Optimising cardiovascular care of patients with multiple myeloma.

Multiple myeloma (MM) is the third most common haematological malignancy, with increasing prevalence over recent years. Advances in therapy have improved survival, changing the clinical course of MM into a chronic condition and meaning that management of comorbidities is fundamental to improve clinical outcomes. Cardiovascular (CV) events affect up to 7.5% of individuals with MM, due to a combination of patient, disease and treatment-related factors and adversely impact survival. MM typically affects older people, many with pre-existing CV risk factors or established CV disease, and the disease itself can cause renal impairment, anaemia and hyperviscosity, which exacerabate these further. Up to 15% of patients with MM develop systemic amyloidosis, with prognosis determined by the extent of cardiac involvement. Management of MM generally involves administration of multiple treatment lines over several years as disease progresses, with many drug classes associated with adverse CV effects including high rates of venous and arterial thrombosis alongside heart failure. Recommendations for holistic management of patients with MM now include routine baseline risk stratification including ECG and echocardiography and administration of thromboprophylaxis drugs for patients treated with immunomodulatory drugs. Close surveillance of high-risk patients with collaboration between haematology and cardiology is required, with prompt investigation in the event of CV symptoms, in order to identify and treat complications early. Decisions regarding discontinuation of cardiotoxic therapies should be made in a multidisciplinary setting, taking into account the severity of the complication, prognosis, expected benefits and the availability of effective alternatives.

Applications of cosinor rhythmometry in pharmacology.

Study design and data analysis are two important aspects relevant to chronopharmacometrics. Blunders can be avoided by recognizing that most physiological variables are circadian periodic. Both ill health and treatment can affect the amplitude, phase, and/or period of circadian (and other) rhythms, in addition to their mean. The involvement of clock genes in molecular pathways related to important physiological systems underlies the bidirectional relationship often seen between circadian rhythm disruption and disease risk. Circadian rhythm characteristics of marker rhythms interpreted in the light of chronobiologic reference values represent important diagnostic tools. A set of cosinor-related programs is presented. They include the least squares fit of multiple-frequency cosine functions to model the time structure of individual records; a cosinor-based spectral analysis to detect periodic signals; the population-mean cosinor to generalize inferences; the chronobiologic serial section to follow the time course of changing rhythm parameters over time; and parameter tests to assess differences among populations. Relative merits of other available cosinor and non-parametric algorithms are reviewed. Parameter tests to compare individual records and a self-starting cumulative sum (CUSUM) make personalized chronotherapy possible, where the treatment of each patient relies on an N-of-1 design. Methods are illustrated in a few examples relevant to endocrinology, cancer and cardiology. New sensing technology yielding large personal data sets is likely to change the healthcare system. Chronobiologic concepts and methods should become an integral part of these evolving systems.

Strengths and Opportunities of Network Medicine in Cardiovascular Diseases.

Network medicine can advance current medical practice by arising as response to the limitations of a reductionist approach focusing on cardiovascular (CV) diseases as a direct consequence of a single defect. This molecular-bioinformatic approach integrates heterogeneous "omics" data and artificial intelligence to identify a chain of perturbations involving key components of multiple molecular networks that are closely related in the human interactome. The clinical view of the network-based approach is greatly supported by the general law of molecular interconnection governing all biological complex systems. Recent advances in bioinformatics have culminated in numerous quantitative platforms able to identify CV disease modules underlying perturbations of the interactome. This might provide novel insights in CV disease mechanisms as well as putative biomarkers and drug targets. We describe the network-based principles and discuss their application to classifying and treating common CV diseases. We compare the strengths and weaknesses of molecular networks in comparison with the classical current reductionist approach, and remark on the necessity for a two-way approach connecting network medicine with large clinical trials to concretely translate novel insights from bench to bedside.

Reducing the hospital burden associated with the treatment of pulmonary embolism.

