Amyloid Cardiomyopathy Patients Research Articles

Prognostic Utility of Left Atrial Strain to Predict Thrombotic Events and Mortality in Amyloid Cardiomyopathy

BackgroundThere is currently no thromboembolic risk stratification tool for amyloid cardiomyopathy (ACM) and the current survival staging systems for ACM have only modest discriminatory ability. ObjectivesThis study aims to evaluate the prognostic value of left atrial (LA) strain to predict incident thrombotic event (TE) and improve survival staging systems in ACM. MethodsThe authors identified patients with light chain (AL) or transthyretin (ATTR) ACM and no history of atrial fibrillation (AF) at diagnosis. Three components of LA strain (reservoir, conduit, and contractile) were measured and their predictive value for TE and mortality was determined. In addition, the authors evaluated the incremental utility of adding LA strain to current prognostic staging systems. ResultsThe authors included 448 patients (50.2% AL; 49.8% ATTR) with median follow-up of 3.8 years. There were 64 (14.3%) TE cases, 103 (23%) AF cases, and 234 (52.2%) deaths. Notably, 75% of TEs occurred without preceding AF documented. LA strain reservoir and LA contractile strain significantly predicted both events: HRs for TE were 2.22 (95% CI: 1.27-3.85; P = 0.006) and 2.63 (95% CI: 1.25-5.00; P = 0.01) per SD decrease in LA strain reservoir and LA contractile strain, respectively. The respective HRs for mortality were 1.32 (95% CI: 1.09-1.59; P < 0.001) and 1.49 (95% CI: 1.22-1.75; P < 0.001). Also, LA strain reservoir and LA contractile strain significantly improved the C-statistics of the Mayo AL staging from 0.65 to 0.68 and 0.70, respectively (P ≤ 0.02); Mayo ATTR staging (0.73 to 0.79 and 0.80, respectively; P < 0.001); and Gillmore ATTR staging (0.70 to 0.79 and 0.80, respectively; P < 0.001). ConclusionsLA strain identifies ACM patients with high thrombotic risk (independent of AF) and improves current ACM-specific survival staging.

Trends and Outcomes of Patients With Amyloid Cardiomyopathy Listed for Heart Transplantation.

Heart transplantation in patients with amyloid cardiomyopathy (ACM) has been historically underused owing to the risk of amyloid recurrence. Using data from the United Network for Organ Sharing database on patients listed for single-organ heart transplant between 2010 and 2019, we evaluated trend in heart transplant and compared waitlist mortality and graft survival between patients with ACM and dilated cardiomyopathy (DCM). Also, we evaluated for independent predictors of outcomes. Over the study period, 411 adult patients with ACM were added to the heart transplant waitlist. In the propensity-matched cohorts, the rates of waitlist mortality were significantly higher for ACM compared with DCM (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.16-2.65). Over the study period, 330 patients with ACM underwent heart transplant. The number of transplants increased from 22 in 2010 to 59 in 2019 (168% increase). The 5-year graft survival rate was, however, significantly worse for ACM (78%) compared with DCM (82%) (HR,1.46, 1.03-2.08). We identified 2 predictors of graft failure among patients with ACM: namely, renal failure requiring dialysis (HR, 5.4, 1.6-17) and previous history of malignancy (HR, 1.6, 1.0-28). Patients with ACM with neither risk factor had 5-year graft survivals of 82%, which is comparable with DCM (HR, 1.28, 0.90-1.91). On the other hand, patients with ACM and either risk factor had worse 5-year graft survivals of 62% (HR, 2.44, 1.39-4.28). Increasing numbers of patients with ACM are undergoing heart transplants. Although patients with ACM experience higher waitlist mortality and worse graft survival compared with DCM, selecting carefully screened ACM patients may result in improved outcomes following heart transplant.

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy

Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM. We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30). In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.

