Cardiac AL Amyloidosis Research Articles

Sustained ventricular arrhythmia and sinus node dysfunction revealing a cardiac amyloidosis: A case report

Amyloidosis is an infiltrative multisystem disease due to extracellular deposition of fibrils in tissues and organs. Cardiac involvement can result in progressive heart failure, conduction abnormalities and arrhythmias and is associated with a poor prognosis. Atrial arrhythmias and non-sustained ventricular arrhythmias are the most common arrhythmias in cardiac amyloidosis. However, the association of sinus node dysfunction and sustained ventricular arrhythmia is quite exceptional. A 59-year-old male patient was admitted with a gradually worsening dyspnea with a lipothymic discomfort. Upon emergency department, an initial electrocardiogram revealed a severe bradycardia related to a sinus node dysfunction. A transthoracic echocardiography and cardiac magnetic resonance imaging showed features suspicious for cardiac amyloidosis. The diagnosis of AL cardiac amyloidosis with multiple myeloma was confirmed based on histological evidence. During hospitalization, the patient presented a sustained unstable ventricular tachycardia which has been converted by electrical cardioversion. He was treated with an implantable cardioverter-defibrillator (ICD) for secondary prevention with one episode of appropriate therapy. Unfortunately, the patient died few weeks later. The AL subtype of cardiac amyloidosis is associated with higher rates of arrhythmias, especially VT. The management of arrhythmias in cardiac amyloidosis is complex and remains challenging given the lack of evidence. ICD was not associated with longer survival; these findings underscore the importance of careful patient selection for ICD. As prognosis improves with the advances made in the medical treatment of cardiac amyloidosis, further studies are required to guide the management of all types of arrhythmias in cardiac amyloidosis.

1-Year Results from a Phase 2 Study to Determine Safety and Tolerability of Treating Patients with Light-Chain (AL) Amyloidosis with Cael-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia

Background: Light-chain (AL) amyloidosis is a rare, systemic disease caused by plasma cell dyscrasia (PCD). Excess immunoglobulin light chains misfold and form insoluble amyloid fibrils that deposit in organs, primarily the heart. Survival depends largely on the extent of heart involvement. Current therapies target PCD to halt fibril formation but do not treat existing fibril deposited in organs. CAEL-101 is a novel, investigational, potentially first-in-class therapy designed to remove amyloid fibrils from organs. Safety, tolerability, and biomarker data after all patients with AL amyloidosis enrolled in the trial received 1 year of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab, are presented. Methods: Adult patients with AL amyloidosis (European Modification of Mayo Stage I-IIIa) and measurable hematologic disease were eligible for this ongoing, open-label, phase 2 study (NCT04304144). Other forms of amyloidosis and multiple myeloma were excluded. CAEL-101 ≤1000 mg/m2 is administered every other week with anti-PCD therapy as directed by the investigator. In addition to safety assessments, cardiac and renal response were assessed by change over time in N-terminal pro-brain natriuretic peptide (NT-proBNP) and proteinuria, respectively. Results: Patients (n = 25; mean age 65 years; 72% male) with Mayo Stage I (8%), II (76%), and IIIa (16%) AL amyloidosis were treated with CAEL-101 for 1 year at this analysis. Patients presented with cardiac involvement (n = 22), renal involvement (n = 9, reported from one site), and prior anti-PCD therapy (n = 20). All 25 patients experienced treatment-emergent adverse events (TEAEs), and 6 (24%) experienced at least possibly treatment-related TEAEs. Five patients discontinued for non-treatment-related reasons (Table). Fifteen (60%) patients experienced TEAEs of Grade ≥3 severity and 13 (52%) experienced ≥1 serious adverse event (SAE). The most common TEAEs were nausea (n = 10), constipation or fatigue (n = 9 each), anemia, insomnia, or diarrhea (n = 8 each), and dizziness, cough, or rash (n = 7 each). After 1 year of CAEL-101 treatment of the 22 cardiac evaluable patients (baseline NT-proBNP ≥332 pg/mL), 10 (46%) patients experienced ≥30% NT-proBNP decrease from baseline, 4 (18%) were stable (±30% change from baseline), and 3 (14%) showed disease progression (≥30% NT-proBNP increase from baseline); data for 5 patients were missing. Of the 9 renal evaluable patients from a single site as reported by the investigator, 8 showed ≥30% decrease from baseline in proteinuria. Conclusions: The long-term safety evaluation of CAEL-101 continues in this study. All patients currently enrolled have been treated for at least 1 year. At this 1-year time point, CAEL-101 has been generally well tolerated without evidence of organ toxicity. Organ response persisted even after cessation of anti-PCD treatment. Most TEAEs were mild to moderate. A phase 3 program has commenced to elucidate the efficacy and safety of CAEL-101 in cardiac AL amyloidosis European Modification Mayo Stages IIIa and IIIb. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 11818: Daratumumab Containing Regimens Improved Survival in Patients With Light-Chain Cardiac Amyloidosis

Background: Immunoglobulin light-chain (AL) amyloidosis is a lethal condition resulting from misfolded immunoglobulin ALs produced by clonal CD38-positive plasma cells. Daratumumab, an anti-human CD38 monoclonal antibody, led to higher frequencies of complete hematologic responses and better clinical outcomes compared to conventional treatment. Therefore, daratumumab-containing regimens has become the standard of care in patients with systemic AL amyloidosis and multiple myeloma. This study sought to evaluate the survival benefit of daratumumab-containing regimens in patients with AL cardiac amyloidosis. Methods and Results: We examined 65 consecutive patients with AL cardiac amyloidosis (mean age: 67.2±10.4 years old, male: 69%) who underwent chemotherapy. We divided the patients into two groups, daratumumab group (n=32: treated with daratumumab containing regimens within the first two lines of chemotherapy) and conventional treatment group (n=33). Compared to conventional treatment group, daratumumab group tended to be older (69.2±9.6 vs. 65.2±11.0; p=0.12), while no significant differences in biomarkers and echocardiographic parameters were observed. A total of 26 patients (40%) were deceased (median follow up period: 395 days). Kaplan-Meier survival curves showed that daratumumab group had significantly lower mortality compared to conventional treatment group (p=0.04; log-rank test; Figure). Cox hazard analysis revealed that daratumumab containing regimens were associated with lower mortality after adjustment for revised Mayo staging system for AL amyloidosis (hazard ratio: 0.32; 95% confidence interval: 0.12 to 0.85; p=0.02). Conclusion: Daratumumab containing regimens might be associated with improved survival in AL cardiac amyloidosis.

Abstract 13845: Atrial Fibrillation in Patients With Biopsy-Proven Cardiac Al Amyloidosis; A Cancer Center Experience

Introduction: Atrial fibrillation (AF) is common in cardiac amyloidosis and often symptomatic. Commonly used therapeutics may be poorly tolerated. Patients with cardiac AL amyloidosis carry a high risk of stroke and bleeding, making anticoagulation challenging. This study examined the incidence of AF, treatment patterns, and incidence of thrombotic or bleeding complications. Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at a tertiary cancer center between 6/2011 and 6/2020 were identified. Demographic and clinical data were abstracted. Outcomes included the development of AF, stroke and bleeding. Severe bleeding was defined as intracranial bleeding, hemorrhagic pericardial tamponade, or bleeding requiring endoscopic investigation. Results: Out of 43 patients with cardiac AL amyloidosis, 51% were diagnosed with AF during the follow up period (median 4.2 years (95% CI, 2.8-8.6)). Of those, 41% were women and 73% were white. Median age was 65.5 years (61-70). No significant demographic differences were identified between patients with and without AF. Beta-blockers were initiated in 86% and continued for more than 3 months in 59% of patients. Amiodarone was initiated in 50% and continued for more than 3 months in 18%. Treatment with digoxin and diltiazem were less common (27% and 14%, respectively). Pulmonary vein isolation was performed in 14% of patients. Anticoagulation (AC) was used in 59% of patients with AF and 19% of patients without AF for a different indication. Bleeding was common; 23% of AF patients reported an episode of severe bleeding, 60% of whom were on AC, in comparison to 19% in patients without AF, 50% of whom were on AC. Stroke was diagnosed in 14% of patients with AF, 67% of whom received AC, compared to 14% of patients without AF, 33% of whom received AC. Conclusions: Although AF is common (51%) in patients with cardiac AL amyloidosis, treatment with rate or rhythm control strategies is challenging. Many patients do not tolerate treatment for more than 3 months. While a significant number did not receive AC, there was a substantial risk of severe bleeding (1/4) and stroke (1/7). Given improved survival with newer therapies for AL amyloidosis, a greater focus on improving management of AF and outcomes is needed.

