Hospitalization Rates Research Articles

Epidemiological characteristics of the 2019 Measles outbreak in central Tunisia

Abstract Background Measles is still an important public health problem worldwide causing significant morbidity and mortality. Measles represents a vaccine-preventable disease. In Tunisia, vaccination against measles was launched in 1983. In spite of the progress made towards measles elimination, Tunisia experienced an outbreak in 2019. We aimed to describe the measles outbreak in the central region of Tunisia in 2019. Methods We carried out a descriptive study using surveillance data from January to December 2019 in four governorates in Tunisia (Monastir, Mahdia, Kairouan, and Kasserine). All suspected measles cases and declared to regional directorate of primary health care were included. A suspected measles case was defined as any person with fever and generalized maculo-papular rash plus one of the following symptoms: cough or coryza or conjunctivitis. A laboratory confirmed measles case is a suspected case of measles that has been confirmed positive by testing (IgM+). Results A total of 2,688 suspected cases were recorded, of which 369 cases were (14.7%) were confirmed measles through serological testing. The sex ratio was 1.06 for suspected cases and 1.12 for measles cases. Infants under one year old accounted 42.2% of suspected cases. The majority of suspected cases (67.3%) were not vaccinated. Among confirmed measles cases, positivity rates were 81.8% for unvaccinated, 70.0% for those with one dose and 27.2% for those with two doses. The hospitalization rate was 61.5 %; highest rates were observed in infants under one year of age (65.7%) and in the age group over 38 years (69.0%). In total, 27 deaths were reported. The highest lethality rate was observed in the age group under 12 months (2%). Conclusions The 2019 measles outbreak in Tunisia highlighted that this disease remains a serious viral infection. Unvaccinated populations could be a potential source for new outbreaks, imposing substantial public health burdens. Key messages • The country needs to establish a national review committee to monitor measles elimination status. • To address future challenges, immunity gaps in the population should be closed.

Comparative safety outcomes of leadless versus transvenous cardiac pacemaker: a systematic review and meta-analysis

Abstract Introduction Leadless Cardiac Pacemakers (LCP) have emerged as a promising alternative to Transvenous Pacemakers (TVP) for managing bradyarrhythmias, especially in cases where TVP options are limited, such as venous access issues in haemodialysis patients or high infection risk individuals. However, long-term safety data, including mortality and hospitalisation rates, are lacking, hindering informed clinical adoption decisions. Purpose This systematic review and meta-analysis compares safety endpoints of LCP with TVP. Methods A systematic search of PubMed, Medline, Embase, Scopus, Web of Sciences, and gray literature was conducted following PRISMA guidelines from release of the Micra LCP to market until May 15, 2023. Meta-analysis was performed using RevMan 5.4. Results Twenty-four studies including data from 33,450 patients (12,802 LCP, 20,648 TVP) were evaluated. The mean age of the population was 77.5 ± 10.6 years, with a mean left ventricular ejection fraction (LVEF) of 58.6 % ± 6.7. Follow-up durations ranged from 6 to 36 months. Compared to TVP, the LCP was associated with significantly fewer overall complications, major complications, acute, mid-term complications, hospitalisations, re-interventions, and device dislodgements (p<0.05). Mortality, tricuspid regurgitation, pacemaker-induced cardiomyopathy, and heart failure hospitalisation rates did not significantly differ. Although LCP showed higher cardiac injury risk, no significant difference in cardiac tamponade rates was observed (Figure 2). LCP exhibited increased vascular-related complications but decreased lung injury, endocarditis, device, and pocket-related issues. Conclusion In the largest review of LCPs, we report that LCP is associated with significantly lower rates of overall complications compared to conventional TVP. This knowledge is critically important as more LCPs enter clinical practice and serves as a baseline against which future data can be evaluated. Nevertheless, proper skill training may help to mitigate the risk of vascular and cardiac injury. These findings underscore the importance of conducting randomized controlled trials to comprehensively evaluate the safety of LCP compared to TVP.Cardiac complication

Transthyretin stabiliser therapy in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

Abstract Introduction The safety and efficacy of transthyretin (TTR) stabilisers in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains unclear. Objectives We aimed to assess whether TTR stabilisers are effective and safe to promote medical optimisation in patients with ATTR-CM. Methods We systematically searched PubMed, Embase and Cochrane for studies comparing the use of TTR stabilisers with placebo or no TTR stabilisers in patients with ATTR-CM. Statistical analyses were performed using RevMan 5.1.7. Heterogeneity was examined with the Cochran Q test and I2 statistics. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were computed with a random-effects model for binary endpoints. Results We included 2 randomised controlled trials (RCT) and 12 observational studies, comprising 3324 patients, of whom 1563 (47,02%) received TTR stabilisers. Follow-up ranged from 7 to 36 months. TTR stabilisers were significantly associated with lower all-cause mortality (RR 0.32; 95% CI 0.18-0.57; p<0.01) and cardiovascular hospitalisation (RR 0.67; 95% CI 0.52-0.86; p=0.02) as compared with control group. In a sub analysis of RCTs and multivariate-adjusted data, the composite endpoint of all-cause mortality, heart transplant, and cardiac assist device implantation yielded significant lower rates in the TTR stabiliser group (HR 0.46; 95% CI 0.28-0.73; p=0.01). Conclusion In patients with ATTR-CM, TTR stabilisers were associated with significant lower rates of all-cause mortality and cardiovascular hospitalisations as compared with control group.

