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Myocardial infarction with nonobstructed coronary arteries (MINOCA) can be triggered by intense emotions. We report 5 cases of emotional stress–related death where forensic examination attributed myocardial infarction to a coronary spasm, with the ultimate cause of death being arrhythmias in 4 cases and cardiac rupture in the fifth. (Level of Difficulty: Beginner.), Graphical abstract, Myocardial infarction with nonobstructed coronary arteries (MINOCA) can be triggered by intense emotions. We report 5 cases of emotional…

Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care.

ObjectiveTo assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19).MethodsThis single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE). Patients with poor acoustic window (n=11) were excluded. Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion ResultsA total of 200 patients were included in the final analysis (median age 62 (IQR 52–74) years, 65.5% men). The prevalence of PH and RVD was 12.0% (24/200) and 14.5% (29/200), respectively. Patients with PH were older and had a higher burden of pre-existing cardiac comorbidities and signs of more severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (radiological lung involvement, laboratory findings and oxygenation status) compared with those without PH. Conversely, patients with RVD had a higher burden of pre-existing cardiac comorbidities but no evidence of more severe SARS-CoV-2 infection compared with those without RVD. The presence of PH was associated with a higher rate of in-hospital death or ICU admission (41.7 vs 8.5%, pConclusionsAmong hospitalised non-ICU patients with COVID-19, PH (and not RVD) was associated with signs of more severe COVID-19 and with worse in-hospital clinical outcome.Trial registration numberNCT04318366

BACKGROUND Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms

Background The outcomes of patients presenting with acute myocarditis and life-threatening ventricular tachyarrhythmias (LT-VA) are unclear. The aim of this study was to assess incidence and predictors of recurrence of major arrhythmic events (MAEs) after hospital discharge in such patients. Methods and results We retrospectively analysed 156 patients (median age 44 years; 77% males) discharged with a diagnosis of acute myocarditis and LT-VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or on the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death (SCD) or ventricular fibrillation defibrillated successfully or sustained ventricular tachycardia (sVT) requiring implantable cardioverter-defibrillator therapy or synchronized external cardioversion. Median follow-up period was 23 months (first to third quartile [Q1-Q3] 7-60). Fifty-eight (37.2%) patients experienced MAEs after discharge, at a median time of 8 months (Q1-Q3 2.5-24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated to MAEs were presentation with sVT (hazard ratio [HR] 2.90, 95% confidence interval [CI] 1.38-6.11); late gadolinium enhancement (LGE) involving ≥2 myocardial segments (HR 4.51, 95% CI 2.39-8.53); and absence of positive short-tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40-4.79) at first CMR. Conclusions Among patients discharged with the diagnosis of myocarditis and LT-VA, 37.2% had recurrences of MAEs during follow-up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmic recurrence.

When acute myocardial injury is found in a clinical setting suggestive of myocardial ischemia, the event is labeled as acute myocardial infarction (MI), and the absence of ≥50% coronary stenosis at angiography or greater leads to the working diagnosis of myocardial infarction with non-obstructed coronary arteries (MINOCA). Determining the mechanism of MINOCA and excluding other possible causes for cardiac troponin elevation has notable implications for tailoring secondary prevention measures aimed at improving the overall prognosis of acute MI. The aim of this review is to increase the awareness that establishing the underlying cause of a MINOCA is possible in the vast majority of cases, and that the proper classification of any MI should be pursued. The initial diagnosis of MINOCA can be confirmed or ruled out based on the results of subsequent investigations. Indeed, a comprehensive clinical evaluation at the time of presentation, followed by a dedicated diagnostic work-up, might lead to the identification of the pathophysiologic abnormality leading to MI in almost all cases initially labeled as MINOCA. When a specific cause of acute MI is identified, cardiologists are urged to transition from the “all-inclusive” term “MINOCA” to the proper classification of any MI, as evidence now exists that MINOCA does not provide conceptual clarity for actionable decision-making in MI with angiographically normal coronary arteries.

Takotsubo syndrome (TTS) is estimated to account for 1–3% of all patients presenting with suspected ST-segment elevation myocardial infarction. A sudden surge in sympathetic nervous system is considered the cause of TTS. Nonetheless, no specific recommendations have been provided regarding β-blocking therapy. Apart from specific contra-indications (severe LV dysfunction, hypotension, bradycardia and corrected QT interval >500 ms), treatment with a β-blocker seems reasonable until full recovery of LV ejection fraction, though evidence is limited to a few animal studies, case reports or observational studies. In this review, we will reappraise the rationale for β-blocker therapy in TTS and speculate on the pathophysiologic basis for preferring non-selective agents with vasodilating activity over β1-selective drugs.

The role of cardiac magnetic resonance (CMR) in identifying mechanisms for myocardial infarction with non-obstructed coronary arteries (MINOCA) is well established. Recent reports have highlighted the potentially key role of invasive management in this diagnostic process. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) allow precise evaluation of coronary anatomy, and assessment of coronary physiology in the catheter laboratory provides information on the hemodynamic significance of sub-critical atherosclerosis and on coronary microvascular dysfunction (CMD). We reviewed the evidence for the contribution of invasive diagnostic techniques in identifying provisional causes for MINOCA. Overall, among 82 studies including 8457 patients were selected. In the acute phase, 16 studies with IVUS or OCT (1207 patients) disclosed that plaque disruption and spontaneous coronary artery dissection had a pooled prevalence of 38% (95% confidence intervals (CI): 29% to 51%) and 16% (95% CI: 9% to 27%), respectively. In 18 studies, coronary function testing (1449 patients) showed a pooled prevalence of spontaneous and/or provoked epicardial coronary spasm of ~28% (95% CI:17% to 41%). In 3 studies (456 patients), the pooled prevalence of CMD was ~32% (95% CI: 20% to 49%). In the subacute phase, 42 CMR studies (5821 patients) showed that a pooled prevalence of myocarditis, takotsubo syndrome and cardiomyopathy of 26% (95% CI: 12% to 40%), 11% (95% CI: 5% to 25%), and 7% (95% CI: 1% to 19%), respectively. In 12 studies on thrombophilia screening (n = 834), the pooled prevalence of thrombotic disorder was ~11% (95% CI: 7%% to 25%). In conclusion, the pathophysiology of MINOCA can be established in the majority of cases using both invasive and non-invasive tools to provide direction for appropriate management.

