Intervention, improved prevention, imaging, inflammation, and innovation: the five I's cardiovascular highlights in EHJ Open 2024

Intervention, Improved prevention, Imaging, Inflammation, and Innovation are highlights of some major insights from European Heart Journal Open 2024. Those I's also put spotlight on five of the future perspectives in cardiology trajectories towards optimization of diagnosis, interventions, and treatments, as well as novel innovative targets and methods.

Intervention

To balance potent P2Y₁₂ inhibitors after percutaneous coronary intervention (PCI), a guided selection of P2Y₁₂ inhibiting therapy has been associated with the most favourable balance between efficacy and adverse bleeding effects in a meta-analysis.¹ In the case of co-morbidities requiring both anti-coagulation and anti-platelet therapy, such as concomitant atrial fibrillation and PCI, a large nation-wide registry study showed a lower ischaemic risk without increased bleeding with ticagrelor or prasugrel over clopidogrel,² which aligns with the real-world PERSEO registry³ and supports an individualized choice of P2Y₁₂ inhibitors.

Beyond optimizing post-intervention care, novel interventional cardiology technologies also emphasize pre-intervention patient selection to improve treatment success. Mitral valve transcatheter edge-to-edge repair (TEER) significantly reduced the combined endpoint of heart failure hospitalizations and mortality compared with medical therapy in the RESHAPE-HF2 (Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation) trial.⁴ The results highlight possible need for a reconsidered severity threshold for secondary mitral regurgitation intervention as well as an integrated approach including also left ventricular remodelling for optimizing patient selection and TEER success.⁵

Improved prevention

Successful prevention, both before and after an optimized intervention, relies on life-style modifications and pharmacological interventions. Although recent evidence suggests electronic cigarettes as a potential addition to counselling for quitting regular smoking,⁶ a contemporary meta-analysis showed that electronic cigarettes containing nicotine are not without risks and affect the cardiovascular system acutely similar to regular combustible cigarettes.⁷ In addition to life-style changes, polypills may facilitate the attainment of guideline-recommended prevention linked to better outcomes, less side effects, and being cost saving compared with other therapeutic options.⁸ Those results support and extend other findings on the use of polypill in secondary prevention in patients with coronary artery disease.⁹

Lipoprotein(a) [Lp(a)] is emerging in prevention, for risk prediction¹⁰ and with therapeutic potential.¹¹ Although Lp(a) levels are predominantly genetically determined, temporal-related changes in Lp(a) variability suggests that repeat Lp(a) measures allow more precise cardiovascular risk prediction.¹² Prevention with available lipid-lowering is also challenging in some special populations, such as the need for establishing safety and efficacy of dyslipidaemia treatment during pregnancy.¹³ Finally, improved prevention through lipid lowering also comprises novel targets and potential personalized medicine approaches. A drug-target Mendelian randomization analysis supports lowering plasma ANGPTL3, ANGPTL4, and APOC3 levels as promising novel strategies for reducing cardiovascular disease risk.¹⁴

Imaging

Extracellular volume (ECV), a marker of myocardial fibrosis and other conditions, traditionally assessed via cardiac magnetic resonance, can also be evaluated using coronary computed tomography angiography (CTA).¹⁵ In a study retrospectively evaluating 874 patients who underwent CTA for the evaluation of coronary artery disease myocardial ECV fraction was obtained from the CTA data.¹⁶ The results detected 12% of patients with an ECV fraction >35%, which was associated with several pathologic conditions, among which cardiac amyloidosis was diagnosed in 15 patients.¹⁶ This cohort is considerably larger than all studies combined from a recent meta-analysis¹⁵ and points to ECV fraction as a clinically meaningful parameter extractable from clinically indicated CTA.

Inflammation

Chronic inflammation is well-established as a residual risk for atherosclerotic cardiovascular disease.¹⁷ Among the currently implemented anti-inflammatory targets, colchicine inhibits cytoskeletal microtubule formation leading to decreased vesicle transport and secretion, but its use may be limited by adverse effects.¹⁸ Despite previous outcome trials reporting significantly reduced cardiovascular events with low-dose colchicine¹⁹ and new ESC recommendations for colchicine in chronic coronary syndromes,²⁰ its use remains limited. The most recent results from the CLEAR trial however showed that treatment with colchicine after myocardial infarction for a median of 3 years did not reduce the incidence of the composite primary cardiovascular outcome.²¹ Nevertheless, colchicine decreased CRP compared with placebo,²¹ pointing to decreased inflammation. Colchicine's potential effects on lower-extremity peripheral artery disease (PAD) evaluated in emulation of target trials using a real-world sample of patients with PAD and gout, did not conclude that colchicine decreased the cardiovascular or limb events,²² and the ongoing randomized clinical trial LEADER-PAD (NCT04774159) is evaluating the effects of colchicine in PAD.²³

Among other anti-inflammatory targets, IL-6's broad effects has made it an attractive target for anti-inflammatory cardiovascular risk reduction,²⁴ which is currently evaluated in an ongoing trial of the monoclonal anti-IL-6 ziltivekimab (NCT05021835).¹⁹ Importantly, myeloid-specific IL-6 has been shown to significantly impact vascular function²⁵ and to be linked to a newly identified population of monocyte-derived lipid-laden pro-inflammatory macrophages that can accelerate atherosclerosis.²⁶ These findings suggest that not only the secreted IL-6 protein but also the cells overexpressing it should be considered for future anti-inflammatory cardiovascular therapies.