Ferric derisomaltose versus usual care in patients with heart failure, reduced ejection fraction, and iron deficiency: a short-term UK cost-utility analysis based on the IRONMAN RCT

Abstract Background In the IRONMAN trial, patients with heart failure (HF), a reduced ejection fraction and iron deficiency who were randomly assigned to ferric derisomaltose (FDI), rather than usual care, had a lower rate of the composite of hospitalization for heart failure (HHF) and cardiovascular (CV) death (rate ratio, RR, 0.82; 95% CI 0.66 to 1.02; p=0.07). A COVID-19 sensitivity analysis, censoring data at 1 year of follow-up showed a greater magnitude of treatment effect (RR 0.66; 95% CI 0.48 to 0.91; p=0.011). Purpose Patient-level data from IRONMAN were used to evaluate the effectiveness and cost-utility of FDI compared to usual care for patients with a current or recent HHF, or raised plasma natriuretic peptide concentrations, from a UK National Health Service (NHS) perspective. Methods A cost-utility analysis (CUA) was conducted covering the first year after randomization. Numbers-needed-to-treat (NNTs) were calculated for the primary endpoint censored at 1 year. In the CUA model, patient survival and rates of (re)hospitalization due to HF, other CV events, infections, respiratory conditions, and other non-CV events were modeled based directly on data from the IRONMAN RCT. UK-specific costs were obtained from the national schedule of NHS costs. Quality of life was estimated based on EQ-5D-5L data collected from patients included in the IRONMAN RCT. Results were undiscounted and reported as absolute and incremental costs in 2023 pounds sterling, and quality-adjusted life expectancy in quality-adjusted life years (QALYs). A willingness-to-pay threshold of £20,000 per QALY was adopted to allow calculation of a net monetary benefit (NMB), a summary measure of the overall value of FDI in monetary terms, capturing changes in both cost and QALY outcomes. Results The NNT analysis showed that 9 patients would need to be treated with FDI to avoid one composite primary endpoint event (CV death and HHF) over 1 year. Relative to usual care, FDI was associated with an improvement of 0.01 QALYs per patient over 1 year (0.58 versus 0.57 QALYs). Total average costs per-patient were £1,672 for FDI, versus £1,975 for usual care, leading to a saving of £302 per patient with FDI. The cost of iron procurement was more than offset by reductions in costs of (re)hospitalizations (Figure). FDI was therefore dominant over usual care, yielding an NMB of £483 over 1 year. Conclusions This short-term, within-trial CUA suggests that FDI both improves QALYs and reduces healthcare expenditure versus usual care when administered to patients with HF and iron deficiency in the UK. Iron repletion with FDI may be a prudent allocation of healthcare resources in this patient population.Breakdown of costs

Influence of process-focused patient care on clinical outcomes among hospitalized heart failure patients in the cardiology ward

Abstract Background The implementation of a process-oriented organizational structure in patient care allows for a comprehensive and optimized approach. In the context of heart failure (HF), it remains uncertain whether the establishment of a specialized hospitalisation team can contribute to improved major clinical outcomes. Purpose To analyse the rates of all-cause hospitalisation, cardiovascular hospitalization, HF hospitalization and overall mortality at 180 days among patients admitted to the Cardiology ward for HF, both prior to and after the implementation of a specialized HF hospitalisation team. Methods The study included all patients discharged from the Cardiology department with HF as the primary diagnosis and subsequent outpatient follow-up by the Community HF Unit in both 2019 and 2022. Clinical outcomes were compared between two distinct periods: the pre-implementation year of 2019 and the subsequent year of 2022, characterized by process-oriented HF care. Statistical analyses were performed using Kaplan-Meier and adjusted Cox proportional-hazards models. Results A total of 140 patients were enrolled in the study, comprising 55 individuals receiving care from a conventional ward team in 2019 and 85 under the specialized HF team in 2022. The mean age of the cohort was 69.4 years (+/-11.8), with a mean LVEF of 40.6%. The pre-implementation group showed a higher percentage of male patients (73% vs. 47%; p=0.003) and LVEF was lower in the HF team period (38.9% vs. 43.4%; p=0.045), with no statistically significant differences in other baseline variables. As shown in figure 1, over 180 days of follow-up, 15 patients (27.6%) were admitted to hospital in the conventional ward team period and 13 (15.3%) in the HF team period (hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.19 to 0.99; P=0.047). Of these hospitalisations, 13 patients (23.6%) in pre-implementation period and 10 (11.8%) in post-implementation period were attributed to cardiovascular events (HR 0.40; 95% CI 0.16 to 0.99; P=0.049). Additionally, there was a reduction in the rate of heart failure admissions in the post-implementation period compared to the pre-implementation time (HR 0.30; 95% CI 0.09 to 0.94; P=0.039). Furthermore, a significant decline in all-cause of death was observed in patients treated by HF-team in 2022 compared to patients receiving care from the conventional ward team (log-rank test, p=0.015). Conclusions The implementation of a process-oriented organizational model within the Cardiology unit consisting in the provision of patient care by a team specialized in HF management, is associated with a statistically significant reduction in major clinical outcomes such as all-cause hospitalization, cardiovascular hospitalization and HF readmission, alongside a reduction in overall mortality rates at 180 days.

Effect of severe tricuspid regurgitation on the prognosis of patients with atrial functional mitral regurgitation: the REVEAL-AFMR registry

Abstract Background Tricuspid regurgitation (TR) often coexists with atrial functional mitral regurgitation (AFMR), resulting from tricuspid annular dilatation by right atrial enlargement/dysfunction without balanced leaflet area enlargement. The clinical impact of TR coexisting with AFMR have not been well understood. Purpose We aimed to investigate the prevalence and prognostic value of TR coexisting with AFMR. Methods In 26 facilities in Japan, patients with AFMR defined with significant functional MR with dilated left atrium and preserved left ventricular ejection fraction were enrolled. The primary endpoint was all-cause death, and the secondary endpoints were the composite of all-cause death and re-hospitalization for HF readmission. Results We analyzed 829 cases (age 77±9 years, 55% male) with moderate or severe AFMR excluding moderate or greater valvular stenosis and severe valvular regurgitation. Of these, 14.5% (n=120) had severe TR. The prevalence of severe TR increased as the severity of AFMR worsened (Figure A). Patients with severe TR had a longer history of atrial fibrillation, elevated NT-proBNP levels, a higher rate of prior heart failure hospitalizations, and a higher rate of prescription of loop diuretics than those with non-severe TR. There were no significant differences in tricuspid annular plane systolic excursion (TAPSE) and right ventricular S′ between the groups. In a multivariate logistic regression analysis, existence of atrial fibrillation and its duration, and higher right atrial pressure were independent determinants of severe TR. Kaplan-Meier curves showed prognostic stratification by severe or non-severe TR for both all-cause mortality and the composite endpoints (p<0.001). Severe TR was significantly associated with both all-cause deaths and the composite endpoints after adjusted for covariates regardless of the severity of MR (adjusted hazard ratio (HR) 1.74 [95% confidence interval 1.05-2.87], p=0.031 for all-cause deaths and adjusted HR 1.54 [1.03-2.30], p=0.033 for the composite endpoints) (Figure B). Conclusion Severe TR was associated with increased adverse events in patients with AFMR, independently of the severity of MR.

The association of NT-proBNP levels in atrial fibrillation patients and 3-year risk of heart hospitalization and death

Abstract Background NT-proBNP-levels are often elevated in patients with atrial fibrillation (AF), but their clinical use and interpretation for predicting subsequent cardiovascular events has not been explored in an all-comers setting. Aim To determine whether NT-proBNP levels are associated with the risk of subsequent heart failure (CHF) and/or death in patients with AF and its relation to prior CHF diagnosis Method All patients with new-onset AF (defined by ICD-code I48) who had an NT-proBNP-level within +/- 14 days of the date of the AF date measured in a regional laboratory repository between 2000-2021 were included in the analysis cohort. Patients were categorized into NT-proBNP level (pg/mL) <1000, 1000-1999, ≥2000. If several NT-proBNP-levels were measured, the maximal value was used. The association between NT-proBNP level and the outcome CHF hospitalization and/or death within 3 years of diagnosis was assessed in Cox regression analyses adjusted for baseline characteristic and medications. Since there was an interaction (p<0.001) between Nt-proBNP-level and prior/new-onset CHF at time of AF diagnosis and no known CHF, two separate analyses were performed in patients with or new-onset CHF and those without prior CHF. Results There were 10559 patients with AF and no CHF, and 11 257 with AF and CHF. There were 14% of patients with new-onset CHF at time of new-onset AF diagnosis. These were grouped together with patients with known CHF. Patients with no prior CHF were younger (76 years (95% CI 68-83) vs 80 (72-87), p<0.001), and healthier with less often diabetes (18.4% vs 24.5%, p<0.001), prior myocardial infarction (12.0% vs 24.3%), a lower CHA2DS2-VASc score (3.0 vs 5.0, p<0.001) and a lower median NT-proBNP level (1650 pg/mL (95% CI 702-3549) vs 4240 pg/mL (2160-8860), p<0.001). Among patients with AF and no prior CHF, the incidence rate in the lowest NT-proBNP level was low, but increased with higher levels (Table). Adjusting for covariates and medications, the risk of both CHF hospitalization and CHF/death compared to the reference category NTproBNP< 1000 pg/mL was nearly 2 and 3 times higher among those who with initial NT-proBNP level 1000-1999 and ≥ 2000. Among patients with AF and known CHF, the incidence rate of CHF hospitalization or CHF hospitalization/death at the same NT-proBNP-strata was several times higher compared to patients without known CHF. Adjusting for covariates, the risk increased for CHF hospitalization or CHF/hospitalization similarly for each strata as for patients without known CHF. AF patients without known HF but with the highest elevation of NTproBNP-level had a risk of subsequent hospitalization of heart failure which was higher than those with known heart failure and lowest NTproBNP-level. Conclusion A higher NTproBNP-level in patients with AF identifies patients at higher risk of CHF hospitalization and/or death in both patients with no and prior CHF.Table

Atrial Fibrillation in young patients: Insights from the National Inpatient Sample

Abstract Background The burden of atrial fibrillation (AF) in young patients is not well characterized. We aimed to study trends in AF burden and management over time in patients aged 18-45 years. Methods We conducted a retrospective analysis of all primary AF hospitalizations in patients 18-45 years of age using the United States National Inpatient Sample (NIS) data from 01/01/2008 to 12/31/2019. We collected data on clinical and socioeconomic features including demographics, comorbidities, ZIP Code income, resource utilization, and various clinical outcomes. Quartile classification of the median household income of the zip code of the patient’s residence was used to classify socioeconomic status. Results The rate of AF hospitalizations decreased over time from 18.7 per 100,000 in 2008 to 13.0 per 100,000 in 2019 (p<0.001) (Figure 1). AF hospitalizations were higher amongst males compared to females (24.0 vs. 7.5 per 100,000), and higher in black patients compared to other ethnicities (20.4 for black vs. 15.6 for white vs. 8.5 Hispanic per 100,000) (Figure 2). The utilization of electrical cardioversion increased from 17.6% in 2008 to 21.9% in 2019 (p<0.001), and the utilization of catheter ablation decreased from 7.1% in 2008 to 4.3% in 2019 (p<0.001) (Figure 1). Men were more likely to undergo electrical cardioversion than women (20.1% vs. 14.8%, p <0.001). White patients were more likely to undergo electrical cardioversion (20.8% vs. 14.3%) and catheter ablation (6.1% vs. 3.3%, p <0.001) compared to black patients. Patients in the highest socioeconomic status quartile were more likely to undergo electrical cardioversion (21.9% vs. 16.4%, p<0.001) and catheter ablation (8.0% vs. 3.7%, p<0.001) compared to patients in the lowest socioeconomic status quartile. Conclusions We found significant differences in inpatient AF burden across different patient populations. We identified differences in inpatient AF management based on sex, ethnicity, and socioeconomic status. Further research is needed to better understand these differences, their impact on clinical outcomes, and strategies to improve healthcare disparities.

