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Biomedical subjects

A Khaghani

Publications and source records attributed to A Khaghani.

At least 19 recordsLinked to original sources

Clinical performance with the Levitronix Centrimag short-term ventricular assist device.

BACKGROUND: The Levitronix ventricular assist device (VAD) is a centrifugal pump designed for extracorporeal support and that operates without mechanical bearings or seals. The rotor is magnetically levitated so that rotation is achieved without friction or wear, which seems to minimize blood trauma and mechanical failure. The aim of this study is to report our early results with the Levitronix Centrimag device. METHODS: Between June 2003 and April 2005, 18 patients (pts) were supported using the Levitronix at our institution. Fourteen were male. Mean age was 40.3 +/- 18.3 (range 8 to 64) years. Indications for support at implantation were: post-cardiotomy cardiogenic shock in 12 cases (Group A), and bridge to decision regarding long-term ventricular support in 6 cases (Group B). RESULTS: Mean support time was 14.2 +/- 15.2 days for all patients (range 1 to 64 days). Operative (30-day) mortality was 50% (9 pts). Six pts were in Group A and 3 pts were in Group B. Overall, 6 pts (33%) were discharged home and are presently alive and well (mean follow-up 13 months, range 5 to 17 months). Bleeding requiring re-operation occurred in 8 cases (44%), cerebral thromboembolism in 1 and pulmonary embolism in 1. There were no device failures. CONCLUSIONS: The Levitronix functioned well and proved to be useful in patients with extremely poor prognosis previously considered non-suitable for a long-term assist device. The device was technically easy to implant and manage. There was no device dysfunction and complications were acceptable or consistent with other devices. Survival to explant or a definitive procedure (VAD or transplantation) was encouraging.

Adolescent↗

Clinical recovery from end-stage heart failure using left-ventricular assist device and pharmacological therapy correlates with increased sarcoplasmic reticulum calcium content but not with regression of cellular hypertrophy.

BACKGROUND: Left ventricular assist device (LVAD) treatment is known to lead to structural and functional cellular modifications in the heart. The relevance of these changes for clinical recovery is unknown. METHODS AND RESULTS: We compared properties of cardiomyocytes obtained from tissue taken at explantation of the LVAD in patients with clinical recovery with those obtained from hearts of patients who did not show clinical recovery, thus requiring transplantation. Compared with myocytes taken at implantation, both the recovery and nonrecovery groups showed approximately 50% reduction in cell capacitance, an index of cell size. However, action potential duration shortened, L-type Ca2+ current fast inactivation was more rapid, and sarcoplasmic reticulum Ca2+ content was increased in the recovery compared with the nonrecovery group. CONCLUSIONS: These results show that specific changes in excitation-contraction coupling, and not regression of cellular hypertrophy, are specifically associated with clinical recovery after LVAD and further identify sarcoplasmic reticulum Ca2+ handling as a key functional determinant in patients with heart failure.

Caffeine↗

Incidence and clinical management of life-threatening left ventricular assist device failure.

BACKGROUND: Mechanical device failure can be life-threatening and is becoming increasingly important as left ventricular assist devices (LVADs) are being used for longer periods as a bridge to transplantation (period lengthening due to donor shortage) or recovery, or as destination therapy. However, its incidence and clinical management have not been widely studied. METHODS: We investigated the incidence and management of major device failure for a total of 102 Thoratec/TCI HeartMate and Thoratec PVAD devices implanted at our institution since 1995. RESULTS: The cumulative probability of device failure was 6%, 12%, 27% and 64% at 6 months, 1 year, 18 months and 2 years, respectively. Major failure occurred in 8 (7.8%) patients. Four patients presented as emergency cases with vented electric (VE) failure, and 3, with failure due to a seized motor, were supported on the pneumatic driver to explantation, transplantation or device change. Another patient had a ruptured pump diaphragm and was maintained for 12 hours, but died of a Type B aortic dissection. Four patients underwent elective device change, including 2 of a VE pump, 1 with inlet valve regurgitation and fractured power cable at 414 days, and 1 with inlet valve regurgitation at 656 days, all of whom underwent transplantation or explantation. One patient with VE failure was maintained on the pneumatic driver, then underwent Thoratec paracorporeal ventricular assist device (PVAD) implantation and was transplanted. One Thoratec PVAD patient developed LVAD thrombus, underwent pump replacement, and was transplanted. A further patient on the implantable pneumatic (IP) HeartMate developed a pneumoperitoneum due to a leak at the junction of the pneumatic driveline, which was repaired by inserting a new driveline, and underwent heart/kidney transplantation. CONCLUSIONS: Life-threatening mechanical device failure is not uncommon and increases with time, but can be managed successfully in most patients. Improvements in design and manufacture should further enhance outcome with LVADs.

