Search Results (2,183)

The trained heart adapts through geometric changes influenced by concentric and eccentric hypertrophy, depending on the predominance of the isometric or dynamic components of the exercise performed. Additionally, alterations in heart rhythm may occur due to increased vagal system activity. Cardiological evaluation with an electrocardiogram (ECG) aims to identify cardiac conditions that could temporarily or permanently disqualify an athlete from competition. This study sought to compare electrocardiographic findings in regular exercisers with those observed in athletes and to correlate these findings with training duration and load. A cross-sectional study was conducted with 154 participants divided into two groups: exercisers (EG) and athletes (AG). Data were collected on exercise type, weekly training time and practice duration. Each participant underwent a resting ECG, analyzed by two independent physicians, with a third review in case of disagreement. The Seattle criteria were applied to categorize ECG changes as physiological, borderline or abnormal. The findings revealed that 75% of athletes exhibited ECG changes, with left and/or right ventricular hypertrophy and incomplete right bundle branch block (IRBBB) being the most prevalent. Age (PR = 0.92; p = 0.004) and exercise duration (PR = 1.00; p = 0.004) significantly influenced the observed electrocardiographic changes. The majority of both regular exercisers and athletes displayed ECG alterations, with the prevalence increasing with age and training duration. Full article

Anderson–Fabry (or Fabry) disease is a rare lysosomal storage disorder caused by a functional deficiency of the enzyme alpha-galactosidase A. The partial or total defect of this lysosomal enzyme, which is caused by variants in the GLA gene, leads to the accumulation of glycosphingolipids, mainly globotriaosylceramide in the lysosomes of different cell types. The clinical presentation of Fabry disease is multisystemic and can vary depending on the specific genetic variants associated with the disease. To date, more than 1000 different variants have been identified in the human GLA gene, including missense and nonsense variants, as well as small and large insertions or deletions. The identification of novel variants in individuals exhibiting symptoms indicative of Fabry disease, expands the molecular comprehension of the GLA gene, providing invaluable insights to physicians in the diagnosis of the disease. In this article, we present the case of two members of the same family, mother and son, in whom a new pathogenic variant was identified. This variant has not been previously described in the literature and is not present in databases. The two family members presented with a number of typical clinical manifestations of the disease, including cornea verticillata, neuropathic pain, left ventricular hypertrophy, angiokeratomas and abdominal pain. The son, but not his mother, showed reduced alpha-galactosidase A activity, while high levels of Lyso-Gb3 in the blood, a specific substrate accumulation biomarker, were found in both. Sequencing of the GLA gene revealed the presence of a variant, c.484delT, which is characterised by the deletion of a single nucleotide, a thymine, in exon 3 of the gene. This results in a frameshift variant, which introduces a premature stop codon, thereby generating a truncated and consequently non-functional protein. Therefore, the clinical and laboratory data indicate that the novel p.W162Gfs*3 variant described herein is associated with the classical form of Fabry disease. Full article

Hypertrophic cardiomyopathy (HCM) is a heterogeneous cardiac disease and one of its major challenges is the limited accuracy in stratifying the risk of sudden cardiac death (SCD). Positron emission tomography (PET), through the evaluation of myocardial blood flow (MBF) and metabolism using fluorodeoxyglucose (FDG) uptake, can reveal microvascular dysfunction, ischemia, and increased metabolic demands in the hypertrophied myocardium. These abnormalities are linked to several factors influencing disease progression, including arrhythmia development, ventricular dilation, and myocardial fibrosis. Fibroblast activation can also be evaluated using PET imaging, providing further insights into early-stage myocardial fibrosis. Conflicting findings underscore the need for further research into PET’s role in risk stratification for HCM. If PET can establish a connection between parameters such as abnormal MBF or increased FDG uptake and SCD risk, it could enhance predictive accuracy. Additionally, PET holds significant potential for monitoring therapeutic outcomes. The aim of this review is to provide a comprehensive overview of the most significant data on disease progression, risk stratification, and prognosis in patients with HCM using cardiac PET-CT imaging. Full article

