Review Articles

  • Review Article |

    By stimulating the His–Purkinje network directly, His bundle pacing results in synchronized, physiological ventricular activation, which might improve clinical outcomes compared with the use of right ventricular apical pacing. Sharma and colleagues summarize early clinical observations, implantation techniques and outcome data with permanent His bundle pacing.

    • Parikshit S. Sharma
    • , Pugazhendhi Vijayaraman
    •  & Kenneth A. Ellenbogen
  • Review Article |

    The role of aspirin for the primary prevention of cardiovascular disease is controversial. In this Review, Patrono and Baigent discuss the new randomized trials on aspirin for the primary prevention of cardiovascular disease in the context of previous evidence, and appraise whether the new evidence is likely to enable a more targeted use of aspirin

    • Carlo Patrono
    •  & Colin Baigent
  • Review Article |

    In this Review, Mallat and colleagues critically evaluate the studies on the origin, fate and functions of vascular smooth muscle cells (VSMCs) in atherosclerosis, highlighting the importance of developmental origin, clonal expansion and plasticity of VSMCs cells in atherosclerosis and summarizing the roles of VSMCs and VSMC-derived cells in plaque development and progression.

    • Gemma L. Basatemur
    • , Helle F. Jørgensen
    • , Murray C. H. Clarke
    • , Martin R. Bennett
    •  & Ziad Mallat
  • Review Article |

    Neuromodulation therapy might be clinically useful in the management and prevention of lethal arrhythmias. In this Review, the authors discuss the neuroanatomical and neurophysiological basis for neuromodulation therapy, critically appraise the latest data on the clinical efficacy of this approach and highlight areas in the field of cardiac autonomic control that show the most promise for clinical translation.

    • Neil Herring
    • , Manish Kalla
    •  & David J. Paterson
  • Review Article |

    With the increase in the availability of RNA screening tools, numerous non-coding RNAs with important functions in the heart have been identified. In this Review, Lu and Thum discuss the non-coding RNA candidates with diagnostic and therapeutic potential in cardiovascular disease.

    • Dongchao Lu
    •  & Thomas Thum
  • Review Article |

    G protein-coupled receptor (GPCR) kinases (GRKs) can desensitize and downregulate GPCRs. In this Review, Pfleger and colleagues describe the changes in GPCR and GRK signalling in the heart under disease conditions and how GRKs can be targeted to treat heart failure.

    • Jessica Pfleger
    • , Kenneth Gresham
    •  & Walter J. Koch
  • Review Article |

    Antiretroviral therapy has transformed HIV infection into a chronic disease, and cardiovascular diseases are an important health concern in this setting. This Review discusses the clinical features of cardiovascular disease in patients with HIV infection, including the mechanisms underlying HIV-associated atherosclerosis and approaches to reduce the cardiovascular risk.

    • Priscilla Y. Hsue
    •  & David D. Waters
  • Review Article |

    Infective endocarditis (IE) is not a common disease, but it has a poor prognosis. In this Review, contemporary findings concerning the epidemiology, diagnosis, therapeutic management and prevention of IE are highlighted, with a particular emphasis on innovations and changes in guidelines.

    • Bernard Iung
    •  & Xavier Duval
  • Review Article |

    The use of polypills containing multiple pharmaceutical agents targeting the cardiovascular system in the primary prevention of cardiovascular disease is controversial. In this Review, Chow and Meng discuss the barriers to the use of polypills and focus in detail on the use of fixed-dose combination pills containing low doses of multiple blood pressure-lowering drugs.

    • Clara K. Chow
    •  & Qingtao Meng
  • Review Article |

    Conflicting findings about the effects of testosterone replacement therapy on the risk of cardiovascular disease have been reported in various studies and clinical trials. In this Review, Gagliano-Jucá and Basaria discuss the design, outcomes and shortcomings of studies on testosterone replacement therapy, as well as studies examining the cardiovascular effects of testosterone in vitro, in animals and in humans.

    • Thiago Gagliano-Jucá
    •  & Shehzad Basaria
  • Review Article |

    Dietary fats comprise heterogeneous molecules with diverse structures and complex health effects. This Review discusses the effects of different dietary fats on cell processes and cardiometabolic disease risk factors and clinical events, highlighting areas of controversy and future research directions to improve the prevention and management of cardiometabolic diseases through optimization of dietary fat intake.

