The role of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a common condition with few effective therapies and hence represents a major healthcare burden. The clinical syndrome of HFpEF can be caused by varying pathophysiological processes, with coronary microvascular dysfunction (CMD) proposed as one of the aetiologies, although confirming causality has been challenging. CMD is characterised by the inability of the coronary vasculature to augment blood flow in response to a physiological stressor and has been established as the driver of angina in patients with non-obstructed coronaries (ANOCA), and this has subsequently led to efficacious endotype-directed therapies. CMD is also highly prevalent among sufferers of HFpEF and may represent a novel treatment target for this particular endotype of this condition. This review aims to discuss the role of the microcirculation in the healthy heart how it's dysfunction may precipitate HFpEF and explore the current diagnostic tools available. We also discuss the gaps in evidence and where we believe future research should be focussed.

Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.

BACKGROUND: Infective endocarditis (IE) remains a life-threatening disease with high morbidity and mortality. OBJECTIVES: To describe temporal trends in IE incidence, mortality and survival over the last 30 years. METHODS: Nineteen high-income countries (the 'EU 15+') were included. Age-standardised and sex-stratified incidence rates (ASIRs) and mortality rates (ASMRs) for IE were extracted from the Global Burden of Disease (GBD) database between 1990 and 2019, and mortality to incidence ratios (ASMIRs) were calculated. Trends were analysed using Joinpoint regression analysis. RESULTS: ASIRs were higher in males than females and increased in both sexes in all countries between 1990 and 2019. A recent steep rise in ASIRs was noted in several countries including the UK, the USA and Germany. ASMRs increased for both sexes in all countries except Finland and Austria. The largest increase in ASMR was observed in females in Italy (+246%). ASMIRs were generally higher in females compared to males, with large increases in ASMIRs (indicating worsening survival) at the end of the 20th century, but more recent stabilisation or decline across the study cohort. CONCLUSIONS: While the incidence and mortality of IE have increased over the last 30 years, recent data suggest that these trends have plateaued or reversed in most countries studied. However, a recent surge in incidence in several countries (including the USA and UK) is of concern, while unfavourable outcomes in females also merit attention. More encouragingly, this analysis provides the first indication of improving IE survival at population level, supporting recent advances in diagnosis and treatment.

Temporal trend analysis of rheumatic heart disease burden in high-income countries between 1990 and 2019.

AIMS: To assesses trends in rheumatic heart disease (RHD) burden in high-income, European Union 15+ (EU15+) countries between 1990 and 2019. METHODS AND RESULTS: Cross-sectional analysis of the incidence and mortality of RHD was conducted using data from the Global Burden of Disease Study (GBD) database. Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were extracted for EU15 + countries per sex for each of the years from 1990-2019, inclusive, and mortality-to-incidence indices (MII) were computed. Joinpoint regression analysis was used for the description of trends. Over 29 years, an overall declining trend in RHD incidence and mortality across EU 15 + nations were observed. There was significant variability in RHD incidence and mortality rates across high-income countries. However, both RHD incidence and mortality were higher among females compared to males across EU15 + countries over the observed period. The most recent incidence trend, starting predominantly after 2014, demonstrated a rise in RHD incidence in most countries for both sexes. The timing of this RHD resurgence corresponds temporally with an influx of migrants and refugees into Europe. The recent increasing RHD incidence rates ranged from + 0.4% to + 24.7% for males, and + 0.6% to + 11.4% for females. CONCLUSIONS: More than half of EU15 + nations display a recent increase in RHD incidence rate across both sexes. Possible factors associated with this rise are discussed and include increase in global migration from nations with higher RHD prevalence, host nation factors such as migrants' housing conditions, healthcare access and migrant health status on arrival.

Paradoxical impact of socioeconomic factors on outcome of atrial fibrillation in Europe: trends in incidence and mortality from atrial fibrillation.

