Comparison and Effectiveness of Regadenoson Versus Dipyridamole on Stress Electrocardiographic Changes During Positron Emission Tomography Evaluation of Patients With Hypertrophic Cardiomyopathy

doi:10.1016/j.amjcard.2012.05.038

The American Journal of Cardiology

Volume 110, Issue 7, 1 October 2012, Pages 1033-1039

https://doi.org/10.1016/j.amjcard.2012.05.038 Get rights and content

Dipyridamole is the most common vasodilator used with positron emission tomography for the evaluation of patients with hypertrophic cardiomyopathy (HC). The aim of this study was to evaluate whether positron emission tomographic quantification of regional myocardial perfusion (rMP), myocardial blood flow (MBF), and coronary flow reserve are comparable between dipyridamole and the newer vasodilator regadenoson in HC. An additional aim was to evaluate the association between vasodilator-induced ST-segment depression on electrocardiography and myocardial flow in HC. Nitrogen-13 ammonia positron emission tomography was performed in 57 patients with symptomatic HC at rest and during vasodilator stress (peak) with either dipyridamole (0.56 mg/kg during 4-minute infusion) or regadenoson (0.4 mg fixed bolus dose) for assessment of electrocardiographic findings, rMP (17-segment American Heart Association summed difference score), MBF, and coronary flow reserve. The dipyridamole and regadenoson groups consisted of 28 and 29 patients respectively. Baseline characteristics, including rest MBF (0.92 ± 0.22 vs 0.89 ± 0.23 ml/min/g, p = 0.60), were similar between the 2 groups. During stress, the presence and severity of abnormal rMP (summed difference score 5.5 ± 5.5 vs 5.8 ± 6.7, p = 0.80), peak MBF (1.81 ± 0.44 vs 1.82 ± 0.50 ml/min/g, p = 0.90), and coronary flow reserve (2.02 ± 0.53 vs 2.12 ± 0.12, p = 0.50) were comparable between the dipyridamole and regadenoson groups. Fewer patients exhibited side effects with regadenoson (2 vs 7, p = 0.06). Vasodilator-induced ST-segment depression showed high specificity (about 92%) but low sensitivity (about 34%) to predict abnormal rMP (summed difference score ≥2). In conclusion, measurement of rMP and quantitative flow with positron emission tomography is similar between regadenoson and dipyridamole in patients with symptomatic HC. Regadenoson is tolerated better than dipyridamole and is easier to administer. Vasodilator-induced ST-segment depression is a specific but nonsensitive marker for the prediction of abnormal rMP in patients with HC.

Section snippets

Methods

We performed a retrospective analysis of consecutive patients with histories of HC diagnosed by echocardiography, who were referred for cardiac PET imaging for clinical indications from June 2009 to February 2012. Subjects with histories of coronary artery disease, previous surgical myectomy, or alcohol septal ablation were excluded. The diagnosis of HC was based on echocardiographic criteria by demonstrating left ventricular (LV) hypertrophy with wall thickness ≥15 mm.¹ LV outflow tract

Results

A total of 57 patients with HC were included in this cohort: 28 were stressed with dipyridamole (group 1) and 29 with regadenoson (group 2). Baseline and echocardiographic characteristics, including maximal wall thickness, were highly comparable between the 2 groups (Table 1). Heart rate and mean arterial blood pressure were statistically similar between the groups before the administration of either stress agent, although there was a trend toward higher rate-pressure products in the

Discussion

The main results of this study are as follows: (1) regadenoson and dipyridamole are comparable as vasodilators for stress testing in patients with HC, (2) regadenoson is better tolerated than dipyridamole, (3) vasodilator-induced ST-segment depression is specific but nonsensitive to predict abnormal rMP, and (4) chest pain elicited during vasodilator stress is likely due to myocardial ischemia in patients with HC.

We observed similar values of peak MBF and CFR after the infusion of dipyridamole

Acknowledgment

We would like to thank Judy Buchanan, Division of Nuclear Medicine, Johns Hopkins University, for her helpful editorial assistance.