Background: Charcot–Marie–Tooth (CMT) disease is an inherited peripheral neuropathy primarily involving motor and sensory neurons. Mutations in INF2, an actin assembly factor, cause two diseases: peripheral neuropathy CMT-DIE (MIM614455) and/or focal segmental glomerulosclerosis (FSGS). These two phenotypes arise from the progressive degeneration affecting podocytes and Schwann cells. In general, nerve enlargement has been reported in 25% of the demyelinating CMT subtype (CMT1), while little is known about the CMT-DIE caused by INF2 variants. Methods: To characterize the peripheral nerve phenotype of INF2-related CMT, we studied the clinical course, imaging, histology, and germline genetic variants in two unrelated CMT-DIE patients. Results: Patient 1 (INF2 p.Gly73Asp) and patient 2 (p.Val108Asp) first noticed walking difficulties at 10 to 12 years old. Both of them were electrophysiologically diagnosed with demyelinating neuropathy. In patient 2, the sural nerve biopsy revealed an onion bulb formation. Both patients developed nephrotic syndrome almost simultaneously with CMT and progressed into renal failure at the age of 16 to 17 years. Around the age of 30 years, both patients manifested multiple hypertrophy of the trunk, plexus, and root in the cervical, brachial, lumbosacral nerves, and cauda equina. The histology of the cervical mass in patient 2 revealed Schwannoma. Exome analysis showed that patient 2 harbors a germline LZTR1 p.Arg68Gly variant, while patient 1 has no schwannomatosis-related mutations. Conclusions: Peripheral neuropathy caused by INF2 variants may lead to the development of multifocal hypertrophy with age, likely due to the initial demyelination and subsequent Schwann cell proliferation. Schwannoma could co-occur when the tissues attain additional hits in schwannomatosis-related genes (e.g., LZTR1). Full article

Hypertension is a major risk factor of various cardiac complications, including hypertensive heart disease (HHD). This condition can lead to a number of structural and functional changes in the heart, such as left ventricular hypertrophy, diastolic dysfunction, and, eventually, systolic dysfunction. In the management of hypertensive heart disease, early diagnosis and appropriate treatment are crucial for preventing the progression to congestive heart failure. One potential diagnostic marker that has gained attention in recent years is the N-terminal pro-brain natriuretic peptide (NT-proBNP). The natriuretic peptides, including the brain natriuretic peptide (BNP) and its inactive N-terminal fragment, are secreted by the myocardium in response to increased wall stress and volume overload. In patients with hypertensive heart disease, increased NT-proBNP levels may reflect the structural and functional changes occurring in the myocardium as a result of chronic pressure overload. Several studies have investigated the diagnostic utility of NT-proBNP in hypertensive heart disease. NT-proBNP levels can be a useful adjunct in the diagnosis of hypertensive heart disease, particularly in the assessment of diastolic dysfunction and left ventricular hypertrophy. This review paper explores the role of NT-proBNP levels in the diagnosis of hypertensive heart disease. Full article

Background: Myocardial disease is an important component of the wide field of cardiovascular disease. However, the phenomenon of multiple myocardial diseases in a single patient remains understudied. Aim: To investigate the prevalence and impact of myocarditis in patients with genetic cardiomyopathies and to evaluate the outcomes of myocarditis treatment in the context of cardiomyopathies. Methods: A total of 342 patients with primary cardiomyopathies were enrolled. The study cohort included 125 patients with left ventricular non-compaction (LVNC), 100 with primary myocardial hypertrophy syndrome, 70 with arrhythmogenic right ventricular cardiomyopathy (ARVC), 60 with dilated cardiomyopathy (DCM), and 30 with restrictive cardiomyopathy (RCM). The diagnosis of myocarditis was based on data from myocardial morphological examination or a non-invasive diagnostic algorithm consisting of an analysis of clinical presentation, anti-cardiac antibody (Ab) titres, and cardiac MRI. Results: The prevalence of myocarditis was 74.3% in ARVC, 56.7% in DCM, 54.4% in LVNC, 37.5% in RCM, and 30.9% in HCM. Myocarditis had a primary viral or secondary autoimmune nature and manifested with the onset or worsening of chronic heart failure (CHF) and arrhythmias. Treatment of myocarditis in cardiomyopathies has been shown to stabilise or improve patient condition and reduce the risk of adverse outcomes. Conclusions: In cardiomyopathies, the genetic basis and inflammation are components of a single continuum, which forms a complex phenotype. In genetic cardiomyopathies, myocarditis should be actively diagnosed and treated as it is an important therapeutic target. Full article

