Chronic kidney disease and risks of adverse clinical events in patients with atrial fibrillation

BACKGROUNDChronic kidney disease (CKD) is highly prevalent in patients with atrial fibrillation (AF). However, the association between CKD and clinical consequences in AF patients is still under debate.METHODSWe included 19,079 nonvalvular AF patients with available estimated glomerular filtration rate (eGFR) values in the Chinese Atrial Fibrillation Registry from 2011 to 2018. Patients were classified into no CKD (eGFR ≥ 90 mL/min per 1.73 m²), mild CKD (60 ≤ eGFR < 90 mL/min per 1.73 m ²), moderate CKD (30 ≤ eGFR < 60 mL/min per 1.73 m ²), and severe CKD (eGFR < 30 mL/min per 1.73 m ²) groups. The risks of thromboembolism, major bleeding, and cardiovascular mortality were estimated with Fine-Gray regression analysis according to CKD status. Cox regression was performed to assess the risk of all-cause mortality associated with CKD. RESULTSOver a mean follow-up of 4.1 ± 1.9 years, there were 985 thromboembolic events, 414 major bleeding events, 956 cardiovascular deaths, and 1,786 all-cause deaths. After multivariate adjustment, CKD was not an independent risk factor of thromboembolic events. As compared to patients with no CKD, those with mild CKD, moderate CKD, and severe CKD had a 45%, 47%, and 133% higher risk of major bleeding, respectively. There was a graded increased risk of cardiovascular mortality associated with CKD status compared with no CKD group: adjusted hazard ratio [HR] was 1.34 (95% CI: 1.07−1.68,P = 0.011) for mild CKD group, 2.17 (95% CI: 1.67−2.81,P < 0.0001) for moderate CKD group, and 2.95 (95% CI: 1.97−4.41, P < 0.0001) for severe CKD group, respectively. Risk of all-cause mortality also increased among patients with moderate or severe CKD. CONCLUSIONSCKD status was independently associated with progressively higher risks of major bleeding and mortality, but didn’t seem to be an independent predictor of thromboembolism in AF patients.

Atrial fibrillation (AF) is the most common arrhythmia worldwide, being associated with increased risks of cardiovascular diseases and death. Chronic kidney disease (CKD) often coexists with AF,^[1,2] present in 10% to 40% of AF patients.^[3,4] Besides, CKD is an independent risk factor of incident AF^[5] and shares common risk factors with AF, such as older age, hypertension and diabetes mellitus.^[6,7] Both CKD and AF were associated with poor prognosis, bringing growing burden to healthcare systems.^[8,9]Nevertheless, whether CKD independently confers increased risks of cardiovascular outcomes and mortality in AF patients remains controversial.^[10-14] Although studies have indicated that CKD was an independent predictor of stroke,^{[10, 11, 15]} the widely-used CHA₂DS₂-VASc stroke score recommended by the current guidelines did not include CKD.^{[6, 16]} Abnormal renal function was also precluded from a biomarker-based death score,^[17] but was incorporated into the HAS-BLED score for bleeding risk prediction. Thus, a better understanding of the relationship between CKD and adverse outcomes is essential to the comprehensive management of AF patients. Using data from the large, prospective Chinese Atrial Fibrillation Registry (China-AF) cohort, we intend to determine the risks of thromboembolism, major bleeding, cardiovascular mortality and all-cause mortality associated with CKD in individuals with AF.     

Difficulty of falling asleep and non-high-density lipoprotein cholesterol level among Canadian older adults: a cross-sectional analysis of the Canadian Longitudinal Study for Aging baseline data

OBJECTIVETo examine whether difficulty of falling asleep (DoFA) is associated with non-high-density lipoprotein cholesterol (non-HDL-C) level among Canadian older adults.METHODS26,954 individuals aged 45–85 years from the baseline data of the Canadian Longitudinal Study for Aging were included in this study. DoFA was categorized into five groups by answer to the question “Over the last month, how often did it take you more than 30 min to fall asleep?” Response options are “Never, < 1 time/week, 1−2 times/week, 3−5 times/week, or 6−7 times/week”. Non-HDL-C, the difference of total cholesterol and HDL-C, were categorized into five categories based on these cut-offs (< 2.6 mmol/L, 2.6−3.7 mmol/L, 3.7−4.8 mmol/L, 4.8−5.7 mmol/L, and ≥ 5.7 mmol/L). Ordinal logistic regression (logit link) continuation ratio models were used to estimate the odds of higher non-HDL-C levels for DoFA status. Adjusted means of non-HDL-C by DoFA status were estimated by general linear models. All analyses were sex separately using analytic weights to ensure generalizability.RESULTSThe proportions of DoFA in five categories were 41.6%, 25.7%, 13.6%, 9.4%, 9.7% for females and 52.9%, 24.9%, 10.5%, 6.1%, 5.6% for males, respectively. After adjustment of demographical and other covariates (such as depression, comorbidity, sleeping hour, etc.) compared to those who reported never having DoFA, the ORs (95% CIs) of higher levels of non-HDL-C for those whose DoFA status in < 1 time/week, 1−2 times/week, 3−5 times/week, and 6−7 times/week were 1.12 (1.05−1.21), 1.09 (0.99−1.18), 1.20 (1.09−1.33), 1.29 (1.17−1.43) in females and 1.05 (0.98−1.13), 0.95 (0.87−1.05), 1.21 (1.08−1.37), 0.97 (0.85−1.09) in males, respectively. The adjusted means of non-HDL-C among the five DoFA status were 3.68 mmol/L, 3.73 mmol/L, 3.74 mmol/L, 3.82 mmol/L, 3.84 mmol/L for females and 3.54 mmol/L, 3.58 mmol/L, 3.51 mmol/L, 3.69 mmol/L, 3.54 mmol/L for males, respectively.CONCLUSIONSThe results of this study have identified a risk association pattern between DoFA status and non-HDL-C levels in females but not in males. Further research is needed to confirm these findings.

The increased level of non-high-density lipoprotein cholesterol (non-HDL-C) is a reliable risk predictor for future coronary heart disease (CHD).^[1–3] Evidence from studies of the relationship between non-HDL-C reduction and CHD risk has suggested that non-HDL-C is an important target of therapy for CHD prevention.^[4] Non-HDL-C, the difference between total cholesterol (TC) and HDL-C, includes low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol; they are all proatherogenic lipoproteins containing apolipoproteins B (Apo B).^[5] Currently, LDL-C is the primary target of treatment of CHD since it contains the majority of Apo B and lowering its level reduces CHD risk.^[6] However, LDL-C level in clinic is most likely estimated indirectly and its levels depend on fasting status and the levels of triglycerides.^[7] The level of non-HDL-C is not related to triglycerides measurement and not affected by fasting status, thus, it is considered superior to LDL-C as a treatment target for CHD risk management. Sleep disorders are conditions that changes the way people sleep and affects the overall health and quality of life. In a study conducted among 2,000 Canadians aged 18 years or older, 40.2% of individuals reported having either trouble falling or staying asleep, or early morning awakening for at least three nights per week in a previous month.^[8] Serious sleep disorders not only affects persons’ life quality,^[9,10] and increases risk for motor vehicle accidents,^[11] but also found to be associated with an increased risk for cardiovascular diseases (CVD).^[12–14] Sleep disturbance was observed to be highly associated with the increased risk of CVD, it was considered as a potential risk predictor of CVD.^[13] However, whether sleep disorders are associated with dyslipidemia is uncertain since studies showed contradictory results.^[15] Short sleep duration was found to be associated with an increased risk of CVD,^[16,17] but there is no conclusion whether sleep duration is linked to dyslipidemia.^[18] Furthermore, there is no study examined the relationship between sleep disorders and non-HDL-C levels. Therefore, the aim of this study is to examine how sleep disturbance is associated with lipid profile, particularly the levels of non-HDL-C among older adults. To explore this association, we used the baseline data collected by the Canadian Longitudinal Study on Aging (CLSA), a large population-based cohort study.     

