Post myocardial infarction left ventricular intramural dissecting hematoma: a case report describing a very rare complication.

BACKGROUND: Dissecting intramural hematoma is a rare complication of acute myocardial infarction (AMI) and has been associated with increased mortality. There has been paucity of literature to establish protocols and guidelines for management in such cases. CASE PRESENTATION: We hereby report the case of a 45-year-old male patient with left ventricular intramural dissecting hematoma (LV-IDH) who presented with chest pain and breathlessness and diagnosed as non-ST-elevation myocardial infarction (NSTEMI). Transthoracic echocardiography (TTE) was performed showing LV-IDH, confirmed with cardiac magnetic resonant imaging (cMRI). Selective coronary arteriography (CAG) was performed showing significant obstructive coronary artery disease (CAD). Further management with conservative approach involved discussion with patient, cardiothoracic surgeon and cardiology team including heart failure specialist and interventional cardiology. CONCLUSIONS: This case describes a rare complication of AMI and also focuses on utility of TTE and cMRI in the diagnosis of this rare complication. Both diagnosis and management are challenging and have to be individualized in similar cases. Multidisciplinary care coordination is important in management of patients with this diagnosis.

Cardiac amyloidosis: pathogenesis, clinical context, diagnosis and management options.

Amyloidosis covers a group of disorders that can manifest in virtually any organ system in the body and is thought to be secondary to misfolding of extracellular proteins with subsequent deposition in tissues. The precursor protein that is produced in excess defines the specific amyloid type. This requires histopathological confirmation using Congo-red dye with its characteristic demonstration of green birefringence under cross-polarized light. There are three main types of amyloidosis associated with cardiac involvement: light-chain (AL), familial or senile (ATTR), and secondary (AA) amyloidosis. The frequency of cardiac involvement and prognosis varies among each type. Amyloid cardiomyopathy commonly manifests as heart failure and the presenting features are usually dyspnoea, oedema, angina, pre-syncope and syncope. The diagnosis of cardiac amyloidosis is very hard and can easily be misdiagnosed. Although the imaging studies (such as echocardiography and cardiovascular magnetic resonance) may guide the diagnosis, tissue biopsy is needed for confirmation. Management of cardiac amyloidosis initially is to treat the underlying heart failure. Pacemaker implantation is usually required in patients with any conduction abnormalities. Transplantation is the next step with worsening heart failure. However, the aim of any treatment in amyloidosis, irrespective of type, is to prevent further deposition of amyloid while managing concurrent symptoms. In this manuscript, we will discuss the pathogenesis of cardiac amyloidosis, diagnostic methods and management options.

A perspective on sympathetic renal denervation in chronic congestive heart failure.

Medical therapy has indisputably been the mainstay of management for chronic congestive heart failure. However, a significant percentage of patients continue to experience worsening heart failure (HF) symptoms despite treatment with multiple therapeutic agents. Recently, catheter-based interventional strategies that interrupt the renal sympathetic nervous system have shown promising results in providing better symptom control in patients with HF. In this article, we will review the pathophysiology of HF for better understanding of the interplay between the cardiovascular system and the kidney. Subsequently, we will briefly discuss pivotal renal denervation (RDN) therapy trials in patients with resistant hypertension and then present the available evidence on the role of RDN in HF therapy.

Clinical markers in heart failure: a narrative review.

Heart failure is a complex clinical syndrome that is one of the causes of high mortality worldwide. Additionally, healthcare systems around the world are also being burdened by the aging population and subsequently, increasing estimates of patients with heart failure. As a result, it is crucial to determine novel ways to reduce the healthcare costs, rate of hospitalizations and mortality. In this regard, clinical biomarkers play a very important role in stratifying risk, determining prognosis or diagnosis and monitoring patient responses to therapy. This narrative review discusses the wide spectrum of clinical biomarkers, novel inventions of new techniques, their advantages and limitations as well as applications. As heart failure rates increase, cost-effective diagnostic tools such as B-type natriuretic peptide and N-terminal pro b-type natriuretic peptide are crucial, with emerging markers like neprilysin and cardiac imaging showing promise, though larger studies are needed to confirm their effectiveness compared with traditional markers.

