Orthotopic Cardiac Transplant Recipients Research Articles

The Role of Biventricular Implantable Defibrillator in Heart Transplant Recipients

Background Sudden cardiac death and heart failure are common complications following orthotopic heart transplantation. The role of biventricular implantable cardioverter-defibrillators (BiV ICDs) in this population is unknown with minimal available data. Objective Highlight the safety and utility of BiV ICD placement among orthotopic heart transplant recipients. Case A 69-year-old male with a medical history notable for type II diabetes, and prior non-ischemic cardiomyopathy requiring BiV ICD and after that, he needed left ventricular assist device (LVAD) placement and ultimately heart transplantation and explantation of his prior BiV ICD. He developed ischemic cardiomyopathy. Cardiac MRI revealed left ventricular dilation, thinning and dyskinesis in the distribution of the left anterior descending (LAD coronary artery and a reduced ejection fraction of 25%. Cardiac catheterization demonstrated 100% occlusion of the middle left anterior descending coronary artery with distal collateralization. ECG demonstrated RBBB with QRS duration of 157 milliseconds. We proceeded with new BiV ICD on the right side due to vein occlusion on the left side. On 24-month follow up, the patient is doing well with no heart failure admission and no ICD therapy. Conclusions BiV ICD placement might be a safe and viable option among orthotopic cardiac transplant recipients to manage heart failure and prevent sudden cardiac death.

Temporal trends of dialysis requiring acute kidney injury after orthotopic cardiac and liver transplant hospitalizations

BackgroundThe epidemiology and outcomes of acute kidney injury (AKI) in prevalent non-renal solid organ transplant recipients is unknown.MethodsWe assessed the epidemiology of trends in acute kidney injury (AKI) in orthotopic cardiac and liver transplant recipients in the United States. We used the Nationwide Inpatient Sample to evaluate the yearly incidence trends (2002 to 2013) of the primary outcome, defined as AKI requiring dialysis (AKI-D) in hospitalizations after cardiac and liver transplantation. We also evaluated the trend and impact of AKI-D on hospital mortality and adverse discharge using adjusted odds ratios (aOR).ResultsThe proportion of hospitalizations with AKI (9.7 to 32.7% in cardiac and 8.5 to 28.1% in liver transplant hospitalizations; ptrend<0.01) and AKI-D (1.63 to 2.33% in cardiac and 1.32 to 2.65% in liver transplant hospitalizations; ptrend<0.01) increased from 2002-2013. This increase in AKI-D was explained by changes in race and increase in age and comorbidity burden of transplant hospitalizations. AKI-D was associated with increased odds of in hospital mortality (aOR 2.85; 95% CI 2.11-3.80 in cardiac and aOR 2.00; 95% CI 1.55-2.59 in liver transplant hospitalizations) and adverse discharge [discharge other than home] (aOR 1.97; 95% CI 1.53-2.55 in cardiac and 1.91; 95% CI 1.57-2.30 in liver transplant hospitalizations).ConclusionsThis study highlights the growing burden of AKI-D in non-renal solid organ transplant recipients and its devastating impact, and emphasizes the need to develop strategies to reduce the risk of AKI to improve health outcomes.

Safety of adenosine pharmacologic stress myocardial perfusion imaging in orthotopic cardiac transplant recipients: a single center experience of 102 transplant patients

Denervation super-sensitivity to adenosine is well described in cardiac transplant (CT) patients particularly early after transplant. The safety and hemodynamic effects of adenosine SPECT (A-SPECT) has not been described in a large series of CT patients. Single center retrospective study of 102 CT patients undergoing A-SPECT were compared to an age-gender matched patients in a 2:1 fashion who underwent A-SPECT in the same time period. Multivariate logistic regression model were used to identify independent predictors of advanced AV block. The average time from CT to A-SPECT was 8.5±4.5years. Average age was 57years with 80% males. In comparison to the control group, adenosine infusion was associated with a higher incidence of sinus pause (4.9% vs. 0%), 2nd (11.8% vs. 4.9%) and 3rd degree AVB (2.9% vs. 0%) in CT patients (all P<0.05). Prior use of aspirin and baseline 1st degree AVB were significant independent predictors of adenosine induced AVB. Baseline right or left bundle branch block, beta-blockers, calcium blockers or digoxin were not associated with occurrence of AVB. Only 1.9% of A-SPECT studies were terminated due to bradyarrythmia with 1 patient requiring aminophylline. There were no significant immediate or long term adverse events in these patients. Adenosine pharmacologic stress is associated with a higher incidence of AVB and sinus pause in CT patients reflecting persistence of super sensitivity late after CT. Nevertheless these bradyarrythmias are transient without any sequelae suggesting that A-SPECT can be performed safely in CT patients.