    • Jason H. Y. Wu
    • , Renata Micha
    •  & Dariush Mozaffarian
  • Review Article |

    Mutations in genes that encode components of desmosomes are the predominant cause of arrhythmogenic cardiomyopathy, a genetic disorder characterized by fibrofatty replacement of myocardial tissue and the risk of life-threatening arrhythmias. In this Review, the authors discuss the molecular mechanisms underlying the pathogenesis of this condition.

    • Karyn M. Austin
    • , Michael A. Trembley
    • , Stephanie F. Chandler
    • , Stephen P. Sanders
    • , Jeffrey E. Saffitz
    • , Dominic J. Abrams
    •  & William T. Pu
  • Review Article |

    Tricuspid valve disease, particularly tricuspid regurgitation, is a highly prevalent condition with complex pathophysiology and long-term adverse consequences. In this Review, Rodés-Cabau and colleagues discuss the latest insights on the natural history and clinical and imaging assessment of tricuspid valve disease, highlighting the surgical management and emerging transcatheter therapies that are transforming clinical practice for this challenging disease.

    • Lluis Asmarats
    • , Maurizio Taramasso
    •  & Josep Rodés-Cabau
  • Review Article |

    Circular RNAs (circRNAs) are emerging as a new class of non-coding RNA molecules. In this Review, the authors discuss the current understanding of circRNA biogenesis and function, with a particular emphasis on the cardiovascular system.

    • Simona Aufiero
    • , Yolan J. Reckman
    • , Yigal M. Pinto
    •  & Esther E. Creemers
  • Review Article |

    Neuroimmune crosstalk has a potential role in the development and maintenance of arterial hypertension. Parati and colleagues discuss the interplay between the bone marrow, microglia and immune mediators, in particular through mechanisms involving cytokines and peptides, such as neuropeptide Y, substance P, angiotensin II and angiotensin-(1–7).

    • Laura Calvillo
    • , Mariela M. Gironacci
    • , Lia Crotti
    • , Pier Luigi Meroni
    •  & Gianfranco Parati
  • Review Article |

    Various models of cardiac arrhythmia have been developed in several different animal species to study the mechanisms of disease. In this Review, Clauss and colleagues summarize the advantages and disadvantages of the models and species used in arrhythmia research and provide guidance to investigators planning experiments in this field.

    • Sebastian Clauss
    • , Christina Bleyer
    • , Dominik Schüttler
    • , Philipp Tomsits
    • , Simone Renner
    • , Nikolai Klymiuk
    • , Reza Wakili
    • , Steffen Massberg
    • , Eckhard Wolf
    •  & Stefan Kääb
  • Review Article |

    Endothelin 1 is the most potent vasoconstrictor in the human cardiovascular system. In this Review, Dhaun and Webb discuss the biology of the endothelins and endothelin receptors and how these pathways can be therapeutically targeted in cardiovascular and renal diseases.

    • Neeraj Dhaun
    •  & David J. Webb
  • Review Article |

    In this Review, Berg and colleagues discuss how to maximize the likelihood of successful resuscitation after out-of-hospital cardiac arrest. The ‘chain of survival’ includes immediate recognition of cardiac arrest, early bystander cardiopulmonary resuscitation, rapid defibrillation, advanced emergency medical services and integrated post-cardiac arrest care.

    • David D. Berg
    • , Bentley J. Bobrow
    •  & Robert A. Berg
  • Review Article |

    Atherosclerosis is characterized by low-grade, chronic inflammation, and the balance between pro-inflammatory and inflammation-resolving mechanisms dictates the clinical outcomes. This Review discusses the specific causes of inflammation and the mechanisms underlying the impaired resolution of inflammation that characterize clinically dangerous atherosclerotic lesions and highlights the potential of pro-resolving mediator therapy for the prevention and treatment of atherosclerotic cardiovascular disease.

    • Magnus Bäck
    • , Arif Yurdagul Jr
    • , Ira Tabas
    • , Katariina Öörni
    •  & Petri T. Kovanen
  • Review Article |

    Many cardiovascular functions and the onset of adverse cardiovascular events are influenced by the circadian rhythm that exists in all cell types. In this Review, the authors summarize the role of the molecular clock in cardiovascular physiology and disease and suggest how circadian rhythms can be exploited, such as in chronotherapy, or targeted therapeutically.

