Ratio For All-cause Mortality Research Articles

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis.

To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.

Risk of all-cause mortality in subjects with varying degrees of renal impairment with or without dietary protein restriction

Background and objectiveLow-protein diet (less than 0.8g/kg/day) has been practiced in the management of chronic kidney disease (estimated glomerular filtration rate [eGFR]<60ml/min/1.73m2 or urine albumin-to-creatinine ratios [UACR] ≥30mg/g) for decades. However, its effect on all-cause mortality is unclear. We investigated the association between a low-protein intake and all-cause mortality in subjects with varying degrees of renal impairment. Materials and methodsWe analyzed participants in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2010. They were divided into four groups according to their eGFR (≥60 or <60ml/min/1.73m2) and UACR (≥30 or <30mg/g). Daily protein intake of the NHANES participants could be assessed using information from the dietary interview questionnaires. The mortality data was retrieved by linking to the National Death Index till the end of 2011. The hazard ratios for all-cause mortality were evaluated by the weighted Cox proportional hazards regression models. ResultsA total of 8093 participants were analyzed. During a median follow-up of 4.7 years, participants with UACR≥30mg/g (with or without eGFR<60ml/min/1.73m2) had a higher risk of all-cause mortality compared with those having UACR<30mg/g and eGFR≥60ml/min/1.73m2 (reference group). The higher risk of mortality in participants with UACR≥30mg/g was consistently observed in those with or without a low-protein intake. ConclusionsA low-protein intake was not associated with a lower risk of all-cause mortality in subjects with varying degrees of renal impairment.

33. Evaluation of Rural-Urban Differences in Hospitalization and Mortality Rates for US COVID-19 Patients in the United States

BackgroundRural communities are among the most vulnerable and resource-scarce populations in the United States. Rural data is rarely centralized, precluding comparability across regions, and no significant studies have studied this population at scale. The purpose of this study is to present findings from the National COVID Cohort Collaborative (N3C) to provide insight into future research and highlight the urgent need to address health disparities in rural populations.N3C Patient Distribution This figure shows the geospatial distribution of the N3C COVID-19 positive population. N3C contains data from 55 data contributors from across the United States, 40 of whom include sufficient location information to map by ZIP Code centroid spatially. Of those sites, we selected 27 whose data met our minimum robustness qualifications for inclusion in our study. This bubble map is to scale with larger bubbles representing more patients. A. shows all N3C patients. B. shows only urban N3C distribution. C. shows the urban-adjacent rural patient distribution. D. shows the nonurban-adjacent rural patient distribution, representing the most isolated patients in N3C.MethodsThis retrospective cohort of 573,018 patients from 27 hospital systems presenting with COVID-19 between January 2020 and March 2021, of whom 117,897 were admitted (see Data Analysis Plan diagram for inclusion/exclusion criteria), analyzes outcomes and 30-day survival for the hospitalized population by the degree of rurality.Multivariate Cox regression analysis and mixed-effects models were used to estimate the association between rurality, hospitalization, and all-cause mortality, controlling for major risk factors associated with rural-urban health discrepancies and differences in health system outcomes. The difference in distribution by rurality is described as well as supplemented by population-level statistics to confirm representativeness.Data Analysis Plan This data analysis plan includes an overview of study inclusion and exclusion criteria, the matrix for data robustness to determine potential sites to include, and our covariate selection, model building, and residual testing strategy.ResultsThis study demonstrates a significant difference between hospital admissions and outcomes in urban versus urban-adjacent rural (UAR) and nonurban-adjacent rural (NAR) lines. Hospital admissions for UAR (OR 1.41, p< 0.001, 95% CI: 1.37 – 1.45) and NAR (OR 1.42, p< 0.001, 95% CI: 1.35 – 1.50) were significantly higher than their urban counterparts. Similar distributions were present for all-cause mortality for UAR (OR 1.39, p< 0.001, 95% CI: 1.30 – 1.49) and NAR (OR 1.38, p< 0.001, 95% CI: 1.22 – 1.55) compared to urban populations. These associations persisted despite adjustments for significant differences in BMI, Charlson Comorbidity index Score, gender, age, and the quarter of diagnosis for COVID-19.Baseline Characteristics Hospitalized COVID-19 Positive Population by Rurality Category, January 2020 – March 2021 Survival Curves in Hospitalized Patients Over 30 Days from Day of Admission This figure shows a survival plot of COVID-19 positive hospitalized patients in N3C by rural category (A), Charlson Comorbidity Index (B), Quarter of Diagnosis (C), and Age Group (D) from hospital admission through day 30. Events were censored at day 30 based on the incidence of death or transfer to hospice care. These four factors had the highest predictive power of the covariates evaluated in this study.Unadjusted and Adjusted Odds Ratios for Hospitalization and All-Cause Mortality by Rural Category, January 2020 – March 2021 This figure shows the adjusted and unadjusted odds ratios for being hospitalized or dying after hospitalization for the COVID-19 positive population in N3C. Risk is similar between adjusted and unadjusted models, suggesting a real impact of rurality on all-cause mortality. A shows the unadjusted odds ratios for admission to the hospital after a positive COVID-19 diagnosis for all N3C patients. B shows the unadjusted odds ratios for all-cause mortality at any point after hospitalization for COVID-19 positive patients. C shows the adjusted odds ratios for being admitted to the hospital after a positive COVID-19 diagnosis for all N3C patients. D shows the adjusted odds ratios for all-cause mortality for all-cause mortality at any point after hospitalization for COVID-19 positive patients. Adjusted models include adjustments for gender, race, ethnicity, BMI, age, Charlson Comorbidity Index (CCI) composite score, rurality, and quarter of diagnosis. The data provider is included as a random effect in all models.ConclusionIn N3C, we found that hospitalizations and all-cause mortality were greater among rural populations when compared to urban populations after adjustment for several factors, including age and co-morbidities. This study also identified key demographic and clinical disparities among rural patients that require further investigation.Disclosures Sally L. Hodder, M.D., Gilead (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member)

Assessing the relationship between systemic immune-inflammation index and mortality in patients with hypertrophic cardiomyopathy.

BackgroundThis study investigates the predictive value of the systemic immune-inflammation index (SII), which was calculated as platelet × neutrophil/lymphocyte ratio, for all-cause mortality in patients with hypertrophic cardiomyopathy (HCM).MethodsA total of 360 HCM patients were enrolled. They were divided into three groups based on the tertiles of baseline SII. The association between SII and all-cause mortality was analyzed.ResultsThere were 53 HCM patients who died during a mean follow-up time of 4.8 years (min: 6 days and max: 10.8 years), and the mortality rate was 3.0 per 100 person years. The cumulative mortality rate was significantly different among the three tertiles of SII (P = 0.004), and the mortality rate in tertile 3 was much higher than that in the first two tertiles. In reference to tertile 1, the fully adjusted hazard ratios of all-cause mortality were 1.02 for the tertile 2 (95% confidence interval [CI]: 0.45–2.31, P = 0.966) and 2.31 for tertile 3 (95% CI: 1.10–4.87, P = 0.027). No significant interactions between SII and other variables were observed during subgroup analysis. The discriminative power was better for mid-term outcome than that for short-term or long-term outcomes. Sensitivity analyses including patients with normal platelet and white blood cell count have revealed similar results.ConclusionSII was a significant risk factor for all-cause mortality in HCM patients. However, the discriminative power was poor to moderate. It could be used in combination with other risk factors in mortality risk stratification in HCM.

Using Point-in-Time Homeless Counts to Monitor Mortality Trends Among People Experiencing Homelessness in Los Angeles County, California, 2015‒2019.

Objectives. To report trends in mortality rates, mortality rate ratios (MRRs), and causes of death among people experiencing homelessness (PEH) in Los Angeles County, California, by using annual point-in-time homeless counts and to compare findings to published longitudinal cohort studies of homeless mortality. Methods. We enumerated homeless deaths and determined causes by using 2015-2019 medical examiner‒coroner data matched to death certificate data. We estimated midyear homeless population denominators by averaging consecutive January point-in-time homeless counts. We used annual demographic surveys of PEH to estimate age- and gender-adjusted MRRs. We identified comparison studies through a literature review. Results. Mortality rates increased from 2015 to 2019. Drug overdose was the leading cause of death. Mortality was higher among White than among Black and Latino PEH. Compared with the general population, MRRs ranged from 2.8 (95% confidence interval [CI] = 2.7, 3.0) for all causes to 35.1 (95% CI = 31.9, 38.4) for drug overdose. Crude mortality rates and all-cause MRRs from comparison cohort studies were similar to those in the current study. Conclusions. These methods can be adapted by other urban jurisdictions seeking to better understand and reduce mortality in their homeless populations. (Am J Public Health. 2021;111(12):2212-2222. https://doi.org/10.2105/AJPH.2021.306502).

Timing of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study

ObjectiveTo identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.DesignNationwide observational cohort study.SettingNational Swedish Renal Registry of patients referred...

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

BackgroundConvalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX).MethodsIn this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.ResultsA total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.ConclusionsConvalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Abstract 11665: Does the Benefit of Secondary Prevention Implantable Cardioverter-Defibrillators Vary Based on the Estimated Proportional Risk of Sudden Death?

Introduction: The Seattle Proportional Risk Model (SPRM) is a validated model developed in systolic heart failure patients without implantable cardioverter-defibrillators (ICDs) to estimate the proportion of all-cause mortality (ACM) due to sudden death. This study aims to ascertain if SPRM has utility in risk stratification for secondary prevention ICD. Methods: The AVID (Antiarrhythmics Versus Implantable Defibrillators) trial was a multicenter, randomized clinical trial in which 1,016 patients presenting with ventricular fibrillation or sustained, symptomatic ventricular tachycardia were randomized to ICD or antiarrhythmic (AA) drug therapy. Using routine clinical variables, we applied the SPRM to patient-level data (n=995 with complete data) and assessed if the ICD benefit for ACM varied with SPRM-predicted probability of sudden death. Results: SPRM was predictive of sudden death vs. non-sudden death in patients without an ICD (logistic regression p=0.005). The ICD hazard ratio for ACM was 0.59. ICD survival benefit varied with SPRM for ACM (p=0.013) with benefit (ICD HR≤0.80) seen in patients with SPRM&gt;40%. ICD benefit trended higher in patients with a history of heart failure (HF) vs no HF (HR=0.52 vs. 0.81, interaction p=0.13) (Figure 1). In comparison to the AA group, patients with either HF or SPRM&gt;51% (median) had a meaningful ICD benefit (HR=0.60, p=0.017), and patients with both HF and SPRM&gt;51% had the greatest ICD benefit (HR=0.38, p&lt;0.001). There was no ICD benefit if no HF and SPRM&lt;51% (HR=1.17). Conclusions: In a population of patients with VF or sustained VT, secondary prevention ICDs decreased ACM by 41%. ICD survival benefit varied with SPRM-predicted proportion of sudden death, and trended higher in patients with HF. SPRM may therefore provide a useful tool for risk stratifying patients for secondary prevention ICD. Figure 1: Survival benefit for ICD therapy varies with SPRM-estimated proportion of sudden death, and HF versus no HF.

Treatment with Multiple Therapeutic Classes of Medication Is Associated with Survival after Stroke

Introduction: Treatment with several therapeutic classes of medication is recommended for secondary prevention of stroke. We analyzed the associations between the number of classes of prevention medications supplied within 90 days after discharge for ischemic stroke (IS)/transient ischemic attack (TIA) and survival. Methods: This is a retrospective cohort study of adults with first-ever IS/TIA (2010–2014) from the Australian Stroke Clinical Registry individually linked with data from national pharmaceutical and Medicare claims. Exposure was the number of classes of recommended medications, i.e., blood pressure-lowering, antithrombotic, or lipid-lowering agents, supplied to patients within 90 days after discharge for IS/TIA. The longitudinal association between the number of classes of medications and survival was evaluated with Cox proportional hazards regression models using the landmark approach. A landmark date of 90 days after hospital discharge was used to separate exposure and outcome periods, and only patients who survived until this date were included. Results: Of 8,429 patients (43% female, median age 74 years, 80% IS), 607 (7%) died in the year following 90 days after discharge. Overall, 56% of patients were supplied all 3 classes of medications, 28% 2 classes of medications, 11% 1 class of medications, and 5% no class of medications. Compared to patients supplied all 3 medication classes, adjusted hazard ratios for all-cause mortality ranged from 1.43 (95% confidence interval [CI]: 1.18–1.72) in those supplied 2 medication classes to 2.04 (95% CI: 1.44–2.88) in those supplied with no medication class. Discussion/Conclusion: Treatment with all 3 classes of guideline-recommended medications within 90 days after discharge was associated with better survival. Ongoing efforts are required to ensure optimal pharmacological intervention for secondary prevention of stroke.

