarction, angina, heart failure, and cerebrovascular accidents. RESULTS Off-pump coronary artery bypass grafting confers similar overall mid-term survival when compared with ONCAB (hazard ratio, 1.06; 95% confidence interval, 0.95 to 1.19; p=0.31). On-pump coronary artery bypass grafting was associated with a significant trend towards a long-term survival advantage (hazard ratio, 1.06; 95% confidence interval, 1.00 to 1.13; p=0.05); however, this was no longer present when subgroup analysis of only randomized controlled trials, registry-based studies, and propensity-matched studies was performed. There was an increase in angina recurrence among two studies after OPCAB, but no difference was seen in 11 other studies reporting data as odds ratio. No significant differences were observed in other secondary outcomes. CONCLUSIONS This analysis demonstrates comparable mid-term mortality and mid- to long-term morbidity between OPCAB and ONCAB. On-pump coronary artery bypass grafting may be associated with improved long-term survival when all study types are analyzed; however, analysis of only randomized controlled trials and propensity-matched studies demonstrates comparable long-term mortality between OPCAB and ONCAB.

Surgical management of superior vena cava syndrome following pacemaker lead infection: a case report and review of the literature

Superior vena cava (SVC) syndrome is a known but rare complication of pacemaker lead implantation, accounting for approximately less than 0.5% of cases. Its pathophysiology is due to either infection or endothelial mechanical stress, causing inflammation and fibrosis leading to thrombosis, and therefore stenosis of the SVC. Due to the various risks including thrombo-embolic complications and the need to provide symptomatic relief, medical and surgical interventions are sought early. We present the case of a 48-year Caucasian male who presented with localised swelling and pain at the site of pacemaker implantation. Inflammatory markers were normal, but diagnostic imaging revealed three masses along the pacemaker lead passage. A surgical approach using cardiopulmonary bypass and circulatory arrest was used to remove the vegetations. Culture from the vegetations showed Staphylococcus epidermidis. The technique presented here allowed for safe and effective removal of both the thrombus and infected pacing leads, with excellent exposure and minimal post-procedure complications.

Does off-pump coronary artery bypass graft surgery have a beneficial effect on long-term mortality and morbidity compared with on-pump coronary artery bypass graft surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether off-pump coronary artery bypass grafting (CABG) surgery offered superior long-term outcomes compared with on-pump CABG surgery. Best evidence papers were considered to be those that had a follow-up period of ≥5 years, had >50 patients in either cohort, did not utilize concomitant interventions nor comprised low-risk, high-risk or sub-population groups. Where potential duplicate data sets from the same institution were likely, the more credible and recently published study was included. Two hundred and fifty-six papers were found as a result of the reported search, of which 16 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The 16 studies comprised 4 prospective randomized controlled trials (RCTs), with the remaining 12 retrospective, of which 8 were propensity-score matched. All 4 RCTs contained fewer than 450 participants. Two studies concluded with a survival advantage towards on-pump CABG: one, a large registry-based study, the Veterans Affairs, with >25 000 patients, and another, a propensity-matched retrospective study involving almost 8000 patients. The remaining 14 studies all provided evidence to suggest comparable long-term survival. In addition, all other long-term outcomes mentioned within these studies including angina recurrence, myocardial infarction heart failure, need for revascularization, stroke, graft patency, cognitive and quality of life showed similar results between the two groups. We conclude that off-pump CABG surgery may have similar or slightly reduced long-term survival compared with on-pump CABG surgery. Other long-term indicators such as cardiovascular or cerebrovascular events or neuro-psychological outcomes were similar between the two groups. Despite these conclusions, the evidence is limited by substantial variability in patient selection and study methods. The CORONARY (coronary artery bypass surgery off- or on-pump revascularization study) trial recently presented results, which showed no significant differences in composite outcomes at 1 year; it will be interesting to observe whether these comparable outcomes are maintained for a much longer time frame.

Surgical management of infected cardiac implantable electronic devices

The growing use of cardiac implantable electronic devices (CIED) has led to infections requiring intervention. These are traditionally managed using a percutaneous transvenous approach to fully extract the culpable leads. Indications for such strategies are well-established and range from simple traction to the use of powered extraction tools including laser sheaths. Where such attempts fail, or if there are further complications, then there may be need for a cardiothoracic surgical approach. Limited evidence is currently available on the merits of individual strategies, and these are mainly drawn from case reports or series. Most utilise cardiopulmonary bypass, cardioplegic arrest and entry within the right atrium to allow direct visualisation of any vegetation and safely explant all CIED components whilst avoiding perforation, valvular and paravalvular damage. In this review, we describe a number of these and the unique challenges faced by surgeons when attempting to extract CIED. It is clear that future work should concentrate on creating clear consensus and guidelines on indications, risks and measures of efficacy outcomes for various surgical techniques.

