Journal: Heart

Sorted by: date / impact
Abstract

Machine learning in cardiovascular medicine: are we there yet?

Shameer K, Johnson KW, Glicksberg BS, Dudley JT, Sengupta PP
Artificial intelligence (AI) broadly refers to analytical algorithms that iteratively learn from data, allowing computers to find hidden insights without being explicitly programmed where to look. These include a family of operations encompassing several terms like machine learning, cognitive learning, deep learning and reinforcement learning-based methods that can be used to integrate and interpret complex biomedical and healthcare data in scenarios where traditional statistical methods may not be able to perform. In this review article, we discuss the basics of machine learning algorithms and what potential data sources exist; evaluate the need for machine learning; and examine the potential limitations and challenges of implementing machine in the context of cardiovascular medicine. The most promising avenues for AI in medicine are the development of automated risk prediction algorithms which can be used to guide clinical care; use of unsupervised learning techniques to more precisely phenotype complex disease; and the implementation of reinforcement learning algorithms to intelligently augment healthcare providers. The utility of a machine learning-based predictive model will depend on factors including data heterogeneity, data depth, data breadth, nature of modelling task, choice of machine learning and feature selection algorithms, and orthogonal evidence. A critical understanding of the strength and limitations of various methods and tasks amenable to machine learning is vital. By leveraging the growing corpus of big data in medicine, we detail pathways by which machine learning may facilitate optimal development of patient-specific models for improving diagnoses, intervention and outcome in cardiovascular medicine.

Heart: 18 Jan 2018; epub ahead of print
Shameer K, Johnson KW, Glicksberg BS, Dudley JT, Sengupta PP
Heart: 18 Jan 2018; epub ahead of print | PMID: 29352006
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiopulmonary resuscitation: the science behind the hands.

Harris AW, Kudenchuk PJ
Sudden cardiac arrest is a leading cause of death worldwide. Despite significant advances in resuscitation science since the initial use of external chest compressions in humans nearly 60 years ago, there continues to be wide variability in rates of successful resuscitation across communities. The American Heart Association (AHA) and European Resuscitation Council emphasise the importance of high-quality chest compressions as the foundation of resuscitation care. We review the physiological basis for the association between chest compression quality and clinical outcomes and the scientific basis for the AHA\'s key metrics for high-quality cardiopulmonary resuscitation. Finally, we highlight that implementation of strategies that promote effective chest compressions can improve outcomes in all patients with cardiac arrest.

Heart: 19 Jan 2018; epub ahead of print
Harris AW, Kudenchuk PJ
Heart: 19 Jan 2018; epub ahead of print | PMID: 29353251
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Contemporary management and outcomes in congenitally corrected transposition of the great arteries.

Kutty S, Danford DA, Diller GP, Tutarel O
Congenitally corrected transposition of the great arteries (ccTGA) can occur in isolation, or in combination with other structural cardiac anomalies, most commonly ventricular septal defect, pulmonary stenosis and tricuspid valve disease. Clinical recognition can be challenging, so echocardiography is often the means by which definitive diagnosis is made. The tricuspid valve and right ventricle are on the systemic arterial side of the ccTGA circulation, and are therefore subject to progressive functional deterioration. The natural history of ccTGA is also greatly influenced by the nature and severity of accompanying lesions, some of which require surgical repair. Some management strategies leave the right ventricle as the systemic arterial pump, but carry the risk of worsening heart failure. More complex \'double switch\' repairs establish the left ventricle as the systemic pump, and include an atrial baffle to redirect venous return in combination with either arterial switch or Rastelli operation (if a suitable ventricular septal defect permits). Occasionally, the anatomic peculiarities of ccTGA do not allow straightforward biventricular repair, and Fontan palliation is a reasonable option. Regardless of the approach selected, late cardiovascular complications are relatively common, so ongoing outpatient surveillance should be established in an age-appropriate facility with expertise in congenital heart disease care.

Heart: 10 Jan 2018; epub ahead of print
Kutty S, Danford DA, Diller GP, Tutarel O
Heart: 10 Jan 2018; epub ahead of print | PMID: 29326110
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pulmonary arterial hypertension in adult congenital heart disease.

Brida M, Gatzoulis MA
Pulmonary arterial hypertension (PAH) is commonly associated with congenital heart disease (CHD) and relates to type of the underlying cardiac defects and repair history. Large systemic to pulmonary shunts may develop PAH if untreated or repaired late. PAH, when present, markedly increases morbidity and mortality in patients with CHD. Significant progress has been made for patients with Eisenmenger syndrome in pathophysiology, prognostication and disease-targeting therapy (DTT), which needs to be applied to routine patient care. Patients with PAH-CHD and systemic to pulmonary shunting may benefit from late defect closure if pulmonary vascular resistance (PVR) is still normal or near normal. Patients with PAH and coincidental defects, or previous repair of CHD should be managed as those with idiopathic PAH. Patients with a Fontan circulation, despite not strictly fulfilling criteria for PAH, may have elevated PVR; recent evidence suggests that they may also benefit from DTT, but more data are required before general recommendations can be made. CHD-PAH is a lifelong, progressive disease; patients should receive tertiary care and benefit from a proactive DTT approach. Novel biomarkers and genetic advances may identify patients with CHD who should be referred for late defect closure and/or patients at high risk of developing PAH despite early closure in childhood. Ongoing vigilance for PAH and further controlled studies are clearly warranted in CHD.

Heart: 01 May 2018; epub ahead of print
Brida M, Gatzoulis MA
Heart: 01 May 2018; epub ahead of print | PMID: 29720395
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hyperpolarised magnetic resonance for in vivo real-time metabolic imaging.

Apps A, Lau J, Peterzan M, Neubauer S, Tyler D, Rider O
Although non-invasive perfusion and viability imaging often provide the gateway to coronary revascularisation, current non-invasive imaging methods only report the surrogate markers of inducible hypoperfusion and presence or absence of myocardial scar, rather than actually visualising areas of ischaemia and/or viable myocardium. This may lead to suboptimal revascularisation decisions. Normally respiring (viable) cardiomyocytes convert pyruvate to acetyl-CoA and CO/bicarbonate (via pyruvate dehydrogenase), but under ischaemic conditions characteristically shift this conversion to lactate (by lactate dehydrogenase). Imaging pyruvate metabolism thus has the potential to improve upon current imaging techniques. Using the novel hyperpolarisation technique of dynamic nuclear polarisation (DNP), the magnetic resonance signal of injected [1-C]pyruvate can be transiently magnified >10 000 times over that seen in conventional MR spectroscopy, allowing the characteristic metabolic signatures of ischaemia (lactate production) and viability (CO/bicarbonate production) to be directly imaged. As such DNP imaging of the downstream metabolism of [1-C]pyruvate could surpass the diagnostic capabilities of contemporary ischaemia and viability testing. Here we review the technique, and with brief reference to the salient biochemistry, discuss its potential applications within cardiology. These include ischaemia and viability testing, and further characterisation of the altered metabolism seen at different stages during the natural history of heart failure.

Heart: 26 Apr 2018; epub ahead of print
Apps A, Lau J, Peterzan M, Neubauer S, Tyler D, Rider O
Heart: 26 Apr 2018; epub ahead of print | PMID: 29703741
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Validity of inducible ischaemia as a surrogate for adverse outcomes in stable coronary artery disease.

Timmis A, Raharja A, Archbold RA, Mathur A
Regional myocardial ischaemia is commonly expressed as exertional angina in patients with stable coronary artery disease (CAD). It also associates with prognosis, risk tending to increase with the severity of ischaemia. The validity of myocardial ischaemia as a surrogate for adverse clinical outcomes, however, has not been well established. Thus, in cohort studies, ischaemia testing has failed to influence rates of myocardial infarction and coronary death. Moreover, in clinical studies, pharmacological and interventional treatments that are effective in correcting ischaemia have rarely been shown to reduce cardiovascular (CV) risk. This contrasts with statins and other anti-inflammatory drugs that have no direct effect on ischaemia but improve CV outcomes by modifying the atherothrombotic disease process. Despite this, and with little evidence of patient benefit, stress testing is commonly used during the follow-up of patients with stable CAD when the demonstration of ischaemic change may be seen as a target for treatment, independently of symptomatic status. Substitution of a symptom-driven management strategy has the potential to reduce rates of non-invasive stress testing, unnecessary downstream revascularisation procedures and use of valuable resources in patients with stable CAD without adverse consequences for CV risk.

Heart: 30 Oct 2018; 104:1733-1738
Timmis A, Raharja A, Archbold RA, Mathur A
Heart: 30 Oct 2018; 104:1733-1738 | PMID: 29875140
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart failure with preserved ejection fraction: controversies, challenges and future directions.

Zakeri R, Cowie MR
Heart failure with preserved ejection fraction (HFpEF) comprises almost half of the population burden of HF. Because HFpEF likely includes a range of cardiac and non-cardiac abnormalities, typically in elderly patients, obtaining an accurate diagnosis may be challenging, not least due to the existence of multiple HFpEF mimics and a newly identified subset of patients with HFpEF and normal plasma natriuretic peptide concentrations. The lack of effective treatment for these patients represents a major unmet clinical need. Heterogeneity within the patient population has triggered debate over the aetiology and pathophysiology of HFpEF, and the neutrality of randomised clinical trials suggests that we do not fully understand the syndrome(s). Dysregulated nitric oxide-cyclic guanosine monophosphate-protein kinase G signalling, driven by comorbidities and ageing, may be the fundamental abnormality in HFpEF, resulting in a systemic inflammatory state and microvascular endothelial dysfunction. Novel informatics platforms are also being used to classify HFpEF into subphenotypes, based on statistically clustered clinical and biological characteristics: whether such subclassification will lead to more targeted therapies remains to be seen. In this review, we summarise current concepts and controversies, and highlight the diagnostic and therapeutic challenges in clinical practice. Novel treatments and disease management strategies are discussed, and the large gaps in our knowledge identified.

Heart: 04 Jan 2018; epub ahead of print
Zakeri R, Cowie MR
Heart: 04 Jan 2018; epub ahead of print | PMID: 29305560
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diastolic stress echocardiography: from basic principles to clinical applications.

Prasad SB, Holland DJ, Atherton JJ
Heart failure with preserved ejection fraction (HFpEF) looms as a major public heart challenge with increasing prevalence due to an ageing population. Diagnosis can be challenging due to non-specific symptomatology, low natriuretic peptide levels and equivocal diastology on resting echocardiography. Diastolic stress echocardiography represents a non-invasive option to refining the diagnosis in this subset of patients. Diastolic responses to exercise are most commonly measured with a non-invasive measure of left ventricular filling pressures (LVFP) estimated by the ratio of the early mitral inflow wave to early diastolic tissue velocity (E/e\' ratio). This is measured pre- and post-exercise , and is highly feasible. An elevation of exercise E/e\' >15 is classified as an abnormal response as per current guidelines. An alternative measure of exercise-related diastolic performance, the Diastolic Functional Reserve Index has also been proposed, but has not been as well studied as exercise E/e\'. A number of studies have validated exercise E/e\' as a measure of LVFP against invasively measured LVFP using simultaneous echocardiography-catheterisation studies. The independent prognostic value of exercise E/e\' has also been well delineated in a number of studies. While diastolic stress echocardiography can be considered for all patients with suspected HFpEF, it is of particular value in patients with normal or equivocal diastolic indices on resting echocardiography.

Heart: 19 Jul 2018; epub ahead of print
Prasad SB, Holland DJ, Atherton JJ
Heart: 19 Jul 2018; epub ahead of print | PMID: 30030333
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cost-effectiveness of cardiac rehabilitation: a systematic review.

Shields GE, Wells A, Doherty P, Heagerty A, Buck D, Davies LM
Patients may be offered cardiac rehabilitation (CR), a supervised programme often including exercises, education and psychological care, following a cardiac event, with the aim of reducing morbidity and mortality. Cost-constrained healthcare systems require information about the best use of budget and resources to maximise patient benefit. We aimed to systematically review and critically appraise economic studies of CR and its components. In January 2016, validated electronic searches of the National Health Service Economic Evaluation Database (NHS EED), Health Technology Assessment, PsycINFO, MEDLINE and Embase databases were run to identify full economic evaluations published since 2001. Two levels of screening were used and explicit inclusion criteria were applied. Prespecified data extraction and critical appraisal were performed using the NHS EED handbook and Drummond checklist. The majority of studies concluded that CR was cost-effective versus no CR (incremental cost-effectiveness ratios (ICERs) ranged from $1065 to $71 755 per quality-adjusted life-year (QALY)). Evidence for specific interventions within CR was varied; psychological intervention ranged from dominant (cost saving and more effective) to $226 128 per QALY, telehealth ranged from dominant to $588 734 per QALY and while exercise was cost-effective across all relevant studies, results were subject to uncertainty. Key drivers of cost-effectiveness were risk of subsequent events and hospitalisation, hospitalisation and intervention costs, and utilities. This systematic review of studies evaluates the cost-effectiveness of CR in the modern era, providing a fresh evidence base for policy-makers. Evidence suggests that CR is cost-effective, especially with exercise as a component. However, research is needed to determine the most cost-effective design of CR.

Heart: 12 Apr 2018; epub ahead of print
Shields GE, Wells A, Doherty P, Heagerty A, Buck D, Davies LM
Heart: 12 Apr 2018; epub ahead of print | PMID: 29654096
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiovascular imaging in Turner syndrome: state-of-the-art practice across the lifespan.

Mortensen KH, Young L, De Backer J, Silberbach M, ... Lopez L, Roos-Hesselink JW
Cardiovascular imaging is essential to providing excellent clinical care for girls and women with Turner syndrome (TS). Congenital and acquired cardiovascular diseases are leading causes of the lifelong increased risk of premature death in TS. Non-invasive cardiovascular imaging is crucial for timely diagnosis and treatment planning, and a systematic and targeted imaging approach should combine echocardiography, cardiovascular magnetic resonance and, in select cases, cardiac CT. In recent decades, evidence has mounted for the need to perform cardiovascular imaging in all females with TS irrespective of karyotype and phenotype. This is due to the high incidence of outcome-determining lesions that often remain subclinical and occur in patterns specific to TS. This review provides an overview of state-of-the-art cardiovascular imaging practice in TS, by means of a review of the most recent literature, in the context of a recent consensus statement that has highlighted the role of cardiovascular diseases in these females.

Heart: 17 Sep 2018; epub ahead of print
Mortensen KH, Young L, De Backer J, Silberbach M, ... Lopez L, Roos-Hesselink JW
Heart: 17 Sep 2018; epub ahead of print | PMID: 30228249
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Percutaneous coronary intervention for stable coronary artery disease.

Al-Lamee RK, Nowbar AN, Francis DP
The adverse consequences of stable coronary artery disease (CAD) are death, myocardial infarction (MI) and angina. Trials in stable CAD show that percutaneous coronary intervention (PCI) does not reduce mortality. PCI does appear to reduce spontaneous MI rates but at the expense of causing some periprocedural MI. Therefore, the main purpose of PCI is to relieve angina. Indeed, patients and physicians often choose PCI rather than first attempting to control symptoms with anti-anginal medications as recommended by guidelines. Nevertheless, it is unclear how effective PCI is at relieving angina. This is because, whereas anti-anginal medications are universally required to be tested against placebo, there is no such requirement for procedural interventions such as PCI. The first placebo-controlled trial of PCI showed a surprisingly small effect size. This may be because it is overly simplistic to assume that the presence of a stenosis and inducible ischaemia in a patient means that the clinical chest pain they report is caused by ischaemia. In this article, we review the evidence base and argue that if we as a medical specialty wish to lead the science of procedures for symptom control, we should recognise the special merit of placebo-controlled experiments.

Heart: 20 Sep 2018; epub ahead of print
Al-Lamee RK, Nowbar AN, Francis DP
Heart: 20 Sep 2018; epub ahead of print | PMID: 30242142
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Exercise recommendations in patients with valvular heart disease.

Gati S, Malhotra A, Sharma S
Valvular heart disease affects 1%-2% of young individuals, many of whom aspire to partake in competitive sport or high intensity recreational exercise. There are limited reports on the impact of intensive physical activity on the progression of valvular heart disease; therefore, current recommendations are based on consensus opinion. The management of exercising individuals with valvular heart disease requires a structured approach that incorporates several key factors including symptomatic status, functional capacity, type and nature of the valvular lesion, impact on ventricular structure and function and effect on pulmonary artery pressure. Asymptomatic individuals with minor valvular abnormalities may engage in all forms of competitive sport, whereas those with lesions of moderate severity may exercise intensively if an exercise stress test tailored to the relevant physical activity reveals good functional capacity without myocardial ischaemia, haemodynamic disturbances or arrhythmia. Symptomatic athletes and those with severe valvular heart disease, impaired ventricular function, pulmonary hypertension and arrhythmias should refrain from most competitive sports. Athletes with a bicuspid aortic valve and aortic root diameter >40 mm should avoid sport with a strong isometric component even with minimal valvular dysfunction. There is an association between mitral valve prolapse and sudden cardiac death in the general population; however, there is limited evidence of increased risk with competitive sport. Athletes undergoing corrective surgery may return to exercise after 3 months if ventricular function and exercise capacity are preserved. Individuals anticoagulated for mechanical bioprosthetic valves should avoid contact or collision sport to minimise the risk of bleeding.

