Background: Myocardial bridging (MB) may represent a cause of myocardial ischemia in patients with non‐obstructive coronary artery disease (NOCAD). Herein, we assessed the interplay between MB and coronary vasomotor disorders, also evaluating their prognostic relevance in patients with myocardial infarction and non‐obstructive coronary arteries (MINOCA) or stable NOCAD. Methods and Results: We prospectively enrolled patients with NOCAD undergoing intracoronary acetylcholine provocative test. The incidence of major adverse cardiac events, defined as the composite of cardiac death, non‐fatal myocardial infarction, and rehospitalization for unstable angina, was assessed at follow‐up. We also assessed angina status using Seattle Angina Questionnaires summary score. We enrolled 310 patients (mean age, 60.6±11.9; 136 [43.9%] men; 169 [54.5%] stable NOCAD and 141 [45.5%] MINOCA). MB was found in 53 (17.1%) patients. MB and a positive acetylcholine test coexisted more frequently in patients with MINOCA versus stable NOCAD. MB was an independent predictor of positive acetylcholine test and MINOCA. At follow‐up (median, 22 months; interquartile range, 13–32), patients with MB had a higher rate of major adverse cardiac events, mainly driven by a higher rate of hospitalization attributable to angina, and a lower Seattle Angina Questionnaires summary score (all P <0.001) compared with patients without MB. In particular, the group of patients with MB and a positive acetylcholine test had the worst prognosis. Conclusions: Among patients with NOCAD, coronary spasm associated with MB may predict a worse clinical presentation with MINOCA and a higher rate of hospitalization attributable to angina at long‐term follow‐up with a low rate of hard events.

Myocardial bridging (MB) is the most frequent congenital coronary anomaly characterized by a segment of an epicardial coronary artery that passes through the myocardium. MB is an important cause of myocardial ischemia and is also emerging as a possible cause of myocardial infarction with non-obstructed coronary arteries (MINOCA). There are multiple mechanisms underlying MINOCA in patients with MB (i.e., MB-mediated increased risk of epicardial or microvascular coronary spasm, atherosclerotic plaque disruption and spontaneous coronary artery dissection). The identification of the exact pathogenetic mechanism is crucial in order to establish a patient-tailored therapy. This review provides the most up-to-date evidence regarding the pathophysiology of MINOCA in patients with MB. Moreover, it focuses on the available diagnostic tools that could be implemented at the time of coronary angiography to achieve a pathophysiologic diagnosis. Finally, it focuses on the therapeutic implications associated with the different pathogenetic mechanisms of MINOCA in patients with MB.

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.

Coronary microvascular dysfunction (CMD) plays a crucial role across the spectrum of heart failure (HF) pathology, contributing to disease development, progression, and outcomes. The pathophysiological mechanisms linking CMD to HF are complex and still not completely understood and include chronic inflammation, oxidative stress, and neurohormonal activation. Despite the diagnostic and prognostic relevance in patients with HF, there is no specific therapeutic strategy targeting CMD to date. Moreover, the diagnosis of this clinical condition is challenging. In this review article, we aim to discuss the different clinical pathogenetic mechanisms linking CMD to HF across the different spectra of these diseases, their prognostic relevance, and the possible therapeutic targets along with the remaining knowledge gaps in the field.

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.