Circulating C-type natriuretic peptide is increased in orthotopic cardiac transplant recipients and associated with cardiac allograft vasculopathy

Circulating C-type natriuretic peptide is increased in orthotopic cardiac transplant recipients and associated with cardiac allograft vasculopathy

Circulating C-type natriuretic peptide is increased in orthotopic cardiac transplant recipients and associated with cardiac allograft vasculopathy

C-type natriuretic peptide (CNP) is a potent, endothelial-derived relaxant and growth-inhibitory factor. Accelerated vascular disease is an important cause of morbidity in cardiac transplant recipients, and endothelial dysfunction is now well recognized in patients with cardiovascular disease. CNP has not previously been investigated following cardiac transplantation. We therefore studied plasma levels of immunoreactive CNP in patients early and late after heart transplantation, compared with levels in healthy subjects. We measured CNP in extracted human plasma using an antibody against human CNP-(1-22). CNP levels were significantly elevated in 13 cardiac recipients 2 weeks post-transplant [2.64+/-0.26 pmol/l (mean+/-S.E.M.)] compared with those in the normal healthy subjects (0.62+/-0.04 pmol/l; n=20, P<0.001). Plasma levels of CNP were also significantly elevated in a second group of established cardiac transplant recipients (1.15+/-0.07 pmol/l; n=46) studied 1-13 years post-transplant when compared with the healthy subjects (P<0.001). In the group studied later after transplantation, CNP levels were significantly associated with systolic blood pressure (P<0.05) and were higher in patients with angiographic post-transplant coronary artery disease (P=0.032). In conclusion, these findings clearly demonstrate that CNP is elevated soon after cardiac transplantation and remains raised in patients even several years post-transplant. CNP may be important as a circulating or local hormone involved in vascular contractile function and in the pathophysiology of cardiac allograft vasculopathy following heart transplantation.

Investigation of the plasma concentrations and circulating forms of BNP and ANP in orthotopic cardiac transplant recipients.

Investigation of the plasma concentrations and circulating forms of BNP and ANP in orthotopic cardiac transplant recipients

Exercise response of the recipient atrial remnant after orthotopic cardiac transplantation: implications for recipient atrial triggered pacing.

The assumption that the recipient atrial remnant in the cardiac transplant recipient is normal has led to the suggestion that it is an appropriate trigger for permanent pacing in transplant recipients who need pacing or to restore chronotropic competence and/or mechanical synchrony of the composite atrium. We examined the chronotropic response to exercise in 12 orthotopic cardiac transplant recipients (mean age 49 years) at a mean time of 17 months posttransplantation. Recipient and donor atrial rates were noted and compared and chronotropic competence determined. Two of 12 recipient atrial remnants were in atrial fibrillation. Only six of the remaining 10 recipient atria exhibited chronotropic competence. Seven of 10 recipient atria had rates higher than that of the donor. Only four of ten recipient atria in sinus rhythm satisfied both criteria. Two of these had abnormally high atrial responses early into exercise. Of the remaining two, only one recipient atrial remnant demonstrated a > or = 20% increase in heart rate above that of the donor at peak exercise. Hence only 1 of 12 (8.3%) transplant recipients potentially could benefit from recipient atrial triggered pacing. While recipient atrial triggered pacing is an attractive theoretical concept for restoring chronotropic competence following orthotopic cardiac transplantation, it may rarely be practical because the recipient atrial remnant displays rhythm abnormalities, chronotropic incompetence, and abnormalities in its exercise response.

