Review Articles

  • Review Article |

    In this Review, Padmanabhan and Dominiczak discuss how genomics has transformed our understanding of blood pressure regulation and hypertension, summarizing the current knowledge of blood pressure genomics and highlighting the opportunities and challenges for drug repurposing and pharmacogenomics for the treatment of hypertension.

    • Sandosh Padmanabhan
    •  & Anna F. Dominiczak
  • Review Article |

    This Review summarizes the latest evidence indicating that platelet and endothelial dysfunction are essential components of COVID-19 pathology, describes the potential mechanisms underlying the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19, and highlights the roles of coagulopathy, thrombocytopathy and endotheliopathy in COVID-19 pathogenesis.

    • Sean X. Gu
    • , Tarun Tyagi
    • , Kanika Jain
    • , Vivian W. Gu
    • , Seung Hee Lee
    • , Jonathan M. Hwa
    • , Jennifer M. Kwan
    • , Diane S. Krause
    • , Alfred I. Lee
    • , Stephanie Halene
    • , Kathleen A. Martin
    • , Hyung J. Chun
    •  & John Hwa
  • Review Article |

    In this Review, Bax and colleagues summarize the effects of obesity and diabetes on myocardial structure and function and evaluate the role of multimodality cardiac imaging to elucidate the pathophysiology of myocardial dysfunction, prognosticate long-term clinical outcomes and potentially guide treatment strategies.

    • Arnold C. T. Ng
    • , Victoria Delgado
    • , Barry A. Borlaug
    •  & Jeroen J. Bax
  • Review Article |

    Cardiovascular disease is one of the major factors contributing to the reduced life expectancy of patients with severe mental illness. In this Review, Nielsen and colleagues discuss the current knowledge of risk factors, diagnosis, treatment and outcomes of cardiovascular disease in patients with schizophrenia or bipolar disorder.

    • René Ernst Nielsen
    • , Jytte Banner
    •  & Svend Eggert Jensen
  • Review Article |

    Effective stroke prevention with oral anticoagulation is a cornerstone of the management of patients with atrial fibrillation. Caution is required in patients with atrial fibrillation at high risk of stroke and bleeding. In this Review, Lip and colleague discuss strategies for reducing the risk of stroke in patients with atrial fibrillation.

    • Agnieszka Kotalczyk
    • , Michał Mazurek
    • , Zbigniew Kalarus
    • , Tatjana S. Potpara
    •  & Gregory Y. H. Lip
  • Review Article |

    In this Review, Stone and colleagues compare the outcomes after complete or incomplete revascularization with PCI or CABG surgery in patients with multivessel disease and stable ischaemic heart disease, NSTE-ACS or STEMI, with or without cardiogenic shock.

    • Prakriti Gaba
    • , Bernard J. Gersh
    • , Ziad A. Ali
    • , Jeffrey W. Moses
    •  & Gregg W. Stone
  • Review Article |

    Catheter ablation is an important rhythm-control strategy for atrial fibrillation (AF). In this Review, Kalman and colleagues discuss the recommended and evolving indications for catheter ablation of AF, describing the different ablation techniques and highlighting the latest advances in technology that aim to improve its safety and efficacy.

    • Ramanathan Parameswaran
    • , Ahmed M. Al-Kaisey
    •  & Jonathan M. Kalman
  • Review Article |

    In this Review, Tschöpe and colleagues summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with special focus on virus-induced and virus-associated myocarditis. The authors also identify knowledge gaps, appraise available experimental models and propose future directions for the field.

    • Carsten Tschöpe
    • , Enrico Ammirati
    • , Biykem Bozkurt
    • , Alida L. P. Caforio
    • , Leslie T. Cooper
    • , Stephan B. Felix
    • , Joshua M. Hare
    • , Bettina Heidecker
    • , Stephane Heymans
    • , Norbert Hübner
    • , Sebastian Kelle
    • , Karin Klingel
    • , Henrike Maatz
    • , Abdul S. Parwani
    • , Frank Spillmann
    • , Randall C. Starling
    • , Hiroyuki Tsutsui
    • , Petar Seferovic
    •  & Sophie Van Linthout
  • Review Article |

    In this Review, Lucia and colleagues discuss the epidemiological evidence on the benefits of major lifestyle interventions in the prevention and adjuvant treatment of hypertension, including regular physical exercise, body weight management, healthy diet, adequate sleep patterns, circadian entrainment and stress management. The authors also describe the main physiological mechanisms underlying these benefits.

