Sunil Ohri - Academia.edu (original) (raw)

Papers by Sunil Ohri

Research paper thumbnail of Aortic valve replacement with biological prosthesis in patients aged 50–69 years

European Journal of Cardio-Thoracic Surgery, 2020

OBJECTIVES There is no consensus regarding the use of biological or mechanical prostheses in pa... more OBJECTIVES There is no consensus regarding the use of biological or mechanical prostheses in patients 50–69 years of age. Previous studies have reported a survival advantage with mechanical valves. Our goal was to compare the long-term survival of patients in the intermediate age groups of 50–59 and 60–69 years receiving mechanical or biological aortic valve prostheses. METHODS We conducted a retrospective analysis of patients in the age groups 50–59 years (n = 329) and 60–69 years (n = 648) who had a first-time isolated aortic valve replacement between 2000 and 2019. Kaplan–Meier and competing risk analyses were performed to compare survival, incidence of aortic valve reoperation, haemorrhagic complications and thromboembolic events for mechanical versus biological prostheses. RESULTS Patients aged 50–59 years with a biological prosthesis had a higher probability of aortic valve reintervention (26.3%, biological vs 2.6% mechanical; P < 0.001 at 15 years). The incidence of haem...

Research paper thumbnail of Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease

Journal of cardiothoracic surgery, Jan 22, 2018

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1... more Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter ≥ 45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify pr...

Research paper thumbnail of Endotoxaemia detected during cardiopulmonary bypass with a modified Limulus amoebocyte lysate assay

Perfusion, 1995

Cardiopulmonary bypass (CPB) is associated with blood heparin level fluctuations and a reduction ... more Cardiopulmonary bypass (CPB) is associated with blood heparin level fluctuations and a reduction in haematocrit due to crystalloid haemodilution. The effect of these changes on the reliability of the Limulus amoebocyte lysate (LAL) chromogenic microassay for the measurement of plasma endotoxin was assessed in vitro. It was shown that the assay could be significantly compromised by twofold haemodilution which can occur during CPB. The interference effect on the assay caused by CPB-associated heparin was not significant if a comparatively large amount of heparin (25 IU/ml) was added to the blood at the time of sampling. The effect of haemodilution was counteracted by prediluting plasma samples with crystalloid by a factor dependent on the sample haematocrit (to ensure that the proportion of plasma was similar in all samples). A correction was then required to determine the endotoxin level in the original sample. The modified assay was used to determine sequential plasma endotoxin leve...

Research paper thumbnail of Initial experience with xenograft bioconduit for the treatment of complex prosthetic valve endocarditis

Perfusion, 2017

Introduction: The treatment of complex prosthetic valve endocarditis (PVE) with aortic root absce... more Introduction: The treatment of complex prosthetic valve endocarditis (PVE) with aortic root abscess remains a surgical challenge. Several studies support the use of biological tissues to minimize the risk of recurrent infection. We present our initial surgical experience with the use of an aortic xenograft conduit for aortic valve and root replacement. Methods: Between October 2013 and August 2015, 15 xenograft bioconduits were implanted for complex PVE with abscess (13.3% female). In 6 patients, concomitant procedures were performed: coronary bypass (n=1), mitral valve replacement (n=5) and tricuspid annuloplasty (n=1). The mean age at operation was 60.3±15.5 years. The mean Logistic European system for cardiac operating risk evaluation (EuroSCORE) was 46.6±23.6. The median follow-up time was 607±328 days (range: 172-1074 days). Results: There were two in-hospital deaths (14.3% mortality), two strokes (14.3%) and seven patients required permanent pacemaker insertion for conduction ...

Research paper thumbnail of Endogenous Reference Genes for Gene Expression Studies on Bicuspid Aortic Valve Associated Aortopathy in Humans

PLOS ONE, 2016

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisp... more Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisposes patients to life-threatening aortic complications including aortic aneurysm. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most commonly used methods to investigate underlying molecular mechanisms involved in aortopathy. The accuracy of the gene expression data is dependent on normalization by appropriate housekeeping (HK) genes, whose expression should remain constant regardless of aortic valve morphology, aortic diameter and other factors associated with aortopathy. Here, we identified an appropriate set of HK genes to be used as endogenous reference for quantifying gene expression in ascending aortic tissue using a spin column-based RNA extraction method. Ascending aortic biopsies were collected intra-operatively from patients undergoing aortic valve and/or ascending aortic surgery. These patients had BAV or tricuspid aortic valve (TAV), and the aortas were either dilated (!4.5cm) or undilated. The cohort had an even distribution of gender, valve disease and hypertension. The expression stability of 12 reference genes were investigated (ATP5B,

Research paper thumbnail of Open and closed distal anastomosis for acute type A aortic dissection repair: early and long-term outcomes from a contemporary series of 204 patients

Journal of Cardiothoracic Surgery, 2015

Background/Introduction The current general consensus favours an open distal anastomosis for aort... more Background/Introduction The current general consensus favours an open distal anastomosis for aortic dissection repair. A limited number of studies have compared the results between open and closed repair strategies.