Circulating C-Type Natriuretic Peptide is Increased in Orthotopic Cardiac Transplant Recipients

Circulating C-Type Natriuretic Peptide is Increased in Orthotopic Cardiac Transplant Recipients

Coronary artery stenting postcardiac transplant: A report of two cases

Coronary atherosclerosis remains a significant cause of morbidity and mortality following cardiac transplantation. Coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and directional coronary atherectomy have all been presented as attempted treatment options in this population with generally suboptimal results. Endovascular stenting is a new transcatheter treatment modality with unique potential advantages as compared to other transcatheter revascularization techniques. This report presents the use of endovascular stenting and 6-mo follow-up in two orthotopic cardiac transplant recipients with proximal stenotic posttransplant graft atherosclerosis. Cathet Cardiovasc Diagn 40:92–96, 1997. © 1997 Wiley-Liss, Inc.

Permanent pacemaker use after cardiac transplantation: completing the audit cycle.

To determine the effects of delaying permanent pacemaker implantation in cardiac transplant recipients from less than tree weeks to three weeks or more post transplantation-a change prompted by an earlier audit. Retrospective review of resting 12 lead electrocardiograms and prospective 24 hour ambulatory electrocardiograms. Comparison of pacemaker usage before (period 1) and after (period 2) the policy change in November 1990. Outpatient department, supra-regional cardiopulmonary transplant unit. All 30 consecutive orthotopic cardiac transplant recipients who received a permanent pacemaker within one month of transplantation between May 1985 and August 1995. Presence of pacing on the 12 lead electrocardiogram and during 24 hour ambulatory electro-cardiogram monitoring (pacemaker programmed to 50 beats per minute). 16/152 (10.5%) cardiac transplant recipients received permanent pacemakers in period 1 compared with 14/180 (7.8%) in period 2 (P = NS). Evidence of pacing was seen on 12 lead electrocardiograms at three months in 37.5% recipients in period 1 compared with 78.6% in period 2 (P = 0.03). At six months pacemaker usage had declined to 18.8% in period 1 and 35.7% in period 2 and at three years to 13.3% in period 1 and 40% in period 2 (P = NS for both). 21% patients in period 1 paced on ambulatory 24 hour monitoring compared with 38.5% in period 2 (P = NS). Delaying permanent pacemaker implantation to three weeks or more after cardiac transplantation reduced the proportion of permanent pacemaker implantations, slightly but not significantly. There was a significant increase in permanent pacemaker usage at three months post transplantation with trends towards increased usage at later times, suggesting more appropriate selection of patients for permanent pacing.

Hemodynamic response to anesthesia and pneumoperitoneum in orthotopic cardiac transplant recipients.

Hemodynamic response to anesthesia and pneumoperitoneum in orthotopic cardiac transplant recipients.

Biopsy-induced flail tricuspid leaflet and tricuspid regurgitation following orthotopic cardiac transplantation

Damage to the tricuspid valve apparatus has been described after endomyocardial biopsy and may be associated with hemodynamically significant tricuspid regurgitation (TR). This study was performed to determine the prevalence of TR and flail tricuspid leaflet in cardiac transplant recipients and to evaluate the use of a 45 cm sheath placed directly in the right ventricle during endomyocardial biopsy to reduce the incidence of these complications. Echocardiograms and right heart catheterization data of 72 orthotopic cardiac transplant recipients were assessed for the presence of flail tricuspid leaflet, TR, and right-sided cardiac dysfunction 29 ± 20 months (mean ± SD) after transplantation. Moderate or severe TR was present in 23 patients (32%). Ten patients (14%) had flail tricuspid leaflet, with 7 of these having severe TR. Right atrial pressure (10 ± 5 vs 6 ± 5 mm Hg, p < 0.05) was higher, cardiac index (2.0 ± 0.2 vs 2.5 ± 0.7 L/min/m 2, p < 0.05) was lower, and right-sided cardiac dimensions were greater in patients with flail leaflets than in those without flail leaflets. Both the prevalence of flail tricuspid leaflet (41% to 6%, p < 0.0001) and mean grade of TR (2 to 1, p < 0.0001) were reduced after the use of a 45 cm sheath. We conclude that TR secondary to biopsy-induced damage to the valve apparatus occurs in cardiac transplant recipients and is associated with signs of early right-sided heart failure. Use of a 45 cm sheath during endomyocardial biopsy reduces the prevalence of flail tricuspid leaflet and the severity of TR.