Heart: 26 Sep 2018; epub ahead of print
Gati S, Malhotra A, Sharma S
Heart: 26 Sep 2018; epub ahead of print | PMID: 30262455
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Evaluation of aortic regurgitation with cardiac magnetic resonance imaging: a systematic review.

Lee JC, Branch KR, Hamilton-Craig C, Krieger EV
This review summaries the utility, application and data supporting use of cardiac magnetic resonance imaging (CMR) to evaluate and quantitate aortic regurgitation. We systematically searched Medline and PubMed for original research articles published since 2000 that provided data on the quantitation of aortic regurgitation by CMR and identified 11 articles for review. Direct aortic measurements using phase contrast allow quantitation of volumetric flow across the aortic valve and are highly reproducible and accurate compared with echocardiography. However, this technique requires diligence in prescribing the correct imaging planes in the aorta. Volumetric analytic techniques using differences in ventricular volumes are also highly accurate but less than phase contrast techniques and only accurate when concomitant valvular disease is absent. Comparison of both aortic and ventricular data for internal data verification ensures fidelity of aortic regurgitant data. CMR data can be applied to many types of aortic valve regurgitation including combined aortic stenosis with regurgitation, congenital valve diseases and post-transcatheter valve placement. CMR also predicts those patients who progress to surgery with high overall sensitivity and specificity. Future studies of CMR in patients with aortic regurgitation to quantify the incremental benefit over echocardiography as well as prediction of cardiovascular events are warranted.

Heart: 30 Dec 2017; 104:103-110
Lee JC, Branch KR, Hamilton-Craig C, Krieger EV
Heart: 30 Dec 2017; 104:103-110 | PMID: 28822982
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Achieving high-quality care: a view from NICE.

Leng G, Partridge G
The National Institute for Health and Care Excellence (NICE) was established in 1999 to provide evidence-based guidance. The task of producing guidance by reviewing primary research data and using an advisory committee to develop evidence-based recommendations, is not straightforward. Guidance production is, however, less challenging than the task of putting evidence-based recommendations into practice.NICE is very sensitive to this challenge as, since 1999, over 1500 pieces of NICE guidance have been published. A number of pieces of guidance relate to heart disease, including pharmaceutical agents, new medical technologies and clinical guidelines. Examples include guidelines on acute heart failure and atrial fibrillation, and advice on technologies including edoxaban and implantable cardioverter defibrillators.The research evidence is clear that a change in practice rarely comes about as a result of simply disseminating guidance on best practice. Simple dissemination is particularly ineffective if the guidance has not been produced by a well-respected, credible organisation. It is also clear from the literature that implementation is more successful when more than one approach is taken, and when there is alignment between efforts at organisational, local and national levels.At an organisational level, there should be support from the Board for quality improvement, with ongoing measurement of progress. Resources should be provided for targeted change programmes, particularly where new guidance suggests improvements are required. A systematic process for putting change in place should include identifying barriers to change, agreeing interventions to overcome the barriers and drive forward improvement and planning for implementation and evaluation.

Heart: 30 Dec 2017; 104:10-15
Leng G, Partridge G
Heart: 30 Dec 2017; 104:10-15 | PMID: 28912290
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Computational modelling for congenital heart disease: how far are we from clinical translation?

Biglino G, Capelli C, Bruse J, Bosi GM, Taylor AM, Schievano S
Computational models of congenital heart disease (CHD) have become increasingly sophisticated over the last 20 years. They can provide an insight into complex flow phenomena, allow for testing devices into patient-specific anatomies (pre-CHD or post-CHD repair) and generate predictive data. This has been applied to different CHD scenarios, including patients with single ventricle, tetralogy of Fallot, aortic coarctation and transposition of the great arteries. Patient-specific simulations have been shown to be informative for preprocedural planning in complex cases, allowing for virtual stent deployment. Novel techniques such as statistical shape modelling can further aid in the morphological assessment of CHD, risk stratification of patients and possible identification of new \'shape biomarkers\'. Cardiovascular statistical shape models can provide valuable insights into phenomena such as ventricular growth in tetralogy of Fallot, or morphological aortic arch differences in repaired coarctation. In a constant move towards more realistic simulations, models can also account for multiscale phenomena (eg, thrombus formation) and importantly include measures of uncertainty (ie, CIs around simulation results). While their potential to aid understanding of CHD, surgical/procedural decision-making and personalisation of treatments is undeniable, important elements are still lacking prior to clinical translation of computational models in the field of CHD, that is, large validation studies, cost-effectiveness evaluation and establishing possible improvements in patient outcomes.

Heart: 30 Oct 2016; epub ahead of print
Biglino G, Capelli C, Bruse J, Bosi GM, Taylor AM, Schievano S
Heart: 30 Oct 2016; epub ahead of print | PMID: 27798056
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Acute stress-induced (takotsubo) cardiomyopathy.

Dawson DK
Acute stress-induced (takotsubo) cardiomyopathy has a dramatic clinical presentation, mimicking an acute myocardial infarction and is triggered by intense emotional or physical stress. In this paper, we review the current state of knowledge of the mechanistic physiology underlying the left ventricular ballooning. The pathophysiology of the recovery from this acute heart failure syndrome is presented. The short-term and long-term outlook puts this new syndrome on a different perspective compared with recently held views. Current knowledge on susceptibility and predisposition already define distinctive characteristics of patients with takotsubo compared with myocardial infarction. Gaps in knowledge and future directions of research are identified in order to best direct efforts for identifying specific therapies for this condition, in the acute setting, to mitigate postacute symptoms or to prevent recurrences, none of which exist.

Heart: 30 Dec 2017; 104:96-102
Dawson DK
Heart: 30 Dec 2017; 104:96-102 | PMID: 28824005
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Exercise-induced syncope in a 22-year-old man.

Yeo C, Tan VH, Wong KC
A 22-year-old man was referred to us for syncope during a game of Captain\'s ball. There was no prodrome. His friends did not notice any ictal movements. He was otherwise well prior to passing out. He was not taking any medications or supplements. He was not usually physically active, but was otherwise well with no significant medical history. This is his first episode of syncope. There was no history of cardiac arrest or seizures. There is no family history of premature sudden cardiac death.Physical examination was normal. ECG at rest demonstrated sinus rhythm with corrected QT interval of 400 ms. Echocardiography revealed a structurally normal heart. Holter monitoring was normal. Treadmill exercise stress test demonstrated the following rhythm on figure 1 during stage 4 Bruce protocol. Stress test was terminated in view of sustained arrhythmia as illustrated. He felt light-headed during the period, but otherwise felt that he could carry on with the exercise. ECG during recovery was unremarkable.

Heart: 30 Oct 2016; epub ahead of print
Yeo C, Tan VH, Wong KC
Heart: 30 Oct 2016; epub ahead of print | PMID: 27798055
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Chronic heart failure management and remote haemodynamic monitoring.

Wolfson AM, Fong M, Grazette L, Rahman JE, Shavelle DM
Heart failure (HF) has a large societal and economic burden and is expected to increase in magnitude and complexity over the ensuing years. A number of telemonitoring strategies exploring remote monitoring and management of clinical signs and symptoms of congestion in HF have had equivocal results. Early studies of remote haemodynamic monitoring showed promise, but issues with device integrity and implantation-associated adverse events hindered progress. Nonetheless, these early studies established that haemodynamic congestion precedes clinical congestion by several weeks and that remote monitoring of intracardiac pressures may be a viable and practical management strategy. Recently, the safety and efficacy of remote pulmonary artery pressure-guided HF management was established in a prospective, single-blind trial where randomisation to active pressure-guided HF management reduced future HF hospitalisations. Subsequent commercial use studies reinforced the utility of this technology and post hoc analyses suggest that tight haemodynamic management of patients with HF may be an additional pillar of therapy alongside established guideline-directed medical and device therapy. Currently, there is active exploration into utilisation of this technology and management paradigm for the timing of implantation of durable left ventricular assist devices (LVAD) and even optimisation of LVAD therapy. Several ongoing clinical trials will help clarify the extent and utility of this strategy along the spectrum of patient with HF from individuals with chronic, stable HF to those with more advanced disease requiring heart replacement therapy.

Heart: 17 Aug 2018; epub ahead of print
Wolfson AM, Fong M, Grazette L, Rahman JE, Shavelle DM
Heart: 17 Aug 2018; epub ahead of print | PMID: 30121633
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Electrocardiography in athletes: normal and abnormal findings.

Prutkin JM, Wilson MG
Many sporting organisations recommend a pre-participation ECG to screen for disorders which predispose to sudden cardiac arrest (SCA). The ability of the ECG to perform accurately is dependent on the ECG criteria used and the experience of the operator. There have been several ECG criteria over the last decade, though these were recently superseded with the publication of the \'International Consensus Criteria for ECG Interpretation in Athletes\'. These criteria use the latest evidence to improve specificity while maintaining sensitivity for ECG-detectable pathologies associated with SCA. Accordingly, this review describes the normal, borderline and abnormal ECG findings in an asymptomatic athlete aged 12-35 years.

Heart: 17 Aug 2018; epub ahead of print
Prutkin JM, Wilson MG
Heart: 17 Aug 2018; epub ahead of print | PMID: 30121634
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Demonstration of living anatomy clarifies the morphology of interatrial communications.

Mori S, Nishii T, Tretter JT, Spicer DE, Hirata KI, Anderson RH
Inferences made regarding the postnatal anatomy of the atrial septum still tend to be based on developmental evidence. Although atrial septation is a well-defined process, it is remarkably complex and remains poorly understood. It is now established, however, that the process involves the conjugation of several myocardial structures and mesenchymal tissues of both intracardiac and extracardiac origin. The resultant postnatal morphology is equally complex, evidenced by the fact that, in the normal heart, only the floor of the oval fossa, along with its anteroinferior muscular buttress, are true anatomical septums. In this regard, septums can be defined as partitions that can be removed without creating communications with the extracavitary space. The true septal components are surrounded by grooves, which themselves largely represent infolding of the atrial walls. These anatomical features can now accurately be revealed using virtual dissection of CT data sets. These images, when carefully reconstructed, demonstrated the anatomy with as much accuracy as when hearts are dissected in the autopsy room. Such virtual dissection, furthermore, shows the components as they are seen within the chest, thus facilitating understanding for those intending to undertake interventional therapeutic procedures. By preparing such images, we show the complexity of the normal atrial septum and its surrounds. We show that it is only defects within the oval fossa, or the much rarer vestibular defects, which can appropriately be illustrated in the context of a normally constructed heart.

Heart: 03 Sep 2018; epub ahead of print
Mori S, Nishii T, Tretter JT, Spicer DE, Hirata KI, Anderson RH
Heart: 03 Sep 2018; epub ahead of print | PMID: 30181201
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Genetics of syndromic and non-syndromic mitral valve prolapse.

Le Tourneau T, Mérot J, Rimbert A, Le Scouarnec S, ... Levine RA, Schott JJ
Mitral valve prolapse (MVP) is a common condition that affects 2%-3% of the general population. MVP is thought to include syndromic forms such as Marfan syndrome and non-syndromic MVP, which is the most frequent form. Myxomatous degeneration and fibroelastic deficiency (FED) are regarded as two different forms of non-syndromic MVP. While FED is still considered a degenerative disease associated with ageing, frequent familial clustering has been demonstrated for myxomatous MVP. Familial and genetic studies led to the recognition of reduced penetrance and large phenotypic variability, and to the identification of prodromal or atypical forms as a part of the complex spectrum of the disease. Whereas autosomal dominant mode is the common inheritance pattern, an X linked form of non-syndromic MVP was recognised initially, related to Filamin-A gene, encoding for a cytoskeleton protein involved in mechanotransduction. This identification allowed a comprehensive description of a new subtype of MVP with a unique association of leaflet prolapse and paradoxical restricted motion in diastole. In autosomal dominant forms, three loci have been mapped to chromosomes 16p11-p12, 11p15.4 and 13q31-32. Although deciphering the underlying genetic defects is still a work in progress, DCHS1 mutations have been identified (11p15.4) in typical myxomatous disease, highlighting new molecular pathways and pathophysiological mechanisms leading to the development of MVP. Finally, a large international genome-wide association study demonstrated the implication of frequent variants in MVP development and opened new directions for future research. Hence, this review focuses on phenotypic, genetic and pathophysiological aspects of MVP.

Heart: 18 Jan 2018; epub ahead of print
Le Tourneau T, Mérot J, Rimbert A, Le Scouarnec S, ... Levine RA, Schott JJ
Heart: 18 Jan 2018; epub ahead of print | PMID: 29352010
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic importance of late gadolinium enhancement cardiovascular magnetic resonance in cardiomyopathy.

Ismail TF, Prasad SK, Pennell DJ
Cardiovascular magnetic resonance has revolutionised the diagnosis of cardiomyopathy, particularly through the use of late gadolinium enhancement imaging which provides the unique opportunity to assess myocardial fibrosis in vivo. More recently, the prognostic capability of cardiovascular magnetic resonance to predict outcomes has been assessed. Traditional risk markers do not at present adequately predict outcomes in either dilated cardiomyopathy or hypertrophic cardiomyopathy, which are the two most common causes of primary heart muscle disease. Many of these existing markers reflect underlying disease severity. Given the important role fibrosis is thought to play in the pathogenesis and sequelae of these cardiomyopathies, the presence and amount of fibrosis has been proposed as a potential novel risk factor for adverse events. This paper reviews the evidence for late gadolinium enhancement as a prognostic marker in dilated and hypertrophic cardiomyopathy and highlights the challenges ahead.

Heart: 30 Nov 2011; epub ahead of print
Ismail TF, Prasad SK, Pennell DJ
Heart: 30 Nov 2011; epub ahead of print | PMID: 22128204
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

24 Oxidative stress and endothelial dysfunction in high-fat diet-induced obesity in mice.

Du J, J-Mei
Dietary overweight is a major risk factor for the development of cardiovascular diseases. However the effects of high-fat diet (HFD) on vascular oxidative status and endothelial function remain unknown. In this study, we used a mouse model of HFD-induced obesity in C57BL/6 J mice and investigated the relationship between HFD, metabolic disorders and vascular dysfunction. Mice (7 m, n=10/group) were fed with a HFD (45% kcal fat) for 16 weeks. The control mice were fed with a normal chow diet (NCD, 12% kcal fat). Body weight, blood pressure and fasting blood glucose were taken before and after diet intervention. Compared to age-matched control mice, HFD increased significantly the body weight (NCD 42±2.3 vs HFD 56±3.2 g), the fasting blood glucose (NCD 7.4±3.3 vs HFD 8.8±2.2 mM) and the blood pressure (NCD 127±8 vs HFD 142±12 mm Hg). Vascular function was examined using aorta rings by an organ bath. Compared with control mice, HFD increased significantly the levels of vasoconstriction to phenylephrine (Emax NCD 0.15±0.03 vs HFD 0.32±0.07 g), and decreased endothelium-dependent vessel relaxation to acetylcholine (Emax NCD 80.45±7.39% vs HFD 74.41±1.74%), and these were corrected to the control levels by adding a superoxide scavenger, tiron. Accompanied with the vascular dysfunction, there were significant increases (42±5%) in the levels of ROS production in the aortas of HFD-fed mice as compared to the control aortas. In conclusion, HFD and obesity-related metabolic disorders induce vasculature oxidative stress, which contributes to endothelial dysfunction and high blood pressure.

Heart: 25 Nov 2011; 97:x-e8
Du J, J-Mei
Heart: 25 Nov 2011; 97:x-e8 | PMID: 22116930
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

22 The role of oxidative stress in the development of endothelial dysfunction and hypertension in ageing.

Cahill-Smith S, Li JM
Excess endothelial production of reactive oxygen species (ROS) has been found to play a major role in the pathogenesis of many cardiovascular diseases. Ageing is a primary risk factor of cardiovascular diseases, however the role of oxidative stress in the development of vascular dysfunction in the elderly remains unknown. In this study we used wild-type C57BL/6 J mice, at young (3-4 m) and old (20-24 m) age to investigate the potential role of ROS in age-related metabolic disorders and vascular dysfunction. The body weight, heart weight and fasting serum glucose were recorded. There was no significant difference in the heart/body weight ratio, and the fasting glucose between the two groups. However, there was a significant increase in blood pressure in ageing mice (141 mm Hg) compared to young mice (126 mm Hg) measured by volume pressure recording tail plethysmography. Vascular tone was examined using aortic rings in an organ bath. There was no significant difference in vessel relaxation to a NO donor (sodium nitroprusside) between the young and ageing mice. However, there was a significant decrease in endothelium- dependent vessel relaxation to acetylcholine in ageing mice compared to young mice. There was a significant increase in the levels of superoxide production by the ageing vessels compared to the young controls as measured using lucigenin-chemiluminescence. In conclusion, there was a significant increase in the levels of ROS production in the vasculature of ageing mice, which might contribute to the age-related endothelial dysfunction and high blood pressure.

Heart: 25 Nov 2011; 97:v-e8
Cahill-Smith S, Li JM
Heart: 25 Nov 2011; 97:v-e8 | PMID: 22116929
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

18 Hypoxia-driven Hand1 expression controls changes in cardiac metabolism around birth.

Breckenridge RA, Neary MT, Bennett M, Kotecha S, Griffin J, Mohun TJ
Little is known about the changes occurring in the heart at birth. Immediately following birth, cardiac output rapidly increases, and to facilitate this, the predominant mode of cardiac energy generation shifts from glycolysis to Î(2)-oxidation of lipid. This is relevant to adult cardiac failure, as energy metabolism in failing hearts shifts back to glycolysis. Currently, control of cardiac energy substrate selection is incompletely understood. The b-HLH transcription factor Hand1 has been implicated in cardiac development, and levels of Hand1 RNA are altered in several types of cardiac failure associated with metabolic remodelling. Here we show that cardiac Hand1 RNA levels fall rapidly after birth, directly in response to changes in cardiac hypoxia signalling. Prevention of the postnatal fall in cardiac Hand1 transcription in transgenic neonates results in a lethal phenotype of cardiac rupture. We observe alterations in gene expression, cardiac acyl-carnitine metabolism and overall lipid metabolism consistent with reduced fatty acid mitochondrial import. We speculate that Hand1 transcription is regulated by hypoxia signalling and thus link ambient oxygen concentration to metabolic substrate selection. This is a novel function for Hand1, which has been implicated in control of development of the heart, placenta and neural tube-all processes that are known to be in some way influenced by hypoxia signalling.

Heart: 25 Nov 2011; 97:e8
Breckenridge RA, Neary MT, Bennett M, Kotecha S, Griffin J, Mohun TJ
Heart: 25 Nov 2011; 97:e8 | PMID: 22116908
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Influenza vaccine as a coronary intervention for prevention of myocardial infarction.

MacIntyre CR, Mahimbo A, Moa AM, Barnes M
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Influenza is one of the leading infectious causes of morbidity and mortality globally, and evidence is accumulating that it can precipitate acute myocardial infarction (AMI). This is thought to be due to a range of factors including inflammatory release of cytokines, disruption of atherosclerotic plaques and thrombogenesis, which may acutely occlude a coronary artery. There is a large body of observational and clinical trial evidence that shows that influenza vaccine protects against AMI. Estimates of the efficacy of influenza vaccine in preventing AMI range from 15% to 45%. This is a similar range of efficacy compared with the accepted routine coronary prevention measures such as smoking cessation (32-43%), statins (19-30%) and antihypertensive therapy (17-25%). Influenza vaccine should be considered as an integral part of CVD management and prevention. While it is recommended in many guidelines for patients with CVD, rates of vaccination in risk groups aged <65 years are very low, in the range of 30%. The incorporation of vaccination into routine CVD prevention in patient care requires a clinical practice paradigm change.

Heart: 29 Sep 2016; epub ahead of print
MacIntyre CR, Mahimbo A, Moa AM, Barnes M
Heart: 29 Sep 2016; epub ahead of print | PMID: 27686519
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A case of recent myocardial infarction with cardiac failure.

Nair A, Sajeev CG, Muneer K
A 50-year-old hypertensive smoker presented with a typical angina of 2 days duration. An urgent ECG revealed extensive anterior wall myocardial infarction. In view of the delayed presentation, the patient was conservatively managed with heparin. In-hospital echocardiogram showed akinesia of entire left anterior descending artery (LAD) territory with severe left ventricular (LV) dysfunction. He was discharged with a plan for early coronary intervention. However, he presented a fortnight later with acute pulmonary oedema. General appraisal revealed a restless individual who was dyspnoeic and diaphoretic at rest. On clinical examination, the patient was in hypotension with features of biventricular failure. A 12-lead ECG showed QS pattern with persistent ST segment elevation in precordial leads. The chest radiograph demonstrated features of pulmonary oedema, cardiomegaly and bilateral pleural effusion. Creatine Phosphokinase-MB (CPK-MB) was negative. A preliminary transthoracic echocardiography was done (figure 1 and see online supplementary video 1).

Heart: 29 Sep 2016; epub ahead of print
Nair A, Sajeev CG, Muneer K
Heart: 29 Sep 2016; epub ahead of print | PMID: 27686517
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Toxicity of cancer therapy: what the cardiologist needs to know about angiogenesis inhibitors.

Dobbin SJH, Cameron AC, Petrie MC, Jones RJ, Touyz RM, Lang NN
Clinical outcomes for patients with a wide range of malignancies have improved substantially over the last two decades. Tyrosine kinase inhibitors (TKIs) are potent signalling cascade inhibitors and have been responsible for significant advances in cancer therapy. By inhibiting vascular endothelial growth factor receptor (VEGFR)-mediated tumour blood vessel growth, VEGFR-TKIs have become a mainstay of treatment for a number of solid malignancies. However, the incidence of VEGFR-TKI-associated cardiovascular toxicity is substantial and previously under-recognised. Almost all patients have an acute rise in blood pressure, and the majority develop hypertension. They are associated with the development of left ventricular systolic dysfunction (LVSD), heart failure and myocardial ischaemia and can have effects on myocardial repolarisation. Attention should be given to rigorous baseline assessment of patients prior to commencing VEGFR-TKIs, with careful consideration of baseline cardiovascular risk factors. Baseline blood pressure measurement, ECG and cardiac imaging should be performed routinely. Hypertension management currently follows national guidelines, but there may be a future role forendothelin-1 antagonism in the prevention or treatment of VEGFR-TKI-associated hypertension. VEGFR-TKI-associated LVSD appears to be independent of dose and is reversible. Patients who develop LVSD and heart failure should be managed with conventional heart failure therapies, but the role of prophylactic therapy is yet to be defined. Serial monitoring of left ventricular function and QT interval require better standardisation and coordinated care. Management of these complex patients requires collaborative, cardio-oncology care to allow the true therapeutic potential from cancer treatment while minimising competing cardiovascular effects.

Heart: 17 Sep 2018; epub ahead of print
Dobbin SJH, Cameron AC, Petrie MC, Jones RJ, Touyz RM, Lang NN
Heart: 17 Sep 2018; epub ahead of print | PMID: 30228246
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex differences in cardiovascular ageing.

Merz AA, Cheng S
Despite recent progress in identifying and narrowing the gaps in cardiovascular outcomes between men and women, general understanding of how and why cardiovascular disease presentations differ between the sexes remains limited. Sex-specific patterns of cardiac and vascular ageing play an important role and, in fact, begin very early in life. Differences between the sexes in patterns of age-related cardiac remodelling are associated with the relatively greater prevalence in women than in men of heart failure with preserved ejection fraction. Similarly, sex variation in how vascular structure and function change with ageing contributes to differences between men and women in how coronary artery disease manifests typically or atypically over the adult life course. Both hormonal and non-hormonal factors underlie sex differences in cardiovascular ageing and the development of age-related disease. The midlife withdrawal of endogenous oestrogen appears to augment the age-related increase in cardiovascular risk seen in postmenopausal compared with premenopausal women. However, when compared with intrinsic biological differences between men and women that are present throughout life, this menopausal transition may not be as substantial an actor in determining cardiovascular outcomes.

Heart: 25 Feb 2016; epub ahead of print
Merz AA, Cheng S
Heart: 25 Feb 2016; epub ahead of print | PMID: 26917537
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Percutaneous repair of paravalvular prosthetic regurgitation: patient selection, techniques and outcomes.

Sorajja P, Bae R, Lesser JA, Pedersen WA
Paravalvular prosthetic regurgitation is common, affecting 5-10% of surgical prostheses and 40-70% of transcatheter valves. While many patients may suffer no significant morbidity, paravalvular prosthetic regurgitation can lead to heart failure and haemolytic anaemia, and, in some studies, has been associated with impaired survival. Over the past several years, percutaneous repair of paravalvular prosthetic regurgitation has been demonstrated to be a highly efficacious therapy. When performed in experienced centres, procedural success with percutaneous repair occurs in 90% of patients. Due to the complex nature of the techniques, there is a significant learning curve with a high potential for prolonged procedures (∼2.5 h) and complications (∼5%), although death is rare (∼0.5%). Percutaneous repair of paravalvular prosthetic regurgitation requires a close collaboration between imaging specialists, surgeons and the interventional operators. Importantly, successful percutaneous repair obviates the need for open surgical correction, which can be high risk or prohibitive due to the need for reoperation in the setting of comorbidities. Herein, we discuss appropriate patient selection, the catheter-based techniques and outcomes of percutaneous repair for symptomatic paravalvular prosthetic regurgitation.

Heart: 12 Feb 2015; epub ahead of print
Sorajja P, Bae R, Lesser JA, Pedersen WA
Heart: 12 Feb 2015; epub ahead of print | PMID: 25678496
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart failure in a neonate with multiple cardiac masses.

Nasr E, Ibrahim M, Yacoub M
A 16-day-old male neonate weighing 3.4 kg presented with severe heart failure. His heart rate was 190/min, normal sinus rhythm, blood pressure was 55/30 mm Hg and respiratory rate was 65/min. Transthoracic echocardiography and cardiac MRI showed multiple intracardiac masses; the largest was filling most of the left ventricular cavity (figure 1A) (see online supplementary video 1 and figure S1), measuring around 2.8 cm×1.8 cm and arising from the apical septum. Left ventricular function was moderately impaired with an ejection fraction of 40%. Due to accelerated haemodynamic instability, the mass was excised surgically. Through left ventriculotomy, a large mass could be identified which was attached with a pedicle to the apical septum. This mass was excised with its pedicle.During early postoperative course, the patient developed subdural and intraventricular haemorrhage, necessitating insertion of a ventriculoperitoneal shunt. MRI of the brain showed dark-signalled subependymal nodules and multiple cortical patches of high T2 signals (see online supplementary figure S2). The patient had no neurological sequelae and was discharged home.The patient was discharged home with no neurological sequelae. During the 2-year follow-up period, serial echocardiograms showed regression of the rest of the cardiac tumours and improvement of cardiac functions (see online supplementary figure S3). However, fibrous plaques were observed on the child\'s forehead.

Heart: 21 Sep 2016; epub ahead of print
Nasr E, Ibrahim M, Yacoub M
Heart: 21 Sep 2016; epub ahead of print | PMID: 27655257
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Asymptomatic severe aortic stenosis: challenges in diagnosis and management.

Izumi C
Optimal management for asymptomatic severe aortic stenosis (AS) remains controversial. Considering the increase in elderly patients, improved surgical outcomes and the introduction of transcatheter aortic valve implantation, we must reconsider the optimal management of asymptomatic severe AS. In this article, previous studies regarding the natural history of asymptomatic severe AS were reviewed to obtain a clinical perspective of AS in the growing elderly patient population. The incidence of sudden death in asymptomatic severe AS varies among studies from 0.25% to 1.7% per year, with differences related to study design and patient background. Except for very severe AS, sudden death or AS-related cardiac death without preceding symptoms is uncommon if \'watchful\' waiting strategy is possible. Therefore, early operation is reasonable in very severe AS, but it is not recommended for all patients with severe AS. Using exercise tests, plasma levels of natriuretic peptides and other parameters, risk stratification of asymptomatic severe AS is needed to select patients who may have greater benefit following early operation. On the other hand, \'watchful\' waiting is not always possible in real world of our practice. Patient education and periodic echocardiography are essential in \'watchful\' waiting, which is not simply waiting strategy without careful monitoring. Individualised discussion regarding the indication for early operation is necessary, considering age, clinical background, predicted natural history and operative risk in each patient.

Heart: 18 Apr 2016; epub ahead of print
Izumi C
Heart: 18 Apr 2016; epub ahead of print | PMID: 27091844
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiac issues in adults with the mucopolysaccharidoses: current knowledge and emerging needs.

Braunlin E, Wang R
The growing availability of innovative treatments for rare genetic diseases with a cardiac component-such as the mucopolysaccharidoses (MPSs)-has changed these syndromes from \'back of the textbook\' curiosities of childhood to chronic, but rare, adult cardiac conditions that require both centres of expertise and knowledgeable subspecialists. The MPSs are inherited progressive lysosomal storage diseases, occurring in about 1:25 000 births and resulting from absence of functional hydrolases responsible for the degradation of glycosaminoglycans, naturally occurring complex sugars ubiquitous throughout the body. In the heart, accumulation of glycosaminoglycans occurs within the cardiac valves, the epicardial coronary arteries, the myocytes and cardiac interstitium and the walls of the great vessels. As a consequence, cardiac valve regurgitation and stenosis, diffuse coronary artery stenosis, myocardial dysfunction and aortic root dilation often occur. Haematopoietic cell transplantation and enzyme replacement therapy have changed the previously lethal natural history of the MPSs to one of survival well into adulthood. Despite this improved lifespan, the left-sided cardiac valves continue to show progressive functional involvement and cardiac valve replacement is not uncommon, especially in adults. The risk of any intervention is increased in these patients because of the systemic effects of the disease on the respiratory system and cervical cord. Our current understanding of other cardiac issues in adults with the MPSs, especially with the coronary circulation and myocardium, is meagre and more needs to be known to effectively care for this emerging population of adults. Incorporation of the MPSs, as well as other now-treatable rare diseases, into the educational curriculum of current and future adult subspecialists is an important next step.

Heart: 21 Apr 2016; epub ahead of print
Braunlin E, Wang R
Heart: 21 Apr 2016; epub ahead of print | PMID: 27102649
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The emerging burden of hospital admissions of adults with congenital heart disease.

Verheugt CL, Uiterwaal CS, van der Velde ET, Meijboom FJ, ... Grobbee DE, Mulder BJ
Objective To assess the extent and the characteristics of hospital admissions in registered adult patients with congenital heart disease. Design Observational cohort study. Setting The Netherlands. Patients 5798 adult patients with congenital heart disease from the Dutch CONCOR national registry linked to the Dutch National Medical Registration (Prismant). Main outcome measures All hospital admissions from the years 2001 up until 2006. Results During 28 990 patient-years, 2908 patients (50%) were admitted to hospital. Median age at admission was 39 years (range 18-86 years); 46% were male. Admission rate in CONCOR patients was high among all ages (range 11-68%) and exceeded that of the general Dutch population two to three times; this difference was most pronounced in the older age groups. Altogether there were 8916 admissions, 5411 (61%) of which were for cardiovascular indications. Among cardiovascular admissions, referrals for arrhythmias were most common (31%). Of 4926 interventions, 2459 (50%) were cardiovascular, most often reparative interventions or cardioversion (53%). Most non-cardiovascular admissions were obstetric. Among defects, univentricular heart and tricuspid atresia had the highest incidence and duration of admission. Conclusions Healthcare utilisation in registered and medically supervised adult patients with congenital heart disease is high and increases with age. Admission rates are at least two times higher than in the general population, and most marked in the older age groups. With the ageing of this population, a major increase in healthcare utilisation is imminent in the near future. Timely preparation of healthcare resources is crucial to sustain optimal care.

Heart: 21 Apr 2010; epub ahead of print
Verheugt CL, Uiterwaal CS, van der Velde ET, Meijboom FJ, ... Grobbee DE, Mulder BJ
Heart: 21 Apr 2010; epub ahead of print | PMID: 20406765
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Physical activity in the prevention of coronary heart disease: implications for the clinician.

Varghese T, Schultz WM, McCue AA, Lambert CT, ... Franklin BA, Sperling LS
Cardiovascular disease (CVD) continues to be a leading cause of death worldwide. Because regular physical activity (PA) independently decreases the risk of coronary heart disease (CHD) while also having a positive, dose-related impact on other cardiovascular (CV) risk factors, it has increasingly become a focus of CHD prevention. Current guidelines recommend 30 min of moderate-intensity PA 5 days a week, but exercise regimens remain underused. PA adherence can be fostered with a multilevel approach that involves active individual participation, physician counselling and health coaching, community involvement, and policy change, with incorporation of cardiac rehabilitation for patients requiring secondary prevention. Viewing exercise quantity as a vital sign, prescribing PA like a medication, and using technology, such as smartphone applications, encourage a global shift in focus from CVD treatment to prevention. Community-wide, home-based and internet-based prevention initiatives may also offer a developing pool of resources that can be tapped into to promote education and PA compliance. This review summarises the underlying rationale, current guidelines for and recommendations to cultivate a comprehensive focus in the endorsement of PA in the primary and secondary prevention of CHD.

Heart: 03 Mar 2016; epub ahead of print
Varghese T, Schultz WM, McCue AA, Lambert CT, ... Franklin BA, Sperling LS
Heart: 03 Mar 2016; epub ahead of print | PMID: 26941396
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Familial transposition of great arteries caused by multiple mutations in laterality genes.

De Luca A, Sarkozy A, Consoli F, Ferese R, ... Marino B, Dallapiccola B
Background: The pathogenesis of transposition of the great arteries (TGA) is still largely unknown. In general, TGA is not associated with the more common genetic disorders nor with extracardiac anomalies, while it can be found in individuals with lateralization defects, heterotaxy and asplenia syndrome (right isomerism). Objective: Analyze genes previously associated to heterotaxy in order to assess mutations in familial TGA unassociated with other features of laterality defects. Methods: Probands of 7 families with isolated TGA and family history of concordant or discordant CHDs were screened for mutations in the ZIC3, ACVR2B, LEFTYA, CFC1, NODAL, FOXH1, GDF1, CRELD1, GATA4 and NKX2.5 genes. Results: Mutation analysis allowed the identification of 3 sequence variations in 2 out of 7 TGA probands. A FOXH1 (Pro21Ser) missense variant was found in a proband who was also heterozogous for an amino acid substitution (Gly17Cys) in ZIC3 gene. This ZIC3 variant was also found in another family member with a second sequence variation (Val150Ile) in the NKX2.5 gene homeodomain who was affected by multiple ventricular septal defects. A second proband was found to harbor a splice site variant (IVS2-1G>C) in NODAL gene. Conclusions: The present study provides evidence that some cases of familial TGA are caused by mutations in laterality genes and thereby are part of the same disease spectrum of heterotaxy syndrome, and argues for an oligogenic or complex mode of inheritance in these pedigrees.