Research paper thumbnail of The outcomes of triple-valve surgery: eleven years' experience from a single center

The Journal of heart valve disease, 2014

Triple-valve surgery is a challenging and complex procedure with significant risk, even at center... more Triple-valve surgery is a challenging and complex procedure with significant risk, even at centers experienced at performing such operations. The study aim was to investigate the early and late outcomes of this surgery, performed at a single center for the past 11 years. A total of 45 consecutive patients (19 males, 26 females; mean age 69.42 +/- 12.72 years) underwent triple-valve surgery at the authors' institution between 2000 and 2011. The mean logistic EuroSCORE was 22.46 +/- 12.8%. The most common aortic valve pathology was calcific degeneration (40%), while the mitral valves were mostly rheumatic (31%) or degenerative (26%). The tricuspid valve pathology was functional regurgitation in 64% of patients. The aortic valve procedures were all replacements, while the mitral valves were either repaired (n = 20) or replaced (n = 25). The tricuspid valves were almost exclusively repaired (n = 43). Univariate and multivariate analyses were performed to highlight predictors of mort...

Research paper thumbnail of Outcome after redo-mitral valve replacement in adult patients: a 10-year single-centre experience

Interactive cardiovascular and thoracic surgery, 2012

The aim of this study was to investigate the overall outcome of adult patients undergoing redo-mi... more The aim of this study was to investigate the overall outcome of adult patients undergoing redo-mitral valve replacement (redo-MVR) at our institution. Forty-nine patients (24 males) underwent redo-MVR with either bioprosthetic (n = 24) or mechanical valves (n = 25) between January 2000 and 2010. Median age of patients was 63 years (range 21-80 years), and the mean additive EuroSCORE was 12 ± 4. Median time to re-operation was 8.2 ± 6.6 years for first time redo-MVR and 6.4 ± 5.6 years for second-time redo-MVR. Indications included prosthetic endocarditis (n = 22), para-prosthetic leak (n = 12), structural valve degeneration (n = 8), prosthetic valve thrombosis (n = 6) and malignancy (n = 1). The mean follow-up was 47.5 ± 37.0 months (range 0.1-112.3 months). In-hospital mortality was 12% (n = 6). Mean hospital stay was 17 ± 11 days (range 8-50 days). Actuarial survival at 1 and 5 years was 81 ± 5% and 72 ± 6%, respectively. Three patients required re-intervention: two for prosthetic...

Research paper thumbnail of Tricuspid valve replacement: bioprostheses are preferable

The Journal of heart valve disease, 1999

Tricuspid valve replacement (TVR) is rarely undertaken, most surgeons preferring to use conservat... more Tricuspid valve replacement (TVR) is rarely undertaken, most surgeons preferring to use conservative tricuspid valve procedures. Thus, limited data are available in patients following TVR. The purpose of this study was to analyze the early and late results in 87 patients (52 tissue valves, 35 mechanical prostheses) who underwent TVR between January 1973 and September 1996. The patient group comprised 74 (85%) females and 13 (15%) males; mean (+/- SD) age was 59.4 +/- 12.8 years; range: 15 to 81 years). Forty-four patients (51%) had undergone at least one previous cardiac operation. There were 19 (23%) isolated TVRs, 43 (49%) triple valve replacements, and 25 (29%) double valve replacements. Total cumulative follow up was 707 patient-years (pt-yr) (tissue valves 393 pt-yr, mechanical valves 314 pt-yr); mean follow up was 8.1 years (range: 0 to 23.6 years). The early (30-day) mortality rate was 10.3% (n = 9; tissue 7, mechanical 2, p = 0.28). Logistic regression identified prolonged c...

Research paper thumbnail of Long-term outcome following repair of acute type A aortic dissection after previous cardiac surgery

Interactive cardiovascular and thoracic surgery, 2011

We evaluated the outcome after repair for acute spontaneous type A aortic dissection in patients ... more We evaluated the outcome after repair for acute spontaneous type A aortic dissection in patients with previous cardiac surgery. From January 2000 to December 2009, 114 patients underwent emergency repair for acute spontaneous type A dissection at Southampton University Hospital. Eleven (median age 64 years; range 36-83 years; two females) patients (9.8%) had undergone previous cardiac surgery and were included in this study. Aortic root replacement was performed in three patients (27%), aortic arch replacement in four patients (36%) and two patients (18%) required aortic valve re-suspension. The elephant trunk operation was performed in two patients (18%). There were two hospital deaths (18%). Two patients (18%) suffered a stroke, two needed re-opening for bleeding (18%) and two patients (18%) required haemofiltration postoperatively. Median length of hospital stay was 16 days (range 6-34 days). Actuarial survival at five and eight years for redo compared to first-time surgery was 6...

Research paper thumbnail of Early in-vivo hemodynamic comparison of supra-annular aortic bioprostheses: Trifecta versus Perimount Magna Ease

The Journal of heart valve disease, 2014

The study aim was to compare early postoperative hemodynamic gradients after supra-annular implan... more The study aim was to compare early postoperative hemodynamic gradients after supra-annular implantation of the Trifecta and Perimount Magna Ease aortic bioprostheses. Between January 2010 and December 2011, a total of 235 patients (105 males, 130 females; mean age at surgery 73.8 +/- 10.2 years) underwent supra-annular aortic valve replacement (AVR), with or without concomitant procedures. The patients were divided into 2 groups receiving either the Perimount Magna Ease (n = 117) or Trifecta (n = 118). Concomitant procedures were performed in 133 patients (56.6%), and 25 procedures (10.6%) were redos. Patients with postoperative severe left ventricular dysfunction and moderate to severe mitral regurgitation were excluded. Gradients were calculated pre-discharge using transthoracic echocardiography. Effective orifice area calculations were not performed. Data were collected retrospectively from hospital databases and analyzed using SPSS 17. Both groups compared well for 14 variables....