    • Sandra Crnko
    • , Bastiaan C. Du Pré
    • , Joost P. G. Sluijter
    •  & Linda W. Van Laake
  • Review Article |

    Postoperative atrial fibrillation complicates 20–40% of cardiac surgical procedures. In this Review, the authors summarize the epidemiological and clinical features of postoperative atrial fibrillation, the available pathophysiological evidence and the recommended prophylactic and therapeutic approaches.

    • Dobromir Dobrev
    • , Martin Aguilar
    • , Jordi Heijman
    • , Jean-Baptiste Guichard
    •  & Stanley Nattel
  • Review Article |

    This Review summarizes the preclinical data on the role of T cell co-stimulatory and co-inhibitory pathways in cardiovascular disease (CVD) and discusses the therapeutic potential of targeting co-stimulation and inhibition molecules to treat CVD, as well as the evidence of an association between the use of immune checkpoint inhibitors and cardiovascular toxicity.

    • Karin H. Simons
    • , Alwin de Jong
    • , J. Wouter Jukema
    • , Margreet R. de Vries
    • , Ramon Arens
    •  & Paul H. A. Quax
  • Review Article |

    In this Review, the authors summarize mechanoregulated pathways in cardiac myocytes and fibroblasts that lead to altered gene expression and cell remodelling under physiological and pathophysiological conditions. They also discuss the use of systems modelling to discover new therapies to target mechanosignalling in heart disease.

    • Jeffrey J. Saucerman
    • , Philip M. Tan
    • , Kyle S. Buchholz
    • , Andrew D. McCulloch
    •  & Jeffrey H. Omens
  • Review Article |

    In this Review, Boffa and Koschinsky discuss the role of lipoprotein(a) (Lp(a)) as a risk factor for atherothrombotic cardiovascular disease and calcific aortic valve disease, highlighting the important function of oxidized phospholipid modifications of Lp(a), which elicit harmful signalling processes in the arterial wall and the valve leaflet, in mediating the effects of this lipoprotein on both disorders.

    • Michael B. Boffa
    •  & Marlys L. Koschinsky
  • Review Article |

    Transient receptor potential (TRP) channels are a family of 28 nonselective cationic channels that are heterogeneously expressed in different regions and cell types of the heart. In this Review, the authors summarize the various physiological and pathological cardiac processes in which TRP channels are involved.

    • Thomas Hof
    • , Sébastien Chaigne
    • , Alice Récalde
    • , Laurent Sallé
    • , Fabien Brette
    •  & Romain Guinamard
  • Review Article |

    Paravalvular leak (PVL) is a common complication after surgical prosthetic valve implantation. This Review details the role of cardiac imaging in the assessment and management of PVL, summarizes the clinical evidence for percutaneous closure of PVL and compares this procedure with surgical closure.

    • Joel P. Giblett
    • , Bushra S. Rana
    • , Leonard M. Shapiro
    •  & Patrick A. Calvert
  • Review Article |

    Fully bioresorbable scaffolds (BRS) were designed to overcome the limitations of metallic drug-eluting stents, but long-term results with these devices have been disappointing. In this Review, the authors discuss the available preclinical and clinical data for BRS and how this information can inform the development of next-generation BRS.

    • Hiroyuki Jinnouchi
    • , Sho Torii
    • , Atsushi Sakamoto
    • , Frank D. Kolodgie
    • , Renu Virmani
    •  & Aloke V. Finn
  • Review Article |

    This Review summarizes the mechanisms of ectopic calcification processes in the cardiovascular system, with an emphasis on emerging knowledge obtained from advances in imaging methods, experimental models and multiomics-generated big data. This Review highlights the potential and challenges of artificial intelligence, machine learning and deep learning to integrate imaging and mechanistic data to identify biomarkers and effective treatments for cardiovascular calcification

    • Maximillian A. Rogers
    •  & Elena Aikawa
  • Review Article |

    Stent thrombosis is a rare but severe complication of coronary intervention and has a complex underlying pathophysiology. In this Review, Gori and colleagues describe the risk factors for stent thrombosis and discuss how a better understanding of the mechanisms underlying this complication can inform its prevention and treatment.

    • Tommaso Gori
    • , Alberto Polimeni
    • , Ciro Indolfi
    • , Lorenz Räber
    • , Tom Adriaenssens
    •  & Thomas Münzel
  • Review Article |

    Cardiovascular disease (CVD) is the leading cause of death in China. In this Review, Zhao and colleagues summarize eight important features of the evolving epidemiology of CVD in China and discuss how this information can help to develop effective and timely strategies to prevent and treat CVD.

    • Dong Zhao
    • , Jing Liu
    • , Miao Wang
    • , Xingguang Zhang
    •  & Mengge Zhou
  • Review Article |

    This Review discusses the latest findings and current theories on the pathogenesis of abdominal aortic aneurysm (AAA) and highlights potential medical therapies for AAA, summarizing previous, ongoing, and potential clinical trials of medical interventions for small AAAs. This expanding volume of research is expected to result in a range of novel medical therapies for AAA within the next decade.

    • Jonathan Golledge
  • Review Article |

    This Review provides an update of the latest developments in our understanding of platelet functions and populations in normal physiology and in haemorrhagic, thrombotic, and inflammatory conditions. These advancements can aid in tailoring new strategies to target platelets in disease states while avoiding the increased risk of bleeding associated with current antiplatelet therapies.

    • Paola E. J. van der Meijden
    •  & Johan W. M. Heemskerk
  • Review Article |

    Three cardiovascular outcome trials have now demonstrated the clinical benefit of achieving lower plasma LDL-cholesterol levels with the addition of PCSK9 inhibitors to statin therapy. In this Review, Marc Sabatine discusses the safety and efficacy data from these trials and their possible implications, such as the definition of new plasma LDL-cholesterol targets.

    • Marc S. Sabatine
  • Review Article |

    This Review describes the effects of short sleep duration on cardiovascular health and diseases, and the authors discuss the main pathophysiological mechanisms involved, taking into account both experimental data and clinical evidence.

    • Eleonora Tobaldini
    • , Elisa M. Fiorelli
    • , Monica Solbiati
    • , Giorgio Costantino
    • , Lino Nobili
    •  & Nicola Montano
  • Review Article |

    Metabolites produced by gut microorganisms from dietary metabolism have been linked to the pathogenesis of heart failure, suggesting that the gut microbiome functions like an endocrine organ. In this Review, Tang and colleagues discuss the gut microbial metabolic pathways involved in heart failure and propose the gut microbiome as a therapeutic target.

    • W. H. Wilson Tang
    • , Daniel Y. Li
    •  & Stanley L. Hazen
  • Review Article |

    Antibody-producing B cells perform a unique role in responses to stress, injury, and infection. In this Review, Sage and colleagues discuss the spectrum of B cell involvement in dyslipidaemia and atherosclerotic plaque development.

    • Andrew P. Sage
    • , Dimitrios Tsiantoulas
    • , Christoph J. Binder
    •  & Ziad Mallat
  • Review Article |

    The current guidelines recommending the use of higher-intensity statin therapy to reduce the risk of cardiovascular disease have raised concerns about potential adverse effects associated with long-term statin therapy. In this Review, Adhyaru and Jacobson discuss the evidence for the efficacy and safety of statins to help clinicians and patients make informed decisions about statin therapy.

    • Bhavin B. Adhyaru
    •  & Terry A. Jacobson
  • Review Article |

    In this Review, Yacoub and McLeod summarize the rationale for monitoring patients with heart failure or pulmonary arterial hypertension to detect haemodynamic changes that predict the deterioration from subclinical to overt disease, the transition from noninvasive to implantable devices and the current and anticipated clinical use of these devices.

    • Magdi H. Yacoub
    •  & Christopher McLeod
  • Review Article |

    Computational models are increasingly used in cardiology to integrate multiple data sets from individual patients and create virtual-patient simulations. In this Review, Niederer and colleagues discuss how multi-scale models of cardiac electrophysiology and mechanics can support diagnostic assessment and clinical decision-making and pave the way to personalized cardiac care.

    • Steven A. Niederer
    • , Joost Lumens
    •  & Natalia A. Trayanova
  • Review Article |

    The cardiac lymphatic system has a physiological role in the maintenance of cardiac health, and its structure and function are altered in cardiovascular diseases such as atherosclerosis and myocardial infarction. Cardiac lymphatics might be a therapeutic target to reduce myocardial oedema and chronic inflammation.

    • Ebba Brakenhielm
    •  & Kari Alitalo
  • Review Article |

    This Review summarizes the current knowledge on the biology and regional variability of the adipose tissue, highlighting the molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system. Current state-of-the-art techniques in adipose tissue imaging for cardiovascular risk stratification and the potential of the adipose tissue as a target for the treatment of cardiovascular disease are also described.