Heart: 25 Nov 2009; epub ahead of print
De Luca A, Sarkozy A, Consoli F, Ferese R, ... Marino B, Dallapiccola B
Heart: 25 Nov 2009; epub ahead of print | PMID: 19933292
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

20 Increased activity of mitochondrial complex II in rabbit heart failure is associated with reactive oxygen species generation and impaired excitation-contraction coupling.

Seidlmayer L, Blatter LA, Dedkova EN
Background In heart failure (HF), the increase in cardiac adrenergic tone, while initially beneficial, ultimately contributes to damage to the failing heart. The aim of this study was to evaluate the mechanisms responsible for cell damage during β-adrenergic stimulation in a rabbit volume- and pressure-overload HF model. Methods and Results Field stimulation (1 Hz) of single left ventricular HF myocytes in combination with β-adrenergic stimulation (isoproterenol, 1 μM) was accompanied by spontaneous pro-arrhythmogenic Ca(2+) release (Ca(2+) waves), contractile dysfunction, and a robust increase in reactive oxygen species (ROS) production, eventually leading to cell death. Surprisingly, in HF myocytes FAD/FADH2 levels remained reduced and mitochondrial complex II (succinate dehydrogenase) activity was significantly elevated (by 86%). Increased complex II activity, however did not lead to an increase in ADP-dependent respiration, indicative of an electron leak at complex II. Mitochondrial complex I-mediated state-3 respiration was decreased by 77%, while state-2 respiration remained unchanged. Supplementation of HF myocytes with substrate for complex II (10 mM dimethyl-succinate) caused a dramatic increase in rotenone-sensitive mitochondrial ROS generation compared to control cells and to HF cells treated with complex I substrates. Moreover, dimethyl-succinate itself induced spontaneous Ca(2+) release in form of Ca(2+) waves that was further augmented by isoproterenol. Cell treatment with complex II inhibitor thenoyl-trifluoroacetone (100 μM) significantly decreased mitochondrial ROS generation and normalised isoproterenol-induced Ca(2+)-transients and cell shortening. Conclusion Increased activity of mitochondrial complex II in rabbit HF is a major mediator of oxidative stress leading to impairment of Ca(2+) handling and contractility.

Heart: 25 Nov 2011; 97:e8
Seidlmayer L, Blatter LA, Dedkova EN
Heart: 25 Nov 2011; 97:e8 | PMID: 22116910
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Serelaxin and acute heart failure.

Tietjens J, Teerlink JR
Attempts at developing novel therapeutic agents for acute heart failure (AHF) over the past two decades have been marked by disappointment. Relaxin is a human peptide hormone believed to mediate many adaptive haemodynamic changes that occur during pregnancy. Because these effects may be useful for treating AHF, a recombinant version of human relaxin-2, serelaxin, has been developed as a novel therapeutic agent. Studies have confirmed serelaxin\'s haemodynamic effects of decreasing pulmonary and systemic resistance and increasing renal blood flow. A 1161-patient, placebo-controlled Phase III trial, RELAX-AHF, demonstrated significant improvement in symptoms, reduced worsening of heart failure, decreased hospital length of stay and increased 180-day survival after index hospitalisation. Additional Phase III trials (RELAX-AHF-2; RELAX-AHF-ASIA) are underway to further evaluate the efficacy of serelaxin in patients with AHF. This article will review the physiological function, mechanism of action, clinical trial results and future directions of serelaxin in the treatment of AHF.

Heart: 24 Nov 2015; epub ahead of print
Tietjens J, Teerlink JR
Heart: 24 Nov 2015; epub ahead of print | PMID: 26603680
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and meta-analysis.

Janda S, Shahidi N, Gin K, Swiston J
Context Right heart catheterisation is the gold standard for the diagnosis of pulmonary hypertension. However, echocardiography is frequently used to screen for this disease and monitor progression over time because it is non-invasive, widely available and relatively inexpensive. Objective To perform a systematic review and quantitative meta-analysis to determine the correlation of pulmonary pressures obtained by echocardiography versus right heart catheterisation and to determine the diagnostic accuracy of echocardiography for pulmonary hypertension. Data Sources MEDLINE, EMBASE, PapersFirst, the Cochrane collaboration and the Cochrane Register of controlled trials were searched and were inclusive as of February 2010. Study Selection Studies were only included if a correlation coefficient or the absolute number of true-positive, false-negative, true-negative and false-positive observations was available, and the \'reference standards\' were described clearly. Data Extraction Two reviewers independently extracted the data from each study. Quality was assessed with the quality assessment for diagnostic accuracy studies. A random effects model was used to obtain a summary correlation coefficient and the bivariate model for diagnostic metaanalysis was used to obtain summary sensitivity and specificity values.

Heart: 01 Mar 2011; epub ahead of print
Janda S, Shahidi N, Gin K, Swiston J
Heart: 01 Mar 2011; epub ahead of print | PMID: 21357375
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Reducing myocardial infarct size: challenges and future opportunities.

Bulluck H, Yellon DM, Hausenloy DJ
Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is \'myocardial reperfusion injury\', a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies-however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury.

Heart: 16 Dec 2015; epub ahead of print
Bulluck H, Yellon DM, Hausenloy DJ
Heart: 16 Dec 2015; epub ahead of print | PMID: 26674987
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

CT coronary angiographic evaluation of suspected anginal chest pain.

Moss AJ, Newby DE
: Non-invasive imaging plays a critical role in the assessment of patients presenting with suspected angina chest pain. However, wide variations in practice across Europe and North America highlight the lack of consensus in selecting the appropriate first-line test for the investigation of coronary artery disease (CAD). CT coronary angiography (CTCA) has a high negative predictive value for excluding the presence of CAD. As such, it serves as a potential \'gatekeeper\' to downstream testing by reducing the rate of inappropriate invasive coronary angiography. Two recent large multicentre randomised control trials have provided insights into whether CTCA can be incorporated into chest pain care pathways to improve risk stratification of CAD. They demonstrate that using CTCA enhances diagnostic certainty and improves the targeting of appropriate invasive investigations and therapeutic interventions. Importantly, reductions in cardiac death and non-fatal myocardial infarction appear to be attained through the more appropriate use of preventative therapy and coronary revascularisation when guided by CTCA. With this increasing portfolio of evidence, CTCA should be considered the non-invasive investigation of choice in the evaluation of patients with suspected angina pectoris due to coronary heart disease.

Heart: 08 Dec 2015; epub ahead of print
Moss AJ, Newby DE
Heart: 08 Dec 2015; epub ahead of print | PMID: 26647079
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart failure risk predictions in adult patients with congenital heart disease: a systematic review.

Wang F, Harel-Sterling L, Cohen S, Liu A, ... Paradis G, Marelli AJ

To summarise existing heart failure (HF) risk prediction models and describe the risk factors for HF-related adverse outcomes in adult patients with congenital heart disease (CHD). We performed a systematic search of MEDLINE, EMBASE and Cochrane databases from January 1996 to December 2018. Studies were eligible if they developed multivariable models for risk prediction of decompensated HF in adult patients with CHD (ACHD), death in patients with ACHD-HF or both, or if they reported corresponding predictors. A standardised form was used to extract information from selected studies. Twenty-five studies met the inclusion criteria and all studies were at moderate to high risk of bias. One study derived a model to predict the risk of a composite outcome (HF, death or arrhythmia) with a c-statistic of 0.85. Two studies applied an existing general HF model to patients with ACHD but did not report model performance. Twenty studies presented predictors of decompensated HF, and four examined patient characteristics associated with mortality (two reported predictors of both). A wide variation in population characteristics, outcome of interest and candidate risk factors was observed between studies. Although there were substantial inconsistencies regarding which patient characteristics were predictive of HF-related adverse outcomes, brain natriuretic peptide, New York Heart Association class and CHD lesion characteristics were shown to be important predictors. To date, evidence in the published literature is insufficient to accurately profile patients with ACHD. High-quality studies are required to develop a unique ACHD-HF prediction model and confirm the predictive roles of potential risk factors.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2019; 105:1661-1669
Wang F, Harel-Sterling L, Cohen S, Liu A, ... Paradis G, Marelli AJ
Heart: 30 Oct 2019; 105:1661-1669 | PMID: 31350277
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Quantitation of mitral regurgitation with cardiac magnetic resonance imaging: a systematic review.

Krieger EV, Lee J, Branch KR, Hamilton-Craig C
In this review discuss the application of cardiac magnetic resonance (CMR) to the evaluation and quantification of mitral regurgitation and provide a systematic literature review for comparisons with echocardiography. Using the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we searched Medline and PubMed for original research articles published since 2000 that provided data on the quantification of mitral regurgitation by CMR. We identified 220 articles of which 33 were included. Four main techniques of mitral regurgitation quantification were identified. Reproducibility varied substantially between papers but was high overall for all techniques. However, quantification differed between the techniques studied. When compared with two-dimensional echocardiography, mitral regurgitation fraction and regurgitant volume measured by CMR were comparable but typically lower. CMR has high reproducibility for the quantification of mitral regurgitation in experienced centres, but further technological refinement is needed. An integrated and standardised approach that combines multiple techniques is recommended for optimal reproducibility and precise mitral regurgitation quantification. Definitive outcome studies using CMR as a basis for treatment are lacking but needed.

Heart: 12 Oct 2016; epub ahead of print
Krieger EV, Lee J, Branch KR, Hamilton-Craig C
Heart: 12 Oct 2016; epub ahead of print | PMID: 27733535
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diagnosis and treatment of cardiac sarcoidosis.

Kusano KF, Satomi K
Sarcoidosis is a systemic granulomatous disease of unknown aetiology. The frequency of cardiac involvement (cardiac sarcoidosis (CS)) varies in the different geographical regions, but it has been reported that it is an absolutely important prognostic factor in this disease. Complete atrioventricular block is the most common, and ventricular tachycardia/ventricular fibrillation the second most common arrhythmia in this disease, both of which are associated with cardiac sudden death. Diagnosing CS is sometimes difficult because of the non-specific ECG and echocardiographic findings, and CS is sometimes misdiagnosed as dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or an idiopathic ventricular aneurysm, and therefore, endomyocardial biopsy is important, but has a low sensitivity. Another problem is the recognition of isolated types of CS. Recently, MRI and (18)F-fluorodeoxyglucose positron emission tomography have been demonstrated to be useful tools for the non-invasive diagnosis of CS as well as therapeutic evaluation tools, but are still unsatisfactory. Treatment of CS is usually done by corticosteroid therapy to control inflammation, prevent fibrosis and protect from any deterioration of the cardiac function, but the long-term outcome is still in debate. Despite the advancement of non-pharmacological approaches for CS (pacing, defibrillators and catheter ablation) to improve the prognosis, there are still many issues remaining to resolve diagnosing and managing CS. Here, we attempt a review of the clinical evidence, with special focus on the current understanding of this disease and showing the current strategies and remaining problems of diagnosing and managing CS.

Heart: 07 Dec 2015; epub ahead of print
Kusano KF, Satomi K
Heart: 07 Dec 2015; epub ahead of print | PMID: 26643814
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of cardiac resynchronisation therapy on dilated cardiomyopathy with isolated ventricular non-compaction.

Bertini M, Ziacchi M, Biffi M, Biagini E, ... Rapezzi C, Boriani G
Objective To compare the effects of cardiac resynchronisation therapy (CRT) on left ventricular (LV) reverse remodelling in patients with dilated cardiomyopathy (DCM) associated or not with isolated ventricular non-compaction (IVNC). Methods and results 52 patients with heart failure, candidates for CRT, were recruited: 20 patients with IVNC associated with DCM (IVNC-DCM) without other coexisting cardiac diseases and 32 patients with DCM without IVNC matched for age, gender, body surface area and LV systolic function. Standard and contrast echocardiography were used to assess LV volumes and function and to optimise visualisation of the endocardial border at baseline and at 6 months\' follow-up. Patients with heart failure were subsequently classified as CRT negative responders, non-responders, responders or super-responders based on different LV reverse remodelling 6&emsp14;months after CRT implantation. Different types of CRT response were observed in IVNC-DCM and DCM patients. In particular, in IVNC-DCM patients the percentage of super-responders was significantly higher than for patients with DCM (60% vs 28%, respectively, p=0.023). In addition, the number of IVNC segments had a trend towards reduction with respect to baseline (4 (3-6)) at 6&emsp14;months\' follow-up (3 (1-5); p=0.067). Finally, in IVNC-DCM, the patients with a higher number of IVNC segments at baseline (>4) were more likely to be responders or super-responders than patients with ≤4 IVNC segments (p=0.003). Conclusions Patients with IVNC-DCM had greater LV reverse remodelling after CRT than patients with DCM. The greater the area of non-compaction (higher number of IVNC segments) the greater the chance of achieving CRT response and greater LV reverse remodelling.

Heart: 17 Dec 2010; epub ahead of print
Bertini M, Ziacchi M, Biffi M, Biagini E, ... Rapezzi C, Boriani G
Heart: 17 Dec 2010; epub ahead of print | PMID: 21163889
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Unique cardiovascular risk factors in women.

Young L, Cho L

Despite an overall reduction in cardiovascular disease (CVD) mortality in the USA, the rate of coronary heart disease and CVD mortality is on the rise in younger women aged 35 to 54 years. This has been attributed to an increasing prevalence of CVD risk factors, which can portend disparate outcomes in women versus men. Women with diabetes and those who smoke have an excess relative risk of CVD when compared with their male counterparts. In addition to these discrepancies in traditional risk factors, a number of clinical conditions unique to women have been shown to increase CVD risks such as pre-eclampsia, gestational diabetes, polycystic ovary syndrome, early menopause and autoimmune diseases. The majority of these sex-specific risk factors can be identified at an early age, allowing for aggressive risk factor modification through lifestyle changes and, in certain patients, medications. The recently published 2018 American College of Cardiology and American Heart Association (ACC/AHA) hypercholesterolaemia and 2019 ACC/AHA primary prevention guidelines reflect this, citing pre-eclampsia, early menopause and autoimmune diseases as \'risk enhancers\' that if present may favour initiation of statin therapy in borderline or intermediate risk patients. This comprehensive review addresses both traditional and unique risk factors of CVD in women, as well as sex-specific risk stratification and management options.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2019; 105:1656-1660
Young L, Cho L
Heart: 30 Oct 2019; 105:1656-1660 | PMID: 31315936
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Management of supraventricular arrhythmias in adults with congenital heart disease.

Wasmer K, Eckardt L
Supraventricular arrhythmias are a frequent complication in adults with congenital heart disease (ACHD). The prevalence increases with time since surgery, complexity of the underlying defect, type of repair and older age at surgery. Arrhythmias are the most frequent reason for hospital admission and along with heart failure the leading cause of death. The arrhythmia-associated increase in morbidity and mortality makes their management a key task in patients with ACHD. Intra-atrial re-entry is the most frequent arrhythmia mechanism. Less common arrhythmia mechanisms are supraventricular tachycardias in the presence of an accessory pathway, atrioventricular nodal re-entrant tachycardia or focal tachycardias. Patient management includes stroke prevention, acute termination and prevention of arrhythmia recurrence. Acute treatment depends on patients\' symptoms. In cases of haemodynamic instability, immediate cardioversion is warranted. For stable patients, acute treatment includes rate control and termination by antiarrhythmic drugs or electrical cardioversion. Following a symptomatic arrhythmia, catheter ablation or treatment with antiarrhythmic drugs is recommended to prevent recurrences. Advances in mapping and ablation technology are now associated with high success rates of catheter ablation. In patients with a complex substrate recurrence rates of 50% remain high. However, in the presence of side effects and complications associated with long-term antiarrhythmic drug therapy, redo procedures are encouraged by current guidelines.

Heart: 16 Jun 2016; epub ahead of print
Wasmer K, Eckardt L
Heart: 16 Jun 2016; epub ahead of print | PMID: 27312002
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mitral regurgitation in patients with severe aortic stenosis: diagnosis and management.

Sannino A, Grayburn PA
Severe aortic stenosis (AS) and mitral regurgitation (MR) frequently coexist. Although some observational studies have reported that moderate or severe MR is associated with higher mortality, the optimal management of such patients is still unclear. Simultaneous replacement of both aortic and mitral valves is linked to significantly higher morbidity and mortality. Recent advances in minimally invasive surgical or transcatheter therapies for MR allow for staged procedures in which surgical or transcatheter aortic valve replacement (SAVR/TAVR) is done first and MR severity re-evaluated afterwards. Current evidence suggests MR severity improves in some patients after SAVR or TAVR, depending on several factors (MR aetiology, type of valve used for TAVR, presence/absence of atrial fibrillation, residual aortic regurgitation, etc). However, as of today, the absence of randomised clinical trials does not allow for evidence-based recommendations about whether or not MR should be addressed at the time of SAVR or TAVR. A careful patient evaluation and clinical judgement are recommended to distinguish patients who might benefit from a double valve intervention from those in which MR should be left alone. The aim of this review is to report and critique the available data on this subject in order to help guide the clinical decision making in this challenging subset of patients.