Abstract 14545: Extramedullary Plasmacytoma of Tonsil Presenting as Cardiac Amyloidosis

Introduction: AL amyloidosis is a systemic disease characterized by the deposition of misfolded immunoglobulin light chains produced from clonal plasma cells in multiple organs of the body causing its dysfunction. We present you an unusual case of AL cardiac amyloidosis in a patient with extramedullary plasmacytoma of the tonsils. Case Presentation 61-year-old female presented with dyspnea on exertion with NT-proBNP elevated to 1439 pg/ml. CXR showed increased pulmonary vascular congestion. The patient was started on IV furosemide 40 mg BID with good urine output. Transthoracic echocardiogram revealed left ventricular hypertrophy with an ejection fraction of 60-65% with a global longitudinal strain of -9.0% and regional longitudinal strain reduced in the basal and mid-left ventricular segment but preserved in apical segment consistent with infiltrative cardiomyopathy. The patient underwent a nuclear (nuclear technetium pyrophosphate) scan of the heart consistent with cardiac amyloid deposition. She also was noted to have increased tonsillar mass which was biopsied. In the hospital, the patient had a cardiac arrest with the initial rhythm being ventricular fibrillation. The patient received 6 rounds of shock, and multiple injections of epinephrine, amiodarone, and bicarbonate push. The patient died despite all efforts of resuscitation. Histopathology results of tonsillar mass were consistent with plasmacytoma with amyloid deposition on Congo-red stain. Lambda: Kappa ratio was 70:1. Discussion: In cardiac amyloidosis, light chain deposits between cardiac myocytes disrupt cell-cell interaction. It can present as restrictive cardiomyopathy, conduction system abnormalities, or sudden cardiac death. It is essential to diagnose cardiac amyloidosis earlier. If untreated, the median survival of patients with cardiac AL amyloidosis is 6 months from the onset of heart failure. Conclusion: Our case was unusual in which a rare tumor of tonsils had plasma cell tumor which led to cardiac amyloidosis

Abstract 12022: Predictors of Mortality in Patients With Biopsy-Proven Cardiac AL Amyloidosis

Introduction: Cardiac involvement occurs in ~50% of patients with light-chain (AL) amyloidosis and conveys a poor prognosis. This study examined the role of histopathologic and echocardiographic parameters in predicting mortality. Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images were processed for longitudinal strain (global [GLS], apical, mid, basal) as well as radial and circumferential strain of the left ventricle (LV), right ventricle (RV) free wall, left atrium (LA), and right atrium, using the Epsilon EchoInsight Software. A detailed histomorphologic characterization of stored endomyocardial biopsy samples was performed by a cardiac pathologist and scored as < or > 5% AL deposits. Results: We identified 43 patients; 44% were women and 63% white. Median age was 65 years (IQR 59-70). Twenty-two (51%) underwent stem cell transplantation (SCT). A total of 29 patients (67%) died during follow up period (median follow up: 4.2 years (95% CI, 2.8-8.6)). Median overall survival (OS) was 18 months (95% CI, 8.1-37). Lower LA GLS and absence of SCT as a time-varying covariate were significantly and independently associated with increased risk of death in the multivariable cox regression analysis (HR 3.8, 95% CI 1.4-10.2 for LA GLS < 13.5 vs >13.5, p=0.008 and 0.20, 0.06-0.65 for SCT vs no SCT, p<0.001, respectively). Higher LV mass and lower RV TAPSE were associated with increased odds of having >5% of interstitial amyloid deposition on biopsy in the multivariable logistic regression analysis (OR 5.5, 95% CI 1.1-26.8 for >195.6g vs ≤195.6g, p=0.036 and 8.1, 1.2-54.3 for RV TAPSE<1.6cm vs ≥1.6cm, p=0.032, respectively). Conclusions: LA GLS < 13.5 was an independent predictor of mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be justified. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. This finding needs to be confirmed by larger studies in the era of contemporary systemic therapies. Although LV mass and RV TAPSE were associated with higher interstitial amyloid deposition, histopathologic parameters did not predict mortality in this cohort.

Abstract 13860: Heart Failure With Preserved Ejection Fraction Induced by Amyloid Light Chain Amyloidosis: A Case Report

