Light chain cardiac amyloidosis - a rare cause of heart failure in a young adult

SUMMARY Cardiac amyloidosis is an infiltrative cardiomyopathy, resulting from amyloid deposition within the myocardium. In primary systemic (AL-type) amyloidosis, the amyloid protein is composed of light chains resulting from plasma-cell dyscrasia, and cardiac involvement occurs in up to 50% of the patients We present a case of a 43-year-old man, with complaints of periodical swollen tongue and xerostomia, bleeding gums and haematuria for two months. His blood results showed normocytic anaemia, thrombocytopenia and a high spontaneous INR, therefore he was referred to the Internal Medicine clinic. In the first visit, he showed signs and symptoms of overt congestive heart failure and was referred to the emergency department. The electrocardiogram showed sinus tachycardia and low voltage criteria. Echocardiography showed biventricular hypertrophy with preserved ejection fraction, restrictive physiology with elevated filling pressures, thickened interatrial septum and atrioventricular valves, small pericardial effusion and relative “apical sparing” on 2D longitudinal strain. Cardiac MRI showed diffuse subendocardial late enhancement. Serum protein electrophoresis was inconclusive, however urine analysis revealed nephrotic range proteinuria, positive Bence Jones protein and an immunofixation test with a monoclonal lambda protein band. Abdominal fat biopsy was negative for Congo red stain, nevertheless a bone marrow biopsy was performed, revealing lambda protein monoclonal plasmocytosis, confirming the diagnosis of primary systemic amyloidosis. This case represents a rare cause of heart failure in a young adult. Low-voltage QRS complexes and typical echocardiography features should raise the suspicion for cardiac amyloidosis. Prognosis is dictated by the level of cardiac involvement; therefore, early diagnosis and treatment are crucial.

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Increases In B-Type Natriuretic Peptide (BNP) During Treatment with Lenalidomide In AL Amyloidosis

Blood ◽

10.1182/blood.v116.21.3021.3021 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3021-3021

Author(s):

Umit Tapan ◽

David C Seldin ◽

Kathleen T Finn ◽

Salli Fennessey ◽

Anthony C Shelton ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Cardiac Involvement ◽

Troponin I ◽

Medical Center ◽

Nyha Class ◽

Early Time ◽

Response To Therapy ◽

Plasma Cell Dyscrasia ◽

Al Amyloidosis

Abstract Abstract 3021 The combination of lenalidomide and dexamethasone can produce partial and complete hematologic responses in previously treated patients with AL amyloidosis (Blood 2007; 109: 492–496). Since this prospective study was initiated, NT-proBNP and BNP have been found to be useful biomarkers for cardiac involvement, prognosis, and response to therapy in AL amyloidosis patients. Here we report on the retrospective analysis of the prospectively collected data on changes in BNP during lenalidomide therapy on this trial. Increase in BNP was defined as > 30% increase from baseline value at enrollment on the trial after cycles 1 and 3. Patients with BNP of < 100 pg/mL at baseline, and after 1 and 3 cycles as well as patients in whom BNP levels were not measured were excluded in this analysis. Sixty-eight patients with AL amyloidosis were treated with lenalidomide and dexamethasone (ClinicalTrials.gov: NCT00091260) at Boston Medical Center. The median age was 64 years (range, 42 to 85); and 69% were male. Fifty-one patients (75%) had lambda clonal plasma cell dyscrasia, and 38 (56%) had cardiac involvement. All patients received lenalidomide and dexamethasone as described in our previous report. Twenty-four of the 68 total patients enrolled did not meet the eligibility to be included in this analysis due to either BNP levels of < 100 pg/mL at baseline and at 1 and 3 months after treatment or unavailability of BNP measurement after 1 or 3 cycles of lenalidomide. Therefore, 44 patients are included in this analysis. Thirty-eight patients (86%) had > 30% increase in BNP level from baseline after initiation of lenalidomide treatment. Of these 38 patients, 30 (79%) had an increase after 1 cycle and additional 8 (21%) patients after 3 cycles of lenalidomide. The mean dose of lenalidomide for patients with increase in BNP after 1 cycle was 15 mg (range, 5–25) and after 3 cycles was 10 mg (range, 5–15). Forty % (n=12/30) and 63% (n=5/8) of patients did not receive dexamethasone with lenalidomide when increase in BNP was seen after 1 and 3 cycles, respectively. Of the patients with increase in BNP, only 5 patients (13%) had worsening of renal function from baseline. Moreover, increase in BNP after 1 and 3 cycles occurred in 23 of 29 patients (79%) with cardiac involvement. Cardiac troponin I levels were not measured after 1 and 3 cycles of lenalidomide. All the patients with increase in BNP were asymptomatic without association of modification in NYHA class congestive heart failure. The median survival of these 44 patients is 53 months since initiation of lenalidomide therapy. At these early time pointsof 1 and 3 months, 20% (n=9/44) of patients had >50% improvement in serum free light chain levels, and 2% (n=1/44) of patients had improvement in BNP of 30% or more. In conclusion, BNP increased by > 30% in a substantial proportion of patients with AL amyloidosis during treatment with lenalidomide. The mechanism for asymptomatic rise in BNP is not clear; however, the temporal relationship with lenalidomide initiation, the relatively rapid increase, and the absence of other identifiable precipitants for most of the patients suggest that lenalidomide may be playing a role. Moreover, patients with AL amyloidosis receiving lenalidomide whose BNP rises should not be assumed to be failing therapy without other signs of disease progression, but should be monitored closely and treated as needed for signs or symptoms of congestive heart failure should they occur. Disclosures: Off Label Use: Use of lenalidomide in AL amyloidosis. Zeldis:Celgene Corp: Employment.

