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Aims: The prognosis of advanced cardiac light-chain amyloidosis is poor. Heart transplantation might enable causative therapy and ultimately improve prognosis., Methods and Results: Nineteen patients with cardiac amyloidosis but no obvious involvement of other organs were scheduled for heart transplantation. Four to 6 months later, high-dose melphalan chemotherapy and autologous stem cell transplantation (HDM-ASCT) was planned in patients not in complete remission. Seven of nineteen patients died while waiting for heart transplantation. The remaining 12 patients (complete remission, n = 4) underwent surgery. Chemotherapy in patients not in complete remission consisted of HDM-ASCT (n = 5/12; subsequent complete remission, n = 2; partial remission, n = 3) or melphalan-prednisolone (partial remission, n = 1). Two of twelve patients were ineligible for any chemotherapy. Three of twelve patients died [423.5 (105-2131) days] from progressive disease, relapse, or sepsis. The 1- and 3-year survival rates were 83 and 83%, respectively, similar to those of patients undergoing heart transplantation for standard indications. Corresponding survival rates stratified by haematological response were 100 and 100% for complete remission (partial remission, 100 and 100%; progressive disease, 0 and 0%)., Conclusion: Heart transplantation in advanced cardiac amyloidosis is a promising approach to interrupting the vicious circle of ineligibility for potential curative chemotherapeutic treatment and extremely poor prognosis of cardiac amyloidosis without chemotherapy. Highly urgent heart transplantation combined with subsequent HDM-ASCT appears to offer a successful treatment option to improve the poor outcome of cardiac amyloidosis. However, it should be restricted to highly selected patients in specialized centres.

Introduction: The purposes of this study are to identify a patient cohort that would benefit from the use of mechanical circulatory support (MCS) in the presence of the Eurotransplant high-urgency (HU) program., Methods: Sixty-five patients (heart transplantation (HTx) group, 77%) underwent heart transplantation and 17 patients (D group, 20%) died while on the HU waiting list. These 82 patients were included in this retrospective study., Results: The mean waiting time on HU list was 18.3+/-17.7 days in HTx group and 12.5+/-9.4 days in D group (p=0.075). The average weekly allocation rate from the active HU list was 27.7%, and the mean weekly waiting-list mortality was 12.1%. The use of intra-aortic balloon pumping (p=0.005), mechanical ventilation (p=0.007), higher dose of dobutamine (0.005), lower serum level of sodium (p=0.046), and higher serum level of C reactive protein (CRP) (0.040) at the registration of HU listing were associated with waiting-time mortality, and the serum creatinine level more than 1.5mg/dl (p=0.007, odds ratio; 14.5, 95% CI; 2.1-102.0) and the serum CRP level more than 10mg/l (p=0.026, odds ratio; 6.3, 95%CI; 1.2-31.4) were identified as significant predictors., Conclusion: It would be appropriate that a patient who would not be able to tolerate one or two weeks waiting time to be considered as a candidate for MCS implantation in the presence of the HU program. The patient selection criteria for MCS implantation should include not only hemodynamic parameters, but also the aspect of a beginning multi-organ failure.

Background: Cardiac amyloidosis (CA) is the most problematic cause of heart failure because medical treatment strategies are not well tolerated. Due to its high mortality, identification of patients at high risk is crucial for treatment strategies such as heart transplantation prior to chemotherapy for amyloid disease., Methods: Left ventricular wall thickness (LVT) progression was retrospectively compared with electrocardiographic and echocardiographic parameters for risk prediction in 39 patients with histologically proven cardiac amyloidosis., Results: Seventeen deaths occurred, equivalent to 1- and 3-year survival rates of 62.1% and 55.0%, respectively. LVT progression in deceased patients was 2.02 +/- 0.85 mm/month compared with 0.19 +/- 0.03 mm/month in survivors (p < 0.001). Autologous stem-cell transplantation (n = 22, or 54%) reduced LVT progression as compared with not receiving stem cells (0.21 +/- 0.04 mm/month vs 1.45 +/- 0.57 mm/month, p < 0.005). LVT progression correlated with maximal LVT and absolute LVT increase. Progression of LVT was more rapid in patients with impaired LV ejection fraction (LVEF) than preserved LVEF (2.16 +/- 1.04 mm/month vs 0.30 +/- 0.13 mm/month, p < 0.001). LVT closely correlated with survival, whereas initial, maximum or absolute increase in LVT did not. Further predictors of survival were LVEF, autologous stem-cell transplantation and low voltage, but not diastolic dysfunction. Multivariate analysis identified LVT progression as the strongest independent parameter for survival., Conclusions: LVT progression is a powerful risk predictor in light-chain CA, superior to parameters such as LVEF, LVT or a low-voltage pattern. Improved survival by high-dose chemotherapy and stem-cell transplantation is paralleled by a reduction in LVT progression. Repetitive echocardiographic assessment appears indicated in CA patients to identify candidates for heart transplantation in amyloidosis.

