Myocardial Extracellular Volume Quantification by Cardiovascular Magnetic Resonance and Computed Tomography

Purpose of review

This review article discusses the evolution of extracellular volume (ECV) quantification using both cardiovascular magnetic resonance (CMR) and computed tomography (CT).

Recent findings

Visualizing diffuse myocardial fibrosis is challenging and until recently, was restricted to the domain of the pathologist. CMR and CT both use extravascular, extracellular contrast agents, permitting ECV measurement. The evidence base around ECV quantification by CMR is growing rapidly and just starting in CT. In conditions with high ECV (amyloid, oedema and fibrosis), this technique is already being used clinically and as a surrogate endpoint. Non-invasive diffuse fibrosis quantification is also generating new biological insights into key cardiac diseases.

Summary

CMR and CT can estimate ECV and in turn diffuse myocardial fibrosis, obviating the need for invasive endomyocardial biopsy. CT is an attractive alternative to CMR particularly in those individuals with contraindications to the latter. Further studies are needed, particularly in CT.

     

Left Ventricular Hypertrophy in Athletes: Differentiating Physiology From Pathology

Purpose of review

The changes that occur in athlete’s heart are influenced by a number of factors including age, gender, ethnicity and the type of cardiovascular training. It is therefore important that the clinician is able to integrate all of these factors when assessing athletes to be able to guide investigations appropriately and to distinguish pathology from physiology. This review discusses the potential diagnostic conundrums when trying to differentiate physiological left ventricular hypertrophy from pathological hypertrophic cardiomyopathy in athletes. The mechanism of physiological and pathological hypertrophy is discussed together with history, clinical and investigational findings that can help to identify pathology.

Recent findings

Athletes with hypertrophic cardiomyopathy are more likely to have non-concentric left ventricular hypertrophy (LVH), an elevated relative wall thickness, lateral ECG changes and a smaller LV cavity than athletes with physiological LVH. Certain diastolic echocardiographic parameters when used as part of an algorithm (e′; E/E′; E/A) can help to distinguish physiology from pathology, and there is evidence that assessment of global longitudinal strain during exercise echocardiography may be of use in the future. Cardiac MRI is an important imaging modality that can have an additive effect over echocardiography in the diagnosis of cardiomyopathy. Late gadolinium enhancement is a recognised advantage for cardiac magnetic resonance to allow detection of fibrosis in hypertrophic cardiomyopathy. T1 mapping and extracellular volume quantification may be a tool for the future to help distinguish athlete’s heart from HCM.

Summary

Cardiac adaptation to exercise and training in athletes, the athlete’s heart causes electrophysiological and geometric changes that may mimic mild phenotypes of a pathological cardiomyopathy. This review article summarises a systematic approach to the assessment of left ventricular hypertrophy in athletes and describes pertinent clinical and investigation findings that can help to differentiate physiology from pathology.

     

Low frequency of cardniac arrhythmias and lack of structural heart disease in medically-naïve acromegaly patients: a prospective study at baseline and after 1 year of somatostatin analogs treatment

Background

The incidence of arrhythmias may be increased in acromegaly, but the pathophysiologic mechanisms involved are still unclear, and it has never been correlated with structural heart changes analyzed by the gold-standard method cardiac magnetic resonance (CMR).

Aim

Evaluate the frequency of arrhythmias in drug-naïve acromegaly patients at baseline and after 1 year of somatostatin analogs (SA) treatment and to correlate the occurrence of arrhythmias with the presence of structural heart changes.

Patients and methods

Consecutive drug-naïve acromegaly patients were recruited. The occurrence of arrhythmias and structural heart changes were studied through 24-h Holter and CMR, respectively, at baseline and after 1-year SA treatment.

Results

Thirty-six patients were studied at baseline and 28 were re-evaluated after 1 year of SA treatment. There were 13 females and median age was 48 years (20–73 years). Nine patients (32 %) were controlled after treatment. No sustained arrhythmias were reported in the 24-h Holter. No arrhythmia-related symptoms were observed. Only two patients presented left ventricular hypertrophy and three patients presented fibrosis at baseline. There was no correlation of the left ventricular mass with the number of episodes of arrhythmias and they were not more prevalent in the patients presenting cardiac fibrosis.

Conclusion

We found no sustained arrhythmias and a lack of arrhythmia-related symptoms at baseline and after 1 year of SA treatment in a contemporary cohort of acromegaly patients that also present a low frequency of structural heart changes, indicating that these patients may have a lower frequency of heart disease than previously reported.

