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Radioisotope Scintigraphy to Establish Incidence of Cardiac Amyloidosis Among Patients With Otherwise Unexplained Cardiac Disease

Primary Purpose

Cardiac TTR Amyloidosis

Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Tc99m-labeled pyrophosphate scan
Sponsored by
Kaplan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Cardiac TTR Amyloidosis focused on measuring TTR Amyloidosis, Heart Failure with Preserved Ejection Fraction, Ventricular arrhythmia, Cardiac Conduction Disturbances

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Heart Failure with Preserved Ejection Fraction not explained by either hypertension or any other clinical condition.
  2. Systolic dysfunction and non-significant coronary artery disease.
  3. Diabetic cardiomyopathy
  4. Otherwise unexplained left ventricular hypertrophy (LVH).
  5. Under age of 65 and idiopathic ventricular fibrillation (VF) or multiple ventricular premature beats (VPB) or ventricular tachycardia (VT) with a structurally normal heart.
  6. Under age of 65, and unexplained sinus node disease, sinoatrial block, complete or high-degree atrio-ventricular block or significant intraventricular conduction defect, with structurally normal heart whether having or not having received permanent implanted pacemaker.

Exclusion Criteria:

  1. Primary amyloidosis cannot be excluded,
  2. Acute or recent (3 months) myocardial infarction,
  3. Acute or recent (12 months) myocarditis,
  4. Oncologic or any other co-morbidity, which can shorten the patient's survival to less than one year,
  5. End stage renal disease treated with dialysis,
  6. Ischemic cardiomyopathy,
  7. Non-TTR amyloidosis known or suspected,
  8. Another type of cardiomyopathy (for ex. arrhythmogenic right ventricular dysplasia),
  9. Any disease or clinical condition that can lead to cardiomyopathy (history of anthracyclines treatment, history of alcohol abuse, multiple myeloma, sarcoidosis, carcinoid, inflammatory and autoimmune diseases).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Other

    Arm Label

    no other arm

    Arm Description

    Outcomes

    Primary Outcome Measures

    diagnosis or exclusion of any type of cardiac amyloidosis;
    diagnosis of cardiac TTR amyloidosis, or any other type of cardiac amyloidosis, or diagnosis of another condition other than amyloidosis explaining the patient's clinical cardiological findings

