Opinion

In this Perspectives article, Rodés-Cabau and colleagues discuss the evolving indications and future applications of transcatheter aortic valve implantation (TAVI). The steady improvement in prosthetic heart valves and the development of novel devices have enabled the continued expansion of TAVI indications, including the use of this procedure in low-risk patients or in aortic pathologies such as pure aortic regurgitation and bicuspid valve disease.

Several macromolecular structures coexist in the intercalated discs, which connect cardiomyocytes and control cell-to-cell communication. In this Perspectives article, Moncayo-Arlandi and Brugada suggest that the structures of the intercalated disc form an interactive 'connexome'. They also propose a link between arrhythmogenic cardiomyopathy and Brugada syndrome on the basis of overlapping genetic, molecular, and pathophysiological mechanisms.

In this Perspectives article, Ruilope and colleagues discuss the relevance and caveats of the SPRINT trial, with particular focus on patient cohort characteristics, the method used to measure blood-pressure levels, and applicability of the SPRINT blood-pressure targets in real-world clinical practice and future hypertension management guidelines.

In this Perspectives article, Lauer and colleagues discuss the causes for the increasing costs and inefficiencies in current clinical research, and provide potential strategies to transform clinical research business models, highlighting examples of innovative approaches that have been used successfully to conduct large-scale clinical trials and epidemiological research at relatively low cost.

In this Perspectives article, Captur et al. explain the fundamental principles of fractal geometry, and summarize cardiovascular studies in which fractal methods have been used to investigate disease mechanisms. The authors propose that clinical researchers can deploy innovative fractal solutions to common cardiac problems, which might ultimately translate into advancements in patient care.

Takotsubo syndrome is often thought to be the result of catecholamine-mediated myocardial stunning triggered by emotional or physiological stress. In this Perspectives article, Kastaun and colleagues discuss the latest studies evaluating the psychoneuroendocrinological and psychosocial mechanisms underlying the pathophysiology of Takotsubo syndrome.

In this Perspectives article, Ormerod et al. propose that dynamic left ventricular systolic dysfunction provoked by obstruction in hypertrophic cardiomyopathy is a manifestation of inefficient cardiac energy utilization. This mid-systolic drop in left ventricular Doppler ejection velocities has been termed the 'lobster claw abnormality'. Energy insufficiency is also present in nonobstructive hypertrophic cardiomyopathy, and this paradigm might suggest novel therapies.

Diagnosis and treatment in patients with an aborted cardiac arrest (ACA) pose a challenge for cardiologists, because the underlying causes of ACA and the appropriate therapies are varied. In this Perspectives article, Schwartz and Dagradi offer their view on how genetics is shaping the management of survivors of ACA, and discuss the importance of genetic testing for the protection of these patients and their families.

Renal denervation for the treatment of drug-resistant hypertension has been studied extensively in the past few years. Although early trials reported dramatic reductions in blood pressure after renal denervation, later trials testing denervation against a sham procedure showed neutral results. In this Perspectives article, Gulati and colleagues suggest potential reasons why results from these early trials could not be replicated, and summarize the current available trial data, newly designed devices, and recommendations for future trial design.

The quest for a practical total artificial heart (TAH) stems from the large number of patients with advanced heart failure, and the limited number of donor hearts available for transplantation. In this Perspectives article, Cohn et al. give their expert insight into the development of TAHs over the past 50 years. They describe the evolution from positive-displacement, pulsatile pumps to continuous-flow devices, and give their opinion on the most promising avenues for future innovation.

Randomized clinical trials are the gold-standard clinical trial design, because they can control for confounding factors. However, they also limited by large financial costs and rigid selection criteria. A possible solution to these limitations is the registry-based randomized clinical trial (RRCT). In this Perspectives article, James et al. discuss the features of RRCTs, and how this trial design can be used to conduct studies efficiently and cost-effectively.

Preparicipation screening for cardiovascular disease in young competitive athletes is a controversial topic. Moreover, young people not engaged in competitive sports can harbour the same conditions that cause sudden death in athletes. In this Perspectives article, Maron et al. question whether arbitrarily excluding individuals from potentially life-saving clinical screening because they do not engage in competitive sports programmes is ethical.

Transcatheter aortic valve implantation (TAVI) is an established therapeutic option for high-risk patients with a tricuspid aortic valve, but patients with a bicuspid aortic valve (BAV) are contraindicated. In this Perspectives article, Zhao and colleagues summarize the available evidence for the use of TAVI in patients with a BAV and propose that this procedure might be appropriate in high-risk or inoperable individuals, but that more evidence is required before indications for TAVI can be extended to other patients with a BAV.

The global epidemic of cardiovascular disease is being fuelled by the spread of a Western lifestyle characterized by a high prevalence of cardiovascular risk factors. In this Perspectives article, Valentin Fuster highlights 10 therapies and interventions that, in his opinion, will be most useful in combating cardiovascular disease and promoting cardiovascular health over the next decade.

Cardiovascular and renal disease often have similar origins and shared risk factors. With the progression of chronic kidney disease, additional risk factors develop, contributing to the evolution of both diseases. In this Perspectives article, Ruiz-Hurtado and Ruilope postulate that that simultaneous protection for both cardiovascular and renal disease can be achieved with the same therapy. They review the evidence from clinical trials supporting this theory, and discuss strategies to prevent both cardiovascular and chronic kidney disease.

Mutations in theSCN5A gene, which encodes the cardiac sodium channel, are well known to cause gain or loss of channel function and, consequently, various cardiac arrhythmias. However, greater phenotypic variability exists than can be ascribed directly to mutation-dependent changes in channel biophysical properties. In this Perspectives article, Liu et al. propose that additional intrinsic and extrinsic modifiers of channel behaviour might help to explain this variability and to improve genotype–phenotype correlations.

Blood motion in the heart features vortices, the stability of which is vital to the dynamic balance between rotating blood and myocardial tissue and to the development of cardiac dysfunction. In this Perspectives article, Pedrizzetti et al. examine cardiac vortex flow as a sensitive pathogenetic indicator and modulator of left ventricular remodelling towards heart failure, and the role of cardiac vortices for risk stratification of patients following cardiac surgery or device therapy.

Coronary 'no-reflow' is a substantial clinical problem, even after successful percutaneous coronary intervention for myocardial infarction. In this Perspectives, article, O'Farrell and Attwell describe the similarities between this phenomenon and no-reflow in the brain after ischaemic stroke, and propose that pericytes contribute to the underlying pathophysiology in both situations. Cardiac pericytes might, therefore, be a novel therapeutic target for coronary no-reflow.

Adherence to medication is a prerequisite for treatment to be effective, but fewer than half of patients are adherent to long-term therapies for cardiovascular diseases, such as antihypertensive drugs and statins. In this Perspectives article, Tajouri and colleagues propose that multifaceted, individually tailored strategies that harness incentives schemes and modern technology are required to improve both adherence to medication and patient health.

Chelation therapy with ethylenediamine tetra acetic acid is increasingly being used in patients with cardiovascular disease, without definitive evidence for its efficacy. In this Perspectives article, Sidhu et al. discuss data from major studies of chelation therapy in this field, with particular emphasis on TACT. They opine that the findings from this trial are not robust and do not marshal evidence in support of the potential clinical use of chelation therapy for cardiovascular disease.