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Biomedical subjects

Stephen Westaby

Publications and source records attributed to Stephen Westaby.

At least 19 recordsLinked to original sources
PubMed2008

Ventricular septal rupture following abciximab infusion.

Ventricular septal rupture is a rare complication of myocardial infarction. Despite a significant reduction in its incidence with reperfusion therapy, thrombolysis has been implicated in the pathogenesis of septal rupture. There is little information regarding the impact of glycoprotein IIb-IIIa receptor blockers on ventricular septal rupture. We report a case of rupture of the ventricular septum occurring after treatment with the glycoprotein IIb-IIIa receptor blocker abciximab, in the absence of thrombolysis.

Abciximab↗
PubMed2006

Upregulation of Bcl-2 proteins during the transition to pressure overload-induced heart failure.

BACKGROUND: Cardiomyocyte apoptosis is implicated in the pathogenesis of heart failure and mitochondria play an important role in this mode of cell death. In this study, activity of the Bcl-2 family of mitochondrial apoptotic proteins and their regulator (p53) were assessed during the transition to heart failure. METHODS: Ten adult male sheep were banded with a variable aortic constriction device. This was progressively inflated to increase left ventricular (LV) afterload. The sheep were monitored echocardiographically, measuring LV Mass Index (LVMI), diastolic LV Internal Diameter (LVIDd) and Fractional Shortening (FS). Serial LV endomyocardial biopsies were obtained, to measure expression of p53 and Bcl-2 family proteins by Western blotting. RESULTS: Over the first 3-4 weeks, the sheep developed hypertrophy (LVMI 79.5+/-4.6 vs. 44.0+/-3.0 g/m2, p<0.01), followed by gradual LV dilatation (LVIDd 4.23+/-0.08 vs. 3.39+/-0.07 cm, p<0.01). Ventricular function remained stable until 7-8 weeks post banding, when there was significant deterioration (FS 18.3+/-2.4 vs. 46.9+/-2.6%, p<0.01), associated with clinical heart failure. Upregulation of the Bax/Bcl-2 ratio, associated with increased levels of p53, was demonstrated in each of the echocardiographically defined stages (LV hypertrophy, LV dilatation and LV failure). In parallel, significantly higher levels of anti-apoptotic protein (Bcl-xL) was associated with LV dilatation and failure. CONCLUSIONS: Upregulation of Bax/Bcl-2 ratio occurs during the transition to heart failure and in particular with the initial hypertrophic response. Increase in expression of the anti-apoptotic protein Bcl-xL suggests possible concomitant compensatory mechanisms being activated during the transition to heart failure.

Animals↗
PubMed2006

Activation of apoptotic caspase cascade during the transition to pressure overload-induced heart failure.

OBJECTIVES: A pressure overload model was developed to simulate aortic stenosis and assess caspase activity during the transition to heart failure. BACKGROUND: Cardiomyocyte apoptosis is implicated in the pathogenesis of heart failure, and caspase activation is central to this pathophysiological process. METHODS: A total of 10 sheep were banded with variable aortic constriction devices, progressively inflated to increase left ventricular (LV) afterload. Serial LV endomyocardial biopsy samples were obtained to measure caspase activity and presence of apoptosis. RESULTS: Over the first 3 to 4 weeks, hypertrophy developed in the sheep (LV mass index 90.8 +/- 4.9 g/m2 vs. 44.0 +/- 3.0 g/m2, p < 0.01), followed by gradual dilatation of the left ventricle (diastolic LV internal diameter 4.23 +/- 0.08 cm vs. 3.39 +/- 0.07 cm, p < 0.01). Ventricular function remained stable until 7 to 8 weeks after banding, when there was significant deterioration (fractional shortening 18.3 +/- 2.4% vs. 46.9 +/- 2.6%, p < 0.01), associated with clinical heart failure. Serial LV endomyocardial biopsy samples were obtained at each echocardiographically defined stage (LV hypertrophy, LV dilation, and LV failure). Activity of caspases-3, -8, and -9 (measured by specific fluorogenic peptide substrates and immunohistochemistry) increased progressively, particularly with the onset of myocardial dysfunction (caspase-3 7.92 +/- 1.19 vs. 1.00 +/- 0.15, caspase-8 1.94 +/- 0.21 vs. 1.00 +/- 0.04, caspase-9 5.87 +/- 0.97 vs. 1.00 +/- 0.18 relative fluorescent units, p < 0.05). No evidence of deoxyribonucleic acid (DNA) fragmentation, however, was identified by immunohistochemical assays. CONCLUSIONS: Activation of cardiomyocyte caspase enzymes occurs during the transition to heart failure, without completion of apoptotic DNA fragmentation. Increased activity of caspase-8 and -9 suggests both mitochondrial and death-receptor mediated pathways are involved in this pathological process. Further knowledge of these pathways may stimulate development of apoptosis-based strategies for slowing progression of heart failure in aortic stenosis patients.

Animals↗
PubMed2006

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↗
PubMed2005

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↗
PubMed2005

Anterior approach to implant the Jarvik 2000 with retroauricular power supply.

The retroauricular power supply of the Jarvik 2000 (Jarvik Heart Inc, New York, NY) left ventricular assist device is suitable for permanent support, as it is associated with fewer infections than conventional drivelines. Implantation through a left-lateral thoracotomy limits the performance of additional cardiac procedures. We describe a technique that used a sternotomy for the implantation of the Jarvik 2000 with retroauricular power supply in two patients. The retroauricular power supply of the Jarvik 2000 can be provided with an anterior approach, allowing full surgical access to the heart. If the outflow graft to the ascending aorta indeed reduces aortic stasis and thromboembolic events, the anterior approach with retroauricular power delivery might evolve into a standard procedure.

