Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

Assessment of Inflammatory Hematological Ratios (NLR, PLR, MLR, LMR and Monocyte/HDL-Cholesterol Ratio) in Acute Myocardial Infarction and Particularities in Young Patients.

Cardiovascular disease, particularly coronary artery disease (CAD), remains a predominant cause of mortality globally. Factors such as atherosclerosis and inflammation play significant roles in the pathogenesis of CAD. The nexus between inflammation and CAD is underscored by the role of immune cells, such as neutrophils, lymphocytes, monocytes, and macrophages. These cells orchestrate the inflammatory process, a core component in the initiation and progression of atherosclerosis. The activation of these pathways and the subsequent lipid, fibrous element, and calcification accumulation can result in vessel narrowing. Hematological parameters derived from routine blood tests offer insights into the underlying inflammatory state. Recent studies have highlighted the potential of inflammatory hematological ratios, such as the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio and lymphocyte/monocyte ratio. These parameters are not only accessible and cost-effective but also mirror the degree of systemic inflammation. Several studies have indicated a correlation between these markers and the severity, prognosis, and presence of CAD. Despite the burgeoning interest in the relationship between inflammatory markers and CAD, there remains a paucity of data exploring these parameters in young patients with acute myocardial infarction. Such data could offer valuable insights into the unique pathophysiology of early-onset CAD and improve risk assessment and predictive strategies.

A Systematic Review on the Risk Modulators of Myocardial Infarction in the "Young"-Implications of Lipoprotein (a).

The presence of a myocardial infarction at a younger age is of special interest, considering the psychological and socioeconomic impact, as well as long-term morbidity and mortality. However, this group has a unique risk profile, with less traditional cardiovascular risk factors that are not well studied. This systematic review aims to evaluate traditional risk factors of myocardial infarction in the "young", highlighting the clinical implications of lipoprotein (a). We performed a comprehensive search using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards; we systematically searched the PubMed, EMBASE, and Science Direct Scopus databases, using the terms: "myocardial infarction", "young", "lipoprotein (a)", "low-density lipoprotein", "risk factors". The search identified 334 articles which were screened, and, at the end, 9 original research articles regarding the implications of lipoprotein (a) in myocardial infarction in the "young" were included in the qualitative synthesis. Elevated lipoprotein (a) levels were independently associated with an increased risk of coronary artery disease, especially in young patients, where this risk increased by threefold. Thus, it is recommended to measure the lipoprotein (a) levels in individuals with suspected familial hypercholesterolaemia or with premature atherosclerotic cardiovascular disease and no other identifiable risk factors, in order to identify patients who might benefit from a more intensive therapeutic approach and follow-up.

An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiomyopathy that follows an autosomal dominant inheritance pattern. The majority of HCM cases can be attributed to mutation of the MYBPC3 gene, which encodes cMyBP-C, a crucial structural protein of the cardiac muscle. The manifestation of HCM's morphological, histological, and clinical symptoms is subject to the complex interplay of various determinants, including genetic mutation and environmental factors. Approximately half of MYBPC3 mutations give rise to truncated protein products, while the remaining mutations cause insertion/deletion, frameshift, or missense mutations of single amino acids. In addition, the onset of HCM may be attributed to disturbances in the protein and transcript quality control systems, namely, the ubiquitin-proteasome system and nonsense-mediated RNA dysfunctions. The aforementioned genetic modifications, which appear to be associated with unfavorable lifelong outcomes and are largely influenced by the type of mutation, exhibit a unique array of clinical manifestations ranging from asymptomatic to arrhythmic syncope and even sudden cardiac death. Although the current understanding of the MYBPC3 mutation does not comprehensively explain the varied phenotypic manifestations witnessed in patients with HCM, patients with pathogenic MYBPC3 mutations can exhibit an array of clinical manifestations ranging from asymptomatic to advanced heart failure and sudden cardiac death, leading to a higher rate of adverse clinical outcomes. This review focuses on MYBPC3 mutation and its characteristics as a prognostic determinant for disease onset and related clinical consequences in HCM.