Research paper thumbnail of Risk of reoperation for structural failure of aortic and mitral tissue valves

The Journal of heart valve disease, 2002

The study aim was to assess the risk of reoperation for patients with a failing stented tissue va... more The study aim was to assess the risk of reoperation for patients with a failing stented tissue valve. Between 1980 and 1999, 259 patients (118 males, 141 females; mean age 60.1+/-15.4 years) underwent redo valve replacement to replace a failing stented tissue valve. Of these patients, 94 (36.3%) underwent redo aortic valve replacement (AVR), 105 (40.5%) redo mitral valve replacement (MVR), and 60 (23.2%) redo aortic and mitral valve replacement (DVR). Twenty patients (7.7%) had previous coronary artery bypass grafting (CABG); further CABG were performed in 32 cases (12.4%). Preoperatively, 216 patients (83.3%) were in NYHA functional class III or IV. The early mortality was (6.5%; n = 17), including three patients who had AVR, five DVR, and nine MVR. A higher preoperative NHYA status (p <0.0004) and emergency surgery (p <0.0001) were significantly associated with an increased risk of operative death (univariate analysis). Age at surgery (p = 0.45), previous CABG (p = 0.45), po...

Research paper thumbnail of The effect of cardiopulmonary bypass on gastric and colonic mucosal perfusion: a tonometric assessment

Perfusion, 1994

In a study to assess the potential effect of nonpulsatile hypothermic cardiopulmonary bypass (CPB... more In a study to assess the potential effect of nonpulsatile hypothermic cardiopulmonary bypass (CPB), intramucosal pH (pHi) of the gastric and colonic mucosae was determined by tonometry ( n = 8). During the hypothermic phase of CPB, gastric and colonic pHi did not change significantly. Forty minutes after the start of rewarming, despite increases in the cardiac index and mean arterial blood pressure, gastric pHi fell from 7.53 ± 0.02 to 7.31 ± 0.03 ( p = 0.017) and colonic pHi fell from 7.50 ± 0.02 to 7.32 ± 0.03 ( p = 0.028). Forty minutes after the end of CPB both the colonic ( p = 0.017) and gastric ( p = 0.046) pHi remained depressed below pre-CPB values. The difference in the arterial (pHa) and the gastric mucosal pH changed from -0.097 before CPB to 0.016, 40 minutes after the end of CPB ( p = 0.027). This alteration in the pHa-pHi underlines the importance of measuring intramucosal pH by tonometry, since the pHa and pHi may move in opposite directions during episodes of haemod...

Research paper thumbnail of Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice

British Journal of Nutrition, 2009

In rodents, adverse prenatal nutrition, such as a maternal diet rich in fat during pregnancy, enh... more In rodents, adverse prenatal nutrition, such as a maternal diet rich in fat during pregnancy, enhances susceptibility of the offspring to hypertension, type 2 diabetes and other features of the human metabolic syndrome in adulthood. However, previous experimental studies were confined to shortterm modifications of the maternal diet during pregnancy and/or lactation periods, a situation uncommon in humans. Moreover in humans, the offspring may also consume a high-fat diet, which may take them beyond the range to which their development has adapted them to respond healthily. We examined in C57 mice the effects on offspring of feeding their mothers a high-fat (HF) or standard chow (C) diet from weaning through pregnancy and lactation, and whether there are additive phenotypic effects of feeding the offspring an HF diet from weaning to adulthood (dam-offspring dietary group HF-HF). This group was compared with offspring from HF-fed dams fed a C diet from weaning to adulthood (HF

Research paper thumbnail of Long-Term Outcomes in Octogenarians Following Aortic Valve Replacement

Journal of Cardiac Surgery, 2011

The aging of the population has resulted in an increasing number of elderly patients undergoing c... more The aging of the population has resulted in an increasing number of elderly patients undergoing cardiac operations. We reviewed our experience in patients over the age of 80 undergoing primary aortic valve replacement (AVR) with or without CABG. Between 2000 and 2008, 345 patients (226 male) ≥80 years underwent primary AVR in our unit. The notes of these patients were retrospectively reviewed and follow-up information was obtained from their general practitioners. They had a mean age of 82.9 ± 2.3 years and a median logistic EuroSCORE of 13.4 (IQR 9.4, 19.1). Isolated AVR was performed in 161 patients (45.5%), and 184 (51.6%) patients underwent combined AVR and CABG. A quality of life questionnaire was sent to all survivors. Hospital mortality occurred in 17 patients (4.9%), which was significantly lower than the mortality predicted by logistic EuroSCORE (16.2%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Hospital mortality was comparable between patients undergoing isolated AVR and those undergoing additional CABG (4.3% vs. 5.4%, respectively). Actuarial survival at one and five years was 90.1 ± 1.6% and 77.2 ± 2.9%, respectively. There was a 62% response on the questionnaire showing 70% of the patients were NYHA I and 83.7% were satisfied with the operation outcome. AVR can be undertaken with excellent results in octogenarians and the current risk is significantly lower than what is predicted with conventional risk-scoring systems. Patients with advanced age should not necessarily be excluded from being candidates for AVR.

