In patients with multi-vessel coronary artery diseases, does hybrid revascularization provide similar outcomes to conventional coronary artery bypass grafting?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In [patients with multivessel coronary artery diseases (CAD)] is [hybrid revascularization (HCR)] equal to [coronary artery bypass grafting (CABG)] in regard to [mortality, myocardial infarction, stroke and target vessel revascularization (TVR)]? Three-hundred and fifty-five papers were found using the reported search, of which 8 represented the best evidence to answer the question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The studies included 4 observational studies, 3 randomized controlled trials (RCTs) and 1 meta-analysis. The meta-analysis consisted of predominantly observational data with 1 randomized controlled trial and suggested non-significant differences in all major clinical outcomes. The observational studies generally cited benefit towards hybrid revascularization on the basis of equivalent major clinical outcomes rates compared to coronary artery bypass grafting, yet favourable in-hospital outcomes. One randomized controlled trial provided robust evidence of equivalent 5-year outcomes; however, the others were insufficiently powered for an effective comparison. There is a paucity of robustly designed studies to answer our clinical question effectively, given hybrid procedures are not routine in clinical practice. On the basis of mostly observational and small randomized cohorts with relatively short follow-up intervals, we conclude that current evidence suggests similar mid-term rates of major clinical outcomes after hybrid revascularization and coronary artery bypass grafting. However, without longer-term follow-up, the comparison of the two techniques, particularly relating to repeat revascularization, is still very much uncertain.

In patients undergoing coronary artery bypass grafting is semi-skeletonization superior to pedicled harvesting of the left internal mammary artery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, 'in patients undergoing coronary artery bypass grafting is semi-skeletonized harvesting superior to pedicled harvesting of the left internal mammary artery (LIMA) in terms of conduit length, flow, rate of sternal wound infections and post-operative bleeding?'. Altogether, 235 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. Three studies were cohort studies and 2 were randomized controlled trials. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. One randomized controlled trial showed superiority with semi-skeletonized harvesting in terms of conduit length (P < 0.001), flow (P = 0.004) and diastolic filling (P = 0.005). Three studies included data on surgical wound infections/mediastinitis, all of which reported n = 0. One randomized controlled trial and 3 cohort studies reported that semi-skeletonized harvesting reduced postoperative bleeding. No studies reported a statistically significant difference in operative time. This review suggests that semi-skeletonized harvesting could possibly be associated with favourable outcomes when compared to pedicled harvesting with respect to graft length and flow, and lower postoperative bleeding, without increasing operative time; although there is insufficient data to compare sternal wound infections or long-term outcomes. In conclusion, the limited evidence base prevents robust informed decision-making when comparing both techniques.

Pre-injury use of antiplatelet and anticoagulations therapy are associated with increased mortality in a cohort of 1038 hip fracture patients.

BACKGROUND: Hip fractures are a large burden on the health care systems of developed nations. Patients usually have multiple co-morbidities and the pre-injury use of anticoagulants and anti-platelet medication is common. MATERIALS AND METHODS: This study used a single hospital hip fracture database to facilitate a retrospective analysis of the impact of anti-coagulation and anti-platelet therapy on mortality and complications after surgical management of hip fractures. There were 92 patients on warfarin, 69 on DOAC, 260 antiplatelet patients and 617 control patients. RESULTS: Mortality rates at 30 days were 4.8% for the control group, 12.6% for the antiplatelet group, warfarin 7.0%, 9.5% for Direct Oral Anticoagulant (DOAC) group, p = 0.004. Mortality rates at 1 year were 22.4% for the control group, 32.3% for the antiplatelet group, 29.3% for the warfarin group and 29.0% for DOAC group (p=0.007). Amongst complications, significant differences were found in transfusion (DOAC) and wound ooze (warfarin) rates, but the study did not detect significant clinical consequences arising from these differences. A matched analysis for age, sex, and ASA was undertaken to look in more detail at mortality data. Some mortality differences remained between groups with anti-platelet medication associated with increased mortality, but the differences no longer appeared to be significant. Our data suggests that this is a non-causal association, which could be incorporated into predictive mortality risk scores such as the Nottingham hip fracture score. CONCLUSION: We believe that pre-injury antiplatelet therapy is a strong indicator for high risk patients with higher expected mortality after hip fracture surgery. We saw no evidence to support delayed surgery in patients taking DOACs.

