Expanding knowledge in atrial fibrillation, blood pressure treatment, and management of coronary and peripheral artery disease

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Focus Issue on interventional cardiology, arrhythmias, epidemiology, prevention, and health care policies contains the State of the Art Review ‘Coronary artery disease management in older adults: revascularization and exercise training’ by Rita Pavasini from the Universitaria di Ferrara in Italy, and colleagues.1 The authors remind us that coronary artery disease (CAD) remains a leading cause of death although the mean age of patients with CAD is steadily increasing.2–7 In older patients, there is a tendency to underutilize an invasive approach, coronary revascularization, up-to-date pharmacological therapies, and secondary prevention strategies, including cardiac rehabilitation. Older adults with CAD commonly exhibit atypical symptoms, multivessel disease involvement, complex coronary anatomy, and a higher presence of risk factors and comorbidities. Although both invasive procedures and medical treatments are characterized by a higher risk of complications, avoidance may result in a suboptimal outcome. Often, overlooked factors, such as coronary microvascular disease, malnutrition, and poor physical performance, play a key role in determining prognosis, yet they are not routinely assessed or addressed in older patients. Historically, clinicians have relied on subanalyses or observational findings to make clinical decisions, as older adults were frequently excluded or under-represented in clinical studies. Recently, dedicated evidence through randomized clinical trials has become available for older CAD patients. Nevertheless, the management of older CAD patients still raises several important questions. This review aims to comprehensively summarize and critically evaluate this emerging evidence, focusing on invasive management and coronary revascularization. Furthermore, it seeks to contextualize these interventions within the framework of improved risk stratification tools for older CAD patients, through user-friendly scales along with emphasizing the importance of promoting physical activity and exercise training to enhance the outcomes of invasive and medical treatments. This comprehensive approach may represent the key to improving prognosis in the complex and growing patient population of older CAD patients. In a State of the Art Review article entitled ‘Atrial fibrillation burden: a new outcome predictor and therapeutic target’, Nina Becher from the University Medical Center Hamburg-Eppendorf in Germany, and colleagues note that atrial fibrillation (AF), the most common sustained cardiac arrhythmia,8–12 is not a dichotomous disease trait.13 Technological innovations enable long-term rhythm monitoring in many patients and can estimate AF burden. These technologies are already used to detect and monitor AF. This review describes the relationship between AF burden and outcomes and potential effects of AF burden reduction. A lower AF burden is associated with a lower risk of stroke and heart failure in patients with AF: stroke risk without anticoagulation is lower in patients with device-detected AF and a low AF burden (stroke rate 1%/year) than in patients with persistent and permanent AF (stroke rate 3%/year). Paroxysmal AF shows intermediate stroke rates (2%/year). AF burden-reducing interventions can reduce cardiovascular outcomes in patients with AF: early rhythm control reduces cardiovascular events including stroke and heart failure in patients with recently diagnosed AF and cardiovascular conditions. In patients with heart failure and AF, early rhythm control and AF ablation are interventions that reduce AF burden, mortality, and heart failure events. Recent technological innovations allow estimation of AF burden in clinical care, creating opportunities and challenges. While evidence remains limited, the existing data already suggest that AF burden reduction could be a therapeutic goal. In addition to anticoagulation and treatment of cardiovascular conditions, AF burden reduction emerges as a therapeutic goal. Future research will define the AF burden that constitutes a relevant risk of stroke and heart failure. Technologies quantifying AF burden need careful validation to advance the field. In a Fast Track Clinical Research article entitled ‘Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial’, Young-Guk Ko from Yonsei University College of Medicine in Seoul, Korea, and colleagues indicate that drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease.14 However, uncertainty remains as to whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. Between May 2016 and August 2022, a total of 237 patients were enrolled and 204 (86%) completed the trial (median follow-up 363 days). The IVUS guidance group showed significantly higher primary patency (84% vs. 70%; P = .01), increased freedom from clinically driven target lesion revascularization (92% vs. 83%; P = .02), and sustained clinical (89% vs. 76%; P = .01) and haemodynamic improvement (82% vs. 67%; P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.9 vs. 3.71 mm; P = .03). The authors conclude that IVUS guidance significantly improves the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. The contribution is accompanied by an Editorial by Bruno Scheller from the University of Saarland and Thomas Zeller from the University of Freiburg in Germany.15 The authors note that in the study by Ko et al., IVUS-optimized treatment with the paclitaxel urea-coated DCB led to an improved outcome due to a more aggressive primary treatment strategy. This calls the old doctrine of gain associated with loss into question. The results of the coronary TRANSFORM I study, where a reduction in angiographic late luminal loss was seen for the paclitaxel iopromide-coated DCBs with increasing dissection volume, also fit in with this. This means that, at least for paclitaxel coatings with iopromide and urea as excipients, the old axiom no longer exists and is now simply ‘the more you gain, the more you get’. Guidelines suggest similar blood pressure (BP) targets in patients with and without diabetes and recommend ambulatory BP monitoring (ABPM) to diagnose and classify hypertension.16 In a Clinical Research article entitled ‘Office measurement vs. ambulatory blood pressure monitoring: associations with mortality in patients with or without diabetes,’ Michael Böhm from the Saarland University in Germany, and colleagues explored whether different levels of ABPM and office BP and different hypertension phenotypes are associated with differences in risk in diabetes and no diabetes.17 This analysis assessed outcome data from the Spanish ABPM Registry in 59 124 patients with complete available data from 223 primary care centres in Spain. The associations between office, mean, daytime, and night-time ambulatory BP with the risk in patients with or without diabetes were explored. The effects of diabetes on mortality in different hypertension phenotypes, i.e. sustained hypertension, white-coat hypertension, and masked hypertension, compared with normotension were studied. Cox regression analyses were performed and adjusted for demographic and clinical confounders. The majority had an office systolic BP >140 mmHg and 41% of patients were untreated. Diabetes was diagnosed in 11 391 patients (19%). Twenty-four-hour mean, daytime, and night-time BP levels at ABPM were associated with increased risk in diabetes and no diabetes, while office BP levels did not show a clear association, with no differences with or without diabetes. While the relative association of BP with cardiovascular death risk was similar in diabetes compared with no diabetes (mean interaction P = .80, daytime interaction P = .97, and night-time interaction P = .32), increased event rates occurred in diabetes for all ABPM parameters for cardiovascular death and all-cause death. White-coat hypertension was not associated with risk for cardiovascular death and slightly reduced risk for all-cause death in no diabetes [hazard ratio (HR) 0.89] without significant interaction between diabetes and no diabetes. Sustained hypertension and masked hypertension in diabetes and no diabetes were associated with even higher risk. There were no significant interactions in hypertensive phenotypes between diabetes and no diabetes and cardiovascular death risk (interaction P = .26), while some interaction was present for all-cause death (interaction P = .043) and non-CV death (interaction P = .053) (Figure 1). Main findings on office vs. ambulatory blood pressure monitoring and their association with mortality in patients with and without diabetes from the Spanish Ambulatory Blood Pressure Monitoring Registry on 59 124 patients. SBP, systolic blood pressure.17 The authors conclude that these results support recommendations of international guidelines for strict BP control and using ABPM for classification and assessment of risk and control of hypertension, particularly in patients with diabetes. This manuscript is accompanied by an Editorial by Giuseppe Mancia, Rita Facchetti, and Guido Grassi from the University Milano-Bicocca in Italy.18 The authors highlight that the study by Bohm et al. provides clear evidence on the superior ability of ABPM to stratify the cardiovascular risk of diabetic patients compared with office BP measurement. It further shows that the increased ability of ABPM to predict outcomes is shared by both the daytime and the night-time mean BP values, separately considered. It finally shows that at each ambulatory BP level, diabetic patients exhibit a greater risk compared with non-diabetic patients. There are some results in the study that are not entirely in line with what is the current prevailing view on the BP–outcome relationship, such as the apparently similar prognostic value of day-time and night-time SBP, the overall prognostic insensitivity of office SBP, especially in non-diabetic patients, and the absence of an adverse prognostic effect of white-coat hypertension. This will keep research on these issues alive and active, without detracting from the evidence on the crucial importance of collecting ambulatory BP data in patients with diabetes, whenever this is feasible. Increasing evidence suggests that some reproductive factors/hazards are associated with a future risk of cardiovascular disease (CVD) in women. In