Arterial hypertension has a high prevalence in the population and is considered both a cardiovascular disease and an important risk factor for the development of other cardiovascular diseases. Tea consumption shows antihypertensive effects due to its composition in terms of bioactive substances such as flavan-3-ols and xanthines. The aim of this study was to assess the possible beneficial effects of two tea extracts, one of white tea (ADM^® White Tea; WTE) and another one composed of a mixture of black tea and green tea (ADM^® Tea Complex; CTE), on the cardiovascular alterations induced by angiotensin II (AngII) infusion in mice. For this purpose, four groups of C57BL/6J male mice were used: (1) mice fed on a standard diet for 8 weeks and infused with saline for the last 4 weeks (controls); (2) mice fed on a standard diet for 8 weeks and infused with AngII for the last 4 weeks (AngII); (3) mice fed on a standard diet supplemented with 1.6% WTE and infused with AngII for the last 4 weeks (AngII + WTE); (4) mice fed on a standard diet supplemented with 1.6% TC and infused with AngII for the last 4 weeks (AngII + CTE). Both tea extracts exerted anti-inflammatory and antioxidant effects in arterial tissue and reduced AngII-induced endothelial dysfunction in aorta segments. Moreover, supplementation with WTE or CTE reduced the Ang-II-induced overexpression of AT1R and increased AngII-induced downregulation of AT2R in arterial tissue. However, only supplementation with CTE significantly increased the circulating levels of angiotensin 1-7 and reduced systolic blood pressure. In the heart, supplementation with both tea extracts attenuated AngII-induced cardiac hypertrophy and reduced ischemia-reperfusion-induced oxidative stress and apoptosis in myocardial tissue. In conclusion, supplementation with WTE or CTE attenuates AngII-induced cardiovascular damage through their anti-inflammatory, antioxidant, and antiapoptotic effects. In addition, supplementation with CTE also exerts antihypertensive effects, and so it may constitute an avenue through which to support cardiovascular health. Full article

Even if rarely detected, right atrial (RA) masses represent a diagnostic challenge due to their heterogeneous presentation. Para-physiological RA structures, such as a prominent Eustachian valve, Chiari’s network, and lipomatous atrial hypertrophy, may easily be misinterpreted as pathological RA masses, including thrombi, myxomas, and vegetations. Each pathological mass should always be correlated with adequate clinical, anamnestic, and laboratory data. However, the differential diagnosis between pathological RA masses may be challenging due to common constitutional symptoms, as in the case of vegetations and myxoma, which present with fever and analogous complications such as systemic embolism. The implementation of transthoracic echocardiography (TTE) with pulsed wave (PW) tissue Doppler imaging (TDI) may improve the visualization and differentiation of intracardiac masses through different color coding of the pathological structure compared to surrounding tissue. More remarkably, PW-TDI can provide a detailed assessment of the specific pattern of motion of each intracardiac mass, with important clinical implications. Specifically, a TDI-derived pattern of incoherent motion is typical of right-sided thrombi, myxomas, and vegetations, whereas right-sided pseudomasses are generally associated with a TDI pattern of concordant motion synchronous with the cardiac cycle. An increased TDI-derived mass peak antegrade velocity may represent an innovative marker of the embolic potential of mobile right-sided pathological masses. During the last two decades, only a few authors have used TTE implemented with PW-TDI for the characterization of intra-cardiac masses’ morphology and mobility. Herein, we report two clinical cases of totally different right-sided cardiac masses diagnosed using a multimodality imaging approach, including PW-TDI, followed at our institution. The prevalence and physiopathological characteristics of the most relevant RA masses and pseudomasses encountered in clinical practice are described in the present narrative review. In addition, we will discuss the principal clinical applications of PW-TDI and its potential value in improving the differential diagnosis of pathological and para-physiological right-sided cardiac masses. Full article

