Partial aortic valve fusion induced by left ventricular assist device.

BACKGROUND: Left ventricular assist devices (LVADs) may be used (1) as a bridging device to cardiac transplantation, (2) for permanent replacement of left ventricular function, and (3) as a bridge to recovery of ventricular function, for example, in recoverable myocardial disease. In this third group of patients, it is important that the LVAD does not produce changes in the heart that will have a deleterious effect on cardiac function once the device is removed. Furthermore, if the LVAD fails, survival depends on optimal function of the diseased heart. METHODS: All hearts with LVADs encountered as surgical specimens following heart transplantation or at autopsy at the Fairview-University of Minnesota Medical Center during the 5-month period August 1998 to January 1999 were examined for native valvular heart disease. The nature and extent of commissural fusion was noted and measured. Light microscopy was performed on any valve lesions. RESULTS: Four of 6 patients with HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) LVADs showed evidence of commissural fusion (acquired aortic stenosis). In 1 patient, this condition was caused by an organizing thrombus uniting a 14-mm length of the commissural region of the right coronary and noncoronary cusps of the aortic valve. Fibrous commissural fusion due to totally organized thrombus in the other 3 patients affected one aortic commissure (2 patients, 2 mm and 4 mm, respectively) and two commissures (1 patient, 2 mm and 5 mm). Partial cuspal fusion in each case was due to permanent closure of the native aortic valve induced by the LVAD's operating in its automatic setting. Mean length of commissural fusion was 5.4 mm (range, 2 to 14 mm; standard deviation [SDI = +/-5.0 mm). Mean duration of implantation of the six LVADs was 180.3 days (range, 26 to 689 days; SD = +/-253.8 days). The LVADs of the 3 patients with fibrous fusion of the commissures had been implanted for an average of 252.3 days (range, 26 to 689 days; SD = +/-378.2 days). CONCLUSIONS: Normal function of the LVAD produces permanent closure of the native aortic valve. Stasis on the ventricular aspect of the aortic valve, combined with a low level of anticoagulation, favors thrombosis at this site. Thrombus organization leads to aortic stenosis of variable severity. This previously unsuspected complication was not detected clinically in any of our patients. Aortic stenosis may hold serious implications for patients in whom the LVAD acts as a bridge to recovery or in those in whom the LVAD fails. Prevention may be achieved by intermittently reducing LVAD pumping action. A built-in venting cycle would be of value in long-term implants. Thrombi on the aortic valve may also predispose patients to infective endocarditis, because bloodstream infection is common in patients with LVADs.

Venular thrombosis is the key event in the pathogenesis of antibody-mediated cardiac rejection.

A review of the histopathologic features of serial biopsies and excised grafts of 117 experimental and clinical cardiac allografts and xenografts revealed a common sequence in the development of histopathologic changes in grafts showing antibody-mediated (hyperacute and acute vascular) rejection. Based on these observations, we propose the new concept that thrombosis of cardiac veins and venules is the initial key event in antibody-mediated rejection. This is followed by the development of congestion in the subtended venules and capillaries accompanied by interfascicular and, later, intermyocyte edema. Subsequently, focal or diffuse interstitial hemorrhage affecting the subendocardium, extending sometimes to involve the inner half of the ventricular myocardium, is observed. Antibody-mediated rejection therefore appears to be analogous to incomplete venous infarction of the heart. The observed histopathology (in which venular thrombosis plays a key role) favors a thrombogenic basis for the classical features of antibody-mediated rejection, namely edema, vascular thrombi and interstitial hemorrhage. A key role for venular thrombosis would explain the non-uniform distribution of the changes and may suggest new ways of preventing antibody-mediated xenograft rejection.

Clinicopathologic heterogeneity in hypertrophic cardiomyopathy with regard to age, asymmetric septal hypertrophy, and concentric hypertrophy beyond the pediatric age group.

BACKGROUND: To our knowledge, no histopathologic study of the differences between hypertrophic cardiomyopathy in different age groups or that contrasts the pathologic findings in the asymmetric septal hypertrophy and concentric hypertrophy forms of hypertrophic cardiomyopathy has been published. METHODS: The clinicopathologic findings of younger (< or =60 years) (n = 35) and older (>60 years) (n = 20) patients with hypertrophic cardiomyopathy were assessed. Each group was subdivided into groups of patients with asymmetric septal hypertrophy or concentric hypertrophy. RESULTS: Among the young patients, asymmetric septal hypertrophy was more prevalent than concentric hypertrophy, whereas among the elderly patients, concentric hypertrophy was more common. Sudden death was prevalent only among the young. Most young patients had a mirror-image endocardial fibrous septal plaque, whereas most elderly patients with concentric hypertrophy did not. Ventricular septal myocyte disarray and intramural coronary artery thickening were far more marked among the young with asymmetric septal hypertrophy than the young with concentric hypertrophy and the elderly. CONCLUSIONS: Key differences exist between younger and older patients with hypertrophic cardiomyopathy. Much higher degrees of ventricular disarray and intramural coronary artery disease were noted in younger patients with asymmetric septal hypertrophy compared to the elderly patients and the younger patients with concentric hypertrophy.

