Inflammation and acute cardiotoxicity in adult hematological patients treated with CAR-T cells: results from a pilot proof-of-concept study.

AIMS: Chimeric Antigen Receptor-T (CAR-T) cell infusion is a rapidly evolving antitumor therapy; however, cardiovascular (CV) complications, likely associated with cytokine release syndrome (CRS) and systemic inflammation, have been reported to occur. The CARdio-Tox study aimed at elucidating incidence and determinants of cardiotoxicity related to CAR-T cell therapy. METHODS: Patients with blood malignancies candidate to CAR-T cells were prospectively evaluated by echocardiography at baseline and 7 and 30 days after infusion. The study endpoints were i) incidence of cancer therapy-related cardiac dysfunction (CTRCD), CTRCD were also balanced for any grade CRS, but CTRCD occurred of Cardiology Guidelines on Cardio-Oncology (decrements of left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS) and/or elevations of cardiac biomarkers (high sensitivity troponin I, natriuretic peptides) and ii), correlations of echocardiographic metrics with inflammatory biomarkers. RESULTS: Incidence of CTRCD was high at 7 days (59,3%), particularly in subjects with CRS. The integrated definition of CTRCD allowed the identification of the majority of cases (50%). Moreover, early LVEF and GLS decrements were inversely correlated with fibrinogen and interleukin-2 receptor levels (p always ≤ 0.01). CONCLUSIONS: There is a high incidence of early CTRCD in patients treated with CAR-T cells, and a link between CTRCD and inflammation can be demonstrated. Dedicated patient monitoring protocols are advised.

Coronary Spasm Testing with Acetylcholine: A Powerful Tool for a Personalized Therapy of Coronary Vasomotor Disorders.

Coronary vasomotor disorders (CVD) are characterized by transient hypercontraction of coronary vascular smooth muscle cells, leading to hypercontraction of epicardial and/or microvascular coronary circulation. CVDs play a relevant role in the pathogenesis of ischemia, angina and myocardial infarction with non-obstructive coronary arteries. Invasive provocative testing with intracoronary Acetylcholine (ACh) administration is the gold standard tool for addressing CVD, providing relevant therapeutic and prognostic implications. However, safety concerns preclude the widespread incorporation of the ACh test into clinical practice. The purpose of this review is to shed light on the pathophysiology underlying CVD and on the clinical role of the ACh test, focusing on safety profile and prognostic implications. We will also discuss contemporary evidence on the management of CVD and the role of the ACh test in driving a personalized approach of patients with CVD.

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.

Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1.

BACKGROUND: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs). METHODS: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin-1" and "treatment." RESULTS: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine-rich repeat and pyrin-domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL-1ß, the prototypical pro-inflammatory cytokine involved in CVDs. Other pro-inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL-1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome. CONCLUSION: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies.

Management of high and intermediate-high risk pulmonary embolism: A position paper of the Interventional Cardiology Working Group of the Italian Society of Cardiology.

Pulmonary embolism (PE) is a potentially life-threatening condition that remains a major global health concern. Noteworthy, patients with high- and intermediate-high-risk PE pose unique challenges because they often display clinical and hemodynamic instability, thus requiring rapid intervention to mitigate the risk of clinical deterioration and death. Importantly, recovery from PE is associated with long-term complications such as recurrences, bleeding with oral anticoagulant treatment, pulmonary hypertension, and psychological distress. Several novel strategies to improve risk factor characterization and management of patients with PE have recently been introduced. Accordingly, this position paper of the Working Group of Interventional Cardiology of the Italian Society of Cardiology deals with the landscape of high- and intermediate-high risk PE, with a focus on bridging the gap between the evolving standards of care and the current clinical practice. Specifically, the growing importance of catheter-directed therapies as part of the therapeutic armamentarium is highlighted. These interventions have been shown to be effective strategies in unstable patients since they offer, as compared with thrombolysis, faster and more effective restoration of hemodynamic stability with a consistent reduction in the risk of bleeding. Evolving standards of care underscore the need for continuous re-assessment of patient risk stratification. To this end, a multidisciplinary approach is paramount in refining selection criteria to deliver the most effective treatment to patients with unstable hemodynamics. In conclusion, the current management of unstable patients with PE should prioritize tailored treatment in a patient-oriented approach in which transcatheter therapies play a central role.