Inter‐ and Intra‐Ethnic Group Comparison of Metabolic Syndrome Components Among Morbidly Obese Adolescents

J Clin Hypertens(Greenwich). 2010;12:645–652. © 2010 Wiley Periodicals, Inc.This study explored inter‐ (between) and intra‐ (within) ethnic group differences in metabolic syndrome components among a clinical sample of morbidly obese (body mass index [BMI] ≥97th percentile for age and sex) 12‐ to 18‐year‐olds originating from Latin America and the Caribbean Basin and a matched (age/ethnicity/sex/BMI percentile) national sample (N=208, both samples) of Mexican American and non‐Hispanic blacks from the 1999 to 2006 National Health and Nutrition Examination Survey (NHANES). Mexican American and non‐Hispanic black boys from the NHANES/national sample had significantly higher mean fasting glucose levels compared with Latin and Caribbean blacks (98.50 vs 85.42 mg/dL, 97.34 vs 86.44 mg/dL, respectively, (P<.001 for both comparisons). Conversely, both diastolic/systolic blood pressure was consistently higher among Latin/Caribbean adolescents vs Mexican American and non‐Hispanic blacks for all age/sex/ethnic groups. These results indicate that morbidly obese adolescents from both major ethnic groups and subgroups within these groups show health‐related comorbidities in both clinic‐ and population‐based settings.

Currently, more than 17% of children in the Unites States aged 2 to 19 are obese (≥95th percentile for body mass index [BMI] for age and sex), and another 34% are at‐risk for becoming obese (≥85th percentile for BMI for age and sex). ¹ Data consistently show that non‐Hispanic blacks and Hispanics have higher obesity prevalence rates compared with their non‐Hispanic white counterparts. ^{1 , 2 , 3} A secular trend analysis of US national data showed that non‐Hispanic black children and adolescents experienced the largest increase in the prevalence of obesity (12.2%) compared with non‐Hispanic white (8.0%) and Mexican Americans (4.9%) during the past 20 years. ⁴ Moreover, national prevalence estimates from 1999 to 2002 show that extreme obesity (>99th percentile for BMI) approached 6% to 7% among non‐Hispanic black girls and Mexican American boys. ² Recent studies have reported an association between childhood obesity and the subsequent development of a constellation of cardiometabolic risk factors characterized by insulin resistance, dyslipidemia, and hypertension, which some have termed the metabolic syndrome (MetS). ^{5 , 6 , 7 , 8} In turn, this clustering is associated with type 2 diabetes and long‐term vascular complications in both childhood and adulthood. ^{9 , 10 , 11} Previous population‐based studies have shown that ethnic minorities have higher rates of MetS compared with their white counterparts. ^{12 , 13 , 14 , 15 , 16} Because components of the MetS are relatively stable characteristics that tend to track from childhood into adulthood, ^{5 , 6 , 17 , 18 , 19 , 20} the identification of adolescents with these risk factors is of great clinical and public health interest.Few studies have addressed the prevalence of morbid obesity and health‐related consequences among subgroups of non‐Hispanic black and non‐Mexican Hispanic adolescents residing in the United States, such as those originating from Latin America and the Caribbean region. ²¹ Little is known about how these groups compare with their national ethnic group counterparts in the prevalence and severity of individual MetS components. Therefore, this analysis sought to compare the prevalence of individual MetS components among a multiethnic sample of morbidly obese adolescents from Central and South America (Latin) and the Caribbean region (Caribbean/West Indian black) with the National Health and Nutrition Examination Survey (NHANES), a population‐based sample that included predominantly Mexican American and non‐Hispanic black children not from Central/South American (with the exception of Mexico) and the Caribbean.     

A comparison of carotid atherosclerosis in symptomatic patients between 2002–2005 and 2012–2015 cohorts using multi-contrast magnetic resonance vessel wall imaging

OBJECTIVETo compare the morphological and compositional characteristics of carotid plaques in two cohorts (2002−2005 and 2012−2015) of Chinese patients using magnetic resonance vessel wall imaging.METHODSSymptomatic patients with carotid atherosclerotic plaques who underwent carotid vessel wall magnetic resonance imaging between 2002−2005 and 2012−2015 were retrospectively recruited. Plaque morphology [including mean wall area, wall thickness, and maximum normalized wall index (NWI)] and composition [including calcification, intraplaque hemorrhage, and lipid-rich necrotic core (LRNC)] in symptomatic carotid arteries were evaluated and compared between patients in these two time periods.RESULTSA total of 258 patients, including 129 patients in the 2002−2005 cohort and 129 patients in the 2012−2015 cohort, were recruited. Statin use (49.6%vs. 32.6%, P = 0.004) and hypertension (76.0% vs. 62.8%, P = 0.015) were significantly more common in the 2012–2015 cohort than in the 2002−2005 cohort. Patients in the 2012−2015 cohort also exhibited significantly low plaque burden parameters (allP < 0.05), as well as a lower prevalence (68.2% vs. 89.9%, P < 0.001) and volume percentages of LRNC (11.2% ± 14.2% vs. 25.7% ± 17.7%, P < 0.001). These differences remained significant after adjustment for clinical factors. The differences in the volume percentages of LRNC also remained significant after an additional adjustment for maximum NWI ( P < 0.001). CONCLUSIONSPatients in the 2012−2015 cohort had a lower plaque burden and volume percentages of LRNC in symptomatic carotid arteries than those in the 2002−2005 cohort. These findings indicate that carotid plaques in the recent cohort had a lower severity and vulnerability.

The morphological and compositional features of carotid plaques are closely associated with clinical risk factors and administered medications.^[1–4] As the diet,^[5] incidence of chronic diseases,^[6,7] and level of medical care^[8] have greatly changed in the Chinese population in the past decade, it is likely that the features of carotid plaques have also changed. Knowledge of the changes in carotid plaques and clinical characteristics in the Chinese population that have taken place over a decade may provide valuable information for the prevention and treatment of carotid atherosclerosis. A recent study of carotid plaque burden in patients from Western countries reported a decline in both stenosis and plaque area from 2002 to 2014.^[9] However, plaque morphology was assessed with carotid ultrasound, which does not provide information on compositional features related to plaque vulnerability, such as intraplaque hemorrhage (IPH) and the lipid-rich necrotic core (LRNC).^[10–12] Therefore, it was unclear as to whether carotid plaque vulnerability varied over the ten-year period in symptomatic patients. Multi-contrast magnetic resonance imaging (MRI) has been widely used to simultaneously characterize carotid plaque burden and composition,^[13] this approach has been shown to have a good to excellent agreement with histological assessments.^[14,15]The purpose of this study was to compare the morphology and composition of carotid plaques in Chinese patients between two time periods (2002−2005 and 2012−2015) using multi-contrast MRI of the vessel wall.     

Pre-hospital delay in patients with acute myocardial infarction in China: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project

OBJECTIVETo describe the duration of the pre-hospital delay time and identify factors associated with prolonged pre-hospital delay in patients with acute myocardial infarction (AMI) in China.METHODSData were collected from November 2014 to December 2019 as part of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project. A total of 33,386 patients with AMI admitted to the index hospitals were included in this study. Two-level logistic regression was conducted to explore the factors associated with the pre-hospital delay and the associations between different pre-hospital delay and in-hospital outcomes.RESULTSOf the 33,386 patients with AMI, 70.7% of patients arrived at hospital ≥ 2 h after symptom onset. Old age, female, rural medical insurance, symptom onset at early dawn, and non-use of an ambulance predicted a prolonged pre-hospital delay (all P < 0.05). Hypertension and heart failure at admission were only significant in predicting a longer delay in patients with ST-segment elevation myocardial infarction (STEMI) (all P < 0.05). A pre-hospital delay of ≥ 2 h was associated with an increased risk of mortality [odds ratio (OR) = 1.36, 95% CI: 1.09–1.69, P = 0.006] and major adverse cardiovascular events (OR = 1.22, 95% CI: 1.02–1.47, P = 0.033) in patients with STEMI compared with a pre-hospital delay of < 2 h. CONCLUSIONSProlonged pre-hospital delay is associated with adverse in-hospital outcomes in patients with STEMI in China. Our study identifies that patient characteristics, symptom onset time, and type of transportation are associated with pre-hospital delay time, and provides focuses for quality improvement.