     

Role of Cardiac Magnetic Resonance Imaging in Valvular Heart Disease: Diagnosis,Assessment, and Management

Purpose of Review

This article will review the current techniques in cardiac magnetic resonance imaging (CMR) for diagnosing and assessing primary valvular heart disease.

Recent Findings

The recent advancements in CMR have led to an increased role of this modality for qualifying and quantifying various native valve diseases. Phase-contrast velocity encoded imaging is a well-established technique that can be used to quantify aortic and pulmonic flow. This technique, combined with the improved ability for CMR to obtain accurate left and right ventricular volumetrics, has allowed for increased accuracy and reproducibility in assessing valvular dysfunction. Advancements in CMR technology also allows for improved spatial and temporal resolution imaging of various valves and their regurgitant or stenotic jets. Therefore, CMR can be a powerful tool in evaluation of native valvular heart disease.

Summary

The role of CMR in assessing valvular heart disease is growing and being recognized in recent guidelines. CMR has the ability to assess valve morphology along with qualifying and quantifying valvular disease. In addition, the ability to obtain accurate volumetric measurements may improve more precise management strategies and may lead to improvements in mortality and morbidity.

     

Left Ventricular Trabeculations in Athletes: Epiphenomenon or Phenotype of Disease?

Purpose of review

Excessive trabeculation attracting a diagnosis of left ventricular noncompaction cardiomyopathy (LVNC) has been reported in ostensibly healthy athletes. This review aims to explain why this occurs and whether this represents a spectrum of athletic physiological remodelling or unmasking of occult cardiomyopathy.

Recent findings

Genetic studies have yet to identify a dominant mutation associated with the LVNC phenotype and reported gene mutations overlap with many distinct cardiomyopathies and ion channel disorders, implying that the phenotype is shared across different genetic conditions. Large contemporary cohort studies indicate that current LVNC imaging criteria are oversensitive and not predictive of adverse clinical outcomes.

Summary

The majority of excessive LV trabeculation, as assessed by current quantification methods, is not due to cardiomyopathy but forms part of the normal continuum in health with potential contributions from cardiac remodelling processes. The study of rare, severe LVNC phenotypes may yield insights into an underlying molecular pathogenesis but in the absence of a universally accepted definition, contamination with aetiologically distinct conditions expressing a similar phenotype will remain an issue. Automated, objective quantification of trabeculation will help to define the normal distribution using big data without the constraint of wide interobserver variation.

     

S100A4 and P53 in myocardial collagen fibers of hypertrophic cardiomyopathy

Objective

The purpose of this work is to investigate the expression of S100A4 and P53 and their correlation with myocardial collagen fibers in hypertrophic cardiomyopathy (HCM).

Patients and methods

Myocardial tissue obtained from 10 patients undergoing HCM surgery (HCM group) was compared to myocardial tissue obtained from 10 traffic accident deaths (healthy control group). Collagen volume fractions were visualized and compared using sirius red F3B(SR) staining. Immunohistochemistry S-P and in situ hybridization techniques were used to test the different expressions of S100A4, P53 proteins, and their mRNA. Imaging and statistical methods were used for quantitative analysis.

Results

The collagen volume fraction in the HCM group was significantly higher than that in the control group. The integral optical density values of S100A4 and P53 in cardiomyocytes of the HCM group were also significantly higher than in the control group.

Conclusion

The increased content of collagen fibers and overexpression of S100A4 and P53 may play an important role in myocardial fibrosis of HCM, and they can be used in future HCM research. Blockade of S100A4 may have therapeutic potential in HCM by attenuating cardiac fibrosis.

     

Diagnosis and Management of Chagas Cardiomyopathy in the United States

Purpose of Review

Chagas cardiomyopathy is an emerging form of non-ischemic cardiomyopathy in the USA. This review aims to summarize current concepts in pathophysiology, disease transmission, medical therapy, and heart transplantation for patients with chronic Chagas cardiomyopathy.

Recent Findings

The incidence of Chagas cardiomyopathy is increasing in the USA, driven mainly by immigration from countries where Chagas disease is endemic. Chagas cardiomyopathy is a chronic, progressive myocarditis, with hallmark features of biventricular dysfunction, ventricular arrhythmias, thromboembolic complications, and a high risk of mortality. Currently, there is no effective treatment for chronic Chagas cardiomyopathy. Heart transplantation is the only treatment for patients with end-stage Chagas cardiomyopathy, but is associated with unique challenges including risk of reactivation.