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A Case Report of Cardiac Amyloidosis Highlighting the Importance of Strain Analysis

Case Reports in Cardiology ◽

10.1155/2021/5673364 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Andres Cordova Sanchez ◽

Ryan Murphy ◽

Suman Rao ◽

Fidel Martinez ◽

Stephanie Bryant ◽

...

Keyword(s):

Heart Failure ◽

Case Report ◽

High Mortality ◽

Light Chain ◽

Cardiac Amyloidosis ◽

Inverse Relationship ◽

Cardiac Involvement ◽

Strain Analysis ◽

Al Amyloidosis ◽

Cardiac Symptoms

Cardiac involvement in light-chain (AL) amyloidosis has a high mortality. Once cardiac symptoms are present, it is important to make a diagnosis as there is an inverse relationship between mortality and time of diagnosis. Echocardiography is usually one of the first tests performed. But strain analysis, which can provide important clues, is not routinely performed. This is a case of AL amyloidosis presenting with heart failure in which echocardiographic strain analysis was vital for its diagnosis.

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Cardiac metastases from soft-tissue sarcomas.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.11.1662 ◽

1986 ◽

Vol 4 (11) ◽

pp. 1662-1669 ◽

Cited By ~ 31

Author(s):

D E Hallahan ◽

N J Vogelzang ◽

K M Borow ◽

D G Bostwick ◽

M A Simon

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Soft Tissue ◽

Cardiac Involvement ◽

Conduction Block ◽

Soft Tissue Sarcomas ◽

Signs And Symptoms ◽

Atrial Myxoma ◽

Cardiac Symptoms ◽

Cardiac Metastases

Cardiac metastases were present in 30 of 120 (25%) consecutive autopsies of patients with soft-tissue sarcoma (STS). Fifty percent of the patients had metastases to the myocardium, while 33% had pericardial metastases and 17% had both. Congestive heart failure was present in ten patients and was commonly caused by diffuse myocardial or restrictive pericardial metastases. Other signs and symptoms of cardiac involvement by STS included chest pain (three patients), arrhythmias (two), conduction block (two), simulation of an atrial myxoma (one), and sudden death (one). Echocardiography was used infrequently, but was diagnostic in 80% of cases in which it was used. We conclude that metastatic STS commonly involves the heart and produces cardiac symptoms.

