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PLOS One logoLink to PLOS One
. 2023 Oct 12;18(10):e0292950. doi: 10.1371/journal.pone.0292950

Safety and clinical impact of adenosine stress perfusion cardiac magnetic resonance in Asian patients with known or suspected coronary artery disease

Yodying Kaolawanich 1, Thammarak Songsangjinda 1,2, Kanchalaporn Jirataiporn 1, Ahthit Yindeengam 1, Rungroj Krittayaphong 1,*
Editor: Vikramaditya Samala Venkata3
PMCID: PMC10569532  PMID: 37824593

Abstract

Background

Adenosine stress cardiac magnetic resonance (CMR) imaging is increasingly utilized for evaluating patients with known or suspected coronary artery disease (CAD). This study aims to assess the safety and clinical impact of adenosine stress CMR in a tertiary care setting in Thailand.

Methods

A total of 3,768 consecutive patients aged 18 years and above who underwent adenosine stress CMR between 2017 and 2020 were included in the study. Patient records were reviewed to collect data on clinical characteristics, hemodynamic measurements, complications during or immediately after CMR, and the rates of clinical changes resulting from CMR.

Results

Among the included patients, the primary indications for adenosine stress CMR were risk stratification in suspected CAD (70.8%) and the assessment of myocardial ischemia/viability in patients with known CAD (26.5%). There were no reported deaths or acute myocardial infarctions during the procedure. Major complications, specifically acute pulmonary edema requiring hospital observation or admission for further management, occurred in four patients (0.11%), all of whom were elderly (ranging from 75 to 91 years) with a history of heart failure. Non-major complications were observed in 13.7% of patients, with dyspnea (9.8%) and mild chest pain (5.6%) being the most common. CMR provided a completely new diagnosis in 26.2% of patients. Overall, stress CMR resulted in a change in diagnosis or management for 48% of patients.

Conclusion

Adenosine stress CMR was found to be safe and to have a significant impact on clinical management in Asian patients with known or suspected CAD. These findings support the use of adenosine stress CMR as a valuable tool for evaluating and guiding treatment decisions in this patient population.

Introduction

Coronary artery disease (CAD) is a significant global health burden, with a high prevalence and impact on individuals and healthcare systems. Accurate diagnosis and risk stratification of patients with known or suspected CAD are of utmost importance. Stress cardiac magnetic resonance (CMR), commonly using adenosine, is increasingly being utilized. CMR provides a comprehensive assessment of CAD with very high accuracy [1]. It can assess global and regional ventricular function, myocardial ischemia, and infarction in a single study. Moreover, stress CMR offers strong evidence for prognosis, including mortality, in patients with known or suspected CAD [2, 3].

Stress CMR has demonstrated a significant impact on the diagnosis and management of a large patient population, as evidenced by The EuroCMR registry, which included more than 9,500 patients suspected of CAD or suspected ischemia in known CAD who underwent stress tests [4]. Previous studies have reported that stress CMR resulted in a substantial alteration in clinical care for approximately 60–70% of patients [4, 5]. The safety profile of stress CMR has been documented in prior studies. Menadas et al. demonstrated that dipyridamole stress CMR was feasible and safe, with a rate of severe immediate complications of 0.06% [6]. Bruder et al. also showed a very low rate of severe complications of stress CMR using adenosine and dobutamine, with a rate of 0.026% [4]. However, there are limited studies regarding the clinical impact and safety of stress CMR in Asia, and most of them were relatively small in scale [7, 8].

This study aims to assess the safety and clinical impact of adenosine stress CMR in a tertiary care setting in Thailand.

Methods

Study population

This was a retrospective observational study conducted at Siriraj Hospital, an academic medical center in Bangkok, Thailand. We included consecutive patients aged 18 years or older who were referred for adenosine stress CMR for clinical purposes during 2017 to 2019. Patients were excluded if they had incomplete CMR scans or if they did not have follow-up data after CMR. Information on baseline demographic variables was obtained from the electronic medical record. Hypertension was defined as a self-reported history of hypertension, the use of antihypertensive medication, or an office blood pressure of ≥140/90 mmHg. Diabetes was defined as a self-reported history of diabetes and/or receiving anti-diabetic treatment, or a fasting glucose level of ≥126 mg/dL. Dyslipidemia was defined as a total cholesterol level of ≥240 mg/dL, a low-density lipoprotein (LDL) cholesterol level of ≥130 mg/dL, a high-density lipoprotein (HDL) cholesterol level of <40 mg/dL, a triglyceride level of ≥200 mg/dL, and/or treatment with a lipid-lowering agent. The protocol for this study was approved by the Siriraj Institutional Review Board. The Ethics Committee waived the requirement of written informed consent for participation due to the retrospective design of the study. Data were accessed for research purposes between 1st April 2020 and 30th January 2023.

CMR protocol and analysis

CMR was performed using standardized protocols recommended by the Society of Cardiovascular Magnetic Resonance (SCMR) [9] on a 3T scanner (Philips Medical Systems, Best, The Netherlands) and interpreted by experienced readers. The CMR protocol included ventricular function assessment using a standard steady-state free precession sequence obtained in short and long-axis views, myocardial first-pass perfusion, and late gadolinium enhancement (LGE). Three short-axis slices at the apical, mid, and basal left ventricular levels were chosen for perfusion imaging with an electrocardiographic (ECG)-triggered, T1-weighted, inversion recovery single-shot turbo gradient echo sequence. Typical image parameters were described elsewhere [10].