Valvular Regurgitation and Right-sided Cardiac Pressures in Heart Transplant Recipients by Complete Doppler and Color Flow Evaluation

To define normal profiles of cardiac structure, function, and hemodynamics postcardiac transplantation using Doppler echocardiography. Retrospective clinical case series with mean follow-up of 5.1 months. Institutional tertiary care center, ambulatory setting. A consecutive sample of 48 orthotopic cardiac transplant recipients. Aortic regurgitation was present in two patients, and was trivial in both cases. Mitral regurgitation was present in 29 of 48 patients, was trivial in 19 of 29 patients, and was mild in 10 of 29 patients. Tricuspid regurgitation was present in 41 of 48 patients and was graded as follows: trivial, 23 of 41; mild, 12 of 41; and moderate, 6 of 41. Septal hypokinesis was present in 33 of 49 patients, and no patient had evidence of other wall motion abnormalities. A pericardial effusion was present in 13 of 48 patients. Hemodynamic values were comparable to those of a nontransplant, normal population with pulmonary artery systolic pressures having a mean value of 31 +/- 6 mm Hg (range, 15 to 45 mm Hg) and estimates of right atrial pressure being 0 to 5 mm Hg in 12 of 48, 5 to 10 mm Hg in 32 of 48, and 10 to 15 mm Hg in 1 patient. There was no correlation between the degree of mitral or tricuspid regurgitation and sex, transplant interval, hemodynamic indices, or endomyocardial biopsy specimen grade. Right ventricular enlargement was associated with the presence of moderate tricuspid regurgitation. Cardiac transplantation recipients commonly display the following: (1) trivial or mild degrees of mitral regurgitation; (2) as much as moderate tricuspid regurgitation; (3) septal hypokinesis; and (4) small pericardial effusions. There is an association between the presence of right ventricular enlargement and moderate tricuspid regurgitation.

Cardiac transplantation affects ventricular expression of brain natriuretic peptide.

The aim was to examine the ventricular expression of brain natriuretic peptide (BNP) in the transplanted human heart. Serial right ventricular biopsies (n = 68) and plasma samples (n = 68) were obtained for measurement of BNP and atrial natriuretic peptide (ANP) from 14 orthotopic cardiac transplant recipients from 1-74 weeks after transplantation. Right ventricular specimens (n = 10) were also obtained from normal hearts during necropsy as controls. Mean ventricular BNP in cardiac transplant recipients was higher (p < 0.05) than in normal hearts, at 13531(SEM 2244) pg.mg-1 soluble protein (range 3232-109448) v 56(11) pg.mg-1 (range 16-91). Ventricular BNP and ANP values were correlated (r = 0.57, p < 0.05). Plasma BNP concentrations were higher (p < 0.05) than plasma ANP concentrations, at 202(16) pg.ml-1 (range 84-655) v 100(12) pg.ml-1 (range 8-484), and were raised (p < 0.05) in comparison with normal plasma BNP concentrations of 20(1.8) pg.ml-1 (range 10-23). Mean ventricular BNP was correlated with time after transplant (r = 0.72, p < 0.05, n = 68) and with mean plasma BNP (r = 0.80, p < 0.05, n = 14). There was no significant relationship between BNP levels and intracardiac or systemic blood pressure, or prednisolone dose (0.1-0.3 mg.kg-1.d-1). The increase in ventricular BNP with time after transplant was not explained by cardiac rejection assessed from histology, and plasma BNP was not significantly increased during rejection episodes. High levels of BNP are synthesised and secreted by the transplanted human ventricle, and the transplanted ventricle may be an important source of circulating BNP. The significant positive association between ventricular BNP and time after transplant suggests a possible self compensatory mechanism or functional adaptation of the transplanted heart which may be beneficial to ventricular function.