Background. Myocarditis lacks systematic characterization in COVID-19 patients. Methods. We enrolled consecutive patients with newly diagnosed myocarditis in the context of COVID-19 infection. Diagnostic and treatment strategies were driven by a dedicated multidisciplinary disease unit for myocarditis. Multimodal outcomes were assessed during prospective follow-up. Results. Seven consecutive patients (57% males, age 51 ± 9 y) with acute COVID-19 infection received a de novo diagnosis of myocarditis. Endomyocardial biopsy was of choice in hemodynamically unstable patients (n = 4, mean left ventricular ejection fraction (LVEF) 25 ± 9%), whereas cardiac magnetic resonance constituted the first exam in stable patients (n = 3, mean LVEF 48 ± 10%). Polymerase chain reaction (PCR) analysis revealed an intra-myocardial SARS-CoV-2 genome in one of the six cases undergoing biopsy: in the remaining patients, myocarditis was either due to other viruses (n = 2) or virus-negative (n = 3). Hemodynamic support was needed for four unstable patients (57%), whereas a cardiac device implant was chosen in two of four cases showing ventricular arrhythmias. Medical treatment included immunosuppression (43%) and biological therapy (29%). By the 6-month median follow-up, no patient died or experienced malignant arrhythmias. However, two cases (29%) were screened for heart transplantation. Conclusions. Myocarditis associated with acute COVID-19 infection is a spectrum of clinical manifestations and underlying etiologies. A multidisciplinary approach is the cornerstone for tailored management.

AIMS Coronary microvascular dysfunction (CMD) represents a powerful independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). No treatment for CMD exists. The angiotensin-converting enzyme (ACE)-inhibitor perindopril improves myocardial blood flow (MBF) in animal models of cardiac hypertrophy and in hypertensive patients. Whether HCM patients with CMD may benefit is unknown. METHODS Fourteen HCM patients aged 18-60 years with CMD [MBF post 0.56 mg/kg dipyridamole (Dip) infusion

Systemic arterial hypertension is a highly prevalent chronic disease associated with hypertensive cardiomyopathy. One important feature of this condition is remodelling of intramural small coronary arteries and arterioles. Here, we investigated the implications of this remodelling in the downstream vascular organization, in particular at the capillary level. We used Spontaneously Hypertensive Rats (SHR) exhibiting many features of the human hypertensive cardiomyopathy. We generated 3D high-resolution mesoscopic reconstructions of the entire network of SHR hearts combining gel-based fluorescent labelling of coronaries with a CLARITY-based tissue clearing protocol. We performed morphometric quantification of the capillary network over time to assess capillary diameter, linear density, and angular dispersion. In SHRs, we found significant remodelling of the capillary network density and dispersion. SHR capillary density is increased in both ventricles and at all ages, including before the onset of systemic hypertension. This result suggests that remodelling occurs independently from the onset of systemic hypertension and left ventricular hypertrophy. On the contrary, capillary angular dispersion increases with time in SHR. Consistently, our multi-modal imaging underlined a strong correlation between vascular dispersion and cellular disarray. Together our data show that 3D high-resolution reconstruction of the capillary network can unveil anatomic signatures in both physiological and pathological cardiac conditions, thus offering a reliable method for integrated quantitative analyses.

Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface of the organ providing tissue perfusion through an intricate network of penetrating small vessels. Both organs rely on fine tuning of local blood flow to match metabolic demand. Blood flow regulation requires adequate functioning of the microcirculation in both organs, with loss of microvascular function, termed small vessel disease (SVD) underlying different potential clinical manifestations. SVD in the heart, known as coronary microvascular dysfunction, can cause chronic or acute myocardial ischemia and may lead to development of heart failure. In the brain, cerebral SVD can cause an acute stroke syndrome known as lacunar stroke or more subtle pathological alterations of the brain parenchyma, which may eventually lead to neurological deficits or cognitive decline in the long term. Coronary microcirculation cannot be visualized in vivo in humans, and functional information can be deduced by measuring the coronary flow reserve. The diagnosis of cerebral SVD is largely based on brain magnetic resonance imaging, with white matter hyperintensities, microbleeds, and brain atrophy reflecting key structural changes. There is evidence that such structural changes reflect underlying cerebral SVD. Here, we review interactions between SVD and cardiovascular risk factors, and we discuss the evidence linking cerebral SVD with large vessel atheroma, atrial fibrillation, heart failure, and heart valve disease.

This consensus document, a summary of the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), appraises the importance of ischaemia with non-obstructive coronary arteries (INOCA). Angina pectoris affects approximately 112 million people globally. Up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease, more common in women than in men, and a large proportion have INOCA as a cause of their symptoms. INOCA patients present with a wide spectrum of symptoms and signs that are often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. INOCA can result from heterogeneous mechanism including coronary vasospasm and microvascular dysfunction and is not a benign condition. Compared to asymptomatic individuals, INOCA is associated with increased incidence of cardiovascular events, repeated hospital admissions, as well as impaired quality of life and associated increased health care costs. This consensus document provides a definition of INOCA and guidance to the community on the diagnostic approach and management of INOCA based on existing evidence from research and best available clinical practice; noting gaps in knowledge and potential areas for further investigation.

Myocardial infarction in the absence of obstructive coronary stenosis (MINOCA) is a syndrome with several causes, characterized by clinical evidence of myocardial infarction and coronary angiographically normal or almost normal (stenosis ≤50%). MINOCAs represent about 10% of acute coronary syndromes. The causes of MINOCA are manifold and can be classified on the basis of the mechanism in epicardial (unstable plaque not manifested by angiography, epicardial spasm and coronary dissection) or microvascular. The latter in turn can be divided into intrinsic (microvascular spasm, Takotsubo syndrome and coronary embolization) and extrinsic (myocarditis). In the former, the dysfunctional microcirculation causes myocardial necrosis due to reduction of the lumen due to vasoconstriction and / or obstruction, while in the latter, the compression of the lumen occurs ab extrinsic due to myocardial edema. Note that the prognosis of MINOCA is extremely variable and depends on the underlying cause with high risk clinical subsets. A correct diagnostic procedure includes first level tests (clinical / anamnestic examination, ECG, myocardial necrosis enzyme dosage, trans-thoracic echocardiogram, coronary angiography, ventriculogram) and second level tests (intracoronary imaging, coronary vasomotor test, cardiac nuclear magnetic resonance and trans-esophageal or contrast ultrasound). Through this process, it is possible to identify the cause of MINOCA, fundamental for targeting therapy on the disease mechanism, thus constituting a typical example of precision medicine.