[Myocardial infarction with non-obstructive coronary artery disease: diagnostic work-up in the catheterization laboratory]. / L'infarto miocardico in assenza di coronaropatia ostruttiva: work-up diagnostico nel laboratorio di Emodinamica.

Myocardial infarction with non-obstructive coronary artery disease (MINOCA) is a heterogeneous clinical condition affecting 5% to 8% of patients presenting with acute myocardial infarction. Initially it was considered a favorable clinical diagnosis, nowadays it is known that MINOCA can significantly affect patient quality of life and portends a guarded prognosis. Therefore, it is of utmost importance to identify the specific pathophysiological mechanism underlying this clinical condition in order to set up a targeted pharmacological and non-pharmacological therapy. Coronary angiography is still a mandatory diagnostic test to rule out obstructive coronary artery disease but has limited capability to identify other potential functional and structural etiologies of MINOCA. The purpose of this review is to provide an overview of the invasive diagnostic work-up of patients with MINOCA, highlighting the diagnostic tools warranted beyond coronary angiography inside the cath lab (intracoronary provocation tests, intracoronary imaging and indexes for the assessment of coronary microvascular dysfunction), and the remaining essential knowledge gaps in this field.

Immediate versus staged complete revascularization in acute coronary syndrome: A meta-analysis of randomized controlled trials.

BACKGROUND: Clinical guidelines recommend a complete revascularization (CR) in patients with acute coronary syndromes (ACS) and multivessel disease (MVD). However, its optimal timing is unclear. The aim of this meta-analysis was to compare the clinical outcomes following immediate versus staged CR in ACS. METHODS: PubMed and Scopus were searched until March 2023 for randomized controlled trials (RCTs) comparing immediate versus staged CR. The primary endpoint was major adverse cardiovascular event (MACE) at the longest follow-up. Secondary outcomes were all-cause death, cardiovascular death, myocardial infarction (MI), any unplanned revascularization, target-vessel revascularization (TVR), and stent thrombosis. Safety outcomes were major bleeding, contrast volume, procedure duration, and length of hospitalization. RESULTS: Eight RCTs were included (3559 patients, weighted mean follow-up 12.5 months). There were no differences in the primary endpoint (OR 0.74, 95%CI: 0.54-1.01) and in the secondary endpoints of death, and stent thrombosis between the two CR strategies. Immediate CR was associated with a lower risk of recurrent MI (OR 0.51, 95% CI 0.34-0.76), any unplanned revascularization (OR 0.59, 95%CI: 0.43-0.80), and TVR (OR 0.61, 95% CI 0.45-0.84) compared to staged CR. Immediate CR was also associated with lower total contrast volume and shorter total procedure duration and hospitalization length compared to staged CR without differences in major bleedings. CONCLUSION: No difference was found between immediate and staged CR regarding MACE, or deaths rates at one year. Immediate CR may be associated with a lower risk of recurrent MI and unplanned coronary revascularization than staged CR.

Early improvement of strain imaging parameters predicts long-term response to sacubitril/valsartan in patients with heart failure with reduced ejection fraction: An observational prospective study.