    • Pedro L. Valenzuela
    • , Pedro Carrera-Bastos
    • , Beatriz G. Gálvez
    • , Gema Ruiz-Hurtado
    • , José M. Ordovas
    • , Luis M. Ruilope
    •  & Alejandro Lucia
  • Review Article |

    Advances in cardiovascular monitoring technologies have resulted in an influx of consumer-targeted wearable sensors that have the potential to detect numerous heart conditions. In this Review, Krittanawong and colleagues describe processes involved in biosignal acquisition and analysis of cardiovascular monitors, as well as their associated ethical, regulatory and legal challenges.

    • Chayakrit Krittanawong
    • , Albert J. Rogers
    • , Kipp W. Johnson
    • , Zhen Wang
    • , Mintu P. Turakhia
    • , Jonathan L. Halperin
    •  & Sanjiv M. Narayan
  • Review Article |

    Chronic liver disease can promote the development of numerous cardiac disorders and circulatory complications. In this Review, Pacher and colleagues describe some of the extrahepatic complications of chronic liver disease and their shared pathophysiological mechanisms, including inflammation and oxidative stress.

    • Csaba Matyas
    • , György Haskó
    • , Lucas Liaudet
    • , Eszter Trojnar
    •  & Pal Pacher
  • Review Article |

    In this Review, Tyrrell and Goldstein discuss vascular intrinsic and extrinsic mechanisms of how ageing promotes atherosclerosis, including changes in myeloid cells, mitochondrial dysfunction, impaired mitophagy and elevated IL-6 levels. They propose future steps for research and potential therapeutic approaches for age-related atherosclerosis.

    • Daniel J. Tyrrell
    •  & Daniel R. Goldstein
  • Review Article |

    Next-generation tissue-engineered heart valves (TEHVs) are a promising therapeutic option for patients with valvular heart disease. In this Review, Emmert and colleagues discuss the current heart valve replacement options, describe the design of TEHVs and summarize the data from preclinical and clinical studies on the use of TEHVs.

    • Emanuela S. Fioretta
    • , Sarah E. Motta
    • , Valentina Lintas
    • , Sandra Loerakker
    • , Kevin K. Parker
    • , Frank P. T. Baaijens
    • , Volkmar Falk
    • , Simon P. Hoerstrup
    •  & Maximilian Y. Emmert
  • Review Article |

    Current estimates of the prevalence of hypertrophic, dilated and arrhythmogenic cardiomyopathies are probably conservative because of the overlapping phenotypes, incomplete and age-related expression, and variable penetrance of these conditions. In this Review, McKenna and Judge discuss the clinical and genetic diagnosis of the inherited cardiomyopathies, with the aim of better defining the epidemiology of these diseases.

    • William J. McKenna
    •  & Daniel P. Judge
  • Review Article |

    The design and limited life of batteries curtails the use of many cardiovascular electronic devices (CEDs). In this Review, Li and colleagues discuss the use of self-powered technology that harvests energy from the body and its ambient environment to power implantable and wearable CEDs.

    • Qiang Zheng
    • , Qizhu Tang
    • , Zhong Lin Wang
    •  & Zhou Li
  • Review Article |

    Patients with coronary artery disease (CAD) are at high risk of perioperative cardiovascular complications related to non-cardiac surgery. In this Review, Mehran and colleagues summarize trial data and guideline recommendations on preoperative risk stratification and periprocedural management of patients with CAD undergoing non-cardiac surgery.