Aims Fabry cardiomyopathy is characterized by glycosphingolipid storage and increased myocardial trabeculation has also been demonstrated. This study aimed to explore by cardiac magnetic resonance whether myocardial trabecular complexity, quantified by endocardial border fractal analysis, tracks phenotype evolution in Fabry cardiomyopathy. Methods and results Study population included 20 healthy controls (12 males, age 32±9) and 45 Fabry patients divided into three groups: 15 left ventricular hypertrophy (LVH)-negative patients with normal T1 (5 males, age 28±13; Group 1); 15 LVH-negative patients with low T1 (9 males, age 33±9.6; Group 2); 15 LVH-positive patients (11 males, age 53.5±9.6; Group 3). Trabecular fractal dimensions (Dfs) (total, basal, mid-ventricular, and apical) were evaluated on cine images. Total Df was higher in all Fabry groups compared to controls, gradually increasing from controls to Group 3 (1.27±0.02 controls vs. 1.29±0.02 Group 1 vs. 1.30±0.02 Group 2 vs. 1.34±0.02 Group 3; P Conclusion Fabry cardiomyopathy is characterized by a progressive increase in Df of endocardial trabeculae together with shortening of T1 values. Myocardial trabeculation is increased before the presence of detectable sphingolipid storage, thus representing an early sign of cardiac involvement.

Supplemental Digital Content is available in the text., Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally

Highlights • Age and fibrocalcific carotid plaques are associated with lower total brain volume. • Fibrocalcific carotid plaques are associated with lower gray matter volumes. • White matter volumes are associated with the extent of carotid atherosclerosis. • Grey and white matter likely have differential susceptibility to processes., Background and aims Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization. Methods and results Sixty-four patients (aged 69 ± 8 years, 45% females) with carotid stenosis

Left ventricular (LV) hypertrophy (LVH) is a growth in left myocardial mass mainly caused by increased cardiomyocyte size. LVH can be a physiological adaptation to physical exercise or a pathological condition either primary, i.e. genetic, or secondary to LV overload. Patients with both primary and secondary LVH have evidence of coronary microvascular dysfunction (CMD). The latter is mainly due to capillary rarefaction and adverse remodelling of intramural coronary arterioles due to medial wall thickening with an increased wall/lumen ratio. An important feature of this phenomenon is the diffuse nature of this remodelling, which generally affects the coronary microvessels in the whole of the left ventricle. Patients with LVH secondary to arterial hypertension can develop both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). These patients can develop HFrEF via a ‘direct pathway’ with an interval myocardial infarction and also in its absence. On the other hand, patients can develop HFpEF that can then progress to HFrEF with or without interval myocardial infarction. A similar evolution towards LV dysfunction and both HFpEF and HFrEF can occur in patients with hypertrophic cardiomyopathy, the most common genetic cardiomyopathy with a phenotype characterized by massive LVH. In this review article, we will discuss both the experimental and clinical studies explaining the mechanisms responsible for CMD in LVH as well as the evidence linking CMD with HFpEF and HFrEF.

Background: In many genetic and acquired non-ischaemic cardiomyopathies (NICM) there have been frequent reports of involvement of the interventricular septum (IVS) by late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR). However, no studies have investigated the relationship between septal LGE and arrhythmias in different NICM subtypes. Methods: This study enrolled 103 patients with septal LGE at baseline CMR and different NICM: hypertrophic (n=29) or lamin A/C gene (LMNA)-associated (n=23) cardiomyopathy, and acute (n=30) or previous (n=21) myocarditis. During follow-up, the occurrences of malignant ventricular arrhythmias (MVA) and major bradyarrhythmias (BA) were evaluated. Results: At 4.9±0.7 years of follow-up, the occurrence of MVA and major BA in genetic vs acquired NICM were 10 of 52 vs 12 of 51, and 10 of 52 vs 4 of 51, respectively (both p=n.s.). However, MVA occurred more frequently in LMNA-NICM (eight of 23 vs two of 29 hypertrophic, p=0.015) and in previous myocarditis (nine of 21 vs three of 30 acute, p=0.016), while major BAs were particularly common in LMNA-NICM patients only (nine of 23 vs one of 29 hypertrophic, p=0.003). Different patterns of septal LGE were consistently retrospectively identified at baseline CMR: junctional and limited to the base in 79.3% of uneventful hypertrophic NICM; extended and focally transmural in LMNA-NICM with follow-up arrhythmias (both p