a Clinical Research article entitled ‘Perinatal depression and risk of maternal cardiovascular disease: a Swedish nationwide study’, Donghao Lu from the Karolinska Institutet in Sweden, and colleagues note that while major (non-perinatal) depression has consistently been associated with CVD, the long-term risk of CVD after perinatal depression (PND) is largely unknown.19 A nationwide population-based matched cohort study involving >55 500 women diagnosed with PND during 2001–14 in Sweden and ∼550 000 unaffected women individually matched on age and year of conception/delivery was conducted. All women were followed-up to 2020. Perinatal depression and CVD were identified from Swedish national health registers. Using multivariable Cox models, the HRs of any and type-specific CVD according to PND were estimated. The mean age at the PND diagnosis was 31 years. During the follow-up of up to 20 years, 6.4% of women with PND and 3.7% of unaffected women developed CVD. Compared with matched unaffected women, women with PND had a 36% higher risk of developing CVD (adjusted HR = 1.36), while, compared with their sisters, women with PND had a 20% higher risk of CVD (adjusted HR = 1.20). The association was observed for all CVD subtypes, with the highest HR in the case of hypertensive disease (HR = 1.50), ischaemic heart disease (HR = 1.37), and heart failure (HR 1.36) (Figure 2). Overview of the study design and the main results: association between perinatal depression (PND) and any subsequent cardiovascular disease (CVD) as well as separate analyses for antepartum and postpartum depression. CI, confidence interval; HR, hazard ratio; IR, incidence rate per 1000 person-years; N, obs., number of CVD events.19 The authors conclude that women with PND are at higher risk of CVD in middle adulthood. Reproductive history, including PND, should be considered in CVD risk assessments of women. The contribution is accompanied by an Editorial by Amani Meaidi from the Danish Cancer Institute in Denmark.20 The author concludes by reminding us that considering the rise in PND and the lack of knowledge on CVD in women, the study by Bränn and colleagues is much needed and welcomed. There is a growing interest in tricuspid regurgitation (TR) mainly because of the increasing opportunities for percutaneous treatment.21,22 Incidence and types of secondary TR are not well defined in AF and sinus rhythm (SR). Atrial secondary TR (A-STR) is associated with pre-existing AF; however, close to 50% of patients with A-STR do not have AF. In a Clinical Research article entitled ‘Secondary tricuspid regurgitation: incidence, types, and outcomes in atrial fibrillation vs. sinus rhythm’, Jwan A. Naser from the Mayo Clinic College of Medicine in Rochester, MN, USA, and colleagues sought to assess incidence, types, and outcomes of ≥ moderate TR in AF vs. SR.23 Adults with and without new-onset AF without structural heart disease or ≥ moderate TR at baseline were followed for the development of ≥ moderate TR. Tricuspid regurgitation types were pacemaker, left-sided valve disease, left ventricular (LV) dysfunction, pulmonary hypertension (PH), isolated ventricular TR, and A-STR. Among about 1350 patients with AF and ∼20 500 in SR, 109 and 378 patients developed ≥ moderate TR, respectively. The individual types of TR occurred more frequently in AF related to the higher pacemaker implantation rates (1.12 vs. 0.19 per 100 person-years, P < .001), larger right atrial size (median 78 vs. 53 mL, P < .001), and higher pulmonary pressures (median 30 vs. 28 mmHg, P < .001). The most common TR types irrespective of rhythm were LV dysfunction-TR and A-STR. Among patients in SR, those with A-STR were older, predominantly women with more diastolic abnormalities and higher pulmonary pressures. All types of secondary TR were associated with all-cause mortality, highest in PH-TR and LV dysfunction-TR. The authors conclude that new-onset AF vs. SR confers a higher risk of the individual TR types related to sequelae of AF and higher pacemaker implantation rates, although the distribution of TR types is similar. Secondary TR is universally associated with increased mortality. The manuscript is accompanied by an Editorial by Denisa Muraru and Luigi P. Badano from the University of Milano-Bicocca.24 The authors conclude that this study serves as a cornerstone for future research delineating the complex interactions between AF, atrial myopathy, diastolic dysfunction, and STR. As our understanding of these relationships deepens, so too will our ability to effectively manage and treat these challenging TR patient phenotypes through a personalized approach. The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Implantable loop recorders in patients with Brugada syndrome: the importance of a correct patient stratification’, Gregory Dendramis from the ARNAS Ospedale Civico Di Cristina Benfratelli in Italy and colleagues comment on the recent publication ‘Implantable loop recorders in patients with Brugada syndrome: the BruLoop study’ by Marco Bergonti from the Cardiocentro Ticino Institute in Switzerland, and colleagues.25,26 Bergonti et al. respond in a separate comment.27 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.