Optic Neuritis in Multiple Sclerosis-A Review of Molecular Mechanisms Involved in the Degenerative Process.

Multiple sclerosis is a central nervous system inflammatory demyelinating disease with a wide range of clinical symptoms, ocular involvement being frequently marked by the presence of optic neuritis (ON). The emergence and progression of ON in multiple sclerosis is based on various pathophysiological mechanisms, disease progression being secondary to inflammation, demyelination, or axonal degeneration. Early identification of changes associated with axonal degeneration or further investigation of the molecular processes underlying remyelination are current concerns of researchers in the field in view of the associated therapeutic potential. This article aims to review and summarize the scientific literature related to the main molecular mechanisms involved in defining ON as well as to analyze existing data in the literature on remyelination strategies in ON and their impact on long-term prognosis.

Multimodality imaging approach of patent foramen ovale: Practical considerations for transient ischemic attack/stroke.

A patent foramen ovale, which is present in up to 25% of the population, is a risk factor for cryptogenic stroke (which accounts for 15%-40% of strokes) and transient ischemic attack via paradoxical embolism. This narrative review focuses on the multimodality imaging approach of the diagnosis and periprocedural guidance of patent foramen ovale, with an emphasis on the use of agitated saline as contrast medium in echocardiography, starting from embryologic aspects. Therefore, we aimed to make a concise and complete presentation of the protocol used for this type of evaluation, along with multimodality imaging approach of the patent foramen ovale and practical considerations for transient ischemic attack/stroke.

From Classic to Modern Prognostic Biomarkers in Patients with Acute Myocardial Infarction.

Despite all the important advances in its diagnosis and treatment, acute myocardial infarction (AMI) is still one of the most prominent causes of morbidity and mortality worldwide. Early identification of patients at high risk of poor outcomes through the measurement of various biomarker concentrations might contribute to more accurate risk stratification and help to guide more individualized therapeutic strategies, thus improving prognoses. The aim of this article is to provide an overview of the role and applications of cardiac biomarkers in risk stratification and prognostic assessment for patients with myocardial infarction. Although there is no ideal biomarker that can provide prognostic information for risk assessment in patients with AMI, the results obtained in recent years are promising. Several novel biomarkers related to the pathophysiological processes found in patients with myocardial infarction, such as inflammation, neurohormonal activation, myocardial stress, myocardial necrosis, cardiac remodeling and vasoactive processes, have been identified; they may bring additional value for AMI prognosis when included in multi-biomarker strategies. Furthermore, the use of artificial intelligence algorithms for risk stratification and prognostic assessment in these patients may have an extremely important role in improving outcomes.

Novel Biomarkers of Atherosclerotic Vascular Disease-Latest Insights in the Research Field.

The atherosclerotic vascular disease is a cardiovascular continuum in which the main role is attributed to atherosclerosis, from its appearance to its associated complications. The increasing prevalence of cardiovascular risk factors, population ageing, and burden on both the economy and the healthcare system have led to the development of new diagnostic and therapeutic strategies in the field. The better understanding or discovery of new pathophysiological mechanisms and molecules modulating various signaling pathways involved in atherosclerosis have led to the development of potential new biomarkers, with key role in early, subclinical diagnosis. The evolution of technological processes in medicine has shifted the attention of researchers from the profiling of classical risk factors to the identification of new biomarkers such as midregional pro-adrenomedullin, midkine, stromelysin-2, pentraxin 3, inflammasomes, or endothelial cell-derived extracellular vesicles. These molecules are seen as future therapeutic targets associated with decreased morbidity and mortality through early diagnosis of atherosclerotic lesions and future research directions.

CPAP Influence on Readily Available Inflammatory Markers in OSA-A Pilot Study.