Introduction: Cardiac amyloidosis is a clinical disorder defined as an extracellular deposition of protein in the heart. Typically, signs and symptoms of heart failure develop in the advanced disease. High index of suspicion is required for the diagnosis of this disorder. Results: A 62 years old male came to the cardiology clinic due to lower extremity edema, fatigue, dyspnea on exertion. He had a 3 month history of progressive lower leg edema. On physical examination he had a positive S4; lung sounds were diminished and there was dullness to percussion over the lower two thirds; and bilateral lower extremity edema. Hospital admission was decided for management of decompensated heart failure. On admission, the surface ECG showed normal sinus rhythm with low QRS voltage in the limb leads, a RBBB and LPFB. Initial laboratory reported elevated NT-proBNP: 13,816 pg/mL. Chest x-ray demonstrated right interstitial infiltration and bilateral pleural effusion. The echocardiogram revealed severe concentric hypertrophy of the left ventricle, an apical sparing left ventricle longitudinal strain, and an ejection fraction of 68%. A cardiac MRI showed concentric biventricular hypertrophy associated with extensive diffuse late gadolinium enhancement, suggestive of cardiac amyloidosis. Screening resulted in a Perugini score of 1 on Tc-PYP scintigraphy, elevated Kappa and Lambda light chains on serum, and kidney biopsy positive for amyloidosis. Hematology-oncology consultation was done and a daratumumab-CyBorD protocol was started. Conclusions: This case elucidated a stepwise diagnostic approach of cardiac amyloidosis in a patient presenting with signs and symptoms of heart failure. Amyloid AL cardiac amyloidosis and its repercussions are severe because it not only compromises by being infiltrative but also by its toxic capacity. A high index of suspicion and a multidisciplinary approach is needed in order to improve quality of life and prolong survival.

Speckle tracking echocardiography in plasma cell disorders: the role of advanced imaging in the early diagnosis of AL (Light Chain) cardiac amyloidosis

Abstract Introduction Cardiac involvement is described as the most important prognostic factor in light chain amyloidosis. An early diagnosis is mandatory to customize the follow-up timing and the best treatment. The aim of the study was to identify the role of advanced echocardiography in the diagnosis of amyloid light chain cardiac amyloidosis (ALCA). Material and methods Seventy-seven patients were prospectively included in the study: 22 patients with biopsy proven ALCA, 28 patients with multiple mieloma, and 27 with monoclonal gammopathy of undetermined significance. All patients underwent first and second level imaging including Speckle Tracking and complete biochemical profile. Univariate and Multivariate analysis was applied to the best multi-chamber predictor assessed with Receiver Operating Curve analysis. Continuous variables were discretized and compared with different subgroups based on multiparametric imaging assessment using available AL score. Results Biochemical indices have been confirmed as the best predictors of ALCA. More specifically, high sensitivity troponin (hsTn) and N-terminal pro brain natriuretic peptide (NT-pro-BNP) showed an AUC of 0.88 and 0.91 respectively. Among left ventricular systolic function parameters, left ventricular longitudinal strain (AUC: 0.92); apical sparing pattern (AUC: 0.75) and relative wall thickness (RWT) (AUC: 0.88) showed the best diagnostic accuracy. Atrial parameters such as left atrial volume index (LAVI) (AUC: 0.74), left atrial stiffness (LAS) (AUC: 0.82) and inter-atrial septum diameter (AUC: 0.75) showed a good diagnostic accuracy in ALCA (Figure 1). LAS and AL score maintained their diagnostic value in the multivariate model analysis (B=2,16; p=0,01 and B= 0,72; p<0.01 respectively). However, only LAS, with a cut off value of 0.65, was able to discriminate ALCA when AL score was not detrimental (P<0.001). Conclusion ALCA diagnosis often relies only on the biochemical profile. A comprehensive cardiac evaluation by a multiparametric imaging approach with LAS estimation is mandatory to ensure early diagnosis and a prompt treatment through a multidisciplinary team assessment. Funding Acknowledgement Type of funding sources: None.

Efficacy of bortezomib, cyclophosphamide and dexamethasone in cardiac AL amyloidosis.

Cardiac light chain (AL) amyloidosis is a condition with a very poor prognosis. We report a retrospective analysis comparing the traditional melphalan and dexamethasone protocol with cyclophosphamide, bortezomib and dexamethasone in late-stage cardiac AL amyloidosis. The primary end points were overall survival and haematological response. Both regimens provided meaningful responses in this difficult to treat patient group.

Feasibility of 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT in Light-Chain Cardiac Amyloidosis