Summary

As the prevalence of Chagas cardiomyopathy increases in the USA, practitioners must be aware of the unique challenges in diagnosis and management that Chagas cardiomyopathy presents.

     

The Female Athlete’s Heart: Facts and Fallacies

Purpose of the review

For many years, competitive sport has been dominated by men. Recent times have witnessed a significant increase in women participating in elite sports. As most studies investigated male athletes, with few reports on female counterparts, it is crucial to have a better understanding on physiological cardiac adaptation to exercise in female athletes, to distinguish normal phenotypes from potentially fatal cardiac diseases. This review reports on cardiac adaptation to exercise in females.

Recent findings

Recent studies show that electrical, structural, and functional cardiac changes due to physiological adaptation to exercise differ in male and female athletes. Women tend to exhibit eccentric hypertrophy, and while concentric hypertrophy or concentric remodeling may be a normal finding in male athletes, it should be evaluated carefully in female athletes as it may be a sign of pathology. Although few studies on veteran female athletes are available, women seem to be affected by atrial fibrillation, coronary atherosclerosis, and myocardial fibrosis less than male counterparts.

Summary

Males and females exhibit many biological, anatomical, and hormonal differences, and cardiac adaptation to exercise is no exception. The increasing participation of women in sports should stimulate the scientific community to develop large, longitudinal studies aimed at a better understanding of cardiac adaptation to exercise in female athletes.

     

The Emerging Role of Cardiac Magnetic Resonance Imaging in the Evaluation of Patients with HFpEF

Purpose of Review

To give an update on the emerging role of cardiac magnetic resonance imaging in the evaluation of patients with heart failure with preserved ejection fraction (HFpEF). This is important as the diagnosis of HFpEF remains challenging and cardiac imaging is pivotal in establishing the function of the heart and whether there is evidence of structural heart disease or diastolic dysfunction. Echocardiography is widely available, although the gold standard in quantifying heart function is cardiac magnetic resonance (CMR) imaging.

Recent Findings

This review includes the recently updated 2016 European Society of Cardiology guidelines on diagnosing HFpEF that define the central role of imaging in identifying patients with HFpEF. Moreover, it includes the pathophysiology in HFpEF, how CMR works, and details current CMR techniques used to assess structural heart disease and diastolic function. Furthermore, it highlights promising research techniques that over the next few years may become more used in identifying these patients.

Summary

CMR has an emerging role in establishing the diagnosis of HFpEF by measuring the left ventricular ejection fraction (LVEF) and evidence of structural heart disease and diastolic dysfunction.

     

Cardiac Adaption to Exercise Training: the Female Athlete

Purpose of review

The number of female athletes participating in sports has increased exponentially over the past century. While cardiac adaptations to exercise have been well described, female athletes have been underrepresented in many prior studies. More recently, important research has embraced gender as an important biologic variable. We will review this work in order to examine how gender influences the impact of exercise on the heart.

Recent findings

Exercise-induced cardiac remodeling (EICR) manifests slightly differently in male and female athletes. Specifically, female athletes have fewer signs of EICR on the electrocardiogram than male athletes, though are more likely to have anterior T wave inversions in the absence of cardiac disease. Cardiac enlargement due to exercise follows a different pattern in female versus male athletes, with females having similar chamber size when adjusted for body size but lower left ventricular mass. Recent research also suggests that female masters athletes may be less likely to have excess coronary disease, atrial fibrillation, and myocardial fibrosis, all of which have been posited though not proven to be sequelae of long-term endurance exercise in males.

Summary

Gender appears to be an important modifier of the relationship between exercise and associated cardiac remodeling. The biological mechanisms underlying gender-based differences in EICR are poorly understood and will be an important area of future research.

     

The Role of Cardiovascular Magnetic Resonance in the Management of Patients with Cancer

Purpose of review

This article reviews the utility of cardiovascular magnetic resonance imaging (CMR) to detect abnormalities of the cardiovascular system that may result from cancer or its treatment.

Recent findings

With CMR, one may assess cardiac anatomy, function, myocardial perfusion, tissue composition, and blood flow. For those with cancer, these capabilities allow one to differentiate myocardial masses that may relate to the presence of cancer and evaluate diseases of the pericardium. These features facilitate measurement of left ventricular (LV) volumes, ejection fraction, mass, strain, T1 and T2 relaxation properties, and the extracellular volume fraction all of which may be useful for detecting subclinical cardiovascular injury that results from the receipt of potentially cardiotoxic cancer treatment.

Summary

CMR can provide an effective and efficient means to identify clinical abnormalities resulting from the diagnosis of cancer or subclinical cardiac injury that may be related to receipt of the therapy for cancer.