Research paper thumbnail of Statin Treatment in Hypercholesterolemic Pregnant Mice Reduces Cardiovascular Risk Factors in Their Offspring

Hypertension, 2008

Increasing evidence suggests that hypercholesterolemia during pregnancy initiates pathogenic even... more Increasing evidence suggests that hypercholesterolemia during pregnancy initiates pathogenic events in the fetus leading to increased risk of cardiovascular disease in the adult offspring. In this study we examined in mice whether pharmacological intervention using statins in late pregnancy could alleviate the detrimental effects of a high-fat, high-cholesterol (45% fat) maternal diet on the health of the dams and their offspring. Pregnant C57 mice on high-fat, high-cholesterol diet were given the 3hydroxy3methylglutaryl-coenzyme A reductase inhibitor pravastatin in the drinking water (5 mg/kg of body weight per day) in the second half of pregnancy and during lactation to lower cholesterol and improve postweaning maternal blood pressure. Weaned offspring were then fed the high-fat, high-cholesterol diet until adulthood (generating dam/offspring dietary groups high-fat, high-cholesterol/high-fat, high-cholesterol and high-fat, high-cholesterol plus pravastatin during the second half ...

Research paper thumbnail of Aortic valve replacement in patients with previous coronary artery bypass grafting: 10-year experience

European Journal of Cardio-Thoracic Surgery, 2011

OBJECTIVES: This study aimed to investigate the early and late outcomes of patients undergoing ao... more OBJECTIVES: This study aimed to investigate the early and late outcomes of patients undergoing aortic valve replacement (AVR) with previous coronary artery bypass grafting (CABG) and patent grafts. METHODS: Between January 2000 and March 2010, 104 patients (87 males) with previous CABG ± concomitant surgery and patent grafts underwent AVR. The median age of the patients was 75 years (range: 37-90 years; inter-quartile range: 69-79 years) and the mean logistic EuroScore was 25.37 ± 16.8. The median time since the previous operation was 9 years (range 1-25; inter-quartile range: 7-14 years). The left internal mammary artery (LIMA) had been used in 75 patients (72.1%) and remained patent in 72 cases (96.0%). RESULTS: Thirty-day mortality was 7.7% (n = 8), which is less than the predicted mean logistic EuroScore. Isolated AVR was performed in 66 patients (63.5%). The LIMA was dissected and isolated (clamped or blocked with balloon) in 60 patients. The median hospital stay was 10 days (range: 4-183 days; inter-quartile range: 7-15.25 days). Nineteen patients (18.3%) had pulmonary complications, while 12 (11.5%) had acute kidney injury. Seven patients (6.7%) required permanent pacemaker. Six LIMAs (8.3%) were injured and repaired. Prolonged aortic cross-clamp (AXC) time (P = 0.038) and the presence of a previous LIMA graft (P = 0.045) were identified as independent predictors of 30-day mortality. The actuarial survival at 1 and 5 years was 89.4 ± 0.3 and 81.5 ± 0.5%, respectively. Perioperative intra-aortic balloon pump use (P = 0.036), prolonged AXC time (P = 0.004) and prolonged cardiopulmonary bypass time (P = 0.022) were associated with worse long-term overall survival on multivariate analysis. CONCLUSIONS: AVR post-CABG with patent grafts can be performed in high-risk patients with excellent short-and long-term outcomes and appears to be superior to published catheter-based interventions. In the absence of randomized trial data, we believe that open AVR remains the treatment of choice for aortic valve disease following prior CABG.

Research paper thumbnail of P1-16 Impact on the developmental profile of the murine heart by maternal protein restriction during pregnancy

Early Human Development, 2007

Results: There were no differences between treatments in fetal weight or body dimensions. Crown-r... more Results: There were no differences between treatments in fetal weight or body dimensions. Crown-rump length, thoracic girth, head circumference and length and mean forelimb cannon bone length were dependent on fetal weight (P < 0.05). Treatment had no effect on weight of any fetal organ. There were no differences between treatments in number, weight or volume of cotyledons or caruncles, or weight of uterus or fetal membranes. Fetuses from the low treatment were a greater (P < 0.01) proportion of maternal live weight than fetuses from the moderate treatment (53±2 versus 44±2 g/100 kg). Conclusions: Fetal growth in the first 90 days of gestation occurred independently of maternal liveweight gain in 15-month-old beef heifers.

Research paper thumbnail of 3B-6 Statin therapy improves blood pressure and lipid profiles in hypercholesterolemic mothers but not C-reactive proteins levels or endothelial progenitor cell expression

Early Human Development, 2007

involvement of GSTM1 in detoxification of paracetamol in pregnancy may result in depletion of glu... more involvement of GSTM1 in detoxification of paracetamol in pregnancy may result in depletion of glutathione, leading to increased susceptibility of the fetal lung to damage from other oxidants. 3B-4 Essential nutrient supplementation preventing adult metabolic disease in a transgenerational model of IUGR is accompanied by epigenetic regulation of gene expression

Research paper thumbnail of Repair of acute type A aortic dissection: results in 100 patients

Asian Cardiovascular and Thoracic Annals, 2012

To determine short- and long-term outcomes after repair of type A aortic dissection, we reviewed ... more To determine short- and long-term outcomes after repair of type A aortic dissection, we reviewed data of 100 consecutive patients (64 men; mean age, 63 ± 12.2 years) who underwent acute type A aortic dissection repair between January 2000 and June 2008. They were divided into group A, open anastomosis (circulatory arrest; n = 59) and group B, closed anastomosis (no circulatory arrest; n = 41). Aortic valve re-suspension or replacement was performed in 77 patients, aortic root replacement in 29, and aortic arch procedures in 31. The median follow-up was 2.8 years (range, 0–8.6 years). The 30-day mortality was 14%; 16.9% in group A and 9.8% in group B. None of the 23 variables analyzed to determine predictors of death or stroke was significant on multivariate analysis. Postoperatively, there was no difference between the 2 groups with respect to stroke, sepsis, renal failure, multiorgan failure, or reoperation. Overall actuarial survival at 1, 3, 5, and 8 years was not significantly d...