Abstract 15821: Patients With Amyloid Cardiomyopathy Who Receive Durable Mechanical Circulatory Support Are at Increased Risk for Mortality and Early Adverse Events

Introduction: Amyloid cardiomyopathy (ACM) is recognized increasingly as a cause of advanced heart failure. There are limited data describing clinical outcomes for ACM patients who receive durable mechanical circulatory support (MCS). Methods: This analysis included adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with a primary diagnosis of dilated cardiomyopathy (DCM, N=19,921), non-amyloid restrictive cardiomyopathy (RCM, N=248), or ACM (N=48) who received durable MCS of any type or strategy from 2005-2017. We compared baseline characteristics and adverse events for the 3 groups. The primary endpoint was death with heart transplantation as a competing risk with follow-up censored at device explantation. Results: Patients with ACM (N=48) were older (61 y [IQR 55-69] versus 58 y [IQR 49-66] for DCM and 55 y [IQR 46-62] for non-amyloid RCM, P&lt;0.001), and more likely to be male (85% versus 79% for DCM and 63% for non-amyloid RCM, P&lt;0.001) and INTERMACS profile 1 (30% versus 18% for DCM and 21% for non-amyloid RCM, P=0.04) at implant. Use of biventricular support (concomitant left and right ventricular assist devices or total artificial heart) was highest in the ACM group (41% versus 7% and 19% for DCM and non-amyloid RCM groups, respectively, P&lt;0.001). ACM patients experienced a higher frequency of major bleeding (48% versus 29% for DCM and 34% for non-amyloid RCM, P=0.005), neurologic dysfunction (22% versus 10% for DCM and 14% for non-amyloid RCM, P=0.006), and renal dysfunction (20% versus 10% for DCM and 17% for non-amyloid RCM, P&lt;0.001) within 3 months. Risk of death at a median follow-up of 1 year was highest for the ACM group compared to DCM and non-amyloid RCM (Log-rank, P=0.014). Conclusion: Compared to DCM or non-amyloid RCM patients, those with durable MCS for ACM have the highest risk of early adverse events and lowest survival. These data highlight concerns with durable MCS for ACM.

Telehealth monitoring for hypertrophic cardiomyopathy and amyloid cardiomyopathy patients: lessons from the coronavirus disease 2019 lockdown in Italy.

To the Editor As a result of the coronavirus disease 2019 (COVID-19) lockdown imposed beginning on 9 March 2020, Italian hospitals were required to postpone or even halt outpatient visits deemed as nonurgent. Methods The Hypertrophic Cardiomyopathy (HCM) Outpatient Clinic at the Ospedale Policlinico San Martino, Genova, regularly follows patients affected by HCM and cardiac amyloidosis. At the beginning of the COVID-19 lockdown an already operating service for patients’ communications (via telephone and E-mail) was implemented, and each patient with a scheduled visit in the forthcoming weeks (up to 15 May 2020) was contacted by a medical trainee to assess urgency related to her/his medical evaluation. According to information collected via the telemedical contact, patients were divided into ‘stable’ (group-A) and ‘potentially unstable’ (group-B). Patients were deemed as ‘potentially unstable’ if one or more of the following were present: signs and/or symptoms of heart failure, in particular if worsening relatively to the precontact condition; known end-stage HCM; heart failure hospitalization(s) and/or more than three outpatients evaluations in the prior 6 months. Those in group-B received weekly telemedical contact to monitor their conditions. Results Forty patients (27 males, median age: 62 years) received a telecontact, of whom 28 were HCM and 12 were cardiac amyloidosis patients. Nineteen patients were deemed as ‘potentially unstable’ (10 cardiac amyloidosis and 9 HCM). The main reason for inclusion in group-B was a recent heart failure hospitalization. Characteristics of patients in group-A versus B are shown in Table 1. As of 7 May 2020 no patients in group-A sought medical attention outside the planned telemedical contacts, and none needed an outpatient visit or hospitalization. In group-B, eight patients needed unplanned medical attention. In four instances, their needs were managed via telecontact without the need for in-person evaluations: two cardiac amyloidosis patients needed optimization of diuretic therapy; two obstructive HCM patients needed optimization of therapy for relief of obstruction. In three other instances, a medical outpatient evaluation was required: two cardiac amyloidosis patients presented worsening heart failure symptoms, and one severely obese HCM patient presented a new-onset atrial fibrillation with high ventricular response. Finally, one cardiac amyloidosis patient required hospitalization due to acute decompensated heart failure.Table 1: Characteristics of patients according to group allocationComment In this series of cardiomyopathy patients managed during the COVID-19 lockdown in Italy, a strategy of telehealth monitoring was feasible and effective, at least in the short term, with even a subset of patients contacted via E-mail. Telemedical contact by trained staff was able to stratify patients in higher and lower heart failure risk. No unplanned medical contact was required by patients deemed at low heart failure risk; moreover, half of the unplanned medical contacts among those at high heart failure risk was managed via repeated telemedical evaluations. Though of course not generalizable to the whole HCM and cardiac amyloidosis cardiomyopathy population, our report may offer suggestions for future management of this increasing cohort of patients. Telemedicine interventions have shown a beneficial effect in the management of heart failure patients.1 In current COVID-19 times, telemedicine served as an emergency tool, yet lessons from its impact on healthcare may be exploited for the future.2 In the case of cardiomyopathies such as HCM or cardiac amyloidosis, telehealth monitoring may be useful, in particular for a specific subset of low-risk patients, such as genotype-positive-phenotype-negative relatives. However, strategies of telehealth monitoring have never been specifically assessed in the case of cardiomyopathies. Implementation of telehealth strategies in Cardiomyopathy Units may help adequate followup for all patients and, at the same time, allow a better allocation of resources for in-hospital visits. Many already available tools may be exploited for telehealth strategies, including: telephone-based follow-up, remote monitoring of devices, use of novel portable devices,3 web-based interactive platforms.4 Telehealth monitoring cannot replace in-hospital in-person medical evaluation, but may be a valid practice in the near future. Acknowledgements Conflicts of interest There are no conflicts of interest.

