Combination use of a TandemHeart with an extracorporeal oxygenator in the treatment of five patients with refractory cardiogenic shock after acute myocardial infarction.

Cardiogenic shock remains the leading cause of in-hospital death for patients admitted with acute myocardial infarction. For patients with refractory cardiogenic shock, early revascularization and intra-aortic balloon pump support are often inadequate to reverse the persistent circulatory collapse. We report 5 cases in which an extracorporeal oxygenator in series with the TandemHeart system was instituted emergently in patients with refractory cardiogenic shock from acute myocardial infarction. From our experience, we showed that the device can be safely and easily inserted and that it is able to reverse circulatory collapse and provide hemodynamic stability in patients who otherwise have a high mortality rate.

A novel two-dimensional echocardiographic finding in cardiac amyloidosis.

BACKGROUND: A number of echocardiographic findings characteristic of cardiac amyloidosis (CA) have been described, each with limitations. METHODS: A distinctive wall motion pattern of preserved myocardial thickening at left ventricular apex with hypokinesis in basal and midsegments was observed in two patients with biopsy proven CA. Following this observation, endomyocaradial biopsy files beginning in 2007 were reviewed. Seven consecutive patients with documented CA were identified. Two-dimensional (2D) echocardiograms for each were reviewed in consensus by two experienced echocardiographers. Clinical and electrocardiographic data were obtained from chart review. RESULTS: All patients were men with class II-IV heart failure. Six had light chain CA, 1 senile CA. Six patients had coronary angiography. One had a 60% left anterior descending coronary artery stenosis. Five had nonobstructive disease. Echocardiograms for all seven patients demonstrated the distinctive pattern of preserved myocardial thickening at apex with hypokinesis in basal and midsegments. Reduced ejection fraction was present in six and increased wall thickness and myocardial echogenicity in seven. Other echo signs of amyloid were variably present. Three had low voltage on electrocardiogram. CONCLUSION: A distinctive 2D echocardiographic pattern of preserved segmental wall motion at left ventricular apex with hypokinesis in basal to midsegments was consistently identified in seven consecutive patients with endomyocardial biopsy-proven CA.

Pulmonary arterial hypertension: pathobiology, diagnosis, treatment, and emerging therapies.

Pulmonary hypertension is a rare disorder caused by vasoconstriction of the pulmonary arteries that leads to elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. Hypertrophy and proliferation of the pulmonary vascular endothelium leads to remodeling of this vascular system, resulting in a progressive disorder. In the past decade the molecular mechanisms and pathobiology of this disorder has become clearer. In addition, a host of new medical treatments and therapies are now available for what has been previously known to be a devastating disorder. Although much needs to be learned, this review will discuss our current knowledge, results of clinical trials, along with treatment options and emerging therapies available for the treatment of this disorder.

Induction of peripheral tolerance by local delivery of dendritic cell progenitors to cardiac allografts in a murine heterotopic heart transplantation model.

OBJECTIVE: Systemic injection of donor-derived dendritic cell (DC) progenitors is reported to prolong cardiac allograft survival in nonimmunosuppressed hosts. Our purpose was to identify whether tolerance limited to the cardiac allograft is inducible by direct delivery of DCs to the myocardium, thus diminishing the potential for systemic side effects. METHODS: The donors were 8- to 12-week-old male B10/ H2b mice. The recipients were 8- to 12-week-old male C3H/H2k mice. For DC culture, DCs were propagated from donor bone marrow with granulocytic/macrophage colony stimulating factor (GM-CSF) (GM-CSF DCs) and/or interleukin-4 (IL-4) (GM-CSF+IL-4 DCs). The phenotypes of DCs were analyzed by flow cytometry (FACScan). For DC assay, the JAM test (a DNA fragmentation assay), the mixed lymphocyte reaction (MLR), and flow cytometry were used. For local DC delivery to the myocardium, DCs were injected retrograde into the ascending aorta, and abdominal heterotopic vascularized heart transplantation was performed. Donor heart survival was recorded. RESULTS: JAM assays confirmed the induction of apoptosis in T cells by both DC preparations. Flow cytometry revealed that the GM-CSF DCs expressed diminished co-stimulatory molecules (B7-1 and B7-2) in comparison with the GM-CSF+IL-4 DCs. The mean survival time of cardiac allografts was 13.1 +/- 4.32 days for the controls, 35.0 +/- 25.7 days for DCs cultured with GM-CSF, and 16.9 +/- 7.30 days for DCs cultured with GM-CSF+IL-4. CONCLUSION: Local delivery of GM-CSF DCs may induce graft tolerance and may prove to be more efficient than systemic delivery of DCs. Local delivery of GM-CSF+IL-4 DCs did not prolong cardiac graft survival, suggesting that the immune response elicited may be immunostimulatory.

Epstein-Barr virus-associated multifocal leiomyosarcomas arising in a cardiac transplant recipient: autopsy case report and review of the literature.

Epstein-Barr virus (EBV) associated smooth muscle tumors (SMTs) have been described in patients with acquired immune deficiency syndrome (AIDS) and, more recently, in association with immunosuppression after solid-organ transplantation. We present the autopsy findings of multiple leiomyosarcomas (LMSs) in a 24-year old man who died 18 months after undergoing orthotopic cardiac transplantation for idiopathic cardiomyopathy. The recognition of EBV-driven LMS developing in cardiac transplant recipients in multiple unusual sites is crucial for the management of these patients and should include complete surgical removal anti-viral therapy and modulation of immunosuppression.

Myocardial expression of fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy.

OBJECTIVES: This study aimed to evaluate the role of gene expression for predicting myocardial recovery in recent-onset cardiomyopathy. BACKGROUND: Apoptosis may limit ventricular recovery. We examined the myocardial expression of Fas, Fas ligand (FasL), tumor necrosis factor (TNF)-alpha, and TNF receptor 1 (TNFR1), and myocardial recovery in patients from the multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC) study. METHODS: Endomyocardial biopsy samples were obtained in 20 patients with recent-onset (<6 months) idiopathic dilated cardiomyopathy (left ventricular ejection fraction [LVEF] < or =0.40). The LVEF was assessed at baseline and at 6 and 12 months by nuclear scans. Myocardial expression was assessed by ribonuclease (RNase) protection, normalized to a constitutively active gene (glyceraldehydes 3-phosphate dehydrogenase [GAPDH]) and reported as percent GAPDH expression. The change in LVEF at 6 and 12 months was compared by tertiles of expression. RESULTS: For all patients (14 men, 6 women; age 46.5 +/- 10.7 years), the mean LVEF was 0.28 +/- 0.05 at baseline and 0.40 +/- 0.14 at six months. Patients in the highest tertile of Fas expression had minimal improvement at six months (DeltaEF = 0.03 +/- 0.05) when compared with the intermediate (DeltaEF = 0.10 +/- 0.13) and lowest tertiles (DeltaEF = 0.21 +/- 0.11, change in LVEF by tertile, p = 0.006). A similar relationship was seen with TNFR1 expression (highest tertile, DeltaEF = 0.06 +/- 0.07; lowest tertile, DeltaEF = 0.21 +/- 0.11, p = 0.02). In contrast with Fas and TNFR1, expression of TNF-alpha and FasL did not predict recovery of LV function. CONCLUSIONS: In cardiomyopathy of recent onset, increased expression of Fas and TNFR1 was associated with minimal recovery of LV function. Apoptosis limits myocardial recovery, and represents a potential target for therapeutic intervention.