Research paper thumbnail of Aortic valve replacement with biological prosthesis in patients aged 50–69 years

European Journal of Cardio-Thoracic Surgery, 2020

OBJECTIVES There is no consensus regarding the use of biological or mechanical prostheses in pa... more OBJECTIVES There is no consensus regarding the use of biological or mechanical prostheses in patients 50–69 years of age. Previous studies have reported a survival advantage with mechanical valves. Our goal was to compare the long-term survival of patients in the intermediate age groups of 50–59 and 60–69 years receiving mechanical or biological aortic valve prostheses. METHODS We conducted a retrospective analysis of patients in the age groups 50–59 years (n = 329) and 60–69 years (n = 648) who had a first-time isolated aortic valve replacement between 2000 and 2019. Kaplan–Meier and competing risk analyses were performed to compare survival, incidence of aortic valve reoperation, haemorrhagic complications and thromboembolic events for mechanical versus biological prostheses. RESULTS Patients aged 50–59 years with a biological prosthesis had a higher probability of aortic valve reintervention (26.3%, biological vs 2.6% mechanical; P < 0.001 at 15 years). The incidence of haem...

Research paper thumbnail of Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease

Journal of cardiothoracic surgery, Jan 22, 2018

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1... more Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter ≥ 45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify pr...

Research paper thumbnail of Endotoxaemia detected during cardiopulmonary bypass with a modified Limulus amoebocyte lysate assay

Perfusion, 1995

Cardiopulmonary bypass (CPB) is associated with blood heparin level fluctuations and a reduction ... more Cardiopulmonary bypass (CPB) is associated with blood heparin level fluctuations and a reduction in haematocrit due to crystalloid haemodilution. The effect of these changes on the reliability of the Limulus amoebocyte lysate (LAL) chromogenic microassay for the measurement of plasma endotoxin was assessed in vitro. It was shown that the assay could be significantly compromised by twofold haemodilution which can occur during CPB. The interference effect on the assay caused by CPB-associated heparin was not significant if a comparatively large amount of heparin (25 IU/ml) was added to the blood at the time of sampling. The effect of haemodilution was counteracted by prediluting plasma samples with crystalloid by a factor dependent on the sample haematocrit (to ensure that the proportion of plasma was similar in all samples). A correction was then required to determine the endotoxin level in the original sample. The modified assay was used to determine sequential plasma endotoxin leve...

Research paper thumbnail of Initial experience with xenograft bioconduit for the treatment of complex prosthetic valve endocarditis

Perfusion, 2017

Introduction: The treatment of complex prosthetic valve endocarditis (PVE) with aortic root absce... more Introduction: The treatment of complex prosthetic valve endocarditis (PVE) with aortic root abscess remains a surgical challenge. Several studies support the use of biological tissues to minimize the risk of recurrent infection. We present our initial surgical experience with the use of an aortic xenograft conduit for aortic valve and root replacement. Methods: Between October 2013 and August 2015, 15 xenograft bioconduits were implanted for complex PVE with abscess (13.3% female). In 6 patients, concomitant procedures were performed: coronary bypass (n=1), mitral valve replacement (n=5) and tricuspid annuloplasty (n=1). The mean age at operation was 60.3±15.5 years. The mean Logistic European system for cardiac operating risk evaluation (EuroSCORE) was 46.6±23.6. The median follow-up time was 607±328 days (range: 172-1074 days). Results: There were two in-hospital deaths (14.3% mortality), two strokes (14.3%) and seven patients required permanent pacemaker insertion for conduction ...

Research paper thumbnail of Endogenous Reference Genes for Gene Expression Studies on Bicuspid Aortic Valve Associated Aortopathy in Humans

PLOS ONE, 2016

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisp... more Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisposes patients to life-threatening aortic complications including aortic aneurysm. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most commonly used methods to investigate underlying molecular mechanisms involved in aortopathy. The accuracy of the gene expression data is dependent on normalization by appropriate housekeeping (HK) genes, whose expression should remain constant regardless of aortic valve morphology, aortic diameter and other factors associated with aortopathy. Here, we identified an appropriate set of HK genes to be used as endogenous reference for quantifying gene expression in ascending aortic tissue using a spin column-based RNA extraction method. Ascending aortic biopsies were collected intra-operatively from patients undergoing aortic valve and/or ascending aortic surgery. These patients had BAV or tricuspid aortic valve (TAV), and the aortas were either dilated (!4.5cm) or undilated. The cohort had an even distribution of gender, valve disease and hypertension. The expression stability of 12 reference genes were investigated (ATP5B,

Research paper thumbnail of Open and closed distal anastomosis for acute type A aortic dissection repair: early and long-term outcomes from a contemporary series of 204 patients

Journal of Cardiothoracic Surgery, 2015

Background/Introduction The current general consensus favours an open distal anastomosis for aort... more Background/Introduction The current general consensus favours an open distal anastomosis for aortic dissection repair. A limited number of studies have compared the results between open and closed repair strategies.

