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Biomedical subjects

Asghar Khaghani

Publications and source records attributed to Asghar Khaghani.

At least 19 recordsLinked to original sources

Bridge to transplantation with a left ventricular assist device for systemic ventricular failure after Mustard procedure.

After Mustard or Senning procedures, transplantation remains the only option for some patients who present at late stage with severe systemic (right) ventricular failure. In some circumstances these patients may require urgent mechanical circulatory support to bridge them to transplantation. The use of mechanical support poses considerable potential and actual specific problems both in terms of insertion and management of the device. We report the case of a 17-year-old patient who had a left ventricular assist device implanted from the right ventricle to the aorta for "end-stage" heart failure 15 years after the Mustard procedure. The specific problems are discussed and a management scheme is proposed.

Adolescent↗

A calcified cardiac mass.

Cardiac fibromas are benign tumours, often diagnosed in childhood, but rarely they may be diagnosed in adults or the elderly. We present an interesting case of a middle-aged lady presenting with exertional chest pain and breathlessness, who was found to have a heavily calcified mass within the myocardium. With a previous history of chest trauma, a calcified myocardial haematoma was initially suspected. Complete surgical excision led to a total resolution of symptoms. Histological examination confirmed the diagnosis of a cardiac fibroma. Complete excision of cardiac fibromas, where possible, is advised and is associated with excellent survival.

Biopsy, Needle↗

Left ventricular assist device and drug therapy for the reversal of heart failure.

BACKGROUND: In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation. METHODS: We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the beta2-adrenergic-receptor agonist clenbuterol was administered to prevent myocardial atrophy. RESULTS: Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (+/-SD) of 320+/-186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64+/-12%, the mean left ventricular end-diastolic diameter was 59.4+/-12.1 mm, the mean left ventricular end-systolic diameter was 42.5+/-13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3+/-6.0 ml per kilogram of body weight per minute. CONCLUSIONS: In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen.

Adolescent↗

Levitronix as a short-term salvage treatment for primary graft failure after heart transplantation.

BACKGROUND: Primary graft failure after heart transplantation is a well-recognized catastrophic complication with a high mortality rate. It is becoming more frequent due to the increasing use of marginal donors. In these difficult cases a ventricular assist device (VAD) as a bridge to recovery or as a bridge to re-transplantation can be used. The recently introduced Levitronix Centrimag centrifugal pump might be an ideal device for this purpose. METHODS: In this study we describe 2 patients with primary graft failure who received a Levitronix in the last 2 years, immediately after failure to wean from cardiopulmonary bypass. Biventricular support was necessary in both patients. RESULTS: One patient was successfully re-transplanted after 2 days of support, and subsequently discharged. After 16 months she has good ventricular function with no symptoms of cardiac failure. The second patient showed signs of ventricular recovery after a few days and was weaned from the device after 7 days, with good graft function. No device-related complications were recorded. After 14 days he was discharged from the intensive care unit (ICU), and a post-operative echocardiogram showed normal dimensions, good ejection fraction and no valvular regurgitation. He was discharged home 26 days after the transplant. CONCLUSIONS: In our experience, the Levitronix Centrimag seems to be safe and effective in the treatment of primary graft failure, achieving effective circulatory support and ventricular off-loading. We propose its use in isolated or biventricular graft failure either as bridge to re-transplant or as a bridge to recovery.

Adolescent↗

Acinetobacter mediastinitis in a heart transplant patient.

We report a 56-year-old who underwent orthotopic heart transplantation following left ventricular assist device bridge to transplantation. His postoperative course was complicated by severe sternal wound infection with Acinetobacter species requiring extensive debridement and reconstruction with a pectoralis major flap. This was followed by a total sternectomy, pectoralis flap debridement, and vacuum-assisted dressing.

Acinetobacter↗

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↗

A quantitative gene expression profile of matrix metalloproteinases (MMPS) and their inhibitors (TIMPS) in the myocardium of patients with deteriorating heart failure requiring left ventricular assist device support.