    Secondary Outcome Measures

    Full Information

    First Posted
    March 28, 2017
    Last Updated
    April 3, 2017
    Sponsor
    Kaplan Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03098901
    Brief Title
    Radioisotope Scintigraphy to Establish Incidence of Cardiac Amyloidosis Among Patients With Otherwise Unexplained Cardiac Disease
    Official Title
    Tc99m-PYP Scintigraphy in Order to Establish Incidence of Cardiac Transthyretin Amyloidosis Among Patients With Otherwise Unexplained Cardiomyopathies
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2017
    Overall Recruitment Status
    Unknown status
    Study Start Date
    April 15, 2017 (Anticipated)
    Primary Completion Date
    April 15, 2018 (Anticipated)
    Study Completion Date
    April 15, 2018 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Kaplan Medical Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Cardiac amyloidosis is a multi-organ syndrome, which usually presents as restrictive cardiomyopathy (RCM). Transthyretin (TTR) amyloidosis (or ATTR) is a subtype of amyloidosis which frequently involves heart. Cardiac ATTR, though infrequently diagnosed during lifetime, may represent a prevalent cause of RCM, especially in elderly. Several medications that can limit progression of the disease are currently under investigation. Presently the golden standard for diagnosis of ATTR is endomyocardial biopsy (EMB) which may entail severe adverse complications causing under-diagnosis of ATTR. Several papers support the evidence that Tc99m-labeled tracers can be used to detect myocardial deposits of TTR amyloid. It was suggested that Tc99m scintigraphy might be a highly sensitive diagnostic tool for cardiac ATTR. In this study the patients with otherwise unexplained cardiomyopathy or heart block will undergo Tc99m scan, which will establish the incidence of this largely underdiagnosed condition in the population.
    Detailed Description
    Amyloidosis is a multi-organ syndrome, which usually presents as a restrictive cardiomyopathy (RCM). Transthyretin (TTR) amyloidosis is a subtype of amyloidosis, further subdivided into familial type and senile type. Its pathophysiology consists primarily of abnormal precipitation of transthyretin - a protein that normally acts as transporter for thyroid hormone and retinoids - in tissues. TTR amyloidosis frequently involves heart, bringing about the same clinical and pathophysiological picture of RCM. Another presentation of TTR Amyloidosis can be atrio-ventricular block or bundle-branch block [1]. There is evidence that the cardiac TTR amyloidosis, though infrequently diagnosed during the lifetime, may represent a widespread cause of restrictive cardiomyopathy especially in elderly. An autopsy study in octogenarians having suffered of heart failure with preserved left ventricular ejection fraction (HFpEF) suggested that up to 25% of them had TTR amyloid deposit in myocardium, though a negligible minority of them had been diagnosed with TTR amyloidosis during their lifetime [2-3]. HFpEF is a very widespread diagnosis, which represents a considerable burden of morbidity, and usually harbours populations of patients poorly responding to treatment. Most of patients with the diagnosis of HFpEF have little or no explanation concerning the aetiology of their disease, especially if they do not respond to conventional treatment. Most of them can benefit only from symptomatic treatment which does not alter the course of the disease. Thus a more widespread diagnosis of TTR amyloidosis could have been very promising as to a better management of this hard-to-treat patient population. Several medications that can limit progression of TTR amyloidosis are currently under investigation. Until now, the golden standard for diagnosis of the disease was endomyocardial biopsy (EMB) which may entail several adverse complications and thus limit widespread diagnosis. Since amyloidosis is a multi-organ disease, extra-cardiac biopsy was proposed as a surrogate tissue diagnosis, though in TTR amyloidosis its sensitivity is below 50% [4]. Recently several papers support the evidence that Tc99m-labeled pyrophosphate (PYP) and bisphosphonates when injected intravenously localize to myocardial deposits of TTR amyloid. It was thus suggested that Tc99m scintigraphy might be a highly sensitive and specific diagnostic tool for cardiac TTR amyloidosis [5-9]. It was shown that almost the only source of false positive Tc99m scintigraphy is primary amyloidosis, which is a different entity, with worse prognosis, different treatment, although frequently involves heart as well [10]. Primary amyloidosis can be diagnosed by means of demonstration of monoclonal immunoglobulin peak in serum and immunoglobulin light chains in serum and urine [11]. Therefore, the specificity of Tc99m scan for TTR amyloidosis can be brought to an extraordinary level, with virtually negligible false positive rate, if primary amyloidosis is excluded prior to referral to Tc99m scan. The other entity where false positive uptake of Tc99m in myocardium can be observed is acute myocardial infarction. Currently the Tc99m-PYP scan is utilised as bone scan according to guidelines in order to diagnose wide spectrum of diseases such as stress fractures or metastatic bone disease. At present the mentioned hypothesis that TTR amyloidosis might be a widespread cause of HFpEF has not been established in a clinical trial due to the fact that until now the most accurate diagnosis of TTR amyloidosis required an invasive procedure with possible adverse outcomes while the extra-cardiac biopsy had low diagnostic yield. Advent of a novel, possibly as accurate, yet non-invasive diagnostic tool opens new opportunities to set such study. The incidence of both familial type and senile type TTR amyloidosis among patients with diagnosis of otherwise unexplained heart failure or heart block will be evaluated in this study by means of Tc99m scan using SPECT technology as described above. The hypothesis is that if the incidence of TTR amyloidosis within the population of patients suffering of HFpEF is as high as it was demonstrated by the autopsy studies, then we will be able to establish the diagnosis in a larger cohort of patients. This will make new developments in the research of the disease, such as treatment and outcome driven trials, possible. Establishing the diagnosis of TTR amyloidosis in patients with HFpEF will improve our decision-making ability regarding the patients' treatment, for example preventing unnecessary invasive measures in patients with comorbidities demanding such measures, the alternative diagnoses being unrevealed.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cardiac TTR Amyloidosis
    Keywords
    TTR Amyloidosis, Heart Failure with Preserved Ejection Fraction, Ventricular arrhythmia, Cardiac Conduction Disturbances