Heart: 30 Dec 2017; 104:16-22
Sannino A, Grayburn PA
Heart: 30 Dec 2017; 104:16-22 | PMID: 28903993
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiovascular risk stratification in familial hypercholesterolaemia.

Sharifi M, Rakhit RD, Humphries SE, Nair D
Familial hypercholesterolaemia (FH) is a common autosomal-dominant disorder in most European countries. Patients with FH are characterised by a raised level of low-density lipoprotein cholesterol and a high risk of premature coronary heart disease (CHD). Currently there is no consensus regarding the clinical utility to predict future coronary events or testing for the presence of subclinical atherosclerotic disease in asymptomatic patients with FH. Family screening of patients with FH as recommended by the UK National Institute of Health and Care Excellence guideline would result in finding many young individuals with a diagnosis of FH who are clinically asymptomatic. The traditional CHD risk scores, that is, the Framingham score, are insufficient in risk prediction in this group of young individuals. In addition, a better understanding of the genetic aetiology of the FH phenotype and CHD risk in monogenic FH and polygenic hypercholesterolaemia is needed. Non-invasive imaging methods such as carotid intima-media thickness measurement might produce more reliable information in finding high-risk patients with FH. The potential market authorisation of novel therapeutic agents such as PCSK9 monoclonal inhibitors makes it essential to have a better screening programme to prioritise the candidates for treatment with the most severe form of FH and at higher risk of coronary events. The utility of new imaging techniques and new cardiovascular biomarkers remains to be determined in prospective trials.

Heart: 28 Apr 2016; epub ahead of print
Sharifi M, Rakhit RD, Humphries SE, Nair D
Heart: 28 Apr 2016; epub ahead of print | PMID: 27126396
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hypereosinophilic syndrome: cardiac diagnosis and management.

Mankad R, Bonnichsen C, Mankad S
Hypereosinophilic syndrome (HES) is a heterogeneous group of conditions that is defined at its core by hypereosinophilia (HE) (blood eosinophil count of >1.5×10(9)/L) and organ damage directly attributable to the HE. Cardiac dysfunction occurs frequently in all forms of HES and is a major cause of morbidity and mortality. Once a significantly elevated eosinophil count is identified, it must be confirmed on repeat testing and the aetiology for the HE must be rigorously sought out with a focus on identifying whether organ dysfunction is occurring. Echocardiography is routinely performed to assess for cardiac involvement, looking for evidence of left ventricular and/or right ventricular apical obliteration or thrombi or a restrictive cardiomyopathy. Cardiac magnetic resonance imaging and CT are often useful adjuncts to establish the diagnosis but endomyocardial biopsy remains the gold standard. To decrease the degree of eosinophilia, treatment can include corticosteroids and/or imatinib based on the aetiology. Anticoagulation, standard heart failure therapy for a restrictive cardiomyopathy and finally cardiac transplantation may be indicated in the treatment algorithm.

Heart: 13 Nov 2015; epub ahead of print
Mankad R, Bonnichsen C, Mankad S
Heart: 13 Nov 2015; epub ahead of print | PMID: 26567231
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prenatal ultrasound screening of congenital heart disease in an unselected national population: a 21-year experience.

Marek J, Tomek V, Skovránek J, Povysilová V, Samánek M
Objective To determine the prevalence and spectrum of congenital heart disease (CHD) and the impact of a national prenatal ultrasound screening programme on outcome in a well-characterised population. Design and setting A comprehensive registry was created of all paediatric and fetal patients with CHD over a 21-year period (1986-2006) in the Czech Republic. The centralised healthcare system enabled confirmation of prenatal and postnatal findings clinically and by post mortem. Patients and results In the entire cohort of 9475 fetuses referred for detailed cardiac evaluation, 1604 (16.9%) had CHD, of which 501 (31.2%) had additional extracardiac anomalies. In the pregnancies which continued, 59 (8.6%) of 685 fetuses died in utero, and 626 (91.4%) babies were born alive. Prenatal detection rate was highest in double outlet right ventricle (77.3%) and hypoplastic left heart (50.6%). Detection rate increased significantly (p<0.001) for 12/17 lesions comparing 1986-1999 and 2000-2006. In recent years, detection of hypoplastic left heart reached 95.8% while transposition of the great arteries was diagnosed antenatally in only 25.6%. Conclusion The nationwide prenatal ultrasound screening programme enabled detection of major cardiac abnormalities in 1/3 of patients born with any CHD and 80% of those with critical forms. Nevertheless, owing to the severity of lesions and associated extracardiac anomalies, the overall mortality of antenatally diagnosed CHD remains high. These findings are important for the understanding natural history of CHD for the establishing of screening programmes in Europe.

Heart: 17 Dec 2010; 97:124-30
Marek J, Tomek V, Skovránek J, Povysilová V, Samánek M
Heart: 17 Dec 2010; 97:124-30 | PMID: 21163892
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effective components of nurse-coordinated care to prevent recurrent coronary events: a systematic review and meta-analysis.

Snaterse M, Dobber J, Jepma P, Peters RJ, ... Buurman BM, Scholte Op Reimer WJ
: Current guidelines on secondary prevention of cardiovascular disease recommend nurse-coordinated care (NCC) as an effective intervention. However, NCC programmes differ widely and the efficacy of NCC components has not been studied. To investigate the efficacy of NCC and its components in secondary prevention of coronary heart disease by means of a systematic review and meta-analysis of randomised controlled trials. 18 randomised trials (11 195 patients in total) using 15 components of NCC met the predefined inclusion criteria. These components were placed into three main intervention strategies: (1) risk factor management (13 studies); (2) multidisciplinary consultation (11 studies) and (3) shared decision making (10 studies). Six trials combined NCC components from all three strategies. In total, 30 outcomes were observed. We summarised observed outcomes in four outcome categories: (1) risk factor levels (16 studies); (2) clinical events (7 studies); (3) patient-perceived health (7 studies) and (4) guideline adherence (3 studies). Compared with usual care, NCC lowered systolic blood pressure (weighted mean difference (WMD) 2.96 mm Hg; 95% CI 1.53 to 4.40 mm Hg) and low-density lipoprotein cholesterol (WMD 0.23 mmol/L; 95% CI 0.10 to 0.36 mmol/L). NCC also improved smoking cessation rates by 25% (risk ratio 1.25; 95% CI 1.08 to 1.43). NCC demonstrated to have an effect on a small number of outcomes. NCC that incorporated blood pressure monitoring, cholesterol control and smoking cessation has an impact on the improvement of secondary prevention. Additionally, NCC is a heterogeneous concept. A shared definition of NCC may facilitate better comparisons of NCC content and outcomes.

Heart: 13 Nov 2015; epub ahead of print
Snaterse M, Dobber J, Jepma P, Peters RJ, ... Buurman BM, Scholte Op Reimer WJ
Heart: 13 Nov 2015; epub ahead of print | PMID: 26567234
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Speckle Myocardial Imaging Modalities for Early Detection of Myocardial Impairment in Isolated Left Ventricular Non-Compaction.

Bellavia D, Michelena HI, Martinez M, Pellikka PA, ... Oh JK, Miller FA
Objective: We hypothesized that speckle myocardial imaging (SMI) modalities, including longitudinal, radial and circumferential systolic (s) and diastolic (d) myocardial velocity imaging (MVI), displacement (D), strain rate (SR) and strain (S), as well as LV rotation/torsion are sensitive for detecting early myocardial dysfunction in isolated LV non-compaction (iLVNC). Design and Results: Twenty patients with iLVNC diagnosed by cardiac magnetic resonance (15) or echocardiography (5) were included. Patients were divided into 2 groups: EF>50% (n=10) and EF inverted exclamation markU50% (n=10). Standard measures of systolic and diastolic function including pulsed-wave tissue Doppler Imaging (PWTDI) were obtained. Longitudinal, radial and circumferential SMI, and LV rotation/torsion were compared to 20 age/sex matched controls. EF, PWTDI E inverted exclamation mark ,E/E inverted exclamation mark and all of the SMI modalities, were significantly abnormal for EF inverted exclamation markU50% patients compared to controls. In contrast, EF and PWTDI E inverted exclamation mark , E/E inverted exclamation mark were not significantly different between controls and iLVNC (EF>50%) patients. However, SMI-derived longitudinal sS, sSR, sDi and radial sS, as well as LV rotation/torsion values were all reduced in iLVNC (EF>50%) compared to controls. Measurements with highest discriminating power between iLVNC (EF>50%) and controls were longitudinal sS mean of the 6 apical segments (AUC = 0.94), sS global average (AUC=0.94), LV rotation apical mean (AUC= 0.94) ; LV torsion (AUC=0.93) LV torsion rate (AUC=0.94). Conclusions: LV SMI values are reduced in patients with iLVNC, even those with normal EF and PWTDI. The most accurate SMI modalities to discriminate between patients and controls is longitudinal sS mean of the 6 apical segments, LV apical rotation, or LV torsion rate.

Heart: 07 Dec 2009; epub ahead of print
Bellavia D, Michelena HI, Martinez M, Pellikka PA, ... Oh JK, Miller FA
Heart: 07 Dec 2009; epub ahead of print | PMID: 19966109
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation.

Logue J, Murray HM, Welsh P, Shepherd J, ... Ford I, Sattar N
Background The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. Objective To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. Methods and results In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55&emsp14;years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2&emsp14;years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7&emsp14;years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25-27.4&emsp14;kg/m(2) as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0-39.9&emsp14;kg/m(2) in both the minimally adjusted model (HR=1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR=1.60 (95% CI 1.02 to 2.53)). Conclusions These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.

Heart: 17 Feb 2011; epub ahead of print
Logue J, Murray HM, Welsh P, Shepherd J, ... Ford I, Sattar N
Heart: 17 Feb 2011; epub ahead of print | PMID: 21324888
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A case of loin pain after cardiac catheterisation.

Chatterjee D, Sadiq A, Garikipati R
A 57-year-old woman with known moderate-to-severe mitral stenosis and atrial fibrillation (AF) presented to the emergency department with acute onset right loin pain after having a coronary angiogram and left and right heart catheterisation through the right femoral route about 28 h ago. The cardiac catheterisation was done after she presented with one episode of troponin-negative chest pain and progressive shortness of breath. She had anterior wall myocardial infarction (MI) 25 years ago, which was thought to be due to coronary artery embolism. Her mitral stenosis was diagnosed at that stage.Her warfarin was stopped for 5 days before cardiac catheterisation and international normalised ratio (INR) on the day of the procedure was 1.1. No bridging heparin/low molecular weight heparin (LMWH) was used and warfarin was restarted on the evening of the procedure at the usual dose. Clinical examination revealed some guarding in the right iliac fossa and some tenderness in the right loin. She was not feverish and there was no dysuria or frequency. There was no lump at the puncture site.On presentation to the emergency department, a contrast-enhanced CT scan of the abdomen was performed (figures 1 and 2).

Heart: 07 Apr 2016; epub ahead of print
Chatterjee D, Sadiq A, Garikipati R
Heart: 07 Apr 2016; epub ahead of print | PMID: 27056971
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Role of imaging in the evaluation of single ventricle with the Fontan palliation.

Kutty S, Rathod RH, Danford DA, Celermajer DS
The Fontan operation for single ventricle palliation consists of the creation of a complete cavopulmonary connection, usually by incorporating inferior vena caval flow into a pulmonary arterial circulation already receiving flow from the superior vena cava. In single ventricle palliated in this way, the anatomy is complex, and the pathophysiological complications are frequent; so, cardiac imaging is a key aspect of clinical surveillance. Common problems that echocardiography and MRI may disclose and characterise in the Fontan palliation of single ventricle include obstruction of systemic venous and pulmonary arterial flow, atrioventricular and semilunar valve dysfunction, unintended collateral flow patterns, ventricular dysfunction, aortic arch obstruction, interatrial obstruction, fenestration flow and patch leaks. Despite the broad scope of these modalities for detection of such problems, often no single imaging method is comprehensive in any given patient. Therefore, physicians must recognise the limitations of each modality, and circumvent these by application of suitable alternatives. New imaging tools are becoming available, which may ultimately prove to be of value in the Fontan circulation. Proper application of diverse new technologies such as four dimensional flow, computational fluid dynamics and three-dimensional printing will require critical evaluation in the single ventricle population.

Heart: 13 Nov 2015; epub ahead of print
Kutty S, Rathod RH, Danford DA, Celermajer DS
Heart: 13 Nov 2015; epub ahead of print | PMID: 26567230
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Colchicine in cardiovascular disease: an ancient drug with modern tricks.

Tong DC, Wilson AM, Layland J
From the dark history of being a poison and purgative, colchicine has risen to become one of the few irrefutable positives in the history of pharmacology in the management of myriad inflammatory conditions. Colchicine exerts its action through binding to tubulin, which in turn affects several cellular processes and pathways modulating the inflammatory response. Despite narrow therapeutic-toxicity window and the most common complaint of gastrointestinal upset, its list of medicinal use is expanding in recent years as we continue to unravel the mystery of this ancient remedy. In this review, we summarise the history of colchicine use, discuss its pharmacokinetics and mechanism of actions, and examine the most up-to-date evidence of colchicine in the treatment of various cardiac conditions with a focus on cardiovascular disease.

Heart: 18 Mar 2016; epub ahead of print
Tong DC, Wilson AM, Layland J
Heart: 18 Mar 2016; epub ahead of print | PMID: 26993138
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prognostic value of cardiac sympathetic nerve activity evaluated by [123I]m-iodobenzylguanidine imaging in patients with ST-segment elevation myocardial infarction.

Kasama S, Toyama T, Sumino H, Kumakura H, ... Sato Y, Kurabayashi M
Background Many studies have shown that cardiac sympathetic nerve activity evaluated by [(123)I]m-iodobenzylguanidine ([(123)I]MIBG) scintigraphic study during a stable period is useful for determining the prognosis of patients with chronic heart failure. Objective To examine whether results of this imaging method performed 3&emsp14;weeks after the onset of ST-segment elevation myocardial infarction (STEMI) are a reliable prognostic marker for patients with STEMI. Methods The study analysed findings for 213 consecutive patients with STEMI undergoing [(123)I]MIBG scintigraphy. The left ventricular (LV) end-diastolic and end-systolic volume and LV ejection fraction (EF) were determined by left ventriculography or echocardiography 3&emsp14;weeks after the onset of STEMI. The delayed total defect score, heart-to-mediastinum ratio and washout rate (WR) were also determined from [(123)I]MIBG scintigraphy at the same time. Results Of the 213 patients, 46 experienced major adverse cardiac events (MACE) during the study. The median follow-up period was 982&emsp14;days. Patients were divided into an event-free group (n=167; 78.4%) and a MACE group (n=46; 21.6%). The LV and [(123)I]MIBG scintigraphic parameters in the event-free group were better than those in the MACE group. Multivariate Cox regression analyses revealed that WR was a significant predictor of MACE along with oral nicorandil (ATP-sensitive potassium channel opener) treatment and undergoing percutaneous coronary intervention. On Kaplan-Meier analysis, the event-free rate of patients with a WR<40% was significantly higher than that in patients with a WR≥40% (p<0.001). Even when confined to patients with LVEF>45%, WR was a predictor of MACE, pump failure death, cardiac death and progression of heart failure in patients with STEMI. Conclusion WR evaluated by [(123)I]MIBG scintigraphy 3&emsp14;weeks after the onset of STEMI is a significant predictor of MACE in patients with STEMI, independent of LVEF.

Heart: 10 Nov 2010; epub ahead of print
Kasama S, Toyama T, Sumino H, Kumakura H, ... Sato Y, Kurabayashi M
Heart: 10 Nov 2010; epub ahead of print | PMID: 21062772
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan.

Jhund PS, McMurray JJ
Inhibition of neurohumoural pathways such as the renin angiotensin aldosterone and sympathetic nervous systems is central to the understanding and treatment of heart failure (HF). Conversely, until recently, potentially beneficial augmentation of neurohumoural systems such as the natriuretic peptides has had limited therapeutic success. Administration of synthetic natriuretic peptides has not improved outcomes in acute HF but modulation of the natriuretic system through inhibition of the enzyme that degrades natriuretic (and other vasoactive) peptides, neprilysin, has proven to be successful. After initial failures with neprilysin inhibition alone or dual neprilysin-angiotensin converting enzyme (ACE) inhibition, the Prospective comparison of angiotensin receptor neprilysin inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) trial demonstrated that morbidity and mortality can be improved with the angiotensin receptor blocker neprilysin inhibitor sacubitril/valsartan (formerly LCZ696). In comparison to the ACE inhibitor enalapril, sacubitril/valsartan reduced the occurrence of the primary end point (cardiovascular death or hospitalisation for HF) by 20% with a 16% reduction in all-cause mortality. These findings suggest that sacubitril/valsartan should replace an ACE inhibitor or angiotensin receptor blocker as the foundation of treatment of symptomatic patients (NYHA II-IV) with HF and a reduced ejection fraction. This review will explore the background to neprilysin inhibition in HF, the results of the PARADIGM-HF trial and offer guidance on how to use sacubitril/valsartan in clinical practice.

