Sivabaskari Pasupathy

Systematic Review of Patients Presenting With Suspected Myocardial Infarction and Nonobstructive Coronary Arteries

Background— Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder. Methods and Results— Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%–7%] with a median patient age of 55 years (95% confidence interval, 51–59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval, 2.6%–6.9%) compared with myocardial infarction associated with obstructive coronary artery disease (6.7%, 95% confidence interval, 4.3%–9.0%). Qualitative assessment of 46 publications evaluating the underlying pathophysiology responsible for MINOCA revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in 14%. Conclusions— MINOCA should be considered as a working diagnosis with multiple potential causes that require evaluation so that directed therapies may improve its guarded prognosis.

Early use of N-acetylcysteine with nitrate therapy in patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction reduces myocardial infarct size (the NACIAM trial [N-acetylcysteine in acute myocardial infarction])

Background: Contemporary ST-segment–elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging–assessed infarct size. Secondary end points included cardiac magnetic resonance–determined myocardial salvage and creatine kinase kinetics. Results: Of 112 randomized patients with ST-segment–elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance–assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P=0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37–79) compared with placebo (27%; interquartile range, 14–42; P<0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively (P=0.08). Conclusions: High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000.

The What, When, Who, Why, How and Where of Myocardial Infarction With Non-Obstructive Coronary Arteries (MINOCA)

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an intriguing clinical entity that is being increasingly recognized with the more common use of coronary angiography during acute myocardial infarction. This review systematically addresses the contemporary understanding of MINOCA, including, (1) what are the diagnostic criteria, (2) when the diagnosis should be considered, (3) who is at risk, (4) why this new syndrome should be diagnosed, (5) how these patients should be managed, and (6) where to next?

Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): The Past, Present, and Future Management

Article, see p 1481 Myocardial infarction with nonobstructive coronary arteries (MINOCA) is clinically defined by the presence of the universal acute myocardial infarction (AMI) criteria, absence of obstructive coronary artery disease (≥50% stenosis), and no overt cause for the clinical presentation at the time of angiography (eg, classic features for takotsubo cardiomyopathy).1 With the more frequent contemporary use of coronary angiography in AMI, clinicians have been regularly confronted with this puzzling problem and seeking guidance in its management. An article by Lindahl et al2 in this issue of Circulation represents a major step forward in MINOCA and thereby warrants taking stock of the past, present, and future management strategies of this intriguing condition. The pioneering early angiography studies of DeWood et al demonstrated that ST-segment–elevation myocardial infarction was often associated with an occluded epicardial artery, but this occurred less frequently in non–ST-segment–elevation myocardial infarction, although in both conditions obstructive coronary artery disease was evident in >95% of patients.3 These findings underscored the importance of the underlying atherothrombotic process and provided the impetus for major advances in AMI management over the next 35 years. However, when angiography failed to reveal the presence of obstructive atheroma or thrombosis in patients with clinical criteria for ST-segment–elevation myocardial infarction, some clinicians labeled these patients as having a false-positive ST-segment–elevation myocardial infarction diagnosis.4 Such a label implies that an AMI has not occurred (despite the clinical presentation) and therefore no further diagnostic investigation or cardiac therapy is required. To avoid such diagnostic complacency, the diagnosis of MINOCA was coined5 with an emphasis on investigating these patients to identify the underlying cause of their AMI presentation. Providing a label for this clinical syndrome was the first …

A comparison of ECG scores for area at risk

To the Editor: Versteylen et al 1 recently evaluated several area at risk (AAR) methods in patients with acute ST elevation myocardial infarction using four physiological principles, and concluded that cardiac MRI methods outperform angiographic methods, which are better than ECG methods. However, this study used the antiquated Aldrich score, rather than the updated ECG index, described by Wilkins et al .2 The Aldrich score is based upon the extent of inferior ST elevation …

Risk of Thrombosis in Patients Presenting with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA)

