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This issue contains three of the Top 10 articles series we publish annually. In ‘The year in cardiovascular medicine 2023: the top 10 papers in interventional cardiology’, Emanuele Barbato, Margaret McEntegart, and Tommaso Gori summarize the top papers of the last year.¹ In ‘The year in cardiovascular medicine 2023: the top 10 papers in ischaemic heart disease’, Juan Carlos Kaski, Rasha Al-Lamee, and William Boden discuss the papers in their area of expertise, which they feel were most important last year.² Finally, in ‘The year in cardiovascular medicine 2023: the top 10 papers in diabetes and metabolic disorders’, Francesco Cosentino, Christopher Paul Cannon, and Nikolaus Marx discuss their top 10 papers.³

The issue continues with a focus on cardio-oncology and arrhythmias. The interest of cardiologists in cardio-oncology keeps increasing, as also witnessed by the recent Guidelines published by the European Society of Cardiology.^4–10 In a State of the Art Review article entitled ‘Ischaemic heart disease in patients with cancer’, Pietro Ameri from the University of Genova in Italy, and colleagues note that cardiologists are encountering a growing number of cancer patients with ischaemic heart disease (IHD).¹¹ Several factors account for the inter-relationship between these two conditions, in addition to improving survival rates in the cancer population. Established cardiovascular (CV) risk factors, such as hypercholesterolaemia and obesity, predispose to both IHD and cancer, through specific mechanisms and via low-grade, systemic inflammation. This latter is also fuelled by clonal haematopoiesis of indeterminate potential. Furthermore, experimental work indicates that IHD and cancer can promote one another, and the CV or metabolic toxicity of anticancer therapies can lead to IHD. The connections between IHD and cancer are reinforced by social determinants of health, non-medical factors that modify health outcomes and comprise individual and societal domains, including economic stability, educational and healthcare access and quality, neighbourhood and built environment, and social and community context. Management of IHD in cancer patients is often challenging, due to atypical presentation, increased bleeding and ischaemic risk, and worse outcomes as compared with patients without cancer. The decision to proceed with coronary revascularization and the choice of antithrombotic therapy can be difficult, particularly in patients with chronic coronary syndromes, necessitating multidisciplinary discussion that considers both general guidelines and specific features on a case-by-case basis. Randomized controlled trial evidence in cancer patients is very limited, and there is urgent need for more data to inform clinical practice. Therefore, the co-existence of IHD and cancer raises important scientific and practical questions that call for collaborative efforts from the cardio-oncology, cardiology, and oncology communities.

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared with subjects free of HF. In a State of the Art Review article entitled ‘Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence’, Nabil Sayour from the Semmelweis University in Budapest, Hungary, and colleagues indicate that while both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy for HF should be modified when cancer is diagnosed in HF patients.¹² The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics, on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data are described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses, are reviewed, and (iii) considerations for future pre-clinical and clinical investigations are provided.

Prior reports have demonstrated a favourable safety and efficacy profile of the Micra leadless pacemaker over mid-term follow-up; however, long-term outcomes in real-world clinical practice remain unknown.^13,14 In a Clinical Research article entitled ‘Leadless pacemakers at 5-year follow-up: the Micra transcatheter pacing system post-approval registry’, Mikhael El-Chami from Emory University in Atlanta, Georgia, USA, and colleagues assessed updated performance of the Micra VR leadless pacemaker through 5 years from the worldwide post-approval registry (PAR).¹⁵ All Micra PAR patients undergoing implant attempts were included. Endpoints included system- or procedure-related major complications and system revision rate for any cause through 60 months post-implant. Rates were compared through 36 months post-implant with a reference dataset of 2667 transvenous pacemaker patients using Fine–Gray competing risk models. A total of 1809 patients were enrolled between July 2015 and March 2018 and underwent implant attempts from 179 centres in 23 countries, with a median follow-up period of 51 months. The major complication rate at 60 months was 4.5%, significantly lower than the 8.5% rate observed for transvenous systems (P < .001). The all-cause system revision rate at 60 months was 4.9%. System revisions among Micra patients were mostly for device upgrades (41%) or elevated thresholds (30.6%). There were no Micra removals due to infection noted over the duration of follow-up. At 36 months, the system revision rate was significantly lower, with Micra vs. transvenous systems (3.2% vs. 6.6%, P < .001) (Figure 1).