Early invasive strategies are the key to improving the survival of patients with acute myocardial infarction (AMI).^[1,2] Previous attention focused on door-to-balloon (DTB) time has resulted in significant improvements; however, several studies have confirmed that mortality is strongly correlated with the total ischemic time and less so with the DTB interval.^[3–5] As the longest component of ischemic time, the pre-hospital delay from symptom onset to admission is an important point of focus.^[6] A previous study showed that the benefit of a short DTB time was restricted to patients who presented early.^[7] These results suggest that although it is imperative to minimize the DTB time as an inseparable part of the ischemic time, the importance of shortening the pre-hospital delay should not be ignored. Several studies reported the duration of the pre-hospital delay and examined the factors associated with the prolonged pre-hospital delay. These studies showed notable differences in the lengths of pre-hospital delay among different countries.^[8–10] According to data from the Global Registry of Acute Coronary Events study, the pre-hospital delay of patients with ST-segment elevation myocardial infarction (STEMI) was shortest in Australia/New Zealand (median: 2.2 h) and longest in Argentina and Brazil (median: 4.0 h).^[10] In China, the China PEACE (China Patients-Centered Evaluative Assessment of Cardiac Events) study reported an average time to hospital of 4.0 h for AMI, and certain factors, such as rural medical insurance, failure to recognize symptoms as cardiac, and a low household income, were associated with a longer pre-hospital delay.^[11] However, the latest national study about the scenario of pre-hospital delay in China was conducted from 2012 to 2014.^[11] An up-to-date evaluation of pre-hospital delay in patients with AMI in China is warranted. In addition, the pathological process of patients with non-ST-segment elevation myocardial infarction (NSTEMI) is different as compared with STEMI, but few studies have explored the clinical outcomes of the prolonged pre-hospital delay in NSTEMI patients.^[12]Using nationwide data from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, we herein provide an up-to-date estimation of the pre-hospital delay time; explore the factors associated with the pre-hospital delay; and investigate the association between the pre-hospital delay and in-hospital outcomes among patients with STEMI and patients with NSTEMI in China.     

Ambulatory diastolic blood pressure: a marker of comorbidity in elderly fit hypertensive individuals?

BACKGROUNDMasked diastolic hypotension is a new blood pressure (BP) pattern detected by ambulatory blood pressure monitoring (ABPM) in elderly hypertensives. The aim of this study was to relate ABPM and comorbidity in a cohort of fit elderly subjects attending an outpatient hypertension clinic.METHODSComorbidity was assessed by Charlson comorbidity index (CCI) and CHA₂DS₂VASc score. All subjects evaluated with ABPM were aged ≥ 65 years. CCI and CHA₂DS₂VASc score were calculated. Diastolic hypotension was defined as mean ambulatory diastolic BP < 65 mmHg and logistic regression analysis was carried out in order to detect and independent relationship between comorbidity burden and night-time diastolic BP < 65 mmHg. RESULTSWe studied 174 hypertensive elderly patients aged 72.1 ± 5.2 years, men were 93 (53.4%). Mean CCI was 0.91 ± 1.14 and mean CHA₂DS₂VASc score of 2.68 ± 1.22. Subjects with night-time mean diastolic values < 65 mmHg were higher in females [54.7% vs. 45.3%, P = 0.048; odds ratio (OR) = 1.914, 95% CI: 1.047−3.500]. Logistic regression analysis showed that only CHA₂DS₂VASc score was independently associated with night-time mean diastolic values < 65 mmHg (OR = 1.518, 95% CI: 1.161−1.985; P = 0.002), but CCI was not. CONCLUSIONSABPM and comorbidity evaluation appear associated in elderly fit subjects with masked hypotension. Comorbid women appear to have higher risk for low ambulatory BP.

The global population is ageing, and the number of subjects with long-term disorders is increasing, with heavy consequences on medical commitment and health-care systems burden.^[1] Moreover, multimorbidity is associated with a higher mortality,^[2,3] and hypertension represents a frequent condition involving patients with multiple diseases.^[1] The relationship between multimorbidity and hypertension is bidirectional. Hypertension could cause organ damage and then development of comorbidity; on the other hand, comorbidity could worsen hypertension and its consequences. In elderly subjects, hypertension could cause brain damage that could be the cause of cognitive decline;^[4] moreover, systemic atheroembolic syndrome could worsen blood pressure (BP) variability leading to cardiovascular disease (CVD).^[5]Hypertension, both complicated or not complicated, is a variable taken into consideration in a series of risk scores applied to the general population to estimate the mortality risk, such as the Cumulative Illness Rating Scale,^[6] the Charlson comorbidity index (CCI),^[7] and the Elixhauser index.^[8] The CHA₂DS₂VASc score is widely used as predictor of the risk of stroke in patients with atrial fibrillation, it includes hypertension among the factors considered for score calculation and its importance is underlined by the same weight assigned to congestive heart failure (CHF), age > 75 years, and diabetes mellitus (1 point). ^[9] However, CHA₂DS₂VASc score has also been suggested to be able to stratify adverse clinical events in hypertensive patients.^[10]In patients with comorbidities, out-of-office monitoring of BP has been shown to be associated with reduced systolic BP (SBP) compared to usual care, representing a very useful tool in routine clinical practice.^[11] However, the discrepancy of measures between office and out-of-office BP measures, such as ambulatory blood pressure monitoring (ABPM), is known since two decades,^[12] and these two approaches have pros and cons depending also on type of patients. In untreated older patients with isolated systolic hypertension, for example, ambulatory SBP was a significant predictor of cardiovascular risk over and above conventional BP.^[13,14]It is widely accepted that ABPM is a crucial informative tool for the evaluation of BP behaviour in everyday clinical practice,^[15] and is recommended to identify white-coat hypertension and masked hypertension.^[15,16] However, its importance goes greatly beyond due to its capacity to provide information for clinical use.^[15] In fact, night-time evaluation of BP is crucial to detect abnormal patterns of night-time behaviour, such as non-dipping, inverse dipping, extreme dipping and the morning surge,^[17] and asleep SBP is a significant BP derived risk factor for CVD events.^[18,19]Recently, a novel BP pattern defined masked diastolic hypotension, frequently found in older patients under antihypertensive treatment, has raised attention.^[20] Knowledge related to clinical use of ABPM in elderly subjects is still a matter of debate, and information about BP components and circadian profiles in subjects with high comorbidity burden is scarce.^[21]The aim of this study was investigate the possible relationship between the BP components (recorded by ABPM) and the comorbidity burden (assessed by means of CCI and CHA₂DS₂VASc score) in a cohort of fit elderly subjects attending an outpatient hypertension clinic.     

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study)

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.     

Prognostic relevance of normocytic anemia in elderly patients affected by cardiovascular disease

BACKGROUNDAnemia associated with cardiovascular diseases (CVD) is a common condition in older persons. Prevalence and prognostic role of anemia were extensively studied in patients with myocardial infarction (MI) or congestive heart failure (CHF) whereas limited data were available on patients with atrial fibrillation (AF). This study was conducted to assess the clinical prevalence and prognostic relevance of anemia in elderly patients affected by AF and other CVDs.METHODSA total of 866 elderly patients (430 men and 436 women, age: 65−98 years, mean age: 85 ± 10 years) were enrolled. Among these patients, 267 patients had acute non-ST-segment elevation MI (NSTEMI), 176 patients had acute CHF, 194 patients had acute AF and 229 patients were aged-matched healthy persons (CTR). All parameters were measured at the hospital admission and cardiovascular mortality was assessed during twenty-four months of follow-up.RESULTSThe prevalence of anemia was higher in NSTEMI, CHF and AF patients compared to CTR subjects (50% vs. 15%, P < 0.05), with normocytic anemia being the most prevalent type (90%). Adjusted mortality risk was higher in anemic patient versus non-anemic patient in all the groups of patients [NSTEMI: hazard ratio (HR) = 1.81, 95% CI: 1.06−2.13; CHF: HR = 2.49, 95% CI: 1.31−4.75; AF: HR = 1.98, 95% CI: 1.01−3.88]. Decreased hemoglobin levels ( P = 0.001) and high reticulocyte index (P = 0.023) were associated with higher mortality in CVD patients. CONCLUSIONSThe significant associations between CVD and anemia and the prognostic relevance of anemia for elderly patients with CVD were confirmed in this study. The presence of anemia in AF patients is associated with a two-fold increased mortality risk compared with non-anemic AF patients. Low hemoglobin and high reticulocyte count independently predict mortality in elderly patients with CVD.