Innovation

Among machine learning methods that enable novel and innovative approaches, spectral regression learning is emerging as a promising technique for advanced data analysis applicable to measures of aortic stiffness, which represents structural changes of the arterial system and associates with future cardiovascular events and mortality.²⁷ Wave separation analysis is a tool for decomposing the components of blood pressure waveform, but the need for concurrent measurements of pressure and flow limits its applicability. A recent study introduced a spectral regression learning method for pressure-only wave separation analysis using data from the Framingham Heart Study to evaluate the accuracy of pressure-only estimates, and their association with aortic stiffness, assessed by carotid-femoral pulse wave velocity (cf-PWV).²⁸ After adjustments for potential confounders, the results suggested that the pressure-only evaluations of wave separation parameters predicted cf-PWV, with forward wave amplitude being the only significant factor. The authors propose that aortic stiffness estimated through this spectral regression learning and single pressure waveform measurements outperform methods used in previous studies²⁹ and provide a valuable non-invasive tool for cardiovascular assessment.

In summary, the 5 I's put forward here highlights European Heart Journal Open as an open access forum for providing important insights into the recent development of cardiovascular medicine and surgery. We encourage you to explore the journal's full content, which is freely available, and welcome submissions that contribute to a continued open and interactive cardiovascular forum with global sharing of science.

Acknowledgements

Editors

Section Editors gratefully acknowledge the work of the EHJ Open Managing Editor Claudia Welburn.

Volume 4 of EHJ Open has been completed with the invaluable help of the following Associate Editors, who have handled submissions during 2024:

Ana Almeida

Athanase Benetos

Marie-Luce Bochaton-Piallat

Mats Börjesson

Ronny Buechel

Christian de Chillou

Jérémy Fauconnier

Dipender Gill

Nicolas Girerd

Joerg Herrmann

Stefan Koudstaal

Seth Martin

Edit Nagy

Jens Cosedis Nielsen

John Pernow

Davide Stolfo

Giuseppe Vergaro

Faiez Zannad

Michal Zembala

Editorial board reviewers:

All editors of EHJ Open would like to thank those who reviewed papers for the journal. The peer reviewers who contributed to the Journal in 2024 are as follows.

Adrian Covic

Bruna Gigante

Daniel Andersson

Gustavs Latkovskis

Jane Stubbe

Michael Shapiro

Nailin Li

Niki Katsiki

Patrick Lacolley

Sven-Christian Pawelzik

Wael Jaber

Yury Lopatin

External reviewers:

