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Biomedical subjects

John Pepper

Publications and source records attributed to John Pepper.

At least 19 recordsLinked to original sources

Aortic root dilation secondary to giant cell aortitis in a human immunodeficiency virus-positive patient.

HIV-associated vasculitis rarely involves the aorta. There is no well-established association of HIV and giant cell arteritis. We present the case of a 31-year-old HIV positive Indian woman who was referred to us with complaints of dyspnea and chest pain. Physical examination revealed a diastolic murmur in the aortic area and echocardiography showed a dilated aortic root causing severe aortic regurgitation. She was being adequately treated with anti-HIV therapy. She underwent aortic valve and root replacement and the histopathological findings of the aortic specimen showed giant cell arteritis.

Adult↗

The effect of aortic valve replacement on plasma B-type natriuretic peptide in patients with severe aortic stenosis--one year follow-up.

BACKGROUND: B-type natriuretic peptide (BNP) is synthesized in cardiac tissue in response to increased wall stress and myocardial hypertrophy. AIMS: In patients with severe aortic stenosis (AS) we examined the effect of aortic valve replacement (AVR) on plasma BNP and association between BNP and left ventricular mass index (LVMI) preoperatively and in the reverse-remodeling phase twelve months postoperatively. We also examined the correlation between BNP and NYHA-class and between BNP and age. METHODS AND RESULTS: Plasma BNP analyses and echocardiographic measurements were performed preoperatively, before discharge after AVR, and at twelve months in twenty-two patients. BNP was additionally measured at six months. Preoperatively, BNP was 283+/-45 pg/ml (mean+/-SEM). Following an immediate postoperative increase (441+/-38 pg/ml), BNP values decreased towards normal values at six and twelve months (139+/-25 and 130+/-18 pg/ml, respectively). LVMI was 206.5+/-15.8 g/m(2) preoperatively and decreased to 119.7+/-7.2 g/m(2) at twelve months with a correlation between LVMI and BNP preoperatively only (r=0.45, p<0.05). There was no correlation between BNP and NYHA-class, whereas BNP correlated to age both pre- and post-operatively. CONCLUSION: We report an increase in plasma BNP in patients with AS. Following a further transient increase postoperatively, BNP levels decreased at six and twelve months after AVR. BNP correlated with LVMI preoperatively, and with age both preoperatively and at twelve months.

Aged↗

Mechanical reliability of the Jarvik 2000 Heart.

BACKGROUND: Device failure is a limitation of permanent mechanical circulatory support. We studied the mechanical reliability of the Jarvik 2000 Heart, an axial flow pump with ceramic bearings designed to provide more than 10 years' durability. METHODS: The Jarvik 2000 Heart was implanted in 102 patients between April 2000 and December 2004. Eighty-three pumps with an abdominal driveline were implanted as a bridge-to-transplantation, and 19 with postauricular power supply as lifetime therapy. Eighteen pumps were recovered intact after clinical use and run continuously on the bench to further assess durability. RESULTS: No implantable component failure occurred either in patients or during bench testing. The cumulative pump run-time was 110 years: 59 years overall in vivo and 51 years in vitro. The mean support time for bridge-to-transplant recipients was 159 days, and for discharged lifetime-therapy recipients 551 days. Six recipients were supported moer than 2 years, with the longest ongoing approaching 5 years. External cables caused three system failures, with a 95% freedom from system failure at 4 years. Device malfunctions, related to external cables (9) and lack of a backup battery (1), caused no adverse consequences. Before introduction of noncorrosive, gold-plated stainless steel connectors, corrosion was observed on three connectors to the retroauricular power supply. CONCLUSIONS: The Jarvik 2000 Heart has had no implantable component failure. Meaningful durability data and failure mode can only be established by real-time testing in patients. The reliability and dependability of this device, in addition to the exchangeability of external components, give promise for long-term circulatory support in critically ill heart failure patients.

Equipment Failure Analysis↗

Randomized comparison of stentless versus stented valves for aortic stenosis: effects on left ventricular mass.

BACKGROUND: Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve. We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. METHODS AND RESULTS: The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus < or =25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176+/-62 and 182+/-63 g/m2, respectively) or at 6 months (142+/-49 and 131+/-45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. CONCLUSIONS: Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months.

Aged↗

Objective assessment of technical skills in cardiac surgery.