The prevalence of anemia significantly rises with advancing age in both men and women. Patients over 75 years have a 10% incidence of anemia, while those over 90 years have an incidence higher than 25%.^[1–3] Numerous causes may explain an anemic state in older persons, including macro-/micro-hemorrhages, iron deficiency, and chronic inflammation. Interestingly, the puzzling entity of unexplained anemia in the elderly represents 30% to 46% of elderly patients.^[4]An anemic state in older individuals is associated with a number of negative outcomes, including heart disease, hospitalization, and death.^[5,6] It has been recently shown that a pre-existing state of anemia is correlated with the development and progression of acute coronary syndrome.^[7] For example, anemic patients who develop acute myocardial infarction (AMI) have an increased risk of death and in-hospital cardiovascular complications.^[8,9] In addition, the unfavorable impact of anemia has been reported also in patients with AMI undergoing percutaneous coronary intervention.^[10] It is also widely recognized that a high prevalence of anemia is common in heart failure (HF) patients and is associated with significantly higher mortality rates.^[11,12]Atrial fibrillation (AF) is the most common cardiac arrhythmia in older persons and it is associated with increased morbidity and mortality.^[3] AF is also a potent risk factor for ischemic stroke and reduces physical and cardiac performance as well as patient quality of life.^[13,14] However, only few reports have investigated the prevalence of anemia in patients with AF and its relevance on the clinical outcomes. It has been recently reported that anemia was associated with increased mortality and hospitalization in elderly patients with AF.^[15] However, in this previous study, anemia was defined based on hematocrit (Hct) levels and not hemoglobin (Hb) levels (< 13 g/dL in men and < 12 g/dL in women) as currently recommended by World Health Organization (WHO).^[16] The Hct value depends on plasma volume and consequently can be modulated from many different variables, including hemodynamic compensation, pharmacological treatment, hydro-electrolytic balance, hydration state, which are highly variable in patients with chronic heart disease. Thus, we aimed at investigating the association between anemia (defined by Hb level) and commonly observed heart diseases [congestive HF (CHF), AMI and AF] in a large sample of older patients. We also aimed at testing the prognostic value of anemia on mortality over time. According to current AF management guidelines, oral anticoagulant therapy (OAT) is the cornerstone for the prevention of severe outcomes. However, OAT increases the risk of severe bleeding affecting the mortality rate, especially in elderly patients.^[17] Thus, to reduce the possible bias related to different AF pharmacological treatments, we included in the survival analysis only patients with OAT therapy.     

Tongmai Yangxin Pill combined with metoprolol or metoprolol alone for the treatment of symptomatic premature ventricular complex: a multicenter,randomized, parallel-controlled clinical study

OBJECTIVETo investigate the effects of Tongmai Yangxin Pill (TMYXP) combined with metoprolol tartrate or metoprolol alone for the treatment of premature ventricular complex (PVC) in patients with symptomatic frequent PVC.METHODSA total of 584 patients with symptomatic frequent PVC were randomly assigned (in a 1:1 ratio) into two groups: study group [n = 292, TMYXP (40 pills twice/day, orally) combined with metoprolol tartrate (25 mg twice/day, orally)] and control group [n = 292, metoprolol tartrate (25 mg twice/day, orally) plus placebo pill (40 pills twice/day, orally)]. The total treatment period was eight weeks. RESULTSAfter eight weeks of treatment, the total effective rate of reduction of PVC in the study group and the control group were 76.4% and 51.4%, respectively (P < 0.001). TMYXP combined with metoprolol tartrate demonstrated a significantly greater reduction of the frequency of PVCs compared with the metoprolol tartrate alone (−4537 times/24 h vs. −3013 times/24 h, P < 0.001). The study group also showed a better result compared with the control group with respect to PVC related symptoms. In terms of New York Heart Association classification improvement, the total effective rates were 21.9% in the study group and 12.4% in the control group ( P < 0.05). Both the study group and the control group exhibited improvements in echocardiographic indexes. Left ventricular ejection fraction was significantly improved in the study group compared with the control group ( P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. CONCLUSIONSCompared with metoprolol tartrate alone, TMYXP combined with metoprolol tartrate could more effectively reduce the frequency of PVC and alleviated PVC related symptoms, and improve cardiac function in patients with symptomatic PVC.

Premature ventricular complex (PVC) is a common type of arrhythmia, particularly in patients with structural heart diseases. It is often accompanied by symptoms such as palpitation, chest tightness, dizziness, and fatigue, some of the patients are highly symptomatic with impaired quality of life. Observational studies in general populations have revealed that frequent PVCs are associated with substantial elevations of risk for sudden cardiac death (SCD) and total cardiac death.^[1] Several studies have demonstrated an association between frequent PVCs and potentially reversible cardiomyopathy.^[2] Most clinical guidelines recommend beta-blockers as initial treatment for frequent PVCs with persistent symptoms, due to the tolerable safety profile and effectiveness in treating ventricular arrhythmia and reducing the risk of SCD.^[2–4] The Cardiac Arrhythmia Suppression Trial study showed that sodium channel blockers can enhance post-myocardial infarction mortality.^[5] Commonly used antiarrhythmic drugs have adverse effects (AEs) on liver, kidney, and thyroid function, most of these drugs are arrhythmogenic.^[6,7] Catheter ablation can eliminate PVCs in 74%–100% of patients by selectively inhibiting the reentrant excitation pathway.^[8] The application of an implantable cardioverter defibrillator greatly reduced the rate of sudden death in patients with high-risk ventricular tachycardia.^[9] However, these invasive therapies have strict indications, in particular, catheter ablation of PVCs is recommended for a small number of patients who remain symptomatic despite conservative treatment, as well as for patients with very high PVC burdens associated with the decline in left ventricular systolic function.^[2] In some hospitals within China, more than 10,000 daily PVCs is the indication for catheter ablation.^[4] Medication therapy, therefore, is used for the majority of patients with symptomatic PVC. Consequently, there is an unmet medical need to explore other alternative treatment options with low toxicity and good efficacy profiles for frequent PVCs and could improve quality of life. Although no terms are corresponding to “arrhythmia” in traditional Chinese medicine (TCM), the symptoms of arrhythmia are classified as “chest bi” and “palpitation”. Arrhythmia is presumably deficiency in origin and excess in superficiality; its origin is the deficiency of “Qi”, “blood”, “Yin” and “Yang”, whereas its superficiality is Qi stagnation, blood stasis, and retention of water. Thus, clinical manifestations are mostly a mixture of deficiency and excess. According to clinical practice and the published literature, TCM treatment of PVC has clear clinical efficacy and is widely used.^[10–12]Tongmai Yangxin Pill (TMYXP) is a Chinese patent medicine developed over many years of clinical practice. Previous research suggests that TMYXP exhibits significant overall efficacy and improvement of individual symptoms (e.g., chest tightness, palpitations, shortness of breath, fatigue, and dizziness),^[12–14] however, the data of which are mainly from non-randomized controlled studies or small sample size studies, and the reported endpoints varied in different studies. Therefore, this multicenter, randomized, parallel-controlled clinical study was conducted to further investigate the effectiveness and safety of TMYXP combined with metoprolol tartrate compared with metoprolol tartrate alone for the treatment of PVC.     

