Improving understanding and management of acute heart failure, myocarditis, pericarditis, amyloidosis, mitochondrial cardiomyopathies, hypertrophic cardiomyopathy, and takotsubo syndrome
Year: 2025
Type: article
Abstract: For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Issue starts with an Editors’ Page entitled ‘A new journal for the cardiovascular community’ by Thomas Lüscher and Filippo Crea which introduces a new addition to the ESC Journal Family: European Heart Journal—Valvular and Structural Heart Disease.1 Over the past two decades, the European Society of Cardiology (ESC) Journal Family has grown significantly, establishing itself as a leading scientific and data resource in cardiovascular medicine. At the heart of this portfolio is its flagship publication, the European Heart Journal, complemented by a wide range of titles that span the entire spectrum of cardiovascular medicine. However, a few key areas remain underrepresented. To address these gaps, the ESC is introducing a new addition to the ESC Journal Family: European Heart Journal—Valvular and Structural Heart Disease. This emerging speciality area of cardiology has developed rapidly with the introduction of transarterial valve implementation and numerous studies and trials thereof, providing an attractive opportunity for a specialized journal. In an ESC Guidelines entitled ‘2025 ESC Guidelines for the management of myocarditis and pericarditis’ by Jeanette Schulz-Menger from the HELIOS Hospital Berlin-Buch in Germany, and colleagues. The Guidelines introduce the term ‘inflammatory myopericardial syndrome’ (IMPS) in the first ESC clinical practice guidelines covering myocarditis and pericarditis.2 The Guidelines also emphasize a personalized, multimodal approach to diagnosis and treatment, stressing the importance of cardiovascular magnetic resonance as a diagnostic cornerstone. Key recommendations include individualized treatment plans using non-steroidal anti-inflammatory drugs and colchicine for pericarditis, with immunosuppressive therapies reserved for autoimmune cases. The Guidelines advocate for a multidisciplinary team approach and provide structure and clarity to improve diagnosis and outcomes, including tailored exercise and return-to-work guidance. More than 64 million people worldwide have heart failure (HF), and these numbers are expected to rise. Acute HF (AHF) is the leading cause of hospitalization in patients over 65 years old and is linked to high mortality and readmission rates.3–9 In a Special Article entitled ‘Acute heart failure in non-cardiac surgery: a clinical consensus statement of the Association for Acute CardioVascular Care (ACVC) and the Heart Failure Association (HFA) of the ESC’, Danielle Gualandro from the University of Basel in Switzerland, and colleagues summarize the available evidence regarding the pathophysiology, prevention, diagnosis, treatment, and prognosis of AHF after non-cardiac surgery.10 AHF may also be a frequent complication in patients hospitalized for other medical reasons as well as after cardiac or non-cardiac surgery. These three entities are summarized as secondary AHF. As secondary AHF has been largely overlooked by medical research and education, little is known about its pathophysiology, phenotypes, diagnosis, management, and prognosis. Secondary AHF occurring after non-cardiac surgery warrants particular attention due to its very high mortality rates of up to 44% within 1 year and is therefore the focus of this review. Key to prevention is understanding and addressing the pathophysiology of AHF after non-cardiac surgery, which involves close monitoring of fluid status to avoid volume overload and/or hypovolaemia, avoiding hypo- and/or hypertension, treating pain and anaemia to prevent tachycardia, and avoiding electrolyte disturbances to prevent arrhythmias. Cardiac biomarkers, such as cardiac troponins and natriuretic peptides, serve as important diagnostic tools and enhance risk stratification in the perioperative setting. A low threshold to perform echocardiography in this population is suggested. Vigilant post-operative care is essential for the early recognition and treatment of AHF after non-cardiac surgery, which could help improve outcomes for patients. The role of mitochondria in cardiovascular disease is gaining growing attention.11–13 Mitochondrial disorders are rare genetic conditions caused by primary defects in mitochondrial function due to alterations in either nuclear or mitochondrial DNA. As mitochondria are central to oxidative metabolism, these disorders primarily affect energy-demanding organs such as the central nervous system and the heart. However, the variability in organ involvement and consequent heterogeneity in clinical manifestations often complicates the diagnostic process. In a State of the Art Review article entitled ‘Mitochondrial cardiomyopathies: pathogenesis, diagnosis, and treatment’ by Christoph Maack