Pentoxifylline for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility, and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating people with PAD, but results of these studies are variable. This is the second update of a review first published in 2012. OBJECTIVES: To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of people with stable intermittent claudication, Fontaine stage II. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 January 2020. There were no language restrictions. SELECTION CRITERIA: We included all double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in people with IC Fontaine stage II. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed the included studies, matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies using the Cochrane 'Risk of bias' tool and collected results related to the outcomes of interest, pain-free walking distance (PFWD), total walking distance (TWD), ankle-brachial pressure index (ABI), quality of life (QoL) and side effects. Comparison of studies was based on duration and dose of pentoxifylline. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified no new eligible studies for this update. This review includes 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. The seven remaining studies compared pentoxifylline with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies), and buflomedil and nifedipine (one study). Risk of bias for the individual studies was generally unclear because there was a lack of methodological reporting for many of the included studies, especially regarding randomisation and allocation methods. Most included studies did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis for comparisons which included more than one study, was not possible. Pentoxifylline compared to placebo Of 17 studies comparing pentoxifylline with placebo, 11 reported PFWD and 14 reported TWD; the difference in percentage improvement in PFWD for pentoxifylline over placebo ranged from -33.8% to 73.9% and in TWD ranged from 1.2% to 155.9%. It was not possible to pool the data of the studies because data were insufficient and findings from individual trials were unclear. Most included studies suggested a possible improvement in PFWD and TWD for pentoxifylline over placebo (both low-certainty evidence). The five studies which evaluated pre-exercise ABI comparing pentoxifylline and placebo found no evidence of a difference (moderate-certainty evidence). Two of the three studies that evaluated QoL between people who received pentoxifylline and placebo were larger studies that used validated QoL tools and generally found no evidence of a difference between groups. One small, short-term study, which did not specify which QoL tool was used, reported improved QoL in the pentoxifylline group (moderate-certainty evidence). Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea (low-certainty evidence). Certainty of the evidence from this review was low or moderate, with downgrading due to risk of bias concerns, inconsistencies between studies and the inability to evaluate imprecision because meta-analysis could not be undertaken. The seven remaining studies compared pentoxifylline with either flunarizine, aspirin, Gingko biloba extract, nylidrin hydrochloride, prostaglandin E1, or buflomedil and nifedipine; data were too limited to allow any meaningful conclusions to be made. AUTHORS' CONCLUSIONS: There is a lack of high-certainty evidence for the effects of pentoxifylline compared to placebo, or other treatments, for IC. There is low-certainty evidence that pentoxifylline may improve PFWD and TWD compared to placebo, but no evidence of a benefit to ABI or QoL (moderate-certainty evidence). Pentoxifylline was reported to be generally well tolerated (low-certainty evidence). Given the large degree of heterogeneity between the studies, the role of pentoxifylline for people with IC Fontaine class II remains uncertain.

Early Hemodynamic Performance of the Crown PRT Aortic Prosthesis: A Prospective Study.

BACKGROUND: Currently, only limited data are available on the rate of hemodynamic progression with clinical outcome in patients receiving the latest Crown PRT aortic prosthesis. The study aim was to report clinical and hemodynamic outcomes in 55 consecutive patients for a follow up of up to one year after Crown PRT implantation. METHODS: Between February and September 2015, a total of 55 patients (34 males, 21 females; mean age 77.3 ± 1.2 years) underwent aortic valve replacement (AVR) with the latest LivaNova Crown PRT bioprosthesis at the authors' institution. Left ventricular function was preserved in 79% of patients. Data relating to the patients' clinical, echocardiographic and functional capacities were obtained prospectively. RESULTS: There were no in-hospital deaths. Significant perioperative complications included stroke (3.6%), atrial fibrillation (27%), and permanent pacemaker insertion (1.8%). Pre-discharge echocardiography demonstrated peak (PG) and mean (MG) transprosthetic gradients of 24.4 ± 10.4 mmHg and 12.9 ± 6.2 mmHg, respectively. The Doppler velocity index (DVI) was 0.49 ± 0.13, and the effective orifice area index (EOAi) 0.89 ± 0.12 cm2/m2. At a mean follow up of 1.3 ± 0.3 years, the transprosthetic gradients, DVI and EOAi were not significantly different from postoperative or pre-discharge values. The patients' NYHA status was I or II in 95% of cases, and the mean left ventricular mass had decreased by 36% at the end of follow up. CONCLUSIONS: The Crown PRT is an effective bioprosthesis, with a low incidence of valve-related complications comparable to those of other current bioprostheses. The bioprosthesis demonstrated satisfactory results in terms of hemodynamics and freedom from reoperation.