Association between coronary artery calcification and cognitive function in a Chinese community-based population

BackgroundCoronary atherosclerosis and cognitive impairment are both age-related diseases, with similar risk factors. Coronary artery calcium (CAC), a marker of coronary atherosclerosis, may play a role in early detection of individuals prone to cognitive decline. This study aimed to investigate the relationship between CAC and cognitive function, and the capability of CAC to identify participants with a high risk of dementia in a Chinese community-based population.MethodsA total of 1332 participants, aged 40−80 years and free of dementia from a community located in Beijing were included. All participants completed neurocognitive questionnaires and noncontrast CT examinations. Cognitive performance tests (including verbal memory, semantic fluency, executive function, and global cognitive function tests), the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CIDE) risk score, and the CAC score (CACS) were evaluated by questionnaires and CT. A CAIDE score ≥ 10 was considered to indicate a high risk of dementia in late-life. Participants were divided into three groups according to CACS (0, 1−399, ≥ 400).ResultsAfter adjusting for risk factors, CACS was significantly associated with verbal memory (r = −0.083, P = 0.003) and global cognitive function (r = −0.070, P = 0.012). The prevalence of a high risk of dementia in the subgroups of CACS = 0, 1−399, and ≥ 400 was 4.67%, 13.66%, and 24.79%, respectively (P < 0.001). Individuals with CACS ≥ 400 had a higher risk of CAIDE score ≥ 10 [OR = 2.30 (1.56, 4.56), P = 0.014] than those with CACS = 0. The receiver-operating characteristic curves showed that the capability of CACS to identify participants with a high risk of dementia was moderate (AUC = 0.70, 95% CI: 0.67−0.72,P < 0.001). ConclusionsCAC, a marker of subclinical atherosclerosis, was significantly associated with cognitive performance in verbal memory and global cognitive function. CAC had a moderate capability to identify participants with a high risk of dementia, independent of age, education, and other risk factors.

Coronary atherosclerosis and cognitive impairment are both age-related diseases. The incidences of the two diseases are increasing with the rapid aging of the population. There are 50 million people with dementia in the world, and this number is likely to rise to 152 million by 2015. The cost of dementia is forecasted to be approximately two trillion dollars by 2030.^[1,2] Therefore, early prevention of cognitive impairment is of great significance. Cognitive decline has risk factors similar to those for atherosclerosis such as smoking, hypertension, and diabetes.^[3] Intracranial and carotid artery atherosclerosis has been indicated to be related to a higher risk of cognitive decline or dementia.^[4,5] Coronary artery calcium (CAC), a marker of coronary atherosclerosis, may play a role in the early identification of individuals who are prone to cognitive decline. However, several studies investigating the association between CAC assessed by CT and cognitive function have reported controversial results.^[6–10] In addition, these previous studies mainly focused on Europeans and Americans, and the relationship between CAC and cognitive function in the Chinese population is still uncertain. The Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score was the first dementia risk score developed to predict late-life dementia risk. Individuals with a CAIDE score ≥ 9 or ≥ 10 were considered to have a high risk of dementia.^[11–13] The capability of CAC to identify participants with a high risk of late-life dementia (CAIDE score ≥ 9 or ≥ 10) was discrepant as well.^[14] Moreover, CAC is currently available convenient in clinical practice, and non-contrast chest CT scans and cardiac computed tomography angiography could both be used to assess CAC, especially in smokers undergoing lung cancer screening and patients suspected with coronary artery disease. This study was designed to determine: (1) whether CAC is related to cognitive performance, including verbal memory, semantic fluency, executive function and global cognitive function, and (2) the capability of CAC to identify participants with a high risk of late-life dementia in a Chinese community-based population.     

Associations of body mass index and hospital-acquired disability with post-discharge mortality in older patients with acute heart failure

OBJECTIVESTo investigate the effect of hospital-acquired disability (HAD) on all-cause mortality after discharge according to the body mass index (BMI) in older patients with acute decompensated heart failure.METHODSWe included 408 patients aged ≥ 65 years who were hospitalized for acute decompensated heart failure and had undergone an acute phase of cardiac rehabilitation at the Sakakibara Heart Institute between April 2013 and September 2015 (median age: 82 years, interquartile range (IQR): 76–86; 52% male). Patients were divided into three groups based on BMI at hospital admission: underweight (< 18.5 kg/m²), normal weight (18.5 to 25 kg/m²), and overweight (≥ 25 kg/m²). HAD was defined as a decrease of at least five points at discharge compared to before hospitalization according to the Barthel Index. RESULTSThe median follow-up period was 475 (IQR: 292–730) days, and all-cause mortality during the follow-up period was 84 deaths (21%). According to multivariate Cox regression analysis, being underweight (HR: 1.941, 95% CI: 1.134−3.321,P = 0.016) or overweight (HR: 0.371, 95% CI: 0.171−0.803,P = 0.012), with normal BMI as the reference, and HAD (HR: 1.857, 95% CI: 1.062−3.250,P = 0.030) were independently associated with all-cause mortality. Patients with HAD exhibited a significantly lower cumulative survival rate in the underweight group (P = 0.001) and tended to have a lower cumulative survival rate in the normal weight group (P = 0.072). HAD was not significantly associated with cumulative survival in the overweight group (P = 0.392). CONCLUSIONSBMI and HAD independently predicted all-cause mortality after discharge in older patients with acute decompensated heart failure. Furthermore, HAD was significantly associated with higher all-cause mortality after discharge, especially in the underweight group.

In recent years, the prevalence of patients with heart failure has increased rapidly.^[1] As the population ages in Japan, there is a growing concern that the prevalence of heart failure will continue to increase.^[2] Therefore, there is an urgent need to treat and manage older patients with heart failure by determining the risk factors associated with poor prognoses. Being overweight and obese are associated with all-cause and cardiovascular mortality.^{[3, 4]} Moreover, individuals who are overweight or obese reportedly have a higher risk of developing heart failure than those with normal body weight.^[5] Conversely, the “obesity paradox” shows that being underweight, rather than being overweight or obese, is associated with a poorer prognosis in patients with heart failure.^{[6, 7]}A decline in physical function during hospitalization is called hospital-acquired disability (HAD), and has a reported incidence rate of approximately 35% in older patients.^[8] HAD is a poor prognostic factor in older patients with heart disease.^[9] In a previous study, underweight patients with heart failure had low scores for activities of daily living measured at admission, and the decline tended to continue even at discharge.^[10] However, it remains unclear whether HAD influences patient prognosis according to the body mass index (BMI) after discharge. This study aimed to investigate the association of HAD with all-cause mortality after discharge according to BMI categories in patients with acute decompensated heart failure.     

Periprocedural complications and one-year outcomes after catheter ablation for treatment of atrial fibrillation in elderly patients: a nationwide Danish cohort study

OBJECTIVESTo investigate complications within 30-days following first-time ablation for atrial fibrillation (AF), including a composite of cardiac tamponade, hematoma requiring intervention, stroke or death, in patients ≥ 75 years of age, compared to patients aged 65−74 years. In addition, one-year all-cause mortality and AF relapse were compared.METHODS & RESULTSAll patients receiving their first catheter ablation for AF between 2012 and 2016 were identified using Danish nationwide registries. Patients aged 65−74 years served as the reference group for patients ≥ 75 years. Relapse of AF within one year was defined as cardioversion following a three-month blanking period, re-ablation or confirmed relapse within follow-up. The composite complication outcome did not differ between the two age groups, with 39/1554 (2.8%) in patients 65−74 years of age, versus 5/199 (2.5%) in older patients (adjusted HR = 0.94), 95% CI: 0.37−2.39, P = 0.896). Patients ≥ 75 years or older had no increased hazard of death within 30 days after the procedure, with an incidence of 3/1554 (0.2%) in younger patients and 2/199 (1.0%) in patients ≥ 75 years of age (adjusted HR = 4.71, 95% CI: 0.78−28.40, P = 0.091). There was no difference in relapse of AF after one year between age groups (≥ 75 years adjusted HR = 1.00, 95% CI: 0.78-1.26, P = 0.969). CONCLUSIONIn patients ≥ 75 years of age selected for catheter ablation for AF, the incidence of periprocedural complications, as well as one-year freedom from AF showed no statistical difference, when compared to patients 65−74 years of age.

