Life-Threatening Arrhythmias in Patients With Takotsubo Syndrome: Insights Into Pathophysiology and Treatment Innovations.

Takotsubo syndrome (TTS) is a reversible form of acute myocardial injury due to a neurocardiogenic mechanism associated with a relevant risk for life-threatening ventricular arrhythmias, occurring in up to 25% of all patients and including both ventricular arrhythmias (especially) in the context of QT prolongation and atrial tachy- or bradyarrhythmias. The pathogenetic mechanisms of TTS-related arrhythmic complications are not completely understood, and there are no randomized clinical trials addressing the pharmacologic and nonpharmacologic management in this specific setting. In this narrative review, the authors provide an overview of the pathogenesis and the therapeutic management of arrhythmic complications in patients with TTS, along with the future perspectives and the remaining knowledge gaps in this field.

Predicting the response to acetylcholine in ischemia or infarction with non-obstructive coronary arteries: The ABCD score.

BACKGROUND AND AIMS: Acetylcholine (ACh) provocation testing can detect vasomotor disorders in patients with ischemia and non-obstructed coronary arteries (INOCA) or myocardial infarction and non-obstructed coronary arteries (MINOCA). We aimed to derive and validate a simple risk score to predict a positive ACh test response. METHODS: We prospectively enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. Patients were split in two cohorts (derivation and validation) according to time of enrolment. The score was derived in 386 patients (derivation cohort) and then validated in 165 patients (validation cohort). RESULTS: 551 patients were enrolled, 371 (67.3%) INOCA and 180 (32.7%) MINOCA. ACh test was positive in 288 (52.3%) patients. MINOCA, myocardial bridge (MB), C-reactive protein (CRP) and dyslipidaemia were independent predictors of a positive ACh test in the derivation cohort. The ABCD (Acute presentation, Bridge, CRP, Dyslipidaemia) score was derived: 2 points were assigned to MINOCA, 3 to MB, 1 to elevated CRP and 1 to dyslipidaemia. The ABCD score accurately identified patients with a positive ACh test response with an AUC of 0.703 (CI 95% 0.652-0.754,p < 0.001) in the derivation cohort, and 0.705 (CI 95% 0.626-0.784, p < 0.001) in the validation cohort. In the whole population, an ABCD score ≥4 portended 94.3% risk of a positive ACh test and all patients with an ABCD score ≥6 presented a positive test. CONCLUSIONS: The ABCD score could avoid the need of ACh provocation testing in patients with a high score, reducing procedural risks, time, and costs, and allowing the implementation of a tailored treatment strategy. These results are hypothesis generating and further research involving larger cohorts and multicentre trials is needed to validate and refine the ABCD score.

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Vaccines and Myocardial Injury in Patients Hospitalized for COVID-19 Infection: the CardioCOVID-Gemelli Study.

BACKGROUND: Myocardial injury is prevalent among patients hospitalized for COVID-19. However, the role of COVID-19 vaccines in modifying the risk of myocardial injury is unknown. OBJECTIVES: To assess the role of vaccines in modifying the risk of myocardial injury in COVID-19. METHODS: We enrolled COVID-19 patients admitted from March 2021 to February 2022 with known vaccination status and ≥1 assessment of hs-cTnI within 30 days from the admission. The primary endpoint was the occurrence of myocardial injury (hs-cTnI levels >99th percentile upper reference limit). RESULTS: 1019 patients were included (mean age 67.7±14.8 years, 60.8% male, 34.5% vaccinated against COVID-19). Myocardial injury occurred in 145 (14.2%) patients. At multivariate logistic regression analysis, advanced age, chronic kidney disease and hypertension, but not vaccination status, were independent predictors of myocardial injury. In the analysis according to age tertiles distribution, myocardial injury occurred more frequently in the III tertile (≥76 years) compared to other tertiles (I tertile:≤60 years;II tertile:61-75 years) (p<0.001). Moreover, in the III tertile, vaccination was protective against myocardial injury (OR 0.57, CI 95% 0.34-0.94; p=0.03), while a previous history of coronary artery disease was an independent positive predictor. In contrast, in the I tertile, chronic kidney disease (OR 6.94, 95% CI 1.31-36.79, p=0.02) and vaccination (OR 4.44, 95% CI 1.28-15.34, p=0.02) were independent positive predictors of myocardial injury. CONCLUSIONS: In patients ≥76 years, COVID-19 vaccines were protective for the occurrence of myocardial injury, while in patients ≤60 years, myocardial injury was associated with previous COVID-19 vaccination. Further studies are warranted to clarify the underlying mechanisms.