Aged↗
PubMed2004

Diagnosis and management of aortoesophageal fistula caused by a foreign body.

Aortoesophageal fistula is a rare cause of gastrointestinal hemorrhage often resulting in mortality. A case of aortoesophageal fistula caused by a swallowed fish bone leading to respiratory arrest is reported. The clinical presentation was unusual. The successful treatment required the use of hypothermic circulatory arrest.

Aortic Diseases↗
PubMed2004

Ventricular assist devices as destination therapy.

The prospects for long-term mechanical circulatory support are improving. Axial flow pumps are a promising competitor to pulsatile first-generation LVADs, although the two may serve different patient populations. Centrifugal pumps are in the development phase and seem to require less anticoagulation. Clinical experience has established the safety of diminished pulse pressure circulation, and mechanical unloading appears to promote recovery of the native left ventricle. Under these circumstances, true left ventricular assist is preferable to ventricular replacement and detailed medical management improves patient outcomes. Further clinical trials of destination therapy are indicated and must use more reliable blood pumps implanted before terminal decline into multiorgan failure.

Cardiac Output, Low↗
PubMed2004

Clinical experience with an implantable, intracardiac, continuous flow circulatory support device: physiologic implications and their relationship to patient selection.

BACKGROUND: We have been investigating continuous-flow circulatory support devices for 20 years. Unlike pulsatile assist devices, continuous-flow pumps have a simplified pumping mechanism and they do not require compliance chambers or valves. In the 1980s, clinical experience with the Hemopump proved a high-speed, intravascular, continuous-flow pump could safely augment the circulation. Subsequently, a decade of animal experiments with a larger, longer-term continuous-flow pump (the Jarvik 2000) confirmed the safety and efficacy of intraventricular placement, leading to its clinical application. METHODS: We analyzed the physiologic and anatomic effect of using the Jarvik 2000 pump for cardiac support in 23 patients in whom the device was applied as a bridge to transplant under the protocol approved by the Food and Drug Administration Investigational Device Exemption. The device was used as a bridge to transplantation in 20 patients and as destination therapy in 3 patients. RESULTS: In the bridge-to-transplant group, 14 patients underwent transplantation, 5 died during the circulatory support period and 1 is in an ongoing study. The support period lasted an average of 90 days. For the survivors, the follow-up period has averaged 16 months. Within the first 48 postoperative hours, the average cardiac index increased by 65% (from 1.77 +/- 0.24 to 2.92 +/- 0.60 L. min(-1). m(-2), p = 0.00000002), the systemic vascular resistance decreased by 42% (from 1604 +/- 427 to 930 +/- 330 dynes/sec per cm(2), p = 0.00001), and the pulmonary capillary wedge pressure (PCWP) decreased by 41.8% (from 23 +/- 5.1 to 13.4 +/- 6.6 mm Hg, p = 0.00009). Similar results were seen for the patients undergoing destination therapy. Cardiac index increased 89.5% (from 1.9 +/- 0.1 to 3.6 +/- 0.6, p = 0.046) and PCWP decreased by 52.2% (from 23 +/- 10 to 11 +/- 2, p = 0.22). In that group, 1 patient died unexpectedly from an accident 382 days after device implantation. The 2 survivors remain in New York Heart Association (NYHA) functional class I at 700 to 952 days after implantation. CONCLUSIONS: The Jarvik 2000 can offer effective long-term support for patients with chronic heart failure and NYHA class IV status. However, the new physiology produced by continuous offloading of the heart throughout the cardiac cycle has introduced unique clinical problems. The understanding of the problems generated by this biotechnological interface is essential for obtaining optimal clinical outcomes.

Adult↗
PubMed2004

Coronary revascularization in ischemic cardiomyopathy.

This article first discusses coronary artery disease, including left-ventricular dysfunction, hibernating myocardium, the relationship between stunning, hibernation, and heart failure, and molecular mechanisms underlying myocardial hibernation. Left ventricular function and the prognosis and pathophysiology of left-ventricular dysfunction are then examined. Selection of patients for revascularization is discussed, to include which coronary patients should be investigated for myocardial viability, and other surgical considerations are outlined. The outcome following revascularization in the heart failure patient, the results of revascularization, and the time course of functional recovery after coronary artery bypass graft are also covered.

Angioplasty, Balloon, Coronary↗
PubMed2004

Hemodynamics of chronic nonpulsatile flow: implications for LVAD development.

Both experimental and clinical evidence suggest that pulse pressure is not required from a blood pump. End-organ function is well maintained with nonpulsatile systems, though pulse pressure may accelerate recovery from cardiogenic shock. Form follows function, so the effects of reduced pulse pressure on the arterial wall are not surprising. The ability to alter aortic wall morphology by reducing pulse pressure may have important implications for the future treatment of arterial pathology. Both centrifugal and axial-flow pumps can be miniaturized and are silent. Their reliability and user-friendly status may soon allow implantation at an earlier stage of cardiac deterioration. Doubts about the feasibility of long-term pulseless circulation are disappearing.

Animals↗
PubMed2004

Spontaneous echocardiographic contrast in the ascending aorta mimicking the appearance of aortic dissection in a patient with a left ventricular assist device.

We describe a patient with a previously implanted Jarvik 2000 left ventricular assist device (LVAD), who presented with bacteraemia and with features suspected for aortic dissection at the CT scan. However, transesophageal echocardiography showed competition in the ascending aorta between the retrograde pump flow and the anterograde transaortic output, which mimicked true aortic dissection and could be resolved by lowering the pump speed. As patients with LVAD are increasing in number, clinicians should be aware of this possible effect.

Aged↗