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Cited by (20)

Sex-specific cardiac phenotype and clinical outcomes in patients with hypertrophic cardiomyopathy
2020, American Heart Journal
Citation Excerpt :
Approximately 370 MBq (10 mCi) of 13N-ammonia was injected intravenously, followed by PET acquisition in two-dimensional list mode for 20 minutes. Vasodilator stress was induced approximately 60 minutes after injection of the rest dose.32 Semi-automated analysis of the resulting myocardial perfusion images was performed using QPET (Cedars Sinai, Los Angeles, California).
It is unknown whether sex-specific differences in mortality observed in HCM are due to older age of women at presentation, or whether women have greater degree of LV myopathy than men.
We retrospectively compared clinical/imaging characteristics and outcomes between women and men in our overall cohort composed of 728 HCM patients, and in an age-matched subgroup comprised of 400 age-matched patients. We examined sex-specific differences in LV myopathy, and dissected the influence of age and sex on outcomes. LV myopathy was assessed by measuring LV mass, LVEF, global peak longitudinal systolic strain (LV-GLS), diastolic function (E/A, E/e′), late gadolinium enhancement (LV-LGE) and myocardial blood flow (MBF) at rest/stress. The primary endpoint was a composite outcome, comprising heart failure (HF), atrial fibrillation (AFib), ventricular tachycardia/fibrillation (VT/VF) and death; individual outcomes were defined as the secondary endpoint.
Women in the overall cohort were older by 6 years. Women were more symptomatic and more likely to have obstructive HCM. Women had smaller LV cavity size, stroke volume and LV mass, higher indexed maximum wall thickness (IMWT), more hyperdynamic LVEF and higher/similar LV-GLS. Women had similar LV-LGE and E/A, but higher E/e′ and rest/stress MBF. Female sex was independently associated with the composite outcome in the overall cohort, and with HF in the overall cohort and age-matched subgroup after adjusting for obstructive HCM, LA diameter, LV-GLS.
Our results suggest that sex-specific differences in LV geometry, hyper-contractility and diastolic function, not greater degree of LV myopathy, contribute to a higher, age-independent risk of diastolic HF in women with HCM.
Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy
2018, American Journal of Cardiology
Citation Excerpt :
Approximately 370 MBq (10 mCi) of 13N-ammonia was injected intravenously, followed by PET acquisition in 2-dimensional list mode for 20 minutes. Vasodilator stress was induced by dipyridamole or regadenoson, approximately 60 minutes after injection of the rest dose.12 Semiautomated analysis of the resulting myocardial perfusion images was performed using QPET (Cedars Sinai, Los Angeles, California).
Patients with hypertrophic cardiomyopathy (HC) are at increased risk of sudden cardiac death. Abnormalities in myocardial blood flow (MBF) detected by positron emission tomography (PET) are common in HC, but a PET marker that identifies patients at risk of sudden cardiac death is lacking. We hypothesized that disparities in regional myocardial perfusion detected by PET would identify patients with HC at risk of ventricular arrhythmias. To test this hypothesis, we quantified global and regional MBFs by ¹³NH₃-PET at rest and at stress, and developed a heterogeneity index to assess MBF heterogeneity in 133 symptomatic patients with HC. The MBF heterogeneity index was computed by dividing the highest by the lowest regional MBF value, at rest and after vasodilator stress, in each patient. High stress MBF heterogeneity was defined as an index of ≧1.85. Patients with HC were stratified by the presence or the absence of ventricular arrhythmias, defined as sustained ventricular tachycardia (VT) and/or nonsustained VT, during follow-up. We found that global and regional MBFs at rest and stress were similar in patients with HC with or without ventricular arrhythmias. Variability in regional stress MBF was observed in both groups, but the stress MBF heterogeneity index was significantly higher in patients with HC who developed ventricular arrhythmias (1.82 ± 0.77 vs 1.49 ± 0.25, p <0.001). A stress MBF heterogeneity index of ≧1.85 was an independent predictor of both sustained VT (hazard ratio 16.1, 95% confidence interval 3.2 to 80.3) and all-VT (sustained-VT + nonsustained VT: hazard ratio 3.7, 95% confidence interval 1.4 to 9.7). High heterogeneity of stress MBF, reflected by an MBF heterogeneity index of ≥1.85, is a PET biomarker for ventricular arrhythmias in symptomatic patients with HC.
Relationships between left ventricular asynchrony and myocardial blood flow