     

Gender Differences in Ischemic Cardiomyopathy

Purpose of Review

Cardiovascular disease remains the leading cause of death among women globally, majority of which are due to ischemic heart disease. Despite the recent advances in the overall management of CVD, there are unique challenges in the diagnosis and management of women as well as poorer outcomes.

Recent Findings

Women with ischemic cardiomyopathy experience significant morbidity and mortality. Differences in underlying pathology, delays in presentation, diagnosis, and treatment as well as the under-representation of women in clinical trials contribute to these poor outcomes.

Summary

In this review, we discuss the nuances of gender-specific differences in the burden, clinical presentation, and outcomes of ischemic cardiomyopathy in women, in addition to discussion of areas needing further research.

     

The Role of Cardiovascular Magnetic Resonance for Surveillance of Cardiac Performance upon Receipt of Potentially Cardiotoxic Cancer Therapeutics

Purpose of Review

Advancements in cancer treatment have resulted in improved cancer-related survival and consequently an increase in the number of cancer survivors. Unfortunately, associated with this increase in cancer-related survivorship, cardiac events have occurred with increasing frequency in cancer survivors. Recognition that cancer survivors are at increased risk for cardiovascular (CV) morbidity has generated interest to develop cardiac imaging techniques that identify subclinical CV disease during receipt of potentially cardiotoxic cancer treatment. Since subclinical cardiovascular disease precedes future cardiac events, early recognition of subclinical CV disease during receipt of potentially cardiotoxic cancer treatment offers the opportunity to initiate strategies that prevent further evolution of subclinical CV disease as well as cardiac events.

Recent Findings

Cardiovascular magnetic resonance imaging (CMR) is an advanced imaging technique that identifies imaging markers of subclinical cardiovascular disease in patients receiving potentially cardiotoxic cancer treatment regimens. In this article, we review the use of CMR for identifying subclinical cardiac disease in patients receiving potentially cardiotoxic cancer treatment regimens.

Summary

The ability of contemporary CMR to accurately define cardiac anatomy, function, and tissue characteristics may represent a critical tool to assess patients with cancer.

     

The “Extreme Exercise Hypothesis”: Recent Findings and Cardiovascular Health Implications

Purpose of review

The “Extreme Exercise Hypothesis” is characterized by a U-shaped or reverse J-shaped, dose-response curve between physical activity volumes and cardiovascular health outcomes. In this review, we summarize recent findings that may support or refute the “Extreme Exercise Hypothesis.” Furthermore, we discuss potential cardiovascular health implications of the cardiac anatomical, structural, contractility, and biomarker abnormalities that have been reported in some veteran endurance athletes.

Recent findings

Emerging evidence from epidemiological studies and observations in cohorts of endurance athletes suggest that potentially adverse cardiovascular manifestations may occur following high-volume and/or high-intensity long-term exercise training, which may attenuate the health benefits of a physically active lifestyle. Accelerated coronary artery calcification, exercise-induced cardiac biomarker release, myocardial fibrosis, atrial fibrillation, and even higher risk of sudden cardiac death have been reported in athletes.

Summary

There is primarily circumstantial evidence that supports the “Extreme Exercise Hypothesis.” Subclinical and atherosclerotic coronary artery disease (CAD) as well as structural cardiovascular abnormalities and arrhythmias are present in some of the most active veteran endurance athletes and need appropriate clinical follow-up to reduce the risk for adverse cardiovascular outcomes. Future studies are warranted to establish the long-term cardiovascular health effects of these findings in veteran endurance athletes.

     

Die Rolle der Selbsthilfegruppen in der Onkologie

Background

Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.

Objectives

The psychosocial support given by self-help associations in different phases is evaluated.

Materials and methods

Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.

Results

On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.

Conclusions

The removal of barriers and development of effective structures are overdue.

     

Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients

Background and Aims

The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing methodologies are applied.

Methods

HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias.

Results

Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48% of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had clinically relevant mutations to DAA directed at NS5A.

Conclusion

While the clinical significance of this observation may be limited in highly drug adherent populations, some HCV/HIV coinfected persons may be at greater risk of viral resistance if suboptimal dosing occurs.