AIMS: The aim of this study was to understand the changing trends in atrial fibrillation (AF) incidence and mortality across Europe from 1990 to 2017, and how socioeconomic factors and sex differences play a role. METHODS AND RESULTS: We performed a temporal analysis of data from the 2017 Global Burden of Disease Database for 20 countries across Europe using Joinpoint regression analysis. Age-adjusted incidence, mortality, and mortality-to-incidence ratios (MIRs) to approximate case fatality rate are presented. Incidence and mortality trends were heterogenous throughout Europe, with Austria, Denmark, and Sweden experiencing peaks in incidence in the middle of the study period. Mortality rates were higher in wealthier countries with the highest being Sweden for both men and women (8.83 and 8.88 per 100 000, respectively) in 2017. MIRs were higher in women in all countries studied, with the disparity increasing the most over time in Germany (43.6% higher in women vs. men in 1990 to 74.5% higher in women in 2017). CONCLUSION: AF incidence and mortality across Europe did not show a general trend, but unique patterns for some nations were observed. Higher mortality rates were observed in wealthier countries, potentially secondary to a survivor effect where patients survive long enough to suffer from AF and its complications. Outcomes for women with AF were worse than men, represented by higher MIRs. This suggests that there is widespread healthcare inequality between the sexes across Europe, or that there are biological differences between them in terms of their risk of adverse outcomes from AF.

Meta-Analysis of Randomized Controlled Trials of Atrial Fibrillation Ablation With Pulmonary Vein Isolation Versus Without.

OBJECTIVES: This meta-analysis examined the ability of pulmonary vein isolation (PVI) to prevent atrial fibrillation in randomized controlled trials (RCTs) in which the patients not receiving PVI nevertheless underwent a procedure. BACKGROUND: PVI is a commonly used procedure for the treatment of atrial fibrillation (AF), and its efficacy has usually been judged against therapy with anti-arrhythmic drugs in open-label trials. There have been several RCTs of AF ablation in which both arms received an ablation, but the difference between the treatment arms was inclusion or omission of PVI. These trials of an ablation strategy with PVI versus an ablation strategy without PVI may provide a more rigorous method for evaluating the efficacy of PVI. METHODS: Medline and Cochrane databases were searched for RCTs comparing ablation including PVI with ablation excluding PVI. The primary efficacy endpoint was freedom from atrial fibrillation (AF) and atrial tachycardia at 12 months. A random-effects meta-analysis was performed using the restricted maximum likelihood estimator. RESULTS: Overall, 6 studies (n = 610) met inclusion criteria. AF recurrence was significantly lower with an ablation including PVI than an ablation without PVI (RR: 0.54; 95% confidence interval [CI]: 0.33 to 0.89; p = 0.0147; I2 = 79.7%). Neither the type of AF (p = 0.48) nor the type of non-PVI ablation (p = 0.21) was a significant moderator of the effect size. In 3 trials the non-PVI ablation procedure was performed in both arms, whereas PVI was performed in only 1 arm. In these studies, AF recurrence was significantly lower when PVI was included (RR: 0.32; 95% CI: 0.14 to 0.73; p = 0.007, I2 78%). CONCLUSIONS: In RCTs where both arms received an ablation, and therefore an expectation amongst patients and doctors of benefit, being randomized to PVI had a striking effect, reducing AF recurrence by a half.

Outcomes of paroxysmal atrial fibrillation ablation studies are affected more by study design and patient mix than ablation technique.

OBJECTIVE: We tested whether ablation methodology and study design can explain the varying outcomes in terms of atrial fibrillation (AF)-free survival at 1 year. BACKGROUND: There have been numerous paroxysmal AF ablation trials, which are heterogeneous in their use of different ablation techniques and study design. A useful approach to understanding how these factors influence outcome is to dismantle the trials into individual arms and reconstitute them as a large meta-regression. METHODS: Data were collected from 66 studies (6941 patients). With freedom from AF as the dependent variable, we performed meta-regression using the individual study arm as the unit. RESULTS: Success rates did not change regardless of the technique used to produce pulmonary vein isolation (PVI). Neither was adjunctive lesion sets associated with any improvement in outcome. Studies that included more males and fewer hypertensive patients were found more likely to report better outcomes. The electrocardiography method selected to assess outcome also plays an important role. Outcomes were worse in studies that used regular telemonitoring (by 23%; P < 0.001) or in patients who had implantable loop recorders (by 21%; P = 0.006), rather than those with the less thorough periodic Holter monitoring. CONCLUSIONS: Outcomes of AF ablation studies involving PVI are not affected by the technologies used to produce PVI. Neither do adjunctive lesion sets change the outcome. Achieving high success rates in these studies appears to be dependent more on patient mix and on the thoroughness of AF detection protocols. These should be carefully considered when quoting the success rates of AF ablation procedures that are derived from such studies.