Adult↗

Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a leading cause of morbidity and mortality after lung and heart-lung transplantation. Present treatment is directed at the augmentation of pharmacologic immunosuppression. METHODS: This study examines the effect of substituting cyclosporine with tacrolimus on the forced expiratory volume in 1 second (FEV(1)) and on the forced expiratory flow between 25% and 75% of vital capacity (FEF(25%-75%)) in 32 patients who developed BOS. The proportional rates of decline of FEV(1) and FEF(25%-75%) before and after treatment with tacrolimus were calculated. The actuarial survival of responders and non-responders to tacrolimus was compared. Pre-operative and post-operative factors were investigated to determine any difference between the 2 groups. RESULTS: There were significant reductions in the rates of decline of FEV(1) and FEF(25%-75%) when the rates in the 3 months before conversion to tacrolimus were compared with subsequent rates at 0 to 3 months, 3 to 6 months, 6 to 9 months and 9 to 12 months after conversion. The rates of decline of FEV(1) and FEF(25%-75%) in the 3 months before conversion were 0.11 liters/month and 0.13 liters/s per month, respectively. This compares with the rates of decline for FEV(1) and FEF(25%-75%) for the 3 months after conversion to tacrolimus of 0.04 liters/month (p = 0.023) and 0.04 liters/s per month (p = 0.022), respectively. The actuarial survival at 1 year from the time of conversion to tacrolimus for the responder sub-group and the non-responder sub-group were 89.2% and 75%, respectively, and at 4 years after conversion were 61.3% and 56.3%, respectively (p = 0.92). CONCLUSIONS: Tacrolimus rescue therapy is effective at stabilizing lung function in patients with BOS, and this effect is apparent up to 12 months after conversion from cyclosporine.

Bronchiolitis Obliterans↗

Determinants of outcome after heterotopic heart transplantation.

BACKGROUND: Donor availability is currently the major factor limiting the use of heart transplantation as a treatment for severe heart failure. Heterotopic heart transplantation may address this issue by allowing the use of smaller donor organs, which otherwise may not be used. METHODS: We analyzed the outcome of 42 consecutive, adult heterotopic transplantations performed between 1993 and 1999 at our center and compared them with the 303 consecutive orthotopic transplants performed in adult patients during the same period. METHODS: Univariate analysis showed a relative risk for death of 1.8 at 1 year after transplantation for the heterotopic group compared with the orthotopic transplantation group (p = 0.04). Multiple regression analysis using a proportional hazards model showed that donor-recipient size-mismatch, i.e., donor body surface area < or =75% of recipient body surface area (p = 0.0001), donor age (p = 0.0001), and use of a female donor (p = 0.04) were significant risk factors but heterotopic transplantation per se was not. A Kaplan-Meier survival analysis of heterotopic vs orthotopic transplantation showed that 30-day survival was 76% vs 87%. By 1 year, this was 59% vs 74%. At 3 years, the comparison was 56% vs 69%. Repeating this analysis after sub-dividing the heterotopic group into those size-matched vs size-mismatched, the 1-year survival was 81% vs 45%, respectively (p = 0.02). CONCLUSIONS: Heterotopic transplantation using a size-matched graft resulted in similar survival to that seen after orthotopic transplantation during the same period. Heterotopic transplantation with an undersized graft resulted in significantly decreased survival.

Cause of Death↗

Primary lung carcinoma after heart or lung transplantation: management and outcome.

OBJECTIVE: We sought to examine our management and outcome of lung carcinoma occurring after thoracic organ transplantation. METHODS: We performed a retrospective review of cases of primary lung carcinoma diagnosed between 1990 and 2000 in patients who have previously undergone thoracic transplantation at our institution. RESULTS: Seventeen patients were identified (1 lung and 16 heart transplants). Median time from transplantation to diagnosis of lung carcinoma was 89 months (range, 46-138 months). Predominant presentation was as an incidental finding at chest radiography (13/17). All patients had smoked cigarettes before transplantation, with 5 continuing to smoke after transplantation. Histologic types were squamous (n = 11), adenocarcinoma (n = 3), small cell (n = 2), and undifferentiated (n = 1). Revised International Union Against Cancer (UICC) clinical stage at the time of diagnosis was stage I or II in 11 of 17 patients. Of these, 9 underwent surgical resection; 2 patients unfit for surgical intervention had radiotherapy. Surgical procedures were lobectomy (n = 5), wedge excision (n = 3), and no resection (n = 1). Median survival after diagnosis was 12 months for all patients and 24 months if the tumor was resected. Six patients who had surgical resection subsequently died (survival of 2, 9, 21, 21, 36, and 67 months); 2 remain alive after 12 and 54 months, respectively. CONCLUSIONS: When possible, surgical intervention should be undertaken for early stage lung cancer occurring after thoracic transplantation because medium-term survival is achievable. Sublobar excisions and definitive radiotherapy should be considered if comorbidity prevents optimal surgical treatment.