Funding Acknowledgements none Background The distinction between proportionate and disproportionate functional mitral regurgitation (FMR), based on the relationship between effective regurgitant orifice area (EROA) and left ventricle end diastolic volume (LVEDV), has recently been proposed as a possible new clinical and physiopathological framework to identify patients that could likely benefit from transcatheter mitral repair. Purpose The aim of our study was to explore the possible prognostic implications of the EROA/LVEDV ratio in patients with FMR treated with MitraClip. Methods – Baseline EROA/LVEDV was calculated in 137 patients with at least moderate-to-severe, symptomatic FMR treated with MitraClip. All patients underwent clinical, biochemichal and echocardiographic evaluation before MitraClip. EROA was calculated using PISA method. The primary outcome was a composite end-point of all-cause death or re-hospitalization for heart failure (HF). Results – The median follow-up was 1.1 years. The primary outcome occurred in 59 patients (43 %). Population study showed a LVEDVi 113.52± 32.16 mL/m2, LVEF 29.75± 10.06% and EROA 39.45± 15.43 mm2.. The cut-off value of EROA/LVEDV ratio for primary outcome, identified by receiver operating characteristic curve, was 0.15 (AUC 0,65, p = 0.002) with a sensitivity and specificity of 78% and 52%, respectively. Patients were divided in two groups according to the identified cut-off. Patients with higher ratio (Group I, n = 88) presented a less dilated LV (LVEDVi: 105.1 ± 29.6 mL/m2 vs 128.2 ± 31.9 mL/m2, p < 0.001; LVESVi: 73.1 ± 27.7 mL/m2 vs 94.9 ± 29.05 mL/m2, p < 0.001), and a more severe MR (EROA: 47.9 ± 12.1 mm2 vs 25.1 ± 8.3 mm2, p < 0.001; vena contracta: 7.2 ± 1.3 mm vs 6.5 ± 1.3 mm, p = 0.008). There were no significant differences of left ventricle ejection fraction, right ventricle systolic function and systolic pulmonary pressure between the groups. At univariate analysis, EROA/LVEDV ratio >0.15 (HR = 2.223, 95% CI 1.121-4.411, p = 0.022), baseline evidence of atrial fibrillation (HR = 1.949, 95% CI 1.156-3.283, p = 0.012) and baseline pro-BNP (HR= 1.000, 95% CI 1.000-1.000, p = 0,001) were associated with a worse clinical outcome. At multivariate Cox-regression analysis, both EROA/LVEDV ratio >0.15 and baseline pro-BNP values were identified as independent predictors (HR 2.941, 95% CI 1.035-8.353, p = 0.043; HR = 1.000, 95% CI 1.000-1.000, p = 0.002, respectively). At Kaplan-Meier survival analysis, patients with EROA/LVEDV >0.15 had a significant lower freedom from composite endpoint (log-rank χ2 =5.517, p= 0.019; Fig. 1). Conclusion Our data show that EROA/LVEDV ratio was an independent predictor of adverse clinical outcome in FMR patients treated with MitraClip. This preliminary experience shows that this index could help to identify subgroups of patients with potential different clinical benefits from Mitraclip therapy. However, further and extended data are needed to provide more precise evidence. Abstract 428 Figure. Fig. 1

Although current guidelines on the management of stable coronary artery disease acknowledge that multiple mechanisms may precipitate myocardial ischemia, recommended diagnostic, prognostic and therapeutic algorithms are still focused on obstructive epicardial atherosclerotic lesions, and little progress has been made in identifying management strategies for non-atherosclerotic causes of myocardial ischemia. The purpose of this consensus paper is three-fold: 1) to marshal scientific evidence that obstructive atherosclerosis can co-exist with other mechanisms of ischemic heart disease (IHD); 2) to explore how the awareness of multiple precipitating mechanisms could impact on pre-test probability, provocative test results and treatment strategies; and 3) to stimulate a more comprehensive approach to chronic myocardial ischemic syndromes, consistent with the new understanding of this condition.

Aims In ST-segment-elevation myocardial infarction (STEMI), cardiovascular magnetic resonance (CMR) holds the potentiality to improve risk stratification in addition to Thrombolysis in Myocardial Infarction (TIMI) risk score. Nevertheless, the optimal timing for CMR after STEMI remains poorly defined. We aim at comparing the prognostic performance of three stratification strategies according to the timing of CMR after STEMI. Methods and results The population of this prospective registry-based study included 492 reperfused STEMI patients. All patients underwent post-reperfusion (median: 4 days post-STEMI) and follow-up (median: 4.8 months post-STEMI) CMR. Left ventricular (LV) volumes, function, infarct size, and microvascular obstruction extent were quantified. Primary endpoint was a composite of all-death and heart failure (HF) hospitalization. Baseline-to-follow-up percentage increase of LV end-diastolic (EDV; ΔLV-EDV) ≥20% or end-systolic volumes (ESV; ΔLV-ESV) ≥15% were tested against outcome. Three multivariate models were developed including TIMI risk score plus early post-STEMI (early-CMR) or follow-up CMR (deferred-CMR) or both CMRs parameters along with adverse LV remodelling (paired-CMRs). During a median follow-up of 8.3 years, the primary endpoint occurred in 84 patients (47 deaths; 37 HF hospitalizations). Early-CMR, deferred-CMR, and paired-CMR demonstrated similar predictive value for the primary endpoint (C-statistic: 0.726, 0.728, and 0.738, respectively; P = 0.663). ΔLV-EDV ≥20% or ΔLV-ESV ≥15% were unadjusted outcome predictors (hazard ratio: 2.020 and 2.032, respectively; P = 0.002 for both) but lost their predictive value when corrected for other covariates in paired-CMR model. Conclusion In STEMI patients, early-, deferred-, or paired-CMR were equivalent stratification strategies for outcome prediction. Adverse LV remodelling parameters were not independent prognosticators.

Chest pain stands as one of the most frequent patient presentations in the emergency department (ED). Despite established diagnostic algorithms for identifying several important causes of chest pain, such as acute myocardial infarction (AMI), aortic dissection, and pulmonary embolism, guidance on managing patients with recurrent chest pain, one of the top 3 reasons for repeated hospitalization in the United States, is less defined. The assessment of symptoms, serial ECG, and necrosis biomarkers plays a major role in patient management. Notably, the recently introduced high-sensitivity troponin T (hs-TnT) assay is helping to identify ischemia in patients previously undiagnosed by conventional testing. In Europe, with the use of this assay for over a decade, the identification of patients with AMI has substantially increased, particularly of patients with type 2 AMI, which is seen in the absence of atherosclerotic obstruction of the epicardial coronaries on angiography. Use of hs-TnT is in particular relevant in women, in whom the use of a sex-specific threshold for elevated hs-TnT has almost doubled the diagnosis of AMI. With the advent of the hs-TnT assay in the United States in 2017, a similar phenomenon is expected. Thus, it is important to learn from the European experience and to develop sex-specific nuanced algorithms for the evaluation of additional causes of myocardial ischemia/necrosis, such as coronary artery vasomotor disorders and coronary microvascular dysfunction. The latter has a high prevalence among symptomatic women presenting to the ED, a group in whom recurrent chest pain is common. This commentary describes the tools available for diagnosing epicardial- and non–epicardial-related myocardial ischemia in patients with recurrent chest pain in the ED setting. A sex-specific, nuanced approach applied to select groups of patients being observed in the ED has the potential to reduce admissions and to allow for the initiation of timely, appropriate medical treatment and outpatient follow-up in an at-risk population. The costs and availability of advanced diagnostics may pose some limitation to the widespread adoption of such protocols.