Pulmonary vein isolation by means of catheter ablation has become a commonly used therapy for drug-resistant atrial fibrillation (AF) and as a result of a steadily increase in life expectancy along with improved methods to diagnose AF, the incidence of AF is on the rise.^[1] Pulmonary vein isolation has a success rate of 50%−70% after one procedure, and short-term procedural complications including death, stroke, cardiac tamponade and atrio-esophageal fistula vary from 2%−3%.^[1,2] Other complications include pericardial effusion, phrenic nerve injury, pulmonary vein stenosis and vascular complications, including hematomas and pseudo-aneurisms, with complication rates ranging from < 1%−4%. ^[1] Regarding the treatment of elderly patients with catheter ablation, the 2016 ESC guidelines for the management of atrial fibrillation states that “In general, better rhythm outcome and lower procedure-related complications can be expected in younger patients with a short history of AF and frequent, short AF episodes in the absence of significant structural heart disease”, and “although the evidence base is smaller for other treatment options in AF, the available data support the use of available rate and rhythm control interventions, including pacemakers and catheter ablation, without justification to discriminate by age group”.^[3] However, many studies referred to in this guideline have a relatively low volume of elderly patients, as the mean age of patients included were between 52.6−66 years. The 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation stated that outcome data was needed in “high-risk populations”, including the very elderly.^[4]In the latest 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation, AF catheter ablation is stated as it “may be an effective and safe option in selected older individuals with success rates comparable to younger patients and acceptable complication rates”.^[1] This change in recommendation compared to 2016 guidelines is based on several observational studies.^[5-8] Using a nationwide register-based cohort, consisting of all patients receiving their first catheter ablation procedure for AF in Denmark, the present study aimed to investigate the incidence of periprocedural complications within 30 days post-ablation. These include cardiac tamponade, hematoma requiring intervention, stroke or death and a composite endpoint of these complications in patients ≥ 75 years of age, compared to patients aged 65-74 years. In addition, one-year outcomes including AF relapse and all-cause mortality after catheter ablation were compared between the two age groups.     

Association between non-culprit healed plaque and plaque progression in acute coronary syndrome patients: an optical coherence tomography study

BACKGROUNDHealed plaques are frequently found in patients with acute coronary syndrome, but the prognostic value is debatable. This study investigated the clinical features of non-culprit healed plaques detected by optical coherence tomography (OCT) with the aim of predicting plaque progression of healed plaques.METHODSThis study retrospectively analyzed 113 non-culprit lesions from 85 patients who underwent baseline OCT imaging and follow-up angiography from January 2015 to December 2019. Plaque progression predictors were assessed by multivariate analysis.RESULTSAmong 113 non-culprit lesions, 27 healed plaques (23.9%) were identified. Patients with non-culprit healed plaques had prior antiplatelet therapy (65.0% vs. 33.8%, P = 0.019), hypertension (85.0% vs. 50.7%, P = 0.009), and dyslipidemia (70.0% vs. 41.5%, P = 0.04) which were more frequently than those without healed plaques. The thickness (r = 0.674, P < 0.001), arc ( r = 0.736, P < 0.001), and volume ( r = 0.541, P = 0.004) of healed plaque were correlated with minimum lumen diameter changes. At a mean follow-up of 11.5 months, the non-culprit healed plaques had a lower minimum lumen diameter (1.61 ± 0.46 mm vs. 1.91 ± 0.73 mm, P = 0.016), lower average lumen diameter (1.86 mm vs. 2.10 mm, P = 0.033), and a higher degree of diameter stenosis (41.4% ± 11.9% vs. 35.5% ± 13.1%, P = 0.031) when compared to baseline measurements. The plaque progression rate was higher in the healed plaque group (33.3% vs. 8.1%, P = 0.002), and multivariate analysis identified healed plaques [odds ratio (OR) = 8.49, 95% CI: 1.71−42.13] and lumen thrombus (OR = 10.69, 95% CI: 2.21−51.71) as predictors of subsequent lesion progression. CONCLUSIONSHealed plaques were a predictor for rapid plaque progression. The quantitative parameters of healed plaque showed a good agreement with plaque progression. Patients with healed plaque were associated with prior antiplatelet therapy and high level of low-density lipoprotein cholesterol. Bifurcation lesions might be the predilection sites of healed plaques.

Coronary artery diseases originate from pathological changes in the vessel endothelium, present as plaque development and lumen stenosis, that finally lead to clinical coronary symptoms.^[1] Finding the ideal time to intervene in the atherosclerosis process is difficult, especially with non-culprit lesions.^[2–4] Revascularization benefits are challenged by the quick progression of previously untreated mild to moderate lesions.^[2] Several clinical trials suggested that the rapid step-wise pattern of plaque growth may play an important role in lumen narrowing.^[5,6] This mechanism was described as a healing process that was initiated by a plaque rupture or erosion to protect the integrity of the vessel structure.^[7,8] Re-endothelialization results in a new layer of organized thrombus and collagen distinguished from the underlying ruptured or eroded site,^[9] and plaques with two or more layers of different densities are called healed plaques or layered plaques.^[8,10] Autopsy studies found that healed plaques were frequent in patients dying of sudden death or asymptomatic myocardial infarction.^[11] Optical coherence tomography (OCT) is a high-resolution intravascular imaging tool that is highly sensitive and specific for in vivo identification of layered plaque patterns by histopathology.^[12,13] A previous OCT study suggested that layered plaques at the culprit site were associated with more vulnerable features and a high degree of lumen stenosis in patients with acute coronary syndrome (ACS).^[14] However, serial observations of plaque progression at the exact site were only reported in rare cases.^[15] In this study, we investigated the OCT features, quantitative parameters, and predictive value of non-culprit healed plaques, which may help minimize plaque progression and stenosis risk.     

Clinical benefit of left atrial appendage closure in octogenarians

OBJECTIVESWhether left atrial appendage closure (LAAC) in octogenarians yield similar net clinical benefit compared to younger patients, was the purpose of the present study.METHODSTwo real-world LAAC registries, enrolling 744 consecutive Amplatzer and Watchman patients from 2009 to 2018, were retrospectively analyzed.RESULTSAll events are reported per 100 patient-years. Two hundred and sixty one octogenarians and 483 non-octogenarians with a mean follow-up of 1.7 ± 1.3 and 2.3 ± 1.6 years, and a total of 1,502 patient-years were included. Octogenarians had a higher risk for stroke (CHA₂DS₂-VASc score: 5.2 ± 1.2 vs. 4.3 ± 1.7, P < 0.0001) and bleeding (HAS-BLED score: 3.3 ± 0.8 vs. 3.1 ± 1.1, P = 0.001). The combined safety endpoint of major periprocedural complications and major bleeding events at follow-up was comparable (30/446, 6.7% vs. 47/1056, 4.4%; hazard ratio [HR] = 1.2; 95% confidence interval [CI]: 0.73−1.98;P = 0.48) between the groups. The efficacy endpoint of all-cause stroke, systemic embolism, and cardiovascular/unexplained death occurred more often in octogenarians (61/446, 13.7% vs. 80/1056, 7.6%; HR = 7.0; 95% CI: 4.53−10.93;P < 0.0001). Overall, octogenarians had a lower net clinical benefit, i.e., the composite of all above mentioned hazards, from LAAC compared to younger patients (82/446, 18.4% vs. 116/1056, 11.0%; HR = 4.6; 95% CI: 3.11−7.0;P < 0.0001). Compared to the anticipated stroke rate, the observed rate decreased by 41% in octogenarians and 53% in non-octogenarians. The observed bleeding rate was reduced by 10% octogenarians and 41% non-octogenarians. CONCLUSIONSLAAC can be performed with similar safety in octogenarians as compared to younger patients. On the long-term, it both reduces stroke and bleeding events, although to a lesser extent than in non-octogenarians.