Hypoxia-mediated regulation of the secretory properties of mitral valve interstitial cells.

The sophisticated function of the mitral valve depends to a large extent on its extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important stimulus is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVICs) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulfated glycosaminoglycans (sGAG) in cultured porcine MVICs. Increased gene expression of matrix metalloproteinases-1 and -9 and their tissue inhibitors 1 and 2 was also observed after incubation under hypoxic conditions for up to 24 h. Hypoxia had no effect on MVIC viability, morphology, or phenotype. MVICs expressed hypoxia-inducible factor (HIF)-1α under hypoxia. Stimulating HIF-1α chemically caused a reduction in the amount of sGAG produced, similar to the effect observed under hypoxia. Human rheumatic valves had greater expression of HIF-1α compared with normal or myxomatous degenerated valves. In conclusion, hypoxia affects the production of certain ECM proteins and expression of matrix remodeling enzymes by MVICs. The effects of hypoxia appear to correlate with the induction of HIF-1α. This study highlights a potential role of hypoxia and HIF-1α in regulating the mitral valve, which could be important in health and disease.NEW & NOTEWORTHY This study demonstrates that hypoxia regulates extracellular matrix secretion and the remodeling potential of heart valve interstitial cells. Expression of hypoxia-induced factor-1α plays a role in these effects. These data highlight the potential role of hypoxia as a physiological mediator of the complex function of heart valve cells.

Pentoxifylline for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating individuals with PAD, but results of these studies are variable. This is an update of a review first published in 2012. OBJECTIVES: To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of individuals with stable intermittent claudication, Fontaine stage II. SEARCH METHODS: For this update, the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3). SELECTION CRITERIA: All double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in patients with IC Fontaine stage II. DATA COLLECTION AND ANALYSIS: Two review authors separately assessed included studies,. matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies by using the Cochrane 'Risk of bias' tool and collected results related to pain-free walking distance (PFWD) and total walking distance (TWD). Comparison of studies was based on duration and dose of pentoxifylline. MAIN RESULTS: We included in this review 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. In the seven remaining studies, pentoxifylline was compared with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies) and buflomedil and nifedipine (one study). The quality of the evidence was generally low, with large variability in reported findings.. Most included studies did not report on random sequence generation and allocation concealment, did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis was not possible.Of 17 studies comparing pentoxifylline with placebo, 14 reported TWD and 11 reported PFWD; the difference in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2% to 155.9%, and in PFWD from -33.8% to 73.9%. Testing the statistical significance of these results generally was not possible because data were insufficient. Most included studies suggested improvement in PFWD and TWD for pentoxifylline over placebo and other treatments, but the statistical and clinical significance of findings from individual trials is unclear. Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea. AUTHORS' CONCLUSIONS: Given the generally poor quality of published studies and the large degree of heterogeneity evident in interventions and in results, the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain. Pentoxifylline was shown to be generally well tolerated.Based on total available evidence, high-quality data are currently insufficient to reveal the benefits of pentoxifylline for intermittent claudication.

In-hospital outcomes of pedicled bilateral internal mammary artery use in diabetic and nondiabetic patients undergoing off-pump coronary artery bypass grafting: single-surgeon, single-center experience.