Research paper thumbnail of The outcomes of triple-valve surgery: eleven years' experience from a single center

The Journal of heart valve disease, 2014

Triple-valve surgery is a challenging and complex procedure with significant risk, even at center... more Triple-valve surgery is a challenging and complex procedure with significant risk, even at centers experienced at performing such operations. The study aim was to investigate the early and late outcomes of this surgery, performed at a single center for the past 11 years. A total of 45 consecutive patients (19 males, 26 females; mean age 69.42 +/- 12.72 years) underwent triple-valve surgery at the authors' institution between 2000 and 2011. The mean logistic EuroSCORE was 22.46 +/- 12.8%. The most common aortic valve pathology was calcific degeneration (40%), while the mitral valves were mostly rheumatic (31%) or degenerative (26%). The tricuspid valve pathology was functional regurgitation in 64% of patients. The aortic valve procedures were all replacements, while the mitral valves were either repaired (n = 20) or replaced (n = 25). The tricuspid valves were almost exclusively repaired (n = 43). Univariate and multivariate analyses were performed to highlight predictors of mort...

Research paper thumbnail of Outcome after redo-mitral valve replacement in adult patients: a 10-year single-centre experience

Interactive cardiovascular and thoracic surgery, 2012

The aim of this study was to investigate the overall outcome of adult patients undergoing redo-mi... more The aim of this study was to investigate the overall outcome of adult patients undergoing redo-mitral valve replacement (redo-MVR) at our institution. Forty-nine patients (24 males) underwent redo-MVR with either bioprosthetic (n = 24) or mechanical valves (n = 25) between January 2000 and 2010. Median age of patients was 63 years (range 21-80 years), and the mean additive EuroSCORE was 12 ± 4. Median time to re-operation was 8.2 ± 6.6 years for first time redo-MVR and 6.4 ± 5.6 years for second-time redo-MVR. Indications included prosthetic endocarditis (n = 22), para-prosthetic leak (n = 12), structural valve degeneration (n = 8), prosthetic valve thrombosis (n = 6) and malignancy (n = 1). The mean follow-up was 47.5 ± 37.0 months (range 0.1-112.3 months). In-hospital mortality was 12% (n = 6). Mean hospital stay was 17 ± 11 days (range 8-50 days). Actuarial survival at 1 and 5 years was 81 ± 5% and 72 ± 6%, respectively. Three patients required re-intervention: two for prosthetic...

Research paper thumbnail of Tricuspid valve replacement: bioprostheses are preferable

The Journal of heart valve disease, 1999

Tricuspid valve replacement (TVR) is rarely undertaken, most surgeons preferring to use conservat... more Tricuspid valve replacement (TVR) is rarely undertaken, most surgeons preferring to use conservative tricuspid valve procedures. Thus, limited data are available in patients following TVR. The purpose of this study was to analyze the early and late results in 87 patients (52 tissue valves, 35 mechanical prostheses) who underwent TVR between January 1973 and September 1996. The patient group comprised 74 (85%) females and 13 (15%) males; mean (+/- SD) age was 59.4 +/- 12.8 years; range: 15 to 81 years). Forty-four patients (51%) had undergone at least one previous cardiac operation. There were 19 (23%) isolated TVRs, 43 (49%) triple valve replacements, and 25 (29%) double valve replacements. Total cumulative follow up was 707 patient-years (pt-yr) (tissue valves 393 pt-yr, mechanical valves 314 pt-yr); mean follow up was 8.1 years (range: 0 to 23.6 years). The early (30-day) mortality rate was 10.3% (n = 9; tissue 7, mechanical 2, p = 0.28). Logistic regression identified prolonged c...

Research paper thumbnail of Long-term outcome following repair of acute type A aortic dissection after previous cardiac surgery

Interactive cardiovascular and thoracic surgery, 2011

We evaluated the outcome after repair for acute spontaneous type A aortic dissection in patients ... more We evaluated the outcome after repair for acute spontaneous type A aortic dissection in patients with previous cardiac surgery. From January 2000 to December 2009, 114 patients underwent emergency repair for acute spontaneous type A dissection at Southampton University Hospital. Eleven (median age 64 years; range 36-83 years; two females) patients (9.8%) had undergone previous cardiac surgery and were included in this study. Aortic root replacement was performed in three patients (27%), aortic arch replacement in four patients (36%) and two patients (18%) required aortic valve re-suspension. The elephant trunk operation was performed in two patients (18%). There were two hospital deaths (18%). Two patients (18%) suffered a stroke, two needed re-opening for bleeding (18%) and two patients (18%) required haemofiltration postoperatively. Median length of hospital stay was 16 days (range 6-34 days). Actuarial survival at five and eight years for redo compared to first-time surgery was 6...

Research paper thumbnail of Early in-vivo hemodynamic comparison of supra-annular aortic bioprostheses: Trifecta versus Perimount Magna Ease

The Journal of heart valve disease, 2014

The study aim was to compare early postoperative hemodynamic gradients after supra-annular implan... more The study aim was to compare early postoperative hemodynamic gradients after supra-annular implantation of the Trifecta and Perimount Magna Ease aortic bioprostheses. Between January 2010 and December 2011, a total of 235 patients (105 males, 130 females; mean age at surgery 73.8 +/- 10.2 years) underwent supra-annular aortic valve replacement (AVR), with or without concomitant procedures. The patients were divided into 2 groups receiving either the Perimount Magna Ease (n = 117) or Trifecta (n = 118). Concomitant procedures were performed in 133 patients (56.6%), and 25 procedures (10.6%) were redos. Patients with postoperative severe left ventricular dysfunction and moderate to severe mitral regurgitation were excluded. Gradients were calculated pre-discharge using transthoracic echocardiography. Effective orifice area calculations were not performed. Data were collected retrospectively from hospital databases and analyzed using SPSS 17. Both groups compared well for 14 variables....

