Publications
308 results found
Thygesen K, Alpert JS, Jaffe AS, et al., 2019, Fourth universal definition of myocardial infarction (2018), REVISTA ESPANOLA DE CARDIOLOGIA, Vol: 72, ISSN: 0300-8932
Maack C, Lehrke M, Backs J, et al., 2018, Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology, European Heart Journal, Vol: 39, Pages: 4243-4254, ISSN: 1522-9645
Heart failure (HF) is growing to a modern epidemic and despite advances in therapy, it still carries an ominous prognosis and a significant socioeconomic burden.1 Many novel agents that emerged as promising HF drugs failed to improve residual morbidity and mortality.2,3 Since developing and testing new agents has become increasingly costly,4 the concept of repurposing existing drugs for new indications has gained considerable importance.Conceptually, comorbidities such as type 2 diabetes mellitus (T2DM), obesity or chronic kidney disease, all highly prevalent in HF populations, have shifted from being innocent bystanders to drivers of HF. This applies especially to HF with preserved ejection fraction (HFpEF), a phenotype that accounts for more than 50% of HF patients and for which no effective therapy exists thus far.5,6 In particular, the prevalence of T2DM, thereby its combination with HF is rapidly increasing, mainly due to the obesity epidemic.Cardiovascular (CV) outcomes are addressed by an increasing number of clinical studies in T2DM, mainly as safety endpoints for anti-diabetic agents. Some of those drugs have beneficial CV effects independent of their glucose-lowering action. Consequently, anti-diabetic agents have gained interest for their potential repurposing in HF treatment. In this context, the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) organized a workshop on HF and T2DM, focusing on the pathophysiological and therapeutic aspects of this relationship. Here, we summarize the main points raised during this workshop, providing an overview of current evidence and open issues.
Pareek N, Cevallos J, Moliner P, et al., 2018, Activity and outcomes of a cardio-oncology service in the United Kingdom - a five-year experience, European Journal of Heart Failure, Vol: 20, Pages: 1721-1731, ISSN: 1388-9842
AIMS: Cardio-oncology clinics optimise the cardiovascular status of cancer patients but there is a limited description of their structure, case mix, activity and results. The purpose of this paper is to describe the activity and outcomes of a cardio-oncology service, particularly with respect to supporting optimal cancer treatment and survival. METHODS AND RESULTS: We prospectively studied patients referred to our service from February 2011 to February 2016. New York Heart Association (NYHA) class and parameters of cardiac function were measured at baseline and after optimisation by our service. Up-titration of cardiac treatment, continuation of cancer therapy and mortality were used as outcome measures. Of the 535 patients (55.8% females) referred, rates of cardiotoxicity for anthracyclines, anti-HER2 agents and tyrosine kinase inhibitors were 75.8%, 69.8% and 62.1%, respectively. Patients with left ventricular systolic dysfunction (LVSD) (n =128) were younger, had higher rates of hypertension and previous exposure to chemotherapy/radiotherapy (P < 0.001). At a median follow-up of 360 days, 93.8% of the patients with LVSD showed improvement in left ventricular ejection fraction (45% pre vs. 53% post; P < 0.001) and NYHA class (NYHA III-IV in 22% pre vs. 10% post; P = 0.01). All patients with normal left ventricular ejection fraction and biochemical or functional myocardial toxicity and 88% of patients with LVSD were deemed fit for continuation of cancer therapy after cardiovascular optimisation. CONCLUSIONS: Through the establishment of a cardio-oncology service, it is feasible to achieve high rates of cardiac optimisation and cancer treatment continuation.
Anker MS, Lena A, Hadzibegovic S, et al., 2018, Modern-day cardio-oncology: a report from the 'Heart Failure and World Congress on Acute Heart Failure 2018', ESC Heart Failure, Vol: 5, Pages: 1083-1091, ISSN: 2055-5822
During the ‘Heart Failure and World Congress on Acute Heart Failure 2018’, many sessions and lectures focused on cardio‐oncology. This important field of research is constantly growing, and therefore, a great amount of time during the congress focused on it. Prevention and early recognition of side effects is very important in cancer patients. One of the most common and potentially severe problems during antineoplastic therapy is cardiotoxicity. Hence, cardio‐oncology is vital in managing cancer patients. This paper will summarize the topics discussed in three main sessions and many additional lectures throughout the ‘Heart Failure and World Congress on Acute Heart Failure 2018’. The covered topics included pathophysiological mechanisms in the development of heart failure, risk factors, and early signs of cardiotoxicity detectable with different circulating and imaging biomarkers, as well as cardioprotective treatments recommended by different guidelines and position papers.
