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Physiologic Assessment of Microvascular Function in Patients With Cardiac Amyloidosis

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ClinicalTrials.gov Identifier: NCT02798705
Recruitment Status : Recruiting
First Posted : June 14, 2016
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Joo Myung Lee, Samsung Medical Center

Brief Summary:
The aim of the study is to evaluate coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and proportion of overt microvascular disease, defined as depressed CFR as well as elevated IMR in patients with cardiac amyloidosis. The second objective of this study is to compare results of non-invasive test including serum light chain amount, Doppler echocardiography with 2D strain, and cardiac perfusion MRI. The third object of this study is to evaluate the association between physiologic indices and pathologically measured percent area involvement of interstitium.

Condition or disease
Cardiac Amyloidosis

Detailed Description:

Amyloidosis is rare systemic disorder characterized by the extracellular deposition of misfolded protein in various organ system, including heart. Among the several types of amyloid fibrils, the light chain and transthyretin amyloid proteins most commonly affect the heart.

Cardiac amyloid deposits result in increased ventricular wall thickness and produce a restrictive cardiomyopathy presenting primarily as biventricular congestive heart failure. Anginal symptoms and signs of ischemia have been reported in some patients with cardiac amyloidosis without obstructive epicardial coronary artery disease (CAD). Autopsy studies have shown amyloid deposits around and between cardiac myocytes in the interstitium, the perivascular regions, and the media of intramyocardial coronary vessels. Amyloidosis is thus a prime example of a disorder with the potential to cause coronary microvascular dysfunction via 3 major mechanisms: (1) structural (amyloid deposition in the vessel wall causing wall thickening and luminal stenosis), (2) extravascular (extrinsic compression of the microvasculature from perivascular and interstitial amyloid deposits and decreased diastolic perfusion), and (3) functional (autonomic and endothelial dysfunction).

Previous basic research presented that adipose arteriole or atrial coronary arterioles showed endothelial dysfunction even after brief exposure to physiologic amounts of light chain, and also showed increased oxidative stress, reduced NO bioavailability, and peroxynitrite production. All these previous evidences imply that coronary microvascular dysfunction and subsequent global ischemic insult can be precursor of overt diastolic or systolic dysfunction in patients with cardiac amyloidosis.

However, there have only 1 study which evaluated microvascular function in vivo using N13-ammonium positron emission tomography (PET). In that study, Dorbala et al. demonstrated that amyloidosis patients showed depressed global resting myocardial blood flow (MBF), stress MBF, and CFR and higher minimal coronary vascular resistance, compared with patients with left ventricular hypertrophy. However, low availability, high cost, and limited resolution of N13 ammonium PET precludes the generalizability of the results.

Since thermodilution-derived coronary flow reserve and index or microcirculatory reserve using pressure-temperature wire has been well validated prognostic index in assessment of patients with coronary artery disease or functionally insignificant epicardial coronary stenosis, invasive physiologic assessment might more specifically assess macro- and microvascular function in patients with cardiac amyloidosis. Moreover, adding physiologic measurement in the current frame in diagnosis of cardiac amyloidosis might enhance risk stratification of patients.

Therefore, the current study will perform physiologic assessment including fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance in patients with cardiac amyloidosis, and explore correlation among the physiologic indices and conventional measurements of echocardiography, perfusion MRI, serum light chain amount, or NT-proBNP. In addition, the differences of physiologic indices according to disease severity of cardiac amyloidosis, which measured by endomyocardial biopsy findings will be also explored. Since there was no previous study which performed invasive physiologic assessment in amyloidosis patients, this study will be performed as pilot study. Target sample size will be at least 30 patients.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: Physiologic Assessment of Microvascular Function in Patients With Cardiac Amyloidosis: Prospective Registry and Pilot Study
Study Start Date : May 2016
Estimated Primary Completion Date : April 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis




Primary Outcome Measures :
  1. all-cause mortality [ Time Frame: 2 Years ]
    Comparison of all-cause mortality in amyloidosis patients with or without microvascular disease


Secondary Outcome Measures :
  1. Correlation between IMR and echocardiographic parameters [ Time Frame: within 3 months of diagnosis ]
    Correlation between IMR and echocardiographic parameters (E/E', LV ejection fraction, etc.)

  2. Correlation between IMR and serum biochemicalmarkers [ Time Frame: within 3 months of diagnosis ]
    Correlation between IMR and serum biochemicalmarkers (troponin T, NT-proBNP, serum free light chain)

  3. Distribution of CFR or IMR according to pathologic severity of myocardial involvement [ Time Frame: within 3 months of diagnosis ]
    Distribution of CFR or IMR according to pathologic severity of myocardial involvement (Percent amyloid load)

  4. Comparison of CFR or IMR value in amyloidosis patient with or without relative perfusion defect in myocardial perfusion imaging (ex> adenosine-SPECT or perfusion MRI) [ Time Frame: within 3 months of diagnosis ]
  5. Comparison of CFR or IMR value in different type of amyloidosis (AL type, hereditary type, AA type, senile type) [ Time Frame: within 3 months of diagnosis ]
  6. Comparison of CFR or IMR value in amyloidosis patient according to current staging by Troponin T, NT-proBNP and free light chain difference [ Time Frame: within 3 months of diagnosis ]
  7. Optimal cut-off values of physiologic indices (CFR, IMR) for prediction of all-cause mortality [ Time Frame: 2 Years ]
  8. Association between physiologic indices and pathologically measured percent area involvement in myocardial interstitium [ Time Frame: within 3 months of diagnosis ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pathologically confirmed amyloidosis patients with suspected cardiac involvement undergoing coronary angiography for coronary disease evaluation
Criteria

Inclusion Criteria:

  • Subject age 18-85 years old
  • Patients with confirmed cardiac amyloidosis by heart biopsy
  • Patients with confirmed amyloidosis by biopsy other than heart and evidence of cardiac involvement in echocardiography
  • Patients who underwent invasive physiologic assessment within 3 months from diagnosis of primary disease

Exclusion Criteria:

  • Patients with cardiogenic shock
  • Patients with unstable vital sign that precludes coronary angiography
  • Patients with major bleeding in last 3 months
  • Patients with active bleeding
  • Patients with coagulopathy
  • Patients with severe valvular heart disease
  • Patients who refused to provide informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02798705


Contacts
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Contact: Joo Myung Lee, MD, MPH, PhD 82-2-3410-1246 drone80@hanmail.net
Contact: Ki Hong Choi, MD 82-2-3410-1246 cardiokh@gmail.com

Locations
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Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Joo Myung Lee, MD, MPH    82-2-3410-1246    drone80@hanmail.net   
Sponsors and Collaborators
Samsung Medical Center
Investigators
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Principal Investigator: Joo Myung Lee, MD, MPH, PhD Samsung Medical Center
Principal Investigator: Eun-Seok Jeon, MD, PhD Samsung Medical Center

Additional Information:

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Responsible Party: Joo Myung Lee, Assistant professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT02798705    
Other Study ID Numbers: AMYL2016-04-122
First Posted: June 14, 2016    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked
Keywords provided by Joo Myung Lee, Samsung Medical Center:
Cardiac amyloidosis
Fractional flow reserve
Microvascular dysfunction
Coronary flow reserve
Index of microcirculatory resistance
Additional relevant MeSH terms:
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Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases