Search Results (45)

Background/Objectives: Alcoholic cardiomyopathy (ACM) is a major preventable cause of non-ischemic dilated cardiomyopathy (DCM), yet its specific cardiac magnetic resonance (CMR) remains incompletely defined. We aimed to characterize the CMR features of ACM, focusing on late gadolinium enhancement (LGE) subpatterns and biventricular function and to compare them with idiopathic DCM. Methods: In total, 148 consecutive patients (ACM n = 20, idiopathic DCM n = 128) referred for CMR at a single center were retrospectively analyzed. Sequential logistic regression adjusted for age, sex, left ventricular ejection fraction (LVEF), and right ventricular ejection fraction (RVEF) was used to identify independent association with LGE presence. Results: LVEF did not differ between groups (32.5% vs. 35.0%, p = 0.293). ACM patients showed significantly worse RVEF (40.5% vs. 52.0%, p = 0.010) and larger indexed right ventricle (RV) volumes. Any LGE was present in 70% vs. 40% (p = 0.015); when the non-specific RV insertion point pattern (non-RV-IP) was excluded, non-RV-IP LGE was 45% vs. 22.7% (p = 0.051), with a specific midwall linear pattern (25% vs. 8%, p = 0.033). ACM was independently associated with LGE across all models with an adjusted odds ratio (OR) of 3.06 [95% CI 1.05–8.95], p = 0.041, and RV dysfunction (RVEF < 45%) (OR 4.79 [95% CI 1.60–14.32], p = 0.005). No differences in major adverse cardiovascular events (MACEs) were observed at 24 months (log-rank p = 0.697). Conclusions: ACM has a distinct CMR phenotype characterized by midwall linear LGE fibrosis and more severe RV involvement, independent of left ventricle (LV) systolic function. These exploratory findings suggest that CMR may provide clinically relevant phenotypic information in ACM beyond LVEF, warranting confirmation in prospective studies. Full article

Peripartum cardiomyopathy (PPCM) is a distinct condition that presents as heart failure (HF) in a woman who was previously healthy and has no prior cardiovascular issues. It results from idiopathic left ventricular (LV) dysfunction, characterized by a reduced LV ejection fraction below 45%. PPCM is a life-threatening condition with a high mortality rate (MR) that demands urgent treatment. Methods: This narrative review aims to define PPCM and its pathophysiology and conduct a scoping review of the latest data on the management of patients with peripartum cardiomyopathy during pregnancy and the postpartum period. Results: Currently, treatment follows standard HF protocols for reduced ejection fraction, with the possible addition of bromocriptine, and during pregnancy, medications that do not harm the fetus. Conclusions: Early, aggressive therapy is essential for a better prognosis, but managing PPCM can be challenging. Treatment of PPCM patients should be led by a team of highly qualified specialists, known as the Obstetric and Cardiac Care Team, comprising an obstetrician-perinatologist, an anesthesiologist, a cardiologist, and a cardiac intensive care specialist. Baseline left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) are the main prognostic factors. LVEF less than 30%, significant LV dilatation, LVEDD ≥ 6.0 cm, and right ventricular involvement are factors indicative of a poor prognosis. While pregnancy after PPCM is possible, it should be discouraged due to the significant risk of complications and even death. The most common causes of death in patients with PPCM are thromboembolic complications, severe HF, serious ventricular arrhythmias, cardiogenic shock, and sudden cardiac arrest. Full article

Dilated cardiomyopathy (DCM) in children is rare, but carries a high risk of progression to advanced heart failure (HF) and heart transplant (HTx). Improved short-term risk stratification is essential; however, robust pediatric prognostic tools remain limited. We aimed to evaluate the 1-year prognostic value of multichamber speckle-tracking echocardiography (STE) and biomarkers, including age-adjusted N-terminal pro-B-type natriuretic peptide (NT-proBNP) and vitamin D, in children with DCM. In this single-centre prospective cohort study, 29 children with idiopathic DCM and 27 age- and sex-matched healthy controls underwent standardised clinical, laboratory, and echocardiographic assessment. The primary endpoint was a 12-month composite of implantation of an implantable cardioverter-defibrillator (ICD), left-ventricular assist device (LVAD), HTx, or all-cause mortality. During a 1-year follow-up, 9/29 (31%) DCM patients experienced major events. Compared with event-free patients and controls, children with events had more impaired LVGLS (−5.99 ± 2.45% vs. −13.44 ± 6.88% and −19.98 ± 3.25%), lower LASr (10.97 ± 7.67% vs. 25.36 ± 10.28% and 44.0 ± 11.43%), and reduced RVFWSL (−15.32 ± 5.24% vs. −23.13 ± 8.55% and −24.78 ± 4.45%; all p < 0.01). Zlog NT-proBNP was markedly higher in the event group (5.37 [5.00–6.08] vs. 2.28 [0.71–3.68] and 0.14 [−0.02–0.88]). LVGLS, Zlog NT-proBNP, and LASr showed excellent discrimination for 1-year events (AUC 0.91, 0.91, and 0.87, respectively), with clinically applicable cut-offs (LVGLS ≥ −8%, Zlog NT-proBNP ≥ 4.6, LASr ≤ 21%). In conclusion, multichamber strain imaging combined with age-adjusted NT-proBNP provides clinically relevant, exploratory markers for short-term risk stratification in pediatric DCM, supporting earlier intensification of follow-up and timely referral for advanced heart failure therapies. These findings warrant validation in larger multicenter cohorts. Full article

Factor XII is a molecule of unclear physiological function that has attracted increasing research interest across multiple medical disciplines. In recent years, a substantial body of evidence has emerged regarding the contribution of factor XII to the pathogenesis of inflammatory and prothrombotic conditions. FXII has been shown to play a protective role in FXII-driven coagulation during host defence against infections and to protect against multi-organ failure in animal models of sepsis. In acute respiratory distress syndrome (ARDS), FXII activity contributes to the release of pro-inflammatory mediators and is associated with severe clinical outcomes; it also induces fibroblast migration in idiopathic pulmonary fibrosis. FXII deficiency has been associated with reduced neutrophil adhesion and migration in sterile skin wounds and immune complex-induced vasculitis. In neurological conditions, FXII deficiency significantly reduced the number and severity of multiple sclerosis relapses and decreased the volume of post-traumatic brain oedema. In heart failure pathogenesis, FXII deficiency and pharmacological inhibition of FXII activity blocked activation of the renin–angiotensin–aldosterone system (RAAS) in dilated cardiomyopathy, increased median survival, and delayed heart failure onset in murine models. Importantly, FXII inhibition prevented arterial thrombosis without affecting haemostasis. This review summarises the latest findings on the contribution of FXII to inflammatory and prothrombotic states across multiple medical fields, including cardiology. Pharmacological inhibition of FXII has generated considerable interest as a potential future therapeutic strategy; however, to date, human studies remain limited. Full article

Background/Objectives: Fabry disease (FD) is a rare X-linked disease caused by the deficient activity of the enzyme α-galactosidase A. Cardiac involvement is particularly critical, often determining the disease prognosis. Epidemiological data on FD in Portugal are limited and inconsistent, highlighting the need for targeted screening. The F-CHECK study aimed to determine the prevalence of FD through the systematic screening of a Portuguese cohort of patients with unexplained cardiomyopathies. Methods: This multicenter observational study (NCT05409846) assessed the prevalence and clinical characteristics of FD in a Portuguese cohort (n = 409) of patients from 10 central hospitals who presented with unexplained cardiomyopathies, including idiopathic hypertrophic cardiomyopathy (HCM), left ventricular hypertrophy, dilated-phase HCM, and dilated cardiomyopathy with late gadolinium enhancement in the inferolateral segment. Screening was performed using dried blood spot assays to measure α-galactosidase A activity and/or by GLA gene sequencing in whole-blood samples. Results: FD was diagnosed in 14 patients, corresponding to a prevalence of 3.4%. FD diagnosis was significantly associated with systemic manifestations such as acroparesthesias (p = 0.027) and angiokeratomas (p = 0.003), as well as an increased risk of prior arrhythmic events (p = 0.021) and cerebrovascular disease (p = 0.016). Most FD patients (57%) presented a non-founder mutation in the GLA gene; however, they were pathogenically relevant. Conclusions: The observed 3.4% prevalence highlights the importance of systematic FD screening among Portuguese patients with unexplained cardiomyopathy, extending beyond classic hypertrophic presentations to dilated forms. Specific clinical signs, electrocardiogram findings, and cardiac imaging features can serve as valuable indicators to guide targeted genetic testing for FD. Full article

Lipid-soluble vitamins are essential micronutrients that play a vital role in processes such as growth, reproduction, immune regulation, antioxidant defense, anti-inflammatory response and cardiovascular health. This study aimed to evaluate the plasma levels of retinol, cholecalciferol, α-tocopherol and phylloquinone in dogs with dilated cardiomyopathy (DCM). Six dogs diagnosed with DCM and ten healthy control dogs were selected based on clinical, echocardiographic, electrocardiographic and radiographic examinations. Chromatographic analysis was performed to analyze the content of lipid-soluble vitamins. The mean plasma retinol levels were 0.0285 μg/mL and 0.0495 μg/mL in the DCM and control groups, respectively, and the mean cholecalciferol levels were 0.0739 μg/mL and 0.1045 μg/mL in the DCM and control groups, respectively. Retinol and cholecalciferol levels were both statistically lower in the DCM group than in the control group (p < 0.05). The mean plasma α-tocopherol levels were 0.3103 and 0.4322 μg/mL, and the mean plasma phylloquinone levels were 0.03780 and 0.04082 μg/mL in the DCM and control groups, respectively. However, no statistical significance was observed between the two groups for α-tocopherol or phylloquinone levels. Based on our findings, alterations in vitamin A and D metabolism could be associated with the development of idiopathic DCM in dogs. However, given the limited sample size, further investigation in larger populations is needed. Full article

The concepts of “isolated” or “idiopathic” heat failure (CHF/HF) and more recently of “non-dilated cardiomyopathy” lack a clear description of the specific characteristics that help condense the disease into a nomenclature-based list applicable to population studies. This ensued in the absence of primary preventive investigations of CHF/HF. Moreover, in the large spectrum of cardiovascular diseases (CVD), the conditions attributable to coronary heart diseases (CHD) from those related to CHF/HF or other causes are not in general disentangled. We review here current results prompting the operational idea to index heart diseases of uncertain etiology (HDUEs) from a population-based perspective in several contributions, where CHF/HF represented 50% of HDUEs, approximately 10% of all CVD mortality and approximately 5% of all-cause mortality. We wish to stimulate new studies that compare CHD with CHF/HF only, exploiting population data, excluding baseline prevalent heart diseases, including incidence cases and separately studies with large numbers of recruited individuals. These analyses may well be complemented by the use of the Fine-Gray variant of the Cox predictive model that, by the sub-distribution of hazard models, may enable identifying risk factors as the determinants of competition between groups of diseases. The aim is to better define the differences between CHD and CHF/HF along with the possible etiology and even specific risk factors of these independent CHF/HF cases. A surge of interest among the investigators should thus be stimulated. Eventually, also for this “character” (in Pirandello’s acception), an author may hopefully be found, thus complementing with etiology an apparently orphan condition. Full article

Background and Clinical Significance: Infective endocarditis (IE) in patients with cardiac implantable electronic devices (CIED-IE) is a severe condition with high mortality and increasing prevalence. Case Presentation: A 50-year-old man with diabetes, idiopathic dilated cardiomyopathy, and a dual-chamber implantable cardioverter-defibrillator (ICD) for secondary prevention of sudden cardiac death (SCD) presented with fever and peripheral arthritis. Initially evaluated for rheumatic disease, IE was ruled out at an initial cardiac evaluation. A subsequent computed tomography scan revealed a renal tumor, leading to transfer to the urology department. The patient was later evaluated in our cardiology department, where transthoracic and transesophageal echocardiography identified lead vegetations. Blood cultures and serologic tests remained negative. Empirical antibiotic therapy was initiated, and percutaneous ICD lead extraction was performed, with cultures remaining negative. After six weeks of antibiotic therapy the patient had a favorable outcome, then a subcutaneous ICD (S-ICD) was implanted three months later for SCD prevention. The renal tumor required nephrectomy, confirming clear cell renal carcinoma. Conclusions: This case highlights the diagnostic and therapeutic challenges of blood culture-negative CIED-IE and underscores the importance of a multidisciplinary approach in complex cases. Full article

Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPARγ) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPARγ causes dilated cardiomyopathy associated with lipotoxicity in mice. miR-130b-3p has been shown to be downregulated in the plasma of idiopathic dilated cardiomyopathy patients, but its role in modulating cardiomyocyte lipotoxicity via PPARγ remains unclear. Our objective was to investigate the protective role of miR-130b-3p against palmitate-induced lipotoxicity in cardiomyocytes through the modulation of the PPARγ signaling pathway. Human cardiomyoblasts were treated with palmitate. Intracellular lipid accumulation and expression of PPARγ and its downstream targets (CD36, FABP3, CAV1, VLDLR) were analyzed. Mitochondrial oxidative stress was assessed via MitoTracker Green and Redox Sensor Red staining and expression of CPT1B and SOD2. Endoplasmic reticulum stress and apoptosis were determined by examining GRP78, ATF6, XBP1s, CHOP, and caspase-3 expression. miR-130b-3p overexpression was achieved using transfection methods, and its effect on these parameters was evaluated. Luciferase assays were used to confirm PPARγ as a direct target of miR-130b-3p. Palmitate treatment led to increased lipid accumulation and upregulation of PPARγ and its downstream targets in human cardiomyoblasts. Palmitate also increased mitochondrial oxidative stress, endoplasmic reticulum stress and apoptosis. miR-130b-3p overexpression reduced PPARγ expression and its downstream signaling, alleviated mitochondrial oxidative stress and decreased endoplasmic reticulum stress and apoptosis in palmitate-stimulated cardiomyoblasts. Luciferase assays confirmed PPARγ as a direct target of miR-130b-3p. Our findings suggest that miR-130b-3p plays a protective role against palmitate-induced lipotoxicity in cardiomyocytes by modulating the PPARγ signaling pathway. Full article

Overlap syndrome of systemic sclerosis and idiopathic inflammatory myopathies is an increasingly frequent entity, but the association with immune-mediated necrotizing myositis has rarely been described. While myositis or myopathy may be features of scleroderma, it is imperative to correctly diagnose an overlap syndrome of these two, since it can be considered a different entity with specific management and a worse prognosis. Anti-signal recognition particle (anti-SRP) antibodies target the striated muscle fiber and inhibit myoblast regeneration, resulting in myofiber atrophy and necrosis. Anti-SRP antibodies are specific in immune-mediated necrotizing myopathy characterized by myonecrosis and minimal inflammatory reaction, with proximal muscle weakness and typical extra-muscular manifestation. There are controversial data on the association of cardiac manifestations and the presence of these antibodies, and recent studies cannot prove a significant correlation between the two. Myocarditis is a complication with an unpredictable, potentially severe outcome from heart failure and dilated cardiomyopathy to fatality. It can be difficult to diagnose, and a myocardial biopsy can be problematic in daily practice; thus, most practitioners rely on cardiac magnetic resonance with suggestive images for the correct diagnosis. This paper seeks to address the challenges associated with the diagnosis and treatment of collagen diseases by evaluating the role of anti-SRP antibodies in the pathogenesis of cardiac involvement. Full article

Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field. Full article

The discovery of hypertrophic cardiomyopathy (HCM) dates back to 1958, when the pathologist Donald Teare of the St. George’s Hospital in London performed autopsies in eight cases with asymmetric hypertrophy of the ventricular septum and bizarre disorganization (disarray) at histology, first interpreted as hamartoma. Seven had died suddenly. The cardiac specimens were cut along the long axis, similar to the 2D echo. In the same year, at the National Institute of Health U.S.A., Eugene Braunwald, a hemodynamist, and Andrew Glenn Morrow, a cardiac surgeon, clinically faced a patient with an apparently similar morbid entity, with a systolic murmur and subaortic valve gradient. “Discrete” subaortic stenosis was postulated. However, at surgery, Dr. Morrow observed only hypertrophy and performed myectomy to relieve the obstruction. This first Braunwald–Morrow patient underwent a successful cardiac transplant later at the disease end stage. The same Dr. Morrow was found to be affected by the familial HCM and died suddenly in 1992. The term “functional subaortic stenosis” was used in 1959 and “idiopathic hypertrophic subaortic stenosis” in 1960. Years before, in 1957, Lord Brock, a cardiac surgeon at the Guy’s Hospital in London, during alleged aortic valve surgery in extracorporeal circulation, did not find any valvular or discrete subaortic stenoses. In 1980, John F. Goodwin of the Westminster Hospital in London, the head of an international WHO committee, put forward the first classification of heart muscle diseases, introducing the term cardiomyopathy (dilated, hypertrophic, and endomyocardial restrictive). In 1995, the WHO classification was revisited, with the addition of two new entities, namely arrhythmogenic and purely myocardial restrictive, the latter a paradox of a small heart accounting for severe congestive heart failure by ventricular diastolic impairment. A familial occurrence was noticed earlier in HCM and published by Teare and Goodwin in 1960. In 1989–1990, the same family underwent molecular genetics investigation by the Seidman team in Boston, and a missense mutation of the β-cardiac myosin heavy chain in chromosome 14 was found. Thus, 21 years elapsed from HCM gross discovery to molecular discoveries. The same original family was the source of both the gross and genetic explanations of HCM, which is now named sarcomere disease. Restrictive cardiomyopathy, characterized grossly without hypertrophy and histologically by myocardial disarray, was found to also have a sarcomeric genetic mutation, labeled “HCM without hypertrophy”. Sarcomere missense mutations have also been reported in dilated cardiomyopathy (DCM) and non-compaction cardiomyopathy. Moreover, sarcomeric gene defects have been detected in some DNA non-coding regions of HCM patients. The same mutation in the family may express different phenotypes (HCM, DCM, and RCM). Large ischemic scars have been reported by pathologists and are nowadays easily detectable in vivo by cardiac magnetic resonance with gadolinium. The ischemic arrhythmic substrate enhances the risk of sudden death. Full article