In recent years, it has become apparent that coronary microvascular dysfunction plays a pivotal pathogenic role in angina pectoris. Functional and structural mechanisms can affect the physiological function of the coronary microvasculature and lead to myocardial ischemia in people without coronary atheromatous disease and also in individuals with obstructive coronary artery disease. Abnormal dilatory responses of the coronary microvessels, coronary microvascular spasm, and extravascular compressive forces have been identified as pathogenic mechanisms in both chronic and acute forms of ischemic heart disease. The condition characterized by anginal symptoms and evidence of myocardial ischemia triggered by coronary microvascular dysfunction, in the absence of obstructive coronary disease, is known as microvascular angina. The concept of microvascular angina, however, may extend further to include patients with obstructive coronary artery disease and individuals with angina after coronary revascularization or heart transplantation because coronary microvascular dysfunction contributes to myocardial ischemia in many such patients. Patients with microvascular angina constitute a sizeable proportion of all cases of stable angina undergoing diagnostic coronary angiography and of those with persisting angina after successful coronary revascularization. Coronary microvascular dysfunction is also often responsible for angina in individuals with cardiomyopathy and heart valve disease as well as acute coronary syndrome cases such as Takotsubo syndrome and myocardial infarction with no obstructive coronary artery disease. Patients with stable microvascular angina present typically with effort or rest chest pain and a reduced coronary flow reserve or microvascular spasm. This condition, which affects women and men, can markedly impair quality of life and prognosis and represents a substantial cost burden to healthcare systems and individuals alike. In recent years, progress in the diagnosis of myocardial ischemia and the use of tests to investigate functional and structural causes for a reduced coronary flow reserve and microvascular spasm have allowed the identification of an increased number of cases of microvascular angina in everyday clinical practice. Although some of the available anti-anginal drugs may be helpful, treatment of coronary microvascular dysfunction remains a major challenge. The present article discusses the fundamental role that coronary microvascular dysfunction plays in the pathogenesis of ischemic heart disease, the clinical characteristics of patients presenting with microvascular angina, and possible diagnostic and therapeutic strategies.

Ivabradine is a heart rate reducing agent that exhibits anti-ischemic effects through the inhibition of funny electrical current in the sinus node resulting in heart rate reduction, thus enabling longer diastolic perfusion time, and reduced myocardial oxygen consumption without detrimental changes in arterial blood pressure, coronary vasomotion, and ventricular contractility. The current guideline-based clinical use of Ivabradine is reserved for patients with stable angina pectoris who cannot tolerate or whose symptoms are inadequately controlled with beta blockers. In patients with chronic heart failure and reduced ejection fraction, Ivabradine has demonstrated beneficial effects in improving clinical outcomes when added to conventional therapy. However, the role of Ivabradine in acute coronary syndromes has not been established. Based on the results from some relevant preclinical studies and a limited amount of clinical data that were reported recently, the role of Ivabradine in acute ischemic events warrants further investigation. The aim of this review is to provide an overview of the available literature on the potential role of Ivabradine in the clinical context of acute coronary syndromes.

The Cardiovascular Disease in Women Committee of the American College of Cardiology, in conjunction with interested parties (from the National Heart, Lung, and Blood Institute, American Heart Association, and European Society of Cardiology), convened a working group to develop a consensus on the syndrome of myocardial ischemia with no obstructive coronary arteries. In general, these patients have elevated risk for a cardiovascular event (including acute coronary syndrome, heart failure hospitalization, stroke, and repeat cardiovascular procedures) compared with reference subjects and appear to be at higher risk for development of heart failure with preserved ejection fraction. A subgroup of these patients also has coronary microvascular dysfunction and evidence of inflammation. This document provides a summary of findings and recommendations for the development of an integrated approach for identifying and managing patients with ischemia with no obstructive coronary arteries and outlines knowledge gaps in the area. Working group members critically reviewed available literature and current practices for risk assessment and state-of-the-science techniques in multiple areas, with a focus on next steps needed to develop evidence-based therapies. This report presents highlights of this working group review and a summary of suggested research directions to advance this field in the next decade.

Background The presence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has diagnostic and prognostic value in patients with acute myocarditis (AM). Aim of our study was to quantify the changes in LGE extension (LGE%) early after AM and evaluate its relations with biventricular function and morphology. Methods We investigated 76 consecutive patients with AM (acute onset of chest pain/heart failure/ventricular arrhythmias not explained by other causes, and raised troponin) that met CMR criteria based on myocardial oedema at T2-weighted images and LGE on post-contrast images at median time of 6 days from onset of symptoms. We quantified LGE% at baseline and after 148 days in 49 patients. Results Median left ventricular (LV)-ejection fraction (EF) was 64% (interquartile range [Q1–Q3]: 56–67%), and LGE% 9.4% (Q1–Q3: 7.5–13.2%). LGE% was correlated with LV end-systolic volume index (LV-ESVi; r = + 0.34; p = 0.003). LGE% was inversely correlated with LV-EF (r = − 0.31; p = 0.009) and time to CMR scan (r = − 0.25; p = 0.028). In the 49 patients with a second CMR scan, despite no significant variations in LV-EF, a significant decrease of LGE% was observed (p < 0.0001) with a relative reduction of 42% compared with baseline. Patients showing increased LV-ESVi at follow up had a lower decrease of LGE% (p = 0.038). Conclusions In the acute phase of AM the LGE extension is a dynamic process that reflects impairment of LV function and is time dependent. LGE% appears one of the CMR parameters with the largest relative variations in the first months after AM

Many of the patients undergoing chemotherapy or radiotherapy for cancer are at increased risk of developing cardiovascular diseases. Recent evidence suggests that cardiac dysfunction and subsequent heart failure are mainly due to vascular toxicity rather than only to due to myocyte toxicity. However, not all of the vascular toxicity of cancer therapies can be explained by epicardial coronary artery disease. In fact, in the last decades, it has been found that myocardial ischemia may occur as a consequence of structural or functional dysfunction of the complex network of vessels, which cannot be seen by a coronary angiography: the coronary microcirculation. Nowadays many diagnostic and therapeutic options are available both in coronary microvascular dysfunction and cardio-oncology. Aim of this review is to suggest future theranostic implications of the relationship between cardiotoxicity in oncology and coronary microvascular dysfunction, showing common pathophysiologic mechanisms, proposing new diagnostic approaches and therapeutic options for cardioprotection.