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Strange case of biventricular heart failure

BMJ Case Reports ◽

10.1136/bcr-2020-239658 ◽

2021 ◽

Vol 14 (1) ◽

pp. e239658

Author(s):

Carloalberto Biolè ◽

Matteo Bianco ◽

Antonella Parente ◽

Laura Montagna

Keyword(s):

Heart Failure ◽

Pulmonary Embolism ◽

Cardiac Amyloidosis ◽

Left Ventricular ◽

Pulmonary Congestion ◽

Transthyretin Amyloidosis ◽

X Ray ◽

Infiltrative Cardiomyopathy ◽

Mild Reduction ◽

Chest X Ray

Acute heart failure (HF) is commonly caused by a cardiomyopathy with one or more precipitating factor. Here, a case in which a cardiomyopathy is precipitated by pulmonary embolism (PE). A 77-year-old man is admitted for breathlessness and leg swelling. A mild reduction of left ventricular (LV) ejection fraction is found, with moderately increased LV wall thickness and pulmonary hypertension; clinical examination revealed signs of congestion with bilateral leg swelling, and mild signs of left HF with the absence of pulmonary congestion on chest X-ray. The ECG showed Mobitz I second-degree atrioventricular block. The clinical scenario led us to the diagnosis of infiltrative cardiomyopathy due to cardiac amyloidosis (CA) precipitated by PE. Pulmonary embolism is an overlooked precipitant of HF and can be the first manifestation of an underlying misdiagnosed cardiomyopathy, especially CA. 3,3-Diphosphono-1,2-propanodicarboxylic acid scan is a cornerstone in the diagnosis of Transthyretin amyloidosis (ATTR) cardiac amyloidosis.

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Abstract 16240: Knowledge of Clinical Presentation and Diagnostic Pathways for Cardiac Amyloidosis Among Physicians in the Middle East-Gulf Region: on Behalf of the Gulf Cardiac Amyloidosis Working Group

Circulation ◽

10.1161/circ.142.suppl_3.16240 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Firas Al Badarin ◽

Juwairia Al Ali ◽

Feras Bader ◽

Abdulla M Shehab ◽

Said AlSaid ◽

...

Keyword(s):

Heart Failure ◽

Middle East ◽

Cardiac Amyloidosis ◽

Online Survey ◽

Severe Aortic Stenosis ◽

Signs And Symptoms ◽

The United States ◽

Low Flow ◽

Patient Identification ◽

Gulf Region

Background: There is a growing interest in raising awareness about amyloidosis as an under-recognized cause of heart failure and preserved ejection fraction (HFpEF). Recently, the prevalence of cardiac amyloidosis in the United States has increased, which may partly be attributed to initiatives from major professional societies aimed to improve patient identification and disease detection. Whether this has also impacted physicians’ knowledge about cardiac amyloidosis in the Middle East-Gulf region is unknown but critical to assess, as it would identify a need for dedicated regional educational activities. Methods: Physicians practicing in 5 Gulf countries (UAE, Bahrain, Qatar, Oman and Kuwait) were invited to participate in this anonymous, online survey by receiving a unique survey link by email. We assessed awareness of cardiac amyloidosis, knowledge of disease manifestations and approach to diagnosis. Responses to the survey were recorded using a 4- or 5-point Likert scale. Results: A total of 272 physicians participated in the survey. Most participating physicians were men (82%) and have been practicing cardiology (71%) for >10 years (65%). Whereas 83% of responders considered themselves to be somewhat or extremely familiar with signs and symptoms of cardiac amyloidosis, only 63% would consider cardiac amyloidosis as a cause of HFpEF, 59% would consider it in patients with heart failure and orthostatic hypotension while only 39% consider cardiac amyloidosis in patients with low-flow, low-gradient severe aortic stenosis. Furthermore, cardiac MRI was found to be useful for diagnosis of cardiac amyloidosis by 92% of responders, while echocardiography, cardiac scintigraphy with bone-seeking radiotracers and biomarkers were felt to be useful by only 81%, 60% and 31% of survey participants, respectively. Conclusion: Despite perceived familiarity with cardiac amyloidosis among a group of mid-career cardiologists, there is need to raise awareness about the heterogenous manifestations of the disease and about the respective roles of testing modalities in making this diagnosis.

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SARS-CoV-2-induced Multisystem Inflammatory Syndrome in a Young Adult

10.21203/rs.3.rs-451223/v1 ◽

2021 ◽

Author(s):

haldun bulut ◽

Alexandra H.E. Herbers ◽

Ilse M.G. Hageman ◽

Paetrick M. Netten ◽

Hendrik J.M. de Jonge ◽

...