Background: The orthodontist can play an important role in the early detection of sleep-disordered breathing (SDB), aiding in the prevention of dentoskeletal complications and systemic issues. Early intervention supports proper pediatric development, emphasizing the need for SDB screening in orthodontics. SDB involves abnormal breathing during sleep, with obstructive sleep apnea (OSA) in children presenting unique diagnostic challenges compared to adults. Aim: This study aimed to identify children at risk for SDB through a validated screening questionnaire during orthodontic evaluations. Methods: This prospective study recruited children under 12 years of age between July 2023 and July 2024. The Sleep Clinical Record was used to screen for SDB indicators. Results: Among the 48 participants (31 females, 17 males) aged 5–12 years, 69% were identified as being at risk for SDB. Risk factors included oral breathing, nasal obstruction, tonsillar hypertrophy, malocclusion, high Friedman scores, narrow palates, and positive Brouillette phenotypes, all showing significant correlations (p < 0.05). Conclusion: The findings underline the critical importance of early SDB screening in orthodontic settings. These preliminary results encourage further research on larger cohorts to refine diagnostic tools and interventions. Early recognition and management of SDB can significantly enhance systemic health and craniofacial outcomes in pediatric patients. Full article

Chronic exposure to high altitudes causes pathophysiological cardiac changes that are characterized by cardiac dysfunction, cardiac hypertrophy, and decreased energy reserves. However, finding specific pharmacological interventions for these pathophysiological changes is challenging. In this study, we identified tetramethylpyrazine (TMP) as a promising drug candidate for cardiac dysfunction caused by simulated high-altitude exposure. By utilizing hypobaric chambers to simulate high-altitude environments, we found that TMP improved cardiac function, alleviated cardiac hypertrophy, and reduced myocardial injury in hypobaric hypoxic mice. RNA sequencing showed that TMP also upregulated heart-contraction-related genes that were suppressed by hypobaric hypoxia exposure. Mechanistically, TMP inhibited hypobaric hypoxia-induced cardiac Ca²⁺/calmodulin-dependent kinase II (CaMKII) activation and exerted cardioprotective effects by inhibiting CaMKII. Our data suggest that TMP application may be a promising approach for treating high-altitude-induced cardiac dysfunction, and they highlight the crucial role of CaMKII in hypobaric hypoxia-induced cardiac pathophysiology. Full article

Background/Objectives: Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient’s life. Currently, the treatment strategy focuses on restoring blood flow to the myocardium as quickly as possible. However, reperfusion activates several cellular cascades that contribute to organ dysfunction, resulting in the ischaemia/reperfusion (I/R) injury. The search for treatments against AMI and I/R injury is urgent due to the shortage of effective treatments at present. In this regard, histone deacetylase (HDAC) inhibitors emerge as a promising treatment against myocardial infarction. The objective of this systematic review is to analyse the effects of HDAC inhibitors on ventricular function, cardiac remodelling and infarct size, among other parameters, focusing on the signalling pathways that may mediate these cardiovascular effects and protect against AMI. Methods: Original experimental studies examining the effects of HDAC inhibitors on AMI were included in the review using the PubMed and Scopus databases. Non-experimental papers were excluded. The SYRCLE RoB tool was used to assess risk of bias and the results were summarised in a table and presented in sections according to the type of HDAC inhibitor used. Results: A total of 18 studies were included, 10 of them using trichostatin A (TSA) as an HDAC inhibitor and concluding that the treatment improved ventricular function, reduced infarct size, and inhibited myocardial hypertrophy and remodelling after AMI. Other HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), mocetinostat, givinostat, entinostat, apicidin, and RGFP966, were also analysed, showing antioxidant and anti-inflammatory effects, an improvement in cardiac function and remodelling, and a decrease in apoptosis, among other effects. Conclusions: HDAC inhibitors constitute a significant promise for the treatment of AMI due to their diverse cardioprotective effects. However, high risk of selection, performance, and detection bias in the in vivo studies means that their application in the clinical setting is still a long way off and more research is needed to better understand their benefits and possible side effects. Full article

Barth Syndrome (BTHS) is an early onset, lethal X-linked disorder caused by a mutation in tafazzin (TAFAZZIN), a mitochondrial acyltransferase that remodels monolysocardiolipin (MLCL) to mature cardiolipin (CL) and is essential for normal mitochondrial, cardiac, and skeletal muscle function. Current gene therapies in preclinical development require high levels of transduction. We tested whether TAFAZZIN gene therapy could be enhanced with the addition of a cell-penetrating peptide, penetratin (Antp). We found that TAFAZZIN-Antp was more effective than TAFAZZIN at preventing the development of pathological cardiac hypertrophy and heart failure. These findings indicate that a cell-penetrating peptide enhances gene therapy for BTHS. Full article