2017, Journal of Nuclear Cardiology
⁸²Rb PET protocols enable determination of left ventricular asynchrony (LVAS) at rest and stress, along with myocardial blood flow (MBF). We hypothesized that in patients with resting LVAS, MBF differs between those with stress-induced LVAS improvement and those with stress-induced LVAS deterioration.
We retrospectively analyzed ⁸²Rb rest/regadenoson stress PET studies of 195 patients evaluated for known or suspected coronary artery disease. MBF was computed from first-pass data; function and relative perfusion were computed from myocardial equilibrium data. LVAS was defined as phase contraction bandwidth (BW) above ⁸²Rb gender-specific normal limits, with changes defined as BW moving into or out of normal ranges.
Among the 195 patients, 64 had LVAS at rest, of whom 13 reverted to normal and 51 continued to have LVAS with stress. Patients who did not improve had lower stress MBF (1.04 ± 0.69 vs 1.58 ± 0.67, p = .02) and coronary flow reserve (1.94 ± 1.16 vs 3.04 ± 1.22, p = .01) than those who did improve. ROC analysis indicated that the parameter most strongly associated with improvement in asynchrony for patients with resting LVAS was reduction in MBF heterogeneity (ROC area (accuracy) = 84%, sensitivity = 92%, and specificity = 67%).
LVAS is highly correlated with MBF and CVR, with stress-induced improvement in synchronicity most strongly associated with improved MBF homogeneity.
Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by <sup>13</sup>N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy
2016, American Journal of Cardiology
Citation Excerpt :
For Regadenoson, a standard dose of 0.4 mg was injected as a bolus for 15 to 20 seconds, followed by a 5-ml saline flush; 13N-ammonia was administered 30 seconds later followed by immediate start of stress acquisition, using the same parameters as the rest acquisition. Both vasodilator agents have been demonstrated to mediate comparable levels of hyperemic MBF.9 Heart rate, blood pressure, and 12-lead electrocardiogram (ECG) were recorded before, during, and after the stress protocol.
Vasodilator-induced transient left ventricular (LV) cavity dilation by positron emission tomography (PET) is common in patients with hypertrophic cardiomyopathy (HC). Because most patients with PET-LV cavity dilation lack obstructive epicardial coronary artery disease, we hypothesized that vasodilator-induced subendocardial hypoperfusion resulting from microvascular dysfunction underlies this result. To test this hypothesis, we quantified myocardial blood flow (MBF) (subepicardial, subendocardial, and global MBF) and left ventricular ejection fraction (LVEF) in 104 patients with HC without significant coronary artery disease, using ¹³NH₃-PET. Patients with HC were divided into 2 groups, based on the presence/absence of LV cavity dilation (LVvolume_stress/LVvolume_rest >1.13). Transient PET-LV cavity dilation was evident in 52% of patients with HC. LV mass, stress left ventricular outflow tract gradient, mitral E/E′, late gadolinium enhancement, and prevalence of ischemic ST-T changes after vasodilator were significantly higher in patients with HC with LV cavity dilation. Baseline LVEF was similar in the 2 groups, but LV cavity dilation⁺ patients had lower stress-LVEF (43 ± 11 vs 53 ± 10; p <0.001), lower stress-MBF in the subendocardial region (1.6 ± 0.7 vs 2.3 ± 1.0 ml/min/g; p <0.001), and greater regional perfusion abnormalities (summed difference score: 7.0 ± 6.1 vs 3.9 ± 4.3; p = 0.004). The transmural perfusion gradient, an indicator of subendocardial perfusion, was similar at rest in the 2 groups. Notably, LV cavity dilation⁺ patients had lower stress-transmural perfusion gradients (0.85 ± 0.22, LV cavity dilation⁺ vs 1.09 ± 0.39, LV cavity dilation⁻; p <0.001), indicating vasodilator-induced subendocardial hypoperfusion. The stress-transmural perfusion gradient, global myocardial flow reserve, and stress-LVEF were associated with LV cavity dilation. In conclusion, diffuse subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient LV cavity dilation in HC.
Apparent left ventricular cavity dilatation during PET/CT in hypertrophic cardiomyopathy: Clinical predictors and potential mechanisms
2016, Journal of Nuclear Cardiology
Apparent left ventricular cavity dilatation (LVCD) in patients with hypertrophic cardiomyopathy (HCM) is an incompletely understood phenomenon. We aimed at investigating its clinical predictors and potential mechanisms.
Sixty one HCM patients underwent N-13-ammonia PET for visual evaluation of LVCD, transient ischemic dilatation (TID) index, myocardial blood flow (MBF), coronary flow reserve (CFR), and regional myocardial perfusion (rMP). TID index was also derived at 2–4 and 15–20 minutes.