Venous access was obtained in both upper limbs, with one being used for continuous adenosine infusion and the other being used for gadolinium contrast infusion at peak stress. Patients were continuously monitored with peripheral oxygen saturation probe, heart rate, and real‐time electrocardiography (ECG) throughout the CMR scan. Blood pressure (BP) was recorded before starting the infusion and was checked every minute during adenosine infusion. The myocardial first-pass perfusion study was performed by injecting 0.05 mmol/kg of gadolinium contrast agent (Magnevist, Bayer Schering Pharma, Berlin, Germany) at a rate of 4 mL/s immediately after a 4-minute infusion of 140 mcg/kg/min of adenosine [9]. Patients were asked about any symptoms experienced during the infusion in order to assess their hemodynamic response and monitor for any potential complications. The adenosine infusion was discontinued prematurely if requested by the patient or in the presence of progressive or severe angina, dyspnea, a decrease in systolic pressure >40 mmHg, severe arrhythmias, or other adverse effects. LGE imaging obtained 10–15 minutes after administration of intravenous gadolinium (0.15 mmol/kg), as per published guidelines [9]. CMR images were interpreted by standard methods [11]. In brief, perfusion images were read, and each of the 16 segments was visualized (segment-17 at the apex was not visualized). Inducible ischemia was defined as a subendocardial perfusion defect that (i) persisted beyond peak myocardial enhancement and for several RR intervals, (ii) was more than two pixels wide, (iii) followed one or more coronary arteries, and (iv) showed absence of LGE in the same segment. Dark-banding artefacts were recorded if an endocardial dark band appeared at the arrival of contrast in the LV cavity before contrast arrival in the myocardium. LGE images were also analyzed using visual assessment. LGE was considered present only if confirmed on both the short-axis and at least one other orthogonal plane. CMR diagnosis of CAD includes either a stress-inducible perfusion defect or the presence of ischemic LGE. The CMR diagnosis of nonischemic cardiomyopathy includes a nonischemic LGE pattern (e.g., midwall LGE for dilated cardiomyopathy) without stress-induced perfusion defects.

Complications of CMR

Major complications were defined as death, resuscitation, or any other condition related to the CMR procedure that required monitoring as an inpatient for at least 1 night after the CMR scan (e.g., acute myocardial infraction, acute pulmonary edema, ischemic stroke, arrhythmias, and so on). Non-major complications were defined as any complications related to CMR that did not fulfill the criteria for severe complications (e.g., dyspnea, chest pain, allergic reactions without shock, problems related to intravenous lines, and so forth).

Influence of CMR on subsequent clinical management

Two cardiologists, who were blinded to the CMR results, reviewed patient information, including baseline characteristics, indications for CMR, adverse events during CMR studies, and changes in management after CMR. They independently assessed the clinical impact of each stress CMR by reviewing electronic medical records up to the next outpatient visit with the ordering provider. A “completely new diagnosis” was defined as a diagnosis occurring only if it was previously unknown to the referring physician.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY, USA). Continuous variables with a normal distribution were presented as mean ± standard deviation (SD), and continuous variables with a non-normal distribution were presented as median and interquartile range. The normality distribution of the variables was examined using the Kolmogorov-Smirnov test. Categorical variables were presented as absolute numbers and percentages. Differences were compared using Student’s unpaired t-test or Mann-Whitney U test for continuous variables, and the chi-square test or Fisher’s exact test for categorical variables, as appropriate. All statistical tests were two-tailed, and p-values less than 0.05 were considered to indicate statistical significance.

Results

Patient characteristics

A total of 3,785 patients were scanned within a period of 31 months. Flow diagram is presented in Fig 1. Ten patients with a contraindication to adenosine stress CMR (e.g., severe claustrophobia, known or suspected bronchoconstrictive or bronchospastic disease) and 7 patients with incomplete CMR scans were excluded. As a result, 3,768 patients were included in the final analysis. The main indications for adenosine stress CMR were risk stratification in suspected CAD (70.8%) and the assessment of myocardial ischemia/viability in patients with known CAD (26.5%) (Fig 1).

Fig 1. Flow diagram of the study.

Fig 1

Abbreviations: CAD = coronary artery disease, CMR = cardiac magnetic resonance.

Clinical characteristics of the patients are presented in Table 1. The mean age was 67.5±13.6 years, and 1,818 (48.2%) were male. Hypertension was the most prevalent CAD risk factor, observed in 73.9% of the patients. A total of 1,448 (38.4%) had diabetes mellitus. Among the patients, 1,082 had known CAD, with 264 having a prior myocardial infarction (MI). Forty-six percent of the patients presented with dyspnea, while twenty-two percent presented with chest pain.

Table 1. Clinical characteristics of the study population.

Characteristics Total (n = 3,768)
Age (years) 67.5±13.6
Male 1,818 (48.2)
Body mass index (kg/m2) 25.5±4.6
CAD risk factors
    Hypertension 2,785 (73.9)
    Hyperlipidemia 2,401 (63.7)
    Diabetes mellitus 1,448 (38.4)
    Cigarette smoking 115 (3.1)
    Family history of CAD 23 (0.6)
Medical history
    Known CAD 1,082 (28.7)
    Prior myocardial infarction 264 (7.0)
    Revascularization, PCI 469 (12.4)
    Revascularization, CABG 256 (6.8)
    History of heart failure 447 (11.9)
    Atrial fibrillation 392 (10.4)
    Stroke 251 (6.7)
Symptoms
    Chest pain 832 (22.1)
    Dyspnea 1,755 (46.6)
    Other symptoms 24 (0.6)
    No symptom 296 (7.9)
Medications
    Antiplatelet 2,025 (53.7)
    Anticoagulant 303 (8.0)
    ACEI or ARB 1,480 (39.3)
    Beta blocker 1,977 (52.5)
    Calcium channel blocker 1,100 (29.2)
    Diuretic 744 (19.7)
    Nitrate 746 (19.8)
    Oral hypoglycemic agent 891 (23.6)
    Insulin 204 (5.4)

Values are mean ± standard deviation or number (%).

Abbreviations: ACEI = angiotensin-converting enzyme inhibitors, ARB = angiotensin receptor blockers, CABG = coronary artery bypass graft, CAD = coronary artery disease, PCI = percutaneous coronary intervention.

Hemodynamic measurements

An increase in heart rate was observed in 2,973 (79.0%) patients, and a reduction in blood pressure was observed in 2,987 (79.5%) patients. Fig 2 depicts the hemodynamic effects of adenosine in our patients. Overall, there was a significant decrease in mean systolic and diastolic blood pressure (systolic: 135.2 ± 19.9 [rest] versus 124.8 ± 19.4 mmHg [during adenosine infusion], p < 0.001; diastolic: 74.7 ± 13.6 [rest] versus 66.0 ± 12.7 mmHg [during adenosine infusion], p < 0.001, respectively), accompanied by a compensatory increase in mean heart rate (75.7 ± 13.9 [rest] versus 83.4 ± 14.3 beats per minute [during adenosine infusion], p < 0.001).

Fig 2. Hemodynamic parameters at rest and during adenosine infusion.