Rekha B, Velmurugan G, Freddy AJ, et al., 2018, Chronic intake of 4-Methylimidazole induces hyperinsulinemia and hypoglycaemia via pancreatic beta cell hyperplasia and glucose dyshomeostasis, Scientific Reports, Vol: 8, ISSN: 2045-2322
Caramel colours are the preferential food colouring agent globally, reaches wide age groups through eatables. Colas, a sweetened carbonated drink are most common caramel coloured beverage and its consumption is linked with diabetes, obesity, pancreatic cancer and other endocrine disorders. A major by-product produced during caramelization is 4-methylimidazole (4-MEI) that is detected in noteworthy concentrations in colas and other beverages. Previous studies revealed the neurotoxic and carcinogenic potential of 4-MEI in animals at higher doses but the effect of 4-MEI at theoretical maximum daily intake dose on glucose homeostasis is unexplored. Here, mice treated with 4-MEI (32 µg/kg bodyweight/day) for seven weeks exhibited severe hypoglycaemia and hyperinsulinemia mediated by hyperplasia of pancreatic beta cells and induces metabolic alterations. On combinatorial treatment, 4-MEI suppressed the glucogenic potential of non-artificial sweeteners and promotes lipogenesis. Furthermore, increased levels of C-peptide, LDL-cholesterol and triglycerides were observed in the humans with regular intake of 4-MEI containing beverages. In summary, 4-MEI induced pancreatic beta cell hyperplasia and leads to disruption of glucose and lipid homeostasis. This study suggests the need for further assessment and reconsideration of the wide usage of 4-MEI containing caramels as food additives.
Maack C, Eschenhagen T, Hamdani N, et al., 2018, Treatments targeting inotropy, European Heart Journal, Vol: 40, Pages: 3626-3644, ISSN: 1522-9645
Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.
Matthews A, Stanway S, Farmer RE, et al., 2018, Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review, BMJ, Vol: 363, Pages: k3845-k3845, ISSN: 0959-8138
OBJECTIVE: To investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer. DESIGN: Systematic review and meta-analysis of randomised controlled trials and observational studies. DATA SOURCES: Medline and Embase up until June 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they investigated the risk of a specific cardiovascular disease outcome associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of non-metastatic breast cancer. APPRAISAL AND DATA EXTRACTION: Relevant studies were originally identified and results extracted by one researcher, with a full replication of the study identification process by a combination of two other researchers. The Cochrane Collaboration's tool for assessing risk of bias was used to assess risk of bias in randomised controlled trials, and this tool was adapted to assess risk of bias in observational studies. RESULTS: 26 studies were identified, with results for seven specific cardiovascular disease outcomes (venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease). Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non-users and aromatase inhibitor users. Results were also consistent with a higher risk of the vascular diseases myocardial infarction and angina in aromatase inhibitor users compared with tamoxifen users, but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes. Data were limited, and evidence was generally inconsistent for all other cardiovascular disease outcomes. CONCLUSION: This review has collated substantial randomised controlled trial and observational evidence on the effect of endocrine therapies on several specific cardiovascular disease
Lagarto J, Dyer B, Talbot C, et al., 2018, Characterization of NAD(P)H and FAD autofluorescence signatures in a Langendorff isolated-perfused rat heart model, Biomedical Optics Express, Vol: 9, Pages: 4978-4978, ISSN: 2156-7085
Autofluorescence spectroscopy is a promising label-free approach to characterize biological samples with demonstrated potential to report structural and biochemical alterations in tissues in a number of clinical applications. We report a characterization of the ex vivo autofluorescence fingerprint of cardiac tissue, exploiting a Langendorff-perfused isolated rat heart model to induce physiological insults to the heart, with a view to understanding how metabolic alterations affect the autofluorescence signals. Changes in the autofluorescence intensity and lifetime signatures associated with reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) were characterized during oxygen- or glucose-depletion protocols. Results suggest that both NAD(P)H and FAD autofluorescence intensity and lifetime parameters are sensitive to changes in the metabolic state of the heart owing to oxygen deprivation. We also observed changes in NAD(P)H fluorescence intensity and FAD lifetime parameter on reperfusion of oxygen, which might provide information on reperfusion injury, and permanent tissue damage or changes to the tissue during recovery from oxygen deprivation. We found that changes in the autofluorescence signature following glucose-depletion are, in general, less pronounced, and most clearly visible in NAD(P)H related parameters. Overall, the results reported in this investigation can serve as baseline for future investigations of cardiac tissue involving autofluorescence measurements.
Lyon AR, Yousaf N, Battisti NML, et al., 2018, Immune checkpoint inhibitors and cardiovascular toxicity, LANCET ONCOLOGY, Vol: 19, Pages: E447-E458, ISSN: 1470-2045
Immune checkpoint inhibitors are a new class of anticancer therapies that amplify T-cell-mediated immune responses against cancer cells. Immune checkpoint inhibitors have shown important benefits in phase 3 trials, and several agents have been approved for specific malignancies. Although adverse events from immune checkpoint inhibitors are a common occurrence, cardiotoxic effects are uncommon, but are often serious complications with a relatively high mortality. Most cardiotoxic effects appear to be inflammatory in nature. Clinical assessment of a combination of biomarkers, electrocardiography, cardiac imaging, and endomyocardial biopsy can be used to confirm a possible diagnosis. In this Review, we discuss the epidemiology of immune checkpoint inhibitor-mediated cardiotoxic effects, as well as their clinical presentation, subtypes, risk factors, pathophysiology, and clinical management, including the introduction of a new surveillance strategy.
Meijers WC, Maglione M, Bakker SJL, et al., 2018, The failing heart stimulates tumor growth by circulating factors, Circulation, Vol: 138, ISSN: 0009-7322
Background—Heart failure (HF) survival has improved and nowadays many patients with HF die from non-cardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer.Methods—HF was induced by inflicting large anterior myocardial infarction (MI) in APCmin mice, which are prone to develop precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was employed, where an infarcted or sham-operated heart was transplanted into a recipient mouse, while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-MI proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and HF patients. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large prospective general population cohort.Results—The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4fold in APCmin mice (all P<0.0001). The severity of left ventricular (LV) dysfunction and fibrotic scar strongly correlated with tumor growth (P=0.002 and P=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and PON1) that were elevated in human patients with chronic HF (N=101) compared to healthy subjects (N=180, P<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation.
Chari A, Stewart AK, Russell SD, et al., 2018, Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials, Blood Advances, Vol: 2, Pages: 1633-1644, ISSN: 2473-9529
Carfilzomib is a selective proteasome inhibitor approved for the treatment of relapsed and/or refractory multiple myeloma (RRMM). It has significantly improved outcomes, including overall survival (OS), and shown superiority vs standard treatment with lenalidomide plus dexamethasone and bortezomib plus dexamethasone. The incidence rate of cardiovascular (CV) events with carfilzomib treatment has varied across trials. This analysis evaluated phase 1-3 trials with >2000 RRMM patients exposed to carfilzomib to describe the incidence of CV adverse events (AEs). In addition, the individual CV safety data of >1000 patients enrolled in the carfilzomib arm of phase 3 studies were compared with the control arms to assess the benefit-risk profile of carfilzomib. Pooling data across carfilzomib trials, the CV AEs (grade ≥3) noted included hypertension (5.9%), dyspnea (4.5%), and cardiac failure (4.4%). Although patients receiving carfilzomib had a numeric increase in the rates of any-grade and grade ≥3 cardiac failure, dyspnea, and hypertension, the frequency of discontinuation or death due to these cardiac events was low and comparable between the carfilzomib and control arms. Serial echocardiography in a blinded cardiac substudy showed no objective evidence of cardiac dysfunction in the carfilzomib and control arms. Moreover, carfilzomib had no significant effect on cardiac repolarization. Our results, including the OS benefit, showed that the benefit of carfilzomib treatment in terms of reducing progression or death outweighed the risk for developing cardiac failure or hypertension in most patients. Appropriate carfilzomib administration and risk factor management are recommended for elderly patients and patients with underlying risk factors.
Lyon AR, 2018, Heart failure resulting from cancer treatment: still serious but an opportunity for prevention, Heart, Vol: 105, Pages: 6-8, ISSN: 1355-6037
Ghadri J-R, Wittstein IS, Prasad A, et al., 2018, International expert consensus document on Takotsubo syndrome (part II): diagnostic workup, outcome, and management, European Heart Journal, Vol: 39, Pages: 2047-2062, ISSN: 1522-9645
The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians.
Ghadri J-R, Wittstein IS, Prasad A, et al., 2018, International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology, European Heart Journal, Vol: 39, Pages: 2032-2046, ISSN: 1522-9645
Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.