Heart: 20 May 2016; epub ahead of print
Jhund PS, McMurray JJ
Heart: 20 May 2016; epub ahead of print | PMID: 27207980
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

How to prevent and manage radiation-induced coronary artery disease.

Cuomo JR, Javaheri SP, Sharma GK, Kapoor D, Berman AE, Weintraub NL
Radiation-induced coronary heart disease (RICHD) is the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin\'s lymphoma and other prevalent mediastinal malignancies. The risk of RICHD increases with radiation dose. Exposed patients may present decades after treatment with manifestations ranging from asymptomatic myocardial perfusion defects to ostial, triple-vessel disease and sudden cardiac death. RICHD is insidious, with a long latency and a tendency to remain silent late into the disease course. Vessel involvement is often diffuse and is preferentially proximal. The pathophysiology is similar to that of accelerated atherosclerosis, characterised by the formation of inflammatory plaque with high collagen and fibrin content. The presence of conventional risk factors potentiates RICHD, and aggressive risk factor management should ideally be initiated prior to radiation therapy. Stress echocardiography is more sensitive and specific than myocardial perfusion imaging in the detection of RICHD, and CT coronary angiography shows promise in risk stratification. Coronary artery bypass grafting is associated with higher risks of graft failure, perioperative complications and all-cause mortality in patients with RICHD. In most cases, the use of drug-eluting stents is preferable to surgical intervention, bare metal stenting or balloon-angioplasty alone.

Heart: 14 May 2018; epub ahead of print
Cuomo JR, Javaheri SP, Sharma GK, Kapoor D, Berman AE, Weintraub NL
Heart: 14 May 2018; epub ahead of print | PMID: 29764968
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

An immunological perspective on rheumatic heart disease pathogenesis: more questions than answers.

Bright PD, Mayosi BM, Martin WJ
Acute rheumatic fever (ARF) and the related rheumatic heart disease (RHD) are autoimmune diseases thought to be triggered by group A streptococcal (GAS) pharyngitis. RHD is a leading cause of mortality in the developing world. The strong epidemiological association between GAS throat infection and ARF is highly suggestive of causation, but does not exclude other infections as contributory. There is good evidence of both humoral and cellular autoreactivity and GAS/self cross-reactivity in established RHD. RHD pathogenesis could feasibly be triggered and driven by humoral and/or cellular molecular cross-reactivity between GAS and host cardiac tissues (molecular mimicry). However, good evidence of humoral pathogenicity is lacking and the specific triggering event for RHD remains unknown. It is likely that the critical immunological events leading to ARF/RHD occur at the point of contact between GAS and the immune system in the throat, strongly implicating the mucosal immune system in RHD pathogenesis. Additionally, there is circumstantial evidence that continued live GAS may play a role in ARF/RHD pathogenesis. We suggest that future avenues for study should include the exclusion of GAS components directly contributing to RHD pathogenesis; large genome-wide association studies of patients with RHD looking for candidate genes involved in RHD pathogenesis; genome-wide association studies of GAS from patients with ARF taken at diagnosis to look for characteristics of rheumatogenic strains; and performing case/control studies of GAS pharyngitis/ARF/patients with RHD, and controls to identify microbiological, immunological and environmental differences to elucidate RHD pathogenesis.

Heart: 03 Jun 2016; epub ahead of print
Bright PD, Mayosi BM, Martin WJ
Heart: 03 Jun 2016; epub ahead of print | PMID: 27260192
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Reconsidering the back door approach by targeting the coronary sinus in ischaemic heart disease.

De Maria GL, Kassimis G, Raina T, Banning AP
Coronary sinus interventions (CSI) are a class of invasive techniques (surgical and percutaneous) originally proposed in the first half of the 20th century, aiming to treat ischaemic heart disease by acting on the venous coronary system. Three main classes of CSI have been proposed and tested: (1) retroperfusion technique, (2) retroinfusion technique and (3) coronary sinus occlusion techniques. They all share the principle that a controlled increased pressure within the coronary sinus may promote a retrograde perfusion of the ischaemic myocardium with consequent cardioprotection. Development of arterial treatments including coronary aortic bypass grafting and then percutaneous coronary intervention deflected interest from interventions on the coronary venous system. However, CSI may still have a possible niche role today in specific and selected clinical contexts in which existing therapies are insufficient. In this review paper, we aim to revise the rationale for CSI, describing the details and the evidence collected so far about these techniques and to provide insights about the main clinical scenarios in which these strategies may find a contemporary application in combination or as an alternative to existing approaches.

Heart: 10 Jun 2016; epub ahead of print
De Maria GL, Kassimis G, Raina T, Banning AP
Heart: 10 Jun 2016; epub ahead of print | PMID: 27288281
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Walking Speed and Subclinical Atherosclerosis in Healthy Older Adults: The Whitehall Ii Study.

Hamer M, Kivimaki M, Yerramasu A, Lahiri A, ... Marmot MG, Steptoe A
Objective: Extended walking speed is a predictor of incident cardiovascular disease (CVD) in older individuals, but the ability of an objective short-distance walking speed test to stratify the severity of preclinical conditions remains unclear. We examined whether performance in an 8-foot walking speed test is associated with metabolic risk factors and sub-clinical atherosclerosis. Design: Cross sectional Setting: Epidemiological cohort Participants: 530 adults (aged 63+/- 6 yrs, 50.3% male) from the Whitehall II cohort study with no known history or objective signs of CVD. Main outcome: Electron beam computed tomography and ultrasound was used to assess the presence and extent of coronary artery calcification (CAC) and carotid intima-media thickness (IMT), respectively. Results: High levels of CAC (Agatston score>100) were detected in 24% of the sample; the mean IMT was 0.75 (SD 0.15) mm. Participants with no detectable CAC completed the walking course 0.16 seconds (95% CI, 0.04 to 0.28) faster than those with CAC >/=400. Objectively assessed, but not self-reported, faster walking speed was associated with lower risk of high CAC (odds ratio=0.60, 95% CI, 0.40 to 0.96) and lower IMT (beta=-0.04, 95% CI, -0.01 to -0.07 mm) in comparison with the slowest walkers (bottom third), after adjusting for conventional risk factors. Faster walking speed was also associated with lower adiposity, C-reactive protein, and LDL cholesterol. Conclusions: Short distance walking speed is associated with metabolic risk and sub-clinical atherosclerosis in older adults without overt CVD. These data suggest that a non-aerobically challenging walking test reflects the presence of underlying vascular disease.

Heart: 03 Dec 2009; epub ahead of print
Hamer M, Kivimaki M, Yerramasu A, Lahiri A, ... Marmot MG, Steptoe A
Heart: 03 Dec 2009; epub ahead of print | PMID: 19955091
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The site of origin of torsade de pointes.

Birati EY, Belhassen B, Bardai A, Wilde AA, Viskin S
Objective The electrocardiographic (ECG) characteristics and mode of onset of torsade de pointes (TdP) are well described. Less is known about the site of onset of this arrhythmia. This study was conducted to determine if arrhythmias in the long QT syndrome (LQTS) have a predominant site of origin. Design A retrospective analysis of all episodes of LQTS-related arrhythmias recorded in two university hospitals. Patients Patients with LQTS and no structural heart disease, for whom simultaneous 6-12 leads ECG recording of the onset of TdP was available, were included. Interventions None. Main outcome measures The site of origin of TDP was defined according to the morphology of the initiating ventricular complex based on validated criteria. Multiple-lead recordings of 1025 LQTS-related arrhythmias, including 151 episodes of TdP and 874 QT-related extrasystoles (impending TdP) were available for 50 patients. Results The site of origin of TdP was not homogeneously distributed (p<0.001). Instead, the majority of episodes of TdP (56%) and most QT-related extrasystoles (70%) originated from the outflow tract. There was no correlation between site of origin and the aetiology of LQTS or the QT duration. On a given patient, multiple episodes of TdP tended to originate from the same area and the site of origin of QT-related extrasystoles correlated with the site of origin of TdP. Conclusion The most frequent site of origin of TdP is the outflow tract. Further studies are needed to understand why this relatively small area of the ventricle is a predominant site of origin of diverse ventricular arrhythmias.

Heart: 12 May 2011; epub ahead of print
Birati EY, Belhassen B, Bardai A, Wilde AA, Viskin S
Heart: 12 May 2011; epub ahead of print | PMID: 21561894
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pulmonary hypertension associated with acute or chronic lung diseases in the preterm and term neonate and infant. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

Hilgendorff A, Apitz C, Bonnet D, Hansmann G
Persistent pulmonary hypertension of the newborn (PPHN) is the most common neonatal form and mostly reversible after a few days with improvement of the underlying pulmonary condition. When pulmonary hypertension (PH) persists despite adequate treatment, the severity of parenchymal lung disease should be assessed by chest CT. Pulmonary vein stenosis may need to be ruled out by cardiac catheterisation and lung biopsy, and genetic workup is necessary when alveolar capillary dysplasia is suspected. In PPHN, optimisation of the cardiopulmonary situation including surfactant therapy should aim for preductal SpO2between 91% and 95% and severe cases without post-tricuspid-unrestrictive shunt may receive prostaglandin E1 to maintain ductal patency in right heart failure. Inhaled nitric oxide is indicated in mechanically ventilated infants to reduce the need for extracorporal membrane oxygenation (ECMO), and sildenafil can be considered when this therapy is not available. ECMO may be indicated according to the ELSO guidelines. In older preterm infant, where PH is mainly associated with bronchopulmonary dysplasia (BPD) or in term infants with developmental lung anomalies such as congenital diaphragmatic hernia or cardiac anomalies, left ventricular diastolic dysfunction/left atrial hypertension or pulmonary vein stenosis, can add to the complexity of the disease. Here, oral or intravenous sildenafil should be considered for PH treatment in BPD, the latter for critically ill patients. Furthermore, prostanoids, mineralcorticoid receptor antagonists, and diuretics can be beneficial. Infants with proven or suspected PH should receive close follow-up, including preductal/postductal SpO2measurements, echocardiography and laboratory work-up including NT-proBNP, guided by clinical improvement or lack thereof.

Heart: 06 Apr 2016; 102:ii49-ii56
Hilgendorff A, Apitz C, Bonnet D, Hansmann G
Heart: 06 Apr 2016; 102:ii49-ii56 | PMID: 27053698
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Abnormal left ventricular function occurs on exercise in well-treated hypertensive subjects with normal resting echocardiography.

Tan YT, Wenzelburger F, Lee E, Heatlie G, Frenneaux M, Sanderson JE
Objectives This study tests the hypothesis that patients with treated hypertension with well-controlled blood pressure, without ventricular hypertrophy and normal resting echocardiography, may have abnormalities of ventricular function that are apparent only on exercise and contribute to symptoms of exertional dyspnoea. Methods Patients with hypertension with well-controlled blood pressure on medication and normal baseline echocardiography underwent cardiopulmonary exercise testing to determine their peak oxygen consumption (Vo(2)(max)), followed by rest and submaxinal supine exercise echocardiography (standard, tissue Doppler and speckle tracking). Results 30 patients with treated hypertension with a history of exertional dyspnoea (mean age 71+/-8 years; 18 women) and 22 age-matched healthy controls (70+/-6 years; 16 women) had rest and exercise images of sufficient quality for analysis. Both groups had comparable standard echocardiographic findings at rest. On exercise, the patients had reduced systolic longitudinal function (reserve index 0.97+/-1.34 vs 2.32+/-1.24, p=0.001), delayed early untwisting (20.4+/-7.6 vs 30.6+/-7.8%, p=0.001) and reduced ventricular suction (velocity propagation 10.6+/-10.9 vs 24.5+/-12.2 m/s, p<0.001) compared with healthy controls, which correlated with significantly reduced Vo(2)(max). Conclusion Patients with treated hypertension with normal resting echocardiography can have exercise limitation associated with widespread systolic and diastolic left ventricular dysfunction on exercise. Normal resting echocardiography does not preclude the presence of significant functional abnormalities on exercise that can contribute to symptoms.

Heart: 11 Jun 2010; 96:948-55
Tan YT, Wenzelburger F, Lee E, Heatlie G, Frenneaux M, Sanderson JE
Heart: 11 Jun 2010; 96:948-55 | PMID: 20538670
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Bioprosthetic aortic valve durability in the era of transcatheter aortic valve implantation.

Salaun E, Clavel MA, Rodés-Cabau J, Pibarot P
The main limitation of bioprosthetic valves is their limited durability, which exposes the patient to the risk of aortic valve reintervention. Transcatheter aortic valve implantation (TAVI) is considered a reasonable alternative to surgical aortic valve replacement (SAVR) in patients with intermediate or high surgical risk. TAVI is now rapidly expanding towards the lower risk populations. Although the results of midterm durability of the transcatheter bioprostheses are encouraging, their long-term durability remains largely unknown. The objective of this review article is to present the definition, mechanisms, incidence, outcome and management of structural valve deterioration of aortic bioprostheses with specific emphasis on TAVI. The structural valve deterioration can be categorised into three stages: stage 1: morphological abnormalities (fibrocalcific remodelling and tear) of bioprosthesis valve leaflets without hemodynamic valve deterioration; stage 2: morphological abnormalities and moderate hemodynamic deterioration (increase in gradient and/or new onset of transvalvular regurgitation); and stage 3: morphological abnormalities and severe hemodynamic deterioration. Several specifics inherent to the TAVI including valve oversizing, manipulation, delivery, positioning and deployment may cause injuries to the valve leaflets and increase leaflet mechanical stress, which may limit the long-term durability of transcatheter bioprostheses. The selection of the type of aortic valve replacement and bioprosthesis should thus take into account the ratio between the demonstrated durability of the bioprostheses versus the life expectancy of the patient. Pending the publication of robust data on long-term durability of transcatheter bioprostheses, it appears reasonable to select SAVR with a bioprosthesis model that has well-established long-term durability in patients with low surgical risk and long life expectancy.

Heart: 06 May 2018; epub ahead of print
Salaun E, Clavel MA, Rodés-Cabau J, Pibarot P
Heart: 06 May 2018; epub ahead of print | PMID: 29735584
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Treatment of children with pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

Hansmann G, Apitz C
Treatment of children and adults with pulmonary hypertension (PH) with or without cardiac dysfunction has improved in the last two decades. The so-called pulmonary arterial hypertension (PAH)-specific medications currently approved for therapy of adults with PAH target three major pathways (endothelin, nitric oxide, prostacyclin). Moreover, some PH centres may use off-label drugs for compassionate use. Pulmonary hypertensive vascular disease (PHVD) in children is complex, and selection of appropriate therapies remains difficult. In addition, paediatric PAH/PHVD therapy is vastly based on experience and trial data from adult rather than paediatric studies; however, the first randomised paediatric PAH trials have been conducted recently. We present consensus recommendations for the treatment of children with PH. Class of recommendation and level of evidence were assigned based on paediatric data only or on adult studies that included >10% children. After a systematic literature search and analysis of the published data, we developed treatment strategies and algorithms that can guide goal-oriented PH therapy. We discuss early combination therapy (double, triple) in patients with PAH in functional class II-IV and in those with inadequate response to the initial pharmacotherapy. In those children with progressive, severe PAH and inadequate response, advances in drug development, and interventional and surgical approaches provide promising new strategies to avoid, reverse or ameliorate right heart failure and left ventricular compression. In particular, first follow-up data indicate that Potts shunt (left pulmonary artery to descending aorta anastomosis) may be an alternative destination therapy, or bridge to bilateral lung transplantation, in end-stage paediatric PAH.

Heart: 06 Apr 2016; 102:ii67-ii85
Hansmann G, Apitz C
Heart: 06 Apr 2016; 102:ii67-ii85 | PMID: 27053700
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Multimodality imaging in congenital heart disease-related pulmonary arterial hypertension.

D\'Alto M, Dimopoulos K, Budts W, Diller GP, ... Li W, Gatzoulis MA
Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. The present review aims to discuss the clinical applications of invasive and non-invasive diagnostic modalities and to describe the strengths and weaknesses of each technique. Chest radiograph is an inexpensive investigation providing information on pulmonary arterial and hilar dilatation, pruning of peripheral pulmonary arteries and cardiomegaly. Transthoracic two-dimensional and Doppler echocardiography is the most widely used imaging tool. It provides information on cardiac anatomy and an estimate of haemodynamics and biventricular remodelling and function. In addition, echocardiography is valuable in assessing prognosis and monitoring the efficacy of therapy. Structural and functional changes associated with CHD-PAH, mainly affecting the right ventricle and pulmonary circulation, may represent an ideal target for evaluation with cardiac magnetic resonance. This non-invasive imaging modality has a low biological impact. CT plays an important role for patients with limited echocardiographic windows and those who are unable to undergo MRI (claustrophobia, poor compliance, presence of a pacemaker/implantable cardioverter defibrillator). It is the modality of choice for detailed assessment of pulmonary vessel obstruction or thrombosis. Finally, heart catheterisation remains the gold standard for diagnosing and confirming PAH in patients with CHD and for shunt evaluation. The diagnostic assessment of CHD-PAH requires great expertise and a deep knowledge of both CHD and PAH pathophysiology and should take place in a tertiary centre, where multiple data can be appropriately integrated and applied clinically.

