Seismic velocities of CaSiO3 perovskite can explain LLSVPs in Earth's lower mantle.

Seismology records the presence of various heterogeneities throughout the lower mantle1,2, but the origins of these signals-whether thermal or chemical-remain uncertain, and therefore much of the information that they hold about the nature of the deep Earth is obscured. Accurate interpretation of observed seismic velocities requires knowledge of the seismic properties of all of Earth's possible mineral components. Calcium silicate (CaSiO3) perovskite is believed to be the third most abundant mineral throughout the lower mantle. Here we simultaneously measure the crystal structure and the shear-wave and compressional-wave velocities of samples of CaSiO3 perovskite, and provide direct constraints on the adiabatic bulk and shear moduli of this material. We observe that incorporation of titanium into CaSiO3 perovskite stabilizes the tetragonal structure at higher temperatures, and that the material's shear modulus is substantially lower than is predicted by computations3-5 or thermodynamic datasets6. When combined with literature data and extrapolated, our results suggest that subducted oceanic crust will be visible as low-seismic-velocity anomalies throughout the lower mantle. In particular, we show that large low-shear-velocity provinces (LLSVPs) are consistent with moderate enrichment of recycled oceanic crust, and mid-mantle discontinuities can be explained by a tetragonal-cubic phase transition in Ti-bearing CaSiO3 perovskite.

The iTreAD project: a study protocol for a randomised controlled clinical trial of online treatment and social networking for binge drinking and depression in young people.

BACKGROUND: Depression and binge drinking behaviours are common clinical problems, which cause substantial functional, economic and health impacts. These conditions peak in young adulthood, and commonly co-occur. Comorbid depression and binge drinking are undertreated in young people, who are reluctant to seek help via traditional pathways to care. The iTreAD project (internet Treatment for Alcohol and Depression) aims to provide and evaluate internet-delivered monitoring and treatment programs for young people with depression and binge drinking concerns. METHODS: Three hundred sixty nine participants will be recruited to the trial, and will be aged 18-30 years will be eligible for the study if they report current symptoms of depression (score 5 or more on the depression subscale of the Depression Anxiety Stress Scale) and concurrent binge drinking practices (5 or more standard drinks at least twice in the prior month). Following screening and online baseline assessment, participants are randomised to: (a) online monthly self-assessments, (b) online monthly self-assessments + 12-months of access to a 4 week online automated cognitive behaviour therapy program for binge drinking and depression (DEAL); or (c) online monthly assessment + DEAL + 12-months of access to a social networking site (Breathing Space). Independent, blind follow-up assessments occur at 26, 39, 52 and 64-weeks post-baseline. DISCUSSION: The iTreAD project is the first randomised controlled trial combining online cognitive behaviour therapy, social networking and online monitoring for young people reporting concerns with depression and binge drinking. These treatments represent low-cost, wide-reach youth-appropriate treatment, which will have significantly public health implications for service design, delivery and health policy for this important age group. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12614000310662. Date registered 24 March 2014.

Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled study.

BACKGROUND: Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD. METHODS AND RESULTS: One hundred forty-nine consecutive patients (131 men and 18 women aged 48+/-13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7+/-1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43+/-8% versus 60+/-10% (P<0.1). By Cox multivariate analysis, independent predictors of TxCAD were donor age >40 years (relative risk, 2.7; CI, 1.3 to 5.5; P<0.01) and no ganciclovir (relative risk, 2.1; CI, 1.1 to 5.3; P=0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32+/-11% (n=28) for ganciclovir versus 62+/-16% (n=25) for placebo (P<0.03); calcium blockers (n=68), 50+/-14% (n=33) for ganciclovir versus 45+/-12% (n=35) for placebo (P=NS). CONCLUSIONS: TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.

Accelerated atherosclerosis in a cardiac transplant patient.

A cardiac transplant patient with rapidly progressive graft atherosclerosis is described. This case demonstrates the accelerated nature of this disease and problems in diagnosis, as well as an unexpected and previously unreported lack of sensitivity of exercise thallium scintigraphy in its investigation. This case also gives further support to the practice of routinely and frequently obtaining coronary arteriograms in the management of these patients.

Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings.

Annual coronary arteriograms have been obtained from all heart transplant recipients at Stanford University Medical Center since 1969. Angiographic lesions in 81 transplant patients exhibiting coronary vascular disease were classified into three categories: type A, discrete or tubular stenoses; type B, diffuse concentric narrowing; and type C, narrowed irregular vessels with occluded branches. The 81 arteriograms showing transplant coronary vascular disease were contrasted with 32 from nontransplant patients with coronary artery disease analyzed in a similar fashion. The nontransplant angiograms showed 178 lesions, all of type A (discrete or tubular) morphology, 75% of which were located in primary epicardial coronary vessels and 25% in secondary branch vessels. In the patients with transplant coronary vascular disease, 349 (76%) of 461 lesions were type A: 57% in primary vessels, 42% in secondary branches and 1.4% in tertiary branches. Of the 112 type B and C lesions (diffuse narrowing, tapering and obliteration), 25% were in primary vessels, 44% in secondary vessels and 31% in tertiary branches (p less than 0.05 for patients with transplant coronary vascular disease versus patients with nontransplant coronary artery disease). Total vessel occlusion was found in proximal or middle vessel segments in 96% and distally in 4% of patients with "ordinary" coronary artery disease versus 49% distally in patients with transplant coronary disease (p less than 0.002). In the presence of total vessel occlusion, collateral vessels were poor or absent in 92% of transplant versus 7% of nontransplant patients with coronary disease (p less than 0.002). Therefore, coronary artery disease in transplant patients represents a mixture of typical atheromatous lesions and unique transplant-related progressive distal obliterative disease that occurs without collateral vessel development.

Relation of donor age and preexisting coronary artery disease on angiography and intracoronary ultrasound to later development of accelerated allograft coronary artery disease.

OBJECTIVES: This study assessed the influence of donor age and preexisting donor coronary disease on the later development of allograft coronary artery disease, ischemic events and overall survival. BACKGROUND: The increasing demand for heart donors has led to a tendency to liberalize age criteria for donor acceptability. METHODS: A total of 233 consecutive heart transplant recipients who had baseline, early postoperative and follow-up coronary angiograms, as well as a subset of 47 patients with baseline intracoronary ultrasound imaging recordings, were analyzed (mean 3.8 years of follow-up). Patients were subclassified according to the presence of donor coronary artery disease on the baseline angiogram and stratified at age 40 years. RESULTS: patients without evidence of preexisting coronary artery disease on a baseline angiogram (n = 219) were significantly less likely to develop new disease than the 14 patients with preexisting coronary artery disease (p = 0.002). Although older donors exhibited earlier coronary artery disease than younger donors at 3 years of follow-up, there was no difference by 5 years (p = 0.25). There was no difference in survival or probability of developing ischemic events between the groups. Baseline ultrasound imaging revealed substantial disease in 7 of 9 older donated hearts, and in only 7 of 38 younger donated hearts (p = 0.002). Preexisting coronary artery disease, nonuse of calcium channel blocking agents, older donor age, posttransplantation cytomegalovirus infection, elevated very low density lipoprotein levels and previous ischemic heart disease in the recipient were significant predictors of allograft coronary artery disease. CONCLUSIONS: Heart donors with angiographic evidence of preexisting coronary artery disease and older donors are more likely to develop new allograft coronary artery disease by 3 years. However, there is no difference in survival or freedom from ischemic events between younger and older donors at a mean follow-up of 3.8 years.

Early development of accelerated graft coronary artery disease: risk factors and course.