OBJECTIVE: A common perception is that use of pedicled bilateral internal mammary arteries (BIMA) increases the risk of sternal wound complications in diabetic patients undergoing coronary artery bypass grafting (CABG). The purpose of this study was to compare the in-hospital outcomes of CABG using pedicled BIMA in diabetic and nondiabetic patients. METHODS: From September 1998 to September 2010, 390 consecutive diabetic patients and 519 nondiabetic patients underwent isolated off-pump CABG using pedicled BIMA. The 2 groups had comparable preoperative demographics except for a higher prevalence of acute myocardial infarction (18.9% versus 6.1%, P = .01), peripheral vascular disease (17.2% versus 2.7%, P = .001), an ejection fraction <30% (17.7% versus 8.5%, P = .02), and chronic renal failure (4.5% versus 0.9%, P = .01) in the diabetic patients. RESULTS: The operative mortality rate of the diabetic patients was comparable to that of the nondiabetic patients (2.8% versus 2.1%, P = .87). The in-hospital outcomes, including occurrence of superficial and deep sternal wound infections, were similar except for an increased occurrence of wound infection at the vein harvest site (6.6% versus 1.1%, P = .04) and a need for hemofiltration (11.8% versus 2.1%, P = .02) in the diabetic patients. CONCLUSIONS: Pedicled BIMA use is associated with comparable incidences of sternal wound complications and other outcomes in diabetic patients and nondiabetic patients. Strict perioperative glycemic control, adherence to meticulous closure technique, and postoperative management of surgical wounds can make pedicled BIMA use a default strategy for diabetic patients.

Concomitant off-pump coronary artery bypass grafting results in improved in-hospital outcomes for patients with ischemic mitral regurgitation undergoing surgery.

OBJECTIVE: Surgical management of ischemic mitral regurgitation (IMR) has primarily consisted of revascularization with or without the addition of mitral valve repair or replacement. We hypothesize that performing off-pump coronary artery bypass (OPCAB) grafting before fixing MR improves in-hospital outcomes for patients with IMR undergoing surgery. METHODS: From January 2000 through December 2010, a total of 96 consecutive patients with moderate or severe IMR, as determined by preoperative echocardiography, underwent on-pump coronary artery bypass grafting (CABG) (n = 66) or OPCAB (n = 30) revascularization with concomitant mitral valve repair or replacement. A retrospective analysis of a prospectively collected cardiac surgery database (PATS; Dendrite Clinical Systems, Oxford, UK) was performed. In addition, medical notes and charts were reviewed for all study patients. RESULTS: The 2 groups had similar preoperative demographic and EuroSCORE risk-stratification characteristics. The operative mortality rate for the entire cohort was 9.4%. Patients who underwent OPCAB grafting had a lower operative mortality than those who underwent CABG (3.3% versus 12.1%; P = .006). The mean ±SD cardiopulmonary bypass time (82.7 ± 34.7 minutes versus 160.7 ± 45.2 minutes; P < .001) and cross-clamp time (49.0 ± 22.4 minutes versus 103.4 ± 39.5 minutes; P < .001) were significantly shorter in the off-pump group than in the on-pump group. The OPCAB group also had significantly less in-hospital morbidity and shorter stays in the intensive care unit and the hospital. CONCLUSION: Our analysis shows that OPCAB grafting (compared with conventional CABG) before repairing MR is associated with favorable in-hospital outcomes for patients undergoing surgery for IMR.

Role of hypoxia inducible factor HIF-1α in heart valves.

The 2016 Albert Lasker Basic Medical Research Award and subsequently the 2019 Nobel Prize in Physiology or Medicine were awarded to William Kaelin, Jr., Sir Peter Ratcliffe, and Gregg Semenza for their work on how cells sense and adapt to hypoxic conditions. Their work showed that the changes in gene expression, cell metabolism, and tissue remodelling that occur in response to low oxygen concentrations are orchestrated by the transcription factor, hypoxia inducible factor-1α (HIF-1α). While the effects mediated by HIF-1α have been widely studied, its role in heart valves has only recently been investigated. These studies have shown that HIF-1α expression is evident in mechanisms that regulate the structure and function of heart valves. These include embryonic development, the regulation of the extracellular matrix, angiogenesis and the initiation of the calcification process. This review provides a background on the role and function of HIF-1α in response to hypoxia and a discussion of the available evidence of its involvement in the regulation of heart valves in health and disease.