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Model Description
    Patients that suffer of one of the following conditions will be included in the study Patients suffering of HFpEF not explained by either hypertension or any other clinical condition. Patients with systolic dysfunction and non-significant coronary artery disease. Patients with diabetic cardiomyopathy Patients with otherwise unexplained left ventricular hypertrophy (LVH). Patients under age of 65 with idiopathic ventricular fibrillation (VF) or multiple ventricular premature beats (VPB) or ventricular tachycardia (VT) with a structurally normal heart. Patients under age of 65, with unexplained sinus node disease, sinoatrial block, complete or high-degree atrio-ventricular block or significant intraventricular conduction defect, with structurally normal heart whether having or not having received permanent implanted pacemaker.
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    no other arm
    Arm Type
    Other
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    Tc99m-labeled pyrophosphate scan
    Intervention Description
    Intravenous injection of Tc99m-labeled pyrophosphate with consecutive whole body scan using gamma ray scanner for assessment of radioactive uptake in the heart. The results of the scan will be evaluated by a specialist in the field. The uptake will be graded using Perugini scale (0- no uptake, 1- uptake in heart less intense than in bones, 2-uptake in heart as intense as in bones, 3-uptake in heart more intense than in bones).
    Primary Outcome Measure Information:
    Title
    diagnosis or exclusion of any type of cardiac amyloidosis;
    Description
    diagnosis of cardiac TTR amyloidosis, or any other type of cardiac amyloidosis, or diagnosis of another condition other than amyloidosis explaining the patient's clinical cardiological findings
    Time Frame
    immediately at the Tc99m scan performing or within a year form beginning of the recruitment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Heart Failure with Preserved Ejection Fraction not explained by either hypertension or any other clinical condition. Systolic dysfunction and non-significant coronary artery disease. Diabetic cardiomyopathy Otherwise unexplained left ventricular hypertrophy (LVH). Under age of 65 and idiopathic ventricular fibrillation (VF) or multiple ventricular premature beats (VPB) or ventricular tachycardia (VT) with a structurally normal heart. Under age of 65, and unexplained sinus node disease, sinoatrial block, complete or high-degree atrio-ventricular block or significant intraventricular conduction defect, with structurally normal heart whether having or not having received permanent implanted pacemaker. Exclusion Criteria: Primary amyloidosis cannot be excluded, Acute or recent (3 months) myocardial infarction, Acute or recent (12 months) myocarditis, Oncologic or any other co-morbidity, which can shorten the patient's survival to less than one year, End stage renal disease treated with dialysis, Ischemic cardiomyopathy, Non-TTR amyloidosis known or suspected, Another type of cardiomyopathy (for ex. arrhythmogenic right ventricular dysplasia), Any disease or clinical condition that can lead to cardiomyopathy (history of anthracyclines treatment, history of alcohol abuse, multiple myeloma, sarcoidosis, carcinoid, inflammatory and autoimmune diseases).

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    22949539
    Citation
    Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012 Sep 4;126(10):1286-300. doi: 10.1161/CIRCULATIONAHA.111.078915. No abstract available.
    Results Reference
    background
    PubMed Identifier
    18382889
    Citation
    Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, Singleton A, Kiuru-Enari S, Paetau A, Tienari PJ, Myllykangas L. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2008;40(3):232-9. doi: 10.1080/07853890701842988.
    Results Reference
    background
    PubMed Identifier
    24698461
    Citation
    Fine NM, Arruda-Olson AM, Dispenzieri A, Zeldenrust SR, Gertz MA, Kyle RA, Swiecicki PL, Scott CG, Grogan M. Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis. Am J Cardiol. 2014 May 15;113(10):1723-7. doi: 10.1016/j.amjcard.2014.02.030. Epub 2014 Mar 2.
    Results Reference
    background
    PubMed Identifier
    26091765
    Citation
    Maurer MS. Noninvasive Identification of ATTRwt Cardiac Amyloid: The Re-emergence of Nuclear Cardiology. Am J Med. 2015 Dec;128(12):1275-80. doi: 10.1016/j.amjmed.2015.05.039. Epub 2015 Jun 17.
    Results Reference
    background
    PubMed Identifier
    16168294
    Citation
    Perugini E, Guidalotti PL, Salvi F, Cooke RM, Pettinato C, Riva L, Leone O, Farsad M, Ciliberti P, Bacchi-Reggiani L, Fallani F, Branzi A, Rapezzi C. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol. 2005 Sep 20;46(6):1076-84. doi: 10.1016/j.jacc.2005.05.073.
    Results Reference
    background
    PubMed Identifier
    21069320
    Citation
    Rapezzi C, Quarta CC, Guidalotti PL, Longhi S, Pettinato C, Leone O, Ferlini A, Salvi F, Gallo P, Gagliardi C, Branzi A. Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy. Eur J Nucl Med Mol Imaging. 2011 Mar;38(3):470-8. doi: 10.1007/s00259-010-1642-7. Epub 2010 Nov 11.
    Results Reference
    background
    PubMed Identifier
    23400849
    Citation
    Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013 Mar 1;6(2):195-201. doi: 10.1161/CIRCIMAGING.112.000132. Epub 2013 Feb 11.
    Results Reference
    background
    PubMed Identifier
    27143678
    Citation
    Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans AW, Rezk T, Fontana M, Palladini G, Milani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C, Hawkins PN. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016 Jun 14;133(24):2404-12. doi: 10.1161/CIRCULATIONAHA.116.021612. Epub 2016 Apr 22.
    Results Reference
    background
    PubMed Identifier
    7878478
    Citation
    Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995 Jan;32(1):45-59. No abstract available.
    Results Reference
    background

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    Radioisotope Scintigraphy to Establish Incidence of Cardiac Amyloidosis Among Patients With Otherwise Unexplained Cardiac Disease

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