Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study.

AIMS: Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. METHODS AND RESULTS: Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. CONCLUSIONS: Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.

CMR Predictors of Favorable Outcome in Myocarditis: A Single-Center Experience.

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts.

Cardiac Troponin in Patients With Light Chain and Transthyretin Cardiac Amyloidosis: JACC: CardioOncology State-of-the-Art Review.

Cardiac amyloidosis (CA) is an infiltrative disease caused by amyloid fibril deposition in the myocardium; the 2 forms that most frequently involve the heart are amyloid light chain (AL) and amyloid transthyretin (ATTR) amyloidosis. Cardiac troponin (cTn) is the biomarker of choice for the detection of myocardial injury and is frequently found to be elevated in patients with CA, particularly with high-sensitivity assays. Multiple mechanisms of myocardial injury in CA have been proposed, including cytotoxic effect of amyloid precursors, interstitial amyloid fibril infiltration, coronary microvascular dysfunction, amyloid- and non-amyloid-related coronary artery disease, diastolic dysfunction, and heart failure. Regardless of the mechanisms, cTn values have relevant prognostic (and potentially diagnostic) implications in both AL and ATTR amyloidosis. In this review, the authors discuss the significant aspects of cTn biology and measurement methods, potential mechanisms of myocardial injury in CA, and the clinical application of cTn in the management of both AL and ATTR amyloidosis.

Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse.

BACKGROUND: Mitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis. OBJECTIVES: This study investigated the determinants of VA in patients with MVP without significant regurgitation. METHODS: This study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern. RESULTS: The 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA. CONCLUSIONS: In patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA.

Association of Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Agonistic Autoantibodies With Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction.

BACKGROUND: The left ventricular remodeling (LVR) process has limited the effectiveness of therapies after myocardial infarction. The relationship between autoantibodies activating AT1R-AAs (angiotensin II receptor type 1-AAs) and ETAR-AAs (autoantibodies activating endothelin-1 receptor type A) with myocardial infarction has been described. Among patients with ST-segment-elevation myocardial infarction, we investigated the relationship between these autoantibodies with LVR and subsequent major adverse cardiac events. METHODS AND RESULTS: In this prospective observational study, we included 131 patients with ST-segment-elevation myocardial infarction (61±11 years of age, 112 men) treated with primary percutaneous coronary intervention. Within 48 hours of admission, 2-dimensional transthoracic echocardiography was performed, and blood samples were obtained. The seropositive threshold for AT1R-AAs and ETAR-AAs was >10 U/mL. Patients were followed up at 6 months, when repeat transthoracic echocardiography was performed. The primary end points were LVR, defined as a 20% increase in left ventricular end-diastolic volume index, and major adverse cardiac event occurrence at follow-up, defined as cardiac death, nonfatal re-myocardial infarction, and hospitalization for heart failure. Forty-one (31%) patients experienced LVR. The prevalence of AT1R-AAs and ETAR-AAs seropositivity was higher in patients with versus without LVR (39% versus 11%, P<0.001 and 37% versus 12%, P=0.001, respectively). In multivariable analysis, AT1R-AAs seropositivity was significantly associated with LVR (odds ratio [OR], 4.66; P=0.002) and represented a risk factor for subsequent major adverse cardiac events (OR, 19.6; P=0.002). CONCLUSIONS: AT1R-AAs and ETAR-AAs are associated with LVR in patients with ST-segment-elevation myocardial infarction. AT1R-AAs are also significantly associated with recurrent major adverse cardiac events. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR and ST-segment-elevation myocardial infarction prognosis.

Atrial electrofunctional predictors of incident atrial fibrillation in cardiac amyloidosis.

BACKGROUND: Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events. OBJECTIVE: This study was designed to investigate the atrial electrofunctional predictors of incident AF in CA. METHODS: A multicenter, observational study was conducted in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiography and cardiac magnetic resonance imaging. The primary end point was new-onset AF occurrence. RESULTS: Overall, 96 patients (AL-CA, n = 40; ATTR-CA, n = 56) were enrolled. During an 18-month median follow-up (Q1-Q3, 7-29 months), 30 patients (29%) had incident AF. Compared with those without AF, patients with AF were older (79 vs 73 years; P = .001). They more frequently had ATTR (87% vs 45%; P < .001); electrocardiographic interatrial block (IAB), either partial (47% vs 21%; P = .011) or advanced (17% vs 3%; P = .017); and lower left atrial ejection fraction (LAEF; 29% vs 41%; P = .004). Age (hazard ratio [HR], 1.059; 95% CI, 1.002-1.118; P = .042), any type of IAB (HR, 2.211; 95% CI, 1.03-4.75; P = .041), and LAEF (HR, 0.967; 95% CI, 0.936-0.998; P = .044) emerged as independent predictors of incident AF. Patients exhibiting any type of IAB, LAEF <40%, and age >78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by 1 (8.5%) or none (7.6%) of these 3 risk factors. CONCLUSION: In patients with CA, older age, IAB on 12-lead electrocardiography, and reduced LAEF on cardiac magnetic resonance imaging are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features.