Coronary occlusive disease and late graft failure after cardiac transplantation.

Coronary occlusive disease is the main cause of late mortality after cardiac transplantation. It has both similarities and differences compared with conventional atherosclerotic coronary disease. The pathophysiology of late graft failure from coronary occlusive disease is unclear at present. We reviewed the experience of this disorder in our cardiac transplant programme. A retrospective analysis of angiographic and pathological data. A regional cardiothoracic centre and transplant unit. Of a population of 383 orthotopic cardiac transplant recipients operated upon between January 1979 and June 1990, 447 coronary angiograms were available for review in 193 patients. Thirteen of a possible 18 results of post mortem examinations from patients dying from coronary occlusive disease were available. Coronary occlusive disease was defined as any evidence of disease on coronary angiography. Post mortem examinations were performed with standard techniques. The angiographic prevalence of coronary occlusive disease was 3% (1/32 patients) and 40% (19/47 patients) at one and five years respectively. Twenty six grafts failed due to coronary occlusive disease compared with 132 graft failures from all causes during this period. Acute thrombosis was present in a large vessel in seven of 13 fatal cases undergoing necropsy (54%). Noticeable large vessel involvement with disease in smaller distal vessels was present in four patients (31%). The remaining two patients (15%) had small vessel disease alone. Twelve of the 13 patients had significant cardiomegaly (cardiac weight > or = 400 g) with a mean weight of 510 (range 370-740) g. Coronary occlusive disease is the main late complication after cardiac transplantation. A combination of coronary thrombosis, ischaemia from stenoses of large and small coronary vessels, and cardiomegaly contribute to the graft failure of these patients.

Experience of percutaneous transluminal coronary angioplasty in orthotopic cardiac transplant recipients

We evaluated the role of percutaneous transluminal coronary angioplasty (PTCA) in a series of orthotopic cardiac transplant recipients with severe epicardial coronary occlusive disease. Ten orthotopic cardiac transplant patients treated by PTCA up to March 1990 were reviewed. All had significant epicardial coronary artery lesions (greater than 70% stenosis compared with the adjacent healthy artery) and exercise electrocardiogram or isotope perfusion evidence of myocardial ischaemia in the relevant region. Primary angiographic PTCA success was achieved in 12 of the 16 lesions attempted (75%). Mean stenosis improvement was from 80% of adjacent healthy artery (range 70-90%) to 12% (range 0-20%). Median angiographic follow-up of 9 months (2-25 months) is available for all patients. The mean recurrence rate is 33% (4 of 12 successfully treated lesions) defined as greater than 50% reduction in the original gain at the PTCA. We have shown that PTCA is technically possible in a series of cardiac transplant recipients. The primary success and recurrence rates are comparable to the use of PTCA in conventional atherosclerotic coronary disease.

Evolution of heart rate responsiveness after orthotopic cardiac transplantation

Although anatomic reinnervation of the donor heart is unlikely after transplantation, individual subjects have been noted to show near physiologic heart rate (HR) responses to exercise. To assess development of this phenomenon, we studied HR changes in response to orthostasis and treadmill exercise in 52 orthotopic cardiac transplant recipients grouped according to time after transplantation. In group 1 (2.0 ± 0.9 months), no significant increase in HR was seen up to 100 cardiac cycles after standing. A maximal acceleration of 4.0 ± 3.8 beats was seen within 100 cardiac cycles after standing in group 2 (15.8 ± 5.6 months). Patients in group 3 (42.4 ± 12.4 months) showed significant cardioacceleration by 5 cardiac cycles after standing to a maximum of 10.7 ± 5.8 beats/min within the first 100 cardiac cycles. During exercise, HR increased more rapidly during the first minute in group 3 compared with group 1 (p < 0.01). After exercise, HR continued to increase in group 1 but decreased rapidly in the other groups, most notably group 3 (−26.5 ± 16.5 by 2 minutes, p < 0.0001 vs groups 1 and 2). These data indicate development of functional reinnervation after orthotopic heart transplantation. The phenomenon of early acceleration of the HR after orthostasis and rapid deceleration after exercise in transplant recipients implies a local cardiac mechanism rather than response to circulating catecholamines.