Figure 1

Five-year outcomes of patients implanted with a Micra VR leadless pacemaker. The flowchart on the left depicts the disposition of system revisions. The figure on the right shows a comparison of system revision rates for Micra VR and a historical transvenous pacemaker cohort. CI, confidence interval; CRT, cardiac resynchronization therapy; HR, hazard ratio.¹⁵

The authors conclude that long-term outcomes with the Micra leadless pacemaker continue to demonstrate low rates of major complications and system revisions, and an extremely low incidence of infection. This manuscript is accompanied by an Editorial by Panos Vardas from the University of Crete in Greece.¹⁶ Vardas points out that when we look back over the last 50 years to when their experimental models of leadless pacing envisaged devices with 10–12 years’ longevity, up to 25 mm in length and up to 7 mm in diameter, non-thrombogenic, and capable of stable placement in the myocardium, we should be delighted to see these impressive technological developments that have partially realized that dream. However, the vision of leadless pacing should not be limited to today’s conventional, small devices. True leadless pacing requires tiny devices, capable of responding optimally to any need for myocardial pacing or synchronization. Vardas is confident that radically new technologies for energy harvesting from cardiac movement will open the door to fundamentally new concepts of leadless stimulation.

Risk stratification in Brugada syndrome (BrS) remains challenging.¹⁷ Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with BrS are scarce. In a Clinical Research article entitled ‘Implantable loop recorders in patients with Brugada syndrome: the BruLoop study’, Marco Bergonti from the Cardiocentro Ticino Institute in Lugano, Switzerland, and colleagues evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and assess the precise arrhythmic cause of syncopal episodes.¹⁸ A total of 370 patients with BrS and ILRs (mean age 43 years, 34% female, 74% symptomatic) from 18 international centres were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years. During follow-up, an arrhythmic event was recorded in 31% of symptomatic patients [19% atrial arrhythmias (AAs), 10% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. Among patients with recurrent syncope, the aetiology was arrhythmic in 22% (59% BAs, 25% VAs, and 16% AAs). The ILR led to drug therapy initiation in 11%, an ablation procedure in 11%, implantation of a pacemaker in 2.5%, and implantation of a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P = .001] and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs.

The authors conclude that ILRs detect arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation. The contribution is accompanied by an Editorial by Fiorenzo Gaita and Carla Giustetto from the University of Turin, Italy, and Natascia Cerrato from the Cardinal G. Massaia Hospital in Asti, Italy.¹⁹ The authors note that several recent publications, following the 2022 guidelines on the treatment of ventricular arrhythmias,²⁰ demonstrated that there is still great concern among the experts regarding the best stratification and treatment of patients with Brugada ECG pattern, especially those with unexplained syncope and asymptomatic patients. The study by Bergonti et al., in line with other recent articles, points out that ILRs and electrophysiological studies might have a central role, together with alternative therapeutic options to implantation of an implantable cardioverter-defibrillator (ICD), in the management of patients with Brugada ECG pattern at intermediate arrhythmic risk.

