Aims
It has been proposed that an increase of myocardial adiposity is related to left ventricular (LV) diastolic dysfunction. The specific roles of myocardial steatosis including epicardial fat and ...intramyocardial fat for diastolic function are unknown in those patients suffering heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF). This study aims to determine the complex relationship between myocardial adiposity in patients with HFrEF or HFpEF.
Methods and results
Using cardiac magnetic resonance imaging (CMRI), myocardial steatosis was measured in 305 subjects (34 patients with HFrEF, 163 with HFpEF, and 108 non‐HF controls). We also evaluated cardiac structure and diastolic and systolic function by echocardiography and CMRI. Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls intramyocardial fat content (%), 1.56 (1.26, 1.89) vs. 0.75 (0.50, 0.87) and 1.0 (0.79, 1.15), P < 0.05. Intramyocardial fat amount (%) was higher in HFpEF women than in men 1.91% (1.17%, 2.32%) vs. 1.22 (0.87%, 2.02%), P = 0.01. When estimated by CMRI (left ventricular peak filling rate), echocardiographic E/e′ level, or left atrial volume index, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients, and this was independent of age, co‐morbidities, body mass index, gender, and myocardial fibrosis (standardized coefficient: β = −0.34, P = 0.03; β = 0.29, P = 0.025; and β = 0.25, P = 0.02, respectively).
Conclusions
Patients with HFpEF had significantly more intramyocardial fat than HFrEF patients or non‐HF controls. Independent of risk factors or gender, intramyocardial fat correlated with LV diastolic dysfunction parameters in HFpEF patients.
Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the ...Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atherosclerosis, with the aim of establishing whether inhibition of a major product of the Nod-like receptor protein 3 (NLRP3) inflammasome with canakinumab might alter cancer incidence.
We did a randomised, double-blind, placebo-controlled trial of canakinumab in 10 061 patients with atherosclerosis who had had a myocardial infarction, were free of previously diagnosed cancer, and had concentrations of high-sensitivity C-reactive protein (hsCRP) of 2 mg/L or greater. To assess dose–response effects, patients were randomly assigned by computer-generated codes to three canakinumab doses (50 mg, 150 mg, and 300 mg, subcutaneously every 3 months) or placebo. Participants were followed up for incident cancer diagnoses, which were adjudicated by an oncology endpoint committee masked to drug or dose allocation. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT01327846. The trial is closed (the last patient visit was in June, 2017).
Baseline concentrations of hsCRP (median 6·0 mg/L vs 4·2 mg/L; p<0·0001) and interleukin 6 (3·2 vs 2·6 ng/L; p<0·0001) were significantly higher among participants subsequently diagnosed with lung cancer than among those not diagnosed with cancer. During median follow-up of 3·7 years, compared with placebo, canakinumab was associated with dose-dependent reductions in concentrations of hsCRP of 26–41% and of interleukin 6 of 25–43% (p<0·0001 for all comparisons). Total cancer mortality (n=196) was significantly lower in the pooled canakinumab group than in the placebo group (p=0·0007 for trend across groups), but was significantly lower than placebo only in the 300 mg group individually (hazard ratio HR 0·49 95% CI 0·31–0·75; p=0·0009). Incident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0·61 95% CI 0·39–0·97; p=0·034) and 300 mg groups (HR 0·33 95% CI 0·18–0·59; p<0·0001; p<0·0001 for trend across groups). Lung cancer mortality was significantly less common in the canakinumab 300 mg group than in the placebo group (HR 0·23 95% CI 0·10–0·54; p=0·0002) and in the pooled canakinumab population than in the placebo group (p=0·0002 for trend across groups). Fatal infections or sepsis were significantly more common in the canakinumab groups than in the placebo group. All-cause mortality did not differ significantly between the canakinumab and placebo groups (HR 0·94 95% CI 0·83–1·06; p=0·31).
Our hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality. Replication of these data in formal settings of cancer screening and treatment is required.
Novartis Pharmaceuticals.
Canakinumab, a monoclonal antibody targeting interleukin-1β, reduces inflammation and cardiovascular event rates with no effect on lipid concentrations. However, it is uncertain which patient groups ...benefit the most from treatment and whether reductions in the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) correlate with clinical benefits for individual patients.
The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) used computer-generated codes to randomly allocate 10 061 men and women with a history of myocardial infarction to placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given subcutaneously once every 3 months. In a prespecified secondary analysis designed to address the relationship of hsCRP reduction to event reduction in CANTOS, we evaluated the effects of canakinumab on rates of major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality according to on-treatment concentrations of hsCRP. We used multivariable modelling to adjust for baseline factors associated with achieved hsCRP and multiple sensitivity analyses to address the magnitude of residual confounding. The median follow-up was 3·7 years. The trial is registered with ClinicalTrials.gov, number NCT01327846.
Baseline clinical characteristics did not define patient groups with greater or lesser cardiovascular benefits when treated with canakinumab. However, trial participants allocated to canakinumab who achieved hsCRP concentrations less than 2 mg/L had a 25% reduction in major adverse cardiovascular events (multivariable adjusted hazard ratio HRadj=0·75, 95% CI 0·66–0·85, p<0·0001), whereas no significant benefit was observed among those with on-treatment hsCRP concentrations of 2 mg/L or above (HRadj=0·90, 0·79–1·02, p=0·11). For those treated with canakinumab who achieved on-treatment hsCRP concentrations less than 2 mg/L, cardiovascular mortality (HRadj=0·69, 95% CI 0·56–0·85, p=0·0004) and all-cause mortality (HRadj=0·69, 0·58–0·81, p<0·0001) were both reduced by 31%, whereas no significant reduction in these endpoints was observed among those treated with canakinumab who achieved hsCRP concentrations of 2 mg/L or above. Similar differential effects were found in analyses of the trial prespecified secondary cardiovascular endpoint (which additionally included hospitalisation for unstable angina requiring unplanned revascularisation) and in sensitivity analyses alternatively based on median reductions in hsCRP, on 50% or greater reductions in hsCRP, on the median percent reduction in hsCRP, in dose-specific analyses, and in analyses using a causal inference approach to estimate the effect of treatment among individuals who would achieve a targeted hsCRP concentration.
The magnitude of hsCRP reduction following a single dose of canakinumab might provide a simple clinical method to identify individuals most likely to accrue the largest benefit from continued treatment. These data further suggest that lower is better for inflammation reduction with canakinumab.
Novartis Pharmaceuticals.
We used nationwide population-based data to identify optimal hospital and surgeon volume thresholds and to discover the effects of these volume thresholds on operative mortality and length of stay ...(LOS) for coronary artery bypass surgery (CABG).
Retrospective cohort study.
General acute care hospitals throughout Taiwan.
A total of 12,892 CABG patients admitted between 2011 and 2015 were extracted from Taiwan National Health Insurance claims data.
Operative mortality and LOS. Restricted cubic splines were applied to discover the optimal hospital and surgeon volume thresholds needed to reduce operative mortality. Generalized estimating equation regression modeling, Cox proportional-hazards modeling and instrumental variables analysis were employed to examine the effects of hospital and surgeon volume thresholds on the operative mortality and LOS.
The volume thresholds for hospitals and surgeons were 55 cases and 5 cases per year, respectively. Patients who underwent CABG from hospitals that did not reach the volume threshold had higher operative mortality than those who received CABG from hospitals that did reach the volume threshold. Patients who underwent CABG with surgeons who did not reach the volume threshold had higher operative mortality and LOS than those who underwent CABG with surgeons who did reach the volume threshold.
This is the first study to identify the optimal hospital and surgeon volume thresholds for reducing operative mortality and LOS. This supports policies regionalizing CABG at high-volume hospitals. Identifying volume thresholds could help patients, providers, and policymakers provide optimal care.
Diabetes mellitus (DM) is a common comorbidity and risk factor for postoperative complications in head and neck (H&N) microsurgical reconstructions. Our study focused on the association between DM ...and individual complications regarding both surgical and medical aspects. A meta-analysis of English-language articles comparing a series of complications between DM and non-DM H&N free-flap recipients was performed by comprehensive meta-analysis (CMA). Twenty-seven articles presented 14,233 H&N free-flap reconstructions, and a subset of 2329 analyses including diabetic cases was included for final analysis. Total postoperative (RR = 1.194, p < 0.001; OR = 1.506, p = 0.030) and surgical (RR = 1.550, p = 0.001; OR = 3.362, p < 0.001) complications were increased in DM subjects. Free-flap failure/necrosis (RR = 1.577, p = 0.001; OR = 1.999, p = 0.001) and surgical site infections (OR = 2.414, p < 0.001) were also increased in diabetic recipients. However, return to the operating room, dehiscence, fistulas, plate exposures, readmissions, and mortalities were not increased in DM patients. DM increased various complications in H&N free-flap reconstructions. Surgical indications should be cautiously evaluated, and aggressive treatments should be implemented for high-risk recipients.
Cross-sectional studies have described an association between exposure to phthalate esters and cardiovascular risk factors. However, the association with coronary heart disease (CHD) is still ...unclear. A total of 180 subjects randomly selected from 336 CHD patients, and 360 age- and sex-matched non-CHD controls were included from 2008 to 2011. Urinary metabolites of phthalate esters were measured by liquid chromatography–tandem mass spectrometry. The geometric means of urinary phthalates metabolites were significantly higher for the three Di-(2-ethylhexyl)-phthalate (DEHP) metabolites, mono‐2‐ethylhexyl phthalate (MEHP), mono‐(2‐ethyl‐5‐hydroxyhexyl) phthalate, and mono‐(2‐ethyl‐5‐oxohexyl) phthalate among CHD patients in-hospital than those of being discharged. Excluding 89 CHD patients of in-hospital and hospital discharge within 2 days, we found the urinary concentrations of MEHP, mono‐n‐butyl phthalate (MnBP), and mono-isobutyl phthalate (MiBP) of 91 CHD patients discharged ≥ 3 days were higher than those of controls. Among 451 participants, those with higher tertile levels of urinary MEHP, MnBP, and MiBP showed an increased risk for CHD compared to those with lowest tertile levels; the corresponding odds ratios (95% CI) were 2.77 (1.22–6.28), 2.90 (1.32–6.4), and 3.19 (1.41–7.21), respectively, after adjustment for confounders. Higher levels of hs-CRP, fibrinogen, and D-dimer were linked with increased levels of all DEHP metabolites in CHD patients. In conclusion, exposure to DEHP and dibutyl phthalates was positively associated with CHD and this relationship may be probably mediated via atherothrombosis.
Data was adjusted for age, gender, body mass index, diabetes mellitus, hypertension, and hypercholesterolemia, use of statins, smoking, and alcohol consumption according to tertiles of urinary phthalate levels. Display omitted
•Urinary MEHP, MiBP, and MnBP are associated with coronary heart disease (CHD).•DEHP metabolites are associated with hs-CRP, fibrinogen, and D-dimer in CHD patients.•Regulation to reduce phthalates exposure, particularly DEHP and DBP, is important.•The mechanism of phthalates exposure and CHD awaits further investigations.