Fig 2

Abbreviations: DBP = diastolic blood pressure, HR = heart rate, SBP = systolic blood pressure.

Major and non-major complications

Major complications occurred in four patients (0.11%), all of whom had acute pulmonary edema requiring hospital observation or admission for further management. All four patients, aged over 75 (ranging from 75 to 91 years), required hospital observation or admission for further management. They had previously been diagnosed with heart failure, classified as New York Heart Association (NYHA) class II-III, with two having reduced left ventricular ejection fraction and two having preserved left ventricular ejection fraction. Table 2 shows major complications during or immediately after CMR scans. There was no reported death or acute MI during the procedure.

Table 2. Major complications during or immediately after CMR scans.

Total (n = 3,768)
Major complications 4 (0.11)
    Acute pulmonary edema 4 (0.11)
    Acute myocardial infraction 0
    aUnstable angina 0
    Cardiac arrest 0
    Sustained ventricular tachycardia 0
    Ischemic stroke or transient ischemic attack 0
    Severe symptomatic hypotension 0
    Anaphylactic shock 0

Values are number (%).

Abbreviations: CMR = cardiac magnetic resonance.

aChest pain of >20 min duration despite treatment, requiring hospital admission.

Non-major complications occurred in 517 patients (13.7%), with 368 experiencing dyspnea (9.8%) and 209 reporting mild chest pain (5.6%) as the most common symptoms. The remaining patients experienced nausea (n = 7), local complications at intravenous access sites, such as small hematoma, edema, or phlebitis (n = 7), and contrast allergy without shock (n = 3). No patients exhibited atrioventricular block. Among patients with dyspnea, there was no significant difference between those with a history of heart failure (n = 34/447; 7.6%) and those without (n = 334/3321; 10.1%), p = 0.10. Similarly, among patients with mild chest pain, there was no significant difference between those with known CAD (n = 65/1082; 6.0%) and those with suspected CAD (n = 114/2686; 5.4%), p = 0.43. Noted, there is no difference in the rate of patients with positive stress CMR who developed dyspnea or mild chest pain during CMR (p>0.05 for both). Fig 3 demonstrates non-major complications during or immediately after CMR scans.

Fig 3. Non-major complications during or immediately after CMR scans.

Fig 3

Clinical impact of CMR

Table 3 demonstrates the number of patients with a completely new diagnosis and changes in management after CMR. Adenosine stress CMR provided a diagnosis of 650 cases of CAD in patients with unknown CAD (before CMR). Additionally, comprehensive CMR examinations enabled the identification of nonischemic cardiomyopathies, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, and myocarditis. CMR also facilitated the diagnosis of severe valvular disease, necessitating valvular surgery or intervention.

Table 3. Impact of CMR on diagnosis and patient management.

Variables Total (n = 3,768)
Completely new diagnosis 986 (26.2%)
    CAD 650
    Non-CAD 336
     Dilated cardiomyopathy 93
     Hypertrophic cardiomyopathy 55
     Significant valvular disease 53
     Vascular disease 35
     Hypertensive heart disease 19
     Myocarditis 12
     Noncompaction cardiomyopathy 11
     Others 58
Therapeutic consequences 1,110 (29.5%)
    Change in medication 807
    Add new medication 459
     Aspirin 147
     Clopidogrel 127
     Anticoagulation 31
     Beta blocker 147
     Calcium channel blocker 43
     Nitrate 88
     Statin 100
    Discontinued Medication 201
    Dose changed 249
    Invasive procedure 534
Impact on patient management (completely new diagnosis and/or therapeutic consequences) 1,814 (48.1%)

Values are number (%).

Abbreviations: CAD = coronary artery disease.

CMR resulted in therapeutic consequences in 1,110 (29.5%) patients, including changes in medication in 21.4% and invasive procedures in 14.2%. Overall, CMR had an impact on the diagnosis and patient management (completely new diagnosis and/or therapeutic consequences) in 48% of the patients.

Discussion

In this study, we have shown the main following findings: 1) Adenosine stress CMR was found to be safe, with a very low rate of major complications, specifically acute pulmonary edema (0.11%). All cases of acute pulmonary edema occurred in elderly patients with a history of heart failure. 2) Non-major complications were observed in 13.6% of the patients, with the most common being dyspnea and mild chest pain. These symptoms were not associated with patient characteristics such as heart failure or CAD status. 3) Adenosine stress CMR had a significant impact on diagnosis and clinical management, resulting in 48% of patients receiving a new diagnosis or experiencing changes in their management.

Stress CMR has emerged as a prominent imaging modality for the detection and risk stratification of patients with known or suspected CAD. CMR can provide integrated information of cardiac function, structural changes such as LGE, and myocardial ischemia by studying myocardial perfusion in one examination [12]. Stress CMR, whether using vasodilators or dobutamine, has strong evidence for the diagnosis and prognosis of patients with known or suspected CAD [13]. Dipyridamole, one of the vasodilators used for stress CMR, has been shown to be safe. Menadas et al. reported a very low rate of severe immediate complications and demonstrated that inducible ischemia was the only factor identified as being associated with serious complications [6]. Adenosine has been the most commonly used vasodilator for stress CMR and has been shown to exhibit better sensitivity and specificity compared to dipyridamole [13]. Our center has demonstrated good accuracy with adenosine stress CMR, achieving a sensitivity of 89.5% and a specificity of 78.6% compared to invasive coronary angiography [14]. These results are consistent with other published papers that also demonstrate good accuracy [13].

Adenosine stress CMR has also demontrated a favorable safety profile in several studies conducted in Western countries [4, 15]. The safety of adenosine stress CMR in Asia has been studied by Raj et al. [8] in 1,057 patients and Tsang et al. [7] in 98 patients. Both studies demonstrated a very low rate (<0.5%) of adverse events during or immediately after CMR. Our study, conducted with a larger patient population of 3,768 patients, also yielded consistent results. The majority of our patients exhibited a hemodynamic response to adenosine, characterized by a decrease in blood pressure and an increase in heart rate. There were no reported deaths or acute MIs during or immediately after CMR. Four patients with acute pulmonary edema were reported, all of whom were elderly and had symptomatic heart failure. It is known that a comprehensive stress CMR protocol requires patient cooperation, as they have to remain supine in a magnet for at least 30 minutes and repeatedly hold their breath. Patients with symptomatic heart failure, especially those with fluid retention, are at a high risk for a heart failure event during or after CMR. A study by Raj et al. in India demonstrated that three patients experienced severe breathlessness during adenosine infusion and required further management, and one of them had a reduced LVEF [8]. This was consistent with our results.