Endocarditis is a high risk condition.^21–25 In a Clinical Research article entitled ‘Cardiac implantable devices and blood stream infections: management and outcomes’, Tardu Özkartal from the Istituto Cardiocentro Ticino in Lugano, Switzerland, and colleagues note that bloodstream infection (BSI) of any cause may lead to device infection in cardiac implantable electronic device (CIED) patients. Aiming for a better understanding of the diagnostic approach, treatment, and outcome, patients with an ICD or a cardiac resynchronization therapy and defibrillator (CRT-D) hospitalized with BSI were investigated.²⁶ This is a single-centre, retrospective, cohort analysis including consecutive ICD/CRT-D patients implanted between 2012 and 2021. These patients were screened against a list of all hospitalized patients having positive blood cultures consistent with diagnosed infection in any department of a local public hospital. The total cohort consisted of 515 patients. Over a median follow-up of 59 months, there were 47 BSI episodes in 36 patients. The majority of patients with a BSI (92%) were admitted to non-cardiology units, and in 25 episodes (53%) no cardiac imaging was performed. Nearly all patients (85%) were treated with short-term antibiotics, whereas chronic antibiotic suppression therapy (n = 4) and system extraction (n = 3) were less frequent. Patients with BSI had a seven-fold higher rate (HR 6.7) of all-cause mortality as compared to patients without BSI (Figure 2).

Figure 2

Mortality in patients with and without BSI. Blue line: patients without BSI. Red line: patients with BSI. BSI, blood stream infection; CI, confidence interval; CRT-D, cardiac resynchronization therapy and defibrillator; HR, hazard ratio; ICD, implantable cardioverter-defibrillator.²⁶

The authors conclude that diagnostic workup of defibrillator patients with BSI admitted to a non-cardiology unit is often insufficient to characterize lead-related endocarditis. The high mortality rate in these patients with BSI may relate to underdiagnosis and consequently late/absence of system removal. Efforts to increase an interdisciplinary approach and greater use of cardiac imaging are necessary for timely diagnosis and adequate treatment. The manuscript is accompanied by an Editorial by Maria Grazia Bongiorni from University Hospital of Pisa in Italy and Giulio Zucchelli from the University Hospital of Pisa in Italy.²⁷ They conclude that the authors are to be congratulated for their efforts to contribute to our understanding of the current management of patients with suspected CIED infection, shedding light on a significant but underestimated problem. Their work should stimulate the international medical community to seek solutions for improving the prognosis. An international registry coordinated by the European Society of Cardiology, similar to the Electra registry for transvenous lead extraction, would be desirable to gain a better understanding of the impact of BSI due to cardiac and extra-cardiac sources on CIED recipients’ outcomes.

In a Rapid Communications contribution entitled ‘Frailty, genetic predisposition, and incident atrial fibrillation’, Ying Sun from the Shanghai JiaoTong University School of Medicine in Shanghai, China, and colleagues note that atrial fibrillation (AF) is the most prevalent arrhythmia, especially in the ageing population.²⁸ Little is known regarding the association between frailty and new-onset AF in the middle-aged and elderly and the modification effect of genetic susceptibility for AF. In this large prospective cohort study, the authors found that compared with non-frail individuals, frail individuals had an ∼40% higher risk of incident AF. There was a significant interaction between frailty status and genetic risk for AF. The highest AF risk was for participants at high genetic risk and with frailty. However, the most prominent association between frailty and AF was observed among individuals with low genetic risk, suggesting that individuals with low genetic risk may be more susceptible to frailty for incident AF.

They note that this is the first study investigating the longitudinal association among frailty, genetic predisposition, and new-onset AF.

The issue is also complemented by a Discussion Forum contribution. In a commentary entitled ‘Comparative effectiveness research using claims data: meticulous methods don’t solve old problems’, Mohammed Ruzieh from the University of Florida College of Medicine in Gainesville, FL, USA and colleagues comment on the recent publication ‘Sodium–glucose cotransporter 2 inhibitors vs. sitagliptin in heart failure and type 2 diabetes: an observational cohort study’, by Edouard L. Fu from the Brigham and Women’s Hospital and Harvard Medical School in Boston, MA, USA.^29,30

The editors hope that this issue of the European Heart Journal will be of interest to its readers.

Dr. Crea reports speaker fees from Abbott, Amgen, Astra Zeneca, BMS, Chiesi, Daiichi Sankyo, Menarini outside the submitted work.

With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.

References

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