Effects of Sacubitril/Valsartan on all-cause hospitalizations in heart failure: participant-level pooled analysis of PARADIGM-HF and PARAGON-HF

Abstract Background Sacubitril/valsartan is indicated to reduce the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with chronic HF. However, many of these patients are older and have multiple comorbidities that increase the risk of hospitalizations other than HF, yet the effects of sacubitril/valsartan on hospitalizations of any cause have not been well described. Methods PARADIGM-HF and PARAGON-HF were phase-3, global multicenter randomized clinical trials that evaluated sacubitril/valsartan versus enalapril (in PARADIGM-HF) or valsartan (in PARAGON-HF) across the spectrum of left ventricular ejection fraction (LVEF; ≤40% in PARADIGM-HF and ≥45% in PARAGON-HF). We pooled individual participant-level data from these 2 trials to examine the effects of sacubitril/valsartan on time-to-first investigator-reported all-cause and cause-specific hospitalization using Cox proportional hazards models, stratified by geographic region and trial. We additionally examined heterogeneity in treatment response by LVEF. Results Over 2.8 years median follow-up, among 13,194 participants in the pooled PARADIGM-HF/PARAGON-HF, sacubitril/valsartan significantly reduced the risk of all-cause hospitalizations compared with renin-angiotensin system inhibitor (HR 0.92; 95% CI 0.88-0.97; P=0.002); Figure 1 Panel A. The absolute risk reduction (ARR) was 2.1 per 100 patient-years corresponding to a number-needed-to-treat (NNT) of 48 patient-years of treatment exposure to prevent 1 all-cause hospitalization. Reductions in overall hospitalizations among patients with identifiable causes (N=5,783) seemed to be primarily driven by lower rates of cardiac and pulmonary hospitalizations associated with sacubitril/valsartan. Patients treated with sacubitril/valsartan did not have a higher rate of composite non-cardiac hospitalizations (Figure 1 Panel B). Similarly, sacubitril/valsartan reduced the risk of the composite of all-cause hospitalization or all-cause mortality (HR 0.92; 95% CI 0.87-0.96; P<0.001), with an ARR of 2.5 per 100 patients-years and an NNT of 40 patient-years. For all-cause hospitalization, we observed significant heterogeneity by LVEF as a continuous measure (Pinteraction=0.027); treatment effects were most apparent in those with an LVEF below 60% (HR 0.91 95% CI 0.86-0.96; Figure 2). Conclusions In a pooled analysis of >13,000 patients with chronic HF, sacubitril/valsartan reduced hospitalization for any reason with benefits most apparent among those with an LVEF below normal.

Colchicine prevents post-ablation atrial fibrillation recurrence: a systematic review and meta-analysis

Abstract Background Catheter ablation for atrial fibrillation (AF) is a commonly performed procedure with appreciable effectiveness; however, post-AF ablation recurrence is often observed. The pathophysiology behind this recurrence is often inflammation and oxidative stress triggered during the ablation procedure. Colchicine is a potent anti-inflammatory agent that has emerged as a promising therapeutic for preventing post-ablation AF recurrence; however, the data available on its efficacy are limited. Purpose This meta-analysis aimed to investigate the outcomes of post-ablation AF patients who received colchicine in the postoperative period. Methods A comprehensive literature search spanning major bibliographic databases was conducted to retrieve studies comparing outcomes in post-ablation AF patients who received colchicine versus those who did not. The outcomes of interest included AF recurrence, pericarditis, gastrointestinal side effects, and hospitalization. AF recurrence was determined with a 12-lead electrocardiogram and/or Holter monitoring. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were pooled from all studies using the DerSimonian and Laird random-effects model. Statistical significance was set at p ≤ 0.05. Results Six studies were included with 1791 patients (721 in the colchicine group and 1070 in the placebo group). Patients who received colchicine had significantly lower odds of AF recurrence on follow-up [OR: 0.62; 95% CI: 0.48, 0.79; p=0.0001] but had higher gastrointestinal side effects [OR: 2.67; 95% CI: 1.00, 7.12; p=0.05]. There were no statistically significant differences in acute pericarditis [OR: 0.54; 95% CI: 0.27, 1.05; p=0.07] or hospitalization [OR: 1.03; 95% CI: 0.73, 1.45; p=0.87]. Conclusion Prophylactic use of colchicine after catheter ablation in patients with AF leads to a reduction in AF recurrence, albeit with increased gastrointestinal side effects such as diarrhea and nausea. Colchicine use did not lead to a reduction in the rates of pericarditis and hospitalization after ablation. Large randomized controlled trials are necessary to evaluate the efficacy of colchicine in the prevention of AF recurrence, particularly focusing on the dose and duration of treatment to optimize the side effect profile.