Pentoxifylline for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial occlusive disease (PAD). It is associated with high morbidity and mortality. Pentoxifylline is one of many drugs used to treat IC. Pentoxifylline decreases blood viscosity, improves erythrocyte flexibility, and increases microcirculatory flow and tissue oxygen concentration.Many studies have evaluated the efficacy of pentoxifylline in treating PAD but the results of these studies are very variable. OBJECTIVES: To determine the efficacy of pentoxifylline in improving the walking capacity (that is pain-free walking distance and the total (absolute, maximum) walking distance) of patients with stable intermittent claudication, Fontaine stage II. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched January 2011) and CENTRAL (2011, Issue 1). In addition, we searched MEDLINE (Week 2 January 2011) and EMBASE (2011 Week 03). ClinicalTrials.gov and Current Controlled Trials were searched for ongoing or unpublished trials. SELECTION CRITERIA: All double blind, randomised controlled trials (RCTs) comparing pentoxifylline to placebo or any other pharmacological intervention in patients with IC Fontaine stage II. DATA COLLECTION AND ANALYSIS: Included studies were assessed separately by two review authors. Data were matched and disagreements resolved by discussion. The quality of the studies was assessed using the Jadad score and the Cochrane risk of bias tool. Results relating to pain-free walking distance (PFWD) and total walking distance (TWD) were collected. Studies were compared based on the duration and dose of pentoxifylline. MAIN RESULTS: Twenty-three studies with 2816 participants were included in this review. There was considerable heterogeneity between the included studies with regards to multiple variables including duration of treatment, dose of pentoxifylline, baseline walking distance and patient characteristics, and therefore pooled analysis was not possible. The quality of the included studies was generally low. There was very large variability in the reported findings between the individual studies. In a total of 17 studies which compared pentoxifylline with placebo, of which 14 reported TWD and 11 reported PFWD, the difference in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2% to 155.9%, and for PFWD the difference ranged from -33.8% to 73.9%. Testing for statistical significance of these results was generally not possible due to the lack of data. There was no statistically significant difference in ankle brachial pressure index (ABI) between the pentoxifylline and placebo groups. Pentoxifylline was generally well tolerated. AUTHORS' CONCLUSIONS: Given the generally poor quality of the published studies and the large degree of heterogeneity in the interventions and the results, the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain. Pentoxifylline is generally well tolerated.  Based on the totality of the available evidence, it is possible that pentoxifylline could have a place in the treatment of IC as a means of improving walking distance and as a complimentary treatment assuming all other essential measures such as lifestyle change, exercise and treatment for secondary prevention have been taken into account. However, the response to pentoxifylline should be assessed on an individual basis.

Impact of gentamicin-collagen sponge (Collatamp) on the incidence of sternal wound infection in high-risk cardiac surgery patients: a propensity score analysis.

OBJECTIVE: Local delivery of prophylactic antibiotic to the wound site with an implanted, reabsorbable, gentamicin-containing collagen sponge (Collatamp) is a strategy that has been claimed to prevent sternal wound infection after cardiac surgery. The purpose of this study was to review our experience with Collatamp in cardiac surgery patients deemed at high risk for sternal wound infection. METHODS: From January 2007 to December 2010, Collatamp was used in 107 patients deemed at high risk for sternal wound infection. Applying the propensity score, we matched 97 patients with Collatamp (group I) with 97 patients who did not receive Collatamp (group II). All individuals received routine intravenous antimicrobial prophylaxis. Postoperative wound-infection rates as well as routine outcomes were compared. Information for the study was obtained from the cardiac surgical Patients Analysis and Tracking System (PATS) database and from hospital records. RESULTS: The superficial sternal wound infection rate was 2.1% (2/97) in group I and 6.2% (6/97) in group II (P = .01). The rates of deep sternal wound infection rate were similar (2.1% versus 3.1%, P = .87). There was no mediastinitis in the study population. In addition, more patients in group II received an intra-aortic balloon pump (5.2% versus 2.1%, P = .04) and underwent hemofiltration (7.2% versus 3.1%, P = .02). No side effects were noted. CONCLUSION: Gentamicin-containing collagen sponge (Collatamp) is a useful adjunct to meticulous surgical technique and postoperative wound care in reducing the incidence of sternal wound infection in high-risk cardiac surgery patients. An adequately powered study is needed, however, to validate the safety and efficacy of this strategy.

Ten-year outcome analysis of off-pump sequential grafting: single surgeon, single center experience.