Deep learning-based prediction of major arrhythmic events in dilated cardiomyopathy: A proof of concept study.

Prediction of major arrhythmic events (MAEs) in dilated cardiomyopathy represents an unmet clinical goal. Computational models and artificial intelligence (AI) are new technological tools that could offer a significant improvement in our ability to predict MAEs. In this proof-of-concept study, we propose a deep learning (DL)-based model, which we termed Deep ARrhythmic Prevention in dilated cardiomyopathy (DARP-D), built using multidimensional cardiac magnetic resonance data (cine videos and hypervideos and LGE images and hyperimages) and clinical covariates, aimed at predicting and tracking an individual patient's risk curve of MAEs (including sudden cardiac death, cardiac arrest due to ventricular fibrillation, sustained ventricular tachycardia lasting ≥30 s or causing haemodynamic collapse in <30 s, appropriate implantable cardiac defibrillator intervention) over time. The model was trained and validated in 70% of a sample of 154 patients with dilated cardiomyopathy and tested in the remaining 30%. DARP-D achieved a 95% CI in Harrell's C concordance indices of 0.12-0.68 on the test set. We demonstrate that our DL approach is feasible and represents a novelty in the field of arrhythmic risk prediction in dilated cardiomyopathy, able to analyze cardiac motion, tissue characteristics, and baseline covariates to predict an individual patient's risk curve of major arrhythmic events. However, the low number of patients, MAEs and epoch of training make the model a promising prototype but not ready for clinical usage. Further research is needed to improve, stabilize and validate the performance of the DARP-D to convert it from an AI experiment to a daily used tool.

Phenotypic Expression and Clinical Outcomes in Patients With Arrhythmogenic Cardiomyopathies.

BACKGROUND: In recent years, it has become evident that arrhythmogenic cardiomyopathy (ACM) displays a wide spectrum of ventricular involvement. Furthermore, the influence of various clinical phenotypes on the prognosis of the disease is currently being assessed. OBJECTIVES: The purpose of this study was to evaluate the impact of phenotypic expression in ACM on patient outcomes. METHODS: We conducted an analysis of 446 patients diagnosed with ACM. These patients were categorized into 3 groups based on their phenotype: arrhythmogenic right ventricular cardiomyopathy (ARVC) (right-dominant ACM), arrhythmogenic left ventricular cardiomyopathy (ALVC) (left-dominant ACM), and biventricular arrhythmogenic cardiomyopathy (BIV). We compared clinical, instrumental, and genetic findings among these groups and also evaluated their outcomes RESULTS: Overall, 44% of patients were diagnosed with ARVC, 23% with ALVC, and 33% with BIV forms. Subjects showing with ARVC and BIV phenotype had a significantly higher incidence of life-threatening ventricular arrhythmias compared with ALVC (P < 0.001). On the other hand, heart failure, heart transplantation, and death caused by cardiac causes were more frequent in individuals with BIV forms compared to those with ALVC and ARVC (P < 0.001). Finally, patients with an ALVC phenotype had a higher incidence of hot phases compared with those with ARVC and BIV forms (P = 0.013). CONCLUSIONS: The comparison of ACM phenotypes demonstrated that patients with right ventricular involvement, such as ARVC and BIV forms, exhibit a higher incidence of life-threatening ventricular arrhythmias. Conversely, ACM forms characterized by left ventricular involvement, such as ALVC and BIV, show a higher incidence of heart failure, heart transplantation, and hot phases.

Left ventricular assist device in the presence of subcutaneous implantable cardioverter defibrillator: Data from a multicenter experience.

