Endomyocardial nodular calcification as a cause of heart failure.

Massive cardiac calcification is rare, occurring in association with chronic diseases or more commonly with previous myocardial infarction. We present an intriguing case of massive myocardial calcification of the left ventricle in a young patient with restrictive cardiomyopathy and progressive heart failure who required transplantation. The patient's history and clinical presentation did not reveal the etiology of the myocardial calcification.

Is native aortic valve commissural fusion in patients with long-term left ventricular assist devices associated with clinically important aortic insufficiency?

BACKGROUND: Long-term left ventricular assist device (LVAD) support diminishes flow through the native aortic valve and decreases valve motion. This may cause aortic valve commissural fusion. The clinical importance of such fusion is not well understood. METHODS: Thirty-three consecutive patients receiving long-term LVAD support were followed up until transplantation or death. In each case, the native aortic valve was examined pathologically for commissural fusion. Pathology findings were correlated with hemodynamic performance as assessed by both LVAD pump flow and echocardiography. RESULTS: Seventeen of the 33 patients had some degree of native aortic valve commissural fusion. Four patients had fusion at 2 commissures; of these, 2 had clinically significant native valve aortic insufficiency (2+ or greater), and 1 exhibited trace insufficiency of the native aortic valve. Thirteen patients had fusion at only 1 aortic commissure; of these, 2 had clinically significant aortic insufficiency (2+ or greater), and 3 had trace or mild (1+) insufficiency of native aortic valve. Two of the 4 patients with fusion at 2 commissures required increased LVAD support of >3 liters/min/cm2. No patient with fusion of only 1 commissure required increased LVAD support. Three patients with no commissural fusion of the aortic valve required increased LVAD support secondary to sepsis. CONCLUSIONS: Commissural fusion of the native aortic valve occurs in a significant number of patients receiving long-term LVAD support and can necessitate increased levels of LVAD support. Recognition of this phenomenon may allow development of strategies to minimize commissural fusion and extend LVAD pump life.

Acquired commissural fusion of aortic valves in patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) currently are used as bridges for patients who deteriorate clinically while awaiting cardiac transplantation. At the time of transplantation or subsequent death, we can assess the effect of long-term device implantation on cardiac structural changes. We have noted, in our years of experience, that aortic valve commissures may fuse in patients supported by LVADs. These observations may be important in the use of these pumps as long-term destination therapy. METHODS: We examined 33 hearts (both explants and autopsy specimens) from patients supported either with vented-electric (VE) HeartMates (n = 21) or with implantable pneumatic HeartMates (n = 12). We noted commissures involved, fusion length (mm), duration of LVAD support, and type of LVAD. As controls, we examined 49 explanted hearts from patients with heart failure who were not supported by LVADs. RESULTS: We found commissural fusion in 17 of the 33 hearts. Of those 17 hearts, 4 (23.5%) had 2 commissural fusions, and 13 (76.5%) had only 1 fusion. Fusion length ranged from 5 mm to 17 mm (mean, 9.9 mm). The lesion was more common in patients fitted with VE HeartMates (p < 0.0002). We found small amounts of commissural fusion in 8 of the 49 control hearts. CONCLUSIONS: Acquired commissural fusion is common in patients supported by LVADs, particularly the VE HeartMate. The lesion also occurs occasionally in failing hearts of patients not supported by LVADs. The significance of the lesion in patients who require long-term LVAD support either as a bridge to transplantation or as destination therapy is unclear.

Mechanical unloading increases caveolin expression in the failing human heart.

OBJECTIVE: Implantation of a left ventricular assist device (LVAD) in the failing human heart initiates structural and functional changes termed reverse remodeling. Mechanical unloading improves cardiac adrenergic responsiveness and lipid metabolism, processes regulated by caveolar function. We tested the hypothesis that mechanical unloading alters the expression of caveolins and these changes are linked to altered expression of markers of reverse remodeling. METHODS: Paired human myocardial samples were obtained from patients who received an LVAD as a bridge to cardiac transplantation. Transcript levels were measured using real-time Q-RT-PCR in RNA prepared from 34 pairs of formalin-fixed myocardial tissue blocks. Caveolin-1 and -3 protein levels were determined from frozen tissue (n=5) by Western blots. Caveolin-3 localization was demonstrated by immunohistochemistry. RESULTS: Caveolin-1 protein levels were upregulated in all LVAD-patients after mechanical unloading (P=0.002). Caveolin-1 mRNA was increased in 76% of the patients (n=34, P<0.001). Larger induction of caveolin-1 was associated with greater suppression of ANF. Caveolin-3 transcript levels increased in 82% of the cohort, along with a 2.5-fold induction of caveolin-2. Sarcolemmal caveolin-3 staining was increased after LVAD-support, although no change in total caveolin-3 protein was detected. The mRNA levels of the caveolin-associated CD36 also increased with unloading. Patients with ischemic cardiomyopathy showed greater induction of CD36 (P<0.05) than non-ischemic cases, as well as highly correlated changes in the expression of caveolin isoforms. CONCLUSION: Mechanical unloading induces the expression of caveolins and CD36. The induction of caveolin-1 and the reciprocal suppression of ANF suggest that the changes in the expression of both genes are linked to decreased hemodynamic load. Enhanced caveolin expression during mechanical unloading of failing human hearts may be a part of the reverse remodeling of lipid metabolism, nitric oxide production and adrenergic signaling.