BackgroundSystemic amyloid light chain (AL) amyloidosis is the most common type of amyloidosis, leading to cardiomyocyte necrosis and interstitial fibrosis. Gallium-68-labeled fibroblast activation protein inhibitor 04 (68Ga-FAPI-04) has recently been introduced for imaging fibroblast activation in cardiac diseases. To date, cardiac fibroblast and cardiac amyloidosis (CA) phenotype activities have not been mapped. ObjectivesThe aim of this study was to evaluate the feasibility of 68Ga-FAPI-04 positron emission tomography (PET)/computed tomography (CT) in assessing AL CA. MethodsThirty consecutive patients (mean age: 59.1 ± 7.7 years; 20 men, 10 women) with biopsy-proven AL amyloidosis were enrolled prospectively (including 27 with AL CA and 3 without AL CA). All patients underwent 68Ga-FAPI-04 PET/CT (107.4 ± 26.5 MBq). Global standardized uptake values and left ventricular (LV) molecular volume were calculated in correlation to echocardiography (n = 30), cardiac magnetic resonance (n = 18), and clinical biomarkers. Subsequently, the patients were categorized as having patchy (PET-patchy), extensive (PET-extensive), and negative (PET-negative) patterns. ResultsOf all patients, 80% (24 of 30) showed increased LV uptake (PET-patchy [n = 4] vs PET-extensive [n = 20]), whereas 6 patients did not show visible myocardial uptake. Standardized uptake value ratio and LV molecular volume were significantly higher in the PET-extensive than the PET-patchy group (2.79 mL ± 1.22 mL vs 1.53 mL ± 0.66 mL [P = 0.045] and 198.3 mL ± 59.97 mL vs 127.8 mL ± 25.82 [P = 0.005], respectively). Additionally, 68Ga-FAPI-04 uptake was significantly correlated with clinical biomarkers (Mayo stage and N-terminal pro–brain natriuretic peptide), interventricular septal thickness, left ventricular ejection fraction (LVEF), LV end-systolic volume, extracellular volume, and LV global strain (P < 0.05). Conclusions68Ga-FAPI-04 PET/CT is feasible in detecting myocardial fibroblast activation in patients with AL CA in correlation with myocardial remodeling. It might provide complementary information on cardiac molecular characterization and staging of disease.

Cardiovascular magnetic resonance in light-chain amyloidosis to guide treatment.

To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors. In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95-7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01). Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors.

Early cardiac response is possible in stage IIIb cardiac AL amyloidosis and is associated with prolonged survival

AbstractPatients with immunoglobulin light chain (AL) amyloidosis and stage IIIb cardiac involvement have a dismal outcome despite the introduction of novel treatments. However, a rapid hematologic response translates in better survival. We evaluated the impact of early cardiac response and its depth on outcome in 249 patients with newly diagnosed stage IIIb cardiac AL amyloidosis. Hematologic and cardiac responses were evaluated by intent to treat. After a median follow-up of 52 months, 219 (84%) patients died, and median survival was 4.2 months. The 30- and 90-day hematologic response rates were 22% (at least very good partial response [VGPR] in 9%) and 24% (at least VGPR in 15%), respectively. Early hematologic response resulted in better survival. At 90 days, 21 (8%) patients achieved a cardiac response (cardiac very good partial response [cardiac VGPR] in 12 cases and cardiac partial response [cardiac PR] in 9). At the 90-day landmark analysis, cardiac response resulted in longer survival (median, 54 months), also in those patients who have achieved at least VGPR (median, 62 vs 26 months, P = .011). Patients with cardiac VGPR had a longer survival than those with cardiac PR (median, 92 vs 24 months; P = .027), whereas patients without cardiac response had a poor survival (median, 6 months). A baseline difference of involved/uninvolved free light chains > 50 mg/L (odds ratio [OR], 0.21, P = .024) and a bone marrow plasma cell infiltrate > 10% (OR, 0.23, P = .040) were negative predictors of 90-day cardiac response. Early cardiac responses are rare but possible in stage IIIb AL amyloidosis and translate to longer survival.

Prognostic Implication of Longitudinal Changes of Left Ventricular Global Strain After Chemotherapy in Cardiac Light Chain Amyloidosis.

AimCardiac involvement is the main prognostic determinant in AL amyloidosis. We sought to determine the prognostic significance of longitudinal change of left ventricular (LV) global longitudinal strain (GLS) in cardiac light chain (AL) amyloidosis patients undergoing chemotherapy.Methods and ResultWe retrospectively investigated 117 cardiac AL amyloidosis patients who underwent chemotherapy from 2005 to 2019. All patients underwent comprehensive 2D conventional transthoracic echocardiography at baseline and after completion of first-line chemotherapy. Speckle tracking analysis of images was performed offline. Absolute value of LV GLS was expressed as [LV GLS] and change of [LV GLS] after chemotherapy was expressed as Δ [LV GLS]. Clinical outcomes including cardiac response and all-cause mortality were analyzed.Baseline clinical and echocardiographic parameters were similar in patients with and without CR. Δ [LV GLS] significantly differed between the CR and non-CR groups (0.4 ± 2.8% in the CR group vs. −0.6 ± 2.5% in the non-CR group, P-value = 0.046). Δ [LV GLS] showed satisfactory predictive performance for all-cause mortality (cut-off value = 0.8%, AUC 0.643, 95% CI [0.537–0.748]). Adding Δ [LV GLS] to the Mayo stage + pre-chemotherapy [LV GLS] model showed incremental prognostic value (C-index: 0.637 vs. 0.708; Relative Integrated Discrimination Index 0.07, P-value = 0.003; Net Reclassification Improvement 0.54, P-value < 0.001). Δ [LV GLS] showed good correlation with cardiac response (AUC 0.820, 95% CI [0.737–0.904]).ConclusionIn cardiac amyloidosis patients who underwent chemotherapy, longitudinal change of [LV GLS] after chemotherapy showed significant association with overall survival as well as cardiac response.