Elisabetta Abruzzese

Maurizio Acampa

Lina Adwan

Arian Aghilinejad

Vibhor Agrawal

Malik Takreem Ahmad

Alberto Aimo

Noor Albakaa

Joakim Alfredsson

Baravan Al-Kassou

Abdallah Almaghraby

Saed Alnaimat

Till Althoff

Ali Ambreen

Rafael Amorim Belo Nunes

Oskar Angerås

Luca Arcari

Albert Ariza-Solé

Vicente Artola Arita

Alice Assinger

Camillo Autore

Tariq Azam

Luca Baldetti

Noel Balrey-Merz

Anna Baritussio

Fotios Barkas

Ozcan Basaran

Frederico Bastos Gonçalves

Benedikt N. Beer

Ronen Beeri

Alexander E. Berezin

Jutta Bergler-Klein

Marco Bernardi

Kunal Bhatt

Francesco Bianco

Luigi Biasco

Elias Björnson

Hanne Boen

Giuseppe Boriani

Josip Andelo Borovac

Athenais Boucly

Selim Bozkurt

Anna Brand

Axel Brandes

Michele Brignole

Jonas Brinck

Ana Briones

Natale Brunetti

Rosa Maria Bruno

Antonio Cannata

Blase Anthony Carabello

Nicole Carabetta

Andreina Carbone

Lombardi Carlo Mario

Vincenzo Castiglione

Anwar Chahal

Ari Chaouat

Emmanouil Charitakis

Qingui Chen

Jia Ee Chia

Jacob J. Christensen

Ruxandra Christodorescu

Sumeet S. Chugh

Thomas R. Cimato

Giovanni Cimmino

Marc J. Claeys

Alberto Clemente

Paul Collinson

Alberto Cordero

Madalena Costa

Elaine Coutinho

Inês Coutinho dos Santos

Naima Covassin

Mohamed Dafaalla

Fabrizio D'Ascenzo

Tim A.C. de Vries

Emilia D'Elia

Louis Dell'Italia

Borislav Dinov

Erwan Donal

Stavros Drakos

Iryna Dykun

Lars Eckardt

Betty Eipper

Johan Engdahl

Artur Evangelista

Morten Fagerland

Francesca Fasolo

Laurent Fauchier

Jonas Faxén

Abdallah Fayssoil

Gudrun M. Feuchtner

Thomas Fink

Elena Fortin

Eloi Gagnon

Elena Galli

Luna Gargani

Johannes Gho

Federico Giacobbe

Daniele Giacoppo

Angelina Gideon

Robert Giugliano

Diona Gjermeni

Emilia Goanta

Andrew Michael Goldsweig

Rafael González-Manzanares

Shinya Goto

Guillaume Goudot

Felice Gragnano

Karl-Henrik Grinnemo

Tomasz Grodzicki

Luigina Guasti

Diana Ruxandra Hădăreanu

Sigrun Halvorsen

Kristina Hambraeus

Pamela Harding

Mark Haykowsky

Jeroen Hendriks

Alexander Hirsch

Vibeke Hjortdal

Katarzyna Holcman

John Horowitz

Amin Hossein

David Hupin

Ignatios Ikonomidis

Masanobu Ishii

Hideki Itoh

Vikash Jaiswal

Hong Jin

Madeleine Johansson

Elizabeth Jones

Jens Jordan

Christian Jung

Wayne Kaesemeyer

Nobuyuki Kagiyama

Sergio Kaiser

Farhan Katchi

Cormac Kennedy

Yulia Khodneva

Kye Hun Kim

Masatake Kobayashi

Petri Kovanen

Konstantin Krychtiuk

Jeremy Lagrange

Stefan Lange

Alf Inge Larsen

Chu-Pak Lau

Seung-Yul Lee

Georges Leftheriotis

Anthony Leicht

Daniel Lenihan

Isabella Leo

Thorsten Leucker

Christian Lewinter

Hoong Sern Lim

Herbert Loellgen

Cristina Madaudo

Meena Madhur

Ange Maguy

Koon-Hou Mak

Michael Makover

Daniel Malone

Paolo Manca

Benjamin Marchandot

Nassir Marrouche

Antoni Martínez-Rubio

Yuya Matsue

John W. McEvoy

Felix G. Meinel

Thomas Meyer

Dimitri P. Mikhailidis

Emanuele Monda

Luca Monzo

Sara Moscatelli

Andreea Motoc

Marion Mußbacher

Maria Lorenza Muiesan

Toshiyuki Nagai

Bernd Niemann

George Ntaios

W. Charles O’Neill

Marish Oerlemans

Evangelos Oikonomou

Elmir Omerovic

Ariela R. Orkaby

Giuseppe Panuccio

Konstatinos Papadopoulos

Valeria Paradies

Manan Pareek

Claudio Passino

Mubarak Patel

Francesco Pelliccia

Peter Penson

Carl J. Pepine

Gabriele Pesarini

Aurélie Philippe

Indu G. Poornima

Athanase Protogerou

Nicola Pugliese

Juan Carlos Quijano-Campos

Anjali Rao

Vijay Rao

Fabrizio Ricci

David Ripley

Benoit Robaye

Bianca Rocca

Alfredo Rodriguez

Marco Roffi

Nathalie Rosenblatt-Vein

Joy Roy

Eleonora Ruscio

Manel Sabate

Pierre Sabouret

Akinori Sairaku

John Sanderson

Anna Sandström

Ciro Santoro

Carmine Savoia

Marco Schiavone

Christian Schulze

Andreas Schuster

Paolo Sciarrone

Jean Marc Sellal

Bahira Shahim

Arthur Shiyovich

Anwar Siddiqui

Johanne Silvaine

Moa Simonsson

Tomasz Skowerski

Matthew Solomon

Philipp Sommer

Jonas Spaak

Lasse Steffensen

Phyllis K. Stein

Konstantinos Stellos

Lee Sterling

Christian Sticherling

Alexander Sullivan

Toru Suzuki

Emma Svennberg

Sebastian Szmit

Felix Tanner

Giuseppe Tarantini

Jean-Claude Tardif

Konsta Teppo

Ulf Thilén

Per Tornvall

Mileen van de Kar

Erik Van Iterson

Gregoire Vandecasteele

Mani Vannan

Renu Virmani

Niels Voigt

Miao Wang

Liansheng Wang

Samuel Watson

Troels Yndigegn

Shuai Yuan

Sergio Zacà

Emmanuel Zavalis

Hongsong Zhang

Liang Zhong

Andreas Zietzer

Christopher Zörner

Ermir Zulfaj

Data availability

There are no new data associated with this article.

References

Author notes