Cardiac Transplantation Outcomes in Patients with Amyloid Cardiomyopathy

Objective Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease characterized by abnormal proteinaceous deposits within the cardiac extracellular space. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Although the management for each entity is different, heart transplant (HT) remains the definitive treatment for patients who progress to end stage heart failure. To date there is no consensus regarding the usage of heart transplantation in patients with ACM, and studies have shown mixed results. In this study, we perform a contemporary multi-center analysis evaluating post HT survival in patients with ACM. Methods We conducted a multi-center analysis of 62588 adult HT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or Non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. Results 398 patients with a diagnosis of ACM were identified. ACM patients were older (61 vs 52 p= Conclusion In this analysis of HT in ACM, ACM was associated with a higher likelihood of post HT mortality. No differences were observed in episodes of treated rejection, hospitalization for infection or likelihood to return to work for income. Further analysis is warranted to establish the mechanism of higher mortality in ACM patients.

Outcomes of Acute Heart Failure in Patients with Amyloid or Sarcoid Cardiomyopathy: A 10 Year Nationwide Analysis

Background Ischemic Cardiomyopathy is the leading cause of heart failure in the United States. Restrictive cardiomyopathy etiologies like sarcoid and amyloid are less common causes of heart failure and in hospital outcome descriptions are scant across the literature. Purpose describe the outcomes of acute heart failure exacerbations in patients with sarcoid or amyloid cardiomiopathy Methods A retrospective analysis using the 2005-2014 United States Nationwide Inpatient Sample was performed. Patients above 18 years with primary diagnosis of acute heart failure (AHF), systolic heart failure (SHF) and diastolic heart failure (DHF) were included. Secondary diagnosis of Sarcoid Cardiomyopathy (SCM) or Amyloid Cardiomyopathy (ACM) was generated. End stage renal disease patients were excluded. Primary outcome was in-hospital mortality. Secondary outcomes included length of stay, cost of stay, shock, utilization of mechanical ventilation, acute kidney injury requiring dialysis (AKID), use of non-invasive ventilation (NIV), cardiac arrest, and short term mechanical circulatory support. Diagnoses were identified using ICD-9- CM codes . Multivariate logistic regression analysis adjusting for age, race, gender, hospital location was done using STATA 15. Results 2,821,201 patients with primary diagnosis of AHF were identified. In AHF cohort 2,893 patients had a history of ACM, corresponding to 42% patients with SHF and 58% patients with DHF. The SCM cohort was composed of 1,905 with AHF of which 83% had SHF and 17% had DHF. Mean age in ACM with AHF was 73 years. 63% were males. In the SCM, 52 % males with mean age of 53 years. ACM patients had increased mortality in the AHF(OR 2.5 p Conclusions In patients with AHF, mortality is increased in those with ACM compared to those without. SCM is associated with increased mechanical support use and development of shock