Keyword(s):

Heart Failure ◽

Young Adult ◽

Clinical Features ◽

Cardiac Involvement ◽

Volume Loading ◽

Male Athlete ◽

Life Threatening ◽

Life Threatening Complication ◽

Cardiac Status ◽

Inflammatory Syndrome

Abstract We describe a case of a previous healthy 20-year-old male athlete who presented with an atypical clinical profile with multiorgan involvement five weeks after confirmed SARS-CoV-2 infection, suggestive for multisystem inflammatory syndrome (MIS). MIS is a rare, potentially life-threatening complication associated with SARS-CoV-2 and shares several similar clinical features with overlapping hyperinflammatory syndromes that may create a great challenge to distinguish between them. MIS should promptly be considered and treated, as uncontrolled MIS has a high mortality. In MIS cardiac involvement, heart failure may present as an additional problem, especially because volume loading is advised in accordance with proposed therapy. Carefully monitoring of the respiratory and cardiac status in response of resuscitation is therefore warranted.

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Concordance between quantitative and semi-quantitative analysis of Tc-99m-pyrophosphate scintigraphy for the diagnosis of transthyretin cardiac amyloidosis in patients with HFpEF

European Heart Journal ◽

10.1093/eurheartj/ehab724.0854 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Murat ◽

H.E Yalvac ◽

G.O Mert ◽

I.A Sivrikoz ◽

Y Cavusoglu

Keyword(s):

Quantitative Analysis ◽

Cardiac Amyloidosis ◽

Low Voltage ◽

Visual Assessment ◽

Interatrial Septum ◽

Left Ventricular ◽

Myocardial Uptake ◽

Cardiac Uptake ◽

Funding Sources ◽

American Society

Abstract Background Transthyretin (TTR) cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF). Cardiac scintigraphy with 99mTechnetium-pyrophosphate (99mTc-PYP) is referred as a simple, non-invasive and reliable method in the diagnosis of TTR-CA. American Society of Nuclear Cardiology Practice Points recommends two interpretative approaches: the quantitative heart-to-contralateral lung ratio (H/CL) at 1 hour or the semi-quantitative visual assessment at 3 hours after radiotracer injection. Purpose In this study, we evaluated the concordance between semi-quantitative and quantitative approaches in the diagnosis of TTR CA in patients with HFpEF. Methods This single-center, prospective study included 78 patients who had a diagnosis of HFpEF according to 2016 ESC HF guidelines. 99mTc-PYP cardiac scintigraphy was performed in 43 patients who have ≥2 red flags for TTR-CA including left ventricular hypertrophy (LVH) (wall thickness ≥12 mm), biventricular hypertrophy, sparkling pattern, reduction in longitudinal strain with apical sparing, thickening of the interatrial septum (>6mm), low-voltage, pseudo infarct pattern or atrioventricular block on ECG. In the absence of monoclonal protein in the serum and urine, Grade 2 to 3 myocardial uptake in semi-quantitative analysis at 3 hours or a H/CL ratio of ≥1.5 in quantitative analysis at 1 hour post injection of 99mTc-PYP is considered positive for TTR-CA. Grade 2–3 uptake with a H/CL ratio ≥1.5 or Grade 0–1 uptake with a H/CL ratio <1.5 were considered as concordant results. Grade 2–3 uptake with a H/CL ratio <1.5 or Grade 0–1 uptake with a H/CL ratio ≥1.5 were considered as discordant results. Results Mean age of study population was 68.26±9.97 years. 17 (39.5%) of 43 patients who underwent 99mTc-PYP cardiac scintigraphy showed a Grade 2 or 3 cardiac uptake and in these patients with Grade 2–3 uptake, 11 patients (65%) had a H/CL ratio ≥1.5 (concordant results) and 6 patients (35%) had a H/CL ratio <1.5 (discordant results). 26 (60.5%) of 43 patients showed Grade 0–1 cardiac uptake. All patients (100%) with Grade 0–1 uptake had a H/CL ratio <1.5 and therefore, showed concordant results. Overall, 37 (86%) patients had concordant and 6 (14%) patients had discordant results (Table 1). Conclusion The results of this study showed that although there was a high agreement between semi-quantitative and quantitative analysis of 99mTc-PYP cardiac scintigraphy, 14% of patients have discordant results and need further workup to confirm TTR-CA in patients with HFpEF. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer independent grant.