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, chronic hypoxia and a proinflammatory phenotype. The purpose of our study was to evaluate readily available inflammatory biomarkers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), WBC-to-MPV ratio (WMR) and lymphocyte-to-C-reactive protein ratio (LCR)) before and after CPAP in patients with moderate-severe OSA. We performed a prospective study that included patients with newly-diagnosed moderate-severe OSA. The control groups (patients without OSA and with mild OSA) were selected from the hospital polygraphy database. All subjects underwent routine blood panel, which was repeated in moderate-severe OSA patients after 8 weeks of CPAP. Our final study group included 31 controls, 33 patients with mild, 22 patients with moderate and 37 patients with severe OSA. CRP, ESR, NLR and WMR were correlated with OSA severity. After 8-week CPAP therapy, we documented a decrease in weight status, which remained statistically significant in both CPAP-adherent and non-adherent subgroups. Readily available, inexpensive inflammatory parameters can predict the presence of moderate-severe OSA, but are not influenced by short-term CPAP.

Beta-Blocker-Related Atrioventricular Conduction Disorders-A Single Tertiary Referral Center Experience.

Background and Objectives: Drug-related bradyarrhythmia is a well-documented major adverse event among beta-blocker users and a potential cause for hospitalization or additional interventions. Whether beta-blocker use is associated with specific bradyarrhythmia presentations, and how this relates to other predisposing factors, is not well known. We aim to evaluate the association between beta-blocker use and the type of atrioventricular (AV) conduction disorder in patients with symptomatic bradycardia. Materials and Methods: We conducted a retrospective cohort study on 596 patients with a primary diagnosis of symptomatic bradyarrhythmia admitted to a single tertiary referral center. Of the cases analyzed, 253 patients were on beta-blocker treatment at presentation and 343 had no bradycardic treatment. We analyzed demographics, clinical and paraclinical parameters in relation to the identified AV conduction disorder. A multivariate regression analysis was performed to explore factors associated with beta-blocker use. Results: Of the 596 patients (mean age 73.9 ± 8.8 years, 49.2% male), 261 (43.8%) had a third-degree AV block, 92 (15.4%) had a second-degree AV block, 128 (21.5%) had slow atrial fibrillation, 93 (15.6%) had sick sinus syndrome and 21 (3.5%) had sinus bradycardia/sinus pauses. Beta-blocker use was associated with the female gender (p < 0.001), emergency admission (p < 0.001), dilated cardiomyopathy (p = 0.003), the lower left ventricular ejection fraction (p = 0.02), mitral stenosis (p = 0.009), chronic kidney disease (p = 0.02), higher potassium levels (p = 0.04) and QRS duration > 120 ms (p = 0.02). Slow atrial fibrillation (OR = 4.2, p < 0.001), sick sinus syndrome (OR = 2.8, p = 0.001) and sinus bradycardia/pauses (OR = 32.9, p < 0.001) were more likely to be associated with beta-blocker use compared to the most common presentation (third-degree AV block), after adjusting for other patient characteristics. Conclusions: Beta-blocker use is more likely to be associated with slow atrial fibrillation, sick sinus syndrome and sinus bradycardia/pauses, compared to a second- or third-degree AV block, after adjusting for other patient factors such as gender, admission type, ECG, comorbidities, cardiac function and lab testing.

Left atrial strain: A novel "biomarker" for chronic kidney disease patients?

Cardiovascular disease and chronic kidney disease are frequently inter-connected and this association leads to an exponential growth of cardiovascular risk. This risk is currently underestimated by the existing algorithms and there is a constant need for new markers to predict adverse outcomes in this special population. In general population left atrial strain has emerged as an important tool for both the diagnosis and prognostic stratification, but data regarding its role in chronic kidney disease patients is scarce. The purpose of this review is to summarize the current evidence regarding this matter. Left atrial size and function mirror the duration and severity of increased left ventricular filling pressures. Increased left atrial volume index and impaired left atrial strain parameters are independent predictors for adverse cardiovascular events. Left atrial strain is impaired before changes in volume appear, thus being able to predict both diastolic and systolic function in chronic kidney disease patients. Finally, left atrial strain can identify renal patients with impaired exercise capacity and this could have clinical applications in the rehabilitation of this patients.

Well-Known and Novel Serum Biomarkers for Risk Stratification of Patients with Non-ischemic Dilated Cardiomyopathy.

Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient's selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.