Over the last decades, the advances in the treatment of patients with ST-segment–elevation myocardial infarction (STEMI) have resulted in a reduced mortality. However, the incidence of rehospitalization for heart failure (HF) as a consequence of the development of adverse left ventricular (LV) remodeling remains unacceptably high and the long-term mortality is equally worrisome [ [1] Niccoli G. Montone R.A. Ibanez B. Thiele H. Crea F. Heusch G. Bulluck H. Hausenloy D.J. Berry C. Stiermaier T. Camici P.G. Eitel I. Optimized treatment of ST-elevation myocardial infarction. Circ. Res. 2019; 125 : 245-258 Crossref PubMed Scopus (41) Google Scholar ]. Infarct size has long been known to be an independent predictor of LV remodeling and adverse outcomes after myocardial infarction (MI). However, microcirculatory impairment due to microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) has been recently demonstrated as an important independent predictor of adverse LV remodeling and recent evidence supports the notion that MVO may be more predictive of major adverse cardiovascular events (MACE) than infarct size itself [ [2] de Waha S. Patel M.R. Granger C.B. Ohman E.M. Maehara A. Eitel I. Ben-Yehuda O. Jenkins P. Thiele H. Stone G.W. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials. Eur. Heart J. 2017; 38 : 3502-3510 Crossref PubMed Scopus (101) Google Scholar ]. MVO may occur in up to 60% of STEMI patients treated with pPCI [ 3 Niccoli G. Scalone G. Lerman A. Crea F. Coronary microvascular obstruction in acute myocardial infarction. Eur. Heart J. 2016; 37 : 1024-1033 Crossref PubMed Scopus (175) Google Scholar , 4 Montone R.A. Niccoli G. Minelli S. Fracassi F. Vetrugno V. Aurigemma C. Burzotta F. Porto I. Trani C. Crea F. Clinical outcome and correlates of coronary microvascular obstruction in latecomers after acute myocardial infarction. Int. J. Cardiol. 2017; 236 : 30-35 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar , 5 Khorramirouz R. Corban M.T. Yang S.W. Lewis B.R. Bois J. Foley T. Lerman L.O. Herrmann J. Oh J.K. Lerman A. Microvascular obstruction in non-infarct related coronary arteries is an independent predictor of major adverse cardiovascular events in patients with ST segment-elevation myocardial infarction. Int. J. Cardiol. 2018; 273 : 22-28 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar ], and the underlying pathophysiologic mechanisms are still not completely understood, embracing distal embolization, ischemia-reperfusion injury and an individual predisposition to microvascular dysfunction [ [1] Niccoli G. Montone R.A. Ibanez B. Thiele H. Crea F. Heusch G. Bulluck H. Hausenloy D.J. Berry C. Stiermaier T. Camici P.G. Eitel I. Optimized treatment of ST-elevation myocardial infarction. Circ. Res. 2019; 125 : 245-258 Crossref PubMed Scopus (41) Google Scholar , [3] Niccoli G. Scalone G. Lerman A. Crea F. Coronary microvascular obstruction in acute myocardial infarction. Eur. Heart J. 2016; 37 : 1024-1033 Crossref PubMed Scopus (175) Google Scholar ]. Several studies demonstrated that inflammatory activation immediately following the initial ischemic event seems to play a crucial role, contributing to MVO. Indeed, an intense inflammatory response is observed in the acute phase after MI, with the purpose to remove necrotic debris from the MI zone [ [6] Seropian I.M. Toldo S. Van Tassell B.W. Abbate A. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J. Am. Coll. Cardiol. 2014; 63 : 1593-1603 Crossref PubMed Scopus (156) Google Scholar ]. However, a robust inflammatory response may lead to the occurrence of a significant interstitial myocardial oedema that not only is a consequence of sustained myocardial ischemia/reperfusion injury but also contributes to MVO by compressing capillaries and small arterioles and further decreasing flow through this dysfunctional microcirculation. Moreover, the persistence of the inflammatory process in the chronic phase after MI may contribute to the occurrence of adverse LV remodeling [ [6] Seropian I.M. Toldo S. Van Tassell B.W. Abbate A. Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J. Am. Coll. Cardiol. 2014; 63 : 1593-1603 Crossref PubMed Scopus (156) Google Scholar , [7] Tiller C. Reindl M. Holzknecht M. Lechner I. Simma F. Schwaiger J. Mayr A. Klug G. Bauer A. Reinstadler S.J. Metzler B. High sensitivity C-reactive protein is associated with worse infarct healing after revascularized ST-elevation myocardial infarction. Int. J. Cardiol. 2021; 328 : 191-196 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ].