Never too soon to start cardiovascular prevention: the earlier the better (2024)

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This Focus Issue on interventional cardiology, epidemiology, prevention, and healthcare policies contains the meta-analysis contribution ‘Periprocedural myocardial infarction after percutaneous coronary intervention and long-term mortality: a meta-analysis’ by Luca Paolucci from the Mediterranea Cardiocentro in Naples, Italy, and colleagues.¹ The authors point out that conflicting data are available regarding the association between periprocedural myocardial infarction (PMI) and mortality following percutaneous coronary intervention (PCI). The purpose of this study was to evaluate the incidence and prognostic implication of PMI according to the Universal Definition of Myocardial Infarction (UDMI), the Academic Research Consortium (ARC)-2 definition, and the Society for Cardiovascular Angiography and Interventions (SCAI) definition. Studies reporting adjusted effect estimates were systematically searched. The primary outcome was all-cause death, while cardiac death was included as a secondary outcome. A total of 19 studies and about 109 000 patients were included. The incidence of PMI was progressively lower across the UDMI, ARC-2, and SCAI definitions. All PMI definitions were independently associated with all-cause mortality [UDMI: hazard ratio (HR) 1.61; ARC-2: HR 2.07; SCAI: HR 3.24] (Figure 1).

Paolucci et al. conclude that all currently available international definitions of PMI are associated with an increased risk of all-cause death after PCI. The magnitude of this association varies according to the sensitivity of each definition: the lower the sensitivity the higher the prognostic relevance. The contribution is accompanied by an Editorial by Yousif Ahmad and Alexandra Lansky from Yale School of Medicine in New Haven, CT, USA.² The authors note that there are inherent limitations associated with the use of study-level data from non-randomized studies, with the primary weakness being the pooling of data from heterogeneous patient populations and varied clinical settings. Notwithstanding these, this is an important study of a contentious area. The authors believe that the findings support the position that stringent thresholds of biomarker elevation should be utilized for periprocedural myocardial infarction after PCI, and that prognostic relevance should be emphasized above sensitivity. This concept also exists for spontaneous myocardial infarction where the data support that the degree of biomarker elevation is related to prognostic impact. To that end, Ahmad and Lansky would endorse the utilization of the SCAI definition in clinical trials of PCI as one that does not require additional qualifiers and is consistent across different revascularization strategies.

Transcatheter aortic valve implantation (TAVI) is a key form of treatment of severe aortic stenosis.^3–8 In a Fast Track Clinical Research article entitled ‘Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study’, Danny Dvir from the Hebrew University of Jerusalem in Israel, and colleagues sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to TAVI in patients at risk for coronary artery obstruction.⁹ This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI who were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. Sixty eligible patients were treated (mean age 77 years, 70% female, 97% failed surgical bioprosthetic valves, 63% single splitting and 37% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all patients. Procedure time, including imaging confirmation of leaflet splitting, was 31 ± 18 min. Freedom from the primary safety endpoint was achieved in 59 patients (98%), with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95%. Within 90 days, freedom from mortality was 95%, without any cardiovascular deaths.

The authors conclude that modification of bioprosthetic aortic valve leaflets using ShortCut is safe, successful leaflet splitting can be achieved in all patients, and is associated with favourable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI. The contribution is accompanied by an Editorial by Bernard Prendergast, Tiffany Patterson, and Simon Redwood from the Cleveland Clinic London in the United Kingdom.¹⁰ The authors note that the scope and remit of transcatheter valve intervention are increasing year on year, and wider applications of the leaflet splitting concept seem likely. Although the present series focused almost exclusively on TAV-in-SAV procedures, future experience and design refinements will enable exploration of the use of ShortCut in native aortic valve interventions (particularly in younger patients, especially those with bicuspid anatomy), transcatheter mitral valve replacement (to avoid iatrogenic left ventricular outflow tract obstruction), and the anticipated rapid expansion of TAV-in-TAV procedures. It is a general truism that there are no shortcuts to excellent outcomes in interventional cardiology—but this promising first-in-class device may be the exception that proves the rule.

In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation.^11–13 Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. In another Fast Track Clinical Research article entitled ‘Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials’, Yong-Joon Lee from the Yonsei University College of Medicine in Seoul, Korea, and colleagues evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, in patients with ACS.¹⁴ Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups (1.9% vs. 2.5%; adjusted HR 0.79; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome.

The authors conclude that in ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT is associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. The contribution is accompanied by an Editorial by Wout van den Broek and Jurriën ten Berg from St. Antonius Hospital in Nieuwegein, the Netherlands. ¹⁵ The authors highlight that the results provided by Lee et al. are another piece in the complicated puzzle that is the optimal antithrombotic strategy after ACS. However, certain pieces of the puzzle are still missing. The exact timing for omitting aspirin remains uncertain, although the majority of evidence suggests doing so after 1-month post-PCI when the ischaemic risk is highest, particularly in event-free patients. Another missing piece involves the role of a guided approach in selecting P2Y12 inhibitor monotherapy. Unfortunately, there are no studies yet that provide evidence on the potential additional benefit of guided P2Y12 inhibitor monotherapy after an initial period of DAPT. Ultimately, physicians are constrained by the testing facilities and drug availability in their clinical setting. Therefore, it is crucial for physicians to evaluate each patient individually, carefully balancing thrombotic and bleeding risk factors, and devise a personalized antithrombotic strategy tailored to their unique circ*mstances.