OBJECTIVE: Reduced training time combined with no rigorous assessment for technical skills makes it difficult for trainees to monitor their competence. We have developed an objective bench-top assessment of technical skills at a level commensurate with a junior registrar in cardiac surgery. METHODS: Forty cardiothoracic surgeons were recruited for the study, consisting of 12 junior trainees (year 1-3), 15 senior trainees (year 4-6) and 13 consultants. The assessment consisted of four key tasks on standardised bench-top models: aortic root cannulation, vein-graft to aorta anastomosis, vein-graft to Left Anterior Descending (LAD) anastomosis and femoral triangle dissection. An expert surgeon was present at each station to provide passive assistance and rate performance on a validated global rating scale giving rise to a total possible score of 40. Three expert surgeons repeated the ratings retrospectively, using blinded video recordings. Data analysis employed non-parametric tests. RESULTS: Both live and video scores differentiated significantly between performances of all groups of surgeons for all four stations (P < 0.01) (median live and video score for LAD; Junior 19,17; Senior 29,22; Consultant 36,28). Correlations between live and blinded rating were high (r = 0.67-0.84; P < 0.001) as was inter-rater reliability between the three expert video raters (alpha = 0.81). CONCLUSIONS: The use of bench-top tasks to differentiate between cardiac surgeons of differing technical abilities has been validated for the first time. Furthermore, it is unnecessary to perform post-hoc video rating to obtain objective data. These measures can provide formative feedback for surgeons-in-training and lead to the development of a competency-based technical skills curriculum.

Cardiac Surgical Procedures↗

Advanced heart failure: feasibility study of long-term continuous axial flow pump support.

AIMS: A lack of donor hearts has stimulated interest in using blood pumps to treat severe heart failure. We tested the hypothesis that a new continuous flow circulatory assist device could be employed safely to relieve symptoms of heart failure and evaluated the potential to prolong life. METHODS AND RESULTS: An intracardiac axial flow pump was implanted in 17 heart failure patients [idiopathic dilated (12), ischaemic (4), or amyloid cardiomyopathy (1)]. All were deemed ineligible for transplantation. Implantation of the device was by left thoracotomy (15) or median sternotomy (2). Power delivery was by a skull-mounted titanium pedestal. All patients survived surgery. None needed right ventricular support. There were three hospital deaths, two early from subdural haematoma and aortic thrombosis, one late after switching to transplantation. A total of 14 patients left hospital with a cumulative support-time of 15.9 years (median: 293 days, interquartile range: 286 days, 1-44 months). Actuarial 1-, 2-, and 3-year survivals were 56, 47, and 24%, respectively. There was no pump failure. Quality of life scores improved. Two superficial pedestal infections were successfully treated. Four patients had cerebral thrombo-embolism: two early events attributed to inadequate anticoagulation and two late with near-complete resolution. An improved anticoagulant regime addressed this problem. Late death occurred in five patients from battery disconnection, subdural haematoma, bowel ischaemia, respiratory failure, and after cardiac transplantation. CONCLUSION: Continuous flow blood pumps provided symptomatic relief of severe heart failure with high quality of life. Event-free survival reached 4 years. Analysis of adverse events led to improved management strategies. There is potential for widespread use of blood pumps in the community. A controlled trial is required.

Aged↗

Potential difference measurements in the lower airway of children with and without cystic fibrosis.

Nasal potential difference measurements are valuable endpoint assays in clinical studies of novel treatments for cystic fibrosis (CF). Similar measurements made on the lower airway via the bronchoscope have been successful in adults, but have not been reported in children, the group most likely to benefit from such therapies. Here we report the design and validation of a small, single-lumen catheter technique allowing baseline potential difference and chloride secretion to be assessed in the distal airways of children as young as 1 year of age. Tracheal baseline values were significantly higher in children with CF than those without, although this was not the case more distally. In airways between the third and seventh generation, perfusion with a zero chloride solution containing isoprenaline led to a significant change in potential difference in children without CF, whereas no change was seen in those with CF. This measure provided a reliable distinguishing test between the two disease groups. We confirm that invasive bronchoscopic techniques can be performed safely and reliably in small children. Potential difference measurements could form a useful functional endpoint assay for future studies of either the CFTR gene or protein-based therapies in future trials in the pediatric age group.

Bronchi↗

A validated simple model to predict coexistent coronary disease in patients undergoing mitral valve surgery.