Clinical Outcomes and Effectiveness of Heart Transplantation in Patients With Systemic Light-chain Cardiac Amyloidosis.

In systemic light-chain (AL) amyloidosis, cardiac involvement is a major determinant of survival; however, cardiac response is limited even after systemic treatment in a majority of patients, and some require heart transplantation. Additionally, limited information is available on specific indications for heart transplantation. We aimed to explore clinical outcomes of cardiac amyloidosis and its association with heart transplantation, including identifying factors favoring heart transplantation amenability. We retrospectively analyzed data from patients diagnosed with AL amyloidosis with cardiac involvement between January 2007 and December 2020 at a tertiary referral center. Among 73 patients, 72 (99%) received systemic treatment, and 12 (16%) underwent heart transplantation. Characteristics at diagnosis were similar between heart transplant recipients and nonrecipients, although left ventricular ejection fraction tended to be lower in recipients (median 48% versus 57%, P = 0.085). Eight weeks after systemic treatment, 67% and 12% of patients achieved hematologic and brain natriuretic peptide responses. Overall survival was longer among heart transplantation recipients than nonrecipients, with 5-y survival rates of 61.1% (95% confidence interval, 25.5%-83.8%) versus 32.0% (95% confidence interval, 20.3%-44.4%; P = 0.022), respectively. Among the 34 with identifiable causes of death out of 51 deaths, 21 nonrecipients (62%) died of cardiac problems compared with none in the heart transplant recipients. Additionally, survival outcomes favored heart transplant recipients in most subgroups, including patients with higher Mayo 2004 European stage at diagnosis and with extracardiac involvement of amyloidosis. Heart transplantation can achieve long-term survival in appropriately selected patients with AL cardiac amyloidosis.

Determining patterns of vascular function and structure in wild-type transthyretin cardiac amyloidosis. A comparative study

BackgroundThe impact of wild-type transthyretin-related cardiac amyloidosis (ATTRwt) on functional and structural peripheral vascular measures is unknown. In the present study, we explored patterns of vascular dysfunction in patients with ATTRwt in comparison to diseases with similar cardiac phenotype. MethodsTreatment-naïve patients with ATTRwt (n = 32) were compared to: 1. Age-and sex-matched reference population without amyloidosis (n = 32), 2. Age-and sex-matched patients with systemic AL amyloidosis (n = 32), and 3. patients with cardiac AL amyloidosis (AL-HF, n = 23) or elderly patients with heart failure with preserved ejection fraction (HFpEF) (n = 16). All subjects underwent peripheral vascular assessment using carotid artery ultrasonography, brachial artery flow-mediated dilation (FMD), measurement of arterial stiffness and aortic hemodynamics including heart rate-adjusted time of return of reflected waves (Tr/HR). ResultsAfter adjustment for traditional cardiovascular risk factors and coronary artery disease (core model), peripheral and aortic blood pressures (BP) were lower in patients with ATTRwt (p < 0.05) whereas other vascular markers were preserved compared to the reference non-amyloidosis group. ATTRwt was independently associated with lower BP and longer Tr/HR compared to AL. Compared to AL-HF, FMD was lower in ATTRwt (p = 0.033). ATTRwt patients had lower BP and higher Tr/HR than HFpEF (p < 0.05). By ROC analysis, Tr/HR discriminated ATTRwt vs. AL-HF (sensitivity 93%, specificity 75%) and HFpEF (sensitivity 100%, specificity 94%) and lower FMD increased the likelihood for ATTRwt at low Tr/HR values. ConclusionATTRwt patients present a distinct peripheral vascular fingerprint which is different from AL-HF or HFpEF, consisting of lower peripheral and aortic BP, prolonged Tr/HR and FMD at reference-population range.

Potential clinical relevance of cardiac magnetic resonance to diagnose cardiac light chain amyloidosis.