Impella RP has been used to treat right ventricular failure (RVF) developing in various clinical settings that underlay different pathological mechanisms and lead to distinct prognostic implications.This is a single-centre retrospective study including all consecutive patients, from January 2015 to December 2018, with inferior STEMI due to acute thrombotic occlusion of right coronary artery (RCA) and unsuccessful primary percutaneous coronary intervention (PCI) complicated by refractory RVF managed with an Impella RP device.A total of 5 patients have been treated. The mean age was 73 ± 9 years, 80% were males. All patients, except one, were hemodynamically stable at hospital admission. In all patients, PCI resulted unsuccessful (final TIMI flow 3), with subsequent development of refractory RVF and cardiogenic shock in the catheterization laboratory, despite the use of inotropes and intra-aortic balloon pump (IABP). In 80% of the cases, Impella RP was placed immediately after PCI. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in systolic blood pressure from 91 ± 17 to 136 ± 13 mmHg, a decrease in central venous pressure from 16 ± 2.5 to 12 ± 4 mmHg and a resolution in lactates from 4.5 ± 2.5 to 1.6 ± 0.7 mg/dL. Mean duration of IABP and Impella RP support were 4 and 7 days, respectively. RV recovery occurred in 80% of the cases. All patients survived at 30-day.In patients with AMI complicated by unsuccessful revascularization of RCA and refractory RVF, the use of Impella RP device resulted in immediate hemodynamic benefit with reversal of shock and favourable survival at 30-day.

Background Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular (LV) dysfunction requiring inotropes and/or mechanical circulatory support. Based on a retrospective single-center study published in 2000, patients with FM were considered to have better outcomes than those affected by acute non-fulminant myocarditis (NFM) presenting with LV systolic dysfunction (LVSD). Recently, this tenet was challenged, though substantial disagreement still exists. Purpose Aim of the present study is to provide additional evidence on the outcome of FM and to ascertain if patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods Two hundred and twenty patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms Results Patients with FM (N=165) had significantly higher rates of cardiac death and HTx compared with those with NFM (N=55), both at 60 days (28.0% vs. 1.8%, p=0.0001) and at 7-year follow up (47.7% vs. 10.4%, p Outcome of FM vs NFM Conclusions The results of this international registry confirm that patients with FM have higher rates of cardiac death and HTx both in the short and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition. Acknowledgement/Funding None

Background The distinction between proportionate and disproportionate functional mitral regurgitation (FMR), based on the relationship between effective regurgitant orifice area (EROA) and left ventricle end diastolic volume (LVEDV), has recently been proposed as a possible new clinical and physiopathological concept to identify patients that could likely benefit from transcatheter mitral repair. Purpose The aim of our study was to explore the possible prognostic implications of the EROA/LVEDV ratio in patients with FMR treated with MitraClip. Methods Baseline EROA/LVEDV ratio was calculated in 72 patients with moderate-to-severe, symptomatic FMR treated with MitraClip. All patients underwent clinical, biochemichal and echocardiographic evaluation before MitraClip. EROA was calculated using PISA method. The primary outcome was a composite end-point of all-cause death or re-hospitalization for heart failure (HF). Results The median follow-up was 1 year. The primary outcome occurred in 25 patients (34.7%). The cut-off value of EROA/LVEDV ratio for primary outcome, identified by receiver operating characteristic curve, was 0.15 (p=0.007) with a sensitivity and specificity of 72 and 68%, respectively. Patients were divided in two groups according to the identified cut-off. Patients with higher ratio (Group I, n=35) presented a less dilated LV (LVEDVi: 113.2±33.4 mL vs 129.3±29.3 mL, p=0.033; LVESV: 140.7±49.0 mL vs 171.1±47.4 mL, p=0.010), a better LV systolic function (LVEF: 31.9±9.5% vs 27.8±5.8%, p=0.028) and a more severe MR (EROA: 44.5±12.9 mm2 vs 24.5±6.8 mm2, p0.15 (HR = 2.467, 95% CI 1.017–5.982, p=0.046) and severe pulmonary hypertension (HR = 2.481, 95% CI 1.030–5.976, p=0.043) were associated with a worse clinical outcome. At multivariate Cox-regression analysis, both EROA/LVEDV ratio >0.15 and severe pulmonary hypertension were identified as independent predictors (HR 3.203, 95% CI 1–310–7.832, p=0.011; HR = 3.280, 95% CI 1.326–8.116, p=0.010, respectively). Figure 1 Conclusion Our data show that EROA/LVEDV ratio was an independent predictor of adverse clinical outcome in FMR patients treated with MitraClip. This preliminary experience shows that this index could help to identify subgroups of patients with potential different clinical benefits from MitraClip therapy. However, further and extended data are needed to provide more precise evidence. Acknowledgement/Funding None