Female↗

Quantitative myocardial cytokine expression and activation of the apoptotic pathway in patients who require left ventricular assist devices.

BACKGROUND: Molecular mechanisms underlying the deterioration of patients undergoing LV assist device (LVAD) implantation remain poorly understood. We studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and IL-6 and the terminal stage of the apoptotic pathway in patients with decompensating heart failure who required LVAD support and compared them with patients with less severe heart failure undergoing elective heart transplantation. METHODS AND RESULTS: Myocardial and serum samples from 23 patients undergoing LVAD implantation were compared with those from 36 patients undergoing elective heart transplantation. Myocardial TNF-alpha mRNA (1.71-fold; P<0.05) and protein (3.43+/-0.19 versus 2.95+/-0.10 pg/mg protein; P<0.05) were elevated in the LVAD patients. Immunocytochemistry demonstrated TNF expression in the myocytes. Serum TNF-alpha was also elevated (12.5+/-1.9 versus 4.0+/-0.4 pg/mL; P<0.0001) in the LVAD patients. IL-6 mRNA (2.57-fold higher; P<0.005) and protein (27.83+/-9.35 versus 4.26+/-1.24 pg/mg protein; P<0.001) were higher in the LVAD candidates, as was serum IL-6 (79.3+/-23.6 versus 7.1+/-1.6 pg/mL; P<0.0001). Interleukin-1beta mRNA expression was 9.78-fold higher in the LVAD patients (P<0.001). iNOS mRNA expression was similar to that in advanced heart failure patients and was not further elevated in the LVAD patients. Levels of procaspase-9 (8.02+/-0.91 versus 6.16+/-0.43 oligodeoxynucleotide [OD] units; P<0.01), cleaved caspase-9 (10.02+/-1.0 versus 7.34+/-0.40 OD units; P<0.05), intact and spliced DFF-45 (4.58+/-0.75 versus 2.84+/-0.23 OD units; P<0.05) were raised in LVAD patients, but caspase-3 and human nuclease CPAN were not. CONCLUSIONS: Elevated TNF-alpha, IL-1beta, and IL-6 and alterations in the apoptotic pathway were found in the myocardium and elevated TNF-alpha and IL-6 in serum of deteriorating patients who required LVAD support. These occurrences may have therapeutic implications and influence the timing of LVAD insertion.

Adolescent↗

Electron beam tomography for cusp calcification in homograft versus Freestyle xenografts.

BACKGROUND: We have previously shown, by means of electron beam tomography, the pattern of calcification of the aortic root wall of homografts and porcine xenografts after aortic root replacement. However, application of similar methods for cusp calcification raises specific problems that have not been addressed before. METHODS: A new method for localizing and quantifying calcification of the aortic valve cusps has been evolved. Intravenous contrast-enhanced electron beam tomography was introduced to visualize the aortic cusps. This technique was applied to quantify cusp calcification in 37 patients after aortic root replacement with a homograft (group H) or a Medtronic Freestyle valve (group F) at set intervals between 6 months and 2 years. A calcification score in Hounsfield units (HU) and a calcified volume score in cubic millimeters were calculated. RESULTS: The aortic leaflets were clearly visualized in all patients. The mean calcium score in the cusps was 28.8+/-64.4 HU in group F and 62.4+/-66.9 HU in group H (p = not significant). The mean calcified volume score was 327.0+/-425.9 mm3 in group F and 642.0+/-443.0 mm3 in group H (p = not significant). CONCLUSIONS: Contrast enhancement electron beam tomography is a useful tool for quantification of calcium in the aortic valve leaflets. Our preliminary results show a tendency toward more calcification in the homografts. This needs to be studied further in a bigger cohort of patients followed up for longer periods.

Adult↗

Long term results of heart transplantation in patients with amyloid heart disease.