Total left ventricular outflow tract obstruction due to left ventricular assist device-induced sub-aortic thrombosis in 2 patients with aortic valve bioprosthesis.

This report describes 2 patients with an aortic bioprosthesis. Both patients developed total thrombotic occlusion of the sub-aortic left ventricular outflow tract consequent to insertion of a left ventricular assist device (LVAD). Replacing a mechanical valve with a bioprosthesis in patients receiving a left ventricular assist device offers no additional protection against thrombosis of the aortic prosthesis. Pericardial patching below the aortic prosthesis at the time of LVAD implantation may be performed, but will significantly impede or prohibit the native ventricle from ejecting blood and demonstrating any degree of recovery.

Glomangiomatosis.

Neoplasms containing glomus cells are uncommon. Glomus cells within an angiomatosis, so called glomangiomatosis, is exceedingly rare with only three previously reported cases. We are describing the fourth case from a 17-year-old boy which involved his left hand, fingers, and distal forearm. We will review the previously reported cases.

Left ventricular unloading alters receptor tyrosine kinase expression in the failing human heart.

BACKGROUND: Experimental and clinical data suggest that the loss of membrane receptor tyrosine kinase (RTK) activity in cardiac myocytes results in increased frequency of apoptotic cell death and progression of heart failure. The goal of our study was to examine the expression characteristics of RTKs in ventricular myocardium obtained from patients before and after mechanical unloading. METHODS: We extracted RNA from paired formalin-fixed, paraffin-embedded left ventricular tissue blocks obtained at the time of left ventricular assist device (LVAD) implantation and explantation from a cohort of 36 patients (median age 51 years). The duration of LVAD support ranged from 1 to 314 days (median 95 days), 17 patients had ischemic and 19 non-ischemic cardiomyopathy at the time of LVAD implantation. Using real-time reverse transcription-polymerase chain reaction (RT-PCR) we quantitated transcripts for atrial natriuretic factor (ANF) and tumor necrosis factor-alpha (TNF-alpha), markers of heart failure, and the RTKs Her2/neu, Her4 and gp130, regulators of cardiac cell survival. RESULTS: In patients undergoing mechanical unloading, ANF and TNF-alpha mRNA levels were independently suppressed. Her2/neu, along with Her4 was upregulated, mostly in cases of ischemic cardiomyopathy, whereas gp130 levels decreased. Post-LVAD transcript levels of Her2 correlated tightly with gp130 in patients with non-pathologic entry values of gp130. Duration of treatment and age were also determining factors in the change of expression of these genes. CONCLUSION: Real-time quantitative (Q)-RT-PCR can be used to quantitate gene expression in archival myocardial tissue blocks. Mechanical unloading leads to a re-adjustment of RTK transcript levels, but not their reverting to control values in heart failure patients.

Cytokeratins 7 and 20 immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas.

Chromophobe renal cell carcinomas and renal oncocytomas share morphologic similarities and may present a diagnostic challenge on routine hematoxylin-eosin staining. Currently recommended additional studies of Hale's colloidal iron staining and electron microscopy are often difficult to interpret and technically challenging and may not be readily available. Previous studies have reported conflicting results with regard to the cytokeratin 7 staining pattern in chromophobe renal cell carcinomas and renal oncocytomas. Cytokeratin 20 expression in chromophobe renal cell carcinomas has not previously been studied. Formalin-fixed paraffin-embedded tissue of 11 chromophobe renal cell carcinomas and 21 renal oncocytomas were retrieved from the archived files (1984-2000) of four teaching hospitals. Of the 11 chromophobe renal cell carcinomas, eight stained positive (73%) for cytokeratin 7, one stained focally positive (9%), and two cases (18%) were completely negative. Cytokeratin 7 staining of the 21 oncocytomas revealed 4 positive (19%), 7 focally positive (33%), and 10 negative cases (48%). Cytokeratin 20 was uniformly negative on all 11 cases of chromophobe renal cell carcinomas and all 21 cases of oncocytomas. Cytokeratin 7 does not appear to show the consistent immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas, as has been previously suggested. Cytokeratin 20 immunostaining in chromophobe renal cell carcinomas and renal oncocytomas is uniformly negative. Despite the technical and interpretive challenges of Hale's colloidal iron, it is still the most useful stain in differentiating chromophobe renal cell carcinomas from renal oncocytomas.

Solitary fibrous tumor of the tongue: report of a case with immunohistochemical and ultrastructural studies.

Solitary fibrous tumors are rare in extrapleural sites and extremely rare in the oral cavity. We report a case of a solitary fibrous tumor arising from the tongue of a 70-year-old woman. The tumor measured 1.6 cm in maximum diameter and consists of spindle-shaped cells distributed in a haphazard pattern. Immunohistochemical studies show strong positivity for CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin and S-100 protein are negative. Electron microscopy shows uniform neoplastic spindle cells with mesenchymal features. The differential diagnosis for spindle cell neoplasms in the tongue is discussed.