Delayed xenograft rejection of pig-to-baboon cardiac transplants after cobra venom factor therapy.

BACKGROUND: This study sought to (i) investigate the efficacy of cobra venom factor (CVF) in preventing hyperacute rejection (HAR) after pig-to-baboon heart transplantation, (ii) examine the effect of additional splenectomy (Spx) and pharmacologic immunosuppression (IS), and (iii) study delayed graft rejection when HAR is avoided by complement depletion. METHODS: Eleven recipient baboons received heterotopic pig heart transplants. Three received either no therapy or IS (cyclosporine + methylprednisolone +/- cyclophosphamide +/- methotrexate) at clinically well-tolerated doses, with graft survival for only 40, 32, and 15 min, respectively. Two received CVF+/-Spx, which extended survival to 5 and 6 days, respectively. Six underwent Spx + CVF therapy + IS; graft survival was 3 hr (technical complication), 6 days (death from sepsis), 10, 12, and 22 days (vascular rejection), and <25 days (euthanized for viral pneumonia with a functioning graft that showed histopathologic features of vascular rejection). RESULTS: Dense deposition of IgM and, to a lesser extent, IgG and IgA were seen on the endothelial cells within 1 hr of transplantation, but only trace levels of complement deposition were present in CVF-treated recipients. Within approximately 5-12 days, cardiac xenografts showed progressive infiltration by mononuclear cells, consisting primarily of activated macrophages producing tumor necrosis factor-alpha and small numbers of natural killer cells; T and B cells were absent. CONCLUSIONS: We conclude that (i) CVF prevents HAR, (ii) the addition of Spx + IS delays rejection, but (iii) the early deposition of antibody leads to progressive graft injury, resulting in (iv) delayed vascular rejection. Our findings indicate that the features of delayed xenograft rejection described in small animal models also occur in the pig-to-baboon model, and that rejection may occur in a complement-independent manner from the effects of antibody and/or host macrophages.

Ruptured idiopathic left ventricular false aneurysm of the free wall associated with Takayasu's arteritis in a young child.

The co-existence in a young child of long-standing Takayasu's arteritis, chronic myocarditis and a false aneurysm of the left ventricle raises the possibility that a common inflammatory process may have accounted for all three findings. The unique combination of pathology observed in this patient may provide further evidence that widens the spectrum of cardiac involvement associated with Takayasu's disease to include the myocardium.

A histopathologic grading system of hyperacute (humoral, antibody-mediated) cardiac xenograft and allograft rejection.

BACKGROUND: If future attempts to introduce xenografting into clinical practice prove successful, it will be essential to have a clinically relevant, reproducible grading system for vascular rejection. No formal attempt has been made to grade hyperacute or delayed vascular rejection on the basis of a review of both experimental and clinical material. METHODS AND RESULTS: In an attempt to define a microscopic grading system for hyperacute vascular rejection of the heart, we reviewed the clinical and histologic findings in 112 previously personally studied experimental (n = 109) and clinical (n = 3) cardiac xenografts and allografts, most of which showed vascular rejection. The study material comprised 44 discordant xenografts, 41 concordant xenografts, and 27 allografts. We documented, analyzed, and grouped the histopathologic features together with the clinical data. We devised a grading system which allowed us to allocate each sample to one of the following two categories: grade A: unmodified hyperacute rejection; grade B: mixed hyperacute and acute cellular rejection. Both grades A and B can be subcategorized into three stages: (1) mild (initial), (2) moderate (intermediate), or (3) severe (late) stage. CONCLUSIONS: A common grading system can be applied to both hyperacute rejection and mixed (hyperacute and acute) rejection. The proposed grading system provides a basis for meaningful pathologic evaluation of hyperacute rejection.

Inflammatory pseudotumor (plasma cell granuloma) of the heart. Report of two cases and literature review.

We report pathologic findings in two patients with inflammatory pseudotumor of the heart. The first patient was a 15-year-old-boy who died suddenly and unexpectedly of myocardial ischemia caused by an angiocentric inflammatory pseudotumor affecting all of the major coronary arteries and some of their branches. Inflammatory pseudotumor was also centered around some intrasplenic arteries. The second patient was a 5-month-old girl who had subtotal resection of a mass in the right atrial free wall. Her inflammatory pseudotumor was confined to the myocardium and showed no angiocentricity. The patient is doing well 22 months after surgery. Inflammatory pseudotumor is a benign inflammatory response evoked by an unknown agent(s). In both patients, the inflammatory cells comprised a mixture of B and T lymphocytes. Among B cells, a mixture of kappa and lambda plasma cells was evident. A moderate number of tissue macrophages was also observed. The process is usually self-limited but may cause death if vital structures are involved.