Research paper thumbnail of Risk of reoperation for structural failure of aortic and mitral tissue valves

The Journal of heart valve disease, 2002

The study aim was to assess the risk of reoperation for patients with a failing stented tissue va... more The study aim was to assess the risk of reoperation for patients with a failing stented tissue valve. Between 1980 and 1999, 259 patients (118 males, 141 females; mean age 60.1+/-15.4 years) underwent redo valve replacement to replace a failing stented tissue valve. Of these patients, 94 (36.3%) underwent redo aortic valve replacement (AVR), 105 (40.5%) redo mitral valve replacement (MVR), and 60 (23.2%) redo aortic and mitral valve replacement (DVR). Twenty patients (7.7%) had previous coronary artery bypass grafting (CABG); further CABG were performed in 32 cases (12.4%). Preoperatively, 216 patients (83.3%) were in NYHA functional class III or IV. The early mortality was (6.5%; n = 17), including three patients who had AVR, five DVR, and nine MVR. A higher preoperative NHYA status (p <0.0004) and emergency surgery (p <0.0001) were significantly associated with an increased risk of operative death (univariate analysis). Age at surgery (p = 0.45), previous CABG (p = 0.45), po...

Research paper thumbnail of The effect of cardiopulmonary bypass on gastric and colonic mucosal perfusion: a tonometric assessment

Perfusion, 1994

In a study to assess the potential effect of nonpulsatile hypothermic cardiopulmonary bypass (CPB... more In a study to assess the potential effect of nonpulsatile hypothermic cardiopulmonary bypass (CPB), intramucosal pH (pHi) of the gastric and colonic mucosae was determined by tonometry ( n = 8). During the hypothermic phase of CPB, gastric and colonic pHi did not change significantly. Forty minutes after the start of rewarming, despite increases in the cardiac index and mean arterial blood pressure, gastric pHi fell from 7.53 ± 0.02 to 7.31 ± 0.03 ( p = 0.017) and colonic pHi fell from 7.50 ± 0.02 to 7.32 ± 0.03 ( p = 0.028). Forty minutes after the end of CPB both the colonic ( p = 0.017) and gastric ( p = 0.046) pHi remained depressed below pre-CPB values. The difference in the arterial (pHa) and the gastric mucosal pH changed from -0.097 before CPB to 0.016, 40 minutes after the end of CPB ( p = 0.027). This alteration in the pHa-pHi underlines the importance of measuring intramucosal pH by tonometry, since the pHa and pHi may move in opposite directions during episodes of haemod...

Research paper thumbnail of Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice

British Journal of Nutrition, 2009

In rodents, adverse prenatal nutrition, such as a maternal diet rich in fat during pregnancy, enh... more In rodents, adverse prenatal nutrition, such as a maternal diet rich in fat during pregnancy, enhances susceptibility of the offspring to hypertension, type 2 diabetes and other features of the human metabolic syndrome in adulthood. However, previous experimental studies were confined to shortterm modifications of the maternal diet during pregnancy and/or lactation periods, a situation uncommon in humans. Moreover in humans, the offspring may also consume a high-fat diet, which may take them beyond the range to which their development has adapted them to respond healthily. We examined in C57 mice the effects on offspring of feeding their mothers a high-fat (HF) or standard chow (C) diet from weaning through pregnancy and lactation, and whether there are additive phenotypic effects of feeding the offspring an HF diet from weaning to adulthood (dam-offspring dietary group HF-HF). This group was compared with offspring from HF-fed dams fed a C diet from weaning to adulthood (HF

Research paper thumbnail of Long-Term Outcomes in Octogenarians Following Aortic Valve Replacement

Journal of Cardiac Surgery, 2011

The aging of the population has resulted in an increasing number of elderly patients undergoing c... more The aging of the population has resulted in an increasing number of elderly patients undergoing cardiac operations. We reviewed our experience in patients over the age of 80 undergoing primary aortic valve replacement (AVR) with or without CABG. Between 2000 and 2008, 345 patients (226 male) ≥80 years underwent primary AVR in our unit. The notes of these patients were retrospectively reviewed and follow-up information was obtained from their general practitioners. They had a mean age of 82.9 ± 2.3 years and a median logistic EuroSCORE of 13.4 (IQR 9.4, 19.1). Isolated AVR was performed in 161 patients (45.5%), and 184 (51.6%) patients underwent combined AVR and CABG. A quality of life questionnaire was sent to all survivors. Hospital mortality occurred in 17 patients (4.9%), which was significantly lower than the mortality predicted by logistic EuroSCORE (16.2%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Hospital mortality was comparable between patients undergoing isolated AVR and those undergoing additional CABG (4.3% vs. 5.4%, respectively). Actuarial survival at one and five years was 90.1 ± 1.6% and 77.2 ± 2.9%, respectively. There was a 62% response on the questionnaire showing 70% of the patients were NYHA I and 83.7% were satisfied with the operation outcome. AVR can be undertaken with excellent results in octogenarians and the current risk is significantly lower than what is predicted with conventional risk-scoring systems. Patients with advanced age should not necessarily be excluded from being candidates for AVR.

Research paper thumbnail of Statin Treatment in Hypercholesterolemic Pregnant Mice Reduces Cardiovascular Risk Factors in Their Offspring

Hypertension, 2008

Increasing evidence suggests that hypercholesterolemia during pregnancy initiates pathogenic even... more Increasing evidence suggests that hypercholesterolemia during pregnancy initiates pathogenic events in the fetus leading to increased risk of cardiovascular disease in the adult offspring. In this study we examined in mice whether pharmacological intervention using statins in late pregnancy could alleviate the detrimental effects of a high-fat, high-cholesterol (45% fat) maternal diet on the health of the dams and their offspring. Pregnant C57 mice on high-fat, high-cholesterol diet were given the 3hydroxy3methylglutaryl-coenzyme A reductase inhibitor pravastatin in the drinking water (5 mg/kg of body weight per day) in the second half of pregnancy and during lactation to lower cholesterol and improve postweaning maternal blood pressure. Weaned offspring were then fed the high-fat, high-cholesterol diet until adulthood (generating dam/offspring dietary groups high-fat, high-cholesterol/high-fat, high-cholesterol and high-fat, high-cholesterol plus pravastatin during the second half ...