Visual LVCD and quantitative TID (>1.13 abnormal) agreement were excellent (k 0.91; P < .0001). LVCD-positive (n = 32) patients had greater LV thickness (2.26 ± 0.59 vs 1.92 ± 0.41 cm; P = .005), but lower stress MBF (1.66 ± 0.42 vs 2.07 ± 0.46 mL/minute/g; P < .0001), and CFR (1.90 ± 0.46 vs 2.46 ± 0.69; P < .0001) than LVCD-negative (n = 29) patients. Abnormal rMP was present in 31/32 LVCD-positive but only 12/29 (P < .0001) LVCD-negative. TID index was higher at 2–4 (1.30 ± 0.13) than at 15–20 minutes (1.27 ± 0.12; P = .001) in LVCD-positive, whereas it was the same (1.04 ± 0.07 vs 1.04 ± 0.07; P = .9) in LVCD-negative. In multivariate analysis, global peak MBF, abnormal rMP, and LV thickness were the best predictors of LVCD.
Apparent LVCD is a common finding in HCM, intimately related to abnormal myocardial perfusion, globally impaired vasodilator flow reserve, and degree of hypertrophy. In addition to regional and/or diffuse subendocardial ischemia, some degree of true LV chamber dilatation may also contribute to the occurrence of apparent LVCD in HCM.
Comparison of Outcomes in Patients With Nonobstructive, Labile-Obstructive, and Chronically Obstructive Hypertrophic Cardiomyopathy
2015, American Journal of Cardiology
Citation Excerpt :
Patients with angina ≥3 months despite optimal medical therapy were referred for positron emission tomography (PET) scanning and were imaged using a GE Discovery VCT PET/CT system. Regional myocardial perfusion was assessed using a same day rest/stress protocol as described previously.3,21,23,24 Attenuation-corrected PET images were reconstructed by an iterative algorithm with postprocessing filtering and static data sets analyzed using CardIQ Physio (GE Healthcare).
Patients with nonobstructive hypertrophic cardiomyopathy (HC) are considered low risk, generally not requiring aggressive intervention. However, nonobstructive and labile-obstructive HC have been traditionally classified together, and it is unknown if these 2 subgroups have distinct risk profiles. We compared cardiovascular outcomes in 293 patients HC (96 nonobstructive, 114 labile-obstructive, and 83 obstructive) referred for exercise echocardiography and magnetic resonance imaging and followed for 3.3 ± 3.6 years. A subgroup (34 nonobstructive, 28 labile-obstructive, 21 obstructive) underwent positron emission tomography. The mean number of sudden cardiac death risk factors was similar among groups (nonobstructive: 1.4 vs labile-obstructive: 1.2 vs obstructive: 1.4 risk factors, p = 0.2). Prevalence of late gadolinium enhancement (LGE) was similar across groups but more non-obstructive patients had late gadolinium enhancement ≥20% of myocardial mass (23 [30%] vs 19 [18%] labile-obstructive and 8 [11%] obstructive, p = 0.01]. Fewer labile-obstructive patients had regional positron emission tomography perfusion abnormalities (12 [46%] vs nonobstructive 30 [81%] and obstructive 17 [85%], p = 0.003]. During follow-up, 60 events were recorded (36 ventricular tachycardia/ventricular fibrillation, including 30 defibrillator discharges, 12 heart failure worsening, and 2 deaths). Nonobstructive patients were at greater risk of VT/VF at follow-up, compared to labile obstructive (hazed ratio 0.18, 95% confidence interval 0.04 to 0.84, p = 0.03) and the risk persisted after adjusting for age, gender, syncope, family history of sudden cardiac death, abnormal blood pressure response, and septum ≥3 cm (p = 0.04). Appropriate defibrillator discharges were more frequent in nonobstructive (8 [18%]) compared to labile-obstructive (0 [0%], p = 0.02) patients. In conclusion, nonobstructive hemodynamics is associated with more pronounced fibrosis and ischemia than labile-obstructive and is an independent predictor of VT/VF in HC.

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: This work was partially supported by a grant from the National Institutes of Health (HL098046). Dr. Pozios is supported in part by grants from the Hellenic Cardiology Society.

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CardiomyopathyComparison and Effectiveness of Regadenoson Versus Dipyridamole on Stress Electrocardiographic Changes During Positron Emission Tomography Evaluation of Patients With Hypertrophic Cardiomyopathy

Section snippets

Methods

Results

Discussion

Acknowledgment

J Am Coll Cardiol

J Am Coll Cardiol

J Nucl Cardiol

Am Heart J

J Am Coll Cardiol

J Nucl Cardiol

JACC Cardiovasc Imaging

Am Heart J

Cardiomyopathy
Comparison and Effectiveness of Regadenoson Versus Dipyridamole on Stress Electrocardiographic Changes During Positron Emission Tomography Evaluation of Patients With Hypertrophic Cardiomyopathy