In patients undergoing valve-sparing aortic root replacement, is reimplantation superior to remodelling?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: in patients undergoing valve-sparing aortic root replacement, is reimplantation superior to remodelling? The purpose of this best evidence topic was to re-review the updated evidence that has become available in the near decade since the previous review published in 2011. Altogether more than 300 papers were found using the reported search, of which 8 papers 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 included studies have significant limitations relating to low-level evidence study design, variable outcome collection and limited significance testing with direct comparison. Long-term outcomes such as survival, recurrence of aortic regurgitation and valve reintervention were largely equal between the two procedures across the studies. This review, updated from the previous best evidence topic, continues to suggest that there are no clear recommendations or even consensus to guide clinical decision-making when choosing between remodelling or reimplantation approaches to valve-sparing aortic root replacement. To date, no study provides strong clinical benefit to favour either procedure in terms of perioperative outcomes, medium-long term survival or reintervention of the aortic valve. As such, procedure selection should be based upon patient factors and valve evaluation, combined with surgeon preference and experience.

Techniques and approaches for revascularisation of left heart coronary diseases.

Coronary artery disease and its associated clinical sequelae are a significant medical burden to clinicians and patients. Severe coronary artery disease presenting in the context of acute myocardial ischaemia, or stable plaques causing chronic symptoms despite best conservative and pharmacological intervention, are often amenable to further intervention such as coronary artery bypass grafting. This procedure has been extensively compared to newer and less invasive techniques, such as percutaneous coronary intervention, and other minimally invasive procedures such as robotic or endoscopic techniques. This review summarises the current evidence on revascularisation of the left coronary artery system, with particular emphasis on key clinical endpoints of mortality, myocardial infarction, stroke and repeat revascularisation.

A randomised, factorial trial to reduce arterial stiffness independently of blood pressure: Proof of concept? The VaSera trial testing dietary nitrate and spironolactone.

AIMS: To test if spironolactone or dietary nitrate from beetroot juice could reduce arterial stiffness as aortic pulse wave velocity (PWVart), a potential treatment target, independently of blood pressure. METHODS: Daily spironolactone (≤50 mg) vs doxazosin (control ≤16 mg) and 70 mL beetroot juice (Beet-It ≤11 mmol nitrate) vs nitrate-depleted juice (placebo; 0 mmol nitrate) were tested in people at risk or with type-2 diabetes using a double-blind, 6-month factorial trial. Vascular indices (baseline, 12, 24 weeks) were cardiac-ankle vascular index (CAVI), a nominally pressure-independent stiffness measure (primary outcome), PWVart secondary, central systolic pressure and augmentation. Analysis was intention-to-treat, adjusted for systolic pressure differences between trial arms. RESULTS: Spironolactone did not reduce stiffness, with evidence for reduced CAVI on doxazosin rather than spironolactone (mean difference [95% confidence interval]; 0.25 [-0.3, 0.5] units, P = .080), firmer for PWVart (0.37 [0.01, 0.7] m/s, P = .045). There was no difference in systolic pressure reduction between spironolactone and doxazosin (0.7 [-4.8, 3.3] mmHg, P = .7). Circulating nitrate and nitrite increased on active vs placebo juice, with central systolic pressure lowered -2.6 [-4.5, - 0.8] mmHg, P = .007 more on the active juice, but did not reduce CAVI, PWVart or peripheral pressure. Change in nitrate and nitrite concentrations were 1.5-fold [1.1-2.2] and 2.2-fold [1.3, 3.6] higher on spironolactone than on doxazosin respectively; both P < .05. CONCLUSION: Contrary to our hypothesis, in at-risk/type 2 diabetes patients, spironolactone did not reduce arterial stiffness, rather PWVart was lower on doxazosin. Dietary nitrate elevated plasma nitrite, selectively lowering central systolic pressure, observed previously for nitrite.

Management of aortic valve disease during pregnancy: A review.

Cardiovascular disease represents a significant portion of pregnancy-related complications and is associated with high rates of morbidity and mortality in this cohort. Cardiac valvulopathy, and aortic valve pathologies, in particular, pose a significant challenge to women who are pregnant and to the health care professionals who look after them. Depending on the type and severity of aortic valve pathology, pregnancy may exacerbate or accelerate the progression of valvulopathy sequelae because of the hemodynamic changes that occur from conception, throughout gestation, up to Labor and postpartum. Management of such patients ranges from basic conservative measures such as bed-rest, extending to high-risk emergency open heart surgery. This nonstructured review aims to highlight the current evidence available relating to the management of aortic valve disease in pregnancy, with a key focus on cases which requires intervention beyond that of medical therapy. In conclusion, the management of aortic valvulopathy in pregnancy is a challenging field with only a small amount of clinical experience and retrospective study supporting evidence-based decisions in this field. A greater understanding of the most recent advances is recommended to support decision making in this specialist field of clinical medicine.