Innate and adaptive immunity in acute myocarditis.

Acute myocarditis is an acute inflammatory cardiomyopathy associated with cardiac damage triggered by a virus or a pathological immune activation. It may present with a wide range of clinical presentations, ranging from mild symptoms to severe forms like fulminant myocarditis, characterized by hemodynamic compromise and cardiogenic shock. The immune system plays a central role in the pathogenesis of myocarditis. In fact, while its function is primarily protective, aberrant responses can be detrimental. In this context, both innate and adaptive immunity play pivotal roles; notably, the innate system offers a non-specific and immediate defense, while the adaptive provides specialized protection with immunological memory. However, dysregulation in these systems can misidentify cardiac tissue, triggering autoimmune reactions and possibly leading to significant cardiac tissue damage. This review highlights the importance of innate and adaptive immune responses in the progression and treatment of acute myocarditis.

Impact of Impella protected-percutaneous coronary intervention on left ventricle function recovery of patients with extensive coronary disease and poor left ventricular function.

BACKGROUND: The use of Impella support is increasingly adopted to "protect" patients with severe coronary artery disease (CAD) and left ventricle (LV) dysfunction undergoing percutaneous coronary intervention (PCI). AIMS: To evaluate the impact of Impella-protected (Abiomed, Danvers, Massachusetts, USA) PCIs on myocardial function recovery. METHODS: Patients with significant LV dysfunction undergoing multi-vessel PCIs with pre-intervention Impella implantation were evaluated by echocardiography before PCI and at median follow up of 6 months: global and segmental LV contractile function were assessed by LV ejection fraction (LVEF) and wall motion score index (WMSI), respectively. Extent of revascularization was graded using the British Cardiovascular Intervention Society Jeopardy score (BCIS-JS). Study endpoints were LVEF and WMSI improvement, and its correlation with revascularization. RESULTS: A total of 48 high surgical risk (mean EuroSCORE II 8) patients with median LVEF value of 30%, extensive wall motion abnormalities (median WMSI 2.16), and severe multi-vessel CAD (mean SYNTAX score 35) were included. PCIs brought a significant reduction of ischemic myocardium burden with BCIS-JS decrease from mean value of 12 to 4 (p < 0.001). At follow-up, WMSI reduced from 2.2 to 2.0 (p = 0.004) and LVEF increased from 30% to 35% (p = 0.016). WMSI improvement was proportional to the baseline impairment (R - 0.50, p < 0.001), and confined to revascularized segments (from 2.1 to 1.9, p < 0.001). CONCLUSIONS: In patients with extensive CAD and severe LV dysfunction, multi-vessel Impella-protected PCI was associated to an appreciable contractile recovery, mainly determined by regional wall motion improvement in revascularized segments.

Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes.

OBJECTIVE: There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS. METHODS: We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS. RESULTS: Among the 18 patients with a median age of 50 years (Q1-Q3: 40-61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15-33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. CONCLUSIONS: PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed. T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.

Prolonged cardiac monitoring for stroke prevention: A systematic review and meta-analysis of randomized-controlled clinical trials.

Introduction: Prolonged cardiac monitoring (PCM) substantially improves the detection of subclinical atrial fibrillation (AF) among patients with history of ischemic stroke (IS), leading to prompt initiation of anticoagulants. However, whether PCM may lead to IS prevention remains equivocal. Patients and methods: In this systematic review and meta-analysis, randomized-controlled clinical trials (RCTs) reporting IS rates among patients with known cardiovascular risk factors, including but not limited to history of IS, who received PCM for more than 7 days versus more conservative cardiac rhythm monitoring methods were pooled. Results: Seven RCTs were included comprising a total of 9048 patients with at least one known cardiovascular risk factor that underwent cardiac rhythm monitoring. PCM was associated with reduction of IS occurrence compared to conventional monitoring (Risk Ratio: 0.76; 95% CI: 0.59-0.96; I 2 = 0%). This association was also significant in the subgroup of RCTs investigating implantable cardiac monitoring (Risk Ratio: 0.75; 95% CI: 0.58-0.97; I 2 = 0%). However, when RCTs assessing PCM in both primary and secondary prevention settings were excluded or when RCTs investigating PCM with a duration of 7 days or less were included, the association between PCM and reduction of IS did not retain its statistical significance. Regarding the secondary outcomes, PCM was related to higher likelihood for AF detection and anticoagulant initiation. No association was documented between PCM and IS/transient ischemic attack occurrence, all-cause mortality, intracranial hemorrhage, or major bleeding. Conclusion: PCM may represent an effective stroke prevention strategy in selected patients. Additional RCTs are warranted to validate the robustness of the reported associations.