Cardiac magnetic resonance (CMR) imaging has an important emerging role in the evaluation and management of patients with cardiomyopathies, especially in patients with dilated cardiomyopathy (DCM). It allows a non-invasive characterization of myocardial tissue, thus assisting early diagnosis and precise phenotyping of the different cardiomyopathies, which is an essential step for early and individualized treatment of patients. Using imaging techniques such as late gadolinium enhancement (LGE), standard and advanced quantification as well as quantitative mapping parameters, CMR-based tissue characterization is useful in the differential diagnosis of DCM and risk stratification. The purpose of this article is to review the utility of CMR in the diagnosis and management of idiopathic DCM, as well as risk prediction and prognosis based on standard and emerging CMR contrast and non-contrast techniques. This is consistent with current evidence and guidance moving beyond traditional prognostic markers such as ejection fraction. Full article

Inherited forms of arrhythmogenic and dilated cardiomyopathy (ACM and DCM) are characterized by variable disease expression and age-related penetrance. Calcium (Ca²⁺) is crucially important for proper cardiac function, and dysregulation of Ca²⁺ homeostasis seems to underly cardiomyopathy etiology. A polymorphism, c.286T>G p.(Ser96Ala), in the gene encoding the histidine-rich Ca²⁺ binding (HRC) protein, relevant for sarcoplasmic reticulum Ca²⁺ cycling, has previously been associated with a marked increased risk of life-threatening arrhythmias among idiopathic DCM patients. Following this finding, we investigated whether p.(Ser96Ala) affects major cardiac disease manifestations in carriers of the phospholamban (PLN) c.40_42delAGA; p.(Arg14del) pathogenic variant (cohort 1); patients diagnosed with, or predisposed to, ACM (cohort 2); and DCM patients (cohort 3). We found that the allele frequency of the p.(Ser96Ala) polymorphism was similar across the general European–American population (control cohort, 40.3–42.2%) and the different cardiomyopathy cohorts (cohorts 1–3, 40.9–43.9%). Furthermore, the p.(Ser96Ala) polymorphism was not associated with life-threatening arrhythmias or heart failure-related events across various patient cohorts. We therefore conclude that there is a lack of evidence supporting the important role of the HRC p.(Ser96Ala) polymorphism as a modifier in cardiomyopathy, refuting previous findings. Further research is required to identify bona fide genomic predictors for the stratification of cardiomyopathy patients and their risk for life-threatening outcomes. Full article

Dilated cardiomyopathy is one of the important diseases in dogs and humans. The second most common cause of heart failure in dogs is idiopathic dilated cardiomyopathy (iDCM), which results in heart failure or sudden cardiac death due to arrhythmia. This study aimed to determine changes in the plasma metabolome of dogs with iDCM compared to healthy dogs. For that purpose, a multiplatform mass-spectrometry-based approach was used. In this study, we included two groups of dogs: 12 dogs with iDCM and 8 healthy dogs. A total of 272 metabolites were detected in the plasma samples of dogs by combining three approaches but four MS-based platforms (GC-MS, LC-MS (untargeted), LC-MS (targeted), and FIA-MS (targeted) methods). Our findings demonstrated changes in the canine plasma metabolome involved in the development of iDCM, including the different concentrations of amino acids, biogenic amines, acylcarnitines, triglycerides and diglycerides, sphingomyelins, and organic acids. The results of this study will enable the detection and monitoring of pathophysiological mechanisms involved in the development of iDCM in the future. Full article