    • Davide Cao
    • , Rishi Chandiramani
    • , Davide Capodanno
    • , Jeffrey S. Berger
    • , Matthew A. Levin
    • , Mary T. Hawn
    • , Dominick J. Angiolillo
    •  & Roxana Mehran
  • Review Article |

    The presence of cardiovascular comorbidities is linked with worse outcomes in patients with coronavirus disease 2019 (COVID-19), and COVID-19 can induce cardiovascular damage. In this Review, Wu and colleagues summarize the latest mechanistic and clinical studies that contribute to our current understanding of COVID-19-related cardiovascular disease.

    • Masataka Nishiga
    • , Dao Wen Wang
    • , Yaling Han
    • , David B. Lewis
    •  & Joseph C. Wu
  • Review Article |

    In this Review, Gerd Heusch revisits the pathophysiology of myocardial ischaemia–reperfusion injury, discusses the latest developments in cardioprotective interventions and the signalling pathways involved, identifies the challenges for their clinical translation and advocates the use of additive cardioprotective interventions and a focus on patients with severe haemodynamic alterations.

    • Gerd Heusch
  • Review Article |

    In this Review, Alfieri and colleagues focus on new concepts on mitral valve pathophysiology and patient risk profile assessment to guide the indication and timing of the management of mitral valve regurgitation. The authors also describe new imaging modalities and contemporary surgical and transcatheter techniques, highlighting the need for a multidisciplinary approach.

    • Benedetto Del Forno
    • , Michele De Bonis
    • , Eustachio Agricola
    • , Francesco Melillo
    • , Davide Schiavi
    • , Alessandro Castiglioni
    • , Matteo Montorfano
    •  & Ottavio Alfieri
  • Review Article |

    The development of the coronary vasculature involves numerous cellular sources and a multitude of distinct processes. In this Review, Smart and colleagues describe the latest insights into the mechanisms involved in coronary vessel formation during development and disease, which might contribute to the identification of therapeutic targets for the promotion of neovascularization after myocardial infarction.

    • Irina-Elena Lupu
    • , Sarah De Val
    •  & Nicola Smart
  • Review Article |

    Dysregulation of intracellular Ca2+ handling in cardiomyocytes occurs in heart failure and atrial fibrillation. In this Review, Marks and colleagues focus on diastolic Ca2+ leak from the sarcoplasmic reticulum via RYR2 as a feature and potential therapeutic target in both heart failure and atrial fibrillation.

    • Haikel Dridi
    • , Alexander Kushnir
    • , Ran Zalk
    • , Qi Yuan
    • , Zephan Melville
    •  & Andrew R. Marks
  • Review Article |

    In this Review, Roos-Hesselink and colleagues describe how the physiological adaptations during pregnancy can induce cardiometabolic complications or an exacerbation of existing cardiometabolic disease, and discuss the epidemiology, pathophysiology, diagnosis and management of cardiometabolic diseases acquired or presenting during pregnancy, including hypertensive disorders, gestational diabetes mellitus, thromboembolic disorders and peripartum cardiomyopathy.

    • Karishma P. Ramlakhan
    • , Mark R. Johnson
    •  & Jolien W. Roos-Hesselink
  • Review Article |

    Extracellular vesicles are a heterogeneous group of natural particles that can deliver their biologically active molecular cargo to recipient cells. In this Review, the authors outline the endogenous properties of extracellular vesicles that make them natural delivery agents and the features that can be improved by bioengineering for the treatment of cardiovascular diseases.

    • Ricardo Cerqueira de Abreu
    • , Hugo Fernandes
    • , Paula A. da Costa Martins
    • , Susmita Sahoo
    • , Costanza Emanueli
    •  & Lino Ferreira
  • Review Article |

    The heart is an endocrine organ, producing atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in a regulated manner. In this Review, the authors discuss the physiological regulation and actions of the cardiac natriuretic peptides and their clinical use as powerful diagnostic and prognostic biomarkers of heart disease.