The studies by Bruder and Menadas from Western countries showed differences compared to our data [4, 6]. Bruder et al. reported a very low rate of severe complications (0.026%) from the EuroCMR registry, independent of patient gender or age [4]. Similarly, Menadas et al. reported a very low rate of severe complications (0.08%), with no association found between complications and demographic, clinical, hemodynamic, or CMR-derived parameters [6]. Although our results differed from those of Bruder and Menadas, these discrepancies could be due to chance given the very low event rate. It’s worth noting that our study included older patients with a higher prevalence of heart failure, more than double that of Menadas. Non-major complications occurred in 13.7% of our patients, with the most common being dyspnea and mild chest pain. These two symptoms were not related to patient characteristics such as heart failure symptom or CAD status. It is likely that they were effects of adenosine itself, which were not significant and could self-recover without requiring any specific treatment. Overall, we believe that adenosine stress CMR is safe for the majority of referred patients.

Several studies have reported a significant clinical impact of stress CMR. In our study, 48% of patients had a management impact, resulting in new diagnoses or changes in treatment based on CMR results. Approximately 10% of these patients had non-CAD diagnoses such as dilated cardiomyopathy, hypertrophic cardiomyopathy, or severe valvular disease, requiring different treatments including surgery or interventional procedures. These findings underscore the value of stress CMR. It is important to note that our results may differ from previous studies due to variations in endpoint definitions. For instance, McGraw et al. reported that stress CMR led to active changes in clinical care in about 70% of patients [5]. However, their study included subspecialty consultations, preoperative clearances, or discharge from the Cardiology Clinic as criteria for active clinical change. On the other hand, Bruder et al., whose definition was more similar to ours, found that approximately 60% of patients had an impact from CMR results [4]. It is worth mentioning that Bruder’s study included both stress and non-stress CMR. Nonetheless, stress CMR continues to have a significant impact on clinical decision-making, as observed in our study.

Table 4 presents a summary of patients’ profiles, complications, and the clinical impact of stress CMR in our study, compared with previously published data [48]. Our data demonstrated some degree of similarity in patient profiles, such as having 28% with known CAD, consistent with Menadas et al. and McGraw et al. [5, 6] Notably, our study had a lower proportion of male participants compared to most studies, as male patients may have a higher pretest probability of obstructive CAD and may undergo invasive coronary angiography rather than CMR. Regarding complications, our study and all studies had quite similar very low rates of major complications (<0.3% in all studies), showing a consistent safety profile of stress CMR, while there were some differences in baseline characteristics. As for the clinical impact of CMR, although there were differences in the definitions of impact and/or therapeutic consequences, all studies also showed a consistent and significant impact of CMR. Overall, we have added data from Asia showing that CMR is safe and has a clinical impact compared to studies from Western countries.

Table 4. Summary of patients’ characteristics, complications, and clinical impact of stress CMR in published articles.

Kaolawanich, et al. Menadas, et al. [6] Bruder, et al. [4] McGraw, et al. [5] Raj, et al. [8] Tsang, et al. [7]
Year of enrollment 2017–2020 2004–2014 Until 2012 N/A 2018–2019 2013
Number of patients 3,768 11,984 27,781 350 1,057 98
Country Thailand Spain Europe USA India China
Asian 100% 0% 0% 0% 100% 100%
% with stress test 100% 100% 37.4% 100% 100% 100%
Stressors Adenosine • Dipyridamole (95.4%)
• Dobutamine (4.6%)
• Adenosine (78.3%)
• Dobutamine (21.7%)
Regadenoson Adenosine Adenosine
Age (mean) 67.5±13.6 64±12 60 59±13.7 55.5±9.9 64.0±11.4
Male 48.2% 60.4% 65.5% 46.3% 87.6% 71.4%
Hypertension 73.9% 64.2% N/A 74.9% N/A N/A
Hyperlipidemia 63.7% 53.1% N/A 53.4% N/A N/A
Diabetes mellitus 38.4% 26.2% N/A 34.9% N/A N/A
Cigarette smoking 3.1% 18.0% N/A 18.9% N/A N/A
Family history of CAD 0.6% 6.8% N/A N/A N/A N/A
Known CAD 28.7% 29.3% N/A 31.4% 94.8% 52.0%
History of MI 7.0% 17.1% N/A N/A N/A N/A
History of heart failure 11.9% 4.9% N/A N/A N/A N/A
Most common CMR indication Risk stratification in suspected CAD (70.8%) N/A Risk stratification in suspected CAD/Ischemia in known CAD (34.2%) N/A Known CAD Risk stratification in suspected CAD (52.0%)
Complications during or immediately after stress CMR
Death or acute MI 0 0 0 N/A 0 0
Major complication 4 (0.11%)
• Acute pulmonary edema (n = 4)
10 (0.08%)
• Unstable angina (n = 2)
• Acute pulmonary edema (n = 2)
• Sustained VT (n = 1)
• Persistent AF (n = 2)
• Asystole (n•1)
• TIA (n = 1)
• Anaphylactic shock (n = 1)
7 (0.07%)
• Non-sustained VT (n = 2)
• Ventricular fibrillation (n = 1)
• Overt heart failure (n = 2)
• Unstable angina (n = 1)
• Anaphylactic shock (n = 1)
N/A 3 (0.28%)
• Unstable angina required hospital admission (n = 3)
0
Non-major complications/symptoms Non-major complications 13.7% • Non-major complications 1.5%
• Minor symptoms 24.8%
Mild complications 3.6% N/A • Transient hypotension 1.8%
• Severe chest pain 0.5%
• Severe breathlessness 0.9%
Adverse effects 63.3%
Clinical impact of stress CMR
New/change diagnosis 26.2% N/A 8.1%b N/A N/A N/A
Therapeutic consequences
• Change in medication 21.4% N/A 24.3% 18.3% N/A N/A
• Invasive procedure 14.2% N/A 23.1% 13.1%c N/A N/A
Impact on patient managementa 48.1% N/A 71.4% 69.5% d N/A N/A

aDiagnosis and/or therapeutic consequences.

bCompletely new diagnosis not suspected before.

cAngiography with and without revascularization.

dActive change in clinical care.

