Clinical Trial: Physiologic Assessment of Microvascular Function in Patients With Cardiac Amyloidosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: Physiologic Assessment of Microvascular Function in Patients With Cardiac Amyloidosis: Prospective Registry and Pilot Study

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.

Detailed Summary:

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 fun
Sponsor: Samsung Medical Center

Current Primary Outcome: Overt microvascular disease [ Time Frame: 24 months ]

Difference of the proportion of overt microvascular disease (CFR≤2 and IMR≥25) between patients with or without amyloidosis


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Correlation between CFR or IMR and E/E', 2D strain measure by echocardiography [ Time Frame: 24 months ]
  • Comparison of proportion of overt microvascular disease (CFR≤2 and IMR≥25) in amyloidosis patient with or without relative perfusion defect in myocardial perfusion imaging (ex> adenosine-SPECT or perfusion MRI)involvement [ Time Frame: 24 months ]
  • Distribution of CFR or IMR according to pathologic severity of myocardial involvement [ Time Frame: 24 months ]
  • 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: 24 months ]
  • Comparison of CFR or IMR value in different type of amyloidosis (AL type, hereditary type, AA type, senile type) [ Time Frame: 24 months ]
  • Comparison of CFR or IMR value in amyloidosis patient according to current staging by NT-proBNP and cardiac troponin I [ Time Frame: 24 months ]
  • Comparison of all-cause mortality in amyloidosis patients with or without overt microvascular disease (CFR≤2 and IMR≥25) [ Time Frame: 24 months ]


Original Secondary Outcome: Same as current

Information By: Samsung Medical Center

Dates:
Date Received: June 9, 2016
Date Started: May 2016
Date Completion: December 2020
Last Updated: June 14, 2016
Last Verified: June 2016