OBJECTIVES: This study assessed the time of first appearance of angiographic graft coronary artery disease in relation to clinical and laboratory variables and clinical events in heart transplant recipients. BACKGROUND: Graft coronary artery disease is the main factor limiting long-term survival after heart transplantation, and it is important to understand its natural history. METHODS: One hundred thirty-nine consecutive patients who developed angiographic coronary artery disease after heart transplantation were classified according to early (< or = 2 years) versus late (> 2 years) posttransplantation initial detection of coronary artery disease. These subgroups were analyzed for differences in clinical and laboratory demographics, incidence of progression to ischemic events and incidence of antecedent cytomegalovirus infection. RESULTS: The early-onset group (64 patients) had more rapid progression to ischemic events than the late-onset group (75 patients), with 59% of the late group and only 35% of the early group free from ischemic events by 5 years after initial detection (p = 0.02), but there were no significantly correlated clinical or laboratory predictors of ischemic events. The early group had a significantly higher incidence of antecedent cytomegalovirus infection. CONCLUSIONS: We conclude that 1) accelerated graft coronary artery disease develops at variable times after heart transplantation; 2) the early appearance of graft coronary artery disease may be a marker of intrinsically more aggressive disease; 3) cytomegalovirus infection is associated with earlier onset of graft coronary artery disease. Patients with early development of graft coronary artery disease should potentially be given priority for interventional strategies as they are developed.

Incidence and severity of transplant coronary artery disease early and up to 15 years after transplantation as detected by intravascular ultrasound.

OBJECTIVES: The purpose of this study was to quantify the severity of transplant coronary artery disease and to assess lesion characteristics early and up to 15 years after heart transplantation by using intracoronary ultrasound. BACKGROUND: Intravascular ultrasound has the ability to measure the components of the arterial wall and has been shown to be a sensitive method for detection of transplant coronary artery disease. METHODS: A total of 304 intracoronary ultrasound studies were performed in 174 heart transplant recipients at baseline and up to 15 (mean 3.3 +/- 0.2) years after transplantation. Mean intimal thickness and an intimal index were calculated, and lesion characteristics (eccentricity, calcification) were assessed for all coronary sites imaged (mean 3.0 +/- 0.1 sites/study). The Stanford classification was used to grade lesion severity. RESULTS: Compared with findings in patients studied at baseline (< 2 months after transplantation, n = 50), mean intimal thickness (0.09 +/- 0.02 vs. 0.16 +/- 0.02 mm, p < 0.01), intimal index (0.07 +/- 0.01 vs. 0.14 +/- 0.02, p < 0.01) and mean severity class (1.5 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly higher at year 1 (n = 52) after transplantation. Thereafter, all three variables further increased over time and reached highest values between years 5 and 15. Calcification of lesions was detected in 2% to 12% of studies up to 5 years after transplantation, with a significant increase to 24% at years 6 to 10 (p < 0.05). CONCLUSIONS: Severity of transplant coronary artery disease appeared to progress with time after transplantation in this cross-sectional study. This characteristic was most prominent during the 1st 2 years after transplantation, whereas calcification of plaques occurred to a significant extent only later in the process. These data may serve as a reference for comparison of intravascular ultrasound findings in other studies of patients with transplant coronary artery disease.

Toxoplasmosis presenting as brain abscesses. Diagnosis by computerized tomography and cytology of aspirated purulent material.

A patient with brain abscesses caused by Toxoplasma gondii is described. Presence of brain abscesses was confirmed by computerized tomography, and T. gondii was identified as the etiologic agent in cytologic preparations of aspirated purulent material from one of the abscesses.

Coronary artery spasm in the denervated transplanted human heart: a clue to underlying mechanisms.

The mechanism of coronary artery spasm has been poorly understood but there has been some suggestion that cardiac autonomic innervation may play an important role. We report coronary artery spasm in a 43 year old man two years after he had received a transplant. Provocative pharmacologic testing suggested functional denervation of the patient's heart. Thus, coronary artery spasm can occur in the transplanted, denervated human heart. Autonomic innervation of the heart is not essential in all cases of coronary spasm, and circulating catecholamines and/or metabolic of hormonal products may play an important role.

Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection.

PURPOSE: To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection. METHODS AND MATERIALS: Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years. RESULTS: The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort. CONCLUSION: TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not appreciably different than conventional immunosuppression.

Coronary artery intimal thickening in the transplanted heart. An in vivo intracoronary untrasound study of immunologic and metabolic risk factors.