BACKGROUND: Mechanisms underlying the rapid deterioration of heart failure patients who subsequently require left ventricular assist device (LVAD) support are poorly understood. Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play a key role in myocardial remodelling and heart failure. We hypothesized that MMP and TIMP expression would be altered in these patients. METHODS: Quantitative polymerase chain reaction was used to measure myocardial messenger RNA levels of MMP1 to MMP14, TIMP1 to TIMP4, collagen I and collagen III in 24 dilated cardiomyopathy (DCM) patients with deteriorating clinical status who required LVAD support (LVAD Group) and in 7 stable DCM patients undergoing transplantation without need for LVAD support (Tx Group). RESULTS: Levels of MMP1, MMP8 and TIMP4 were higher in the LVAD Group compared with the Tx Group (188% +/- 141%, 646% +/- 432%, and 66% +/- 33% higher, respectively, p < 0.05) whereas MMP2, MMP9, MMP10, MMP11, and MMP14 levels were similar. MMP3, MMP7, MMP12, and MMP13 were undetectable. All TIMPs were generally higher in the LVAD group, but only TIMP4 reached significance. Collagen I and III were not altered. We tested for correlations between MMP and TIMP expression with myocardial cytokine levels. MMP8 correlated positively with interleukin-6 and interleukin-1beta, suggesting a link between cytokines and MMPs in these patients. CONCLUSIONS: The data show that high myocardial collagenase (MMP1 and MMP8) expression without compensatory changes in collagen or TIMP expression is a feature of patients requiring LVAD support. This may be linked in part to elevated cytokine expression and suggests collagenase activity may be an important therapeutic target in deteriorating heart failure.

Adolescent↗

Gene profiling changes in cytoskeletal proteins during clinical recovery after left ventricular-assist device support.

BACKGROUND: After left ventricular-assist device (LVAD) support, a proportion of patients recover sufficient ventricular function to enable explantation of the device. The exact molecular mechanisms involved in myocardial recovery remain unknown. Cytoskeletal proteins are essential for the structure and function of the cardiac myocyte and might play a major role. METHODS AND RESULTS: A total of 15 patients with nonischemic cardiomyopathy who required LVAD implantation were studied; 6 recovered sufficiently to allow explantation of the device compared with 9 who did not recover and required transplantation. LV myocardial samples were collected at implantation and explantation/transplantation. Affymetrix microarray analysis was performed on the paired samples and analyzed with reference to sarcomeric and nonsarcomeric cytoskeletal proteins. In the recovery group, of the nonsarcomeric proteins, lamin A/C increased 1.5-fold (P<0.05) and spectrin 1.6-fold (P<0.05) between the times of implantation and explantation. Integrins beta1, beta6, and alpha7 decreased 1.7-fold (P<0.05), 2.4-fold (P<0.05), and 1.5-fold (P<0.05), respectively, but integrins alpha5 and beta5 increased 2.3-fold (P<0.01) and 1.2-fold (P<0.01) at explantation. The following sarcomeric proteins changed in the recovered group only: beta-actin increased 1.4-fold (P<0.05); alpha-tropomyosin, 1.3-fold (P<0.05); alpha1-actinin, 1.8-fold (P<0.01); and alpha-filamin A, 1.6-fold (P<0.05). Both troponin T3 and alpha2-actinin decreased by 1.6-fold at the time of explantation (P<0.05). Vinculin decreased 1.7-fold (P=0.001) in the recovered group but increased by 1.7-fold (P<0.05) in the nonrecovered group. Vinculin protein levels decreased 4.1-fold in the recovered group. CONCLUSIONS: Myocardial recovery was associated with a specific pattern of changes in sarcomeric, nonsarcomeric, and membrane-associated proteins, which could have important implications in understanding the mechanisms involved.

Adrenergic beta-2 Receptor Agonists↗

Ten year survival after paediatric heart transplantation: a single centre experience.

OBJECTIVE: To report 10 years survival in children under the age of 16 years undergoing heart transplantation in a single institution. METHODS: One hundred and thirty nine/one hundred and ninety three patients (73%) survived more than 1 year after transplant. Seventy four (53%) of these survived more than 10 (10.0-20.1) years. Age at operation was 10 days-15.5 (mean 8.1) years. Patients were maintained on ciclosporin and azathiaprine alone. Routine steroids only given to 4 patients for either persistent rejection or deteriorating renal function. Rejection diagnosed on clinical or echocardiographic grounds. No routine biopsies were performed. Bi-annual coronary angiography was used to diagnose graft coronary disease. RESULTS: Graft coronary disease was found in 8 patients (11%), 2 were re-transplanted and have survived 4.3-7.2 years since. Two patients are alive without intervention 2.0-13.0 years from initial diagnosis. Two patients have undergone interventional procedures 11 and 16 years after transplantation and are alive 3 and 4 years, respectively, later. Seven patients have had post transplant lymphoproliferative disease (PTLD) and 6 have had no recurrence for 3-13 years after treatment. Impaired renal function with abnormal serum creatinine levels is increasingly common-11 patients have developed end stage renal failure, 7 requiring renal transplantation, hypertension occurred in only 3 patients other than those in renal failure. Late rejection episodes associated with probable non-adherence occurred in 7 patients. There were 10 late deaths; 2 from graft coronary disease; 1 from PTLD; 3 from renal failure; 3 from acute rejection and 1 from infection. Conditional actuarial survival from 1 year post transplant was 76 and 67% at 10 and 15 years, respectively. CONCLUSIONS: Survival for more than 10 years is increasingly realistic. In this age group adherence and deteriorating renal function are major challenges.