Background The Impella () percutaneous mechanical circulatory support device is a catheter-based, impeller-driven, axial-flow pump. It reduces left ventricular (LV) stroke work and myocardial oxygen demand while increasing systemic and coronary perfusion in the setting of cardiogenic shock (CS). Purpose The aim of the study was to evaluate clinical characteristics and outcomes of patients with CS treated with Impella at our center. Methods Our single-center, real-world, observational registry included all consecutive patients with CS treated with Impella 2.5, CP, 5.0, or RP at our center from February 2013 to June 2018. Indication for Impella implantation was CS, defined as hypotension (systolic blood pressure Results A total of 130 patients were included in the registry, mean age was 61±12 years, and 79.2% were males. A history of prior MI, chronic heart failure, and chronic kidney disease was present in 28.9%, 26.1%, and 18.3%, respectively. The etiologies of CS were the following: fulminant myocarditis in 6.1% of the patients, acute coronary syndromes in 59.2%, peri-procedural CS during ventricular tachycardia ablation in 7.7% and acute heart failure in 27%. Out-of-hospital cardiac arrest was present in 30.4% of the patients; 60.2% were in INTERMACS I class at presentation. At admission, mean arterial pressure (MAP) was 65±18 mmHg, serum lactate was 6.7±5.5 mmol/L, mean left ventricular ejection fraction 21.4±11.7%, right ventricular dysfunction was indeed present in 48.6% of the patients. Inotropic drugs support was used in 66.4% of the patients. Impella 2.5, CP, and 5.0 were implanted in 76.1%, 15.4%, and 1.5% of the patients, respectively. Impella RP was also used in 11.5% of patients.The mean duration of support was 135±167 hours. Of note, extra-corporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) were implanted before Impella insertion in 42.8% and 46.7% of the patients, respectively. Escalation to ECMO, ventricular assist device, or heart transplantation was needed in 35.8% of the patients. During hospital stay, acute kidney injury occurred in 56.7% of the patients; need of renal replacement therapy (RRT) 31.7%; access site-related bleeding 14.3%; life-threatening bleeding 31.5%; acute limb ischemia 14.5%; hemolysis 33.3%. The rate of all-cause mortality at 30 day was 39.7%. Need of RRT was the only independent predictor of 30-day mortality (OR 6.56; CI 1.71–25.15; p=0.006). Conclusion Our single-center, real-world, observational experience reports acceptable clinical outcomes after Impella implantation in a particularly complex population of patients with CS (INTERMACS class I in 60.2% of patients, prior use of ECMO in 42.8% of patients). All-cause mortality at 30 days was 39.7%, and need of RRT was the only independent predictor for 30-day mortality.

The 3rd generation Mitraclip XTr was recently introduced to improve device performance, through longer clip arms that should allow better grasping of the mitral leaflets, thus improving coaptation and results eventually. Several studies have demonstrated additional effects such as the reshape of the mitral annulus immediately after clip implantation. The aim of our study was to evaluate the mitral valve (MV) annular remodelling with MitraClip XTr. Between March 2018 and November 2018, 75 consecutive patients were enrolled. The population was divided in two groups: functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR). The 3D MV datasets at baseline and immediately after the procedure were acquired and then analysed with semiautomatic MVQ software (QLAB Cardiac 3DQ v.10.0; Philips Medical Systems). The software provides the following parameters: annular diameters (antero-posterior, AP, and inter-commissural, IC), circumference, area, height and ellipsicity (IC/AP ratio as percentage); saddle-index, defined as annular height to IC diameter ratio was derived. The 3D post-processing was feasible in 54 patients (108 3D datasets): 28 had FMR (52%) and 26 had DMR (48%). An average of 1.8 clips per patient were implanted: 2 clips in 38 (70%), 1 clip in 14 (26%) and 3 clips in 2 (4%) patients. The position was central in 93% of the procedures. Results are reported in table 1. In the FMR group, a reduction in the AP diameter (p=0.001), an increase in both IC diameter (p=0.001) and annular ellipsicity (p In the DMR group, an increase in annular ellipsicity (p=0,008) and in saddle-index (p Table 1 Functional mitral regurgitation (N=28) Degenerative mitral regurgitation (N=26) Pre-clip Post-clip P-value Pre-clip Post-clip P-value IC diameter (mm) 39.3±4.2 41.9±4.1 0.001 40.9±6.5 41.8±5.8 0.257 AP diameter (mm) 32.8±4.6 30.4±3.2 0.001 32.6±4.8 31.7±4.5 0.199 Annular Height (mm) 5.1±1.8 5.4±1.8 0.336 4.8±1.9 5.7±2.2 0.026 3D circumference (mm) 122.7±15.1 123.5±11 0.718 123.5±19.0 124.0±17.1 0.812 3D area (mmq) 1128.0±280 1113.7±206 0.752 1160±346.7 1156.8±318.0 0.926 Annular ellipsicity (%) 121.5±12.2 138.5±11.8 0.0005 125.9±9.6 132.4±10.7 0.008 Saddle index 13.0±4 13.0±4 0.957 11.8±4.2 13.6±4.2 0.048 Our study demonstrates that the XTr implantation produces a MV annular remodelling both in FMR and DMR probably with different mechanisms. In FMR the MV annulus resulted more elliptical, wheras in DMR the geometrical modifications involve both the ellipsicity and the saddle-shape morphology.

Background Heart involvement represents the main cause of death in Fabry Disease (FD), thus its early detection is important to define the optimal therapeutic strategy. Recently, a disproportionate increase in myocardial trabeculation has been described in FD by cardiac magnetic resonance (CMR), even in early (prehypertrophic) stage of the disease. In addition, CMR with T1 mapping can identity the presence of myocardial sphingolipid storage (causing lowering of native T1 values) in more than 50% of FD patients with no LVH. However, it is not clear whether a relationship exists between trabecular complexity and sphingolipid storage in FD. Aim To explore the association between myocardial trabecular complexity, quantified by endocardial border fractal analysis, and sphingolipid storage, described by CMR T1 mapping, in different stages of Fabry cardiomyopathy. Methods Study population included 60 subjects: 15 FD patients with no detectable signs of cardiac involvement (no LVH, normal T1; 2 M, age 30.6±14; Group 1); 15 FD patients with early sphingolipid storage (no LVH, low T1; 9 M, age 33±9.6; Group 2); 15 FD patients with LVH (11 M, age 53.5±9.6; Group 3); 15 healthy controls (9 M, age 34±10). Patients and controls underwent CMR with T1 mapping; disease severity was quantified using Mainz Severity Score Index (MSSI). Myocardial trabecular fractal dimension was evaluated, blinded to patients'characteristics, on short axis cine images using the Image J dedicated plug-in FracLac, deriving the following parameters: total, basal, mid-ventricular and apical fractal dimensions. Results Total fractal dimension was higher in all Fabry groups compared to controls. Indeed, a gradient of total fractal dimension was observed, with this parameter gradually increasing from healthy controls to Groups 3 (1.27±0.02 in controls vs 1.29±0.02 in Group 1 vs 1.30±0.02 in Group 2 vs 1.34±0.02 in Group 3; p Conclusion Cardiac involvement in FD is characterized by a progressive increase in fractal dimension of endocardial trabeculae (Figure 1C). Both total and basal myocardial trabeculation are increased in Fabry patients even before the presence of detectable sphingolipid storage, thus representing a very early sign of cardiac involvement.