    • Evangelos K. Oikonomou
    •  & Charalambos Antoniades
  • Review Article |

    In this Review, de la Pompa and colleagues describe the role of the Notch pathway during the differentiation and patterning of cardiac tissues and in valve and ventricular chamber development, discussing the crosstalk with other signalling pathways, how defective Notch signalling is linked to congenital heart diseases, and the relevance of the Notch pathway in heart regeneration and repair.

    • Donal MacGrogan
    • , Juliane Münch
    •  & José Luis de la Pompa
  • Review Article |

    The incidence of atrial fibrillation (AF) and the risk of cognitive impairment both increase with age, and the two pathologies share important risk factors. In this Review, Madhavan and colleagues explore the association and mechanisms of cognitive decline and AF, and discuss potential therapies to prevent cognitive impairment in these patients.

    • Malini Madhavan
    • , Jonathan Graff-Radford
    • , Jonathan P. Piccini
    •  & Bernard J. Gersh
  • Review Article |

    In this Review, Meilhac and Buckingham discuss the origin of cardiac cell populations, their lineage relationships and the genes that regulate their behaviour and differentiation. Characterizing the progenitor cells that form the heart and the gene regulatory networks controlling their deployment is of major importance for understanding the origin of congenital heart malformations and for developing cardiac regeneration therapies.

    • Sigolène M. Meilhac
    •  & Margaret E. Buckingham
  • Review Article |

    Over the past 20 years, new insights into cardiovascular immunopathology have shifted the therapeutic focus from lipids to inflammation. In this Review, Duivenvoorden and colleagues discuss recent discoveries in the immunopathology of atherosclerosis, advances in bioengineering techniques, and how these advances have guided the development of innovative nanoimmunotherapeutic strategies to modulate immune responses in cardiovascular disease.

    • Raphaël Duivenvoorden
    • , Max L. Senders
    • , Mandy M. T. van Leent
    • , Carlos Pérez-Medina
    • , Matthias Nahrendorf
    • , Zahi A. Fayad
    •  & Willem J. M. Mulder
  • Review Article |

    Research on cardiac repair and regeneration is shifting from a stem cell focus towards the dynamic interplay of stromal and immune cells of the cardiac interstitium. This Review provides new insights into the immunoregulatory functions of cardiac interstitial cells and their complex network of interactions, highlighting the therapeutic potential for cardiac disease.

    • Elvira Forte
    • , Milena Bastos Furtado
    •  & Nadia Rosenthal
  • Review Article |

    Mitochondrial dysfunction has a major role in the pathogenesis of multiple cardiovascular disorders. In this Review, Galluzzi and colleagues discuss the therapeutic potential of mitochondria-targeting agents in the treatment of cardiovascular disease, examine the obstacles that have limited their development thus far, and identify strategies for the development of these promising therapeutic tools.

    • Massimo Bonora
    • , Mariusz R. Wieckowski
    • , David A. Sinclair
    • , Guido Kroemer
    • , Paolo Pinton
    •  & Lorenzo Galluzzi
  • Review Article |

    The benefits of regular exercise extend beyond its effect on cardiovascular disease (CVD) risk factors. In this Review, the authors outline the non-traditional mechanisms underlying the benefits of exercise in CVD and highlight the importance of a holistic view of exercise in cardiovascular health.

    • Carmen Fiuza-Luces
    • , Alejandro Santos-Lozano
    • , Michael Joyner
    • , Pedro Carrera-Bastos
    • , Oscar Picazo
    • , José L. Zugaza
    • , Mikel Izquierdo
    • , Luis M. Ruilope
    •  & Alejandro Lucia
  • Review Article |

    This Review summarizes the current understanding on the roles of the Hippo–YAP pathway in cardiac development, growth, homeostasis, disease, and regeneration, with a particular focus on the roles of the Hippo–YAP pathway in endogenous cardiac muscle renewal, including the pivotal role of this pathway in regulating cardiomyocyte proliferation, differentiation, stress response, and mechanical signalling.

    • Jun Wang
    • , Shijie Liu
    • , Todd Heallen
    •  & James F. Martin
  • Review Article |

    Inflammageing is a chronic, pro-inflammatory state that develops with age and is a risk factor for cardiovascular disease, comorbidities, frailty, and death. In this Review, Ferrucci and Fabbri discuss whether therapies to modulate inflammageing can reduce the age-related decline in health.

    • Luigi Ferrucci
    •  & Elisa Fabbri