Prognosis Of Cardiac Amyloidosis Research Articles

Elevated Hepatocyte Growth Factor is Associated With Worse Prognosis in Cardiac Amyloidosis

Elevated Hepatocyte Growth Factor is Associated With Worse Prognosis in Cardiac Amyloidosis

Incidence, Diagnosis and Prognosis of Cardiac Amyloidosis

Background and ObjectivesCardiac involvement is frequent in systemic amyloidosis and is the most important determinant of the clinical outcome. The aims of this study were to assess the incidence and prognosis of cardiac amyloidosis and discuss the diagnostic issues related to cardiac amyloidosis.Subjects and MethodsWe retrospectively studied all patients diagnosed with systemic amyloidosis who presented to our institution from January 1999 to December 2011.ResultsOf the 129 patients with systemic amyloidosis, cardiac amyloidosis was diagnosed in 62 patients. At the 3 years' follow-up of the patients with systemic amyloidosis, there was a statistically significant difference in mortality between patients with cardiac amyloidosis and the rest of the patients (58.1% vs. 37.3%, p=0.008). In the Cox proportional hazard model, old age {hazard ratio (HR) 18.336, p=0.006}, elevation of cardiac troponin I (cTNI) (HR 13.246, p=0.020), left ventricular (LV) systolic dysfunction (HR 5.137, p=0.041) and diastolic dysfunction (HR 64.595, p=0.022) were independently associated with survival in cardiac amyloidosis. In the diagnosis of monoclonal gammopathy, serum or urine protein electrophoresis was not sensitive enough to be used clinically compared to serum free light chain assay (35.8% vs. 96.4%).ConclusionIn systemic amyloidosis, cardiac involvement was the most important determinant of the prognosis, and old age, elevation of cTNI, LV systolic dysfunction and diastolic dysfunction were independently associated with survival in cardiac amyloidosis.

Cardiac Amyloidosis Determines the Prognosis of Systemic Amyloidosis; Roles and Responsibilities of Cardiologist

Refer to the page 752-760 Cardiac amyloidosis is a prognostically critical condition, since it is a frequent cause of death in patients with systemic amyloidosis.1),2) Lee et al.3) reported, for the first time, describing systemic amyloidosis in Korea from the perspective of cardiologists. In this paper, the authors enrolled 129 systemic amyloidosis patients retrospectively from 1999 to 2011. They showed that cardiac involve was the major prognostic factor, and old age, elevation of cardiac troponin I (cTNI), left ventricular (LV) systolic dysfunction and diastolic dysfunction were independent prognostic factors in survival. All cardiac amyloidosis were confirmed to have cardiac involvement by well-established and uncontroversial criteria including mean left ventricular thickness over 12 mm and low voltage in electrocardiogram or pathologically-confirmed amyloid deposit in endomyocardial biopsy. These diagnostic criteria were closely related to poor outcome in systemic amyloidosis.3) The diagnosis and prognosis of cardiac amyloidosis still remains to be clarified, despite the development of more sensitive tools, such as delayed gadolinium enhancement (DGE) in cardiac magnetic resonance imaging (MRI) and cardiac biomarkers. In previous studies, when cardiac MRI was performed in all AL amyloidosis patients, DGE was found in 47% of the patients with normal LV wall thickness in echocardiography.4) Moreover, the level of NT-proBNP proved to be a better discriminating factor than the LV thickness (>12 mm) in echocardiography.5-8) But, it is still not clear whether we should suspect cardiac amyloidosis in patients with normal LV thickness in echocardiography or whether early diagnosis of cardiac amyloidosis improves the prognosis of the patients. Since AL type is the most common type of systemic amyloidosis, chemotherapy and autologous stem cell transplantation are the therapies of choice. As shown,3) the hematologic response in AL amyloidosis is important in improving survival.9) Without hematologic response, it is difficult to obtain the responses in other organs. Likewise, in this paper, cardiac amyloidosis patients with better response to chemotherapy showed better survival compared to the patients with a lesser response.3) Many AL amyloidosis patients achieve hematologic response with high dose of melphalan and dexamethasone therapy or autologous hematologic stem cell transplantation.10) Additionally, bortezomib-based chemotherapy can be applied to achieve hematologic response in patients without hematologic response through melphan-based chemotherapy or autologous stem cell transplantation. Therefore, there is a significant limitation in this retrospective study. The authors did not show data regarding the benefit of additional chemotherapy in patients who had no hematologic response. In the meantime, active assessment of chemotherapy response and effort to achieve hematologic response cannot be overemphasized in the treatment of AL cardiac amyloidosis. To accurately assess multi-organ involvement and treat systemic amyloidosis, an interdisciplinary approach of cardiology, hematooncology, nephrology, pathology, and laboratory medicine and more is needed. Considering that cardiac involvement is a major prognostic factor in systemic amyloidosis, cardiologists have a great responsibility and may play a pivotal role.