Recently, a significant reduction in ST-elevation myocardial infarction (STEMI) admission was reported from the United States and Europe where the coronavirus disease (COVID-19) caused a public ...health crisis.1,2 The door-to-device time of primary percutaneous coronary intervention (PPCI) was also delayed.3 The COVID-19 pandemic has a much less impact in Taiwan because early actions to prevent community outbreak were taken from January 2020 when mystery pneumonia in Wuhan, China was found.4 As to May 2020, there were only 443 confirmed cases in 23 million population in Taiwan and most patients were imported cases from February to April, 2020. ...although there was no reduction of STEMI admission in Taiwan, a significant delay for medical help was found during the COVID-19 pandemic. ...actions are necessary to avoid the negative impact of COVID-19 pandemic on care of STEMI.Disclosures The authors have no conflicts of interest to disclose. 2019 (Feb to Apr) (n = 1,092) 2020 (Feb to Apr) (n = 1,038) p value STEMI case number/hospital 27.3 ± 18.4 26.0 ± 16.7 0.27 Symptom onset-to-door time (min) 142 (75-338) 180 (84-460) <0.01 Door-to-device time (min) 65 (50-81) 66 (52-81) 0.20 Table 1 The case number and primary PCI for STEMI before and after COVID-19 outbreak in Taiwan
Summary Background Extracorporeal life-support as an adjunct to cardiac resuscitation has shown encouraging outcomes in patients with cardiac arrest. However, there is little evidence about the ...benefit of the procedure compared with conventional cardiopulmonary resuscitation (CPR), especially when continued for more than 10 min. We aimed to assess whether extracorporeal CPR was better than conventional CPR for patients with in-hospital cardiac arrest of cardiac origin. Methods We did a 3-year prospective observational study on the use of extracorporeal life-support for patients aged 18–75 years with witnessed in-hospital cardiac arrest of cardiac origin undergoing CPR of more than 10 min compared with patients receiving conventional CPR. A matching process based on propensity-score was done to equalise potential prognostic factors in both groups, and to formulate a balanced 1:1 matched cohort study. The primary endpoint was survival to hospital discharge, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00173615. Findings Of the 975 patients with in-hospital cardiac arrest events who underwent CPR for longer than 10 min, 113 were enrolled in the conventional CPR group and 59 were enrolled in the extracorporeal CPR group. Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0·0001) and a better 1-year survival than those who received conventional CPR (log rank p=0·007). Between the propensity-score matched groups, there was still a significant difference in survival to discharge (hazard ratio HR 0·51, 95% CI 0·35–0·74, p<0·0001), 30-day survival (HR 0·47, 95% CI 0·28–0·77, p=0·003), and 1-year survival (HR 0·53, 95% CI 0·33–0·83, p=0·006) favouring extracorporeal CPR over conventional CPR. Interpretation Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin. Funding National Science Council, Taiwan.
Background Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA
DS
-VASc score is a well-established predictor of AF stroke. Patients with AF have ...an increased risk of stroke if they have diabetes. Use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes. Methods and Results A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016-December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA
DS
-VASc score in the propensity score-matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow-up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA
DS
-VASc score in the propensity score-matched population. The stroke rate was 3.4% (95% CI, 2.8-4.2) patient-years in SGLT2i users and 4.3% (95% CI, 4.0-4.6) in nonusers (
=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 95% CI, 0.64-0.99;
=0.043) after adjustment for the CHA
DS
-VASc score. Conclusions Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first-line treatment in patients with diabetes and AF.
Associations between long-term exposure to air pollution and carotid intima-media thickness (CIMT) have inconsistent findings.
In this study we aimed to evaluate association between 1-year average ...exposure to traffic-related air pollution and CIMT in middle-aged adults in Asia.
CIMT was measured in Taipei, Taiwan, between 2009 and 2011 in 689 volunteers 35-65 years of age who were recruited as the control subjects of an acute coronary heart disease cohort study. We applied land-use regression models developed by the European Study of Cohorts for Air Pollution Effects (ESCAPE) to estimate each subject's 1-year average exposure to traffic-related air pollutants with particulate matter diameters ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5) and the absorbance levels of PM2.5 (PM2.5abs), nitrogen dioxide (NO2), and nitrogen oxides (NOx) in the urban environment.
One-year average air pollution exposures were 44.21 ± 4.19 μg/m3 for PM10, 27.34 ± 5.12 μg/m3 for PM2.5, and (1.97 ± 0.36) × 10-5/m for PM2.5abs. Multivariate regression analyses showed average percentage increases in maximum left CIMT of 4.23% (95% CI: 0.32, 8.13) per 1.0 × 10-5/m increase in PM2.5abs; 3.72% (95% CI: 0.32, 7.11) per 10-μg/m3 increase in PM10; 2.81% (95% CI: 0.32, 5.31) per 20-μg/m3 increase in NO2; and 0.74% (95% CI: 0.08, 1.41) per 10-μg/m3 increase in NOx. The associations were not evident for right CIMT, and PM2.5 mass concentration was not associated with the outcomes.
Long-term exposures to traffic-related air pollution of PM2.5abs, PM10, NO2, and NOx were positively associated with subclinical atherosclerosis in middle-aged adults.
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