    • Jens P. Goetze
    • , Benoit G. Bruneau
    • , Hugo R. Ramos
    • , Tsuneo Ogawa
    • , Mercedes Kuroski de Bold
    •  & Adolfo J. de Bold
  • Review Article |

    Congestion is the main reason for hospitalization in patients with acute decompensated heart failure and is an important target for therapy. In this Review, Boorsma and colleagues distinguish between intravascular congestion and tissue congestion, and hypothesize that specifically treating these two different forms of congestion could improve patient outcomes.

    • Eva M. Boorsma
    • , Jozine M. ter Maaten
    • , Kevin Damman
    • , Wilfried Dinh
    • , Finn Gustafsson
    • , Steven Goldsmith
    • , Daniel Burkhoff
    • , Faiez Zannad
    • , James E. Udelson
    •  & Adriaan A. Voors
  • Review Article |

    Non-hyperaemic pressure measurements have emerged as a useful tool to guide coronary interventions and are recommended as a substitute for fractional flow reserve (FFR). In this Review, van de Hoef and colleagues explain the rationale for the use of non-hyperaemic pressure ratios instead of FFR for stenosis evaluation.

    • Tim P. van de Hoef
    • , Joo Myung Lee
    • , Mauro Echavarria-Pinto
    • , Bon-Kwon Koo
    • , Hitoshi Matsuo
    • , Manesh R. Patel
    • , Justin E. Davies
    • , Javier Escaned
    •  & Jan J. Piek
  • Review Article |

    A strong relationship exists between exposure to air pollution and cardiovascular events. In this Review, Rajagopalan and colleagues summarize the evidence supporting the detrimental effects of air pollution on cardiovascular health and describe the potential mechanisms involved in air pollution-mediated cardiovascular mortality.

    • Sadeer G. Al-Kindi
    • , Robert D. Brook
    • , Shyam Biswal
    •  & Sanjay Rajagopalan
  • Review Article |

    NSAIDs are effective, widely used analgesics, but their use is associated with increased risks of thrombosis and heart failure. In this Review, the authors assess the cardiovascular safety of NSAIDs and present an approach for their use in the holistic management of pain.

    • Anne-Marie Schjerning
    • , Patricia McGettigan
    •  & Gunnar Gislason
  • Review Article |

    Novel strategies to improve blood pressure control and treat drug-resistant hypertension are needed despite the efficacy and widespread availability of current antihypertensive drugs. In this Review, Mahfoud and colleagues summarize the pathophysiological rationale and available clinical evidence for device-based therapies for hypertension, including renal sympathetic denervation.

    • Lucas Lauder
    • , Michel Azizi
    • , Ajay J. Kirtane
    • , Michael Böhm
    •  & Felix Mahfoud
  • Review Article |

    Single-cell RNA sequencing (scRNA-seq) technologies have helped to identify rare cell populations and allowed the comparison of healthy and diseased tissues at single-cell resolution. This Review discusses the available scRNA-seq tools and summarizes the scRNA-seq findings that have contributed to our understanding of cardiovascular development and disease.

    • David T. Paik
    • , Sangkyun Cho
    • , Lei Tian
    • , Howard Y. Chang
    •  & Joseph C. Wu
  • Review Article |

    The cardiotoxicity spectrum of cancer therapies has broadened and is gaining increasing importance with an ever-growing repertoire of therapeutics. This Review provides an updated overview of cardiotoxicity and arrhythmias associated with cancer therapies, summarizing the latest developments at the juncture of cardiology, oncology and haematology and the emerging field of cardio-oncology.

    • Joerg Herrmann
  • Review Article |

    Heart failure with preserved ejection fraction (HFpEF) is the predominant form of heart failure among elderly patients. In this Review, Borlaug describes the challenges of diagnosing HFpEF, summarizes the current recommendations for treatment and describes a new strategy of categorizing patients with HFpEF into phenotypically homogeneous subgroups to facilitate the individualization of treatment.

    • Barry A. Borlaug
  • Review Article |

    This Review outlines the mechanisms of cancer therapy-related vascular toxicity and provides recommendations for screening, treatment and prevention in the context of available evidence and society guidelines. The Review focuses on the main types of arterial toxicity, acute vasospasm, acute thrombosis and accelerated atherosclerosis, and provides an update on cancer therapy-related venous thromboembolism and pulmonary hypertension.