from University Hospital Würzburg in Germany, and colleagues aim to provide a comprehensive overview of the pathophysiology, clinical features, diagnostic approaches, and treatment options for mitochondrial cardiomyopathies, highlighting the ongoing need for research into effective therapies and improved patient outcomes.14 Mitochondrial cardiomyopathies are a heterogeneous group of disorders caused by dysfunction of mitochondrial energy production due to genetic mutations affecting mitochondrial or nuclear DNA. Mitochondrial cardiomyopathies can include a wide range of cardiac manifestations and are frequently associated with other multisystemic symptoms, including skeletal myopathy, neurological deficits, and metabolic disturbances. Advances in genetic testing have improved diagnostic accuracy, but early identification remains challenging due to the variable clinical presentation and clinical overlap with other cardiomyopathies. Therapeutic strategies are still evolving, with current management focusing on symptom control and mitigation of mitochondrial dysfunction (Figure 1). Mechanisms and clinical implications of mitochondrial cardiomyopathies. Mitochondrial cardiomyopathies are a group of rare, genetically and clinically heterogeneous disorders that result from defects in mitochondrial function, often involving impaired oxidative phosphorylation and ATP production. Diagnosing a mitochondrial cardiomyopathy is a complex process that requires the integration of clinical, biochemical, imaging, and genetic data. In this review, we explore the growing class of mitochondrial cardiomyopathies, emphasizing the need for an integrated, multi-speciality approach to diagnosis and management. OXPHOS, oxidative phosphorylation.14 The management of obstructive (oHCM) is rapidly evolving.3,15–18 Patients with oHCM treated with aficamten in the SEQUOIA-HCM trial demonstrated marked improvement in symptoms and functional capacity. In a Fast Track Congress article entitled ‘Efficacy of aficamten in patients with obstructive hypertrophic cardiomyopathy and mild symptoms: results from the SEQUOIA-HCM trial’ Martin Maron from the HCM Center at Lahey Clinic in Burlington, MA, USA, and colleagues explore whether patients with oHCM and mild symptoms experience similar clinical benefits with aficamten as patients with more advanced limitations.19 Patients in SEQUOIA-HCM (N = 282) were grouped at baseline according to symptom severity. Mild symptoms (n = 118) were defined as New York Heart Association (NYHA) class II and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) ≥ 80, and moderate to severe symptoms (n = 150) as NYHA class II/III/IV and KCCQ-CSS < 80. Primary endpoint was change in peak oxygen uptake (pVO2) from baseline to week 24; secondary endpoints included change in NYHA class, KCCQ-CSS, outflow tract gradients, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). In aficamten-treated patients, change in pVO2 at week 24 was not different between moderate to severe and mild symptom groups (P = .8). Likewise, the change in secondary endpoints (NYHA class, resting or Valsalva gradients, and NT-proBNP) did not differ significantly between the two symptom groups. Both groups experienced statistically significant improvements in KCCQ-CSS, but the extent of improvement was greater in the advanced symptom group (P = .02 for interaction). Treatment-emergent serious adverse events were infrequent in both groups. The authors conclude that patients with oHCM and mild symptoms treated with aficamten achieve significant improvement across a range of clinically relevant outcomes and generally similar to that of patients with more advanced symptoms. The manuscript is accompanied by an Editorial by Ali Yilmaz from the University Hospital Münster in Germany.20 The author notes that we are in need of more comprehensive data in a larger study group with an extended follow-up period regarding the potential (clinical) benefits of aficamten in order to establish both: (i) a focused and personalized cardiac phenotype; and (ii) a more holistic and HCM-stage-based patient phenotype that may allow us to precisely identify those patients with HCM and, for example, mild symptoms who will nevertheless substantially benefit from cardiac myosin inhibitors. He concludes that Maron et al. need to be congratulated for this important piece of work, and that the present findings represent an important, but nevertheless small, step forward towards the aforementioned ambitious goal—but there is still a long way to go. In this context upcoming new study data, e.g. from the MAPLE-HCM and FOREST-HCM trials will bring important contributions. Accurate differentiation of cardiac amyloidosis (CA) from phenotypic mimics remains challenging using current clinical and echocardiographic techniques. The accuracy of a novel artificial intelligence (AI) screening algorithm for echocardiography-based CA detection was