Long-term heart failure risk after atrial septal defect closure in elderly

Abstract Background There is concern that atrial septal defect (ASD) closure will unmask underlying diastolic dysfunction or left heart disease in elderly causing heart failure. It is controversial whether fenestrated devices should be used in elderly patients. Purpose To assess the long-term heart failure risk after ASD closure in elderly and risk factors associated with heart failure hospitalization in a single centre. Method From 2003-2023, all elderly patients aged more that 60 years old who had ASD closure performed successfully in this centre were retrospectively studied. Baseline demographics, underlying risk factors and survival without heart failure hospitalization were analyzed. Result From 2003-2023, 73 patients aged more than 60 years old underwent successful ASD closure in our centre. None of these patients had balloon occlusion test for assessment of left atrial pressure. Median age was 66 years old (60-84) at operation and 27 (37.0%) of them were male. Common risk factors included diabetes (n=9, 12.3%), hypertension (n=31, 42.5%) and ischaemic heart disease (n=8, 11%). Thirty-nine (53.4%) patients had pre-existing atrial fibrillation and 17 (23.3%) of them had moderate to severe left sided valvular lesions. Heart failure symptoms were present in 31 (42.5%) of them (Figure 1). During a median follow-up time of 4 years (1-15 years), 80.8% of patients did not experience heart failure hospitalization (Figure 2). Pre-existing atrial fibrillation and left-sided valvular lesions were associated with higher risk of heart failure hospitalization (OR 4.06, 95% CI 1.03-16.06 p=0.036 and OR 4.9, 95% CI 1.41-17.09 p=0.009). Conclusion In a median follow-up time of 4 years, patients aged more than 60 years old had low rate of heart failure hospitalization after ASD closure. Pre-existing atrial fibrillation and left-sided moderate to severe valvular lesions were associated with higher risk of heart failure admission. Further studies should be conducted on ASD closure in these group of patients.Figure 1Figure 2

Advancing prognostic insights in STEMI patients through microvascular resistance reserve evaluation

Abstract Background Coronary microvascular dysfunction (CMD) after ST-Elevation Myocardial Infarction (STEMI) is associated with persistent symptoms and poor outcomes. Microvascular Resistance Reserve (MRR) is an innovative metric for evaluating coronary microvasculature that is unaffected by epicardial stenoses or the hemodynamic impact of vasodilators. While MRR's prognostic ability is recognized in chronic coronary syndrome, its application in ACS remains unestablished. Purpose We sought to investigate the prognostic value of MRR in STEMI patients. Methods This is a prospective study of 210 STEMI patients with multivessel disease who had undergone successful primary percutaneous coronary intervention (PCI). At 3 months follow-up, they returned for complete revascularization and coronary physiology evaluations, including coronary flow reserve (CFR), fractional flow reserve (FFR), and index of microcirculatory resistance (IMR), using bolus thermodilution. MRR was calculated using the formula: MRR = (CFR/FFR) × (Pa rest/Pa hyper), where Pa rest and Pa hyper represent resting and hyperemic aortic pressure, respectively1. We utilized an MRR cutoff of 3.0 based on Boerhour et al. The association between MRR and major adverse cerebrocardiovascular events (MACCE) at 12-month follow-up, defined as the composite of stroke, revascularization, myocardial infarction (MI), heart failure hospitalization, and death, was investigated. Results The median age was 65 years, and 40.48% were female. At a 3-month follow-up, 27% (56 patients) exhibited MRR <3.0, who were predominantly female (62.50% vs 32.47%, p<0.001) with a higher incidence of diabetes (39.29% vs 18.83%, p = 0.004). No significant differences were observed in age, body mass index, or STEMI location (anterior or inferior) when comparing between MRR groups. The MACCE-free survival at 12 months was significantly lower in patients with an MRR < 3.0 (48.2%) compared to those with an MRR ≥ 3.0 (11.0%; log-rank p < 0.001, Fig1A). The MRR < 3.0 group showed higher rates of ischemic stroke (8.93% vs. 1.30%, p = 0.022) and hospitalization for heart failure (21.43% vs. 2.60%, p < 0.001), while the incidence of nonfatal myocardial infarction (MI) and cardiovascular death were similar between the two MRR groups (Figu1B). In multivariable Cox regression analysis, MRR was an independent predictor for 12-month MACCE (Hazard Ratio 0.45 per unit increase, 95% Confidence Interval 0.31-0.67, p<0.001). The areas under the receiver operating characteristic curves for predicting 12-month MACCE using FFR, CFR, IMR, and MRR yielded values of 0.609, 0.762, 0.781, and 0.743, respectively (Fig2). The prognostic performances of CFR, IMR, and MRR were similar and superior to that of FFR. Conclusion This study establishes the novel parameter MRR as a superior prognostic indicator in STEMI patients compared to FFR, and on par with CFR and IMR. MRR is a reliable predictor of MACCE, and various clinical incidents post-STEMI.

The impact of ethnicity on clinical outcomes in patients with heart failure and atrial fibrillation

Abstract Introduction Heart failure (HF) and atrial fibrillation (AF) are increasingly prevalent and associated with substantial morbidity (1,2). When HF and AF co-exist, the outcome profile is significantly worse than for either condition in isolation (3). Ethnic background is known to influence disease outcomes and treatment efficacy (4), but there is limited knowledge about how HF, AF and ethnicity interact on mortality and hospital admission. Purpose This study aims to address the null hypothesis of no difference in death and cardiovascular events comparing non-white and white patients with HF and concomitant AF, and assess the differential impact of ethnicity in patients with these conditions. Methods Individual patient data were obtained from 12 randomized controlled trials (RCTs) in patients with HF. RCT data were harmonised and meta-analysed to investigate the interaction of baseline heart rhythm (sinus rhythm versus atrial fibrillation) and ethnicity (non-white versus white). The primary outcome of all-cause mortality and secondary outcome of cardiovascular (CV)-related mortality were analysed using adjusted Cox regression models and propensity-score matching. Results 16,713 HF patients were included of which 1,899 (11%) were non-white, median age 66 (interquartile range [IQR] 57-73) and 4,703 (28%) women. During median follow-up of 1.4 years (IQR 0.8-2.3), death occurred in 394 (21%) non-white patients and 2,142 (15%) white patients; adjusted hazard ratio (HR) 1.36, 95% CI 1.20-1.54; p<0.001. The impact of ethnicity was greater in patients with coexisting HF and AF (non-white versus white HR 2.05; 95% CI 1.55-2.70; p<0.001), than in those with HF in sinus rhythm (non-white versus white HR 1.24; 95% CI 1.08-1.41; p=0.002). A significant interaction was evident between ethnicity and rhythm status for all-cause mortality (p=0.003), with similar findings using propensity-score matching (Figure 1). An exploratory analysis of beta-blockers versus placebo demonstrated divergent efficacy with respect to mortality for non-white (HR 1.00, 95% CI 0.79-1.27; p=0.99) and white patients (HR 0.70, 95% CI 0.63-0.78; p<0.001); p-interaction=0.008 (Figure 2). For cardiovascular hospitalisation, the non-white cohort also had higher rates, with greatest disparity in patients with combined HF and AF (non-white versus white HR 1.80, 95% CI 1.63-2.37; p<0.001) compared to HF in sinus rhythm (non-white versus white HR 1.23, 95% CI 1.11-1.36; p<0.001); p-interaction=0.012 in propensity-matching. Conclusion Non-white patients with HF suffer from substantially higher rates of death and hospitalisation than corresponding white patients, with the presence of comorbid AF significantly worsening this ethnicity-related disparity. In those with HF in sinus rhythm, beta blockers were found to be significantly less effective at reducing mortality in non-white patients.Figure 1 Figure 2