BACKGROUND: Management of patients affected by heart failure with reduced ejection fraction (HFrEF) has deeply changed thanks to novel pharmacological therapies, such as Sacubitril/Valsartan, which assured morbidity and mortality advantages in this population. These effects may be mediated by both left atrial (LA) and ventricular reverse remodeling, although left ventricular ejection fraction (LVEF) recovery still represents the main parameter of treatment response. METHODS: In this prospective, observational study, 66 patients with HFrEF and naïve from Sacubitril/Valsartan were enrolled. All patients were evaluated at baseline, at 3 months and 12 months from therapy initiation. Echocardiographic parameters, including speckle tracking analysis, LA functional and structural metrics, were collected at three timepoints. The endpoints of our study were: (1) to evaluate the effects of Sacubitril/Valsartan on echo measurements; (2) to assess the predictive role of early modifications of these parameters (expressed as ∆ 3-0 months) on long-term LVEF significant recovery, defined as >15% improvement from baseline. RESULTS: The majority of echocardiographic parameters evaluated progressively improved during the observation period, including LVEF, ventricular volumes and LA metrics. ∆(3-0 months) of LV Global Longitudinal Strain (LVGLS) and LA Reservoir Strain (LARS) were associated with significant LVEF improvement at 12 months (p < 0.001 and p = 0.019 respectively). A cut-off of ∆(3-0 months) LVGLS of 3% and of ∆(3-0 months) LARS of 2% could predict LVEF recovery with satisfactory sensitivity and specificity. CONCLUSIONS: LV and LA strain analysis may identify patients who adequately respond to HFrEF medical treatment and should be routinely used in the evaluation of these patients.

Impact of the exposome on cardiovascular disease.

Air pollution, noise pollution, and light pollution have emerged as important but often overlooked risk factors for cardiovascular disease. In this review, we examine the emerging concept of the exposome, highlighting the close relationship between environmental exposure (e.g. PM2.5, traffic noise, and night light) and cardiovascular disease, finally addressing the possible mitigation strategies that should be implemented to reduce the impact of air, noise, and light pollution on cardiovascular morbidity and mortality.

Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy: A Contemporary Perspective.

Alcohol septal ablation is a minimally invasive procedure for the treatment of left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) who remain symptomatic despite optimal medical therapy. The procedure causes a controlled myocardial infarction of the basal portion of the interventricular septum by the injection of absolute alcohol with the aim of reducing LVOT obstruction and improving the patient's hemodynamics and symptoms. Numerous observations have demonstrated the efficacy and safety of the procedure, making it a valid alternative to surgical myectomy. In particular, the success of alcohol septal ablation depends on appropriate patient selection and the experience of the institution where the procedure is performed. In this review, we summarize the current evidence on alcohol septal ablation and highlight the importance of a multidisciplinary approach involving a team of clinical and interventional cardiologists and cardiac surgeons with high expertise in the management of HOCM patients-the Cardiomyopathy Team.

Cancer incidence and mortality in patients diagnosed with heart failure: results from an updated systematic review and meta-analysis.

BACKGROUND: Several cohort studies aimed at demonstrating an increased risk of cancer incidence and mortality in patients with a pre-existing diagnosis of heart failure (HF); however, conflicting results have been reported that call for systematic review and meta-analysis. METHODS: We conducted a systematic search of multiple databases from their inception through July 2022 and retrieved only papers reporting hazard ratios (HR). Random and fixed-effects models were fit for the study duration. RESULTS: The analysis included nine cohort studies for a total of 515'041 HF cases and 1'365'452 controls without HF. Although high heterogeneity among studies was observed, the HR for incident cancer in HF patients was statistically significant (1.45, 95% CI 1.31-1.61, p < 0.0001), which was confirmed by sensitivity analyses; however, by analyzing the few papers reporting HRs for cancer mortality, no significant difference between HF and non-HF patients could be detected (HR 2.03, 95% CI [0.93-4.43], p = 0.0736). Further scrutiny of studies with adjusted HRs, when available, confirmed that cancer incidence was significantly increased in patients with HF, as was cancer mortality as well. CONCLUSIONS: This meta-analysis shows that HF patients are at an increased risk of incident cancer. Increased mortality could not be firmly demonstrated by the available data. Our results call for inclusion of cancer-related endpoints in HF trials to adequately address this important clinical issue.

Cardiac Imaging in Childhood Cancer Survivors: A State-of-the-Art Review.