assessed in a Clinical Research article entitled ‘Cardiac amyloidosis detection from a single echocardiographic video clip: a novel artificial intelligence-based screening tool’ by Jeremy Slivnick from the University of Chicago in Illinois, USA, and colleagues. The authors sought to: (i) train an AI model to detect CA using echocardiography; (ii) validate model performance in a large multiethnic patient population with echocardiographic data from a variety of ultrasound vendors; and (iii) compare the accuracy of the AI model to an existing clinical risk model for diagnosing CA.21 Utilizing a multisite, multiethnic dataset (n = 2612, 52% CA), a convolutional neural network was trained to differentiate CA from phenotypic controls using transthoracic apical four-chamber video clips. External validation was conducted globally across 18 sites including 597 CA cases and 2122 controls. Classification accuracy was assessed on the entire external validation dataset, and subgroup analyses were performed both on technetium pyrophosphate scintigraphy referrals, and individuals matched for age, sex, and wall thickness. Model accuracy was also compared with the transthyretin CA score and the increased wall thickness score within a subset of older heart failure with preserved ejection fraction patients with increased wall thickness. Cardiac amyloidosis patients and controls displayed similar age, sex, race, and comorbidities. After the removal of uncertain AI predictions (13%), model discrimination and classification were excellent for the entire external validation dataset [area under the receiver operating characteristic curve (AUROC) 0.93, sensitivity 85%, specificity 93%], irrespective of CA subtype (sensitivity: light-chain = 84%, wild-type transthyretin = 85%, and hereditary transthyretin = 86%). Performance was maintained in subgroup analysis in patients clinically referred for technetium pyrophosphate scintigraphy imaging (AUROC 0.86, sensitivity 77%, specificity 86%) and matched patients (AUROC 0.92, sensitivity 84%, specificity 91%). The AI model (AUROC 0.93) also outperformed transthyretin CA score (AUROC 0.73) and increased wall thickness (AUROC 0.80) scores. The authors conclude that this AI screening model—using only an apical four-chamber view—effectively differentiates CA from other causes of increased left ventricular wall thickness. The manuscript is accompanied by an Editorial by Alberto Aimo, Michele Emdin, and Marianna Fontana from Scuola Superiore Sant’Anna, Pisa, Italy, and University College London in the UK.22 The authors underscore that the work by Slivnick et al. provides a compelling foundation for how AI might reshape diagnostic strategies for a notoriously elusive disease. It combines large-scale data, sophisticated training methods, and meaningful validation cohorts to show that a single echocardiographic view can hold sufficient information to detect CA. Nonetheless, these impressive metrics need confirmation in a real-world environment. If prospective studies reveal a good diagnostic performance and satisfactory cost-effectiveness profile, automated amyloid detection could become an integral part of routine echocardiography, offering a powerful new ally in the early identification and management of CA. In a Translational Science article entitled ‘Empagliflozin enhances metabolic efficiency and improves left ventricular hypertrophy in a hypertrophic cardiomyopathy mouse model’, Tomas Baka from Boston University School of Medicine, in MA, USA, and colleagues investigate the therapeutic potential of the sodium–glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin (EMPA) in ameliorating these pathological features in a mouse model carrying the myosin R403Q mutation.23 Male mice harbouring the R403Q mutation were treated with EMPA for 16 weeks. Multi-nuclear magnetic resonance spectroscopy (31P, 13C, and 23Na MRS), echocardiography, transcriptomic, proteomic, and phosphoproteomic profiling were utilized to assess metabolic, structural, and functional changes. Empagliflozin facilitated the coupling of glycolysis with glucose oxidation and normalized elevated intracellular sodium levels. Treatment resulted in a significant reduction in LVH and myocardial fibrosis as evidenced by echocardiography and histopathology. These structural improvements correlated with enhancements in mitochondrial adenosine triphosphate (ATP) synthesis, fatty acid oxidation, and branched-chain amino acid catabolism. Furthermore, EMPA improved left ventricular diastolic function and contractile reserve, underscored by improved ATP production and reduced energy cost of contraction. Notably, these benefits were linked to down-regulation of the mammalian target of rapamycin signalling pathway and normalization of myocardial substrate metabolic fluxes (Figure 2). Early cardiomyocyte changes in hypertrophic cardiomyopathy (HCM) include impaired myofilament relaxation and high myofilament