    • Joerg Herrmann
  • Review Article |

    Accumulating evidence supports the critical role of T cells as drivers and modifiers of atherosclerosis. In this Review, Ley and colleagues describe the latest advances in our understanding of the role of T cell subsets in atherosclerosis, discuss the process of T cell homing to atherosclerotic plaques and highlight potential T cell-related therapies for atherosclerosis.

    • Ryosuke Saigusa
    • , Holger Winkels
    •  & Klaus Ley
  • Review Article |

    Moderate exercise improves cardiovascular health and is associated with physiological cardiac adaptations; by contrast, the hearts of endurance athletes can undergo maladaptations, including myocardial fibrosis and arrhythmias. In this Review, Parry-Williams and Sharma discuss whether excessive endurance exercise might damage both diseased and otherwise normal hearts.

    • Gemma Parry-Williams
    •  & Sanjay Sharma
  • Review Article |

    Diabetic cardiomyopathy occurs as a result of the dysregulated glucose and lipid metabolism, increased oxidative stress and activation of pro-inflammatory pathways associated with diabetes mellitus, which can induce cardiac remodelling and dysfunction. In this Review, Tan and colleagues discuss the pathogenesis of diabetic cardiomyopathy and describe signalling pathways that might be potential therapeutic targets.

    • Yi Tan
    • , Zhiguo Zhang
    • , Chao Zheng
    • , Kupper A. Wintergerst
    • , Bradley B. Keller
    •  & Lu Cai
  • Review Article |

    Cardiac amyloidosis is a life-threatening cause of restrictive cardiomyopathy that is often underdiagnosed or misdiagnosed. This Review summarizes the latest non-invasive imaging techniques used to diagnose cardiac amyloidosis, including echocardiography, bone scintigraphy and cardiac MRI.

    • Ana Martinez-Naharro
    • , A. John Baksi
    • , Philip N. Hawkins
    •  & Marianna Fontana
  • Review Article |

    In this Review, Murry and colleagues describe the hallmarks of cardiomyocyte maturation and the current approaches to mature stem cell-derived cardiomyocytes, highlighting challenges and future directions to generate cardiomyocytes with an optimal maturation state for use in research and regenerative medicine.

    • Elaheh Karbassi
    • , Aidan Fenix
    • , Silvia Marchiano
    • , Naoto Muraoka
    • , Kenta Nakamura
    • , Xiulan Yang
    •  & Charles E. Murry
  • Review Article |

    In this Review, Soehnlein and colleagues discuss the role of neutrophils in cardiovascular inflammation and repair, describing the effect of cardiovascular risk factors on neutrophil production and function, appraising the contribution of neutrophils to the different stages of atherosclerosis and its clinical manifestations, and highlighting the evolving therapeutic strategies for targeting neutrophil numbers, functional status and effector mechanisms.

    • Carlos Silvestre-Roig
    • , Quinte Braster
    • , Almudena Ortega-Gomez
    •  & Oliver Soehnlein
  • Review Article |

    Familial hypercholesterolaemia is a genetic disorder that impairs the hepatic clearance of LDL, leading to premature atherosclerotic cardiovascular disease. In this Review, Watts and colleagues summarize the latest advances that can inform the development and implementation of new models of care for familial hypercholesterolaemia.

    • Gerald F. Watts
    • , Samuel S. Gidding
    • , Pedro Mata
    • , Jing Pang
    • , David R. Sullivan
    • , Shizuya Yamashita
    • , Frederick J. Raal
    • , Raul D. Santos
    •  & Kausik K. Ray
  • Review Article |

    Inflammation has an important role in the pathogenesis of acute and chronic heart failure. This Review summarizes the latest findings on the role of the innate and adaptive immune systems in the pathogenesis of heart failure, and highlights the results of phase III clinical trials of therapies targeting inflammatory processes in this condition, such as anti-inflammatory and immunomodulatory strategies.