Research paper thumbnail of Aortic valve replacement in patients with previous coronary artery bypass grafting: 10-year experience

European Journal of Cardio-Thoracic Surgery, 2011

OBJECTIVES: This study aimed to investigate the early and late outcomes of patients undergoing ao... more OBJECTIVES: This study aimed to investigate the early and late outcomes of patients undergoing aortic valve replacement (AVR) with previous coronary artery bypass grafting (CABG) and patent grafts. METHODS: Between January 2000 and March 2010, 104 patients (87 males) with previous CABG ± concomitant surgery and patent grafts underwent AVR. The median age of the patients was 75 years (range: 37-90 years; inter-quartile range: 69-79 years) and the mean logistic EuroScore was 25.37 ± 16.8. The median time since the previous operation was 9 years (range 1-25; inter-quartile range: 7-14 years). The left internal mammary artery (LIMA) had been used in 75 patients (72.1%) and remained patent in 72 cases (96.0%). RESULTS: Thirty-day mortality was 7.7% (n = 8), which is less than the predicted mean logistic EuroScore. Isolated AVR was performed in 66 patients (63.5%). The LIMA was dissected and isolated (clamped or blocked with balloon) in 60 patients. The median hospital stay was 10 days (range: 4-183 days; inter-quartile range: 7-15.25 days). Nineteen patients (18.3%) had pulmonary complications, while 12 (11.5%) had acute kidney injury. Seven patients (6.7%) required permanent pacemaker. Six LIMAs (8.3%) were injured and repaired. Prolonged aortic cross-clamp (AXC) time (P = 0.038) and the presence of a previous LIMA graft (P = 0.045) were identified as independent predictors of 30-day mortality. The actuarial survival at 1 and 5 years was 89.4 ± 0.3 and 81.5 ± 0.5%, respectively. Perioperative intra-aortic balloon pump use (P = 0.036), prolonged AXC time (P = 0.004) and prolonged cardiopulmonary bypass time (P = 0.022) were associated with worse long-term overall survival on multivariate analysis. CONCLUSIONS: AVR post-CABG with patent grafts can be performed in high-risk patients with excellent short-and long-term outcomes and appears to be superior to published catheter-based interventions. In the absence of randomized trial data, we believe that open AVR remains the treatment of choice for aortic valve disease following prior CABG.

Research paper thumbnail of P1-16 Impact on the developmental profile of the murine heart by maternal protein restriction during pregnancy

Early Human Development, 2007

Results: There were no differences between treatments in fetal weight or body dimensions. Crown-r... more Results: There were no differences between treatments in fetal weight or body dimensions. Crown-rump length, thoracic girth, head circumference and length and mean forelimb cannon bone length were dependent on fetal weight (P < 0.05). Treatment had no effect on weight of any fetal organ. There were no differences between treatments in number, weight or volume of cotyledons or caruncles, or weight of uterus or fetal membranes. Fetuses from the low treatment were a greater (P < 0.01) proportion of maternal live weight than fetuses from the moderate treatment (53±2 versus 44±2 g/100 kg). Conclusions: Fetal growth in the first 90 days of gestation occurred independently of maternal liveweight gain in 15-month-old beef heifers.

Research paper thumbnail of 3B-6 Statin therapy improves blood pressure and lipid profiles in hypercholesterolemic mothers but not C-reactive proteins levels or endothelial progenitor cell expression

Early Human Development, 2007

involvement of GSTM1 in detoxification of paracetamol in pregnancy may result in depletion of glu... more involvement of GSTM1 in detoxification of paracetamol in pregnancy may result in depletion of glutathione, leading to increased susceptibility of the fetal lung to damage from other oxidants. 3B-4 Essential nutrient supplementation preventing adult metabolic disease in a transgenerational model of IUGR is accompanied by epigenetic regulation of gene expression

Research paper thumbnail of Repair of acute type A aortic dissection: results in 100 patients

Asian Cardiovascular and Thoracic Annals, 2012

To determine short- and long-term outcomes after repair of type A aortic dissection, we reviewed ... more To determine short- and long-term outcomes after repair of type A aortic dissection, we reviewed data of 100 consecutive patients (64 men; mean age, 63 ± 12.2 years) who underwent acute type A aortic dissection repair between January 2000 and June 2008. They were divided into group A, open anastomosis (circulatory arrest; n = 59) and group B, closed anastomosis (no circulatory arrest; n = 41). Aortic valve re-suspension or replacement was performed in 77 patients, aortic root replacement in 29, and aortic arch procedures in 31. The median follow-up was 2.8 years (range, 0–8.6 years). The 30-day mortality was 14%; 16.9% in group A and 9.8% in group B. None of the 23 variables analyzed to determine predictors of death or stroke was significant on multivariate analysis. Postoperatively, there was no difference between the 2 groups with respect to stroke, sepsis, renal failure, multiorgan failure, or reoperation. Overall actuarial survival at 1, 3, 5, and 8 years was not significantly d...