Long-term outcomes in patients with dual pathology aortic stenosis and cardiac amyloidosis referred for valve intervention

Abstract Background The coexistence of aortic stenosis (AS) and cardiac amyloidosis (CA) is common. If treated with transcatheter aortic valve implantation (TAVI), patients with the combined phenotype (AS-CA) have a comparable short term survival to those with lone AS, whereas data on longer term outcomes is currently lacking. Purpose This study aimed to evaluate the clinical outcomes of AS-CA compared to lone AS over a 5-year follow-up. Methods Using a prospective, multicentre, observational, case-control design, we screened consecutive patients with severe AS referred for TAVI for co-existing CA. CA screening included blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) with additional SPECT/CT and light chain assessment prior to intervention. Transthyretin CA (ATTR) was diagnosed by bone scintigraphy and unremarkable light chain assessment, light-chain CA (AL) by endomyocardial biopsy. Mortality (all-cause and cardiovascular [CV]) and hospitalisation for heart failure (HHF) were captured as clinical endpoints. Results 376 patients (83±7 years, 52% female, EuroSCORE-II 4.9±2.9) were recruited, of which 43 (11.4%) had AS-CA (42 ATTR, 1 AL). Compared to lone AS, patients with AS-CA were older with higher cardiac biomarkers (NT-proBNP, high-sensitive Troponin-T) and a higher prevalence of atrial fibrillation. Heart team decision yielded valve replacement in 320 (85%) and conservative management in 56 (15%) patients, without differences between AS-CA and lone AS. Over a median follow-up of 5.4 (Q1: 4.9; Q3: 5.7) years, 230 (61.1%) patients died and 67 (17.8%) experienced HHF (with a total HHF number of 91). AS-CA was associated with higher all-cause mortality (crude HR 1.64, 95%CI 1.15-2.35; log-rank, p=0.006), which remained significant after multivariate adjustment for clinical confounders (EuroSCORE-II, valve replacement; adjusted HR 1.63, 95%CI 1.15-2.32; p=0.006). AS-CA was not associated with CV mortality (log-rank, p=0.18) or time to first HHF (log-rank, p=0.43), but the rate of HHF was significantly higher in AS-CA compared to lone AS (5.7 versus 3.5 per 1,000 patient years, p=0.022). Conclusions Among elderly patients referred for TAVI, long-term outcomes of AS-CA are characterized by higher mortality and a higher rate of heart failure hospitalisations compared to patients with lone AS. Studies evaluating the role of CA-specific treatments are warranted in this population.

Influence of prior heart valve intervention on treatment and disease trajectory after diagnosis of heart failure with reduced ejection fraction

Abstract Background and aim Among patients with heart failure with reduced ejection fraction (HFrEF), knowledge is scarce on whether patients with prior valvular heart disease (VHD) intervention are distinct regarding clinical characteristics, treatment, and prognosis. Methods Using the Danish Heart Failure Registry and nationwide administrative registries, we identified patients with new-onset HFrEF from 2008 to 2021. Within this cohort, patients with a prior VHD intervention were identified and matched 1:5 on age-, sex-, in/outpatient presentation, and year of HFrEF diagnosis with remaining patients (controls). Outcomes were 1) baseline use and up-titration of guidelines-directed medical therapy (GDMT) and implementation of implantable cardioverter-defibrillator or cardiac resynchronization therapy with pacemaker/defibrillator (ICD/CRT-P/D) at 6 months follow-up, and 2) a composite of HF hospitalization or all-cause death at 3 years follow-up. The Kaplan-Meier estimator and Cox regression models, adjusted for HF severity, socioeconomic status, and major comorbidities, were used to compare the composite outcome, with patients without prior heart valve intervention as reference. Results The study cohort comprised 32,713 patients, of whom 1196 (3.6%) underwent a prior VHD intervention (median time since intervention 10 months). After matching, the study population were 1151 cases (median age 74 years, 82% men), and 3769 matched controls. Among cases and controls, median left ventricular ejection fraction was similar (30% vs. 30%) and the proportion in New York Heart Association (NYHA) class II was alike (82% vs 83%). At the time of HFrEF diagnosis, numerically more cases were on a beta-blocker (62% vs. 53%), ACEi/ARB/ARNI (48% vs. 44%), MRA (19% vs. 14%), and more had an implementation of (ICD/CRT-P/D) (17 % vs. 7%) (Figure 1). At 6 months, ≥ 50% of the daily target dose was achieved in (46% vs. 46%) for beta-blockers, (47% vs. 47%) for ACEi/ARBs/ARNI, (31% vs. 33%) for MRA, and implementation of ICD/CRT-P/D was attained in (28% vs. 18%), among cases and controls, respectively (Figure 1). The 3-year risk of HF hospitalization or all-cause death was 25% in cases and 24% in controls (Figure 2) with no significant differences (hazard ratio (HR) 0.95 , 95% confidence interval (CI) 0.84-1.08) compared to controls. Conclusions Patients with new-onset HFrEF and prior VHD interventions received more GDMT and had a higher implementation of ICD/CRT-P/D at the time of HFrEF diagnosis. However, following diagnosis, no major differences in GDMT initiation and up-titration, implementation of ICD/CRT-P/D, and the adjusted rates of HF hospitalization or all-cause death were observed among patients with and without prior heart valve intervention.Figure 1 Guideline-directed medicationFigure 2 Crude cumulative risk

Mortality, Clinical Complications, and Healthcare Resource Utilization Associated with Managing Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-occlusive Crises in Italy.