OBJECTIVE: The primary limitation of the American Heart Association/American College of Cardiology guidelines is specificity. To improve the selection process, we proposed a simple additive model including age (1 point for every 5 years above 50), male sex (2 points), hypercholesterolemia (2 points), angina (3 points), and electrocardiographic evidence of ischemia (3 points). We recommend screening angiography at 3 or more points. This model was previously derived from 359 patients at Papworth Hospital. METHODS: The validation cohort was a consecutive series of patients who underwent mitral valve surgery at the Royal Brompton Hospital. Preoperative coronary angiography reports were obtained, and coronary disease was defined as luminal narrowing of 50% in 2 or more views. Sensitivities and specificities were calculated for the American Heart Association/American College of Cardiology criteria, the simple additive model, and a logistic regression model. Receiver operating characteristic curves were used to validate accuracy and compare discrimination with logistic regression. RESULTS: From 1998 through 2003, angiographic details were available for 342 (86%) of 396 patients who underwent mitral valve surgery. The sensitivity and specificity of the American Heart Association/American College of Cardiology guidelines were 100% and 5%, respectively; those of the simple additive model were 91% and 44%, respectively; and those of logistic regression were 93% and 41%, respectively. The receiver operating characteristic areas for the simple additive and logistic regression model were 0.78 (95% confidence interval, 0.73-0.84) and 0.80 (95% confidence interval, 0.74-0.85), respectively. CONCLUSIONS: This is the third independent cohort to highlight the poor specificity of the American Heart Association/American College of Cardiology guidelines. Although high sensitivity is achieved, the cost is the majority of patients requiring screening angiography. Our validated simple model improved the specificity and selection; however, this was achieved at the expense of decreased sensitivity.

Aged↗

Controversies in off-pump coronary artery surgery.

Motivated by a desire to reduce the morbidity of a well-established and effective procedure for coronary artery disease, up to 25% of coronary artery bypass operations are being performed without the use of a heart-lung pump. Concerns remain about the quality of the coronary anastomoses and the completeness of revascularization. Randomized trials have not revealed the significant reduction in morbidity or mortality that the early enthusiasts had hoped for. Yet a number of non-randomized studies have shown clinical benefit from the avoidance of an extracorporeal circulation, but these have been criticized for potential bias in patient selection and management.A majority of surgeons have not yet adopted this technique and are waiting for the accumulation of more evidence.

Age Factors↗

Neuropsychological outcome after percutaneous coronary intervention or coronary artery bypass grafting: results from the Stent or Surgery (SoS) Trial.

BACKGROUND: Coronary artery bypass surgery (CABG) has been associated with a range of neurological and neuropsychological complications from stroke to cognitive problems such as memory and problem solving disturbance. However, little is known about the impact of percutaneous coronary intervention (PCI) on neuropsychological outcome. METHODS AND RESULTS: In the Stent or Surgery Trial (SoS), 988 patients were randomized in equal proportions between PCI supported by stent implantation and CABG. As a substudy of this trial, we undertook an evaluation of neurological and neuropsychological outcomes after intervention. A clinical examination and neuropsychological assessment consisting of 5 tests (Digit Span Forwards and Backwards, Visual Reproduction, Bourdon, and Block Design) were performed at baseline and 6 and 12 months after the procedure. A total of 145 patients were included in the substudy analysis: 77 in the PCI group and 68 in the CABG group. One patient in the PCI arm had a stroke. There was no significant difference between treatment groups at 6 and 12 months for any of the 5 tests. The mean change from baseline was also similar in both groups. CONCLUSIONS: We were not able to demonstrate an important and significant difference in neuropsychological outcome in patients treated with different revascularization strategies. This important finding needs to be examined in further research.

Adrenergic beta-Antagonists↗

Determinants of successful endoscopic internal thoracic artery harvesting: a prospective analysis.