    • Luigi Adamo
    • , Cibele Rocha-Resende
    • , Sumanth D. Prabhu
    •  & Douglas L. Mann
  • Review Article |

    Many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. In this Review, Angiolillo and colleagues discuss the pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with cardiovascular disease.

    • Davide Capodanno
    • , Deepak L. Bhatt
    • , John W. Eikelboom
    • , Keith A. A. Fox
    • , Tobias Geisler
    • , C. Michael Gibson
    • , Jose Ramon Gonzalez-Juanatey
    • , Stefan James
    • , Renato D. Lopes
    • , Roxana Mehran
    • , Gilles Montalescot
    • , Manesh Patel
    • , P. Gabriel Steg
    • , Robert F. Storey
    • , Pascal Vranckx
    • , Jeffrey I. Weitz
    • , Robert Welsh
    • , Uwe Zeymer
    •  & Dominick J. Angiolillo
  • Review Article |

    In this Review, Rosenbaum and colleagues give a broad perspective on the genetic causes of dilated cardiomyopathy to provide a context for a discussion of the pragmatic use of genetic testing in heart failure clinics for patients presenting with new-onset dilated cardiomyopathy.

    • Andrew N. Rosenbaum
    • , Katherine E. Agre
    •  & Naveen L. Pereira
  • Review Article |

    In this Review, Cai and colleagues discuss the complex crosstalk between different oxidase systems and the consequences of this crosstalk in mediating cardiovascular disease processes, focusing on the central role of particular NADPH oxidase isoforms activated in specific cardiovascular diseases.

    • Yixuan Zhang
    • , Priya Murugesan
    • , Kai Huang
    •  & Hua Cai
  • Review Article |

    Inherited arrhythmias are a major cause of sudden cardiac death, particularly among young individuals. In this Review, Offerhaus and colleagues provide an overview of the epidemiology of inherited ventricular arrhythmias, focusing on natural history, prevalence and patient demographics.

    • Joost A. Offerhaus
    • , Connie R. Bezzina
    •  & Arthur A. M. Wilde
  • Review Article |

    Non-atherosclerotic processes are important contributors to a substantial number of acute coronary syndrome events. In this Review, Gulati and colleagues discuss the diagnosis, management and prognosis of patients with spontaneous coronary artery dissection, coronary artery embolism, vasospasm, myocardial bridging or stress-induced cardiomyopathy (Takotsubo syndrome).

    • Thomas M. Waterbury
    • , Giuseppe Tarantini
    • , Birgit Vogel
    • , Roxana Mehran
    • , Bernard J. Gersh
    •  & Rajiv Gulati
  • Review Article |

    This Review summarizes the role of transcription factors and epigenetic remodelling in modulating macrophage plasticity, provides an overview of the cooperative action of transcription factors and epigenetic modifiers controlling macrophage activation in the context of atherosclerosis and inflammation, and highlights the therapeutic potential of modulating transcription factor activity.

    • Tatyana Kuznetsova
    • , Koen H. M. Prange
    • , Christopher K. Glass
    •  & Menno P. J. de Winther
  • Review Article |

    This Review discusses the evolving indications of transcatheter aortic valve implantation (TAVI), including the latest clinical trials in young and low-risk patients with symptomatic severe aortic stenosis and ongoing studies exploring TAVI for other indications, including severe bicuspid aortic valve stenosis and pure native aortic regurgitation, highlighting procedural implications and caveats of new and future indications.

    • Zouhair Rahhab
    • , Nahid El Faquir
    • , Didier Tchetche
    • , Victoria Delgado
    • , Susheel Kodali
    • , E. Mara Vollema
    • , Jeroen Bax
    • , Martin B. Leon
    •  & Nicolas M. Van Mieghem
  • Review Article |

    Rheumatic heart disease is a complication of group A streptococcal infection and rheumatic fever. In this Review, Muhamed and colleagues assess the emerging role of genome-wide association studies in detecting loci associated with genetic susceptibility to rheumatic heart disease.

    • Babu Muhamed
    • , Tom Parks
    •  & Karen Sliwa