Etiology of valvular heart disease.

The incidence of congenital valvular heart disease has not significantly altered in recent decades. Major factors contributing to altered profiles of acquired valvular heart disease in the past few decades include an increased elderly segment of the population and increasing recognition of nonrheumatic forms of valvular heart disease. Mitral valve prolapse, and similar involvement of other valves, together with senile calcific aortic stenosis have emerged as the most common forms of valvular heart disease in developed countries. Body leanness and hypertension are additional etiological factors for senile calcific aortic stenosis. Severe calcification of a congenital bicuspid aortic valve continues to be an important cause of aortic stenosis in the elderly. Idiopathic degeneration of the aortic and mitral valves, apparently a different condition than mitral valve prolapse, has also become recognized. Despite a recent increase in the incidence of acute rheumatic fever in North America, rheumatic heart disease remains an infrequent cause of valvular heart disease in developed nations. Its incidence has diminished in the Middle East, but it is still frequent in underdeveloped countries. Intravenous drug abuse is increasing in importance as a cause of valvular heart disease in urban centers in the United States. Syphilitic heart disease is very rare.

Congenital stenotic arteriopathy with medial dysplasia of aorta, pulmonary artery, and their major branches.

This report describes the morphological findings in a young child with congenital stenotic arteriopathy who died suddenly following arteriography. Hyperplasia of all of the medial components had produced severe thickening of the wall of the aorta (mean number of lamellar units = 133 in the thoracic aorta and 125 in the abdominal aorta), the pulmonary artery, and their major proximal branches, resulting in significant luminal narrowing. Bilateral renal artery stenosis, attributable mainly to intimal longitudinal smooth muscle hyperplasia associated with fibroelastosis, was the cause of her systemic hypertension. The left ventricle showed healed subendocardial infarction.

Idiopathic annular submitral aneurysm associated with Takayasu's aortitis. A report of two cases.

The pathologic findings in two patients with idiopathic annular submitral left ventricular aneurysms and coexistent Takayasu's aortitis are documented. The evidence of chronic persistent myocarditis in one patient and marked myocardial fibrosis in the other supports two theoretical possibilities: first, the aneurysms may have an inflammatory etiology and, second, a common inflammatory process may have accounted for both the myocardial and the aortic lesions.

Pleural Mesocestoides and cardiac shock in an obese vervet monkey (Cercopithecus aethiops).

Only one case of infection by tetrathyridia larvae of the tapeworm genus Mesocestoides was detected in 416 necropsies of captive vervet monkeys (Cercopithecus aethiops). Two hundred nine larvae were distributed between both pleural cavities. Mass and size ranges of larvae were determined. A plasma cell reaction indicated a humoral immune response to parasite antigens, which may have contributed to acute, lethal cardiac shock. Coagulative myocytolysis was confirmed. The history of this case and associated circumstantial evidence and reports in the literature suggest that infection of primates by tetrathyridia probably occurs after capture rather than before.

Extended cardiopulmonary preservation: University of Wisconsin solution versus Bretschneider's cardioplegic solution.

Application of the University of Wisconsin cold storage solution has rapidly expanded to include medium-term to long-term preservation of virtually all intraabdominal organs. Its use in intrathoracic organ transplantation has also been suggested. We therefore examined the efficacy of the University of Wisconsin solution in a primate allotransplantation model for preservation of hearts, and as a simple single-solution system for static preservation of heart-lung blocks, for periods of ischemia ranging from 6 to 24 hours. For comparison, we employed the histidine-tryptophane-ketoglutarate cardioplegic solution of Bretschneider. University of Wisconsin solution provided superior results with regard to clinical outcome and hemodynamic recovery of hearts after ischemic periods of up to 16 hours. This was in contrast to Bretschneider's solution, which allowed storage of hearts for periods of only up to 10 hours. Heart-lung blocks were equally well preserved with either University of Wisconsin or Bretschneider's solution after 6 to 12 hours, although the University of Wisconsin solution group exhibited a more notable increase in pulmonary water content. This was in accordance with histological data, which suggested that, although hemodynamic recovery of hearts stored for periods longer than 10 hours was poor, preservation of pulmonary ultrastructure was far superior using Bretschneider's solution as compared with University of Wisconsin solution after an ischemic period of up to 16 hours.