Coronary reactivity to ergonovine—possible relationship to accelerated coronary arterial disease in cardiac transplant recipients

Severe coronary artery spasm can occur in orthotopic cardiac transplant recipients. To investigate the possible mechanisms and relevance of coronary spasm to the subsequent development of coronary disease, the response of the coronary arteries to intracoronary ergonovine maleate was studied in 10 patients who had undergone orthotopic cardiac transplantation and were shown to have normal coronary arteries at angiography. Ergonovine in doses of 1, 5 and 10 micrograms was injected into the left coronary artery followed by 2 mg of isosorbide dinitrate. Proximal coronary artery luminal diameters were measured using automated computerized quantitative angiography of the left anterior descending (LAD) and circumflex (LCX) vessels. Five patients (responders) demonstrated a dose response curve to intracoronary ergonovine which was similar to that previously seen in non-transplant patients (mean percentage diameter change +/- SEM, -24.68 +/- 1.93 for LAD, -24.06 +/- 3.91 for LCX). The remaining five patients (non-responders) demonstrated a virtually flat dose response curve significantly different from that of the responders (P = 0.001 for LAD, P = 0.013 for LCX). Angiography after 2 years demonstrated significant coronary disease in four of the five responders to ergonovine. In contrast, the five non-responders to ergonovine continue to have no detectable disease by angiography.

Identification of transplant arteriopathy in orthotopic cardiac transplant recipients using exercise spect thallium -201

Identification of transplant arteriopathy in orthotopic cardiac transplant recipients using exercise spect thallium -201

Comparison of hemodynamic responses during dynamic exercise in the upright and supine postures after orthotopic cardiac transplantation

Abnormal hemodynamic responses during supine exercise have been well documented in orthotopic cardiac transplant recipients. To determine the effect or posture, central hemodynamics were studied in 20 patients during a change from supine to sitting and during graded upright bicycle exercise (group U) and were compared with those of 20 patients matched for age, gender and time from transplantation who were studied after passive leg elevation and during exercise in the supine posture (group S).Passive leg elevation resulted in a 9% increase in stroke index (34 ± 6 to 37 ± 6 ml/m2, p < 0.001) and a 10% increase in cardiac index (3.1 ± 0.4 to 3.4 ± 0.5 liters/mm per m2, p < 0.001) in group S patients compared with a 15% reduction in stroke index (34 ± 7 to 29 ± 6 ml/m2, p < 0.001) and a 9% decrease in cardiac index (3.2 ± 0.6 to 2.9 ± 0.5 liters/min per m2, p < 0.001) in group U patients on assuming the sitting posture. Likewise, both the pulmonary capillary wedge pressure and right atrial pressure increased significantly (13 ± 4 to 17 ± 8 mm Hg, p < 0.001 and 5 ± 3 to 7 ± 3 mm Hg, p < 0.001) with passive leg elevation in group S and decreased on sitting (12 ± 6 to 8 ± 5 mm Hg, p < 0.001 and 5 ± 3 to 3 ± 2, p < 0.001) in group U. Exercise heart rate was slow to rise in both postures and peak heart rate did not differ significantly in the two groups. Stroke index and cardiac index increased to a greater extent in group U during early exercise and, as a result, were not different in the two groups at peak exercise. However, pulmonary capillary wedge pressure was 69% higher (27 ± 7 versus 16 ± 7 mm Hg, p < 0.0001) and right atrial pressure 67% higher (15 ± 5 versus 9 ± 5 mm Hg, p < 0.0001) at peak exercise in the supine posture, although the absolute increase was similar in both groups.The marked increase in ventricular filling pressures during exercise and the differences between supine and upright exercise imply an abnormal left-shifted and steep diastolic pressure-volume relation in the transplanted heart.