Patients presenting with myocardial infarction (MI) in the absence of obstructive coronary artery disease (CAD) is termed MI with nonobstructive coronary arteries (MINOCA). The underlying pathophysiology of MINOCA is multifactorial and in situ formation and subsequent spontaneous lysis of a coronary thrombus is often hypothesized as one of the mechanisms. The objective of this study is to determine whether MINOCA patients had a greater prothrombotic tendency in comparison to MI patients with obstructive CAD (MICAD). Prospectively, blood samples of 25 consecutive MINOCA patients (58 (interquartile range [IQR]: 48, 75) years, 48% women) and 25 age-/gender-matched MICAD patients (58 (IQR: 50, 66) years, 48% women) were obtained at 1 month after the initial presentation and overall thrombin generation potential and congenital/acquired thrombophilia states were assessed. As regard to results, overall thrombin generation parameters were similar ( p  > 0.05) between the MINOCA and MICAD groups, highlighting similar endogenous thrombin potential (1,590 nM/min; IQR: 1,380, 2,000 vs. 1,750 nM/min; IQR: 1,500, 2,040, respectively). There were no significant differences between MINOCA and MICAD, respectively, in respect to the numbers of patients with congenital thrombophilia states including factor V Leiden (0 vs. 4%) and prothrombin gene mutation (8 vs. 4%), decreased antithrombin (8 vs. 0%), protein C (0 vs. 0%), and protein S (4 vs. 0%). None of the patients demonstrated presence of lupus anticoagulant and anticardiolipin antibodies. Although MINOCA patients revealed thrombotic characteristics that are similar to those with MICAD, the results from this study are inconclusive and a larger study with healthy control subjects is required to assess the risk of thrombosis in MINOCA.

How Can You Have a Myocardial Infarction Without Significant Coronary Artery Disease? Whither MINOCA

This may seem a simple question that a medical student might ask on a ward round but, like all fundamental questions, the answer is much more complex. Indeed, the attending cardiologist on the ward round may respond with (a) it’s not a myocardial infarction (MI); (b) it’s missed obstructive coronary artery disease (CAD); (c) minor atherosclerotic CAD is responsible; (d) non-atherosclerotic mechanisms such as spasm are involved; or, (e) I am not certain, since we need more research! Even more disquieting is what the patient is told and the formal diagnosis included in the discharge letter, since both will have an important impact on patient care. This question focusses on the evolving condition referred to as MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries). The term was initially coined in an editorial [1]anda recent positionpaper fromthe EuropeanSocietyof Cardiology has summarised contemporary perspectives [2]. The clinical criteria for the diagnosis of MINOCA include (1) universal definition of acute MI; (2) non-obstructive coronary artery disease on angiography, defined as the absence of a coronary stenosis 50%; and, (3) no clinically overt specific cause for the acute presentation. With MINOCA defined, this editorial will endeavour to address the above ‘medical student question’ and discuss the potential responses that could be given by the attending consultant.

Response by Pasupathy et al to Letters Regarding Article, “Early Use of N-acetylcysteine (NAC) With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Reduces Myocardial Infarct Size (The NACIAM Trial [N-Acetylcysteine in Acute Myocardial Infarction])”

We appreciate the correspondence concerning the NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction),1 which focused on the study analytical methods and potential mechanisms contributing to the benefits of N-acetylcysteine (NAC)/nitroglycerin use in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. Ye et al commented on the study analytical methods, raising concerns as to whether (1) propensity score matching between study groups is required, (2) repeated measures ANOVA should be undertaken in the chest pain and creatine kinase (CK) analyses, and (3) a curvilinear relationship exists between infarct size and the predictive clinical variables so that a generalized linear model analysis would be more appropriate. First, concerning study group matching, the groups were balanced in this randomized controlled trial of consecutive eligible patients so that propensity analysis is not required, particularly in light of the limitations of this analytic approach.2 Second, repeated measures ANOVA is appropriate and was conducted for the chest pain analysis, but the …

ST-SEGMENT ELEVATION AND CARDIAC MAGNETIC RESONANCE IMAGING FINDINGS IN MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES

Background: Cardiac magnetic resonance imaging (CMR) is used in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) to help determine whether the underlying MI cause is vascular or non-vascular. ST segment elevation on the electrocardiogram suggests complete

Myocardial Infarction With Non-obstructive Coronary Arteries — Diagnosis and Management

MI with non-obstructive coronary arteries (MINOCA) is an enigma that is being increasingly recognised with the frequent use of angiography following acute MI. To diagnose this condition, it is important to determine the multiple potential underlying mechanisms that may be responsible, many of which require different treatments. This review evaluates the contemporary diagnosis and management of MINOCA.