Abbreviations: AF = atrial fibrillation, CAD = coronary artery disease, CMR = cardiac magnetic resonance, MI = myocardial infarction, VT = ventricular tachycardia, TIA = transiebnt ischemic attack.

For applicability, our data highlights the safety and clinical impact of adenosine stress CMR for patient management. This data will assist clinicians in ensuring that adenosine CMR is indeed very safe and has a clinical impact on patient management. This will also enhance the confidence of clinicians and their patients in the benefits of CMR. Such confidence will promote CMR as a one-stop service offering accurate diagnostic testing with an excellent safety profile and significant clinical impact.

Our study had several limitations. Firstly, the retrospective nature of the study could introduce confounders that cannot be completely eliminated, and reviewing the medical records could potentially introduce some bias. However, the reviewers who assessed the patient information were blinded to the CMR results, which was the best approach we could take. Secondly, it was conducted in a single tertiary center in Thailand, which may limit the generalizability of our findings to different regions. Additionally, the specific definition used in our study may differ from that of others, which could impact the comparability of results. However, our study contributes valuable data from an Asian country, which was previously scarce in this field. Thirdly, certain complications such as bradyarrhythmia, atrioventricular block, or non-sustained ventricular tachycardia might not have been accurately recorded since we were unable to obtain 12-lead ECG recordings during CMR. However, this is a common limitation in many CMR studies, and it’s important to note that no patients in our study required treatment for any arrhythmic events. Fourthly, due to the very low rate of events, we were unable to provide a reliable predictor for major complications. The limited number of events hindered our ability to perform a thorough and accurate analysis in this regard. Finally, our study did not include a cost-effective analysis of CMR compared to invasive coronary angiography or nuclear studies, as this was not our primary aim. However, this could serve as an opportunity for future research on this matter.

Conclusions

This study, the largest in Asia to date, aimed to demonstrate the safety profiles and clinical impact of adenosine stress CMR in Asian patients with known or suspected CAD. The findings of this study confirm that adenosine stress CMR is not only safe but also has a significant impact on clinical management in this patient population. These results provide strong support for the utilization of adenosine stress CMR as a valuable tool for evaluating and guiding treatment decisions in patients with known or suspected CAD.

List of abbreviations

CAD

coronary artery disease

CMR

cardiac magnetic resonance

ECG

electrocardiography

LGE

late gadolinium enhancement

MI

myocardial infarction

NYHA

New York Heart Association

SD

standard deviation

Data Availability

Data from this study are available upon reasonable request. However, the request needs to submit a short document with description specify the reason for the request. The data belong to the Cardiovascular Imaging unit of Siriraj Hospital. Request to use or access the data has to be considered by Cardiovascular Imaging staff whether the request is reasonable. If reasonable, data sharing agreement may be needed. Besides even we remove the ID of patients in the datafile, the remaining data sometime can track or identify the patient. For data inquiries please contact the data manager: Poom Sairat, M.S. e-mail: poom.kaab@gmail.com.

Funding Statement

The author(s) received no specific funding for this work.

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  • 8.Raj V, Pudhiavan A, Hrishikesh VJ, Ali A, Kothari R. Safety profile of adenosine stress cardiac MRI in a tertiary hospital in India. Indian J Radiol Imaging. 2020;30(4):459–64. doi: 10.4103/ijri.IJRI_283_20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Kramer CM, Barkhausen J, Bucciarelli-Ducci C, Flamm SD, Kim RJ, Nagel E. Standardized cardiovascular magnetic resonance imaging (CMR) protocols: 2020 update. Journal of Cardiovascular Magnetic Resonance. 2020;22(1):17. doi: 10.1186/s12968-020-00607-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Kaolawanich Y, Thongsongsang R, Songsangjinda T, Boonyasirinant T. Clinical values of resting electrocardiography in patients with known or suspected chronic coronary artery disease: a stress perfusion cardiac MRI study. BMC Cardiovascular Disorders. 2021;21(1). doi: 10.1186/s12872-021-02440-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
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  • 13.Hamon M, Fau G, Née G, Ehtisham J, Morello R, Hamon M. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease. J Cardiovasc Magn Reson. 2010;12(1):29. doi: 10.1186/1532-429X-12-29 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Krittayaphong R, Boonyasirinant T, Saiviroonporn P, Nakyen S, Thanapiboonpol P, Yindeengam A, et al. Myocardial perfusion cardiac magnetic resonance for the diagnosis of coronary artery disease: do we need rest images? Int J Cardiovasc Imaging. 2009;25 Suppl 1:139–48. doi: 10.1007/s10554-008-9410-5 [DOI] [PubMed] [Google Scholar]
  • 15.Khoo JP, Grundy BJ, Steadman CD, Sonnex EP, Coulden RA, McCann GP. Stress cardiovascular MR in routine clinical practice: referral patterns, accuracy, tolerance, safety and incidental findings. Br J Radiol. 2012;85(1018):e851–7. doi: 10.1259/bjr/14829242 [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Vikramaditya Samala Venkata

10 Sep 2023

PONE-D-23-23709Safety and Clinical Impact of Adenosine Stress Perfusion Cardiac Magnetic Resonance in Asian Patients with Known or Suspected Coronary Artery DiseasePLOS ONE

Dear Dr. Krittayaphong,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

To begin with, this is an excellent study looking at a new diagnostic measure in a specific population and this will surely add to the existing literature and will help guide future studies.

I would suggest a few minor revisions (similar to what the reviewers have noted below)

  1. Author should talk about the cost effectiveness of the study compared to angiogram and nuclear study

  2. Authors should note that retrospective nature of the study is a limitation. (please refer to reviewers concerns below about blinding in a retrospective study)

  3. Please review reviewer's suggestions below.

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We look forward to receiving your revised manuscript.