Outcomes After Heart Transplantation for Amyloid Cardiomyopathy in the Modern Era

We conducted a review of patients undergoing heart transplantation (HT) at our institution for amyloid cardiomyopathy (ACM) between 2008 and 2013. Complete follow-up was available for all patients. Nineteen patients with ACM underwent HT during the study period, accounting for 9.4% of all HT performed at our institution during this period. Amyloid subtype was light chain (AL) in 9 patients and transthyretin (ATTR) in 10 (2 wild-type, 7 familial, 1 unknown). Eight of nine patients with AL amyloidosis began chemotherapy prior to HT, six have resumed chemotherapy since HT, and five have undergone autologous stem cell transplantation. Most recent free light chain levels in AL patients decreased by a median of 85% from peak values. Only one patient developed recurrent graft amyloidosis, occurring at 3.5 years post-HT and asymptomatic. After a median follow-up of 380 days, 17 (89.5%) patients are alive. To our knowledge, this is the largest single-center series reported of ACM patients undergoing HT in the modern era. Our results suggest that acceptable outcomes following HT can be achieved in the short-to-intermediate term and that this is a feasible option for end-stage ACM with careful patient selection and aggressive control of amyloidogenic light chains in AL patients.

Changing outcomes after heart transplantation in patients with amyloid cardiomyopathy

Amyloid cardiomyopathy (ACM) is associated with a poor prognosis. Previous reports have suggested unfavorable post-heart transplant (HT) survival in this population compared with other HT recipients. Data from the United Network for Organ Sharing (UNOS) registry were used to study outcomes among ACM patients undergoing HT in the modern era (Era 2, 2008 to 2013) as compared with the historical era (Era 1, 1987 to 2007). One hundred eighty-eight ACM patients underwent primary single-organ HT. Ninety-seven patients (51.6%) were transplanted in Era 1 and 91 (48.4%) in Era 2. ACM patients undergoing HT in Era 2 were older (p < 0.0001), had higher body mass index (p = 0.008) and longer ischemic times (p = 0.02), and were more likely to be African-American (p < 0.0001), UNOS Status 1A (p < 0.0001), male (p = 0.01) and highly sensitized (p < 0.0001) compared with those in Era 1. Compared with patients with other etiologies of restrictive cardiomyopathy (RCM; n = 339 in Era 1, n = 164 in Era 2), adjusted hazard ratios (HRs) for post-HT mortality of ACM were 2.08 (p < 0.0001) in Era 1 and 1.22 (p = not statistically significant) in Era 2. Adjusted HRs for mortality of ACM vs all other diagnoses (n = 36,334 in Era 1, n = 9,225 in Era 2) were 1.84 (p < 0.0001) in Era 1 and 1.38 (p = NS) in Era 2. Although post-HT survival did not change with time among non-ACM RCM patients, post-HT mortality was lower in Era 2 compared with Era 1 among ACM patients (HR 0.49, p = 0.03). Although historically associated with inferior survival, post-HT outcomes in ACM patients in the modern era are now approaching those of non-ACM patients. Changes in patients' demographics suggest that this may be related to improved patient selection, including an increased proportion of patients with transthyretin ACM. HT should be considered for appropriate candidates with ACM.

(418) - Changing Outcomes After Heart Transplantation in Patients with Amyloid Cardiomyopathy

(418) - Changing Outcomes After Heart Transplantation in Patients with Amyloid Cardiomyopathy