Overall: This is an engaging review article in the field of Type 2 myocardial infarction (T2MI) and myocardial injury after the release of the 4th universal definition. It is well written, and authors made an excellent effort to bring all pieces of the critical research data in this understudied Type 2 MI. It contributes hugely to this specific field. Except for those suggested minor revisions, this review article would create a good impact in the field of cardiology.

Comments on abstract, title, references

This review article is providing updated knowledge on identification, diagnosis, management, and outcomes in the Type 2 Myocardial Infarction (T2MI) population. The title is well suited, and the purpose of the article is clear. There is a significant knowledge gap was present in this understudied population. Plenty of recent references cited in this field.

Introduction: Authors have clear goals and explained the knowledge gap in the definition, diagnosis, and treatment strategies in type 2 myocardial infarction and myocardial injury population.

Q 1: Page 1846, Para 1: Exaplanining difference between myocardial injury and myocardial necrosis may be beneficial.

Clinical Presentation:

Pathophysiology: Well categorized in both coronary and non-coronary etiology with all possible mechanisms. Q 2: Page 1847, Figure 1: Any possibility of concomitant obstructive CAD in pure supply reduction?

Q 3: Page 1847, Figure 1: Venue bar on the top has not described the relationship with the mechanism clearly in figure 1. Confusing

Q 4: Page 1848, para 1: Not explained the role of compensatory mechanisms like a sympathetic response in troponin elevation

Q 5: Page 1848 para 2: There is a lack of explanations in the mechanism of troponin release in the metabolic de-arrangement clinical situations like DKA, hypoglycemia, and acute neurological conditions (stroke, seizures). Occasionally, significant patients would present with elevated troponin levels. --(Myocardial injury with biomarker elevation in diabetic ketoacidosis: J Diabetes Complications. 2005 Nov-Dec;19(6):361-3.) --(Cardiac Troponin I elevation after an epileptic seizure. BMC Neurol. 2012 Jul 17;12:58. DOI: 10.1186/1471-2377-12-58.)

Epidemiology: Comprehensive table 3 and figure 4.

12-Lead ECG and Echocardiography: Q 6: Page 1849, Para 4: Authors did not address other ECHO variables like severe AS, LVH, and EF changes which are crucial in identifying T2MI

(Sandoval et al. Supply/Demand Type 2 Myocardial Infarction: Should We Be Paying More Attention? https://doi.org/10.1016/j.jacc.2014.02.541)

Q 7: Page 1849, Para 3: Any importance in getting frequent ECG to differentiate T2MI / myocardial injury from Unstable angina?

Advanced Imaging and Coronary Angiography: Q 8: Page 1850, para 1, line 2: Please mention the reasons for that the variability of coronary angiography results in different studies? Because from different criteria used in the various studies.

Cardiac Troponin: Q 9: Page 1851, Para 6: Criteria for determining a pathological rise in serial cTn values are assay-dependent. Using different biochemical instruments would change the level of the 99th percentile of the troponin.

(Thygesen K, Alpert JS, Jaffe AS, et al., for the Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol 2018;72: 2231–64.)

Approach to Assessment and Diagnosis: Q 10: Page 1852: Figure Central Illustration: Well defined unstable angina in Figure 6 on page 183. But in the Central Illustration, unstable angina category was not well placed as it comes under the possible ischemic presentation and presents as transient ST and T wave changes

Prognosis: Well represented mortality data in Figure 7 on page 1854.

Treatment: Q 11: Page 1855, Para 4: The proposed concept of phenotype-specific approach may answer some of the management dilemmas in the T2MI and myocardial injury. But not sure whether a similar method should be applied to the group of patients which were categorized as T2MI after Coronary angiography.

Special Scenarios: Perioperative Myocardial Injury and Infarction: Q 12: Page 1856, Para 1: Not addressed significant of perioperative usage of beta-blockers usage to reduce MI incidents. (https://www.acc.org/latest-in-cardiology/articles/2014/07/31/13/36/new-perioperative-cv-guideline-released)

Critical Illness: Q 13: Page 1856, Para 3: Authors did not address the crucial mechanism of elevated cTn in the sepsis population, endotoxin-mediated injury, which is one of the pivotal mechanism in cTn release. (Van Bockel EA et al.; Cardiac troponin I release and cytokine response during experimental human endotoxemia. Intensive Care Med 29:1598–1600)

Challenges and Future Directions and Conclusions: Q 14: Page 1857, Para 2: Major future research also required in providing consensus clinical management.

Q 15: Page 1857, Para 2: Also, future research required to delineate the impact of other cardiovascular risk factors like peripheral artery disease, diabetes, chronic kidney disease, stroke, and aortic diseases on T2MI and myocardial injury

(Chapman AR, Adamson PD, Mills NL Assessment and classification of patients with myocardial injury and infarction in clinical practice Heart 2017;103:10-18)