Unicentric Castleman's disease associated with malignant cardiac Amyloid-A amyloidosis: a case report.

Background: Unicentric Castleman's disease (UCD), a lymphoproliferative disorder characterized by enlargement of the lymph nodes, is a rare cause of Amyloid-A amyloidosis. While patients usually present with impaired kidney function and proteinuria, heart involvement is neither common nor the main cause of signs and symptoms. Case summary: We present a patient who was admitted to the hospital for impaired exercise capacity. Diagnostic work-up revealed severe left ventricular hypertrophy suggestive of cardiac amyloidosis. Although Congo red staining of endomyocardial biopsies was initially negative, subsequent immunohistochemical staining against serum amyloid A finally confirmed the diagnosis of cardiac amyloidosis. 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed a tumour located in dorsal of the duodenum. Fine-needle aspiration biopsy of the tumour was suggestive but could not confirm the presence of UCD beyond reasonable doubt. Rapid worsening of heart failure symptoms warranted urgent surgical tumourectomy, which resulted in immediate post-operative lowering of serum amyloid protein. However, post-operative cardiogenic shock could not be stabilized even with veno-arterial extracorporeal membrane oxygenation, and the patient eventually died. The UCD of the hyaline vascular (HV) subtype was confirmed by pathologic work-up of the excised tumour. Discussion: This case report presents for the first time a patient with malignant cardiac Amyloid-A amyloidosis caused by unicentric Castleman's disease of the HV subtype. Since the disease progresses swiftly, rapid diagnosis is essential for potential curative treatment.

Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

BACKGROUND: Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin (TTR) gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory. This study aimed to assess the prevalence and phenotypic spectrum of hATTR in Austria. METHODS: Within the period of 2014-2019, patients with ATTR-associated cardiomyopathy and/or unexplained progressive polyneuropathies were screened for mutations in the TTR gene. RESULTS: We identified 43 cases from 22 families carrying 10 different TTR missense mutations and confirmed two mutational hot spots at c.323A>G (p.His108Arg) and c.337G>C (p.Val113Leu). Two further patients with late onset ATTR carried TTR variants of unknown significance. The majority of patients initially presented with heart failure symptoms that were subsequently accompanied by progressive polyneuropathy in most cases. A total of 55% had a history of carpal tunnel syndrome before the onset of other organ manifestations. CONCLUSIONS: Our study underlined the relevance of hATTR in the pathogenesis of amyloid-driven cardiomyopathy and axonal polyneuropathy and indicated considerable genetic heterogeneity of this disease in the Austrian population. The estimated prevalence of hATTR in Austria based on this study is 1:200,000 but a potentially higher number of unknown cases must be taken into account. With respect to new therapeutic approaches, we strongly propose genetic testing of the TTR gene in an extended cohort of patients with unexplained heart failure and progressive polyneuropathy.

Coronary subclavian steal syndrome: an extracoronary cause of acute coronary syndrome.

Significant atherosclerotic changes of the coronary arteries are the common cause of cardiac chest pain. We report the case of an 80-year-old woman suffering from unstable angina caused by extracoronary atherosclerosis. The patient had an extensive medical history with severe coronary heart disease and cardiac bypass surgery (LIMA to LAD, two venous bypass grafts). An urgent coronary angiography was performed. The angiogram displayed the already known three-vessel disease, the bypass grafts were in a good functional condition. Subsequently, a stenosis of the proximal segment of the left subclavian artery was detected. Measurement of the pullback pressure gradient confirmed the significance of the stenosis. We suspected a "steal phenomenon" concerning the bypass graft LIMA to LAD. An ad hoc PTA with consecutive stenting (self-expandable stent) enabled a successful revascularization of the left subclavian artery without any adverse effects to the vertebral arteries. Cardiac chest pain did not occur any more. Coronary Subclavian Steal Syndrome should be considered a rare but important differential diagnosis in acute coronary syndrome after bypass surgery.

Benefit of immediate beta-blocker therapy on mortality in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: Despite the recommendations to initiate ß-blockade to all patients with an ST-segment elevation myocardial infarction, data concerning the timing of the administration of ß-blockers are controversially discussed. In view of these controversies, we analyzed the effect of immediate vs. delayed ß-blockade on all-cause mortality of patients with ST-segment elevation myocardial infarction in the Lower Austrian Myocardial Infarction Network. DESIGN: Nonrandomized, prospective observational cohort study. SETTING: Myocardial infarction network including the out-of-hospital emergency services, five primary-care hospitals and a percutaneous coronary intervention-capable hospital in the western part of Lower Austria. PATIENTS: The data of all patients with ST-segment elevation myocardial infarction defined according to the American Heart Association criteria and treated according to the treatment protocol of the network were consecutively collected. For the purpose of survival analyses, the baseline survival time was set to 48 hours after the first electrocardiogram, and in all patients with recurrent MI within the observational period, only the first MI was regarded. INTERVENTIONS: The treatment protocol recommended either the immediate oral administration of 2.5 mg bisoprolol (within 30 min after the first electrocardiogram) or 24 hours after acute myocardial infarction (delayed ß-blockade). MEASUREMENTS AND MAIN RESULTS: In total, out of the 664 patients with ST-segment elevation myocardial infarction, 343 (n = 52%) received immediate ß-blockade and 321 (48%) received delayed ß-blockade. The probability of any death (baseline survival time: 48 hours after first electrocardiogram; 640 patients) was 19.2% in the delayed treatment group and 10.7% in the immediate treatment group (p = 0.0022). Also the probability of cardiovascular mortality was significantly lower in the immediate ß-blocker treatment group (immediate treatment group: 9 (5.2%); delayed treatment group: 30 (13.4%); p = 0.0002). Multivariable Cox regression analysis identified immediate ß-blocker therapy to be independently protective against death of any cause (odds ratio: 0.55, p = 0.033). CONCLUSION: Immediate ß-blocker administration in the emergency setting is associated with a reduction of all-cause and cardiovascular mortality in patients with ST-segment elevation myocardial infarction and seems to be superior to a delayed ß-blockade in our patient cohort.

Prehospital treatment of patients with acute myocardial infarction with bivalirudin.

OBJECTIVES: Patients with acute myocardial infarction are at high risk of dying within the first hours after onset of coronary ischemia. Therefore, pharmacological intervention should be started in the prehospital setting. This study investigates the effect of the prehospital administration of bivalirudin on short-term morbidity and mortality compared to heparin plus abciximab in patients with ST-segment-elevation myocardial infarction (STEMI). METHODS: One hundred ninety-eight patients with STEMI treated with bivalirudin in the prehospital setting were prospectively collected. Coronary angiography was performed to identify the infarct-related artery. In case of a percutaneous coronary intervention, bivalirudin was given according to the guidelines. The historic control group consisted of 171 consecutive patients from the same myocardial infarction network treated with unfractioned heparin and abciximab administration before the admission to the emergency department of the percutaneous coronary intervention center. The primary outcome parameter was the incidence of major adverse cardiac events (recurrent myocardial infarction, stroke, death, target vessel revascularization for ischemia) within 30 days after the primary event. RESULTS: The overall rate of major adverse cardiac events was significantly lower in the bivalirudin group compared to the abciximab group (7.6% vs 14.6%; P = .04). The number of major bleedings was significantly higher in the abciximab group compared to the bivalirudin group (11.8% vs 3.8%; P = .03). CONCLUSIONS: The use of bivalirudin in the prehospital setting leads to a reduced rate of major cardiovascular events compared to a standard treatment with abciximab plus heparin. Bivalirudin is a reasonable choice of treatment in the prehospital setting for patients with STEMI.