Anti-platelet and anti-coagulant therapy in peripheral arterial disease prior to surgical intervention.

OBJECTIVE: Peripheral artery disease is a major clinical co-morbidity that can significantly affect quality of life, especially in the presence of diabetes mellitus and older age. The focus of this literature review is on medical management, through anti-platelet and anti-coagulation, of peripheral artery disease prior to undergoing surgical or endovascular management. METHOD: Extensive electronic literature search performed in four major databases (PubMed, SCOPUD, Embase and Ovid) to identify the published randomized and non-randomized studies that compared and discussed the management of peripheral artery disease with different anti-thrombotic agents. RESULTS: A total of 17 studies were identified to meet the inclusion criteria of this review. Among them, 4 were systematic review and meta-analyses, 1 was observational study and 12 were randomized controlled trials. The reported outcomes in each study are summarized and reported separately within this review. CONCLUSION: Peripheral artery disease is a complex and multifactorial clinical condition. The use of dual anti-platelets, such as aspirin and clopidogrel, are the key in preventing major cardiovascular events as well as stroke and death. Utilization of anti-coagulation such as direct oral anti-coagulants' as additional parameters for the prevention of disease progression, is paramount. Eventually, the choice of either dual-antiplatelet therapy or combined anti-coagulation with anti-platelets should be carefully considered, particularly following the most recent published debatable studies.

It is rocket science - why dietary nitrate is hard to 'beet'! Part I: twists and turns in the realization of the nitrate-nitrite-NO pathway.

Dietary nitrate (found in green leafy vegetables, such as rocket, and in beetroot) is now recognized to be an important source of nitric oxide (NO), via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. While this pathway may now seem obvious, its realization followed a rather tortuous course over two decades. Early steps included the discovery that nitrite was a source of NO in the ischaemic heart but this appeared to have deleterious effects. In addition, nitrate-derived nitrite provided a gastric source of NO. However, residual nitrite was not thought to be absorbed systemically. Nitrite was also considered to be physiologically inert but potentially carcinogenic, through N-nitrosamine formation. In Part 1 of a two-part Review on the nitrate-nitrite-NO pathway we describe key twists and turns in the elucidation of the pathway and the underlying mechanisms. This provides the critical foundation for the more recent developments in the nitrate-nitrite-NO pathway which are covered in Part 2.

It is rocket science - why dietary nitrate is hard to 'beet'! Part II: further mechanisms and therapeutic potential of the nitrate-nitrite-NO pathway.

Dietary nitrate (found in green leafy vegetables such as rocket and in beetroot) is now recognized to be an important source of nitric oxide, via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. Having described key twists and turns in the elucidation of the pathway and the underlying mechanisms in Part I, we explore the more recent developments which have served to confirm mechanisms, extend our understanding, and discover new properties and potential therapeutic uses of the pathway in Part II. Even the established dependency on low oxygen states for bioactivation of nitrite has recently been challenged. Dietary nitrate appears to be an important component of 'healthy diets', such as the DASH diet to lower blood pressure and the Mediterranean diet, with its potential to lower cardiovascular risk, possibly through beneficial interactions with a range of other constituents. The World Cancer Research Foundation report strong evidence for vegetables including spinach and lettuce (high nitrate-containing) decreasing cancer risk (mouth, pharynx, larynx, oesophagus and stomach), summarized in a 'Nitrate-Cancer Risk Veg-Table'. The European Space Agency recommends that beetroot, lettuce, spinach and rocket (high-nitrate vegetables) are grown to provide food for long-term space missions. Nitrate, an ancient component of rocket fuel, could support sustainable crops for healthy humans.

Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress.

BACKGROUND: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs) are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression. METHODS: Rat VSMCs were stimulated by PDGF (50 ng/mL) plus TNF-α (10 ng/mL) or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 µM) or with apocynin (20 nM) for 2 hours, then zoledronate (100 µM) was added into 2% fetal calf serum containing medium for 24 hours. RESULTS AND DISCUSSION: Using isolated rat VSMCs in culture, zoledronate (100 µM) increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-κB pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-κB activation and MMP-9 and MMP-13 up-regulation by zoledronate. CONCLUSION: We conclude that zoledronate increases MMP-9 and MMP-13 expressions in rat VSMCs dependent upon stimulation of the NF-κB pathway by reactive oxygen species. Effects on MMP expression may contribute to the pharmacologic profile of bisphosphonates.