OBJECTIVES: Despite increasing recognition that off-pump coronary artery bypass surgery and sequential grafting strategy individually are associated with improved outcomes, concerns persist regarding the safety and efficacy of combining these 2 techniques. We compared in-hospital and midterm outcomes for off-pump multivessel sequential and conventional coronary artery bypass grafting. METHODS: From September 1998 to September 2008, 689 consecutive patients received off-pump multivessel sequential coronary artery bypass grafting performed by a single surgeon. These patients were propensity matched to 689 patients who underwent off-pump coronary artery bypass grafting without sequential anastomoses. A retrospective analysis of prospectively collected perioperative data was performed. In addition, medical notes and charts of all the study patients were reviewed. The mean duration of follow-up was 5.1 ± 2.0 years. RESULTS: The major in-hospital clinical outcomes in the sequential and control groups were found to be similar. After adjusting for clinical covariates, sequential grafting was not an independent predictor of in-hospital adverse events (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.86-1.50; P = .31), medium-term mortality (hazard ratio [HR], 1.26; 95% CI, 1.06-1.32; P = .92), and readmission to hospital (HR, 1.12; 95% CI, 0.96-1.20; P = .80). Sequential grafting was an independent predictor of receiving more than 3 distal anastomoses (OR, 7.46; 95% CI, 4.27-11.45; P < .0001). Risk-adjusted survival was 89% for sequential grafting patients and 88% for conventional grafting patients (P = .96) during the medium-term follow-up. CONCLUSION: Our analysis confirms the short- and midterm safety and efficacy of off-pump sequential coronary artery bypass grafting.

Atrial Septal Defect Repair in Adolescent and Adult Patients, a Cross Sectional Study at Jordan University Hospital, a Tertiary Hospital in a Developing Country.

Objective: We aim to report our heart team's experience in repair of Secundum atrial septal defect (ASD) in adolescent and adult patients at Jordan University Hospital (JUH). Methodology: A retrospective observational study of 44 patients who underwent secundum ASD closure by transcatheter closure (TCC) or Minimally Invasive Cardiac Surgery (MICS) at JUH. Patients who were treated at an age of 14 years or older regardless of the age of diagnosis were included. SPSS and Microsoft Excel were used to analyze the data. Results: A total of 44 patients with secundum ASD were treated during the period of (January 2015 and December 2019). The mean age was 34.1 (±14.3) years. Thirty-four patients underwent TCC, 9 underwent surgical closure and one had a hybrid procedure. We had no mortality and 2 minor morbidities. After a mean follow-up period of 13.2-/+13.6 months, most patients experienced improved symptoms, and there was a significant reduction of right ventricular dimension from 33.1 (±8.74) to 24 (±4.67) mm (p=0.0001). Conclusion: ASD closure whether TCC or MICS is a safe procedure with very low morbidity. A heart team approach is a necessity in the era of advances in both MICS surgery and TCC approach. A heart team provides the patients with a variety of safe and cosmetic solutions that allow the patients to have a fast management and recovery phase in rapid time through providing the merits and avoiding the complications of each modality, the team allows low volume centers in developing countries to achieve an excellent outcome.

A clinical and economic evaluation of fast-track recovery after cardiac surgery.

BACKGROUND: In the last 5 decades, the care of cardiac surgical patients has improved with the aid of strategies aimed at facilitating patient recovery. One of the innovations in this context is "fast-tracking" or "rapid recovery." This process refers to all interventions that aim to shorten a patient's stay in the intensive care unit (ICU) through accelerating the patient's transfer to a step-down or telemetry unit and to the general ward. METHODS: Patients were allocated to 2 groups. The fast-track group (n = 84) went through an independent theatre recovery unit (TRU). The patients were then transferred on the same day to an intermediate care unit and transferred on the following day to the ward. The intensive care group (52 patients) went to the ICU for at least 1 day, after which they were transferred to the ward. RESULTS AND DISCUSSION: The fast-track pathway significantly reduced the length of stay (LOS) in an intensive care facility (P < .001). The duration of intubation was reduced from a median of 4.08 hours (range, 1.17-13.17 hours) in the intensive care group to 2.75 hours (range, 0.25-18.57 hours) in the fast-track group (P < .001). However, the median values for total hospital LOS, incidences of complications, reintubation, and readmission were similar for the 2 groups. The incidence of failure in the fast-track group was 10%. The mean (SD) cost of the perioperative care was £4182 ± £2284 ($6683 ± 3650) for the fast-track patients, compared with £4553 ± £1355 ($7277 ± $2165) for the intensive care group. CONCLUSION: Fast-track recovery after cardiac surgery decreases the intensive care LOS and the total duration of intubation. It is a cost-effective strategy compared with conventional recovery protocols; however, it does not reduce the total hospital LOS or the incidence of complications.

The Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) randomised controlled trial to evaluate an outpatient pre-cardiac surgery diabetes management intervention: a study protocol.

INTRODUCTION: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK. METHODS AND ANALYSIS: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA1c; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media. TRIAL REGISTRATION NUMBER: ISRCTN10170306.

Developing an intervention to optimise the outcome of cardiac surgery in people with diabetes: the OCTOPuS pilot study.

BACKGROUND: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to improved postoperative outcomes. The aim of this study was to develop and pilot a specialist diabetes team-led intervention to improve surgical outcomes in people with diabetes. DESIGN: Open pilot feasibility study SETTING: Diabetes and cardiothoracic surgery departments, University Hospital Southampton NHS Foundation Trust PARTICIPANTS: Seventeen people with diabetes undergoing cardiothoracic surgery INTERVENTION: Following two rapid literature reviews, a prototype intervention was developed based on a previously used nurse-led outpatient intervention and tested. PRIMARY OUTCOME: Feasibility and acceptability of delivering the intervention SECONDARY OUTCOMES: Biomedical data were collected at baseline and prior to surgery. We assessed how the intervention was used. In depth qualitative interviews with participants and healthcare professionals were used to explore perceptions and experiences of the intervention and how it might be improved. RESULTS: Thirteen of the 17 people recruited completed the study and underwent cardiothoracic surgery. All components of the OCTOPuS intervention were used, but not all parts were used for all participants. Minor changes were made to the intervention as a result of feedback from the participants and healthcare professionals. Median (IQR) HbA1c was 10 mmol/mol (3, 13) lower prior to surgery than at baseline. CONCLUSION: This study has shown that it is possible to develop a clinical pathway to improve diabetes management prior to admission. The clinical and cost-effectiveness of this intervention will now be tested in a multicentre randomised controlled trial in cardiothoracic centres across the UK. TRIAL REGISTRATION: ISRCTN; ISRCTN10170306 . Registered 10 May 2018.

Successful surgical repair of tricuspid valve endocarditis.

Surgical treatment of tricuspid valve endocarditis is challenging especially in intravenous drug users. We present a case of a 30-year-old male active drug user with anterior leaflet endocarditis treated successfully with valve repair. This was achieved through excision of the vegetation with part of the leaflet. Bovine pericardium was used to close the defect. The edges were reinforced with Teflon pledgeted polytetrafluoroethylene Gore-Tex neochordae (W.L. Gore & Associates, Flagstaff, AZ, USA). An annuloplasty ring was used to reinforce the whole annulus. Repair was competent and the patient recovered well. This technique is simple and effective and should be considered for similar cases.

Pericardial calcification: A case report of a three-dimensional disease.

INTRODUCTION: Constrictive pericarditis is an important cause of diastolic heart failure. The relationship between the presence and degree of pericardial calcification with constrictive pericarditis is variable, however this should be an early warning sign to initiate appropriate investigations. PRESENTATION OF CASE: A 64-year-old gentleman presented with dyspnoea and dizziness on exertion. Plain posterior-anterior chest X-ray showed mild to moderate pericardial calcification. He had an episode of atrial fibrillation which resolved spontaneously and thought to be the cause of his symptoms. Patient symptoms progressed. Further investigations including CT scan confirmed extensive constrictive pericarditis. He underwent a successful percardiectomy and full recovery. DISCUSSION: Constrictive pericarditis can be the consequence of different conditions such as tuberculosis, radiation, idiopathic or many others. Pericardial calcification is present in less than 25% of all cases of constrictive pericarditis, and patient with it are prone to develop atrial fibrillation. The presence of pericardial calcification on plain chest radiograph is an important indicator for the possibility of pericardial dysfunction. Many cases of pericardial calcification are benign without any clinical significance; however three-dimensional imaging is required to determine the calcium load and aid in reaching appropriate diagnosis. CONCLUSION: Chest X-ray is valuable detector of pericardial calcification, a surrogate of pericardial constriction, but it is important to remember that pericardial calcification is a three-dimensional condition, and should be further investigated by lateral chest X-ray, CT scan and then appropriate functional imaging.

Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been established as an important independent risk factor for aortic stenosis. T2DM patients present with a higher degree of valve calcification and left ventricular dysfunction compared to patients without diabetes. This may be due to an increase in incidence and severity of myocardial fibrosis. Currently, there is no reliable method of determining the optimal timing of intervention for a patient with asymptomatic aortic stenosis or predicting when a patient will become symptomatic. Research into serum biomarkers to predict subclinical onset and track progression of aortic stenosis is hampered by the multimodal nature of the pathological processes ultimately responsible for aortic stenosis. OBJECTIVE: The aim of this study is to prove that an approach using a combination of serum biomarkers and the echocardiographic parameter global longitudinal strain (GLS) can be used to establish baseline status of fibrocalcific aortic valve disease, predict rate of progression, and quantitatively assess any regression of these processes following aortic valve replacement in patients with T2DM. METHODS: Validated serum biomarkers for the separate processes of calcification, inflammation, oxidative stress and fibrosis can be used to quantify onset and rate of progression of aortic stenosis. This, in combination with the echocardiographic parameter GLS, can be compared with other objective investigations of calcification and fibrosis with the aim of developing a quick, noninvasive one-stop assessment of aortic stenosis in patients with T2DM. The serum biomarkers BNP (B-type natriuretic peptide), Gal-3 (Galectin-3), GDF-15 (growth differentiation factor-15), sST2 (soluble suppression of tumorigenicity 2), OPG (osteoprotegerin), and microRNA 19b and 21 will be sampled from patients undergoing aortic valve replacement (with and without T2DM), patients with T2DM but without aortic valve disease and healthy volunteers. These patients will also undergo computed tomography (CT) scans for calcium scoring, magnetic resonance imaging (MRI) to quantify myocardial fibrosis, and myocardial strain imaging with speckle-tracking echocardiography. Samples of calcified native aortic valve and a biopsy of ventricular myocardium will be examined histologically to determine the quantity and distribution of calcification and fibrosis, and the secretome of these tissue samples will also be analyzed for levels of the same biomarkers as in the serum samples. All patients will be followed up with in 3 months and 12 months for repeat blood sampling, echocardiography, and CT and MRI imaging to assess disease progression or regression. The results of tissue analysis and CT and MRI scanning will be used to validate the findings of the serum biomarkers and echocardiographic assessment. RESULTS: Using all of the information gathered throughout the study will yield a ranking scale for use in the clinic, which will provide each patient with a fibrocalcific profile. This can then be used to recommend an optimal time for intervention. CONCLUSION: A reliable, validated set of serum biomarkers combined with an inexpensive bedside echocardiographic examination can now form the basis of a one-stop outpatient-based assessment service, which will provide an accurate risk assessment in patients with aortic stenosis at first contact. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/13186.

Defective NOTCH signalling drives smooth muscle cell death and differentiation in bicuspid aortic valve aortopathy.

OBJECTIVES: Bicuspid aortic valve disease is common and is associated with ascending aortic aneurysms. Vascular smooth muscle cell (VSMC) apoptosis is characteristic of the ascending aorta of bicuspid patients, and NOTCH1 gene mutations have also been linked to the disease. NOTCH signalling is a fundamental cell signalling pathway, which dictates cell fate decisions including apoptosis. Our objective was to elucidate the role of NOTCH signalling in VSMC apoptosis and differentiation in bicuspid aortopathy. METHODS: Ascending aortic biopsies were obtained from 19 bicuspid and 12 tricuspid aortic valve patients and were sub-classified into 4 groups according to the maximum ascending aortic diameter (aneurysmal ≥45 mm). Apoptotic VSMCs were counted by light microscopy using a TUNEL assay. Gene expression of key regulators of NOTCH signalling (NOTCH1 and HES1), apoptosis (BAX and BCL-2) and VSMC differentiation (MYH11, CNN1 and MYH10) were quantified using quantitative real-time PCR. Primary VSMCs were cultured from 2 tricuspid aortic valve and 2 bicuspid aortic valve patients, NOTCH signalling was inhibited with N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, and the gene expression was again quantified. RESULTS: The apoptotic cell count was significantly higher in bicuspid aortic valve patients (3.2 cells/50 000 µm2 vs 1.1 cells/50 000 µm2; P = 0.033). There was a trend towards lower apoptotic cell count in the aneurysmal versus non-aneurysmal tricuspid and bicuspid groups and an increased ratio of proapoptotic gene expression, which was not statistically significant. This was associated with a 2.8-fold increase in contractile gene expression (P = 0.026) and a 2.0-fold increase in NOTCH signalling gene expression in bicuspid versus tricuspid aortic valve patients (P = 0.022). NOTCH inhibition in cultured VSMCs induced a similar pattern of increased proapoptotic and procontractile gene expressions. CONCLUSIONS: This preliminary study suggests that NOTCH activation in the non-aneurysmal bicuspid aortas may underlie aortopathy by influencing VSMC apoptosis and differentiation. NOTCH signalling manipulation may provide a therapeutic target for preventing aneurysms in bicuspid patients. Further studies with larger sample sizes are needed to substantiate the present findings.