Kind regards,

Vikramaditya Samala Venkata

Academic Editor

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

5. Review Comments to the Author

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Reviewer #1: I would first like to thank to give chance to review this study It is very good study looking at Asian population and safety , clinical effectivity of adenosine CMR stress test, there are few sentences that I recommended needs to be reworded/ restructured , otherwise the study / report clearly outlines the major versus minor complications noted during this test and clinical outcome

Reviewer #2: Well done study which seeks to ascertain the impact of Stress CMR in Asian population. It was a retrospective observational study but the authors mention that the cardiologists reviewing the data were blinded to the results, adverse patient events, etc. which is difficult in a retrospective study. Can authors please explain what precautions/ methodology was adopted to ensure blinding.

Reviewer #3: This is a retrospective observational study conducted in a Tertiary care hospital in Thailand. The authors have studied the safety and clinical impact of adenosine stress cardiac magnetic resonance(CMR) imaging MRI in patients with suspected or diagnosed coronary artery disease. The study is well done and reported methodically. Limited background data from Asia has been mentioned setting the context and need for the study. The authors have provided detailed background evidence and comparison to prior studies. They have collected a large sample size of 3768 patients from Southeast Asia which makes the data robust. Authors have reported on the demographics, clinical characteristics, hemodynamic variables(Blood pressure and heart rate) of the patients, and complications of the stress CMRI test.

The test is reported safe with only 4 major complications of acute pulmonary edema (0.44%). This is similar to the safety profile documented in prior studies.

Adenosine stress CMR had an overall impact on in 48% of the patients. 26% of patients got a new diagnosis ( CAD or non ischemic cardiac problems). 29% of the patient had a change in therapeutic plan( new medication or a procedure).

Overall the study has filled a gap in the knowledge about the safety and impact of adenosine stress CMR in the Asian population.

Reviewer #4: Considering the retrospective nature and region-specific, it is challenging to generalize the result however, other studies have shown a similar result.

It is important to mention the cost-effectiveness compared to nuclear study and CT coronary angiogram.

The table comparing the previous study is helpful. Mentioning the limitation at the end also gives more prospective for future study.

Overall, it is a well-done study.

Reviewer #5: Limited Applicability to Other Settings: This study was exclusively conducted at a single tertiary center in Thailand, which may limit the extent to which the results can be applied to diverse regions and populations with potentially distinct demographic compositions and healthcare systems. Acknowledging this constraint is essential, and the article should delve into the potential ramifications of this restriction.

Clarification of Patient Selection Criteria: The article would benefit from a more comprehensive elucidation of the criteria used to include or exclude patients in the study. For instance, it should explicitly define the criteria for excluding patients with contraindications to adenosine stress CMR.

Illustrating Clinical Impact: While the article highlights that stress CMR significantly impacted diagnosis and clinical management in 48% of patients, it could enhance reader comprehension by furnishing concrete examples of how CMR results influenced patient management. These practical instances would offer valuable insights into the real-world implications of the study's findings.

Contextualizing with Previous Research: While briefly alluding to studies conducted in Western countries, the article must include an opportunity for a more thorough comparative analysis. A more comprehensive examination of how this study's outcomes align with or diverge from prior research would give readers a richer contextual understanding of the findings.

**********

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Reviewer #1: Yes: Gurpreet Kaur Saini

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes: Nihar Jena

Reviewer #5: Yes: Vishal Devarkonda

**********

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Attachment

Submitted filename: PONE-D-23-23709_reviewer.pdf

PLoS One. 2023 Oct 12;18(10):e0292950. doi: 10.1371/journal.pone.0292950.r002

Author response to Decision Letter 0


20 Sep 2023

Editor ‘s comments

To begin with, this is an excellent study looking at a new diagnostic measure in a specific population and this will surely add to the existing literature and will help guide future studies.

We would like to express our sincere gratitude to the Editor for the dedicated time and effort invested in reviewing our manuscript. We highly value the insightful feedback provided by the Reviewers, which has undoubtedly contributed to the enhancement of our work. Below, we present our responses to the Review comments, addressing each point in a comprehensive manner. Your constructive guidance has been instrumental in refining our study, and we are truly appreciative of this invaluable contribution.

I would suggest a few minor revisions (similar to what the reviewers have noted below)

Author should talk about the cost effectiveness of the study compared to angiogram and nuclear study

Thank you for the question. We agree with the editor that the cost-effectiveness analysis of CMR compared to angiogram and nuclear study is interesting. However, this is not a primary aim of our study. It requires several pieces of data that we were unable to obtain. Nevertheless, we have added this point to the limitation section. It is an idea for us to pursue further research in the future.

Limitation section (page 13, line 304-306)

“Finally, our study did not include a cost-effective analysis of CMR compared to invasive coronary angiography or nuclear studies, as this was not our primary aim. However, this could serve as an opportunity for future research on this matter.”

Authors should note that retrospective nature of the study is a limitation. (please refer to reviewers concerns below about blinding in a retrospective study)

Thank you for the comment. We have acknowledged this issue and added it to the limitation section (page 13 line 290-293)

Firstly, the retrospective nature of the study could introduce confounders that cannot be completely eliminated, and reviewing the medical records could potentially introduce some bias. However, the reviewers who assessed the patient information were blinded to the CMR results, which was the best approach we could take

Please review reviewer's suggestions below.

Done.

Review Comments to the Author

Reviewer #1: I would first like to thank to give chance to review this study It is very good study looking at Asian population and safety , clinical effectivity of adenosine CMR stress test, there are few sentences that I recommended needs to be reworded/ restructured , otherwise the study / report clearly outlines the major versus minor complications noted during this test and clinical outcome

We sincerely thank the reviewer for dedicating their time and effort to review our article. The comments provided by the reviewer have greatly benefited our work, enhancing its clarity and overall quality. Our point-by-point response is provided below.

1. Abstract: we added the age of elderly as "elderly (ranging from 75 to 91 years)".

2. Page 2: Comment on sensitivity and specificity of adenosine stress CMR: We described this issue in the discussion section that demonstrated the accuracy data of adenosine stress CMR in our study.

Discussion section (page 10, line 225-229)

“Adenosine has been the most commonly used vasodilator for stress CMR and has been shown to exhibit better sensitivity and specificity compared to dipyridamole.(1) Our center has demonstrated good accuracy with adenosine stress CMR, achieving a sensitivity of 89.5% and a specificity of 78.6% compared to invasive coronary angiography.(2) These results are consistent with other published papers that also demonstrate good accuracy.(1)”

References

1) Hamon M, Fau G, Née G, Ehtisham J, Morello R, Hamon M. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease. J Cardiovasc Magn Reson. 2010;12(1):29.