BACKGROUND: Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure (HF). Subcutaneous implantable cardioverter defibrillator (S-ICD) might be a viable alternative to conventional ICDs with a lower risk of short- and long-term of device-related complications and infections.The aim of this multicenter study was to evaluate the outcomes and management of S-ICD recipients who underwent LVAD implantation. METHODS: The study population included patients with a preexisting S-ICD who underwent LVAD implantation for advanced HF despite optimal medical therapy. RESULTS: The study population included 30 patients (25 male; median age 45 [38-52] years).The HeartMate III was the most common LVAD type. Median follow-up in the setting of concomitant use of S-ICDs and LVADs was 7 months (1-20).There were no reports of inability to interrogate S-ICD systems in this population. Electromagnetic interference (EMI) occurred in 21 (70%) patients. The primary sensing vector was the one most significantly involved in determining EMI. Twenty-seven patients (90%) remained eligible for S-ICD implantation with at least one optimal sensing vector. The remaining 3 patients (10%) were ineligible for S-ICD after attempts of reprogramming of sensing vectors. Six patients (20%) experienced inappropriate shocks (IS) due to EMI. Six patients (20%) experienced appropriate shocks. No S-ICD extraction because of need for antitachycardia pacing, ineffective therapy or infection was reported. CONCLUSIONS: Concomitant use of LVAD and S-ICD is feasible in most patients. However, the potential risk of EMI oversensing, IS and undersensing in the post-operative period following LVAD implantation should be considered. Careful screening for EMI should be performed in all sensing vectors after LVAD implantation.

Hospitalization-based epidemiology of systemic and cardiac amyloidosis in the Veneto Region, Italy.

AIM: Defining the epidemiology of systemic and cardiac amyloidosis (CA) is a contemporary challenge. The present study aimed to estimate incidence and time trends in amyloidosis-related hospitalizations (AH) in Veneto Region (5 million inhabitants, Northeastern Italy). METHODS: International Classification of Diseases (ICD-9) codes were used to identify AH in Veneto from 2010 to 2020. AH were defined as any hospitalization with a discharge summary reporting an ICD-9 code for systemic amyloidosis. Hospitalization for CA was defined as records with ICD-9 code for systemic amyloidosis and ICD-9 code for heart failure,cardiomyopathy or arrhythmia. Hospital/outpatient encounters for carpal tunnel syndrome (CTS) surgeries also were extracted. AH incidence was estimated using a buffer of 5 years. RESULTS: In the time range 2015-2020, the incidence rate of AH was 23.5 cases per 106 (95% confidence interval, CI, 21.8; 25.3), mainly affecting patients>65 years (76.2%) and males (63.5%), with a progressively increasing trend (percent annual increase 17%, 95% CI 12; 22%). The 10 year prevalence of AH in 2020 was 124.5 per 106 (95% CI 114.9; 134.8). In 2020, annual hospitalized prevalent cases of CA were about 70% of all cases (159/228), mainly patients >65 years and males. Among patients with multiple CTS surgeries, a subsequent code for cardiac disease was found in 913 after a median of 3.9 years, more frequently in men than in women (463/6.526 7.1% versus 450/11.406 3.9%). CONCLUSIONS: In Veneto, we recorded a significantly increasing trend in the incidence of AH, with concordant increasing prevalence estimates.

Left ventricular fibrosis in arrhythmic mitral valve prolapse: quantification and comparison of semi-automated techniques assessed by cardiac magnetic resonance.

PURPOSE: Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols. METHODS: 66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard. RESULTS: LGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935). CONCLUSION: The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient.

Efficacy and Safety of Isoprenaline during Unstable Third-Degree Atrioventricular Block.

Unstable and symptomatic complete atrioventricular block represents a potentially fatal condition that requires prompt therapy while waiting for definitive pacemaker implantation. Although transcutaneous pacing is included in acute management, it could be a difficult approach due to its painfulness and the occasional failure of mechanical capture. Drug therapy is a feasible choice, and current guidelines encompass the use of atropine, dopamine, or epinephrine. Isoprenaline has never been investigated in this setting, and no specific indication of its use has been provided despite its potentially more favorable pharmacological profile. The study population included a consecutive series of patients who presented to the emergency department because of unstable third-degree atrioventricular block and were treated with either isoprenaline or dopamine infusion while waiting for definitive pacemaker implantation. Asymptomatic patients or those with reversible causes of complete atrioventricular block were excluded. The clinical response to the drug was deemed poor if, despite achieving a full drug dose, patients remained symptomatic and/or with hemodynamic instability, ventricular rate and rhythm did not improve or worsened, including if ventricular arrhythmias or asystolic pauses and/or irrepressible nausea/vomiting occurred. Isoprenaline infusion has proved to be safe and tolerated with no arrhythmia induction or hypotensive issues. Isoprenaline has also proven to be more satisfactory in achieving an effective clinical response in 84% of patients rather than dopamine (31%, p < 0.001), reducing the need for temporary artificial pacing. Our data point out the efficacy and safety of isoprenaline infusion and its greater tolerability over dopamine in the acute management of unstable third-degree AV block while waiting for definitive pacemaker implantation.