As the most frequent arrhythmia, atrial fibrillation (AF) is associated with an increased risk of cognitive decline, stroke, disability, and mortality. The prevalence of AF is 2% in the general population and roses steadily with age, 3.7%−4.2% of subjects are aged above 60 years and up to 17% are octogenarians (age ≥ 80 years).^[1] Stroke risk from AF increases exponentially with age and is estimated at 23.9% per year in patients aged 80 years and older.^[2] Additionally, patients ≥ 80 years with AF, who are treated with oral anticoagulation (OAC), have a higher incidence of hemorrhagic events than younger patients.^[3] Therefore, octogenarians with AF are at highest risk for both thromboembolic and bleeding events. OAC is the standard of care for stroke risk. However, clinical evidence shows underuse of OAC in the elderly, who would have the highest benefit regarding ischemic stroke risk. This is mainly due to concerns about bleeding or prior bleedings. Factors of comorbidity, like impaired cognition, nonadherence, history of falls or bleedings, renal dysfunction, as well as concomitant drugs are reasons for leaving a substantial fraction of patients without stroke protection by OAC.^[4] Left atrial appendage closure (LAAC) is recommended as an alternative strategy for stroke prevention in AF patients who are not suitable for long-term treatment with OAC.^[5,6] Therefore, LAAC might be an attractive option for elderly AF patients. Several studies reported similar feasibility and safety of LAAC in subjects aged > 75 years compared to younger patients. ^[7–11] Furthermore, those studies showed favorable early clinical outcomes with regard to stroke and bleeding protection. Whether elderly patients have persistent long-term effects of LAAC has not been studied yet. Therefore, the subject of the present study was to compare the clinical benefit of LAAC in octogenarians with non-octogenarians based on the results of two real-world registries.     

Atrial fibrillation in patients with systolic heart failure: pathophysiology mechanisms and management

Heart failure (HF) and atrial fibrillation (AF) demonstrate a constantly increasing prevalence during the 21^st century worldwide, as a result of the aging population and the successful interventions of the clinical practice in the deterioration of adverse cardiovascular outcomes. HF and AF share common risk factors and pathophysiological mechanisms, creating the base of a constant interrelation. AF impairs systolic and diastolic function, resulting in the increasing incidence of HF, whereas the structural and neurohormonal changes in HF with preserved or reduced ejection fraction increase the possibility of the AF development. The temporal relationship of the development of either condition affects the diagnostic algorithms, the prognosis and the ideal therapeutic strategy that leads to euvolaemia, management of non-cardiovascular comorbidities, control of heart rate or restoration of sinus rate, ventricular synchronization, prevention of sudden death, stroke, embolism, or major bleeding and maintenance of a sustainable quality of life. The indicated treatment for the concomitant HF and AF includes rate or/and rhythm control as well as thromboembolism prophylaxis, while the progress in the understanding of their pathophysiological interdependence and the introduction of the genetic profiling, create new paths in the diagnosis, the prognosis and the prevention of these diseases.

Heart failure (HF) and atrial fibrillation (AF) have become epidemics of the 21st century, as a result of the increased longevity and the successful reduction of the cardiovascular (CV) mortality.^[1] The prevalence of both conditions is constantly rising, increasing significantly the cost of treatment to the healthcare systems worldwide.^[2-4] It is estimated that the incidence of AF (2%) is double compared to the last decade. AF is present in 0.12%−0.16% of those < 49 years of age, in 3.7%−4.2% of those aged 60−70 years, and in 10%−17% of those aged ≥ 80 years, occurring more frequently in males, with a male to female ratio of 1.2: 1.^[5] By the year 2030 in Europe alone it is estimated that the patients with AF will be 14−17 million, with an annual number of 120−215,000 new cases,^[5] while the prevalence in the American population will be 12 million.^[6] HF affects approximately 1%−2% of adults in developed countries.^[7] Few individuals under 50 years of age are diagnosed with HF, whereas the prevalence in those aged 75 years or above is more than 10%.^[7,8] The prevalence of HF globally in AF individuals is 33% in patients with paroxysmal AF, 44% in those with persistent and 56% in those with permanent AF.^[9] Among the 5.8 million US adults with heart failure with reduced ejection fraction (HFrEF) or preserved EF (HFpEF), the prevalence of AF is up to 40%.^[10,11] It is clear that the combination of these two conditions will have a significant impact on healthcare and the management of cardiovascular (CV) disease as it is performed so far.^[12,13] The pathophysiology and risk factors for HF and AF are closely related and the coexistence of HF and AF affects elderly patients with a significant burden of comorbidities.^{[9, 14]} The development of AF is connected with complex interactions that lead to impairment of systolic and diastolic function, that are not present in sinus rhythm (SR), resulting in a three-fold increased risk of HF incidence compared with SR.^[15] Conversely, the structural and neurohormonal changes in HF increase the possibility of the AF incidence^[16] both in HFrEF and in HFpEF.^[1] Previous studies have also demonstrated differences in atrial remodeling, prognosis and outcomes^[17] associated with AF development among the HF subtypes,^[18] with greater eccentric LA remodeling in HFrEF, and increased LA stiffness in HFpEF predisposing more evidently in AF.^[19] Regardless which condition develops first, their combined incidence is associated with a worse prognosis than either condition alone.^[20-22] Concerning the adverse outcomes that are associated with HF and AF, an important target of clinical studies is the development of effective therapies for these patients but also an arduous one as the so far applied treatments on either of these conditions alone are shown to be effective or provoke safety concerns in patients with HF and AF.^{[23, 24]}     

Beta-blocker treatment in heart failure patients with atrial fibrillation: challenges and perspectives

Heart failure (HF) and atrial fibrillation (AF) are common conditions that share similar clinical phenotype and frequently coexist. The classification of HF in patients with preserved ejection fraction (> 50%, HFpEF), mid-range reduced EF (40%−49%, HFmrEF) and reduced EF (< 40%, HFrEF) are crucial for optimising the therapeutic approach, as each subgroup responds differently. Beta-blocker constitute an important component of our pharmacological regimen for chronic HF. Beta-blocker administration is reccomended in patients with HF with reduced ejection fraction in stable sinus rhythm, due to improvement of symptoms, the better long term-outcome and survival. The beneficial role of beta-blocker use in patients with preserved EF still remain unclear, as no treatment showed a positive impact, regarding morbidity or mortality reduction. The presence of AF in HF patients increases as the disease severity evolves and is associated with a higher rate of cardiovascular morbidity and mortality. But more question is the use of betablocker in HF patients irrespective of EF and concomitant AF. There are many conflicting data and publications, regarding the beta blocker benefit in this population. Generally, it is supported an attenuation of beta-blockers beneficial effect in HF patients with AF. A design of more randomised trials/studies with HF patients and concomitant AF may improve our clinical approach of beta-blockers use and identify the patients with HF, who mostly profit from an invasive approach.

Atrial fibrillation (AF) and heart failure (HF) with or without systolic dysfunction constitute common cardiac conditions, that frequently coexist and overlap.^[1] These entities share multiple risk factors such as age, hypertension, diabetes, obesity, as well as cardiac substrates as valvular, ischemic, and non ischemic structural heart disease.^{[1, 2]} Their coexistence can be partially explained by the presence of the common risk factors.^[3]The definition of heart failure revised in 2016, based on the measurement of left ventricular ejection fraction (EF).^[4] Especially, HF can be divided in three groups: heart failure with preserved EF(> 50%, HFpEF), mid-range reduced EF (40%−49%, HFmrEF) and reduced EF (< 40%, HFrEF).^[4] Interestingly, up to 50% of chronic HF patients present normal or only mildly impaired left ventricular EF.^[5] The prevalence of AF in HF patients increases as the disease severity evolves.^[6] Specifically, in patients with New York Heart Association (NYHA) I−II is typically about 5%, NYHA III approximately 26% and NYHA IV is presented up to 50%.^[6] According to the data from randomized clinical trials and registries, the presence of AF in HFpEF patients ranges between 15% and 41%.^[7] Patients with HFpEF are more likely to demonstrate prevalent AF or AF at any time up to twice, compared with those with HFrEF.^[7] Data from the natiowide Swedish heart failure registry reported the prevelance of AF among LVEF ranges, specifically 53% in HFrEF, 60% HFmrEF, and 65% inHFpEF.^[8] The presence of AF in HFrEF patients was 27% in an anaylsis of ESC-HF long term registry.^[9] Notably, AF occurs in 24%−44% of patients in the setting of acute HF and in one third of those with chronic HF.^{[10, 11]} Atrial fibrillation is also found in more than half (57%) of patients with new onset of HF.^[12] Furthermore, HF is present in 33%, 44% and 56% of ambulatory patients with paroxysmal, persistent and permanent AF, respectively and in more than one third (37%) of those with new onset AF.^{[12, 13]}     