Hypointense T2 signal predicts worse prognosis in cardiac amyloidosis

Methods We prospectively investigated 36 patients with biopsyproven amyloidosis in a 1.5 T scanner. Amyloidosis type was AL in 32, AA and TTR in 2 cases, each. We obtained SSFP-based long axis cine loops and T2-weighted triple inversion fast spin echo images in short axis (slice thickness 20 mm, TE 64 ms, TR = 2 RR), followed by inversion recovery gradient echo images after 0.2 mmol/kg bw GdDTPA. LV mass, volume, ejection fraction and left atrial area were measured based on biplanar long axis images. T2 ratio was computed as myocardial over skeletal muscle signal intensity in the same image to exclude effects of heart rate. Late enhancement images were evaluated visually for the presence of hyperintense lesions. Outcome was confirmed by chart review and contact of the referring clinician. Results were compared between surviving and deceased patients. In Kaplan-Meyer and Cox regression analysis we tested the predictive value for survival.

Cardiovascular magnetic resonance and prognosis in cardiac amyloidosis.

BackgroundCardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study.Materials and methodsThe pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE).ResultsPatients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205).ConclusionIn cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden.

Non‐invasive predictors of survival in cardiac amyloidosis

Patients with cardiac amyloidosis (CA) have increased mortality. Clinical, electrocardiographic, and echocardiographic parameters were assessed for risk-stratification of CA. 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. 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).

Improvement of Cardiac Diastolic Function and Prognosis After Autologous Peripheral Blood Stem Cell Transplantation in AL Cardiac Amyloidosis

AL amyloidosis is a disease in which immunoglobulin L chain is deposited in multiple organs, and the prognosis of cardiac amyloidosis is extremely poor. Although several treatments based on that for multiple myeloma, have been performed, there is no clear evidence that cardiac function is improved. We report a case of AL cardiac amyloidosis with moderate cardiac dysfunction for which we performed autologous peripheral blood stem cell transplantation (auto-PBSCT) in combination with high-dose melphalan therapy. This treatment resulted in significant improvement in cardiac function and good prognosis for about 3.5 years after the diagnosis. Therefore, auto-PBSCT is a possible option as up-front therapy for AL cardiac amyloidosis.

Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis. A Doppler echocardiography study.

We have previously characterized the left ventricular diastolic filling abnormalities in cardiac amyloidosis by Doppler methods. The various filling patterns were shown to be related to the degree of cardiac amyloid infiltration. The purpose of this study was to determine the value of Doppler diastolic filling variables for assessing prognosis in cardiac amyloidosis. We performed pulsed-wave Doppler studies of the left ventricular inflow and obtained clinical follow-up data in 63 consecutive patients with biopsy-proven systemic amyloidosis. All patients had typical echocardiographic features of cardiac involvement. The patients were subdivided into two groups according to deceleration time: Group 1 (33 patients) had a deceleration time of 150 msec or less, indicative of restrictive physiology, and group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63 patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were from group 1. The 1-year probability of survival in group 1 was significantly less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis revealed that the combination of the Doppler variables of shortened deceleration time and increased early diastolic filling velocity to atrial filling velocity ratio were stronger predictors of cardiac death than were the two-dimensional echocardiographic variables of mean left ventricular wall thickness and fractional shortening. Doppler-derived left ventricular diastolic filling variables are important predictors of survival in cardiac amyloidosis.