While patients with cardiac transthyretin amyloidosis are easily diagnosed with bone scintigraphy, the detection of cardiac light chain (AL) amyloidosis is challenging. Cardiac magnetic resonance (CMR) analyses play an essential role in the differential diagnosis of cardiomyopathies; however, limited data are available from cardiac AL-Amyloidosis. Hence, the purpose of the present study was to analyze the potential role of CMR in the detection of cardiac AL-amyloidosis. We included 35 patients with proved cardiac AL-amyloidosis and two control groups constituted by 330 patients with hypertrophic cardiomyopathy (HCM) and 70 patients with arterial hypertension (HT), who underwent CMR examination. The phenotype and degree of left ventricular (LV) hypertrophy and the amount and pattern of late gadolinium enhancement (LGE) were evaluated. In addition, global and regional LV strain parameters were also analyzed using feature-tracking techniques. Sensitivity and specificity of several CMR parameters were analyzed in diagnosing cardiac AL-amyloidosis. The sensitivity and specificity of diffuse septal subendocardial LGE in diagnosing cardiac AL-amyloidosis was 88% and 100%, respectively. Likewise, the sensitivity and specificity of septal myocardial nulling prior to blood pool was 71% and 100%, respectively. In addition, a LV end-diastolic septal wall thickness ≥ 15 mm had an optimal diagnostic performance to differentiate cardiac AL-amyloidosis from HT (sensitivity 91%, specificity 89%). On the other hand, a reduced global LV longitudinal strain (< 15%) plus apical sparing (apex-to-base longitudinal strain > 2) had a very low sensitivity (6%) in detecting AL-Amyloidosis, but with very high specificity (100%). The findings from this study suggest that CMR could have an optimal diagnostic performance in the diagnosis of cardiac AL-amyloidosis. Hence, further larger studies are warranted to validate the findings from this study.

‘Here comes the story of the Hurricane’: a case report of AL cardiac amyloidosis and myocardial bridging

BackgroundCardiac amyloidosis (CA) is a rapidly progressive infiltrative cardiomyopathy, whose role is emerging as a not-so-rare disorder leading to heart failure (HF). Myocardial bridge (MB) is the most common inborn coronary artery variant, and its clinical relevance is still matter of debate. The exceptional coexistence of these two conditions could accelerate disease progression and worsen the already compromised clinical conditions.Case summaryWe present the case of a 76-year-old female patient experiencing relapsing HF decompensation and presenting to our centre with dyspnoea at rest and severe peripheral congestion. Echocardiogram showed severe concentric hypertrophy, severe biventricular contractile dysfunction, and third-degree diastolic dysfunction. Coronary angiography excluded epicardial atherosclerotic disease, though displaying a long intramyocardial course of left anterior descending artery. Physiological invasive test was achieved in terms of instantaneous wave-free ratio (iFR), both at baseline and after inotropic and chronotropic stimuli, and attested haemodynamic significance. Concurrently, the diagnostic flow chart for CA was accomplished, by means of both invasive (periumbilical fat biopsy, bone marrow aspiration) and non-invasive tests (99mTc-diphosphonate scintigraphy, serum-urine immunofixation) that confirmed the suspect of primary amyloidosis. Acute HF therapy was personalized according to the singularity of the case, avoiding both nitrates and beta-blockers, then first cycle of chemotherapy was started.DiscussionOur clinical case shows a unique interaction between infiltrative cardiomyopathy and coronary artery abnormality. Amyloidosis can contribute to the ischaemic burden of the MB and this may, in turn, abbreviate the path to HF decompensation.

Long Term Hematologic and Graft Outcomes After Cardiac Transplant in Al Amyloidosis

<h3>Purpose</h3> Advances in the systemic treatment of AL amyloidosis have allowed some patients with end-stage cardiac disease to undergo heart transplantation (HT). There is limited data on long-term hematologic and graft outcomes of patients with AL amyloidosis who underwent HT. <h3>Methods</h3> Outcomes of patients with cardiac AL amyloidosis who underwent HT at our center between 2008 and 2020 were analyzed. Descriptive data on treatments and International Myeloma Working Group hematologic response after HT were included. Incidence and interval between HT and development of coronary allograft vasculopathy (CAV, ISHLT classification), incidence of graft rejection and survival were reported. <h3>Results</h3> Eight patients with cardiac AL amyloidosis were included in the study. Three (38%) patients had concurrent multiple myeloma. Median recipient age was 53 years (range 37 - 74 years) and median follow-up was 25.2 months (range 9.6 - 150 months) from HT. Median donor age was 32 years (range 19 - 61 years). Three donors were HCV NAT+. At the time of HT, 4 patients were in complete remission (CR), 1 had stable disease (SD), and 2 had partial response (PR). Three (38%) patients underwent autologous stem cell transplant (SCT) after HT; and seven (87%) received systemic therapy after HT. Five (63%) pts developed CAV (four ISHLT CAV-1 and one ISHLT CAV-3) at a median of 13.2 months after HT. At 3 years post HT, 7 (87%) patients maintained in CR or stringent CR and only 1 (12%) patient had progressive disease (PD). Three patients died during follow-up: two from CAV and one from complications of GI amyloidosis (Figure 1). <h3>Conclusion</h3> In this single center study, most patients with cardiac AL amyloidosis experienced durable CR after HT. However, a significant proportion developed CAV and almost 40% died within three years of transplant. Further studies with larger numbers of patients are required to determine the incidence of CAV in this population. The long term outcome of heart transplantation in patients with cardiac AL amyloidosis remains to be elucidated.