OBJECTIVE: Endoscopic internal thoracic artery (ITA) harvesting is employed during minimal-access coronary artery bypass grafting. To improve case selection, we prospectively analyzed our entire experience to identify variables that predict intraoperative conversion to sternotomy. METHODS: We performed a prospective study from September 1999 to November 2003 of 100 consecutive patients with an endoscopically harvested left ITA (LITA). Success was defined as an endoscopic dissection of the LITA sufficient to reach the anastomosis. Multivariate logistic regression analysis was performed to identify independent preoperative and procedural predictors of success. RESULTS: The measured parameters (mean +/- SD) were age (62 +/- 9 years), height (174 +/- 9 cm), weight (81 +/- 14 kg), and logistic Euroscore (2.0 +/- 1.7). Patients comprised 8 (8%) women, 17 (17%) with urgent operations, 42 (42%) with multiple vessel disease, 17 (17%) with a left ventricular ejection fraction <50%, 2 (2%) redo procedures, and 3 (3%) with pleural disease. The Zeus robot was used in 17 patients (17%). Eight-eight (88%) of the LITA were successfully harvested endoscopically. Among the 12 patients who underwent conversions, pleural adhesions were the most common finding (n = 4, 33%). One LITA was unusable. In the final multivariate model, lung disease was a negative predictor of successful endoscopic harvest (odds ratio, 0.13; 95% confidence interval, 0.02-0.63; P =.012). The variables of age, sex, left ventricular function, logistic Euroscore, operative priority, and use of the Zeus robot did not achieve statistical significance. CONCLUSIONS: Acceptable conversion rates and low conduit wastage are achievable during a unit's initial experience. Lung disease is associated with increased conversion frequency, and surgeons embarking on endoscopic harvesting should consider excluding these patients to improve their chances of success. Pleural adhesions increase the technical difficulty of surgery.

Coronary Artery Bypass↗

A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery.

BACKGROUND: The effect of the use of coronary-artery bypass surgery without cardiopulmonary bypass and cardiac arrest ("off pump") on graft patency remains uncertain. We undertook a prospective, randomized, controlled study to compare graft-patency rates and clinical outcomes in off-pump surgery with conventional, "on-pump" surgery. METHODS: We randomly assigned 50 patients to undergo on-pump coronary-artery bypass grafting and 54 to undergo off-pump surgery. Surgical and anesthetic techniques were standardized for both groups. Clinical outcomes and troponin T levels were measured. Three months later, the patients underwent coronary angiography, including quantitative analysis. RESULTS: The mean age of the patients was 63 years, and 87 percent were men. The on-pump group received a mean of 3.4 grafts, and the off-pump group 3.1 (P=0.41). There were no deaths. There was no significant difference in the median postoperative length of stay between the two groups (seven days in each group). The area under the curve of troponin T levels was higher during the first 72 hours in the on-pump group than in the off-pump group (30.96 hr x microg per liter vs. 19.33 hr x microg per liter, P=0.02). At three months, 127 of 130 grafts were patent in the on-pump group (98 percent), as compared with 114 of 130 in the off-pump group (88 percent, P=0.002). The patency rate was higher for all graft territories in the on-pump group than in the off-pump group. CONCLUSIONS: In this randomized study, off-pump coronary surgery was as safe as on-pump surgery and caused less myocardial damage. However, the graft-patency rate was lower at three months in the off-pump group than in the on-pump group, and this difference has implications with respect to the long-term outcome.

Aged↗

Do off-pump techniques reduce the incidence of postoperative atrial fibrillation in elderly patients undergoing coronary artery bypass grafting?

BACKGROUND: Atrial fibrillation is the most common postoperative complication in patients undergoing coronary artery bypass grafting (CABG) with advancing age having been shown to have a significant association with its incidence. This study aims to assess whether off-pump coronary artery bypass (OPCAB) reduces the incidence of atrial fibrillation in elderly patients. METHODS: A meta-analysis of all observational studies reporting a comparison between the two techniques in elderly patients (> 70 years) between 1999-2003 was performed. The primary outcome of interest was the incidence of postoperative atrial fibrillation. The quality of each study was evaluated by examining three items: patient selection, matching of the off-pump and cardiopulmonary bypass patient groups, and assessment of outcome. Meta-regression analysis was undertaken to see the effects of study size and quality on the calculated odds ratio. RESULTS: Eight studies fulfilled our inclusion criteria, all of which were nonrandomized. In total the studies identified 3017 subjects, of which 764 had off-pump surgery (25%) and 2253 underwent cardiopulmonary bypass (75%). Meta-analysis showed that after off-pump surgery there was a significantly lower incidence of postoperative atrial fibrillation in these patients (odds ratio 0.70, 95% confidence interval [CI] 0.56-0.89). Meta-regression analysis including study characteristics did not show any associations affecting the calculated odds ratio of atrial fibrillation. CONCLUSIONS: Our study demonstrates a reduced incidence of postoperative atrial fibrillation in an elderly population with off-pump as compared with cardiopulmonary bypass techniques. We appreciate, however, that our statistical analysis uses nonrandomized published data and that the results must be treated with caution. If this finding is confirmed by a large-scale randomized trial, it has significant implications on the operative strategy employed for this patient group.

Aged↗