ATP utilization which have been linked with changes in metabolism and ion handling. During progression of disease, hypertrophic remodelling and reduced beta-adrenergic receptor signalling aggravate diastolic dysfunction. SGLT2i and myosin inhibitors may correct the diverse cellular HCM pathomechanisms at early and advanced disease stage.23 The authors conclude that empagliflozin significantly mitigates structural and metabolic dysfunctions in a mouse model of HCM, underscoring its potential as a therapeutic agent for managing this condition. The manuscript is accompanied by an Editorial by Jolanda van der Velden from Amsterdam UMC, The Netherlands.24 The author concludes that the results from the study by Baka et al. are promising as they provide evidence that SGLT2 inhibitors may prevent and even reverse adverse cardiac remodelling via improvement of cardiac metabolism, and energizing the heart of patients with hypertrophic cardiomyopathy. Accurate estimation of left atrial pressure (LAP) is essential in the management of HF patients, pulmonary hypertension (PH), and valvular heart disease. Although pulmonary arterial wedge pressure (PAWP) is commonly used as a surrogate for LAP, discrepancies may arise, particularly in the setting of mitral stenosis, elevated pulmonary vascular resistance (PVR), or patients with high PAWP. Pulmonary vascular disease (PVD) often complicates HF, worsening haemodynamics and outcomes. Accurate assessment of LAP is critical in the evaluation of HF, PH, and valvular heart disease. LAP has been clinically estimated by the occluded pulmonary artery pressure, or PAWP for over 70 years. Early studies reported the potential for PAWP to exceed LAP, but the frequency and clinical significance of this finding is unclear. In a Rapid Communications article entitled ‘Pulmonary arterial wedge pressure exceeding left atrial pressure: clinical implications’, Atsushi Tada from the Mayo Clinic and Foundation in Rochester, MN, USA, and colleagues aim to investigate the clinical and pathophysiologic significance of PAWP exceeding LAP in a large series of patients undergoing simultaneous measurement of PAWP and LAP at the time of cardiac catheterization.25 They found a strong correlation and agreement between mean PAWP and LAP measurements, again validating clinical practice overall. However, patients with PAWP exceeding LAP displayed multiple features indicating greater PVD, including greater venous involvement that may pressurize the lung capillaries out of proportion to LAP, potentially through collateral vessel flow that enables PAWP to exceed LAP even in the absence of flow secondary to upstream balloon occlusion. Clinical significance for PAWP exceeding LAP was underscored by a higher risk of HF hospitalization or death. The authors conclude that some patients with PH have only borderline elevation in PAWP, and the present data suggest that many of these patients may have normal LAP, in which case they may be treated according to pre-capillary PH approaches and guidelines, though greater venous involvement may alter response to conventional pulmonary vasodilators, calling for further study of patients with greater pulmonary venous involvement. Takotsubo syndrome is a life-threatening neuro-cardiac emergency triggered by stress and subtended by systemic inflammation. In a Rapid Communications article entitled ‘Takotsubo syndrome: cognitive behavioural therapy, physical training, and brain function recovery in the BREAKOUT trial’, Hilal Khan from the University of Aberdeen in the UK, and colleagues explore if behavioural modifications elicit responsiveness in brain structure and function after acute takotsubo syndrome.26 In a multi-centre trial, 71 acute takotsubo syndrome patients were randomized 1:1:1 to physical exercise training, cognitive behavioural therapy, or standard care for 12 weeks. Primary outcome was change in hippocampal volume from brain magnetic resonance imaging. Secondary outcomes were changes in total and regional brain volumes, functional connectivity, salivary and symptoms. were years and The primary outcome was by exercise or cognitive behavioural exercise and cognitive behavioural were associated to a of volume (P = were alterations in resting functional in the standard care group compared with either physical exercise or cognitive behavioural at two Both exercise and cognitive behavioural were associated to a reduction of salivary stress (P = and = behavioural was associated to a reduction of (P = and improved stress score (P = The authors conclude that after acute takotsubo behavioural modifications are associated to improvement of brain volumes, functional connectivity, and in systemic stress response and inflammation. The Issue is complemented by contributions. 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Source: European Heart Journal
Author: Filippo Crea
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4415389954