Ameri P, Canepa M, Anker MS, et al., 2018, Cancer diagnosis in patients with heart failure: epidemiology, clinical implications and gaps in knowledge, European Journal of Heart Failure, Vol: 20, Pages: 879-887, ISSN: 1388-9842
Cancer and heart failure (HF) are common medical conditions with a steadily rising prevalence in industrialized countries, particularly in the elderly, and they both potentially carry a poor prognosis. A new diagnosis of malignancy in subjects with pre-existing HF is not infrequent, and challenges HF specialists as well as oncologists with complex questions relating to both HF and cancer management. An increased incidence of cancer in patients with established HF has also been suggested. This review paper summarizes the epidemiology and the prognostic implications of cancer occurrence in HF, the impact of pre-existing HF on cancer treatment decisions and the impact of cancer on HF therapeutic options, while providing some practical suggestions regarding patient care and highlighting gaps in knowledge.
Patel HC, Hayward C, Wardle AJ, et al., 2018, The effect of head-up tilt upon markers of heart rate variability in patients with atrial fibrillation, Annals of Noninvasive Electrocardiology, Vol: 23, ISSN: 1082-720X
BACKGROUND: Heart rate variability (HRV) analysis is uncommonly undertaken in patients with atrial fibrillation (AF) due to an assumption that ventricular response is random. We sought to determine the effects of head-up tilt (HUT), a stimulus known to elicit an autonomic response, on HRV in patients with AF; we contrasted the findings with those of patients in sinus rhythm (SR). METHODS: Consecutive, clinically indicated tilt tests were examined for 207 patients: 176 in SR, 31 in AF. Patients in AF were compared to an age-matched SR cohort (n = 69). Five minute windows immediately before and after tilting were analyzed using time-domain, frequency-domain and nonlinear HRV parameters. Continuous, noninvasive assessment of blood pressure, heart rate and stroke volume were available in the majority of patients. RESULTS: There were significant differences at baseline in all HRV parameters between AF and age matched SR. HUT produced significant hemodynamic changes, regardless of cardiac rhythm. Coincident with these hemodynamic changes, patients in AF had a significant increase in median [quartile 1, 2] DFA-α2 (+0.14 [-0.03, 0.32], p < .005) and a decrease in sample entropy (-0.17 [-0.50, -0.01], p < .005). CONCLUSION: In the SR cohort, increasing age was associated with fewer HRV changes on tilting. Patients with AF had blunted HRV responses to tilting, mirroring those seen in an age matched SR group. It is feasible to measure HRV in patients with AF and the changes observed on HUT are comparable to those seen in patients in sinus rhythm.
Wright PT, Bhogal N, Diakonov I, et al., 2018, Cardiomyocyte membrane structure and cAMP compartmentation produce anatomical variation in β2AR-cAMP responsiveness in murine hearts, Cell Reports, Vol: 23, Pages: 459-469, ISSN: 2211-1247
Cardiomyocytes from the apex but not the base of the heart increase their contractility in response to β2-adrenoceptor (β2AR) stimulation, which may underlie the development of Takotsubo cardiomyopathy. However, both cell types produce comparable cytosolic amounts of the second messenger cAMP. We investigated this discrepancy using nanoscale imaging techniques and found that, structurally, basal cardiomyocytes have more organized membranes (higher T-tubular and caveolar densities). Local membrane microdomain responses measured in isolated basal cardiomyocytes or in whole hearts revealed significantly smaller and more short-lived β2AR/cAMP signals. Inhibition of PDE4, caveolar disruption by removing cholesterol or genetic deletion of Cav3 eliminated differences in local cAMP production and equilibrated the contractile response to β2AR. We conclude that basal cells possess tighter control of cAMP because of a higher degree of signaling microdomain organization. This provides varying levels of nanostructural control for cAMP-mediated functional effects that orchestrate macroscopic, regional physiological differences within the heart.
Harper AR, Patel HC, Lyon AR, 2018, Heart failure with preserved ejection fraction., Clinical medicine (London, England), Vol: 18, Pages: s24-s29, ISSN: 1470-2118
Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous collection of conditions that are unified by the presence of a left ventricular ejection fraction ≥50%, evidence of impaired diastolic function and elevated natriuretic peptide levels, all within the context of typical heart failure signs and symptoms. However, while HFpEF is steadily becoming the predominant form of heart failure, disease-modifying treatment options for this population remain sparse. This review provides an overview of the diagnosis, management and prevention of HFpEF for general physicians.