We are experiencing a pandemic of obesity, a potent cardiovascular risk factor.^16–19 Excess adiposity is associated with poorer cardiac function and adverse left ventricular (LV) remodelling. However, its importance over the adult life course on future cardiac structure and systolic and diastolic function is unknown. In a Clinical Research article entitled ‘Adulthood adiposity affects cardiac structure and function in later life’, Lamia Al Saikhan from the College of Applied Medical Sciences in Dammam, Saudi Arabia, and colleagues studied a total of 1690 participants in the National Survey of Health and Development birth cohort who underwent repeated adiposity [body mass index (BMI)/waist-to-hip ratio (WHR)] measurements over adulthood and investigation, including echocardiography at age 60–64 years.²⁰ The relationship between LV structure [LV mass (LVM), relative wall thickness, and LV internal diameter in diastole (LVIDd)] and function (diastolic: E/eʹ, eʹ, and left atrial volume indexed to body surface area; systolic: ejection fraction, Sʹ, and myocardial contraction fraction) was investigated using multivariable linear regression models. Increased BMI from age 20 years onwards was associated with greater LVM and LVIDd independent of confounders. Associations remained independent of current BMI for LVIDd and at age 26, 43, and 53 years for LVM. Increased BMI from 43 years onwards was associated with greater relative wall thickness, but not when BMI at age 60–64 years was accounted for. Increased BMI at age 26, 36, and 53 years and at 20 years onwards was associated with lower ejection fraction and myocardial contraction fraction, respectively, but not independently of BMI at 60–64 years. Higher BMI from 20 years onwards was associated with poorer diastolic function independent of confounders. Associations between BMI and left atrial volume indexed to body surface area persisted from 26 years onwards after adjustment for BMI at 60–64 years. Similar relationships were observed for WHR from age 43 years onwards.

The authors conclude that higher adiposity (BMI/WHR) over adulthood is associated with evidence of adverse cardiac structure and function. Some of these associations are independent of the presence of adiposity in later life. This manuscript is accompanied by an Editorial by Leonardo Roever from the Brazilian Evidence-Based Health Network in Uberlândia, Brazil, Gary Tse from the Second Hospital of Tianjin Medical University in China, and Giuseppe Biondi-Zoccai from the Sapienza University of Rome in Italy.²¹ The authors note that this study poignantly summarizes the temporal and dimensional continuum of cardiac injury associated with abnormal BMI, and provides compelling evidence that being overweight or obese, even at a younger age, translates into an unfavourable cardiovascular risk profile, basically due to detrimental changes in cardiac function, ranging from structural injury to diastolic and systolic dysfunction. Notably, a temporal dose–response relationship was evident between increasing BMI and adverse changes in cardiac anatomy and function. Thus, greater injury was observed for higher BMI, and even minor increases in such parameters were associated with adverse cardiac effects. In contrast, whilst causation and reverse causation are difficult to ascertain in observational studies, it is likely that improvements in BMI over several decades, such as in a patient who was obese when young but has now successfully lost weight due to dieting and exercising, may translate into significant clinical benefits from prevention or reversal of cardiac injury or dysfunction.

Implementation of an appropriate diet is associated to a lower cardiovascular risk.^22,23 In a Clinical Research article entitled ‘Randomized 20-year infancy-onset dietary intervention, life-long cardiovascular risk factors and retinal microvasculature’, Oskari Repo from the University of Turku in Finland, and colleagues investigated associations of lifelong cardiovascular risk factors and effects of dietary intervention on retinal microvasculature in young adulthood.²⁴ The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project study. The latter is a 20-year infancy-onset randomized controlled dietary intervention study with frequent study visits and follow-up extending to age 26 years. The dietary intervention aimed at a heart-healthy diet. Fundus photographs were taken at the 26-year follow-up, and microvascular measures [arteriolar and venular diameters, tortuosity (simple and curvature) and fractal dimensions] were derived (n = 486). Cumulative exposure as the area under the curve for cardiovascular risk factors and dietary components was determined for the longest available time period (e.g. from age 7 months to 26 years). The dietary intervention had a favourable effect on retinal microvasculature resulting in less tortuous arterioles and venules and increased arteriolar fractal dimension in the intervention group when compared with the control group. The intervention effects were found even when controlled for the cumulative cardiovascular risk factors. Reduced lifelong cumulative intake of saturated fats, main target of the intervention, was also associated with less tortuous venules. Several lifelong cumulative risk factors were independently associated with the retinal microvascular measures, e.g. cumulative systolic blood pressure with narrower arterioles (Figure 2).

Repo and colleagues conclude that infancy-onset 20-year dietary intervention has favourable effects on the retinal microvasculature in young adulthood. Several lifelong cumulative cardiovascular risk factors are independently associated with retinal microvascular structure. The contribution is accompanied by an Editorial by Miriam Mayor, Miquel Camafort, and Ramon Estruch from the University of Barcelona in Spain.²⁵ The authors note that nowadays, the onset of atherosclerosis in children and adolescents appears to be earlier, necessitating the development of new tools to identify young individuals who require special attention and inclusion in intensive community preventive cardiovascular programmes. These programmes should promote a healthier lifestyle by improving adherence to healthy dietary patterns such as Mediterranean or Nordic diets, increasing physical activity, and using behavioural therapies when needed.

The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Time is relative, also when comparing transcatheter edge-to-edge repair to mitral valve surgery’, Ovidio A García-Villarreal from the Mexican College of Cardiovascular and Thoracic Surgery in México and Amedeo Anselmi from the Pontchaillou University Hospital in Rennes, France comment on the recent publication ‘Mitral transcatheter edge-to-edge repair vs. isolated mitral surgery for severe mitral regurgitation: a French nationwide study’ by Pierre Deharo from CHU Timone in Marseille, France.^26,27 Deharo et al. respond in a separate comment.²⁸

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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