OBJECTIVE: To determine the outcome of heart transplantation for end stage amyloid heart disease in patients treated at a single centre. DESIGN: Records of all patients with amyloid heart disease who underwent heart transplantation were examined to determine survival, graft involvement by amyloid, the course of systemic amyloid disease, and the cause of death. PATIENTS: 10 patients, mean (SD) age 54 (8) years, received transplants in the 13 year period 1984 to 1997. RESULTS: Two patients, both with AL amyloid (primary systemic amyloidosis), died perioperatively. Mean follow up in the remaining eight patients was 49.9 (39.5) months (range 3-116 months). Amyloid deposits in the grafts became evident histologically in five patients with AL amyloid at 5, 11, 12, 28, and 30 months after transplantation, and in one patient with familial amyloid at 60 months. Echocardiography showed no evidence of left ventricular systolic impairment at the time of recurrence. Seven patients died, at 3, 11, 26, 32, 49, 85, and 116 months after transplantation; four of these deaths were related to amyloidosis. Actuarial survival at one and two years was 60% and at five years, 30%. CONCLUSIONS: Heart transplantation for amyloid heart disease remains controversial because of the scarcity of hearts for transplantation, the systemic nature of amyloidosis, and the potential for amyloid deposition in the graft. Postoperative mortality was high (20%), reflecting extracardiac amyloid. Heart transplantation for end stage cardiac amyloidosis is feasible but, without treatment of the underlying process, it is a palliative procedure.

Adult↗

Activation of apoptotic and inflammatory pathways in dysfunctional donor hearts.

BACKGROUND: Myocardial dysfunction is common after brain death, but the mechanisms remain unclear. Apoptosis is tightly regulated by enzymes termed the caspases. We have investigated the caspases involved in the terminal part of the apoptotic pathway in dysfunctional (nontransplanted) donor hearts and their relation to inflammatory markers and compared them to hearts with good ventricular function (transplanted donors). METHODS: Thirty-one donor hearts assessed for transplantation were examined. Western blotting was used to measure pro-caspase-9, caspase-3, DFF45, the activated nuclease CPAN and poly (ADP-ribose) polymerase, a DNA repair enzyme inactivated by caspase-3. Caspase-3 activity was also measured. Histologic and immunocytochemical analysis for HLA Class II and Real Time polymerase chain reaction for tumor necrosis factor-alpha and interleukin 6 were performed to detect inflammatory activation. RESULTS: Cleaved caspase-9 was higher (5.53+/-0.6 vs. 3.64+/-0.4 O.D. units, P<0.01) in nontransplanted compared with transplanted donors and there was a trend for higher pro-caspase-9 (5.20+/-1.0 vs. 4.22+/-0.4 O.D. units, P=NS). Levels of pro-caspase-3 were higher in nontransplanted (9.66+/-0.5 vs. 5.15+/-0.5 O.D. units, P<0.00001) donors and cleavage products of caspase-3 were elevated in 14 of 14 nontransplanted and 2 of 17 transplanted donors. Intact DFF-45 (8.94+/-0.36 vs. 6.14+/-0.30 O.D. units, P<0.000005), its spliced product (2.38+/-0.35 vs. 0.4+/-0.21 O.D. units, P=0.0001) and the nuclease caspase-activated nuclease (2.01+/-0.3 vs. 0.66+/-0.16 OD units, P=0.001) were higher in nontransplanted donors. The caspase-3 substrate poly (ADP-ribose) polymerase was higher in nontransplanted (1.16+/-0.13 vs. 0.61+/-0.22 O.D. units, P=0.57) donors. CONCLUSIONS: The caspases are elevated in dysfunctional donor hearts compared with hearts with good ventricular function with a possible link to inflammatory activation supporting the concept that brain death causes inflammatory activation which can lead to apoptosis with a possible important effect on function.

Adult↗

Tumor necrosis factor-alpha is expressed in donor heart and predicts right ventricular failure after human heart transplantation.