Associations of Patients with Pericardial Effusion Secondary to Light-Chain or Transthyretin Amyloidosis- A Systematic Review.

BACKGROUND: Pericardial effusion is associated with amyloidosis, specifically amyloid light chain (AL) and transthyretin (ATTR) subtypes. However, the patients might present with different clinical symptoms. OBJECTIVE: To determine the characteristics and associations of patients with pericardial effusion owing to either AL or ATTR amyloidosis. METHODS: This study reviewed 26 studies from databases such as PubMed, MEDLINE, Web of Science, Google Scholar and CINAHL databases after protocol registration. The data were analyzed in IBM SPSS 21. Many statistical tests, such as Student t- and the Mann-Whitney U tests, were used. Multivariate logistic regression analysis was also performed. A p-value< 0.05 was considered significant. RESULTS: A total of 531 patients with pericardial effusion secondary to amyloidosis were included. The mean age was 58.4±24.5 years. Most of the patients were male (72.9%). Common co-morbid conditions included hypertension (16.8%) and active smoking (12.9%). The most common time from symptom onset to the clinical presentation was less than 1 week (45%). ATTR amyloidosis was more common in older patients (p<0.05). Abdominal and chest discomfort were commonly associated with AL and ATTR amyloidosis, respectively (p<0.05). Patients with AL amyloidosis had a higher association with interventricular septal thickening and increased posterior wall thickness (p<0.05). First-degree atrioventricular block, left bundle branch block (LBBB), and atrial fibrillation (AF) were more associated with ATTR amyloidosis (p<0.05). CONCLUSION: Pericardial effusion in patients with AL amyloidosis was associated with hypertrophic remodeling, while conduction abnormalities were associated with ATTR amyloidosis.

Hypercholesterolemia: a literature review on management using tafolecimab: a novel member of PCSK9 monoclonal antibodies.

Background: Cardiovascular diseases (CVD) persist as the leading cause of mortality globally, with atherosclerotic cardiovascular disease (ASCVD), including hypercholesterolaemia, being a significant contributor. Hyperlipidemia management includes various lipid-lowering drugs, including statins, Bempedoic acid, inclisiran, Lomitapide, ANGPTL3 inhibitors, and PCSK9 inhibitors. Statins have traditionally dominated lipid management therapies; however, a subset of patients remains unresponsive or intolerant to this therapy, necessitating novel therapeutic approaches. Tafolecimab, a promising and novel PCSK9 monoclonal antibody, demonstrated significant LDL-C reduction and a favourable safety profile in clinical trials. Objective: This review aimed to discuss the role and efficacy of Tafolecimab in the management of hypercholesterolaemia. Methods: The authors searched online databases, including PubMed, Scopus, and Embase, for articles related to talofecimab. Discussion: The efficacy of Tafolecimab in diverse patient populations, including those with comorbid conditions and various lipid disorders, has been explored. Ongoing trials, such as CREDIT-1, CREDIT-2, and CREDIT-4, have provided valuable insights into Tafolecimab's potential as a lipid-lowering agent. Moreover, the drug's extended dosing interval may enhance patient compliance and reduce treatment costs. It has also been found that Tafolecimab has more affinity for PCSK9 and a longer duration of LDL-C reduction than other monoclonal antibody drugs such as evolocumab. Thus, this review focuses on Tafolecimab, a novel PCSK9 monoclonal antibody, its mechanism of action, clinical trial outcomes, safety profile, and potential role in hypercholesterolaemia management. Despite its assuring potential, the long-term impact of Tafolecimab on cardiovascular outcomes remains to be fully elucidated, necessitating further research. Regulatory authorities like the FDA and EMA should also evaluate Tafolecimab's risks and benefits. Conclusion: In conclusion, Tafolecimab shows potential as an innovative therapeutic option for hypercholesterolaemia, particularly in patients with specific risk factors, but warrants additional research.

COVID-19 therapy and vaccination: a clinical narrative review.

The SARS-CoV-2 pandemic is the most globally impacting health issue our world has faced over the last century. As of January 7, 2022, around 300 million cases have been reported worldwide, with over 5 million deaths. The SARS-CoV-2 infection causes a hyperactive host immune response leading to an excessive inflammatory reaction with the release of many cytokines - cytokine storm - commonly noticed in acute respiratory distress syndrome, sepsis and fulminant multiorgan failure. Since the beginning of the pandemic, the scientific medical community has worked on therapeutic procedures that interfere with the exaggerated immune response. Thromboembolic complications are widespread in patients who are critically ill with COVID-19. Anticoagulant therapy was initially considered a cornerstone in hospitalized patients and even in the early post-discharge period; however, later trials have aborted the clinical benefits except for suspicion of or confirmed thrombosis. Immunomodulatory therapies are still crucial in moderate to severe COVID-19. Immunomodulator therapies include various medications from steroids to hydroxychloroquine, tocilizumab and Anakinra. Anti-inflammatory agents, vitamin supplements and antimicrobial therapy had initial encouraging evidence, but there are limited data to review. Convalescent plasma, immunoglobulins, eculizumab, neutralizing IgG1 monoclonal antibodies and remdesivir have positively impacted inpatient mortality and hospital length of stay. Eventually, wide population vaccination was proven to be the best tool to overcome the SARS-CoV-2 pandemic and help humanity return to regular life. Many vaccines and various strategies have been used since December 2020. This review discusses how the SARS-CoV-2 pandemic has progressed and surged, and summarizes the safety and efficacy of the most used therapies and vaccines in the light of recent evidence.

Diuretic resistance and the role of albumin in congestive heart failure.

Diuresis with loop diuretics is the mainstay treatment for volume optimization in patients with congestive heart failure, in which perfusion and volume expansion play a crucial role. There are robust guidelines with extensive evidence for the management of heart failure; however, clear guidance is needed for patients who do not respond to standard diuretic treatment. Diuretic resistance (DR) can be defined as an insufficient quantity of natriuresis with proper diuretic therapy. A combination of diuretic regimens is used to overcome DR and, more recently, SGLT2 inhibitors have been shown to improve diuresis. Despite DR being relatively common, it is challenging to treat and there remains a notable lack of substantial data guiding its management. Moreover, DR has been linked with poor prognosis. This review aims to expose the multiple approaches for treatment of patients with DR and the importance of intravascular volume expansion in the response to therapy.

The neurohormonal network in the RAAS can bend before breaking.

The renin-angiotensin-aldosterone system (RAAS) has evolved in humans as one of the main physiological networks by which blood pressure and blood flow to vital organs is maintained. The RAAS has evolved to circumvent life-threatening events such as hemorrhage and starvation. Although short-term activation of this system had been well suited to counteract such catastrophes of early man, excessive chronic activation of the RAAS plays a fundamental role in the development and progression of cardiovascular disease in modern man. The RAAS is an intricate network comprising a number of major organ systems (heart, kidney, and vasculature) and signaling pathways. The main protagonists are renin, angiotensinogen (Ang), angiotensin I (Ang I), angiotensin II (Ang II), and aldosterone (Aldo). The study and delineation of each of these substances has allowed modern medicine to create targets by which cardiovascular disease can be treated. The main modulators that have been synthesized in this respect are angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor blockers (MRBs), and direct renin inhibitors (DRIs). Over the past few decades, each of these substances has proven efficacious to varying degrees amongst a number of clinical settings. Additionally, there exists data for and against the use of these agents in combination. The use of these agents in combination poses a larger question conceptually: can excessive pharmacological inhibition of the RAAS lead to patient harm? This perspective will examine the concept of a neurohormonal inhibition ceiling in pertinent experimental and clinical trials.

Vandetanib-Induced Hyponatremia and Torsades De Pointes: A Case Report.

Medullary thyroid cancer (MTC) is a neuroendocrine tumor of the parafollicular cells of the thyroid gland. The prognosis is very poor in patients with advanced MTC. Vandetanib was approved for advanced MTC after randomized control trials showed that it had therapeutic efficacy and considerably prolonged progression-free survival. Vandetanib therapy is associated with serious cardiovascular side effects including hypertensive crisis and arrhythmias due to prolonged QTc. We present a case of an 83-year-old female with advanced metastatic MTC who is under treatment with vandetanib 300 mg/day and developed medication-related hyponatremia, QTc prolongation, ventricular fibrillation (VF), and torsades de pointes (TdP). Her vandetanib therapy was held. Subsequently, she did not show recurrences of TdP. This is the second such case report in the literature.

Biomarkers in Acute Heart Failure Syndromes: An Update.

Heart failure is one of the leading healthcare problems in the world. Clinical data lacks sensitivity and specificity in the diagnosis of heart failure. Laboratory biomarkers are a non-invasive method of assessing suspected decompensated heart failure. Biomarkers such as natriuretic peptides have shown promising results in the management of heart failure. The literature does not provide comprehensive guidance in the utilization of biomarkers in the setting of acute heart failure syndrome. Many conditions that manifest with similar pathophysiology as acute heart failure syndrome may demonstrate positive biomarkers. The following is a review of biomarkers in heart failure, enlightening their role in diagnosis, prognosis and management of heart failure.

Pathophysiology and treatment options for cardiac anorexia.

The anorexia-cachexia syndrome (ACS) occurs in many chronic illnesses, such as cancer, AIDS, and chronic obstructive pulmonary disease in addition to chronic congestive heart failure (CHF). Comparable to other chronic states, the ACS complicates CHF and impacts its prognosis; however, the available treatment options for this syndrome remain unsatisfactory. This review article focuses on the complex pathophysiology of cardiac anorexia. We focus on the recent data demonstrating the relationships between central appetite-regulating structures, inflammatory processes, and neurohormonal activation, and their respective roles in the development of anorexia. We then describe the different treatment options and discuss some future prospects for the management for cardiac anorexia.

Current treatment in COVID-19 disease: a rapid review.

The world has faced the most challenging pandemic of the modern era, that of severe acute respiratory syndrome coronavirus 2 infection, causing coronavirus disease and affecting over 35 million people globally. The wide range of clinical manifestations associated with this viral disease is thought to be related to the overexpression of inflammatory markers. Due to a dysregulated host response, the most severe form involves multi-organ failure and thromboembolic complications. Immunomodulatory therapies may help prevent its progression and anticoagulation has been shown to reduce the risk of thrombotic complications. As this is a new entity for the medical world, there are no known therapeutic options nor has the prevention of complications been established. Anti-inflammatory agents, antimicrobial therapy, and vitamin supplements are short of clear benefits, but there is limited data to review. Other agents, such as convalescent plasma, eculizumab, immunoglobulins, neutralizing IgG1 monoclonal antibodies, remdesivir, steroids, and tocilizumab, have shown a possible impact on inpatient length of stay and mortality rate. This review aims to assess the efficacy and safety of these available therapies in light of current evidence. We compare these treatment options based on their impact on symptom management, inpatient length of stay, and overall morbidity and mortality.

Mechanisms and management of prothrombotic state in COVID-19 disease.

The novel severe acute respiratory syndrome viral disease outbreak due to SARS-CoV-2 is a rapidly evolving disease and represents one of the greatest medical challenges in recent times. It is believed that SARS-CoV-2 has migrated from bats to an intermediate host and then to humans. This article aims at the mechanism and management of prothrombotic state in COVID-19 positive patients. We tried to present how the SARS-CoV-2 virus can induce thromboembolic events and the incidence of these thromboembolic events. We also tried to depict anticoagulation management in these patients as well as postdischarge plan and follow-up. Invasion of type 2 pneumocytes by the SARS-CoV-2 virus is critical in the course of illness because it results in activation of immune cells leading to elevation of cytokines. The subsequent activation of T cells and macrophages infiltrates the infected myocardial cells causing direct myocardiocyte toxicity and development of arrhythmia. Hypoxia or hypotension during the clinical course causes a mismatch between myocyte oxygen supply and workload demand resulting in cardiac distress. SARS-CoV-2 affects endothelial cells and pericytes that lead to severe micro and macrovascular dysfunction, and together with oxygen supply-demand mismatch, immune hyperresponsivity can potentially cause destabilization and plaque rupture causing acute coronary syndromes. Other mechanisms of injury include myocarditis, pericarditis, stress cardiomyopathy, vasculitis, and DIC (Disseminated intravascular coagulation)/microthrombi. SARS-CoV-2 enters the cells by the Spike protein S whose surface unit, S1, binds to the ACE2 receptor on the host cell. The type II transmembrane serine proteases TMPRSS2 and histone acetyltransferases (HAT) are host cell proteases that are recruited by the virus to cleave ACE2 surface protein S which facilitates the viral entry. Therefore, TMPRSS2 and HAT could be targeted for potential drugs against SARS-CoV-2. SARS-CoV-2 uses an RNA-dependent RNA polymerase for proliferation, which is targeted by remdesivir that is currently approved for emergency use by Food and Drug Administration (FDA). We need to adopt a multifaceted approach when combating SARS-CoV-2 because it presents several challenges including medical, psychological, socioeconomic, and ethical. COVID-19 is the biggest calamity during the 21st century, we need to have a keen understanding of its pathophysiology and clinical implications for the development of preventive measures and therapeutic modalities.

Cardiac Cachexia Associated With Valvular Heart Failure.

Cardiac cachexia (CC) represents a serious complication of heart failure (HF). This condition could be directly related to mortality. The weight or muscle mass loss has to be monitored in our patients with HF to avoid potential complications. We report a case of an elderly patient with a history of aortic stenosis (AS) who presented with progressive shortness of breath limiting his daily activities associated with weight loss. Signs of heart failure were evident on physical examination, and valvulopathy was also evident. His echocardiogram showed reduced ejection fraction (EF) with structural changes and severe aortic stenosis. He was not a candidate for cardiothoracic surgery, and a transcatheter aortic valve replacement (TAVR) was performed. After the procedure, his symptoms improved, and during the outpatient follow-up, his cardiac function and dry weight improved. Cardiac cachexia could be caused by reversible cardiomyopathy. Early assessment and approach are critical for the outcome of our patients, impacting their quality of life and outcome in terms of morbidity and mortality consequences.

Relationship between extreme obesity and mortality in patients with reduced ejection fraction.

AIMS: Although obesity is associated with increased mortality, epidemiologic studies in heart failure have reported lower mortality in obese patients compared with matched nonobese patients (the 'obesity paradox'). However, the relationship between survival and extreme (morbid) obesity (BMI ≥ 40) is poorly understood. We evaluate survival in low ejection fraction patients across a range of BMI categories, including extreme obesity. METHODS: In a retrospective review, 12 181 consecutive patients receiving nuclear stress testing at a tertiary care center were stratified based on BMI and ejection fraction. Eight-year mortality data were collected using the social security death index. RESULTS: Normal ejection fraction patients (internal control, ejection fraction ≥50%) exhibited the J-shaped association between mortality and BMI that is observed in the general population. Among patients with reduced ejection fraction (<50%), survival improved as obesity increased (P < 0.0001). Those with extreme obesity had the lowest mortality (n = 1134, P < 0.05). CONCLUSION: In this cohort of reduced Ejection fraction patients, the obesity paradox was observed in all weight categories, with the highest survival of all observed in the extremely obese BMI category. This further supports hypotheses that an obesity-related physiologic phenomenon affects mortality in reduced ejection fraction patients.