2) Krittayaphong R, Boonyasirinant T, Saiviroonporn P, Nakyen S, Thanapiboonpol P, Yindeengam A, et al. Myocardial perfusion cardiac magnetic resonance for the diagnosis of coronary artery disease: do we need rest images? Int J Cardiovasc Imaging. 2009;25 Suppl 1:139-48.

3. Introduction: We specify clinical impact of stress CMR in patients with known or suspected CAD.

Introduction section (page 3, line 64-66)

“Stress CMR has demonstrated a significant impact on the diagnosis and management of a large patient population, as evidenced by The EuroCMR registry, which included more than 9,500 patients suspected of CAD or suspected ischemia in known CAD who underwent stress tests.(1)”

Reference

1) Bruder O, Wagner A, Lombardi M, Schwitter J, van Rossum A, Pilz G, et al. European cardiovascular magnetic resonance (EuroCMR) registry – multinational results from 57 centers in 15 countries. Journal of Cardiovascular Magnetic Resonance. 2013;15(1):9.

4. Method: A question regarding discontinue of adenosine infusion.

For our CMR protocol, we allow patients to request the discontinuation of adenosine, even though we instruct them to be aware of the adverse effects of adenosine. Very few of them had severe symptom such as dyspnea and chest pain. Despite allowing patients to request the discontinuation of adenosine, there was no record of a patient being unable to tolerate it to the extent that the test had to be stopped.

5. Results: We have revised two sentences regarding characteristics of four patients who had acute pulmonary edema after CMR.

Result section (page 8, line 179-183)

“All four patients, aged over 75 (ranging from 75 to 91 years), required hospital observation or admission for further management. They had previously been diagnosed with heart failure, classified as New York Heart Association (NYHA) class II-III, with two having reduced left ventricular ejection fraction and two having preserved left ventricular ejection fraction.”

6. Results: We clarify local complications at intravenous access site.

Results section (page 8, line 187-188)

“Local complications at intravenous access sites, such as small hematoma, edema, or phlebitis (n=7)”

7. Discussion: We added reasons that acute pulmonary edema has occurred only in patients with heart failure.

Discussion section (page 10-11, line 237-241)

“Four patients with acute pulmonary edema were reported, all of whom were elderly and had symptomatic heart failure. It is known that a comprehensive stress CMR protocol requires patient cooperation, as they have to remain supine in a magnet for at least 30 minutes and repeatedly hold their breath. Patients with symptomatic heart failure, especially those with fluid retention, are at a high risk for a heart failure event during or after CMR.”

Reviewer #2: Well done study which seeks to ascertain the impact of Stress CMR in Asian population. It was a retrospective observational study but the authors mention that the cardiologists reviewing the data were blinded to the results, adverse patient events, etc. which is difficult in a retrospective study. Can authors please explain what precautions/ methodology was adopted to ensure blinding.

Thank you for your comment; this is indeed an important issue. We apologize for any confusion. In our study, two cardiologists reviewed patient information, including baseline characteristics, indications for CMR, adverse events during CMR studies, and changes in management after CMR. Importantly, they did so without access to the CMR results, whether they were positive or negative for ischemia or positive or negative for LGE. We are aware that this approach may introduce bias due to the retrospective nature of the study. Nevertheless, we made every effort to minimize this bias and believe that this was the most suitable approach for a retrospective study. Furthermore, we have revised this section and acknowledged this limitation in the limitations section.

Method section (page 6, line 137-139)

“Two cardiologists, who were blinded to the CMR results, reviewed patient information, including baseline characteristics, indications for CMR, adverse events during CMR studies, and changes in management after CMR. They independently assessed the clinical impact of each stress CMR by reviewing electronic medical records up to the next outpatient visit with the ordering provider. A “completely new diagnosis” was defined as a diagnosis occurring only if it was previously unknown to the referring physician.”

Limitation section (page 13, line 290-293)

Firstly, the retrospective nature of the study could introduce confounders that cannot be completely eliminated, and reviewing the medical records could potentially introduce some bias. However, the reviewers who assessed the patient information were blinded to the CMR results, which was the best approach we could take

Reviewer #3: This is a retrospective observational study conducted in a Tertiary care hospital in Thailand. The authors have studied the safety and clinical impact of adenosine stress cardiac magnetic resonance(CMR) imaging MRI in patients with suspected or diagnosed coronary artery disease. The study is well done and reported methodically. Limited background data from Asia has been mentioned setting the context and need for the study. The authors have provided detailed background evidence and comparison to prior studies. They have collected a large sample size of 3768 patients from Southeast Asia which makes the data robust. Authors have reported on the demographics, clinical characteristics, hemodynamic variables(Blood pressure and heart rate) of the patients, and complications of the stress CMRI test.

The test is reported safe with only 4 major complications of acute pulmonary edema (0.44%). This is similar to the safety profile documented in prior studies.

Adenosine stress CMR had an overall impact on in 48% of the patients. 26% of patients got a new diagnosis (CAD or non-ischemic cardiac problems). 29% of the patient had a change in therapeutic plan( new medication or a procedure).

Overall, the study has filled a gap in the knowledge about the safety and impact of adenosine stress CMR in the Asian population.

We thank the reviewer for their dedicated time and effort in reviewing our study, and we greatly appreciate their compliments suggesting that our study will be beneficial for patient management.

Reviewer #4: Considering the retrospective nature and region-specific, it is challenging to generalize the result however, other studies have shown a similar result.

It is important to mention the cost-effectiveness compared to nuclear study and CT coronary angiogram.

The table comparing the previous study is helpful. Mentioning the limitation at the end also gives more prospective for future study.

Overall, it is a well-done study.

Thank you for the question. We agree with the editor that the cost-effectiveness analysis of CMR compared to angiogram and nuclear study is interesting. However, this is not a primary aim of our study. It requires several pieces of data that we were unable to obtain. Nevertheless, we have added this point to the limitation section. It is an idea for us to pursue further research in the future.

Limitation section (page 13, line 304-306)

“Finally, our study did not include a cost-effective analysis of CMR compared to invasive coronary angiography or nuclear studies, as this was not our primary aim. However, this could serve as an opportunity for future research on this matter.”