Childhood cancer survival has improved significantly in the past few decades, reaching rates of 80% or more at 5 years. However, with improved survival, early- and late-occurring complications of chemotherapy and radiotherapy exposure are becoming progressively more evident. Cardiovascular diseases represent the leading cause of non-oncological morbidity and mortality in this highly vulnerable population. Therefore, the necessity of reliable, noninvasive screening tools able to early identify cardiac complications early is now pre-eminent in order to implement prevention strategies and mitigate disease progression. Echocardiography, may allow identification of myocardial dysfunction, pericardial complications, and valvular heart diseases. However, additional imaging modalities may be necessary in selected cases. This manuscript provides an in-depth review of noninvasive imaging parameters studied in childhood cancer survivors. Furthermore, we will illustrate brief surveillance recommendations according to available evidence and future perspectives in this expanding field.

Adenosine as adjunctive therapy in acute coronary syndrome: a meta-analysis of randomized controlled trials.

AIMS: Adenosine has been tested in several randomized controlled trials (RCTs) to minimize the incidence of coronary microvascular obstruction (CMVO). The aim of this study was to pool all the RCTs comparing intracoronary or intravenous adenosine versus placebo in patients with acute coronary syndrome (ACS) undergoing myocardial revascularization. METHODS AND RESULTS: PubMed and Scopus electronic databases were scanned for eligible studies up to 5th June 2022. A total of 26 RCTs with 5843 patients were included. Efficacy endpoints were major adverse cardiac events (MACE), all-cause death, non-fatal myocardial infarction, and heart failure. Atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were the safety endpoints. Myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, left ventricular ejection fraction (LVEF), infarct size, and ST-segment resolution were also assessed. Adenosine administration was not associated with any clinical benefit in terms of MACE, all-cause death, non-fatal myocardial infarction, and heart failure. However, adenosine was associated with an increased rate of advanced atrioventricular blocks and of VF/SVT in studies with total mean ischaemic time >3 h, compared to placebo. Remarkably, among patients undergoing percutaneous coronary intervention, adenosine was associated with reduced myocardial blush grade 0-1 and TIMI flow grade 0-2, compared to placebo. Furthermore, adenosine did not show favourable effects on LVEF and infarct size. CONCLUSION: Adenosine infusion, as adjunctive therapy in ACS, was associated with an increased risk of advanced atrioventricular blocks and increased rates of adenosine-triggered ventricular arrhythmias in patients with long ischaemic time, without providing any clinical benefit compared to placebo.

Mid-Term Outcome of Ventricular Arrhythmias Catheter Ablation in Patients with Chronic Coronary Total Occlusion Compared to Ischemic and Non-Ischemic Patients.

Chronic coronary total occlusions (CTO) are considered an emerging predictor of ventricular arrhythmias (VAs), but currently there are few data on arrhythmic outcomes in patients affected by CTO undergoing radiofrequency catheter ablation of VAs. This study sought to evaluate the impact of unrevascularized CTO on the recurrence of VAs after catheter ablation. This was a single-center retrospective study enrolling 120 patients between 2015 and 2020. All patients were admitted for ventricular tachycardia (VT) or high premature ventricular contractions burden (>25% detected by Holter ECG), without evidence of acute coronary syndrome; they underwent coronary angiography, electrophysiology (EP) study, and three-dimensional electroanatomic mapping (3D-EAM) followed by VAs ablation. Twenty-eight patients (23%) of 120 patients showed CTO at coronary angiography. At baseline, the CTO group presented with higher prevalence of hypertension, chronic renal disease, systolic ventricular dysfunction, secondary prevention ICD implantation, and higher rate of LAVA by 3D-EAM compared with the non-CTO group. At a median follow-up of 15 months (range 1−96 months) after catheter ablation, the only independent predictor of VAs recurrence was the presence of moderate to severe left ventricular (LV) dysfunction. Therefore, the presence of CTO does not predict VAs recurrence after catheter ablation, which is instead predicted by LV dysfunction.

Gender-differences in antithrombotic therapy across the spectrum of ischemic heart disease: Time to tackle the Yentl syndrome?