Multimodality Imaging in Advanced Heart Failure for Diagnosis, Management and Follow-Up: A Comprehensive Review.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), nuclear imaging and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. Nuclear imaging, CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. The aim is to highlight the novelty and unique aspects of recently published papers in the field. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

Uneventful COVID-19 Infection and Vaccination in a Cohort of Patients with Prior Myocarditis.

Myocarditis has in rare cases been associated with COVID-19 infection and has emerged as a possible rare side effect of vaccination with anti-COVID-19 messenger RNA vaccines. However, little is known about possible COVID-19 infection- and/or vaccination-related myocarditis relapse in patients with previous clinically suspected or biopsy-proven myocarditis. Myocarditis may relapse, particularly in females with immune-mediated/autoimmune features and a predisposing immunogenetic background. We aimed to assess the prevalence of myocarditis relapse during the COVID-19 outbreak and following COVID-19 vaccination in a cohort of patients with prior myocarditis. We included in the analysis myocarditis patients on active follow-up, for whom COVID-19 infection and vaccination statuses were known, and collected data on clinical, laboratory and echocardiographic findings, and myocarditis relapse. We enrolled 409 patients, of whom 114 (28%) reported COVID-19 infection and 347 (85%) completed the vaccination scheme. Only one patient, having COVID-19 infection before the vaccination campaign started, was admitted to hospital because of pneumonia; the remaining patients had an uneventful COVID-19 infection course, with only mild symptoms. No myocarditis relapse was recorded following COVID-19 infection or vaccination. Moreover, the frequency of new myocarditis cases following the COVID-19 outbreak was not different compared to the three-year period preceding the COVID-19 era. In conclusion, in our cohort of patients with prior myocarditis, both COVID-19 infection and vaccination were uneventful.

Left atrial expansion index measured with cardiovascular magnetic resonance estimates pulmonary capillary wedge pressure in dilated cardiomyopathy.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) assessment is fundamental for managing dilated cardiomyopathy (DCM) patients. Although cardiovascular magnetic resonance (CMR) has become the gold-standard imaging technique for evaluating cardiac chamber volume and function, PCWP is not routinely assessed with CMR. Therefore, this study aimed to validate the left atrial expansion index (LAEI), a LA reservoir function parameter able to estimate filling pressure with echocardiography, as a novel CMR-measured parameter for non-invasive PCWP estimation in DCM patients. METHODS: We performed a retrospective, single-center, cross-sectional study. We included electively admitted DCM patients referred to our tertiary center for further diagnostic evaluation that underwent a clinically indicated right heart catheterization (RHC) and CMR within 24 h. PCWP invasively measured during RHC was used as the reference. LAEI was calculated from CMR-measured LA maximal and minimal volumes as LAEI = ( (LAVmax-LAVmin)/LAVmin) × 100. RESULTS: We enrolled 126 patients (47 ± 14 years; 68% male; PCWP = 17 ± 9.3 mmHg) randomly divided into derivation (n = 92) and validation (n = 34) cohorts with comparable characteristics. In the derivation cohort, the log-transformed (ln) LAEI showed a strong linear correlation with PCWP (r = 0.81, p < 0.001) and remained a strong independent PCWP determinant over clinical and conventional CMR parameters. Moreover, lnLAEI accurately identified PCWP ≥ 15 mmHg (AUC = 0.939, p < 0.001), and the optimal cut-off identified (lnLAEI ≤ 3.85) in the derivation cohort discriminated PCWP ≥ 15 mmHg with 82.4% sensitivity, 88.2% specificity, and 85.3% accuracy in the validation cohort. Finally, the equation PCWP = 52.33- (9.17xlnLAEI) obtained from the derivation cohort predicted PCWP (-0.1 ± 5.7 mmHg) in the validation cohort. CONCLUSIONS: In this cohort of DCM patients, CMR-measured LAEI resulted in a novel and useful parameter for non-invasive PCWP evaluation.

New Non-Invasive Imaging Technologies in Cardiac Transplant Follow-Up: Acquired Evidence and Future Options.