Pulmonary embolism (PE) is the most feared clinical presentation of venous thromboembolism (VTE). Patients with PE have traditionally been treated in hospital; however, many are at low risk of adverse outcomes and current guidelines suggest outpatient treatment as an option. Outpatient treatment of PE offers several advantages, including reduced risk of hospital-acquired conditions and potential cost savings. Despite this, patients with low-risk PE are still frequently hospitalized for treatment. This narrative review summarizes current guideline recommendations for the identification of patients with low-risk PE who are potentially suitable for outpatient treatment, using prognostic assessment tools (e.g. the Pulmonary Embolism Severity Index [PESI] and simplified PESI) and clinical exclusion criteria (e.g. Hestia criteria) alone or in combination with additional cardiac assessments. Treatment options are discussed along with recommendations for the follow-up of patients managed in the non-hospital environment. The available data on outpatient treatment of PE are summarized, including details on patient selection, anticoagulant choice, and short-term outcomes in each study. Accumulating evidence suggests that outcomes in patients with low-risk PE treated as outpatients are at least as good as, if not better than, those of patients treated in the hospital. With mounting pressures on health care systems worldwide, increasing the proportion of patients with PE treated as outpatients has the potential to reduce health care burdens associated with VTE.

Management of Patients with Asymptomatic and Symptomatic Carotid Artery Disease: Update on Anti-Thrombotic Therapy.

The most common causes of ischaemic stroke are represented by carotid artery atherosclerotic disease (CAAD) and atrial fibrillation. While oral anticoagulants substantially reduce the incidence of thromboembolic stroke (< 1%/year), the rate of ischaemic stroke and other cardiovascular disease events in patients with CAAD remains high, ranging from 8.4 to 18.1 events per 100 patient-years. Similar to any other atherosclerotic disease, anti-thrombotic therapies are proposed for CAAD to reduce stroke and other cardiovascular events. The 2017 European Society of Cardiology (ESC)/European Society for Vascular Surgery (ESVS) guidelines recommend for patients with asymptomatic CAAD ≥60% the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily at the exception of patient at very high bleeding risk. For patients with symptomatic CAAD ≥50%, the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily is recommended. New perspectives for anti-thrombotic therapy for the treatment of patients with CAAD come from the novel dual pathway strategy combining a low-dose anticoagulant (i.e. rivaroxaban) and aspirin that may help reduce long-term ischaemic complications in patients with CAAD. This review summarizes current evidence and recommendations for the anti-thrombotic management of patients with symptomatic or asymptomatic CAAD or those undergoing carotid revascularization.

Arrhythmias in congenital heart disease: a position paper of the European Heart Rhythm Association (EHRA), Association for European Paediatric and Congenital Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on Grown-up Congenital heart disease, endorsed by HRS, PACES, APHRS, and SOLAECE.

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnormal cardiac anatomy and physiology. Finally, device therapies allowing maintanence of chronotropic competence and AV conduction, improving haemodynamics by cardiac resynchronization, and preventing sudden death are increasingly used. For pharmacological therapy, ablation procedures, and device therapy decision making requires a deep understanding of the individual pathological anatomy and physiology as well as detailed knowledge on natural history and long-term prognosis of our patients. Composing expert opinions from cardiology and paediatric cardiology as well as from non-invasive and invasive electrophysiology this position paper was designed to state the art in management of young individuals with congenital heart defects and arrhythmias.

A Deficiency of Nutrition Education and Practice in Cardiology.

BACKGROUND: Nutrition is one of the foundations of cardiovascular guidelines for risk reduction and treatment. However, little is known about whether cardiologists, cardiology fellows-in-training, and cardiovascular team members have the nutrition education and knowledge necessary to implement these guidelines. The aim of this study was to describe the educational experiences, attitudes, and practices relating to nutrition among cardiovascular professionals. METHODS: Surveys completed by cardiologists, fellows-in-training, and cardiovascular team members inquired about their personal dietary habits, history of nutrition education, and attitudes regarding nutrition interventions. RESULTS: A total of 930 surveys were completed. Among cardiologists, 90% reported receiving no or minimal nutrition education during fellowship training, 59% reported no nutrition education during internal medicine training, and 31% reported receiving no nutrition education in medical school. Among cardiologists, 8% described themselves as having "expert" nutrition knowledge. Nevertheless, fully 95% of cardiologists believe that their role includes personally providing patients with at least basic nutrition information. The percentage of respondents who ate ≥5 servings of vegetables and fruits per day was: 20% (cardiologists), 21% (fellows-in-training), and 26% (cardiovascular team members). CONCLUSIONS: A large proportion of cardiovascular specialists have received minimal medical education and training in nutrition, and current trainees continue to experience significant education and training gaps.