To examine the clinical burden and healthcare resource utilization (HCRU) among patients with transfusion-dependent β-thalassemia (TDT) and patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in Italy. Eligible patients were identified from an administrative claims database from 1 January 2010 and 1 February 2019. Patients with TDT had ≥ 1 iron chelation treatment, ≥ 8 red blood cell transfusions (RBCTs) during any 12-month period, and ≥ 12 months of available data pre- and post-index (i.e., first RBCT claim). Patients with SCD with recurrent VOCs had ≥ 2 VOCs/year in ≥ 2 consecutive years and ≥ 12 months of available data pre- and post-index (second VOC claim in the second of 2 consecutive years). Patients were propensity score matched to five controls by age, sex, geographic area, and index year. Clinical and HCRU outcomes were evaluated post-index. In total, 214 patients with TDT and 111 patients with SCD with recurrent VOCs were matched to 1070 and 555 controls, respectively. Both patient groups had substantially higher mortality rates than controls (TDT: 4.8 versus 0.8 deaths per 100 person-years; SCD: 1.6 versus 0.4 deaths per 100 person-years). Clinical complications were prevalent in both patient groups. Compared with controls, both patient groups had significantly higher mean rates of all-cause hospitalizations (TDT: 1.4 versus 0.1; SCD: 2.0 versus 0.1) and outpatient services (TDT: 21.9 versus 1.6; SCD: 6.2 versus 1.0) per patient per year (all: p < 0.05). Management of TDT and SCD in Italy is associated with significant clinical and health system burden, highlighting the need for new treatments that eliminate RBCTs and VOCs.

Effect of high-dose vs. standard-dose quadrivalent influenza vaccine on death and hospitalizations in older adults with cardiovascular disease: a prespecified analysis of the DANFLU-1 study

Abstract Background The results of the DANFLU-1 trial indicated that high-dose quadrivalent influenza vaccines (HDQIV) as compared to standard-dose quadrivalent influenza vaccines (SDQIV) may reduce the incidence of death and hospitalization with pneumonia or influenza in older adults. Whether this effect differs by the presence of cardiovascular disease is unknown. Purpose To conduct a prespecified analysis aimed at assessing whether the presence of cardiovascular disease at baseline modified the effect of HDQIV vs SDQIV on clinical outcomes in the DANFLU-1 trial. Methods DANFLU-1 was a pragmatic, open-label trial randomizing 12,477 adults aged 65-79 years 1:1 to HDQIV vs SDQIV during the 2021/2022 influenza season. The trial used the Danish nationwide registers to collect both baseline and outcome data. Participants were included in October and November of 2021 and follow-up ended on May 31, 2022. In this prespecified analysis, we assessed the effectiveness of HDQIV vs SDQIV on clinical endpoints according to the presence of cardiovascular disease at baseline and across different cardiovascular subgroups including ischemic heart disease, heart failure and atrial fibrillation. Effectiveness was assessed with Cox proportional hazards regression. In addition, hospitalizations were also assessed with recurrent event analysis using negative binomial regression. Results The mean age of the 12,477 participants in the DANFLU-1 trial was 71.7 years (SD 3.9) and 6600 (53%) were male. During a median follow-up of 237 days (interquartile range 232-239 days), 62 participants died (0.5%), 38 (0.3%) were hospitalized with pneumonia or influenza, 220 (1.8%) were hospitalized with a cardiorespiratory diagnosis, and 192 (1.5%) were hospitalized with a cardiovascular diagnosis. HDQIV was associated with a lower incidence of death during follow-up as compared with SDQIV (HR 0.51 [95% CI 0.30-0.86], p=0.012), and this effect was consistent in participants with CVD and without CVD and across cardiovascular subgroups (Figure 1). HDQIV was also associated with a lower incidence of hospitalization with pneumonia or influenza (IRR 0.30 (95% CI 0.14-0.64, p=0.002), and this effect was consistent irrespective of CVD (subgroup estimates were inestimable due to low power) (Figure 2). There was no difference in the incidence of cardiorespiratory or cardiovascular hospitalization between the HDQIV and SDQIV group. No significant effect modification by the presence of CVD or cardiovascular subgroups was observed (Figure 1 and 2). Conclusions In this prespecified analysis of the DANFLU-1 randomized trial, high-dose influenza vaccine was associated with a reduced rate of death and hospitalization with influenza or pneumonia and this effect was consistent in participants with CVD and across cardiovascular subgroups.Figure 1:Time to event analysisFigure 2:Recurrent event analysis

Post-operative atrial fibrillation during cardiac rehabilitation: incidence and long-term prognostic value