Plummer C, Collins P, Rosario DJ, et al., 2017, Managing cardiovascular risk in high-risk prostate cancer, TRENDS IN UROLOGY & MENS HEALTH, Vol: 8, Pages: 13-18, ISSN: 2044-3730
Gorter TM, van Veldhuisen DJ, Bauersachs J, et al., 2017, Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology, European Journal of Heart Failure, Vol: 20, Pages: 16-37, ISSN: 1388-9842
There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.
Bruengger AAS, Wechalekar K, Khattar R, et al., 2017, Histologically proven myocardial carcinoid metastases: the value of multimodality imaging, Canadian Journal of Cardiology, Vol: 33, Pages: 1336.e9-1336.e12, ISSN: 1916-7075
We present a case of a patient with intramyocardial metastases from a carcinoid tumor. These findings were detected using cardiovascular magnetic resonance imaging, with functional metabolic activity analyzed using nuclear imaging and confirmed by histologic findings at surgical biopsy. This case highlights the value of cardiovascular magnetic resonance imaging and the importance of multimodality imaging.
van Bilsen M, Patel HC, Bauersachs J, et al., 2017, The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology, European Journal of Heart Failure, Vol: 19, Pages: 1361-1378, ISSN: 1388-9842
Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future?
Kato K, Lyon AR, Ghadri J-R, et al., 2017, Takotsubo syndrome: aetiology, presentation and treatment., Heart, Vol: 103, Pages: 1461-1469, ISSN: 1355-6037
In the clinical setting, Takotsubo syndrome (TTS) is one of the most important diseases that must be accurately differentiated from acute coronary syndrome (ACS) to enable appropriate follow-up and medical management. The prevalence of TTS is estimated to be approximately 2%–3% in all patients presenting with suspected ACS.1 However, it may be underestimated because knowledge of diagnostic criteria is often incomplete, such as the possible coexistence of coronary artery disease (CAD). According to the widely used Mayo Clinic Diagnostic Criteria modified in 2008, incidental obstructive CAD not related to the wall motion abnormality may be an inclusion criterion for the diagnosis of TTS. However, this fact has been cited only as a footnote in a paper by Prasad and colleagues.2 In addition, atypical variants are not very well recognised by physicians, which may contribute to the underestimation of TTS.3 In 2015, the International Takotsubo Registry (www.takotsubo-registry.com), which is the largest systematic database on patients suffering from TTS, revealed novel data pertaining to TTS, which aided to the understanding of this enigmatic disease.4 This review summarises current knowledge on the aetiology, presentation and treatment of TTS.
Sikkel MB, Francis DP, Howard J, et al., 2017, Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies, Cardiovascular Research, Vol: 113, Pages: 1743-1752, ISSN: 1755-3245
AimsIt is generally accepted that post-MI heart failure (HF) changes a variety of aspects of sarcoplasmic reticular Ca2+ fluxes but for some aspects there is disagreement over whether there is an increase or decrease. The commonest statistical approach is to treat data collected from each cell as independent, even though they are really clustered with multiple likely similar cells from each heart. In this study, we test whether this statistical assumption of independence can lead the investigator to draw conclusions that would be considered erroneous if the analysis handled clustering with specific statistical techniques (hierarchical tests).Methods and resultsCa2+ transients were recorded in cells loaded with Fura-2AM and sparks were recorded in cells loaded with Fluo-4AM. Data were analysed twice, once with the common statistical approach (assumption of independence) and once with hierarchical statistical methodologies designed to allow for any clustering. The statistical tests found that there was significant hierarchical clustering. This caused the common statistical approach to underestimate the standard error and report artificially small P values. For example, this would have led to the erroneous conclusion that time to 50% peak transient amplitude was significantly prolonged in HF.Spark analysis showed clustering, both within each cell and also within each rat, for morphological variables. This means that a three-level hierarchical model is sometimes required for such measures. Standard statistical methodologies, if used instead, erroneously suggest that spark amplitude is significantly greater in HF and spark duration is reduced in HF.ConclusionCa2+ fluxes in isolated cardiomyocytes show so much clustering that the common statistical approach that assumes independence of each data point will frequently give the false appearance of statistically significant changes. Hierarchical statistical methodologies need a little more effort, but are necessary for relia