The incidence and clinical presentation of ischemic heart disease (IHD), as well as thrombotic and bleeding risks, appear to differ between genders. Compared with men, women feature an increased thrombotic risk, probably related to an increased platelet reactivity, higher level of coagulation factors, and sex-associated unique cardiovascular risk factors, such as pregnancy-related (i.e., pre-eclampsia and gestational diabetes), gynecological disorders (i.e., polycystic ovary syndrome, early menopause) and autoimmune or systemic inflammatory diseases. At the same time, women are also at increased risk of bleeding, due to inappropriate dosing of antithrombotic agents, smaller blood vessels, lower body weight and comorbidities, such as diabetes and chronic kidney disease. Pharmacological strategies focused on the personalization of antithrombotic treatment may, therefore, be particularly appealing in women in light of their higher bleeding and ischemic risks. Paradoxically, although women represent a large proportion of cardiovascular patients in our practice, adequate high-quality clinical trial data on women remain scarce and inadequate to guide decision-making processes. As a result, IHD in women tends to be understudied, underdiagnosed and undertreated, a phenomenon known as a "Yentl syndrome." It is, therefore, compelling for the scientific community to embark on dedicated clinical trials to address underrepresentation of women and to acquire evidence-based knowledge in the personalization of antithrombotic therapy in women.

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.

Safety and effectiveness of post percutaneous coronary intervention physiological assessment: Retrospective data from the post-revascularization optimization and physiological evaluation of intermediate lesions using fractional flow reserve registry.

Background: While the importance of invasive physiological assessment (IPA) to choose coronary lesions to be treated is ascertained, its role after PCI is less established. We evaluated feasibility and efficacy of Physiology-guided PCI in the everyday practice in a retrospective registry performed in a single high-volume and "physiology-believer" center. Materials and methods: The PROPHET-FFR study (NCT05056662) patients undergoing an IPA in 2015-2020 were retrospectively enrolled in three groups: Control group comprising patients for whom PCI was deferred based on a IPA; Angiography-Guided PCI group comprising patients undergoing PCI based on an IPA but without a post-PCI IPA; Physiology-guided PCI group comprising patients undergoing PCI based on an IPA and an IPA after PCI, followed by a physiology-guided optimization, if indicated. Optimal result was defined by an FFR value ≥ 0.90. Results: A total of 1,322 patients with 1,591 lesions were available for the analysis. 893 patients (67.5%) in Control Group, 249 patients (18.8%) in Angiography-guided PCI Group and 180 patients (13.6%) in Physiology-guided PCI group. In 89 patients a suboptimal functional result was achieved that was optimized in 22 cases leading to a "Final FFR" value of 0.90 ± 0.04 in Angiography-Guided PCI group. Procedural time, costs, and rate of complications were similar. At follow up the rate of MACEs for the Physiology-guided PCI group was similar to the Control Group (7.2% vs. 8.2%, p = 0.765) and significantly lower than the Angiography-guided PCI Group (14.9%, p < 0.001), mainly driven by a reduction in TVRs. Conclusion: "Physiology-guided PCI" is a feasible strategy with a favorable impact on mid-term prognosis. Prospective studies using a standardized IPA are warrant to confirm these data.

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.

Ischemic Cardiomyopathy and Heart Failure After Acute Myocardial Infarction.

PURPOSE OF REVIEW: Ischemic cardiomyopathy refers to systolic left ventricular dysfunction in the setting of obstructive coronary artery disease and represents the most common cause of heart failure worldwide. It is often the combination of an irreversible loss of viable mass following an acute myocardial infarction (AMI) with a dysfunctional, but still viable, myocardium in the context of a chronically reduced myocardial blood flow and reduced coronary reserve. Medical treatments aiming at modulating neurohumoral response and restoring blood flow to the ischemic cardiomyocytes were shown to dramatically abate the occurrence of ventricular dysfunction and adverse remodeling in ischemic cardiomyopathy. RECENT FINDINGS: Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, heart failure ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to tackle heart failure risk beyond preservation of left ventricular volumes and systolic function. In this review article, we explore the principal pathophysiological mechanisms and pathways of heart failure in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area.