Postoperative pericardial effusion, pericardiotomy, and atrial fibrillation: An explanatory analysis of the PALACS trial.

BACKGROUND: In the Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery (PALACS) trial, posterior pericardiotomy was associated with a significant reduction in postoperative atrial fibrillation (POAF) after cardiac surgery. We aimed to investigate the mechanisms underlying this effect. METHODS: We included PALACS patients with available echocardiographic data (n = 387/420, 92%). We tested the hypotheses that the reduction in POAF with the intervention was associated with 1) a reduction in postoperative pericardial effusion and/or 2) an effect on left atrial size and function. Spline and multivariable logistic regression analyses were used. RESULTS: Most patients (n = 307, 79%) had postoperative pericardial effusions (anterior 68%, postero-lateral 51.9%). The incidence of postero-lateral effusion was significantly lower in patients undergoing pericardiotomy (37% vs 67%; P < .001). The median size of anterior effusion was comparable between patients with and without POAF (5.0 [IQR 3.0-7.0] vs 5.0 [IQR 3.0-7.5] mm; P = .42), but there was a nonsignificant trend towards larger postero-lateral effusion in the POAF group (5.0 [IQR 3.0-9.0] vs 4.0 [IQR 3.0-6.4] mm; P = .06). There was a non-linear association between postero-lateral effusion and POAF at a cut-off at 10 mm (OR 2.70; 95% CI 1.13, 6.47; P = .03) that was confirmed in multivariable analysis (OR 3.5, 95% CI 1.17, 10.58; P = 0.02). Left atrial dimension and function did not change significantly after posterior pericardiotomy. CONCLUSIONS: Reduction in postero-lateral pericardial effusion is a plausible mechanism for the effect of posterior pericardiotomy in reducing POAF. Measures to reduce postoperative pericardial effusion are a promising approach to prevent POAF.

Left atrial strain analysis improves left ventricular filling pressures non-invasive estimation in the acute phase of Takotsubo syndrome.

AIMS: The aim of our study is to assess the ability of left atrial (LA) strain values to improve left ventricular and diastolic pressure (LVEDP) non-invasive estimation as compared with traditional echocardiographic indexes in the acute phase of Takotsubo syndrome (TTS) and to predict adverse in-hospital outcomes in this population. METHODS AND RESULTS: Consecutive TTS patients were prospectively enrolled. Left ventricular and diastolic pressure was measured at the time of catheterization. Transthoracic echocardiography was performed within 48 h from hospital admission. In-hospital complications (acute heart failure, death from any cause, and life-threatening arrhythmias) were collected. A total of 62 patients were analysed (72.2 ± 10.1 years, female 80%) and in-hospital complications occurred in 25 (40.3%). Left ventricular and diastolic pressure mean value was 24.53 ± 7.92 mmHg. Left atrial reservoir and pump strain values presented higher correlation with LVEDP (r -0.859, P < 0.001 and r -0.848, P < 0.001, respectively) in comparison with E/e ' ratio, left atrial volume index (LAVi), and tricuspid regurgitation (TR) peak velocity. In addition, at receiver-operating characteristic curve analysis, LA reservoir and pump strain resulted to be better predictors of LVEDP above the mean of our population [0.909 (95% CI 0.818-0.999, P < 0.001) and 0.889 (95% CI 0.789-0.988, P < 0.001)], respectively] as compared with E/e' ratio, LAVi, and TR peak velocity.Finally, LA reservoir strain resulted to be an independent predictor of worse in-hospital outcomes, together with LVEDP and left ventricular ejection fraction (all P < 0.001). CONCLUSION: In our study, lower LA reservoir and pump strain values were better predictors of LVEDP as compared with traditional echocardiographic indexes in the acute phase of TTS syndrome. Moreover, LA reservoir strain was an independent predictor of adverse in-hospital outcomes.