Beta-blockers and 1-year clinical outcomes in hospitalized heart failure patients with atrial fibrillation

OBJECTIVETo assess the association between beta-blockers and 1-year clinical outcomes in heart failure (HF) patients with atrial fibrillation (AF), and further explore this association that differs by left ventricular ejection fraction (LVEF) level.METHODSWe enrolled hospitalized HF patients with AF from China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study. COX proportional hazard regression models were employed to calculate hazard ratio of beta-blockers. The primary outcome was all-cause death.RESULTSAmong 1762 HF patients with AF (756 women [41.4%]), 1041 (56%) received beta-blockers at discharge and 1272 (72.2%) had an LVEF > 40%. During one year follow up, all-cause death occurred in 305 (17.3%), cardiovascular death occurred in 203 patients (11.5%), and rehospitalizations for HF occurred in 622 patients (35.2%). After adjusting for demographic characteristics, social economic status, smoking status, medical history, anthropometric characteristics, and medications used at discharge, the use of beta-blockers at discharge was not associated with all-cause death [hazard ratio (HR): 0.86; 95% Confidence Interval (CI): 0.65−1.12; P = 0.256], cardiovascular death (HR: 0.76, 95% CI: 0.52−1.11; P = 0.160), or the composite outcome of all-cause death and HF rehospitalization (HR: 0.97, 95% CI: 0.82−1.14; P = 0.687) in the entire cohort. There were no significant interactions between use of beta-blockers at discharge and LVEF with respect to all-cause death, cardiovascular death, or composite outcome. In the adjusted models, the use of beta-blockers at discharge was not associated with all-cause death, cardiovascular death, or composite outcome across the different levels of LVEF: reduced (< 40%), mid-range (40%−49%), or preserved LVEF (≥ 50%). CONCLUSIONAmong HF patients with AF, the use of beta-blockers at discharge was not associated with 1-year clinical outcomes, regardless of LVEF.

Heart failure (HF) is a leading cause of death and there are approximately 64.3 million patients with HF worldwide.^[1] Among them, atrial fibrillation (AF) is the most common arrhythmia and presents in up to half of HF patients; its prevalence is even higher in those with preserved left ventricular ejection fraction (LVEF).^[2] Given the association between AF and worse prognosis in HF patients,^[3] we need to consider the presence of AF in the treatment of such patients. Beta-blockers are important medications to improve outcomes in HF patients with reduced ejection fraction (HFrEF).^[4] However, an individual-level meta-analysis suggested beta-blockers did not improve survival of HFrEF patients with concomitant AF.^[5] Moreover, current trials have not found sufficient evidence of survival benefits of beta-blockers in HF patients with preserved ejection fraction (HFpEF).^[6,7] But the use of beta-blockers was common in HFpEF patients,^[8,9] partly because the treatment for complications, such as AF.^[4,10] Whether beta-blockers would appear to be ineffective in long-term prognosis in HFrEF patients with AF, and whether this also holds true in those with preserved LVEF are uncertain. The individual-level meta-analysis of 11 randomized controlled trials mainly consisted of HFrEF patients with AF, and only included 73 HFpEF patients with AF, which could make it difficult to draw a reliable conclusion.^[6] Despite lack of evidence, the current guidelines recommend beta-blockers as first-line heart rate control treatment in HFrEF/HFpEF patients with AF. ^[4,10]To fill these knowledge gaps, we explored the association between use of beta-blockers at discharge and 1-year clinical outcomes in a large prospective cohort study of hospitalized HF patients with AF, and further explored this association that differs by LVEF level.     

Biomarkers in the clinical management of patients with atrial fibrillation and heart failure

Atrial fibrillation (AF) and heart failure (HF) are two cardiovascular diseases with an increasing prevalence worldwide. These conditions share common pathophysiologiesand frequently co-exit. In fact, the occurrence of either condition can ‘cause’ the development of the other, creating a new patient group that demands different management strategies to that if they occur in isolation. Regardless of the temproral association of the two conditions, their presence is linked with adverse cardiovascular outcomes, increased rate of hospitalizations, and increased economic burden on healthcare systems. The use of low-cost, easily accessible and applicable biomarkers may hasten the correct diagnosis and the effective treatment of AF and HF. Both AF and HF effect multiple physiological pathways and thus a great number of biomarkers can be measured that potentially give the clinician important diagnostic and prognostic information. These will then guide patient centred therapeutic management. The current biomarkers that offer potential for guiding therapy, focus on the physiological pathways of miRNA, myocardial stretch and injury, oxidative stress, inflammation, fibrosis, coagulation and renal impairment. Each of these has different utility in current clinincal practice.

Atrial fibrillation (AF) is the most common type of arrhythmia having an annual prevalence of 33 million patients worldwide, along with a three times higher prevalence in women than in men.^[1] There are a number associated risk factors including heart failure, diabetes, hypertension, hyperthyroidism, obesity, structural and ischemic heart disease. However, up to 20% of AF cases cannot be connected with those factors.^[2] The development of AF involves a complex interplay between genetic, molecular and environmental factors. Their better identificationcould alter the possible management and treatment of symptomatic and asymptomatic patients, incuding those that are yet diagnosed via the ECG.^[3-5] Atrial fibrosis is likely play a key role in the development and prognsosi of AF. The extent of the fibrotic process can predict the response to the use of ablation as a treatment.^[6-8] The fibrotic mechanism is not yet fully clarified, but according to some studies, the renin-angiotensin axis^[9] and transforming growth factor (TGF) β1, play a key role in the cardiac fibrosis.^[10]Atrial fibrillation is linked with cardiovascular diseases, mortality, central nervous system side effects.^[11] Most specifically, AF often precedes or follows the development of HF, both share pathophysiological paths that contribute to cardiac remodelling and the combined presence of the two conditions is connected with an adverse prognosis.^[12]Heart failure (HF) is a clinical syndrome presenting with typical symptoms (breathlessness on exertion, paroxysmal nocturnal dyspnea, orthopnea and fatigue) and signs (elevated jugular venous pressure, pulmonary oedema and peripheral oedema) as a result of a structural and/or functional cardiac abnormalities. These lead to a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress, which result in many physiological changes, including multiple morphological, biochemical and molecular alterations referred to cardiac remodeling.^[13,14] The current definition includes stages based on the symptoms observed in the patients requiring medical assistance, however prior to any clinical symptoms patients can present with asymptomatic structural or functional cardiac abnormalities [systolic or diastolic left ventricular (LV) dysfunction]. The early recognition of these precursors can lead to better outcomes, in terms of both hospitalization and mortality in patients with HF. The prevalence of HF varies according to the definition used, but is approximately 1%–2% of the adult population in developed countries, rising to ≥ 10% among people > 70 years of age worldwide. ^[15-18] Among people > 65 years old presenting to primary care with breathlessness on exertion, one in six will have undiagnosed HF. ^[19,20] The lifetime possibility of developing HF at age 55 is 33% for men and 28% for women.^[17] The pathophysiology of HF is mediated by a variety of biological mechanisms, with complex interactions between endothelial cells, monocytes, macrophages, cardiomyocytes, fibrocytes and the neuro-endocrine system. On top is the interplay with systemic conditions such as diabetes, advanced age, hypertension, obesity, dyslipidemia and chronic kidney disease. Cardiac troponins and natriuretic peptides are the most widely used diagnostic biomarkers in the management of HF,^[21] although there are a number of novel ones are also available, but not widely used in clinical practice.