Feasibility of a novel, synthetic, self-assembling peptide for suture-line haemostasis in cardiac surgery.

BACKGROUD: To assess the feasibility and efficacy of PuraStat®, a novel haemostatic agent, in achieving suture line haemostasis in a wide range of cardiac surgical procedures and surgery of the thoracic aorta. METHODS: A prospective, non-randomised study was conducted at our institution. Operative data on fifty consecutive patients undergoing cardiac surgery where PuraStat® was utilised in cases of intraoperative suture line bleeding was prospectively collected. Questionnaires encompassing multiple aspects of the ease of use and efficacy of PuraStat® were completed by ten surgeons (five consultants and five senior registrars) and analysed to gauge the performance of the product. RESULTS: No major adverse cardiac events were reported in this cohort. Complications such as atrial fibrillation, pacemaker requirement and pleural effusions were comparable to the national average. Mean blood product use of packed red cells, platelets, fresh-frozen plasma (FFP) and cryoprecipitate was below the national average. There was one incidence of re-exploration, however this was due to pericardial constriction rather than bleeding. Analysis of questionnaire responses revealed that surgeons consistently rated PuraStat® highly (between a score of 7 and 10 in the various subcategories). The transparent nature or PuraStat® allowed unobscured visualisation of suture sites and possessed excellent qualities in terms of adherence to site of application. The application of PuraStat® did not interfere with the use of other haemostatic agents or manipulation of the suture site by the surgeon. CONCLUSION: PuraStat® is an easy-to-use and effective haemostatic agent in a wide range of cardiac and aortic surgical procedures.

External aortic clamping versus endoaortic balloon occlusion in minimally invasive cardiac surgery: a systematic review and meta-analysis.

OBJECTIVES: Minimally invasive cardiac valve surgery is safe, effective and increasingly popular. It is performed worldwide with the use of either external aortic clamping or endoaortic balloon occlusion. METHODS: We conducted a literature search using MEDLINE, EMBASE, Scopus and Web of Science. Primary outcomes included aortic dissection, conversion to sternotomy, mortality, stroke and cross-clamp time. Secondary outcomes included atrial fibrillation, acute kidney injury, reoperation for bleeding, cardiopulmonary bypass times, myocardial infarction, use of intra-aortic balloon pump and length of hospital stay. The random effects model was used to calculate the outcomes of both binary and continuous data. RESULTS: Thirty retrospective studies were included in the meta-analysis. The incidence of aortic dissection (pooled odds ratio = 3.88, 95% confidence interval = 1.06-14.18; P =0.04) and conversion to sternotomy (pooled odds ratio = 3.07, 95% confidence interval = 1.33-7.10; P = 0.009) was higher in the endoaortic balloon occlusion group than in the external aortic clamping group, in whom a direct comparison was possible. The remaining observational studies did not show any significant differences in either group. There was no significant difference in 30-day mortality (P = 0.37), stroke (P = 0.26), cross-clamp time (P = 0.20), atrial fibrillation (P = 0.18), acute kidney injury (P = 0.49), reoperation for bleeding (P = 0.24), cardiopulmonary bypass time (P = 0.06), myocardial infarction (P = 0.74), use of intra-aortic balloon pump (P = 0.11) or length of hospital stay (P = 0.47). CONCLUSIONS: External aortic clamping may be safer than endoaortic balloon occlusion with respect to aortic dissection and conversion to sternotomy. However, mortality, length of stay, stroke, cross-clamp time and other cardiovascular complication rates were similar between the 2 techniques.