Azathioprine↗

Lung transplantation for non-cystic fibrosis bronchiectasis: analysis of a 13-year experience.

BACKGROUND: Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis. METHODS: Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months. RESULTS: One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%-91%), and 5-year survival was 62% (95% CI, 41-83%). One-year survival after SLTX was 57% (95% CI, 20%-94%) vs 73% (95% CI, 51-96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%-97%), and mean forced vital capacity was 68% predicted (range, 53%-94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%-61%), and mean forced vital capacity was 53% predicted (range 46-63%) (n = 4). CONCLUSIONS: Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.

Adult↗

Regurgitation of the native aortic valve caused by thrombus formation after heterotopic heart transplantation.

A 61-year-old man, who had undergone heterotopic heart transplantation, had severe regurgitation through his native aortic valve develop 16 years later, which caused severe heart failure. At operation the regurgitation was found to be due to development of an organized thrombus in the sinuses of Valsalva tethering aortic leaflets. The management of this previously undescribed complication of heterotopic heart transplantation and the implications for other groups of patients (such as those receiving treatment with a left ventricular assist device) are discussed.

Anticoagulants↗

Transplantation using hearts from primary pulmonary hypertensive donors for recipients with a high pulmonary vascular resistance.

BACKGROUND: Transplantation for patients with a high pulmonary vascular resistance (PVR) carries an increased risk of mortality and right heart failure following heart transplantation and continues to be a major problem. We evaluated the use of hearts from patients who underwent heart and lung transplantation for primary pulmonary hypertension (PPH) as part of a domino procedure because these hearts have hypertrophied right ventricles used to increased pulmonary pressures, but could have a compromised left ventricle or irreversible damage of the right ventricle. METHODS: We reviewed 12 patients with PVR >4 Wood units who underwent orthotopic heart transplantation between 1989 and 1998 using hearts from donors with PPH as part of a domino procedure. RESULTS: We studied 10 men and 2 women, mean age 42.9 years. Mean PVR was 5.3 (range, 4-9) Wood units. Mean ischemia time was 85.3 minutes, and mean donor age was 32 years. Actuarial survival was 75% at 1 year and 75% at 5 years. In the early post-operative period, 3 patients had temporary arrhythmias, 2 required permanent pacemaker implantation, 1 had atrial fibrillation, and 1 had ventricular tachycardia that required defibrillator implantation. At a mean follow-up of 7.8 years, 2 patients had developed asymptomatic transplant coronary disease (both at 8.5 years after transplantation), 1 moderate and 1 very mild; the rest had none. Mean left ventricular ejection fraction at latest follow-up was 70.1% (range, 63%-78%). Right ventricular function assessed clinically and by echocardiography was adequate in the short and long term. CONCLUSIONS: Our results suggest that heart and lung recipients with PPH can provide useful donor hearts to patients with increased PVR and that these hearts function well in the intermediate and long term.

Adult↗

Increased toll-like receptor 4 in the myocardium of patients requiring left ventricular assist devices.

BACKGROUND: Cytokine activation in the myocardium of deteriorating patients with heart failure who undergo left ventricular assist-device (LVAD) implantation has been documented, but the underlying mechanisms remain poorly understood. We hypothesized the innate immune system is activated with expression of Toll-like receptor 4 (TLR4), leading to cytokine activation in these patients. METHODS: We used quantitative real-time reverse-transcriptase polymerase chain reaction to measure TLR4, interleukin-1 (IL-1) receptor, IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) mRNA expression in myocardial samples from 36 patients. We compared 18 patients who underwent LVAD implantation with 18 patients with less severe heart failure who underwent elective heart transplantation. RESULTS: Toll-like receptor 4 expression was 1.69-fold greater (p < 0.05) and IL-1 receptor expression was 3.64-fold greater (p < 0.0001) in the deteriorating patients who required LVADs. Myocardial TNF-alpha (1.71-fold, p < 0.05), IL-6 (2.57-fold, p < 0.005), and IL-1 beta (9.78-fold, p < 0.001) also were increased in the LVAD candidates. Toll-like receptor 4 expression correlated strongly with IL-1 receptor expression (r= 0.75, p < 0.0001) and with IL-1 beta expression in individual patients (r = 0.7, p < 0.0001). Interleukin-1 receptor expression also correlated with IL-1 beta expression (r = 0.78, p < 0.0001) within patients. We found no correlation between TLR4 and either TNF-alpha or IL-6 expression. CONCLUSIONS: Patients who required LVAD support showed evidence of innate immune system activation, indicated by an increase in the key effector molecule TLR4 associated with a specific pattern of cytokine expression in the myocardium.