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Efficacy and Tolerability of Daratumumab in Heavily Pretreated AL Amyloidosis: A Systematic Review

Blood ◽

10.1182/blood-2018-99-115214 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2025-2025 ◽

Cited By ~ 1

Author(s):

Muhammad Aadil Rahman ◽

Ali Younas Khan ◽

Awais Ijaz ◽

Muhammad Junaid Tariq ◽

Muhammad Usman ◽

...

Keyword(s):

Heart Failure ◽

Partial Response ◽

Light Chain ◽

Cardiac Amyloidosis ◽

Cardiac Involvement ◽

Renal Involvement ◽

Renal Amyloidosis ◽

Al Amyloidosis ◽

Heavily Pretreated ◽

Organ Response

Abstract Introduction Light chain (AL) amyloidosis is a low burden plasma cell disorder, characterized by deposition of misfolded lambda or kappa light chains. Kidney dysfunction is present in almost two-thirds of patients at the time of initial presentation, followed by diastolic heart failure in about 50% of cases, which is responsible for 75% of deaths in these patients. Autologous stem cell transplant (auto-SCT) remains the gold standard for the management of AL amyloidosis but is often impractical to perform by virtue of patients' age, medical comorbidities including cardiac involvement. Methods We conducted a literature search using three databases (PubMed, Embase,Web of Science). Our search strategy included MeSH terms and key words such as AL amyloidosis, daratumumab and darzalex from date of inception to March 2018. After excluding duplicates, reviews and non-relevant articles, we selected eight studies, including two case reports, two phase II prospective trials and four retrospective trials. Results Data on 129 patients was included, there ages ranged from 43-83 years. Median number of prior therapies were 3 (range: 2-6), 106 (82%) received proteasome inhibitor (bortezomib) based therapy, and 69 (53.5%) received immunomodulatory (lenalidomide) based therapy. Another 41 (32%) received high dose melphalan (HDM) followed by auto-SCT. The time from the diagnosis of AL to the start of daratumumab therapy varied from 0.7-150 months. Eighty-nine (69%) patients had cardiac and 64 (49.6%) patients had renal involvement. A total of 114 (88%) patients received a daratumumab dose of 16 mg/kg weekly for 8 weeks followed by every 2 weeks for the next 8 weeks. A total of 104 patients were evaluable for hematological response, assessed by improvement in free light chain (FLC) levels. Daratumamab achieved an impressive overall response rate (ORR) of 72% (n=75). Complete remission (CR) in 15 (14%) of patients, very good partial response (VGPR) in 44 (42%) and a partial response (PR) in 16 (15%) of patients was noted. Thirty-four patients with cardiac involvement and 26 patients with renal amyloidosis were assessed for organ response across four studies. Thirteen (38%) patients with cardiac amyloidosis demonstrated an improvement in N-terminal pro brain natriuretic peptide (NT-proBNP) levels. Ten (38%) patients with renal involvement responded according to consensus criteria [Palladini et al 2014] for organ response. Another two had improvement in serum creatinine levels. Among the 129 patients treated with daratumumab for AL amyloidosis, 36 (32%) reported infusion related reactions (IRR). Most were mild (grade 1-2). Daratumumab infusion was well tolerated in patients with cardiac (n=54) and renal involvement (n=48). Only one patient needed adjustment in his diuretic dose, another one developed decompensated heart failure and one died due to progression of cardiac disease. Seven patients had worsening of their NT-proBNP levels. Similarly, no dose adjustments were required for patients with renal amyloidosis and one patient tolerated daratumumab infusion at a GFR<20 mL/min without any complications. Conclusion Daratumumab monotherapy is associated with deep and prompt hematological responses in patients with heavily pretreated AL amyloidosis, at the standard dosing regimens used for multiple myeloma, with a favorable safety profile. Furthermore, daratumumab performed well in patients with cardiac amyloidosis even though there is an increased risk of volume overload and infusion related morbidity. Given the high incidence of peripheral neuropathy with bortezomib, cardiotoxicity with carfilzomib based regimens in amyloidosis patients, daratumumab appears to be a suitable alternative. It has already been approved for relapsed amyloidosis (AL) patients in the European Union. Currently, it is being investigated as monotherapy for AL amyloidosis in phase 2 trials (NCT02841033 and NCT02816476) and in combination with bortezomib, cytoxin and dexamethasone (VCd) in a phase III trial (NCT03201965). Disclosures No relevant conflicts of interest to declare.

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