Primary percutaneous coronary intervention is nowadays the preferred reperfusion strategy for patients with acute ST-segment–elevation myocardial infarction, aiming at restoring epicardial infarct-related artery patency and achieving microvascular reperfusion as early as possible, thus limiting the extent of irreversibly injured myocardium. Yet, in a sizeable proportion of patients, primary percutaneous coronary intervention does not achieve effective myocardial reperfusion due to the occurrence of coronary microvascular obstruction (MVO). The amount of infarcted myocardium, the so-called infarct size, has long been known to be an independent predictor for major adverse cardiovascular events and adverse left ventricular remodeling after myocardial infarction. Previous cardioprotection studies were mainly aimed at protecting cardiomyocytes and reducing infarct size. However, several clinical and preclinical studies have reported that the presence and extent of MVO represent another important independent predictor of adverse left ventricular remodeling, and recent evidences support the notion that MVO may be more predictive of major adverse cardiovascular events than infarct size itself. Although timely and complete reperfusion is the most effective way of limiting myocardial injury and subsequent ventricular remodeling, the translation of effective therapeutic strategies into improved clinical outcomes has been largely disappointing. Of importance, despite the presence of a large number of studies focused on infarct size, only few cardioprotection studies addressed MVO as a therapeutic target. In this review, we provide a detailed summary of MVO including underlying causes, diagnostic techniques, and current therapeutic approaches. Furthermore, we discuss the hypothesis that simultaneously addressing infarct size and MVO may help to translate cardioprotective strategies into improved clinical outcome following ST-segment–elevation myocardial infarction.

Background The long-term mortality of patients with myocardial infarction and nonobstructed coronary arteries (MINOCA) remains poorly defined. This study aimed to determine the long-term mortality of patients with MINOCA and to identify potential prognostic determinants of long-term outcome. Methods We searched PubMed, EMBASE, and Cochrane databases and reviewed cited references up to December 31, 2018 to identify studies with >6 months' follow-up data. Results We selected 44 studies including 36,932 patients (20,052 women and 16,880 men). During a median follow-up of 25 months (interquartile range: 23-39 months), 1409 patients had died (3.8%). Overall, annual mortality rate was 2.0% (95% confidence interval [CI]: 1.5% to 2.4%), with significant heterogeneity (I2 = 80%, P Conclusions The long-term mortality after MINOCA is lower than that in patients with myocardial infarction and obstructive coronary artery disease, but it is not trivial. Reduced ejection fraction, nonobstructive coronary artery disease, use of beta-blockers during follow up and ST depression on the admission electrocardiogram are significant predictors of long-term prognosis.

Obstructive disease of the epicardial coronary arteries is the main cause of angina. However, a number of patients with anginal symptoms have normal coronaries or non-obstructive coronary artery disease (CAD) despite electrocardiographic evidence of ischaemia during stress testing. In addition to limited microvascular vasodilator capacity, the coronary microcirculation of these patients is particularly sensitive to vasoconstrictor stimuli, in a condition known as microvascular angina. This review briefly summarizes the determinants and control of coronary blood flow (CBF) and myocardial perfusion. It subsequently analyses the mechanisms responsible for transient myocardial ischaemia: obstructive CAD, coronary spasm and coronary microvascular dysfunction in the absence of epicardial coronary lesions, and variable combinations of structural anomalies, impaired endothelium-dependent and/or -independent vasodilation, and enhanced perception of pain. Lastly, we exemplify mechanism of angina during tachycardia. Distal to a coronary stenosis, coronary dilator reserve is already recruited and can be nearly exhausted at rest distal to a severe stenosis. Increased heart rate reduces the duration of diastole and thus CBF when metabolic vasodilation is no longer able to increase CBF. The increase in myocardial oxygen consumption and resulting metabolic vasodilation in adjacent myocardium without stenotic coronary arteries further acts to divert blood flow away from the post-stenotic coronary vascular bed through collaterals.

The presence of myocardial noncompaction (NC), regardless of the criterion used, does not identify cardiomyopathy per se. The distinction between a morphological variant and the presence of an NC cardiomyopathy is challenging. However, thanks to larger cohorts of patients and longer periods of follow-up, better clinical characterization and prognostic evaluation are becoming available. Indeed, the physician is required to integrate the evidence of NC with the clinical history of the patient, which is supplemented by necessary advanced instrumental investigations before a definite diagnosis of NC cardiomyopathy can be made. Therefore, we extensively revised the current literature in order to help the clinicians to identify clinical features which are pivotal supporting diagnostic element for the correct recognition of Left ventricular noncompaction cardiomyopathy and thus highlighting the difference between a form of cardiomyopathy and a mere intraventricular hypertrabeculation.

Background and aims: Brain white matter hyperintensities (WMHs) have been associated with an increased risk of ischemic stroke and considered as markers of brain ischemia. Progression of WMHs in asymptomatic patients with non-hemodynamically significant carotid plaque could represent a putative marker of plaque vulnerability. We prospectively evaluate progression and determinants of WMHs in this population. Methods: This prospective study included 51 asymptomatic patients with carotid stenosis

Cardiovascular magnetic resonance (CMR) has evolved from a pioneering research tool to an established noninvasive imaging method for detecting inducible myocardial perfusion deficits. In this consensus document, experts of different imaging techniques summarize the existing body of evidence regarding CMR perfusion as a viable complement to other established noninvasive tools for the assessment of perfusion and discuss the advantages and pitfalls of the technique. A rapid, standardized CMR perfusion protocol is described, which is safe, clinically feasible, and cost-effective for centers with contemporary magnetic resonance equipment. CMR perfusion can be recommended as a routine diagnostic tool to identify inducible myocardial ischemia.