Lyon A, 2017, Stress in a dish: exploring the mechanisms of Takotsubo Syndrome, Journal of the American College of Cardiology, Vol: 70, Pages: 992-995, ISSN: 0735-1097
Mareev Y, Ramparsad N, McConnachie A, et al., 2017, Carvedilol vs. metoprolol tartrate on mortality in patients with heart failure with a reduced ejection fraction and atrial fibrillation or sinus rhythm: a post-hoc analysis of COMET, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 42-42, ISSN: 0195-668X
Schobesberger S, Wright P, Tokar S, et al., 2017, T-tubule remodelling disturbs localised β2-adrenergic signalling in rat ventricular myocyte during the progression of heart failure, Cardiovascular Research, Vol: 113, Pages: 770-782, ISSN: 0008-6363
AimsCardiomyocyte β2-adrenergic receptor (β2AR) cyclic adenosine monophosphate (cAMP) signalling is regulated by the receptors’ subcellular location within transverse tubules (T-tubules), via interaction with structural and regulatory proteins, which form a signalosome. In chronic heart failure (HF), β2ARs redistribute from T-tubules to the cell surface, which disrupts functional signalosomes and leads to diffuse cAMP signalling. However, the functional consequences of structural changes upon β2AR-cAMP signalling during progression from hypertrophy to advanced HF are unknown.Methods and resultsRat left ventricular myocytes were isolated at 4-, 8-, and 16-week post-myocardial infarction (MI), β2ARs were stimulated either via whole-cell perfusion or locally through the nanopipette of the scanning ion conductance microscope. cAMP release was measured via a Förster Resonance Energy Transfer-based sensor Epac2-camps. Confocal imaging of di-8-ANNEPS-stained cells and immunoblotting were used to determine structural alterations. At 4-week post-MI, T-tubule regularity, density and junctophilin-2 (JPH2) expression were significantly decreased. The amplitude of local β2AR-mediated cAMP in T-tubules was reduced and cAMP diffused throughout the cytosol instead of being locally confined. This was accompanied by partial caveolin-3 (Cav-3) dissociation from the membrane. At 8-week post-MI, the β2AR-mediated cAMP response was observed at the T-tubules and the sarcolemma (crest). Finally, at 16-week post-MI, the whole cell β2AR-mediated cAMP signal was depressed due to adenylate cyclase dysfunction, while overall Cav-3 levels were significantly increased and a substantial portion of Cav-3 dissociated into the cytosol. Overexpression of JPH2 in failing cells in vitro or AAV9.SERCA2a gene therapy in vivo did not improve β2AR-mediated signal compartmentation or reduce cAMP diffusion.ConclusionAlthough changes in T-tubule structure
Sikkel MB, Kumar S, Maioli V, et al., 2017, Erratum: High speed sCMOS-based oblique plane microscopy applied to the study of calcium dynamics in cardiac myocytes: [J. Biophotonics 9, No. 3, 311-323 (2016)]., J Biophotonics, Vol: 10, Pages: 744-745
In the article by M.B. Sikkel et al. (doi: 10.1002/jbio.201500193), published in J. Biophotonics 9, 311-323 (2016), an error occurred in the computer code that was used to generate Figure 3. This erratum is published to correct Figure 3, the calculated value of tgeom and the experimentally determined value of toptics in the text of the article.
Mareev Y, Lyon AR, Lane R, et al., 2017, Why don't beta-blockers work in patients with heart failure and atrial fibrillation? Pauses?, Publisher: WILEY, Pages: 81-82, ISSN: 1388-9842
Sweeney M, Yiu A, Lyon AR, 2017, Cardiac Atrophy and Heart Failure In Cancer., Cardiac Failure Review, Vol: 3, Pages: 62-65, ISSN: 2057-7540
Functional changes in the heart in patients with cancer can be a result of both the disease itself and various cancer therapies, and limiting cardiac damage has become an increasingly important issue as survival rates in patients with cancer have improved. Processes involved in cancer-induced cardiac atrophy may include cardiomyocyte atrophy and apoptosis, decreased protein synthesis, increased autophagy and proteolysis via the ubiquitin-proteosome system. Further to direct effects of malignancy on the heart, several chemotherapeutic agents are known to affect the myocardium, in particular the anthracyclines. The aim of this report is to review the effects of cancer and cancer treatment on the heart and what is known about the underlying mechanisms. Furthermore, clinical strategies to limit and treat cancer-associated cardiac atrophy are discussed, emphasising the benefit of a multidisciplinary approach by cardiologists and oncologists to optimise models of care to improve outcomes for patients with cancer.
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