How revascularization on the beating heart with cardiopulmonary bypass compares to off-pump? A meta-analysis of observational studies

Off-pump coronary artery bypass surgery has been a controversial area of debate and the outcome profile of the technique has been thoroughly investigated. Scepticism regarding the reported outcomes and the conduct of the randomized trials comparing this technique with conventional on-pump coronary artery bypass surgery has been widely voiced, and the technique of off-pump surgery remains as an infrequently adopted approach to myocardial revascularization worldwide. Criticisms of the technique are related to lower rates of complete revascularization and its unknown long-term consequences, the significant detrimental effects on mortality and major adverse events when emergency conversion is required, and the significant lack of long-term survival and morbidity data. The hybrid technique of myocardial revascularization on the beating heart with the use of cardiopulmonary bypass may theoretically provide the beneficial effects of off-pump surgery in terms of myocardial protection and organ protection, while providing the safety and stability of on-pump surgery to allow complete revascularization. Large randomized comparison to support evidence-based choices is currently lacking. In this article, we have meta-analysed the outcomes of on-pump beating heart surgery in comparison with off-pump surgery focusing on major adverse cardiovascular and cerebrovascular adverse events (MACCE) including mortality, stroke and myocardial infarction and the degree of revascularization and number of bypass grafts performed. It was demonstrated that the beating heart on-pump technique allows a significantly higher number of bypass grafts to be performed, resulting in significantly higher degree of revascularization. We have also demonstrated a slightly higher rate of 30-day mortality and MACCE with the technique although not at a statistically significant level. These results should be considered alongside the population risk profile, where a significantly higher risk cohort had undergone the beating heart on-pump technique. Long-term survival and morbidity figures are required to assess the impact of these findings in the coronary surgery patient population.

Off-pump or on-pump beating heart: which technique offers better outcomes following coronary revascularization?

A best evidence topic was written according to a structured protocol. The question addressed was whether on-pump beating heart coronary artery bypass (BH-ONCAB) surgery has a different outcome profile in comparison to off-pump coronary artery bypass (OPCAB). A total of 205 papers were found by systematic search of which 7 provided the largest and most recent outcome analysis comparing BH-ONCAB with OPCAB, and represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results were tabulated. Reported outcome measures included mortality, stroke, myocardial infarction, renal failure, myocardial damage, change in ejection fraction, number of bypass grafts and completeness of revascularization. With the exception of one study that favoured the off-pump technique, our review did not demonstrate a statistically significant difference in terms of mortality between the groups. We did not identify a statistically significant difference in any reported morbidity outcomes. However, there was a trend towards better outcomes for the on-pump beating heart technique, despite a higher risk profile in terms of age, ejection fraction and burden of coronary disease in this group. Consistent statistically significant differences between the groups were the mean number of grafts performed and the completeness of revascularization, both of which were higher with the on-pump beating heart technique. Limitations to the current evidence include the finding that most of the current data arise from specialist off-pump surgeons or centres that would usually only carry out BH-ONCAB in the higher risk patients where the added safety of cardiopulmonary bypass is desired.

Should we consider beating-heart on-pump coronary artery bypass grafting over conventional cardioplegic arrest to improve postoperative outcomes in selected patients?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether beating-heart on-pump coronary artery bypass grafting (BH-ONCAB) offered superior mortality and morbidity outcomes when compared with conventional on-pump coronary artery bypass grafting (C-ONCAB). Morbidity outcomes consisted of renal failure, stroke (transient or permanent), myocardial infarction, angina, congestive cardiac failure, reintervention and arrhythmias. Best evidence papers investigating BH-ONCAB versus C-ONCAB were considered. Where data were duplicated, the more credible evidence-based and recently published study was included. Two hundred and thirty-one papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. Two were prospective randomized controlled trials and the remaining 10 observational studies, of which one was propensity-matched. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Five of these studies demonstrated significantly improved mortality following BH-ONCAB; however, one study exhibited better survival after C-ONCAB. Notably, this study incorporated BH-ONCAB patients with significantly more haemodynamic instability, thus possibly explaining the worse mortality outcomes. In terms of morbidity, a slightly more mixed picture is drawn. Five studies report morbidity in favour of BH-ONCAB, whereas three studies include individual outcomes favouring C-ONCAB. The remaining studies showed equivalent mortality and morbidity data. In summary, the results presented here suggest that BH-ONCAB may improve survival following coronary artery bypass surgery. A key observation is that the greatest benefits of BH-ONCAB appear to be in studies including patients with considerably higher risk characteristics at the time of surgery (haemodialysis, end-stage coronary artery disease, emergency surgery, low ejection fraction). There are limitations of the current evidence presented. Only two studies were randomized controlled trials. There was variability in sample size, selection criteria and preoperative risk profiles between the studies. The studies span many years, and the outcomes may have been affected by evolving technologies and differing patient profiles between these periods.