Heart: 24 Mar 2016; epub ahead of print
D'Alto M, Dimopoulos K, Budts W, Diller GP, ... Li W, Gatzoulis MA
Heart: 24 Mar 2016; epub ahead of print | PMID: 27013702
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ventricular arrhythmias and sudden cardiac death in adults with congenital heart disease.

Khairy P
Remarkable gains in survival have led to an unprecedented number of adults with congenital heart disease. Arrhythmias collectively comprise the most common complication encountered. Recognising the unique issues and challenges involved in managing arrhythmias in adults with congenital heart disease and the consequential decisions surrounding sudden death prevention, expert societies have proposed evidence-based recommendations. On the whole, acute ventricular arrhythmias are managed according to general cardiology guidelines, while taking into consideration congenital heart disease-specific issues, such as positioning of patches or paddles according to location of the heart. Implantable cardioverter-defibrillators (ICDs) are indicated for secondary prevention in patients with sustained ventricular tachycardia or resuscitated cardiac arrest in the absence of a reversible cause. Pharmacological therapy and catheter ablation can be effective in reducing recurrent ICD shocks. Risk-benefit assessment for primary prevention ICDs is a major challenge. Although a clearer picture has emerged of the high-risk patient with tetralogy of Fallot, ICD indications for those with systemic right ventricles or univentricular hearts remain contentious. Challenges to ICD implantation include obstructed veins, conduits and baffles, atrioventricular valve disease and intracardiac shunts. In selected patients, customised systems with epicardial and/or subcutaneous coils may represent a viable solution. Alternatively, the subcutaneous ICD is an attractive option for patients in whom transvenous access is not feasible or desirable and in whom bradycardia and antitachycardia pacing features are not essential. Continued advances in risk stratification and device technologies carry the potential to further improve efficacy and safety outcomes in this growing population of patients.

Heart: 01 Jun 2016; epub ahead of print
Khairy P
Heart: 01 Jun 2016; epub ahead of print | PMID: 27250216
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

An unusual finding in a 57-year-old woman with new onset hypertension and a diastolic murmur.

Tarkin JM, Rudd JH, Jayne DR, Rusk RA, Gopalan D
A 57-year-old woman presented to our clinic with breathlessness brought on while walking uphill. She had been recently diagnosed with systemic hypertension. There was no known family history of cardiac disease, or prior smoking habit. On examination, pulse was 73 bpm and blood pressure 155/73 mm Hg, which was asymmetrical in her arms. Auscultation revealed a readily audible early diastolic murmur in the aortic area and bilateral subclavian bruits. ECG showed sinus rhythm with no abnormality. Transthoracic echocardiography demonstrated mild-to-moderate aortic regurgitation, and normal left ventricular size and function. The ascending aorta was mildly dilated (41 mm), with para-aortic thickening noted. Owing to the abnormal appearance of the aortic wall, cardiac MRI, and subsequently (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan was performed (figure 1).

Heart: 13 Jul 2016; epub ahead of print
Tarkin JM, Rudd JH, Jayne DR, Rusk RA, Gopalan D
Heart: 13 Jul 2016; epub ahead of print | PMID: 27411841
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pascal\'s Wager, infective endocarditis and the "no-lose" philosophy in medicine.

Shaw D, Conway DI
Doctors and dentists have traditionally used antibiotic prophylaxis in certain patient groups in order to prevent infective endocarditis (IE). New guidelines, however, suggest that the risk to patients from using antibiotics is higher than the risk from IE. This paper analyses the relative risks of prescribing and not prescribing antibiotic prophylaxis against the background of Pascal\'s Wager, the infamous assertion that it is better to believe in God regardless of evidence, because of the prospective benefits should He exist. Many doctors seem to believe the parallel proposition that it is better to prescribe antibiotics, regardless of evidence, because of the prospective benefit conferred upon the patient. This has been called the "no lose philosophy" in medicine: better safe than sorry, even if the evidence inconveniently suggests that following this mantra is potentially more likely to result in sorry than safe. It transpires that, just as Pascal\'s Wager fails to convince because of a lack of evidence to support it and the costs incurred by trying to believe, so the "belts and braces" approach of prescribing antibiotic prophylaxis is unjustifiable given the actual evidence of potential risk and benefit to the patient. Ultimately, there is no no-lose if your clinical decisions, like Pascal\'s Wager, are based on faith rather than evidence.

Heart: 18 Dec 2009; 96:15-8
Shaw D, Conway DI
Heart: 18 Dec 2009; 96:15-8 | PMID: 20019208
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Rheumatic heart disease echocardiographic screening: approaching practical and affordable solutions.

Nascimento BR, Nunes MC, Lopes EL, Rezende VM, ... Sable C, Beaton AZ
Rheumatic heart disease (RHD) affects at least 32.9 million people worldwide and ranks as a leading cause of death and disability in low-income and middle-income countries (LMICs). Echocardiographic screening has been demonstrated to be a powerful tool for early RHD detection, and holds potential for global RHD control. However, national screening programmes have not emerged. Major barriers to implementation include the lack of human and financial resources in LMICs. Here, we focus on recent research advances that could make echocardiographic screening more practical and affordable, including handheld echocardiography devices, simplified screening protocols and task shifting of echocardiographic screening to non-experts. Additionally, we highlight some important remaining questions before echocardiographic screening can be widely recommended, including demonstration of cost-effectiveness, assessment of the impact of screening on children and communities, and determining the importance of latent RHD. While a single strategy for echocardiographic screening in all high-prevalence areas is unlikely, we believe recent advancements are bringing the public health community closer to developing sustainable programmes for echocardiographic screening.

Heart: 18 Feb 2016; epub ahead of print
Nascimento BR, Nunes MC, Lopes EL, Rezende VM, ... Sable C, Beaton AZ
Heart: 18 Feb 2016; epub ahead of print | PMID: 26891757
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

59-year-old female with breathlessness.

Scatteia A, De Garate E, Bucciarelli-Ducci C
A 59-year-old female underwent an electrocardiogram (ECG) and echocardiographic screening. Her brother died at quite a young age of kidney failure. Resting ECG showed borderline voltage criteria for left ventricular hypertrophy (LVH), with marked widespread T-wave inversion. Echocardiogram was normal, but in consideration of exertional breathlessness and abnormal baseline ECG, she underwent a coronary angiogram, which showed unobstructed coronaries. She was then referred to have a cardiac MR (CMR) for further characterisation. CMR images were acquired with a 1.5 T scanner and the imaging protocol included Steady-State Free Precession (SSFP) cine images (Figure 1A) as well as late gadolinium enhancement (LGE) images in the long-axis and short-axis planes covering the whole left ventricle (Figure 1B). In addition, native and postcontrast T1 mapping (Modified Look-Locker (MOLLI)) images were acquired for further tissue characterisation (Figure 1C and D, respectively).

Heart: 22 Jun 2016; epub ahead of print
Scatteia A, De Garate E, Bucciarelli-Ducci C
Heart: 22 Jun 2016; epub ahead of print | PMID: 27333905
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Secondary mitral regurgitation (part 2): deliberations on mitral surgery and transcatheter repair.

Gaasch WH, Meyer TE
Secondary mitral regurgitation (MR) develops as a consequence of postinfarction remodelling of the ventricle or other causes of left ventricular (LV) dilatation and dysfunction. The presence of MR amplifies the poor prognosis of the failing ventricle, but it has not been established whether the adverse outcomes stem from the MR or whether the MR is simply a marker of progressive LV dysfunction. In this article, an attempt will be made to clarify the clinical impact of mitral surgery and transcatheter repair in patients with secondary MR. Observational studies indicate symptomatic improvement, but the results of randomised trials are mixed. Furthermore, neither mitral surgery nor transcatheter repair consistently leads to reversal of the adverse LV remodelling. There is, however, general agreement that these procedures do not have a salutary effect on survival. Certainly mitral surgery and transcatheter repair can substantially reduce the mitral regurgitant flow, but inconsistencies and uncertainties regarding clinical outcomes persist in the published literature. Some such problems could be resolved by utilisation of more accurate and reproducible imaging modalities in randomised studies of patients who are most likely to benefit from a reduction in the regurgitant volume-namely those with the most severe MR.

Heart: 30 Mar 2018; 104:639-643
Gaasch WH, Meyer TE
Heart: 30 Mar 2018; 104:639-643 | PMID: 29437886
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term clinical outcomes of overlapping heterogeneous drug-eluting stents compared with homogeneous drug-eluting stents.

Her SH, Yoo KD, Park CS, Kim DB, ... Seung KB, Kim JH
Objectives To evaluate long-term clinical outcomes of overlapping heterogeneous drug-eluting stents (DES) compared with homogeneous DES. Design and setting The catholic medical centre coronary intervention database is a multicentre database of percutaneous coronary intervention with DES. This database contains data on consecutive patients from eight coronary intervention centres in Korea. Patients Overlapping homogeneous DES were used in 940 patients and overlapping heterogeneous DES in 140 patients between January 2005 and June 2010. Intervention The study enrolled patients with one-vessel disease treated with two overlapping DES in one lesion. Main outcome measures The study end point was the occurrence of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction (MI) or target lesion revascularisation (TRL). Results The two patient groups had similar baseline clinical and angiographic characteristics. MACE, cardiac death, MI and TRL rates, were not significantly different between the homogeneous and heterogeneous DES groups (9.9% vs 11.4%, p=0.574; 2.7% vs 3.6%, p=0.578; 1.5% vs 1.4%, p=1.000; 5.7% vs 6.4%, p=0.747, respectively). In addition, it was found that overlap with second-generation DES may be safe and effective, and the sirolimus-eluting stent (SES)+SES group had higher rate of MACE-free survival than the paclitaxel-eluting stent (PES)+PES group (p=0.014). Conclusions Overlapping heterogeneous DES and overlapping homogeneous DES had similar long-term safety and efficacy outcomes.

Heart: 01 Jul 2011; epub ahead of print
Her SH, Yoo KD, Park CS, Kim DB, ... Seung KB, Kim JH
Heart: 01 Jul 2011; epub ahead of print | PMID: 21719556
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Distinguishing ventricular septal bulge versus hypertrophic cardiomyopathy in the elderly.

Canepa M, Pozios I, Vianello PF, Ameri P, ... Ferrucci L, Abraham TP
The burgeoning evidence of patients diagnosed with sigmoidal hypertrophic cardiomyopathy (HCM) later in life has revived the quest for distinctive features that may help discriminate it from more benign forms of isolated septal hypertrophy often labelled ventricular septal bulge (VSB). HCM is diagnosed less frequently than VSB at older ages, with a reversed female predominance. Most patients diagnosed with HCM at older ages suffer from hypertension, similar to those with VSB. A positive family history of HCM and/or sudden cardiac death and the presence of exertional symptoms usually support HCM, though they are less likely in older patients with HCM, and poorly investigated in individuals with VSB. A more severe hypertrophy and the presence of left ventricular outflow obstruction are considered diagnostic of HCM, though stress echocardiography has not been consistently used in VSB. Mitral annulus calcification is very prevalent in both conditions, whereas a restrictive filling pattern is found in a minority of older patients with HCM. Genetic testing has low applicability in this differential diagnosis at the current time, given that a causative mutation is found in less than 10% of elderly patients with suspected HCM. Emerging imaging modalities that allow non-invasive detection of myocardial fibrosis and disarray may help, but have not been fully investigated. Nonetheless, there remains a considerable morphological overlap between the two conditions. Comprehensive studies, particularly imaging based, are warranted to offer a more evidence-based approach to elderly patients with focal septal thickening.

Heart: 27 Apr 2016; epub ahead of print
Canepa M, Pozios I, Vianello PF, Ameri P, ... Ferrucci L, Abraham TP
Heart: 27 Apr 2016; epub ahead of print | PMID: 27122487
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diagnosis and treatment of cardiac echinococcosis.

Kahlfuß S, Flieger RR, Roepke TK, Yilmaz K
Cardiac echinococcosis is a rare manifestation of cystic echinococcosis (CE) caused by the tapeworm Echinococcus granulosus Among all patients suffering from CE, only 0.5%-2% exhibit a cardiac involvement. In addition, during the past years the number of CE cases reported in Western Europe remained roughly unchanged. However, we postulate that cases of CE in Western Europe will increase due to a growing number of refugees coming from endemic areas such as Southern Europe, Eastern Europe and the Middle East. Importantly, although cardiac echinococcosis is rare the disease can lead to many clinical complications, for instance acute heart failure and life-threatening arrhythmias. With respect to the increasing relevance of cardiac echinococcosis in Western Europe and the danger of fulminant disease courses, here we review diagnosis strategies and treatment options of the disease. Diagnosis of cardiac echinococcosis requires a detailed evaluation of the patients\' case history, specific laboratory analyses and radiological imaging methods. Ultrasound, MRI and CT are key imaging tools for diagnosis, therapy control, prognosis estimation and disease course control. For the therapy of cardiac echinococcosis, a combination of surgical removal and drug treatment should be applied to symptomatic as well as asymptomatic patients. The complete surgical removal of the cyst(s) is the major prognosis factor of the cardiac manifestation of CE.

Heart: 19 May 2016; epub ahead of print
Kahlfuß S, Flieger RR, Roepke TK, Yilmaz K
Heart: 19 May 2016; epub ahead of print | PMID: 27199228
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Fontan circulation after 45 years: update in physiology.

Gewillig M, Brown SC
The Fontan operation was first performed in 1968. Since then, this operation has been performed on thousands of patients worldwide. Results vary from very good for many decades to very bad with a pleiad of complications and early death. A good understanding of the physiology is necessary to further improve results. The Fontan connection creates a critical bottleneck with obligatory upstream congestion and downstream decreased flow; these two features are the basic cause of the majority of the physiologic impairments of this circulation. The ventricle, while still the engine of the circuit, cannot compensate for the major flow restriction of the Fontan bottleneck: the suction required to compensate for the barrier effect cannot be generated, specifically not in a deprived heart. Except for some extreme situations, the heart therefore no longer controls cardiac output nor can it significantly alter the degree of systemic venous congestion. Adequate growth and development of the pulmonary arteries is extremely important as pulmonary vascular impedance will become the major determinant of Fontan outcome. Key features of the Fontan ventricle are early volume overload and overgrowth, but currently chronic preload deprivation with increasing filling pressures. A functional decline of the Fontan circuit is expected and observed as pulmonary vascular resistance and ventricular filling pressure increase with time. Treatment strategies will only be successful if they open up or bypass the critical bottleneck or act on immediate surroundings (impedance of the Fontan neoportal system, fenestration, enhanced ventricular suction).

Heart: 24 May 2016; epub ahead of print
Gewillig M, Brown SC
Heart: 24 May 2016; epub ahead of print | PMID: 27220691
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pulmonary vasoreactivity predicts long-term outcome in patients with Eisenmenger syndrome receiving bosentan therapy.

D\'Alto M, Romeo E, Argiento P, Santoro G, ... Naeije R, Calabrò R
Background Vasoreactivity testing is recommended in the management of pulmonary arterial hypertension (PAH), but its clinical relevance in congenital heart disease (CHD)-associated PAH has not been established. Objective To determine whether residual pulmonary vascular responsiveness to intravenous. epoprostenol is predictive of clinical outcome in patients with CHD-PAH and Eisenmenger syndrome. Methods and results A diagnostic right heart catheterisation with reversibility testing using epoprostenol infusion was performed in 38 consecutive patients with CHD-PAH and Eisenmenger syndrome. Patients were treated with bosentan and were assessed every 3 months. Clinical worsening was defined as death from any cause, heart-lung or lung transplantation (or on the waiting list for this procedure), hospitalisation for PAH, or symptom exacerbation defined as a >/=20% decrease in the 6 min walking distance on two consecutive tests, an increase in WHO functional class, or worsening right heart failure. The mean follow-up was 33+/-17 months. Sixteen patients showed clinical worsening. Although they did not differ from the other patients in their baseline exercise capacity, haemodynamic characteristics and underlying CHD, pulmonary vascular resistance index (PVRi) was less reversible (DeltaPVRi 29+/-21 vs 52+/-14%, p=0.0003). At univariate analysis, systemic vascular resistance, PVRi and DeltaPVRi were significant predictors of clinical worsening. At multivariate Cox proportional hazards regression model, DeltaPVRi was found to be the only independent predictor of clinical worsening (HR=0.973, 95% CI 0.95 to 0.99; p=0.01). DeltaPVRi >/=25% had a positive and negative predictive value for clinical worsening of 100% and 75.9%, respectively. Conclusion Pulmonary vasoreactivity is a significant predictor of clinical worsening in patients with CHD-PAH.

Heart: 29 Jul 2010; epub ahead of print
D'Alto M, Romeo E, Argiento P, Santoro G, ... Naeije R, Calabrò R
Heart: 29 Jul 2010; epub ahead of print | PMID: 20668108
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Bedside mental status and outcome in elderly patients admitted for acute coronary syndromes.