Adiponectin (ApN) is a hormone with potent effects on various tissues. We previously demonstrated its ability to counteract Duchenne muscular dystrophy (DMD), a severe muscle disorder. However, its therapeutic use is limited. AdipoRon, an orally active ApN mimic, offers a promising alternative. While cardiomyopathy is the primary cause of mortality in DMD, the effects of ApN or AdipoRon on dystrophic hearts have not been investigated. Our recent findings demonstrated the significant protective effects of AdipoRon on dystrophic skeletal muscle. In this study, we investigated whether AdipoRon effects could be extended to dystrophic hearts. As cardiomyopathy develops late in mdx mice (DMD mouse model), 14-month-old mdx mice were orally treated for two months with AdipoRon at a dose of 50 mg/kg/day and then compared with untreated mdx and wild-type (WT) controls. Echocardiography revealed cardiac dysfunction and ventricular hypertrophy in mdx mice, which were fully reversed in AdipoRon-treated mice. AdipoRon also reduced markers of cardiac inflammation, oxidative stress, hypertrophy, and fibrosis while enhancing mitochondrial biogenesis via ApN receptor-1 and CAMKK2/AMPK pathways. Remarkably, treated mice also showed improved skeletal muscle strength and endurance. By offering protection to both cardiac and skeletal muscles, AdipoRon holds potential as a comprehensive therapeutic strategy for better managing DMD. Full article

Background/Objectives: Dietary sulfur amino acid restriction (SAAR) elicits various health benefits, some mediated by fibroblast growth factor 21 (FGF21). However, research on SAAR’s effects on the heart is limited and presents mixed findings. This study aimed to evaluate SAAR-induced molecular alterations associated with cardiac remodeling and their dependence on FGF21. Methods: Male C57BL/6J wild-type and FGF21 knockout mice were randomized into four dietary regimens, including normal fat and high-fat diets (HFDs) with and without SAAR, over five weeks. Results: SAAR significantly reduced body weight and visceral adiposity while increasing serum FGF21 levels. In the heart, SAAR-induced molecular metabolic alterations are indicative of enhanced lipid utilization, glucose uptake, and mitochondrial biogenesis. SAAR also elicited opposing effects on the cardiac gene expression of FGF21 and adiponectin. Regarding cellular stress responses, SAAR mitigated the HFD-induced increase in the cardiac expression of genes involved in oxidative stress, inflammation, and apoptosis, while upregulating antioxidative genes. Structurally, SAAR did not induce alterations indicative of cardiac hypertrophy and it counteracted HFD-induced fibrotic gene expression. Overall, most alterations induced by SAAR were FGF21-independent, except for those related to lipid utilization and glucose uptake. Conclusions: Altogether, SAAR promotes cardiac alterations indicative of physiological rather than pathological remodeling, primarily through FGF21-independent mechanisms. Full article

The combination of hypertrophic cardiomyopathy with outflow tract obstruction, severe pre-capillary and post-capillary pulmonary hypertension, and severe primary mitral regurgitation is rare and presents distinct management challenges. Background and Clinical Significance: Pulmonary hypertension is an independent predictor of all-cause mortality in patients with hypertrophic cardiomyopathy managed medically and often precludes patients from undergoing cardiopulmonary bypass due to increased surgical morbidity and mortality. In studies specifically evaluating surgical myectomy, however, survival is favorable in patients with moderate-to-severe pulmonary hypertension. Case Presentation: We present a case of a 74-year-old male with six months of dyspnea with minimal exertion. A diagnostic work-up with transthoracic echocardiogram showed asymmetric left ventricular hypertrophy, left ventricular outflow tract obstruction with a peak gradient of 200 mmHg, right ventricular systolic pressure of 99 mmHg, systolic anterior motion of the mitral valve and flail anterior mitral leaflet. The patient was evaluated by a multi-disciplinary team and underwent extended septal myectomy and mitral valve repair with significant improvement in functional capacity post-operatively. Conclusions: While pulmonary hypertension increases the risk of morbidity and mortality during cardiopulmonary bypass, moderate-to-severe pulmonary hypertension in hypertrophic cardiomyopathy with outflow tract obstruction is a unique indication for septal reduction therapy that may not be associated with higher surgical mortality. Full article