This study examined the hypothesis that immunologic factors are the major correlates of coronary artery intimal thickening and luminal stenosis. The study population included 116 adult heart transplant recipients with a mean age of 44.7 +/- 12.0 years (89 men and 27 women) undergoing annual coronary angiography and intracoronary ultrasound 3.4 +/- 2.7 (range, 1.0-14.6) years after transplantation. Mean intimal thickness was obtained from several distinct sites along the left anterior descending and/or left circumflex coronary artery by intracoronary ultrasound. Coronary artery stenosis defined by angiography was classified as mild (< 30% luminal stenosis), moderate (> or = 30-70% luminal stenosis), or severe (> 70% luminal stenosis or diffuse pruning of distal vessels). Prevalence of any transplant coronary artery disease (TxCAD) was 85% by intracoronary ultrasound and 15% by angiography. By multiple regression analysis, only average fasting plasma triglyceride level (P < 0.006) and average weight (P < 0.007) were significantly correlated with severity of intimal thickening (R = 0.54, P < 0.0001). Donor age (P < 0.006) and average fasting plasma triglyceride level (P < 0.009) were significantly correlated with stenosis by angiography. Correlation of multiple immunologic and metabolic factors with intimal thickness by univariate analysis suggests a multifactorial etiology for TxCAD. Among the multiple univariate correlates of TxCAD, higher fasting plasma triglyceride levels and body weight are the only independent correlates of TxCAD. The absence of acute rejection as an independent predictor of intimal thickening suggests that mechanisms beyond those mediating typical cellular rejection should be targeted for advancing our understanding of Tx-CAD.

Frequency of familial nature of dilated cardiomyopathy and usefulness of cardiac transplantation in this subset.

A familial etiology was identified on the basis of family history in 16 (8.75%) of 184 patients undergoing cardiac transplantation at Stanford for endstage dilated cardiomyopathy (DC). These 16 patients, from 11 families, included 5 sibling pairs. To help determine optimal management of such patients, their case histories and posttransplant courses were reviewed. Mean age of patients at presentation was 23 +/- 15 years. In sibling pairs, duration of symptoms from onset to diagnosis was 14 +/- 5 weeks for the first sibling, but only 4 +/- 2 weeks for the second. Progressive cardiac enlargement was documented radiographically in siblings of transplant recipients in 2 families before the onset of symptoms. The posttransplant course with regard to rejection incidence, infectious complications, coronary artery disease and malignancy was similar to that of the 168 patients with nonfamilial DC. Actuarial survival at 5 years after transplantation was 80%. Thirteen patients (including all sibling pairs) are alive 1 to 11 years after transplantation. Sepsis was the cause of death in 3 patients, occurring during the early postoperative period in 2 and following retransplantation for graft atherosclerosis 7 years after the initial transplant in the third patient. Thus, diagnosis of DC in childhood or adolescence mandates evaluation and surveillance of family members, because this disease can progress rapidly. The favorable results of cardiac transplantation for familial DC suggest that it should be promptly considered for such patients with end-stage disease.

Influence of recipient atrial contraction on left ventricular filling dynamics of the transplanted heart assessed by Doppler echocardiography.

Recipient atrial remnants retain electrical and mechanical activity after orthotopic cardiac transplantation. This study investigated the influence of recipient atrial contraction timing on Doppler ultrasound mitral flow velocity curves, isovolumic relaxation time, peak early mitral flow velocity (M1), mitral valve pressure half-time and peak mitral flow velocity due to atrial systole (M2). Clearly identifiable recipient atrial electrical activity (P waves) was present in 7 of 10 patients studied early postoperatively 2 to 6 months (mean 2.5) (early group) and in 20 of 24 patients seen 1 to 11 years (mean 3) after transplantation (late group). Median age and gender distribution were similar in both groups. For analysis of its influence on isovolumic relaxation time, pressure half-time and M1, recipient atrial contraction was classified by its position in the cardiac cycle as early systole, late systole or diastole. For analysis of M2, it was classified as early diastole, late diastole or systole. Compared with its occurrence in diastole, recipient atrial contraction in late systole was associated with a shorter isovolumic relaxation time, shorter pressure half-time and higher M1. In early systole it was associated with a longer pressure half-time and lower M1 than in diastole; isovolumic relaxation time was unchanged. Recipient atrial contraction in early diastole resulted in a lower M2 than in systole, whereas simultaneous contraction of recipient and donor atria in late diastole resulted in an increase in M2. These results indicate that the timing of recipient atrial contraction and relaxation significantly influences left ventricular filling dynamics.