Briet C, Blanchart K, Lemaître A, Roux I, ... Roule V, Beygui F
Objective
We investigated whether mental status assessed by simple bedside tests in elderly patients admitted for acute coronary syndromes (ACS) was associated with higher risk of mortality.
Methods
We used the data from a prospective, open, ongoing cohort of patients≥75 years old admitted for ACS to a tertiary centre. Cognitive impairment (CogI) was defined by delirium detected by the Confusion Assessment Method or an abnormal Mini Mental State Examination score. A Cox model adjusted on predefined correlates of mortality was used to assess the relationship between CogI and 1-year mortality.
Results
Six-hundred consecutive patients with mental status assessment within 48 hours after admission were included. CogI was identified in 172 (29%) patients among whom 153 (25.5%) had an abnormal Mini Mental State Evaluation and 19 (3.2%) delirium. Death occurred in 49 (28.6%) patients with and 43 (10.5%) patients without CogI at 1 year. There was a significant association between CogI and 1-year mortality (adjusted-HR 2.4, 95% CI 1.53 to 3.62), p<0.001) independent of other covariables. CogI was also independently associated with higher rates of in-hospital bleeding and mortality as well as 3-month rates of all-cause, cardiovascular-related and heart failure-related rehospitalisation.
Conclusions
CogI detected by simple bedside tests in patients≥75 admitted for ACS is associated with an increased risk of 1-year mortality and 3 month rehospitalisation independent of other correlates of poor outcome.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2019; 105:1635-1641
Briet C, Blanchart K, Lemaître A, Roux I, ... Roule V, Beygui F
Heart: 30 Oct 2019; 105:1635-1641 | PMID: 31142593
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiovascular implanted electronic devices in people towards the end of life, during cardiopulmonary resuscitation and after death: guidance from the Resuscitation Council (UK), British Cardiovascular Society and National Council for Palliative Care.

Pitcher D, Soar J, Hogg K, Linker N, ... Mitchell S, CIED Working Group
The Resuscitation Council (UK), the British Cardiovascular Society (including the British Heart Rhythm Society and the British Society for Heart Failure) and the National Council for Palliative Care recognise the importance of providing clear and consistent guidance on management of cardiovascular implanted electronic devices (CIEDs) towards the end of life, during cardiorespiratory arrest and after death. This document has been developed to provide guidance for the full range of healthcare professionals who may encounter people with CIEDs in the situations described and for healthcare managers and commissioners. The authors recognise that some patients and people close to patients may also wish to refer to this document. It is intended as an initial step to help to ensure that people who have CIEDs, or are considering implantation of one, receive explanation of and understand the practical implications and decisions that this entails; to promote a good standard of care and service provision for people in the UK with CIEDs in the circumstances described; to offer relevant ethical and legal guidance on this topic; to offer guidance on the delivery of services in relation to deactivation of CIEDs where appropriate; to offer guidance on whether any special measures are needed when a person with a CIED receives cardiopulmonary resuscitation; and to offer guidance on the actions needed when a person with a CIED dies.

Heart: 08 Jun 2016; 102:A1-A17
Pitcher D, Soar J, Hogg K, Linker N, ... Mitchell S, CIED Working Group
Heart: 08 Jun 2016; 102:A1-A17 | PMID: 27277710
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction in Octogenarians; Trends and Outcomes.

Claessen BE, Kikkert WJ, Engstrom AE, Hoebers LP, ... Piek JJ, Henriques JP
Objective: The general population is gradually aging in the Western world. Therefore, the number of octogenarians undergoing primary Percutaneous Coronary Intervention (PCI) for ST-Elevation Myocardial Infarction (STEMI) is increasing. We aim to provide insight in temporal trends in the annual proportions of octogenarians among STEMI patients undergoing primary PCI and their clinical characteristics and outcomes over an eleven-year observational period. Design: Single-centre observational study. PATIENTS: Between 1997 and 2007, we treated 4506 STEMI patients with primary PCI at our institution. Patients aged >80 years were identified. Main outcome measures: We analyzed temporal trends in the annual proportion of octogenarian STEMI patients, and their baseline characteristics, 30-days and one-year mortality. Results: A total of 379 octogenarians (8.4% of the total population) were treated with primary PCI between 1997 and 2007. Over time, the annual proportion of octogenarians gradually increased from 4/113 (3.5%) in 1997 to 51/579 (8.8%) in 2007 (p for trend <0.01). In the total cohort of 379 patients, 30-day mortality was 21% (81 patients), one-year mortality was 28% (107patients). There was no improvement in survival among octogenarian STEMI patients over the eleven-year study period. Conclusion: The annual proportion of octogenarian STEMI patients increased significantly over the eleven-year study period. Mortality among these high-risk patients was high and did not improve during the study period. Unfortunately, little is known about the optimal treatment of the elderly as they are underrepresented in many randomized clinical trials. Further studies into the optimal STEMI management strategy for the elderly are warranted.

Heart: 07 Dec 2009; epub ahead of print
Claessen BE, Kikkert WJ, Engstrom AE, Hoebers LP, ... Piek JJ, Henriques JP
Heart: 07 Dec 2009; epub ahead of print | PMID: 19966111
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Approach to residual pulmonary valve dysfunction in adults with repaired tetralogy of Fallot.

Kim YY, Ruckdeschel E
Residual right ventricular outflow tract and pulmonary valve disease is common in adults with repaired tetralogy of Fallot. Chronic severe pulmonary regurgitation as a result of surgical repair can lead to myriad complications including right ventricular dysfunction, decreased exercise tolerance, right heart failure and symptomatic arrhythmias. The aim of restoring pulmonary valve integrity is to preserve right ventricular size and function with the intent of mitigating the development of symptoms and poor long-term outcomes. Right ventricular size thresholds by cardiac MRI have emerged beyond which reverse right ventricular remodelling after pulmonary valve replacement is less likely. Though pulmonary valve replacement has been shown to improve right ventricular dimensions and symptoms, no consistent improvement in right ventricular ejection fraction or objective measures of exercise capacity have been demonstrated. Furthermore, there are no long-term studies showing that normalisation of right ventricular size results in improved clinical outcomes. New transcatheter techniques of percutaneous pulmonary valve replacement have emerged with good short-term and mid-term outcomes, further adding to the complexity in determining \'when\' and \'how\' right ventricular outflow tract and pulmonary valve intervention should occur. With improved survival of these patients, the trend towards earlier pulmonary valve replacement at smaller right ventricular size and rapidly evolving transcatheter pulmonary valve techniques, the clinician must balance the goals of preserving right ventricular size and function in an attempt to prevent untoward outcomes with risks of multiple interventions in a patient\'s lifetime.

Heart: 21 Jun 2016; epub ahead of print
Kim YY, Ruckdeschel E
Heart: 21 Jun 2016; epub ahead of print | PMID: 27329296
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Echocardiographic assessment of raised pulmonary vascular resistance: application to diagnosis and follow-up of pulmonary hypertension.

Dahiya A, Vollbon W, Jellis C, Prior D, Wahi S, Marwick T
Objective To optimise an echocardiographic estimation of pulmonary vascular resistance (PVR(e)) for diagnosis and follow-up of pulmonary hypertension (PHT). Design Cross-sectional study. Setting Tertiary referral centre. Patients Patients undergoing right heart catheterisation and echocardiography for assessment of suspected PHT. Methods PVR(e) ([tricuspid regurgitation velocity ×10/(right ventricular outflow tract velocity-time integral+0.16) and invasive PVR(i) ((mean pulmonary artery systolic pressure-wedge pressure)/cardiac output) were compared in 72 patients. Other echo data included right ventricular systolic pressure (RVSP), estimated right atrial pressure, and E/e\' ratio. Difference between PVR(e) and PVR(i) at various levels of PVR was sought using Bland-Altman analysis. Corrected PVR(c) ((RVSP-E/e\')/RVOT(VTI)) (RVOT, RV outflow time; VTI, velocity time integral) was developed in the training group and tested in a separate validation group of 42 patients with established PHT. Results PVR(e)>2.0 had high sensitivity (93%) and specificity (91%) for recognition of PVR(i)>2.0, and PVR(c) provided similar sensitivities and specificities. PVR(e) and PVR(i) correlated well (r=0.77, p<0.01), but PVR(e) underestimated marked elevation of PVR(i)-a trend avoided by PVR(c). PVR(c) and PVR(e) were tested against PVR(i) in a separate validation group (n=42). The mean difference between PVR(e) and PVR(i) exceeded that between PVR(c) and PVR(i) (2.8±2.7 vs 0.8±3.0 Wood units; p<0.001). A drop in PVR(i) by at least one SD occurred in 10 patients over 6&emsp14;months; this was detected in one patient by PVR(e) and eight patients by PVR(c) (p=0.002). Conclusion PVR(e) distinguishes normal from abnormal PVR(i) but underestimates high PVR(i). PVR(c) identifies the severity of PHT and may be used to assess treatment response.

Heart: 19 Nov 2010; 96:2005-2009
Dahiya A, Vollbon W, Jellis C, Prior D, Wahi S, Marwick T
Heart: 19 Nov 2010; 96:2005-2009 | PMID: 21088122
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Perioperative transoesophageal echocardiography: current status and future directions.

Mahmood F, Shernan SK
Transoesophageal echocardiography (TOE) is used in the perioperative arena to monitor patients during life-threatening emergencies, cardiac and high-risk non-cardiac surgeries. It provides qualitative and quantitative information on valvular and ventricular functions, and dynamic cardiac anatomy can be displayed with a physiological perspective. This technology has evolved from two-dimensional (2D) to the ready availability of real-time three-dimensional (RT-3D) imaging in the operating rooms. Enhanced spatial and temporal resolutions with 3D imaging have most significantly impacted the quality of intraoperative surgical valve repair and replacement decisions. Additionally, 3D imaging has facilitated the advent of minimally invasive and percutaneous interventions for structural heart disease. Information derived from TEE is routinely used to evaluate a patient\'s suitability for an intervention, provide guidance during the intervention and eventually comment on the quality and success of the procedure. Expertise in perioperative TEE is an integral component of a cardiac anaesthesiologist\'s skill sets. With structural heart disease interventions becoming more minimally invasive, the intraoperative guidance provided by TEE will continue to be a critical component of these procedures. With improving computational and processing power, the expectations from TEE will continue to be incremental in the perioperative arena.

Heart: 05 Apr 2016; epub ahead of print
Mahmood F, Shernan SK
Heart: 05 Apr 2016; epub ahead of print | PMID: 27048769
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiac MR and CT imaging in children with suspected or confirmed pulmonary hypertension/pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

Latus H, Kuehne T, Beerbaum P, Apitz C, ... Muthurangu V, Moledina S
Childhood pulmonary hypertension (PH) is a heterogenous disease associated with considerable morbidity and mortality. Invasive assessment of haemodynamics is crucial for accurate diagnosis and guidance of medical therapy. However, adequate imaging is increasingly important in children with PH to evaluate the right heart and the pulmonary vasculature. Cardiac MR (CMR) and computed tomography (CT) represent important non-invasive imaging modalities that may enable comprehensive assessment of right ventricular (RV) function and pulmonary haemodynamics. Here, we present graded consensus recommendations for the evaluation of children with PH by CMR and CT. The article provides a structured approach for the use of CMR and CT imaging, emphasises non-invasive variables of RV function, myocardial tissue and afterload parameters that may be useful for initial diagnosis and monitoring. Furthermore, assessment of pulmonary perfusion and characterisation of the lung parenchyma provides structural information about processes that may cause or be due to PH.

Heart: 06 Apr 2016; 102:ii30-ii35
Latus H, Kuehne T, Beerbaum P, Apitz C, ... Muthurangu V, Moledina S
Heart: 06 Apr 2016; 102:ii30-ii35 | PMID: 27053695
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term antiplatelet therapy following myocardial infarction: implications of PEGASUS-TIMI 54.

Parker WA, Storey RF
Dual antiplatelet therapy (DAPT) is standard treatment for patients with acute coronary syndromes (ACS), typically comprising the use of aspirin with either an irreversible thienopyridine P2Y12 inhibitor, clopidogrel or prasugrel, or reversibly binding ticagrelor. Pivotal studies led to guidelines recommending DAPT for up to 12 months post-ACS. Despite this, there remains a significant burden of coronary artery disease (CAD)-related events up to and after this period. Recent meta-analyses, including both patients with ACS and patients with stable CAD treated with DAPT following percutaneous coronary intervention, have suggested that long-term thienopyridine-based DAPT reduces the risks of myocardial infarction (MI) and stent thrombosis but may paradoxically increase all-cause mortality risk. The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 54) study examined the effects of long-term DAPT with aspirin and ticagrelor, compared with aspirin alone, on major adverse cardiovascular events (MACE) and complications, including bleeding in patients with prior history of MI. It showed that, over a 3-year period, ticagrelor reduced the risk of MACE but increased non-fatal bleeding risk. Overall, the PEGASUS-TIMI 54 results demonstrate that patients with a history of ACS deemed to be at high risk of further ischaemic events, particularly those in whom the risks of ischaemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based DAPT. Guidelines are emerging which reflect this. The relationship between aspirin and ticagrelor, particularly with regard to aspirin dosing, remains to be fully elucidated and attention has recently been turned to the option of ticagrelor monotherapy. Future studies will explore optimal individualised strategies for long-term antiplatelet therapy.

Heart: 08 Feb 2016; epub ahead of print
Parker WA, Storey RF
Heart: 08 Feb 2016; epub ahead of print | PMID: 26857211
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Higher left ventricular mass-wall stress-heart rate product and outcome in aortic valve stenosis.

Gerdts E, Saeed S, Midtbø H, Rossebø A, ... Bahlmann E, Devereux R
Objective
Whether increased myocardial oxygen demand could help explain the association of left ventricular (LV) hypertrophy with higher adverse event rate in patients with aortic valve stenosis (AS) is unknown.
Methods
Data from 1522 patients with asymptomatic mostly moderate AS participating in the Simvastatin-Ezetimibe in AS study followed for a median of 4.3 years was used. High LV mass-wall stress-heart rate product was identified as >upper 95% CI limit in normal subjects. The association of higher LV mass-wall stress-heart rate product with major cardiovascular (CV) events, combined CV death and hospitalised heart failure and all-cause mortality was tested in Cox regression analyses, and reported as HR and 95% CI.
Results
High LV mass-wall stress-heart rate product was found in 19% at baseline, and associated with male sex, higher body mass index, hypertension, LV hypertrophy, more severe AS and lower LV ejection fraction (all p<0.01). Adjusting for these confounders in time-varying Cox regression analysis, 1 SD higher LV mass-wall stress-heart rate product was associated with higher HR of major CV events (HR 1.16(95% CI 1.06 to 1.29)), combined CV death and hospitalised heart failure (HR 1.29(95% CI 1.09 to 1.54)) and all-cause mortality (HR 1.34(95% CI 1.13 to 1.58), all p<0.01).
Conclusion
In patients with initially mild-moderate AS, higher LV mass-wall stress-heart rate product was associated with higher mortality and heart failure hospitalisation. Our results suggest that higher myocardial oxygen demand is contributing to the higher adverse event rate reported in AS patients with LV hypertrophy.
Trial registration number
NCT000092677;Post-results.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2019; 105:1629-1633
Gerdts E, Saeed S, Midtbø H, Rossebø A, ... Bahlmann E, Devereux R
Heart: 30 Oct 2019; 105:1629-1633 | PMID: 31154431
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Defective recovery of QT dispersion predicts late cardiac mortality after percutaneous coronary intervention.

Zimarino M, Corazzini A, Tatasciore A, Marazia S, ... Di Iorio C, De Caterina R
Background It has been suggested that corrected QT dispersion (cQTD) provides a measure of repolarisation inhomogeneity; however, the existence of a relationship between cQTD and cardiac outcomes is controversial. Objective To assess whether changes in cQTD following percutaneous coronary intervention (PCI) predict long-term survival. Design Prospective observational study. Setting Single tertiary care centre. Main outcome measures Cardiac mortality. Patients 612 patients had a 12-lead ECG recorded before and 6&emsp14;h after PCI, and were followed-up for 49±10&emsp14;months. Results PCI was associated with a significant overall reduction of cQTD at 6&emsp14;h versus baseline (p<0.001); a reduction in cQTD occurred in 343 patients (56%). During the follow-up, 46 deaths (7.5%) were recorded, 21 of which for non-cardiac and 25 for cardiac causes. At Cox regression analysis, a reduced ΔcQTD (cQTD baseline - 6&emsp14;h) was an independent predictor of cardiac mortality (HR=1.497; 95% CI 1.081 to 2.075 for each 20&emsp14;ms decrease; p=0.015), together with age (HR=1.672; 95% CI 1.039 to 2.691 per 10&emsp14;years increase; p=0.034), diabetes (HR=2.622; 95% CI 1.112 to 6.184; p=0.028), peak CK-MB (HR=1.798; 95% CI 1.063 to 3.039 per each unit increase over normal level; p=0.029), three-vessel coronary artery disease (HR=3.626; 95% CI 1.079 to 12.187; p=0.037) and the number of treated lesions (HR=2.066; 95% CI 1.208 to 3.532; p=0.008). Patients in the lowest tertile of ΔcQTD and having a post-procedural increase of CK-MB had a considerably higher cardiac mortality than the remaining population (14.6 vs 2.4%, p<0.001). Conclusions cQTD decreases after PCI. A defective cQTD recovery, suggesting the persistence of repolarisation inhomogeneities, predicts long-term cardiac mortality.

Heart: 28 Jan 2011; epub ahead of print
Zimarino M, Corazzini A, Tatasciore A, Marazia S, ... Di Iorio C, De Caterina R
Heart: 28 Jan 2011; epub ahead of print | PMID: 21270074
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.