Reviewer #5:

1. Limited Applicability to Other Settings: This study was exclusively conducted at a single tertiary center in Thailand, which may limit the extent to which the results can be applied to diverse regions and populations with potentially distinct demographic compositions and healthcare systems. Acknowledging this constraint is essential, and the article should delve into the potential ramifications of this restriction.

Thank you for your comment. We acknowledge the limitation that our study was conducted in a tertiary center in Thailand, as we stated in the limitations section. However, our study's focus was on Asia, where there is limited data available regarding the safety of CMR and its impact on patient management. Additionally, it is worth noting that, in general, CMR centers tend to be tertiary centers, especially in Asia, like ours. We believe that our study represents patients in typical tertiary centers offering CMR services in Asia.

2. Clarification of Patient Selection Criteria: The article would benefit from a more comprehensive elucidation of the criteria used to include or exclude patients in the study. For instance, it should explicitly define the criteria for excluding patients with contraindications to adenosine stress CMR.

Thank you for the valuable comments. In our study, we retrospectively included consecutive patients aged >18 years who were referred for adenosine stress CMR. This study reflects the real world and includes all patients who underwent a specific CMR protocol at our center. We did not specify the exclusion criteria since patients with contraindications for CMR were not included in the study because they did not undergo the scan. However, we thank the reviewer once again for bringing up this point.

3. Illustrating Clinical Impact: While the article highlights that stress CMR significantly impacted diagnosis and clinical management in 48% of patients, it could enhance reader comprehension by furnishing concrete examples of how CMR results influenced patient management. These practical instances would offer valuable insights into the real-world implications of the study's findings.

As the reviewer stated, our study highlights the safety and clinical impact of adenosine stress CMR for patient management. We believe this data will assist clinicians in ensuring that adenosine CMR is indeed very safe and has a clinical impact on patient management. This will also enhance the confidence of clinicians and their patients in the benefits of CMR. Such confidence will promote CMR as a one-stop service offering accurate diagnostic testing with an excellent safety profile and significant clinical impact. We have emphasized this point in the discussion section.

Discussion section (page 13, line 284-289)

“For applicability, our data highlights the safety and clinical impact of adenosine stress CMR for patient management. This data will assist clinicians in ensuring that adenosine CMR is indeed very safe and has a clinical impact on patient management. This will also enhance the confidence of clinicians and their patients in the benefits of CMR. Such confidence will promote CMR as a one-stop service offering accurate diagnostic testing with an excellent safety profile and significant clinical impact.”

4. Contextualizing with Previous Research: While briefly alluding to studies conducted in Western countries, the article must include an opportunity for a more thorough comparative analysis. A more comprehensive examination of how this study's outcomes align with or diverge from prior research would give readers a richer contextual understanding of the findings.

Thank you for the valuable comment. This enhances our study to be much better. As the reviewer suggested, we added a discussion regarding our results and compared them with other published articles.

Discussion section (page 12, line 272-283)

“Table 4 presents a summary of patients' profiles, complications, and the clinical impact of stress CMR in our study, compared with previously published data.(1-5) Our data demonstrated some degree of similarity in patient profiles, such as having 28% with known CAD, consistent with Menadas et al. and McGraw et al.(2,3) Notably, our study had a lower proportion of male participants compared to most studies, as male patients may have a higher pretest probability of obstructive CAD and may undergo invasive coronary angiography rather than CMR. Regarding complications, our study and all studies had quite similar very low rates of major complications (<0.3% in all studies), showing a consistent safety profile of stress CMR, while there were some differences in baseline characteristics. As for the clinical impact of CMR, although there were differences in the definitions of impact and/or therapeutic consequences, all studies also showed a consistent and significant impact of CMR. Overall, we have added data from Asia showing that CMR is safe and has a clinical impact compared to studies from Western countries.”

References

1) Bruder O, Wagner A, Lombardi M, Schwitter J, van Rossum A, Pilz G, et al. European cardiovascular magnetic resonance (EuroCMR) registry – multi national results from 57 centers in 15 countries. Journal of Cardiovascular Magnetic Resonance. 2013;15(1):9.

2) McGraw S, Romano S, Jue J, Bauml MA, Chung J, Farzaneh-Far A. Impact of Stress Cardiac Magnetic Resonance Imaging on Clinical Care. Am J Cardiol. 2016;118(6):924-9.

3) Monmeneu Menadas JV, Lopez-Lereu MP, Estornell Erill J, Garcia Gonzalez P, Igual Muñoz B, Maceira Gonzalez A. Pharmacological stress cardiovascular magnetic resonance: feasibility and safety in a large multicentre prospective registry. European Heart Journal - Cardiovascular Imaging. 2015;17(3):308-15.

4) Tsang KH, Chan WS, Shiu CK, Chan MK. The safety and tolerability of adenosine as a pharmacological stressor in stress perfusion cardiac magnetic resonance imaging in the Chinese population. Hong Kong Med J. 2015;21(6):524-7.

5) Raj V, Pudhiavan A, Hrishikesh VJ, Ali A, Kothari R. Safety profile of adenosine stress cardiac MRI in a tertiary hospital in India. Indian J Radiol Imaging. 2020;30(4):459-64.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Vikramaditya Samala Venkata

3 Oct 2023

Safety and Clinical Impact of Adenosine Stress Perfusion Cardiac Magnetic Resonance in Asian Patients with Known or Suspected Coronary Artery Disease

PONE-D-23-23709R1

Dear Dr. Krittayaphong,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Vikramaditya Samala Venkata

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Vikramaditya Samala Venkata

5 Oct 2023

PONE-D-23-23709R1

Safety and Clinical Impact of Adenosine Stress Perfusion Cardiac Magnetic Resonance in Asian Patients with Known or Suspected Coronary Artery Disease

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

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    Submitted filename: PONE-D-23-23709_reviewer.pdf

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    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    Data from this study are available upon reasonable request. However, the request needs to submit a short document with description specify the reason for the request. The data belong to the Cardiovascular Imaging unit of Siriraj Hospital. Request to use or access the data has to be considered by Cardiovascular Imaging staff whether the request is reasonable. If reasonable, data sharing agreement may be needed. Besides even we remove the ID of patients in the datafile, the remaining data sometime can track or identify the patient. For data inquiries please contact the data manager: Poom Sairat, M.S. e-mail: poom.kaab@gmail.com.


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