Characteristics of Postoperative Atrial Fibrillation and the Effect of Posterior Pericardiotomy.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery. However, only a few detailed descriptions of the arrhythmia have been reported. We aim to describe the characteristics, outcomes, and variables associated with POAF and to evaluate how posterior pericardiotomy (PP) affects POAF characteristics. METHODS: In this post hoc analysis of the Posterior left pericardiotomy for the prevention of AtriaL fibrillation After Cardiac Surgery (PALACS) trial, we describe POAF characteristics based on continuous in-hospital telemetry data. RESULTS: Of 420 patients, 103 (24.5%) developed POAF. Median time to onset was 50.3 hours; 70.9% of events occurred within 3 days. Hemodynamic instability and rapid ventricular response occurred in 8.7% and 51.5% of cases, respectively. Most POAF patients received antiarrhythmics (97.1%), 22.3% electrical cardioversion, and 40.8% systemic anticoagulation. Median POAF duration was 24.0 hours; 70.9% of cases resolved within 36 hours. Median POAF burden was 15.9%. All patients were in sinus rhythm at follow-up. POAF was associated with longer hospitalization (7 vs 6 days; P < .001), but not increased mortality or morbidity. PP reduced POAF incidence (17.7% vs 31.3%; P = .001), especially after postoperative day 2 (time to POAF onset 41.9 vs 57.1 hours; P = .01). Age was associated with POAF. Female sex, coronary artery bypass grafting, beta blockers, and PP were inversely associated. CONCLUSIONS: POAF remains frequent after cardiac surgery. Hemodynamic instability is rare, although rapid ventricular response and need for electrical cardioversion are frequent. POAF burden is significant, and the arrhythmias resolve within 30 days. PP reduces POAF especially after postoperative day 2.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) with vs. without left ventricular unloading by Impella: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for the treatment of cardiogenic shock (CS) may result in left ventricle overload and distension. Percutaneous microaxial flow pump Impella in addition to VA-ECMO (ECPELLA) is an emerging option to overcome these collateral effects. Aim of this study is to assess whether the addition of Impella to VA-ECMO is an effective and safe unloading strategy. METHODS AND RESULTS: We performed a systematic literature review of studies comparing ECPELLA vs. ECMO alone in patients with CS. The primary endpoint was early mortality (in-hospital or 30-day mortality). The secondary endpoints were bleeding, need for kidney replacement therapy, haemolysis, infections, and limb ischaemia. A total of 3469 potentially relevant articles were screened and eight retrospective studies including 11.137 patients were selected. There was no significant difference in early mortality (Risk Ratio, RR 0.90, 95% CI 0.78-1.03) between ECPELLA and ECMO. Nevertheless, there was a borderline significant reduction in early mortality with ECPELLA (RR 0.74, 95% CI 0.55-1.00) at sensitivity analysis selectively including studies reporting propensity matched analysis. ECPELLA was associated with increased bleeding (RR 1.45, 95% CI 1.20-1.75), need for kidney replacement therapy (RR 1.54, 95% CI 1.19-1.99), haemolysis (RR 1.71, 95% CI 1.41-2.07) and limb ischaemia (RR 1.43, 95% CI 1.17-1.75) and with a non-significant increase in severe infections (RR 1.26, 95% CI 0.84-1.89), compared with ECMO alone. CONCLUSION: Among patients with cardiogenic shock, ECPELLA is associated with increased complications compared with ECMO. Whether reducing ventricular overload with Impella among patients treated with ECMO reduces early mortality needs to be confirmed by further investigations.

What is known in pre-, peri-, and post-procedural anticoagulation in micro-axial flow pump protected percutaneous coronary intervention?

Interest in the use of percutaneous left ventricular assist devices (p-LVADs) for patients undergoing high-risk percutaneous coronary intervention (PCI) is growing rapidly. The Impella™ (Abiomed Inc.) is a catheter-based continuous micro-axial flow pump that preserves haemodynamic support during high-risk PCI. Anticoagulation is required to counteract the activation of the coagulation system by the patient's procoagulant state and the foreign-body surface of the pump. Excessive anticoagulation and the effect of dual antiplatelet therapy (DAPT) increase the risk of bleeding. Inadequate anticoagulation leads to thrombus formation and device dysfunction. The precarious balance between bleeding and thrombosis in patients with p-LVAD support is often the primary reason that patients' outcomes are jeopardized. In this chapter, we will discuss anticoagulation strategies and anticoagulant management in the setting of protected PCI. This includes anticoagulant therapy with unfractionated heparin, direct thrombin inhibitors, DAPT, purge blockage prevention by bicarbonate-based purge solution, and monitoring by activated clotting time, partial thromboplastin time, as well as anti-factor Xa levels. Here, we provide a standardized approach to the management of peri-interventional anticoagulation in patients undergoing protected PCI.

Multicolor flow cytometry on pericardial effusion for a prompt diagnosis and treatment of hematological malignancies with heart involvement.