Abstract Background Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery and is associated with longer in-hospital stay and increased in-hospital death and stroke, but its long-term prognostic value, during cardiac rehabilitation (CR), remains not well understood. Purpose The study aimed to assess the incidence and long-term prognostic values of different types of POAF in a cohort of consecutive patients who undergo CR after cardiac surgery. Methods A consecutive registry of patients admitted to our CR after cardiac surgery represents the present study. POAF was defined as any episode of atrial fibrillation occurring in the post-operative period from post-intensive care unit to hospital discharge after CR; moreover, POAF types were classified as Paroxysmal POAF (early and late) and persistent (early and late). Long-term hard end-points were: cardiovascular (CV) mortality and major adverse cardiovascular and cerebrovascular events (MACCEs defined as a composite of cardiovascular death, heart failure hospitalization, non-fatal myocardial infarction, and stroke). Results A total of 2.020 patients were included, mean age was 67 years and male gender was prevalent (71%). CR post-coronary artery bypass graft (CABG) was the indication of CR in 53% of patients, cardiac valve surgery in 35%, while 11% underwent CR after CABG plus valve surgery. All patients were followed for a mean of 50 months. POAF was found in 392 patients (19.4%) divided into 36% paroxysmal POAF and 64% persistent POAF, while 7.7% had permanent atrial fibrillation (figure 1A). Overall POAF was associated with higher rates of CV death (SR 5.0% vs POAF 7.2% vs pAF 16.5%; p&amp;lt;0.001) and MACCEs (SR 12.4% vs POAF 19.6% vs pAF 25.2%; p&amp;lt;0.001 – figure 1B). By analyzing separately paroxysmal, persistent, early, and late POAF, interestingly only late POAF (both persistent or paroxysmal) was associated with a higher long-term CV risk, in particular, both late persistent and late paroxysmal were associated with a higher risk of MACCEs (late persistent: OR 1.65, p=0.004 / late paroxysmal: OR 1.98, p=0.002 – figure 1C), mainly driven by a higher rate of heart failure hospitalization. Interestingly late paroxysmal POAF showed the worst outcomes among all classified POAF (figure 1D). Conclusions POAF after cardiac surgery is associated with long-term adverse outcomes, but not all POAF have the same prognostic value. Late, rather than early, POAF (whether paroxysmal or persistent) is associated with a poor long-term prognosis after cardiac rehabilitation.Figure 1

Postoperative atrial fibrillation following noncardiac surgery is associated with long-term heart failure: insights from a nationwide cohort

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). Whether postoperative AF (POAF) also confers a greater risk of HF is unclear. Purpose To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients who did not develop POAF after noncardiac surgery. Methods In this cohort study, the Danish nationwide registries were used to identify all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020. These patients were matched in a 1:3 ratio by age, sex, type of surgery, selected comorbidities, and year of inclusion with patients without POAF after noncardiac surgery. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 2,270 patients with POAF were matched with 6,810 patients without POAF (median age: 75 years [25th-75th percentile: 67-82 years]; 53.5% females). The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 versus 1.2 events per 100 person-years; HR 2.39 [95% CI 2.06-2.78]]), HF hospitalization (2.2 versus 1.0 events per 100 person-years; HR 2.33 [95% CI 1.97-2.74]), and all-cause mortality (9.8 versus 7.4 events per 100-person-years; HR 1.55 [95% CI 1.45-1.66]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation following noncardiac surgery had a higher associated long-term rate of incident heart failure compared to those without postoperative atrial fibrillation following noncardiac surgery. These findings highlight the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

Relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine according to time of day of vaccination: a post-hoc analysis of the DANFLU-1 randomised clinical trial

Abstract Background Circadian variations have been shown to affect antibody response following vaccination. We sought to evaluate whether time of day of vaccination (ToV) modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccination, and further whether ToV was independently associated with hospitalisations and mortality. Methods This is a post-hoc analysis of the DANFLU-1 trial which was a randomized trial of QIV-HD vs. QIV-SD in adults aged 65-79 years conducted during the 2021-2022 influenza season. Vaccination took place between 7:05 AM and 8:08 PM. For this study, we stratified participants into early and late vaccination groups according to ToV before or after 11 AM, respectively. Prespecified outcomes included hospitalisations for pneumonia or influenza, respiratory disease, cardiovascular disease, and cardio-respiratory disease as well as all-cause hospitalisations and mortality. Hospitalisations were analysed as recurrent events using negative binomial regression, while mortality was analysed using Cox proportional hazard models, both of which were also used to test for interaction. For multivariable analysis, models were adjusted for baseline risk factors including sex, age, and multiple lung diseases. ToV was furthermore assessed as a continuous variable with 2-hour increments. Results In the final study population, the early group consisted of 5,371 (43%) participants (mean age 71.6±3.9 years, male sex 53.6%, QIV-SD 50.1%), while the late group consisted of 7,106 (57%) (mean age 71.8±4.0 years, male sex 52.4%, QIV-HD 49.9%). During follow-up, we observed 43 hospitalisations for pneumonia or influenza, 76 respiratory hospitalisations, and 62 mortalities. In recurrent event analysis, QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza compared with QIV-SD irrespective of whether administered early (IRR 0.17 (95% CI 0.03-0.86), p=0.032) or late (IRR 0.37 (95% CI 0.16-0.88), p=0.024) (p-value for interaction = 0.69) (Figure 1). Effect estimates were consistent for all outcomes excluding cardiovascular hospitalisations regardless of early or late vaccination, and no effect modification was found (Figure 1). Interestingly, late vaccination was associated with higher incidence rate of respiratory hospitalisation (IRR 3.00 (95% CI 1.13-7.98), p=0.024, Figure 2), irrespective of vaccine type. The same association was found for ToV as a continuous variable (IRR 1.28 per 2-hour increment (95% CI 1.02-1.60), p=0.035). All above associations remained significant in multivariable analysis. Conclusion QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza regardless of time of day for vaccination. In addition, later vaccination was associated with higher incidence of respiratory hospitalisation independent of vaccine type and known risk factors. Due to low power, however, this finding should be regarded as exploratory.Figure 1:Forest plotFigure 2:Incidence rates