Adult↗

The role of bridge to transplantation: should LVAD patients be transplanted?

PURPOSE OF REVIEW: The decrease in useable donor organs means an increasing number of patients are requiring support with a left ventricular assist device (LVAD) for survival when their clinical status deteriorates before transplantation. We address whether these patients should be transplanted, if so, with what priority, and when and if they are not transplanted, what are the alternatives? RECENT FINDINGS: The perioperative mortality and morbidity of LVAD insertion remains high. Infection and device failure still limit the safety of long periods of bridging and might necessitate earlier transplantation. Early results suggest that the smaller impeller pumps may be associated with a lower incidence of device failure and infection, but with more thromboembolic and hemorrhagic complications. Transplantation of LVAD patients results in survival rates as good as those with conventional transplantation, and the survival benefit is better than for non-LVAD-supported patients. A small number of LVAD patients have shown a significant improvement in myocardial function, sufficient enough to allow explantation of the device. The proportion of these patients has previously been reported to be as low as 5%, but a strategy to maximize recovery has allowed pump removal in approximately two thirds of dilated cardiomyopathy patients. In a recent destination therapy trial, survival in LVAD patients was superior to those on medical therapy, but the frequency of infection, bleeding, and malfunction of the device was higher. SUMMARY: LVAD technology is continuing to evolve quickly, while transplantation is here to stay. The interaction between these two powerful modalities requires continued thoughtful evaluation for maximal benefit to patients.

Contraindications↗

Management of an ABO-incompatible lung transplant.

A 24-year-old woman with cystic fibrosis underwent bilateral sequential lung transplantation and unintentionally received an ABO incompatible graft (blood type A(1) graft into a type O recipient). The recipient had a high titer of IgG anti-A antibody (256 by the indirect antiglobulin test). Emergency treatment included antibody removal by plasmapheresis and additional immunosuppression with mycophenolate, rabbit antithymocyte globulin and polyspecific intravenous immunoglobulin. Subsequently, immunoadsorption and the anti-CD20 antibody rituximab were used to remove anti-A antibody and inhibit its resynthesis. Early graft function was good; one episode of rejection at Day 46 responded promptly to treatment with methylprednisolone. Subsequently, graft function continued to improve and anti-A antibody titers remained low. No infectious or other complications were encountered. The treatment regimen that we adopted may prove useful in other cases of unplanned ABO-incompatible organ transplants. The successful outcome suggests that planned ABO-incompatible lung transplants may be possible.

ABO Blood-Group System↗

Mid-term pattern of survival, hemodynamic performance and rate of complications after medtronic freestyle versus homograft full aortic root replacement: results from a prospective randomized trial.

BACKGROUND AND AIM OF THE STUDY: The full homograft root replacement has been regarded as the 'gold standard' for aortic valve replacement (AVR). Xenograft full root AVR may offer similar theoretical advantages, but no prospective randomized trials to compare the two valve substitutes have been reported to date. METHODS: A total of 147 patients (mean age 66.2 years; range: 40-82 years) was randomized to undergo either Medtronic Freestyle (group F; n = 80) or homograft (group H; n = 67) root AVR. Coronary artery bypass grafting was associated with root AVR in 55 patients (37.4%). Follow up included routine clinical and echocardiographic assessments. RESULTS: Overall, there were seven early deaths (4.8%). The early mortality rate for isolated root AVR was 2.1% in group F (1/47) and 2.2% in group H (1/45) (p = NS). There were four late deaths in group F, and two in group H. Actuarial survival was 83+/-5% and 84+/-4% (p = NS) at five years, in groups F and H, respectively. No patient required reoperation on the aortic valve. Overall, there were eight thromboembolic events and six anticoagulant-related bleeding events; these were equally divided between the two groups. After a median follow up of 45 months, most patients in both groups were in NYHA class I, and the mean trans-aortic gradient was 6+/-1 mmHg in group F and 5+/-2 mmHg in group H (p = NS). Mild aortic regurgitation was recorded in 1/26 patients (4%) of group F, and in 1/16 (6%) of group H. CONCLUSION: The Medtronic Freestyle porcine xenograft appears to be a good alternative to homografts for full aortic root replacement, at least in the mid term.

Adult↗