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Characteristics of Endomyocardial Biopsy in HFpEF
Quick Takes
- In a prospective cohort study of 108 HFpEF patients who underwent endomyocardial biopsy, endomyocardial fibrosis (mostly mild in severity) was widespread. Complication rates related to biopsy were very low.
- Overall, 14% of patients had biopsy-proven cardiac amyloidosis. However, only 8/15 of these patients had a clinical suspicion for amyloidosis prior to the biopsy.
- Clinical correlates of cardiac amyloidosis compared to controls included older age, lower comorbidity burden, lower BMI with higher NT-proBNP and troponin I levels, and greater wall thickness on echo with lower global longitudinal strain on echo.
Study Questions:
What are the myocardial tissue histopathological characteristics on endomyocardial biopsy in a large, prospective cohort of heart failure with preserved ejection fraction (HFpEF) patients?
Methods:
This was a prospective analysis of 108 patients referred to the Johns Hopkins University HFpEF clinic from 2014-2018. Patients with known infiltrative or restrictive cardiomyopathy were excluded. Demographics, clinical characteristics, echocardiograms, hemodynamics, and tissue histology were collected and compared to unused donor hearts and to explanted pretransplant hearts with reduced EF.
Results:
Median age for the HFpEF cohort was 66 years, 61% were women, and 57% were African-American with a high comorbidity burden including hypertension in 93% and diabetes in 54%. Median left ventricular EF (LVEF) was 65% with interventricular septal thickness of 1.3 cm, left atrial diameter of 4.2 cm, and E/e’ of 16.8. Invasive hemodynamics were consistent with HFpEF physiology. Overall procedural complication rates for endomyocardial biopsy were 0.17% for sustained arrhythmia and 0.06% for pericardial effusions that required pericardiocentesis.
Among 108 HFpEF patients, 93% had myocardial fibrosis, 88% had myocyte hypertrophy, 14% (n = 15) had cardiac amyloidosis, and one patient had borderline myocarditis. Myocardial fibrosis was mostly mild in severity (45% patients). Patients with nonamyloid HFpEF had more CD68+ monocyte infiltration compared to controls, and this correlated with older age and lower glomerular filtration rate (GFR). Of the 15 patients diagnosed with cardiac amyloidosis, 11 had transthyretin cardiomyopathy (seven wild type and four familial), three had light chain amyloidosis, and one had secondary amyloidosis (AA). At the time of referral, eight patients were clinically suspected to have amyloidosis prior to the biopsy. The other 7 out of 15 patients with biopsy-proven amyloidosis would not have been suspected to have cardiac amyloidosis based on recently published screening guidelines.
Compared with HFpEF without amyloidosis, patients with cardiac amyloidosis were older, had lower blood pressure, lower body mass index (BMI), and less comorbidity burden, but with higher N-terminal pro−B-type natriuretic peptide (NT-proBNP) and troponin I levels. Patients with amyloidosis had greater wall thickness, reduced Doppler e’ velocity, and lower global LV longitudinal strain by 2D speckle tracking.
Conclusions:
In this prospective cohort of 108 patients with HFpEF, histopathological characteristics on endomyocardial biopsy showed myocardial fibrosis and myocyte hypertrophy in most, but were relatively mild in severity. Cardiac amyloidosis was noted in 14% patients (n = 15); however, clinically only 8/15 patients had suspected amyloidosis.
Perspective:
Histopathological characteristics of HFpEF have been poorly described and this study presents the largest prospective cohort of HFpEF patients who underwent endomyocardial biopsy. Rates of procedural complications were low. The vast majority had endomyocardial fibrosis, although mild in extent. Furthermore, CD 68+ monocyte infiltration was more likely in HFpEF patients without amyloidosis compared to controls. The most notable finding includes a prevalence of cardiac amyloidosis in 14% of patients with the condition being suspected in only about 50% of these cases. This finding has significant clinical implications, as therapies for transthyretin amyloidosis have recently seen a revolution. Important clinical clues suggesting amyloidosis noted in this study included older age, lower blood pressure, and lower BMI with a lower comorbidity burden, but with higher levels of NT-proBNP and troponin I. Echocardiographic characteristics noted in patients with amyloidosis compared to HFpEF patients without amyloidosis were increased wall thickness, reduced Doppler e’ velocity, and lower global longitudinal strain.
Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Hypertension
Keywords: Amyloidosis, Biopsy, Body Mass Index, Cardiomyopathies, Diagnostic Imaging, Echocardiography, Endomyocardial Fibrosis, Heart Failure, Hemodynamics, Hypertension, Hypertrophy, Natriuretic Peptide, Brain, Prealbumin, Stroke Volume, Troponin I
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