Correlation of donor characteristics with transplant coronary artery disease as assessed by intracoronary ultrasound and coronary angiography.

The mechanisms responsible for transplant coronary artery disease (CAD) and its predisposing factors remain incompletely understood. The influence of donor characteristics as predisposing factors has not been studied systematically. We examined the correlation of donor demographic, clinical, and immunologic parameters with transplant CAD assessed by both intracoronary ultrasound (ICUS) and coronary angiography in 116 heart transplant recipients (age 44.7 +/- 12.0 years) studied 3.4 years (range 1.0 to 14.6) after transplantation. Quantitative ultrasound data were obtained by calculating mean intimal thickness from several distinct coronary sites. Coronary angiograms were categorized visually as normal or showing any transplant CAD. By multivariate regression analysis, donor undersize of > 20% of recipient weight (p < 0.02) and duration after transplantation (p < 0.005) were independently correlated with the amount of ICUS intimal thickness (r = 0.36, p = 0.0007), and older donor age with angiographic evidence for the disease (r = 0.34, p < 0.006). In a subgroup analysis of the 39 patients studied 1 year after transplantation, white donor race (p < 0.05), fewer human leukocyte antigen-DR mismatches (p < 0.002), shorter ischemic time (p < 0.04), and donor smoking history (p < 0.02) were independent predictors for severity of ICUS intimal thickening (r = 0.92, p = 0.0009); higher donor age (p < 0.006) and higher arterial partial pressure of oxygen (p < 0.003) were independent predictors for angiographic disease (r = 0.67, p < 0.002). In conclusion, donor characteristics may contribute to the probably multifactorial pathogenesis of transplant CAD.

Cardiac function after domino-donor heart transplantation.

A major limitation in cardiac transplantation is donor availability. A possible way to increase the supply of donor hearts is to use explanted hearts from patients undergoing heart-lung transplantation for primary lung disease. One potential advantage of this approach, termed domino-donor transplantation, is the existence of a donor right ventricle already adapted to pulmonary hypertension, which would therefore theoretically decrease the likelihood of acute donor right heart failure in recipients with preexisting elevation of pulmonary vascular resistance. Potential disadvantages include graft failure secondary to chronic effects of pulmonary hypertension on the right ventricle, arrhythmia and infections. Seven domino-donor transplants were performed at Stanford University Hospital; graft and patient survival to date are 100% at a mean follow-up of 20 months (range 1 to 26). Infection and rejection rates have been comparable to those of the current Stanford experience for conventional orthotopic transplantation. Right ventricular function and size have either improved or remained unchanged in all patients after transplantation. Transient early postoperative donor right ventricular dilation, a characteristic adaptive response seen in nondomino transplants, occurred in 4 patients with pulmonary hypertension before surgery. These data indicate that, with adequate assessment before surgery, domino-donor cardiac transplantation is an appropriate means of augmenting the donor pool.

Cardiovascular physiology in a case of heterotopic cardiac transplantation.

Successful heterotopic cardiac transplantation in a 24 year old man with end stage cardiomyopathy provided an opportunity to study cardiovascular physiology. The donor and native hearts, functioning independently in parallel, were studied by serial physical examination, electrocardiography, echocardiography, nuclear angiography and cardiac catheterization. Results indicated that the donor left heart assumed the predominant role in supplying systemic output, possibly contributing to decreasing function of the patient's own (native) heart. Analysis of serial nuclear angiograms revealed an initial postoperative ejection fraction of 52 and 21 percent in the donor and the native left ventricle, respectively; repeat studies 3 months postoperatively showed values of 50 and 9 percent, respectively, indicating significant deterioration in native left ventricular cardiac function. Observation of valve motion of the native heart showed major irregularities of the aortic valve in contrast to seemingly normal, regular mitral valve motion. These data rise interesting questions regarding interpretation of valve motion as an indicator of ventricular function.

Cardiac transplantation in patients with preexisting neoplastic diseases.

Cardiac transplantation has traditionally been reserved for individuals with end-stage congestive heart failure (CHF) in whom there is no history of other life-threatening systemic disorders. In most transplant centers, patients with a history of malignancy and severe heart failure have not been considered acceptable candidates for cardiac transplantation. In the last 4 years at Stanford University Medical Center, 8 cardiac transplants have been performed in 7 patients with a history of neoplastic disease. Six of these patients had already received treatment for lymphoproliferative disorders and in 1 case, a patient underwent a transplant after treatment for adenocarcinoma of the colon. Six of the 7 patients were discharged from the hospital and in that group, the 1-year posttransplant survival rate was 71%. This was comparable to an overall 1-year survival rate of 80% for patients undergoing a cardiac transplant at our center during the same period of time. At follow-up averaging over 2 years, there has been 1 case of recurrent neoplasia. One patient with evidence of radiation-induced pulmonary damage died of respiratory failure 2 days after transplantation. One patient required retransplantation because of intractable rejection and subsequently died from infectious complications. Immunosuppressive therapy in these patients has not been associated with an increased risk for neoplastic recurrence or for the development of posttransplant lymphoproliferative disorders. The current study demonstrates that in a carefully selected group, previously treated neoplastic disease should not represent a contraindication to cardiac transplantation.

Acute myocardial infarction in cardiac transplant recipients.

To characterize the clinical and pathologic features of acute myocardial infarction (AMI) in cardiac transplant recipients, 22 Stanford patients who had 25 documented infarcts at a mean of 3.86 years after transplantation were reviewed. Symptoms included chest pain (2), arm pain (3), weakness (16), dyspnea (11) and palpitations (8). Three episodes were clinically silent, detected only as new electrocardiographic changes during routine follow-up. Of 18 patients hospitalized with symptoms, only 7 had electrocardiographic changes of typical Q-wave AMI; 5 had nonspecific ST-segment changes and 2 had no documented changes. Two had old Q waves. Twelve of the 18 were misdiagnosed at admission as having infection or congestive heart failure. Serial creatine phosphokinase levels were obtained in 13 patients, and values were elevated in 8. Six of 25 AMI episodes were associated with development of congestive heart failure and 4 others led to development of cardiogenic shock. Seven patients died during the acute phase of infarction, 12 were retransplanted from 2 days to 6 months after infarct and 1 died suddenly after discharge. Two healed myocardial infarctions of unknown duration were found at autopsy or on explantation in patients not clinically suspected of having an AMI. All infarcts occurred in patients known to have angiographic evidence of transplant coronary artery disease, based on annual coronary arteriography. At autopsy or explantation all hearts were found to have characteristic diffuse concentric coronary artery narrowing, and 4 (18%) had an unusual pattern of multiple foci of nontransmural AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive assessment of donor and native heart function after heterotopic heart transplantation.

The contribution of the donor heart to total circulatory performance after heterotopic heart transplantation has been difficult to assess. First-pass nuclear angiocardiography and directional Doppler echocardiography were used to examine separately left and right ventricular function of the donor heart after heterotopic transplantation. A comparison was made between two patients, one with a low initial pulmonary vascular resistance and one with a high, relatively fixed pulmonary vascular resistance. In both cases, currently available noninvasive techniques allowed confirmation of the expectation that the donor left ventricle can function effectively as a left ventricular bypass. In neither case was recovery of the native heart demonstrated. The contribution of the donor right ventricle to total right ventricular output appeared to be dependent on the condition of the donor heart and on the pulmonary vascular resistance. In situations with a high pulmonary vascular resistance and end-stage right ventricular failure, it was concluded that the donor heart may not at first constitute an effective assist for the native right ventricle. Native right ventricular failure may then become a major factor influencing survival after heterotopic heart transplantation.