BACKGROUND-Myocardial failure is an important problem after heart transplantation. Right ventricular (RV) failure is most common, although its mechanisms remain poorly understood. Inflammatory cytokines play an important role in heart failure. We studied the expression of tumor necrosis factor (TNF)-alpha and other cytokines in donor myocardium and their relationship to the subsequent development of RV failure early after transplantation. METHODS AND RESULTS-Clinical details were obtained, and ventricular function was assessed by transesophageal echocardiography in 26 donors before heart retrieval. A donor RV biopsy was obtained immediately before transplantation, and each recipient was followed for the development of RV failure. Reverse transcriptase-polymerase chain reaction was performed to detect TNF-alpha, interleukin-2, interferon-gamma, and inducible nitric oxide synthase expression. Eight of 26 recipients (30.8%) developed RV failure. Seven of these 8 (87.5%) expressed TNF-alpha, but only 4 of the 18 (22.2%) who did not develop RV failure expressed TNF-alpha (P<0.005). As a predictor of RV failure, TNF-alpha mRNA had a sensitivity of 87.5%, a specificity of 83.3%, a positive predictive value of 70%, and a negative predictive value of 93.7%. Western blotting demonstrated more TNF-alpha protein in the myocardium of donor hearts that developed RV failure (658+/-60 versus 470+/-57 optical density units, P<0.05). Immunocytochemistry localized TNF-alpha expression to cardiac myocytes. Reverse transcriptase-polymerase chain reaction detected interferon-gamma in 2 (7.7%), interleukin-2 in 1 (3.8%), and inducible nitric oxide synthase mRNA in 1 (3.8%) of the 26 donor hearts, none of which developed RV failure. CONCLUSIONS-TNF-alpha expression in donor heart cardiac myocytes seems to predict the development of RV failure in patients early after heart transplantation.

Adolescent↗

Long-term results after aortic valve replacement in patients with congestive heart failure. Homografts vs prosthetic valves.

OBJECTIVES: The aim of this study was to assess the influence of valve substitute (homograft vs prosthetic valve) on the long-term survival and late valve-related complication rates following aortic valve replacement in patients with aortic valve disease and congestive heart failure. BACKGROUND: The effect of choice of valve substitute on outcome after aortic valve replacement in patients with pre-operative heart failure is unknown. The superior haemodynamic profile of homografts may be of particular benefit. METHODS: We retrospectively analysed pre-operative, operative and follow-up data on 518 adults in functional classes III and IV, who, over the 25 years 1969-1993, had their initial aortic valve replacement at Harefield hospital. Follow-up conducted during 1996 to April 1997 and totalling 4439 patient-years was 96.1% complete. Using multivariate analysis, independent risk factors for different complications and mortality were defined. RESULTS: Overall 5-, 10- and 20-year survival was 80+/-2%, 62+/-2% and 30+/-3%, respectively, with no significant difference between valve types. However, homografts (n=381) independently reduced the rate of serious complications and cardiac death, whereas mechanical valves were an independent adverse risk factor for late mortality. The rates of anticoagulant-related bleeding and thromboembolism were increased by mechanical valves, whereas primary tissue failure was the main complication of homografts. CONCLUSIONS: Long-term outcome of homograft aortic valve replacement in patients with congestive heart failure is acceptable, with a reduced rate of serious complications and cardiac death. Further improvements would be expected if the rate of primary tissue failure could be reduced.

Adolescent↗

A quantitative study of calcium deposition in the aortic wall following Medtronic Freestyle compared with homograft aortic root replacement. A prospective randomized trial.

BACKGROUND AND AIM OF THE STUDY: Unstented aortic valve substitutes offer many of the theoretical advantages of homografts such as superior hemodynamic performance and enhanced durability, particularly when inserted as a root. Many of these depend on the maintained flexibility of the valve components. Calcification of the aortic wall may adversely affect these phenomena. Electron beam computed tomography has been used to evaluate aortic wall calcification in patients undergoing aortic root replacement in a prospective randomized trial designed to compare the Medtronic Freestyle valve with the homograft valve replacement. METHODS: Patients were followed with electron beam computed tomography scans of the aortic root at six-monthly intervals after surgery. A calcification score (Hounsfield units) and a calcified volume score (mm3) were obtained from each scan using a new modified technique. Results were related to hemodynamic data from echocardiography. The prevalence of calcification was also related to the homograft donor age. RESULTS: Seventy-six patients (age range: 40-79 years) were randomized to root replacement with either homograft (n = 31) or Freestyle (n = 45) valves. Fifty-three scans of the aortic root were performed postoperatively in 37 patients. No statistical difference between the two groups was found at six and 12 months after surgery. However, after 18 months the calcified volume score was 5903.8+/-2356.8 mm3 in the homograft versus 2725.6+/-1500.5 mm3 in the Freestyle group (p = 0.017). There was a correlation between calcification score, calcified volume score and left ventricular mass (r = 0.323, p = 0.093 and r = 0.350, p = 0.068, respectively) on the one hand, and calcification score, calcified volume score and valve size on the other hand (r = 0.178, p = 0.466 and r = 0.068, p = 0.780, respectively). CONCLUSIONS: Electron beam computed tomography provides a powerful tool for the detection of calcium in the aortic wall of valve grafts. There is a low rate of calcification during the first 18 months in the Medtronic Freestyle valve, and this appears to be lower than that observed in homografts. Longer-term follow up of the aortic root in these patients is required. This is an ongoing study.