Pushing the Limits of Medical Management in HCM: A Review of Current Pharmacological Therapy Options.

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment.

Neuropsychiatric Consequences of Lipophilic Beta-Blockers.

Beta-blockers are a class of drugs with important benefits in cardiovascular pathology. In this paper, we aim to highlight their adverse and therapeutic effects in the neuropsychiatric field. With respect to permeability, we would like to mention that most beta-blockers are lipophilic and can cross the blood-brain barrier. Observational studies show the presence of neuropsychiatric side effects when taking beta-blockers, and is the reason for which caution is recommended in their use in patients with depressive syndrome. From a therapeutic point of view, most current evidence is for the use of beta-blockers in migraine attacks, essential tremor, and akathisia. Beta-blockers appear to be effective in the treatment of aggressive behavior, beneficial in the prevention of posttraumatic stress syndrome and may play a role in the adjuvant treatment of obsessive-compulsive disorder, which is refractory to standard therapy. In conclusion, the relationship between beta-blockers and the central nervous system appears as a two-sided coin. Summarizing the neuropsychiatric side effects of beta-blockers, we suggest that clinicians pay special attention to the pharmacological properties of different beta-blockers.

From Classical Laboratory Parameters to Novel Biomarkers for the Diagnosis of Venous Thrombosis.

Venous thrombosis is a common and potentially fatal disease, because of its high morbidity and mortality, especially in hospitalized patients. To establish the diagnosis of venous thrombosis, in the last years, a multi-modality approach that involves not only imaging modalities but also serology has been evolving. Multiple studies have demonstrated the use of some biomarkers, such as D-dimer, selectins, microparticles or inflammatory cytokines, for the diagnosis and treatment of venous thrombosis, but there is no single biomarker available to exclusively confirm the diagnosis of venous thrombosis. Considering the fact that there are some issues surrounding the management of patients with venous thrombosis and the duration of treatment, recent studies support the idea that these biomarkers may help guide the length of appropriate anticoagulation treatment, by identifying patients at high risk of recurrence. At the same time, biomarkers may help predict thrombus evolution, potentially identifying patients that would benefit from more aggressive therapies. This review focuses on classic and novel biomarkers currently under investigation, discussing their diagnostic performance and potential benefit in guiding the therapy for venous thrombosis.

CPAP Effect on Cardiopulmonary Exercise Testing Performance in Patients with Moderate-Severe OSA and Cardiometabolic Comorbidities.

Background and Objectives: Obstructive sleep apnea (OSA) is associated with daytime somnolence, cognitive impairment and high cardiovascular morbidity and mortality. Obesity, associated cardiovascular comorbidities, accelerated erythropoiesis and muscular mitochondrial energetic dysfunctions negatively influence exercise tolerance in moderate-severe OSA patients. The cardiopulmonary exercise testing (CPET) offers an integrated assessment of the individual's aerobic capacity and helps distinguish the main causes of exercise limitation. The purpose of this study is to evaluate the aerobic capacity of OSA patients, before and after short-term continuous positive airway pressure (CPAP). Materials and Methods: Our prospective study included 64 patients with newly diagnosed moderate-severe OSA (apnea hypopnea index (AHI) 39.96 ± 19.04 events/h) who underwent CPET before and after CPAP. Thirteen patients were unable to tolerate CPAP or were lost during follow-up. Results: 49.29% of our patients exhibited a moderate or severe decrease in functional capacity (Weber C or D). CPET performance was influenced by gender but not by apnea severity. Eight weeks of CPAP induced significant improvements in maximal exercise load (Δ = 14.23 W, p = 0.0004), maximum oxygen uptake (Δ = 203.87 mL/min, p = 0.004), anaerobic threshold (Δ = 316.4 mL/min, p = 0.001), minute ventilation (Δ = 5.1 L/min, p = 0.01) and peak oxygen pulse (Δ = 2.46, p = 0.007) as well as a decrease in basal metabolic rate (BMR) (Δ = -8.3 kCal/24 h, p = 0.04) and average Epworth score (Δ = -4.58 points, p < 0.000001). Conclusions: Patients with moderate-severe OSA have mediocre functional capacity. Apnea severity (AHI) was correlated with basal metabolic rate, resting heart rate and percent predicted maximum effort but not with anaerobic threshold or maximum oxygen uptake. Although CPET performance was similar in the two apnea severity subgroups, short-term CPAP therapy significantly improved most CPET parameters, suggesting that OSA per se has a negative influence on effort capacity.

Multi-modality cardiac imaging in advanced chronic kidney disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is particularly frequent among those with severe renal impairment. Early diagnosis and therapeutic intervention may help alleviate the burden of cardiovascular complication within this population. In the last years, advances have been made toward developing noninvasive imaging techniques that could offer better insight into the cardiac involvement in end-stage renal disease (ESRD). Conventional transthoracic echocardiography remains the first-line investigation used to assess cardiac function, but encompassing in our daily practice, the newer approaches such as speckle-tracking imaging, cardiac computed tomography, or cardiac magnetic resonance can guide us to a more comprehensive understanding of CVD in ESRD. Given that patients with chronic kidney disease may not present with typical CVD symptoms, the amount of information brought by newer imaging techniques is crucial for an accurate diagnosis, risk stratification, and further management. The purpose of this review is to briefly summarize the specific applications of standard cardiac imaging techniques in patients with ESRD and to offer insight into the novel imaging modalities, highlighting the newest research in this field. By doing so, we aim to identify the most important imaging predictors of clinical outcomes in this population.

Association of Antihyperglycemic Therapy with Risk of Atrial Fibrillation and Stroke in Diabetic Patients.

Type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Atrial fibrillation (AF) and stroke are both forms of CVD that have major consequences in terms of disabilities and death among patients with diabetes; however, they are less present in the preoccupations of scientific researchers as a primary endpoint of clinical trials. Several publications have found DM to be associated with a higher risk for both AF and stroke; some of the main drugs used for glycemic control have been found to carry either increased, or decreased risks for AF or for stroke in DM patients. Given the risk for thromboembolic cerebrovascular events seen in AF patients, the question arises as to whether stroke and AF occurring with modified incidences in diabetic individuals under therapy with various classes of antihyperglycemic medications are interrelated and should be considered as a whole. At present, the medical literature lacks studies specifically designed to investigate a cause-effect relationship between the incidences of AF and stroke driven by different antidiabetic agents. In default of such proof, we reviewed the existing evidence correlating the major classes of glucose-controlling drugs with their associated risks for AF and stroke; however, supplementary proof is needed to explore a hypothetically causal relationship between these two, both of which display peculiar features in the setting of specific drug therapies for glycemic control.

Cardiac Device Therapy in Patients with Chronic Kidney Disease: An Update.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy are scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms, and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy with defibrillator (CRT-D) is preferred in patients who meet the established criteria. The need for cardiac pacing is increased three-fold in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications.

Myocardial infarction (MI) often leads to heart failure (HF) through acute or chronic maladaptive remodeling processes. This establishes coronary artery disease (CAD) and HF as significant contributors to cardiovascular illness and death. Therefore, treatment strategies for patients with CAD primarily focus on preventing MI and lessening the impact of HF after an MI event. Myocardial fibrosis, characterized by abnormal extracellular matrix (ECM) deposition, is central to cardiac remodeling. Understanding these processes is key to identifying new treatment targets. Recent studies highlight SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RAs) as favorable options in managing type 2 diabetes due to their low hypoglycemic risk and cardiovascular benefits. This review explores inflammation's role in cardiac fibrosis and evaluates emerging anti-diabetic medications' effectiveness, such as SGLT2i, GLP1-RAs, and dipeptidyl peptidase-4 inhibitors (DPP4i), in preventing fibrosis in patients with diabetes post-acute MI. Recent studies were analyzed to identify effective medications in reducing fibrosis risk in these patients. By addressing these areas, we can advance our understanding of the potential benefits of anti-diabetic medications in reducing cardiac fibrosis post-MI and improve patient outcomes in individuals with diabetes at risk of HF.