Association between endothelial function and chronotropic incompetence in subjects with chronic heart failure receiving optimal medical therapy.

OBJECTIVE: Impairment of flow-mediated, endothelium-dependent vasodilatation (FMD) of the brachial artery identifies peripheral endothelial dysfunction in subjects with chronic congestive heart failure (CHF) and is associated with increased morbidity and mortality. To further elucidate the interaction of peripheral and central mechanisms in the syndrome of CHF, we examined the association between endothelial function and chronotropic incompetence, an emerging prognostic marker in CHF. METHODS: Thirty subjects with stable New York Heart Association (NYHA) functional class II-III CHF were studied. A vascular ultrasound study was performed to measure brachial artery FMD. The percentage of age-adjusted maximal predicted heart rate (MPHR) reached during cardiopulmonary exercise tolerance testing (CPETT) was used to assess the degree of chronotropic competence. All patients received ACE inhibitors and beta-adrenoceptor blockers. RESULTS: Brachial artery FMD averaged 1.3 +/- 2.4% and age-adjusted % MPHR 74.1 +/- 11.7%. FMD correlated with % MPHR among all patients (r = 0.60, P = 0.01). FMD and resting heart rate (RHR) did not significantly correlate (r = 0.13, P = 0.55). CONCLUSIONS: FMD, a measure of peripheral endothelial dysfunction, and % MPHR, a central determinant of cardiac output, are moderately correlated in heart failure patients receiving optimal medical therapy. Whether a cause-effect relationship underlies this association remains to be investigated.

Venous congestion and endothelial cell activation in acute decompensated heart failure.

Despite accumulating clinical evidence supporting a key role for venous congestion in the development of acute decompensated heart failure (ADHF), there remain several gaps in our knowledge of the pathophysiology of ADHF. Specifically, the biomechanically driven effects of venous congestion on the vascular endothelium (the largest endocrine/paracrine organ of the body), on neurohormonal activation, and on renal and cardiac dysfunction remain largely unexplored. We propose that venous congestion is a fundamental, hemodynamic stimulus for vascular inflammation, which plays a key role in the development and possibly the resolution of ADHF through vascular, humoral, renal, and cardiac mechanisms. A better understanding of the role of venous congestion and endothelial activation in the pathophysiology of ADHF may provide a strong rationale for near-future testing of treatment strategies that target biomechanically driven inflammation. Targeting vascular and systemic inflammation before symptoms arise may prevent progression to overt clinical decompensation in the ADHF syndrome.

COVID-19 and renin-angiotensin system modulators: what do we know so far?

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory system-coronavirus-2 (SARS-CoV-2), is an important medical problem worldwide. Increased risk of mortality has been reported in patients with cardiovascular disease, such as hypertension (HTN). SARS-CoV-2 invades the pulmonary alveolar epithelial cells by binding to the surface receptor, angiotensin-converting enzyme 2 (ACE2). Renin-angiotensin system (RAS) modulators can increase levels of ACE2. Thus, concerns have been raised regarding an increased risk of severe COVID-19 infection in patients receiving RAS antagonists. AREAS COVERED: We reviewed current literature about the potential association between the utilization of RAS inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-inhibitors) and angiotensin-receptor blockers (ARBs) and likelihood of developing severe COVID-19 infection and whether or not continuation of these medications is appropriate in patients with active disease. EXPERT OPINION: The joint statement from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC) and Heart Failure Society of America (HFSA), strongly recommends that physicians should not initiate or withdraw their usual RAS-related treatments (ACE-inhibitor/ARB) to COVID-19 infected patients with cardiovascular disease. The decision should be made based upon each patient's clinical presentation and hemodynamic status.