Adult↗

Heterotopic heart transplantation through a right thoracotomy.

Heterotopic heart transplantation was performed via a right thoracotomy in a patient with elevated pulmonary vascular resistance and previous coronary artery bypass grafting using both internal mammary arteries. The right thoracotomy approach is the safest way to approach the native heart while preserving the patent grafts.

Coronary Artery Bypass↗

Primary aortic valve replacement with allografts over twenty-five years: valve-related and procedure-related determinants of outcome.

OBJECTIVES: Allografts offer many advantages over prosthetic valves, but allograft durability varies considerably. METHODS: From 1969 through 1993, 618 patients aged 15 to 84 years underwent their first aortic valve replacement with an aortic allograft. Concomitant surgery included aortic root tailoring (n = 58), replacement or tailoring of the ascending aorta (n = 56), and coronary artery bypass grafting (n = 87). Allograft implantation was done by means of a "freehand" subcoronary technique (n = 551) or total root replacement (n = 67). The allografts were antibiotic sterilized (n = 479), cryopreserved (n = 12), or viable (unprocessed, harvested from brain-dead multiorgan donors or heart transplant recipients, n = 127). Maximum follow-up was 27.1 years. RESULTS: Thirty-day mortality was 5.0%, and crude survival was 67% and 35% at 10 and 20 years. Ten- and 20-year rates of freedom from complications were as follows: endocarditis, 93% and 89%; primary tissue failure, 62% and 18%; and redo aortic valve replacement, 81% and 35%. Multivariable Cox analyses identified several valve- and procedure-related determinants: rising allograft donor age and antibiotic-sterilized allograft for mortality; donor more than 10 years older than patient for endocarditis; rising donor age minus patient age, rising implantation time (from harvest to aortic valve replacement), and donor age more than 65 years for tissue failure; and rising donor age minus patient age, young patient age, rising implantation time, and subcoronary implantation preceded by aortic root tailoring for redo aortic valve replacement. Estimated 10- and 20-year rates of freedom from tissue failure for a 70-year-old patient with a viable valve from a 30-year-old donor and no other risk factors were 91% and 64%; the figures were 71% and 20% if the donor age was 65 years. The rates of freedom from tissue failure for a 30-year-old patient with a 30-year-old donor were 82% and 39%; the figures were 49% and 3% with a 65-year-old donor. Beneficial influences of a viable valve were largely covered by short harvest time (no delay for allografts from brain dead organ donors or heart transplant recipients) and short implantation time. CONCLUSIONS: Primary allograft aortic valve replacement can give acceptable results for up to 25 years. The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation.

Aged↗

Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy.

BACKGROUND: Impaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end-stage heart failure. MATERIALS AND METHODS: The left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non-diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides. RESULTS: Total creatine levels (phosphocreatine + creatine) were significantly decreased (P < 0.05) in both groups of diseased hearts (3.87 +/- 0.57 in DCM, 5.09 +/- 1.23 in HCM compared with control 10. 7 +/- 3.5 micromol g-1 wet weight). There was a trend for higher guanine nucleotide content in failing hearts, but no significant differences were observed in total adenine nucleotides and total NAD content. CS was markedly reduced (P < 0.05) in both groups of diseased hearts: in the DCM to 13.8 +/- 1.3 micromol min-1 g-1 wet weight, and in HCM to 11.9 +/- 2.4 compared with the control 29.2 +/- 2.2. Glycolytic enzymes were decreased compared with the control, and this decrease was greater in DCM than in HCM. Echocardiographic indices of contractility were considerably better in hypertrophic cardiomyopathy. CONCLUSION: Despite the different mechanisms of cardiac failure and the differences in contractility of the heart we have observed, metabolic changes are very similar in hypertrophic and dilated cardiomyopathy. Depletion of the creatine pool suggests an alteration in the intracellular energy reserves and transfer, whereas the decrease in citrate synthase activity suggests reduced oxidative capacity in both dilated and hypertrophic cardiomyopathy.

Adenine Nucleotides↗