Late-onset Fabry disease: the cardiac sequela.

We describe a patient with Fabry disease (FD) who initially presented with atrial fibrillation without left ventricular hypertrophy (LVH) 14 years before being correctly diagnosed with FD. In the interim, he survived a myocardial infarction complicated by ventricular fibrillation, and his severe LVH was misdiagnosed as sarcomeric hypertrophic cardiomyopathy. In the following 4 years, he developed proteinuric kidney disease, neuropathy, sensorineural hearing loss and gastrointestinal symptoms. The patient was eventually readmitted for an overt heart failure (HF) exacerbation and was seen by an HF cardiologist. The constellation of systemic findings led to further diagnostic testing, including an endomyocardial biopsy, tests to determine alpha-galactosidase A enzyme activity and α-galactosidase A gene (GLA) analysis. The results of the patient's tests were consistent with FD and he was started on enzyme replacement therapy. To our knowledge, this is the first detailed description of a late-onset phenotype of FD with c.146 G>C GLA variant. In addition, this case serves as a potent reminder to pay meticulous attention to 'red flags' accompanying LVH.

Disseminated intravascular coagulation with congestive heart failure and left ventricular thrombus: a case report with literature review of 7 cases.

BACKGROUND: Coagulation abnormalities can accompany acute congestive heart failure (CHF). However, disseminated intravascular coagulation (DIC) is rarely documented in such patients. DIC is characterized by generalized excessive activation of coagulation pathways followed by their depletion with secondary activation of anticoagulation and fibrinolysis. Treatment of the cause is an integral part of management of DIC; thus, recognition of the cause is critical. CASE REPORT: A 55-year-old previously healthy man presented with breathlessness, swelling of both legs, and left leg pain. His physical exam result was consistent with decompensated heart failure. Further testing revealed multiple deep venous thrombi in the upper and lower extremities, arterial occlusion in the left popliteal artery, and an unusual cyst-like left ventricular thrombus. His laboratory evaluation was consistent with severe acute DIC. The patient was managed aggressively with diuretics, transfusions of platelets, and cryoprecipitate and was subsequently anticoagulated. His platelet count and coagulation parameters normalized and coronary angiography did not reveal any obstructive lesions. On day 22, an echocardiogram revealed and MRI confirmed that the intracardiac thrombus had disappeared. He underwent revascularization of the left leg and was successfully discharged from the hospital. CONCLUSIONS: Severe biventricular non-ischemic cardiac dysfunction with intra-cardiac thrombi should be considered in patients presenting with DIC. In addition to anticoagulation, treatment of underlying heart failure is critical in such cases.

Influence of ischemic injury on vein graft remodeling: role of cyclic adenosine monophosphate second messenger pathway in enhanced vein graft preservation.

OBJECTIVE: Endothelial injury during the harvest of saphenous vein grafts might play an important role in the development of vein graft disease after coronary artery bypass grafting. Using a murine autologous arterialized vein patch model, we tested whether the initial ischemic insult of vein grafts was linked to the later development of graft neointimal hyperplasia and whether the restoration of the cyclic adenosine monophosphate second messenger pathway would attenuate the development of neointimal hyperplasia. METHODS: A segment of the external jugular vein of a mouse was grafted onto its abdominal aorta. Three weeks after the operation, the degree of neointimal hyperplasia of the implanted graft was compared among (1) grafts without preservation, (2) grafts with 2 hours of preservation (25 degrees C) in heparinized saline, and (3) grafts with 2 hours of preservation in heparinized saline in the presence of a cyclic adenosine monophosphate analog. In addition, cyclic adenosine monophosphate contents of vein grafts and leukocyte adherence to the graft endothelium were assessed. RESULTS: Cyclic adenosine monophosphate contents were significantly decreased after 2 hours of preservation (212 +/- 8 vs 156 +/- 5 pmol/L, P < .01). The grafts preserved for 2 hours showed greater neointimal hyperplasia compared with the grafts without preservation (neointimal expansion, 68.7% +/- 9.6% vs 46.1% +/- 4.8%; P < .01). The addition of a cyclic adenosine monophosphate analog to the preservation solution significantly suppressed neointimal hyperplasia of grafts preserved for 2 hours (44.3% +/- 5.0%). Inhibiting the cyclic adenosine monophosphate-dependent protein kinase by adding Rp-cAMPS abrogated the beneficial effects. Furthermore, grafts preserved for 2 hours had significantly more leukocytes adhering to the graft endothelium 24 hours after the operation compared with nonpreserved grafts, which was significantly reduced by the cyclic adenosine monophosphate treatment. CONCLUSIONS: Ischemic insult during vein graft harvest and preservation is a key factor in the development of vein graft neointimal hyperplasia at least in part caused by the depletion of cyclic adenosine monophosphate. We conclude that stimulation of the cyclic adenosine monophosphate second messenger pathway might be a potential strategy for the prevention of vein graft disease.