Heart transplantation (HT) is the established treatment for end-stage heart failure, significantly enhancing patients' survival and quality of life. To ensure optimal outcomes, the routine monitoring of HT recipients is paramount. While existing guidelines offer guidance on a blend of invasive and non-invasive imaging techniques, certain aspects such as the timing of echocardiographic assessments and the role of echocardiography or cardiac magnetic resonance (CMR) as alternatives to serial endomyocardial biopsies (EMBs) for rejection monitoring are not specifically outlined in the guidelines. Furthermore, invasive coronary angiography (ICA) is still recommended as the gold-standard procedure, usually performed one year after surgery and every two years thereafter. This review focuses on recent advancements in non-invasive and contrast-saving imaging techniques that have been investigated for HT patients. The aim of the manuscript is to identify imaging modalities that may potentially replace or reduce the need for invasive procedures such as ICA and EMB, considering their respective advantages and disadvantages. We emphasize the transformative potential of non-invasive techniques in elevating patient care. Advanced echocardiography techniques, including strain imaging and tissue Doppler imaging, offer enhanced insights into cardiac function, while CMR, through its multi-parametric mapping techniques, such as T1 and T2 mapping, allows for the non-invasive assessment of inflammation and tissue characterization. Cardiac computed tomography (CCT), particularly with its ability to evaluate coronary artery disease and assess graft vasculopathy, emerges as an integral tool in the follow-up of HT patients. Recent studies have highlighted the potential of nuclear myocardial perfusion imaging, including myocardial blood flow quantification, as a non-invasive method for diagnosing and prognosticating CAV. These advanced imaging approaches hold promise in mitigating the need for invasive procedures like ICA and EMB when evaluating the benefits and limitations of each modality.

Coronary Microvascular Dysfunction in Asymptomatic Patients with Severe Psoriasis.

Severe psoriasis is associated with an increased cardiovascular risk, which may be independent of the traditional risk factors. Coronary microvascular dysfunction (CMD) has been shown to predict a poor cardiovascular prognosis in the general population and in patients with psoriasis. In this study, we assessed the prevalence and predictors of CMD in a large cohort of patients with psoriasis without clinical cardiovascular disease. A total of 503 patients with psoriasis were enrolled and underwent transthoracic Doppler echocardiography to evaluate coronary microcirculation. Of these, 55 patients were excluded from the analyses because of missing data. Of the 448 patients in this study, 31.5% showed CMD. Higher PASI, longer disease duration, the presence of psoriatic arthritis, and hypertension were independently associated with CMD. An increase of 1 point of PASI and 1 year of psoriasis duration were associated with a 5.8% and 4.6% increased risk of CMD, respectively. In our study, CMD was associated with the severity and duration of psoriasis. This supports the role of systemic inflammation in CMD and suggests that the coronary microcirculation may represent an extracutaneous site involved in the immune-mediated injury of psoriasis. We should diagnose and actively search for CMD in patients with severe psoriasis.

Sex differences in diagnostic modalities of coronary artery disease: Evidence from coronary microcirculation.

Although atherosclerosis is usually considered a disease of the large arteries, risk factors for atherosclerosis also trigger structural and functional abnormalities at a microvascular level. In cardiac disease, microvascular dysfunction is especially relevant in women, among whom the manifestation of ischemic disease due to impaired coronary microcirculation is more common than in men. This sex-specific clinical phenotype has important clinical implications and, given the higher pre-test probability of coronary microvascular dysfunction in females, different diagnostic modalities should be used in women compared to men. In this review, we summarize invasive and non-invasive diagnostic modalities to assess coronary microvascular function, ranging from catheter-based evaluation of endothelial function to Doppler echocardiography and positron emission tomography. Moreover, we discuss different clinical settings in which microvascular disease plays an important role, underlining the importance of choosing the right diagnostic modality depending on the sex of the patients.

Fulminant Myocarditis: When One Size Does Not Fit All - A Critical Review of the Literature.

Fulminant myocarditis, rather than being a distinct form of myocarditis, is instead a peculiar clinical presentation of the disease. The definition of fulminant myocarditis has varied greatly in the last 20 years, leading to conflicting reports on prognosis and treatment strategies, mainly because of varied inclusion criteria in different studies. The main conclusion of this review is that fulminant myocarditis may be due to different histotypes and aetiologies that can be diagnosed only by endomyocardial biopsy and managed by aetiology-directed treatment. This life-threatening presentation requires rapid, targeted management both in the short term (mechanical circulatory support, inotropic and antiarrhythmic treatment and endomyocardial biopsy) and in the long term (including prolonged follow-up). Fulminant presentation has also recently been identified as a risk factor for worsened prognosis, even long after the resolution of the acute phase of myocarditis.