We investigated tolerability and efficacy of ezetimibe treatment (10 mg/d) in 25 heart allograft recipients already on stable statin therapy. Total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), triglycerides (TG), immunosuppressant drug levels, laboratory and clinical parameters were assessed before, four months and one yr after initiation of ezetimibe treatment. Mean equivalent statin dose was 53.5 ± 12.3 mg of pravastatin, remaining unchanged throughout the study period. Ezetimibe was generally well tolerated, only two patients (8%) discontinued ezetimibe due to stomach pain or headache. Mean TC decreased from 231.8 ± 6.4 mg/dL before therapy to 202.2 ± 8.8 mg/dL after four months and 192.9 ± 7.0 mg/dL after one yr (p < 0.001). Mean LDL-C decreased from 143.1 ± 5.4 mg/dL to 121.4 ± 7.9 mg/dL (month 4; p < 0.05) and 107.1 ± 5.6 mg/dL (one yr; p < 0.001). TG decreased from 182 ± 14.3 mg/dL to 173.3 ± 17.5 mg/dL after one yr (p < 0.05), whereas HDL-C was unchanged. Initial LDL-C and cardiac diagnosis before transplantation were identified as predictors of absolute LDL-C reduction. Immunosuppressant drug doses and blood concentrations were unchanged as well as other laboratory and clinical parameters. Ezetimibe appears safe and effective for further reduction of TC and LDL-C in heart allograft recipients already on stable statin therapy. Extent of pre-treatment LDL-C and cardiac disorder prior to transplantation appear to correlate with the efficacy of ezetimibe therapy. [ABSTRACT FROM AUTHOR]

Background. Cardiac involvement in light-chain amyloidosis (AL) frequently results in heart failure with dyspnoea. In heart failure due to ischemic or idiopathic etiology, respiratory muscle dysfunction and ventilatory inefficiency contribute to symptoms and are independent prognostic predictors. However, in patients with AL, respiratory muscle function has not been elucidated. Methods. In 46 consecutive male patients with AL, lung function, maximal inspiratory (Pimax) and expiratory (Pemax) mouth occlusion pressures, cardiopulmonary exercise testing, echocardiography, and cardiac biomarkers were prospectively studied. Results. Pimax and Pemax were reduced, P0.1 did not differ between controls and AL. Pimax and Pemax were reduced in AL with congestive heart failure compared with asymptomatic patients (median (range) 5.4 (2.3-12.4) kPa vs 10.4 (6.5-14.0) kPa; p . Respiratory muscle weakness occurred in systolic and diastolic LV dysfunction. Pimax was associated with peak exercise oxygen uptake, respiratory inefficiency, wall thickness, and N-terminal pro-brain natriuretic peptide. Conclusions. Respiratory muscle dysfunction and ventilatory inefficiency correlates well with intraventricular septum thickness and peak oxygen uptake and are present even in patients with diastolic dysfunction. Respiratory muscle dysfunction might contribute to dyspnea and exercise limitation and appears to represent a marker of cardiac impairment even in diastolic heart failure. Further studies of Pimax as a potential non-invasive prognostic marker are needed. [ABSTRACT FROM AUTHOR]

A 63-year-old Caucasian male, diagnosed with dilated cardiomyopathy in 1993, remained clinically stable for several years. In 2003, a marked increase of N-terminal pro-natriuretic peptide serum level (611 ng/ml to 4926 ng/ml) was observed; left ventricular (LV) septum thickness was 10 mm. In addition, sensorimotor polyneuropathy and autonomic dysfunction occurred. Further progression of heart failure occurred despite unchanged systolic LV function. Endomyocardial biopsy in 2006 revealed transthyretin amyloidosis by Congo red and immunohistochemical staining, as well as Val94Ala substitution by transthyretin gene analysis. Cardiac amyloid deposition was quantified by technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy. Mutational search of the relatives (n = 1) was unremarkable. The transthyretin Val94Ala mutation is characterized by sensorimotor polyneuropathy, autonomic dysfunction, and gastrointestinal and cardiac involvement with amyloid. This mutation is an addition to the growing spectrum of transthyretin mutations with late onset of clinical symptoms, but noteworthy because of progressive, finally disabling disease course. Final clinical assessment of severity of cardiac involvement in the present patient is rendered complex by possible concomitant or preceding idiopathic dilated cardiomyopathy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Patients with cardiac amyloidosis (CA) have increased mortality. Aims: Clinical, electrocardiographic, and echocardiographic parameters were assessed for risk-stratification of CA. Methods and results: CA was confirmed by endomyocardial biopsy in 59 patients (54.8±1.2 years) with light-chain (n = 43) or transthyretin amyloidosis (n = 16). Six patients without CA served as controls (NCA). Clinical symptoms, electrocardiographic, and echocardiographic parameters were analyzed for prognostic significance. Of the patients with light-chain amyloidosis, 14 died and 2 underwent heart transplantation. 1-/3-year survival was 68%/63%. Survival depended on left ventricular function (LV-EF), LV mass, radius/wall thickness, septum thickness, low voltage pattern (LVP), conduction delay, NYHA class, and stem cell transplantation. A multivariate model only contained LV-EF and LVP; the beneficial effect of stem cell transplantation was cancelled out as this treatment was withheld in patients with highest cardiac risk. Survival was most limited if both risk factors occurred. Cardiac involvement in transthyretin amyloidosis showed better survival (2 deaths, 1-/3-year survival 91%/83%). Analysis of prognostic risk factor utility in all amyloid patients (light-chain and transthyretin) again revealed LVP and LV-EF, and aetiology of amyloidosis as independent survival parameters. Conclusion: Prognosis of CA is poor, but aetiology of amyloid, LVP, and LV-EF allows identification of patients at highest risk of death, who may require individual treatment approaches (heart transplantation prior to causative therapy). [Copyright &y& Elsevier]

Abstract: Objective: Cardiac amyloidosis (CA) is associated with a poor prognosis and a survival rate of less than 30% 2 years after clinical manifestation. Considered as a semi-malignant disease, CA is often a contraindication for HTx; however, depending on the type of CA, there are excellent treatment regimes that can be combined with HTx. In AL-amyloidosis, chemotherapy and stem cell transplantation are necessary and in TTR-amyloidosis, where the liver is the source of the pathologic protein, liver transplantation is recommended after HTx. Methods and Results: More than 60 patients with AL-amyloidosis and more than 25 patients with ATTR-amyloidosis have been investigated at our centre. Eighteen patients showed signs of end-stage heart failure. Four patients died within 1 month after listing for HTx. Seven patients with AL (mean age 41.8 years) and five patients with ATTR-amyloidosis (mean age 42.6 years) were successfully transplanted with an actual survival rate of 91.6%. One patient died 8 months after HTx due to infection. Five AL patients received chemotherapy and SCT and one ATTR patient was liver transplanted. Three AL patients showed complete remission of amyloidosis. Conclusions: Cardiac amyloidosis is a potentially curative disease after HTx when combined with either chemotherapy and SCT or LiverTx depending on the type of the amyloidosis. Due to the natural course of the disease, urgent HTx after cardiac manifestation is mandatory. With this approach, excellent survival rates and even remission of the underlying disease is possible. [Copyright &y& Elsevier]