Background: Malignancies represent 15-50% of total causes of pericardial effusions (PE). Routine analyses recommended to be performed on pericardial fluid include general chemistry, cytology, polymerase chain reaction, and microbiological cultures. Multicolor flow cytometry (FC) is a laboratory test that already proved to be useful in the detection of lymphoproliferative and metastatic malignancies in pleural and peritoneal effusions, but current guidelines do not mention its use on PE to reach a diagnosis. Methods: Our institutional protocol foresees to routinely perform a multicolor FC analysis on pericardial fluid samples obtained by pericardiocentesis, in addition to other guidelines-recommended analyses. A sample of 15-30 ml is analyzed using a lyse and wash staining method using combination panels of antibodies, allowing to detect specific cellular subpopulations, analyzing tens to hundreds of thousands of cells in few seconds. The present manuscript aims to report our single-center experience with this diagnostic tool in patients presenting with PE requiring pericardiocentesis. Results: Routine use of multicolor FC on pericardial fluid samples in our institution allowed to reach a definite diagnosis of cardiac lymphomas in two patients presenting with otherwise unexplained severe PE. This resulted in immediate start of combined immunotherapy, with patients' clinical improvement. At 6 months follow-up both patients are alive and presented a complete disease regression. Conclusion: Preliminary evidence from routine use of multicolor FC on PE support that this is a promising tool to reach a rapid diagnosis of hematological malignancies with heart involvement, leading to a prompt initiation of targeted therapies.

Myocardial Injury Portends a Higher Risk of Mortality and Long-Term Cardiovascular Sequelae after Hospital Discharge in COVID-19 Survivors.

Background: Cardiovascular sequelae after COVID-19 are frequent. However, the predictors for their occurrence are still unknown. In this study, we aimed to assess whether myocardial injury during COVID-19 hospitalization is associated to CV sequelae and death after hospital discharge. Methods: In this prospective observational study, consecutive patients who were admitted for COVID-19 in a metropolitan COVID-19 hub in Italy, between March 2021 and January 2022, with a ≥ 1 assessment of high sensitivity cardiac troponin I (hs-cTnI) were included in the study, if they were alive at hospital discharge. Myocardial injury was defined as elevation hs-cTnI > 99th percentile of the upper reference limit. The incidence of all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, admission for acute or chronic coronary syndrome, hospitalization for heart failure, and stroke/transient ischemic attack) at follow-up were the primary outcomes. Arrhythmias, inflammatory heart diseases, and/or thrombotic disorders were analyzed as well. Results: Among the 701 COVID-19 survivors (mean age 66.4 ± 14.4 years, 40.2% female), myocardial injury occurred in 75 (10.7%) patients. At a median follow-up of 270 days (IQR 165, 380), all-cause mortality (21.3% vs. 6.1%, p < 0.001), MACCE (25.3% vs. 4.5%, p < 0.001), arrhythmias (9.3% vs. 5.0%, p = 0.034), and inflammatory heart disease (8.0% vs. 1.1%, p < 0.001) were more frequent in patients with myocardial injury compared to those without. At multivariate analysis, myocardial injury (HR 1.95 [95% CI:1.05−3.61]), age (HR 1.09 [95% CI:1.06−1.12]), and chronic kidney disease (HR 2.63 [95% CI:1.33−5.21]) were independent predictors of death. Myocardial injury (HR 3.92 [95% CI:2.07−7.42]), age (HR 1.05 [95% CI:1.02−1.08]), and diabetes (HR 2.35 [95% CI:1.25−4.43]) were independent predictors of MACCE. Conclusion: In COVID-19 survivors, myocardial injury during the hospital stay portends a higher risk of mortality and cardiovascular sequelae and could be considered for the risk stratification of COVID-19 sequelae in patients who are successfully discharged.

Myocardial infarction with nonobstructive coronary arteries: the need for precision medicine.

PURPOSE OF REVIEW: Myocardial infarction with nonobstructive coronary arteries (MINOCA) represents about 6-8% of all patients with myocardial infarction (MI), and several pathophysiological mechanisms showed to be involved in this heterogeneous clinical condition. Of note, MINOCA proved to be associated with a significant risk of mortality, angina burden and socioeconomic costs. RECENT FINDINGS: Results from randomized clinical trials evaluating the clinical effectiveness of a comprehensive diagnostic algorithm, along with the acute and long-term management of patients with MINOCA, are pending. SUMMARY: In this review article, we aim at providing an overview of the clinical features, diagnostic work-up and the therapeutic management of patients presenting with MINOCA, highlighting the recent acquisition along with the remaining important knowledge gaps in this field.