A Closer Evaluation for Refractory Atrial Fibrillation with Heart Failure, a Case Report

<h3>Introduction</h3> Atrial fibrillation (AF) is highly prevalent after the age of 55 years. However, it can be associated with infiltrative cardiomyopathy. <h3>Case Report</h3> A 63 years old had new onset of palpitation and shortness of breath. He presented to ED with rapid AF at rate of 140 bpm treated with metoprolol, diltiazem and rivaroxiban. The patient started to develop lower limb swelling, dizziness, shortness of breath with walking short distance. His blood pressure was 110/60 mmHg off antihypertensive medication. He had NYHA class III symptoms and significant peripheral edema. A TTE showed a moderate concentric left ventricle hypertrophy IVS 16 mm with mild global systolic dysfunction LVEF 50% restrictive diastolic function and pericardial effusion. The patient had significant myocardial hypertrophy, HFpEF and AF with intolerance to medical therapy we proceeded with PYP bone scan which was equivocal for TTR amyloidosis. The bone to heart ration was 1.27. Cardiac MRI showed progressive decline in LVEF to 27% with severe RV systolic dysfunction EF 28% . There was a diffused subendocardial delayed enhanced lesion. Given these findings hematology workup sent which showed serum Free Lambda of 147mg/L; Free Kappa 6.71mg/L and Kappa/Lambda ratio of 0.05 (0.26 - 1.65). Bone marrow biopsy showed plasma cell percentage up to 40%. Flowcytometry showed lambda restricted plasma cell population together with positive CD38, CD138, CD56 and negative CD19. Fat Pad biopsy positive for Congo red stain consistent of amyloid deposits. He received chemotherapy CyBorDex 4 cycles followed by reduction in plasma cells to 2% in the bone marrow. He had cardiac function recovery. <h3>Summary</h3> AL cardiac amyloidosis can present with cardiac manifestation. High suspicion of underlying infiltrative disease should be investigated in refractor cases AF and HFpEF.

Pulmonary Amyloidoma: A Rare Entity Complicating a Post-Heart Transplant Course

<h3>Introduction</h3> Heart transplantation (HT) is a viable, life-prolonging therapy for patients with severe cardiac amyloidosis. Unique amyloid-related pathology may complicate their care. We present a case of a rare manifestation of amyloidosis complicating a post-HT course. <h3>Case Report</h3> A 51-year-old female with cardiac AL amyloidosis (treated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone) and chronic kidney disease was transferred for advanced options evaluation. She presented in cardiogenic shock and PEA arrest requiring escalation to venoarterial-ECMO. Admission sputum culture was positive for <i>Enterobacter cloacae</i>. CT scan revealed right lower lobe consolidation with a 5cm cavitary lesion concerning for aspiration pneumonia. Broad spectrum antibiotics were initiated. Given near-complete resolution of her light chains on chemotherapy, Oncology agreed to proceed with transplantation. She was emergently listed as status 1 and underwent heart-kidney transplantation. One-week post-HT, she developed severe leukocytosis and abdominal discomfort but remained afebrile with only mild dyspnea. Abdominal CT incidentally noted an 11cm right lower lobe cavitary lung lesion. Dedicated CT chest raised concern for aspergilloma or other necrotizing pneumonia (Figure 1). Bronchoalveolar lavage had unremarkable fungal and viral studies but did reveal <i>Acinetobacter</i>. Antibiotics were appropriately adjusted. VATS was attempted but required conversion to thoracotomy with right lower lobectomy. Pathology revealed necroinflammatory findings and Congo-red stain-positive material both inside the cavity and extensively deposited within the cavity walls. These findings were consistent with pulmonary amyloidoma. <h3>Summary</h3> Though rare, pulmonary amyloidomas may be incidentally found as large cavitating lesions amongst patients with systemic amyloidosis. In the post-HT patient, they may serve as a nidus for infections and appear similar to necrotizing pneumonias, resulting in delays in diagnosis.