Engineering Cardiac Muscle Tissue: A Maturating Field of Research.

Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues of different kinds are now generated routinely in many laboratories. Advances in stem cell biology and engineering allow for the generation of constructs that come close to recapitulating the complex structure of heart muscle and might, therefore, be amenable to industrial (eg, drug screening) and clinical (eg, cardiac repair) applications. Whether the more physiological structure of 3-dimensional constructs provides a relevant advantage over standard 2-dimensional cell culture has yet to be shown in head-to-head-comparisons. The present article gives an overview on current strategies of cardiac tissue engineering with a focus on different hydrogel methods and discusses perspectives and challenges for necessary steps toward the real-life application of cardiac tissue engineering for disease modeling, drug development, and cardiac repair.

Simulation-based training for cardiology procedures: Are we any further forward in evidencing real-world benefits?

Simulation-based training as an educational tool for healthcare professionals continues to grow in sophistication, scope, and usage. There have been a number of studies demonstrating the utility of the technique, and it is gaining traction as part of the training curricula for the next generation of cardiologists. In this review, we focus on the recent literature for the efficacy of simulation for practical procedures specific to cardiology, focusing on transesophageal echocardiography, cardiac catheterization, coronary angioplasty, and electrophysiology. A number of studies demonstrated improved performance by those trained using SBT when compared to other methods, although evidence of this leading to an improvement in patient outcomes remains scarce. We discuss this evidence, and the implications for practice for training in cardiology.

Precision medicine in cardiology.

The cardiovascular research and clinical communities are ideally positioned to address the epidemic of noncommunicable causes of death, as well as advance our understanding of human health and disease, through the development and implementation of precision medicine. New tools will be needed for describing the cardiovascular health status of individuals and populations, including 'omic' data, exposome and social determinants of health, the microbiome, behaviours and motivations, patient-generated data, and the array of data in electronic medical records. Cardiovascular specialists can build on their experience and use precision medicine to facilitate discovery science and improve the efficiency of clinical research, with the goal of providing more precise information to improve the health of individuals and populations. Overcoming the barriers to implementing precision medicine will require addressing a range of technical and sociopolitical issues. Health care under precision medicine will become a more integrated, dynamic system, in which patients are no longer a passive entity on whom measurements are made, but instead are central stakeholders who contribute data and participate actively in shared decision-making. Many traditionally defined diseases have common mechanisms; therefore, elimination of a siloed approach to medicine will ultimately pave the path to the creation of a universal precision medicine environment.

Use of smartphone technology in cardiology.

Smartphone-based technologies along with broadband connectivity are changing the way modern cardiology is practiced. The ever broadening connectivity and increasing capabilities of smartphone-based technologies can better monitor, diagnose, and prevent cardiovascular diseases. Researchers can leverage the ubiquitous use of smartphone-based technologies and their constant stream of biometric data to establish large community-based clinical research studies. Patient engagement is enhanced with constant and on-demand access to physicians, daily self-monitoring, and expanding social networks. On the other hand, the exponential growth of smartphone-based technologies invariably disrupts the traditional healthcare model and leaves a vacuum in the infrastructure, medico-legal apparatus, and reimbursement systems that need to be addressed. In this review, we present a comprehensive discussion of the various applications utilizing smartphone-based technologies in cardiology.

Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop.

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting.

Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2) ): an evidence-based mnemonic for the treatment of systolic heart failure.

Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline-based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice, which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID (2) , standing for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine, devices (automatic implantable cardioverter defibrillator, cardiac resynchronisation therapy or both) and digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence-based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition.

Integrating acupuncture into the cardiology clinic: can it play a role?

Despite continued improvement in risk factor recognition and aggressive medical management, heart disease remains the number one killer in the world. Medications for primary or secondary prevention of heart disease can cause unpleasant side effects leading to non-compliance. Novel therapies are needed to serve as a complement to or alternative for current medical management. Acupuncture and more specifically electroacupuncture may serve as a safe and viable option in the cardiology clinic. This review article focuses on both mechanistic and clinical studies evaluating acupuncture's effectiveness with symptomatic heart disease. Although continued research is needed, currently evidence warrants consideration of acupuncture's use with myocardial ischemia, hypertension, arrhythmias, heart failure as well as autonomic dysfunction.