     

Atrial Fibrillation (AF) in Endurance Athletes: a Complicated Affair

Purpose of review

A complex relationship exists between exercise and atrial fibrillation (AF). Moderate exercise reduces AF risk whereas intense strenuous exercise has been shown to increase AF burden. It remains unclear at which point exercise may become detrimental. Overall, endurance athletes remain at lower cardiovascular risk and experience fewer strokes. The questions that arise therefore are whether AF is an acceptable byproduct of strenuous exercise, whether athletes who experience AF should be told to reduce exercise volume and how should they be managed. This review aims to critically review the literature and advise on how best to manage athletes with AF.

Recent findings

Emerging evidence suggests that female athletes may exhibit lower risk of AF, but data is limited in female endurance athletes.

Summary

AF is more prevalent in endurance athletes, particularly men and those who competed at a young age. Data is lacking in females and ethnic minorities. Current evidence suggests that treatment options for AF in athletes are similar to those used in the general population; however, medical therapy may be poorly tolerated. Catheter ablation is effective and can allow return to full competition.

     

Fettleberdiagnostik bei Diabetes mellitus Typ 2

Definition of terms

Under the term non-alcoholic fatty liver disease (NAFLD) both simple hepatic fat accumulation and non-alcoholic steatohepatitis (NASH) are combined. NASH is associated with liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC).

Epidemiological importance

In 2020, NAFLD will be the leading cause for liver transplantation in the USA, with rising financial costs for the healthcare system.

Comorbidities, diagnosis, and treatment

Type 2 diabetes (T2D) and metabolic syndrome (MetS) are important risk factors for the development of NAFLD, whereby these three diseases share similar pathophysiologic conditions, e.g., insulin resistance, obesity, and metabolic inflammation. Due to the rising number of patients with T2D and MetS, clinicians should aim to diagnose NAFLD early in this patient population and if necessary start treatment.

Goal

The aim of this work is to give an overview over the topic of NAFLD and diagnostic approaches in patients with T2D.

     

IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT

Background

Intestinal fibrosis is a common complication of Crohn’s disease (CD). Its exact mechanism is still unclear, and effective treatments to control or reverse the fibrosis process are unavailable. Epithelial–mesenchymal transition (EMT) may promote intestinal fibrosis by increasing deposition of extracellular matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a profibrotic factor as its association with fibrosis of multiple organs was reported.

Aims

To assess the roles of IL-17A and EMT in the initiation and development of intestinal fibrosis and to verify the potential inductive effect of IL-17A on EMT.

Methods

In this study, we evaluated the expression of IL-17A and EMT-related genes in colonic mucosal biopsy tissues of CD patients and control individuals. Then, we examined the changes of EMT-related genes and fibrosis-related genes of IEC-6 cells which cultured for 72 h under increasing concentrations of IL-17A or with TGF-β1, to verify the potential inductive effect of IL-17A on EMT in vitro. We blocked the IL-17A of the mouse model of TNBS-induced experimental intestinal colitis and fibrosis to further verify the potential inductive effect of IL-17A on EMT in vivo.

Results

We found the occurrence of EMT and high-level expression of IL-17A in intestinal mucosa of CD patients. Using IEC-6 cells, we showed that IL-17A may induce EMT in intestinal epithelial cells that come with reduced E-cadherin expression and increased expression of vimentin, snail, and α-SMA. We further found that anti-IL-17A treatment alleviated intestinal fibrosis through reducing EMT in mouse intestine.

Conclusions

Our study confirmed the involvement of IL-17A in the development of intestinal fibrosis through inducing EMT.

     

Strain elastography for assessment of liver fibrosis and prognosis in patients with chronic liver diseases

Background

Estimation of liver stiffness is essential in the treatment of liver diseases. Various procedures alternative to liver biopsy have been developed, and transient elastography using shear wave is an established method for evaluating liver stiffness and has been shown to be a prognostic indicator. In contrast, strain elastography (SE) has been applied to evaluate liver stiffness, however the significance remains uncertain.

Methods

We retrospectively analyzed 598 patients who underwent SE to evaluate the ability of estimating liver stiffness and the prognosis. Elasticity index (EI) was evaluated as an indicator of liver stiffness in this study.

Results

EI was increased as histological fibrosis advanced. EI was significantly different between mild fibrosis (F0–2) and advanced fibrosis (F3, 4). In contrast, EI was similar among those with different activity scores. EI showed better diagnostic performance in estimating advanced fibrosis than other serological markers and good reproducibility. Furthermore, EI was shown to be an independent prognostic factor in patients with chronic liver diseases and also with hepatocellular carcinoma (HCC) with advanced stage.

Conclusions

SE could estimate advanced liver fibrosis without influence of liver inflammation unlike other serological liver fibrosis markers. SE might be a prognostic factor in chronic liver diseases and HCC.