Looking Beyond the Allograft Survival: Long-Term, 5-Year Renal Outcome in Lung Transplant Recipients

With the increased incidence and survival of lung transplant (LTx) recipients, the risk for chronic sequelae such as chronic kidney disease (CKD) is on the rise. Data on the long-term renal outcome are scarce. We performed a retrospective chart review of 171 adults with LTx from January 1, 2014, to January 1, 2019. Primary outcomes were prevalence of CKD/end-stage renal disease, acute kidney injury (AKI) as a risk factor for future CKD, and all-cause mortality in recipients with CKD compared with the non-CKD group. Secondary outcomes were frequency of utilization of modalities for CKD (urinalysis, imaging, biopsy, nephrology consultations). Baseline median creatinine and estimated glomerular filtration rate (eGFR) were 0.8 mg/dL and 90 mL/min/1.73 m2, respectively. Of the participants, 60% (96 of 161), 67% (102 of 153), 79% (37 of 47), 86% (10 of 12) had CKD at the end of 6, 12, 36, and 60 months, respectively, and 16% were on dialysis at the end of the study period; 3% received a subsequent renal transplant, and 27% mortality was noted over a 5-year follow-up period. The odds of CKD development in patients with an AKI during index hospitalization vs no AKI was 6.22 (2.87 to 13.06, P < .0001). The odds ratio of all-cause mortality in patients with CKD compared with non-CKD was 3.36 (95% confidence interval, 1.44-8.64, P=.005). Measurement of hematuria/proteinuria, imaging, and renal biopsy were infrequently used. Given the high prevalence of AKI and CKD in this population, a multidisciplinary team approach with an early nephrology consultation will be key to improve the overall and renal outcomes in LTx recipients.

Cardioversion in patients with newly diagnosed non-valvular atrial fibrillation: observational study using prospectively collected registry data

ObjectiveTo investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation.DesignObservational...

Chemoradiation vs. Radiation Alone in the Management of Inoperable cT1-T2N1 Non-Small Cell Lung Cancer, a Propensity-Weighted Hospital Database Analysis

<h3>Purpose/Objective(s)</h3> Lobectomy followed by adjuvant chemotherapy is the standard of care for patients with clinically T1-T2N1 non-small cell lung cancer (NSCLC). However, the optimal treatment of patients who cannot undergo or refuse to undergo surgical resection is controversial. Currently, NCCN guidelines recommend concurrent chemoradiation; however, limited evidence exists to substantiate this recommendation for this particular patient population. Many groups advocate for radiation alone with standard or hypofractionated approaches. We hypothesized that concurrent chemoradiation would be associated with longer overall survival (OS) compared to hypofractionated or conventionally fractionated radiation. <h3>Materials/Methods</h3> We queried the National Cancer Database (NCDB) for patients with cT1-T2N1M0 NSCLC treated non-surgically with definitive radiation or concurrent chemoradiation between 2004 and 2016. We further restricted our cohort to patients receiving RT doses with an EQD₂ ≥ 58.4 Gy and > 5 fractions. Patients were divided into four treatment groups: standard fractionated radiation (SFRT), hypofractionated radiation (HFRT), standard fractionated chemoradiation (SFRT+CT), and hypofractionated chemoradiation (HFRT+CT). Chemoradiation was defined as chemotherapy and radiation with start dates within 30 days. To address confounding by indication, inverse probability of treatment weights (IPTW) were constructed regressing sociodemographic, clinical, and facility characteristics on treatment group in a multinomial regression model. Weighted Cox proportional hazard regression models were then used to evaluate the relative hazard of death with SFRT set as the referent treatment group. <h3>Results</h3> A total of 2,534 patients met inclusion criteria and of these 2,200 patients (57,462.83 person-months) had complete data for all confounders and were included in the analytic sample. Of the 2,200 patients 26.6% received SFRT, 7% received HFRT, 62.1% received SFRT+CT, and 4.2% received HFRT+CT. The median EQD₂ (IQR) were: SFRT 66 Gy (60-68), HFRT 66.7 Gy (62.5-71.9), SFRT+CT 65.5 Gy (60-66), and HFRT+CT 67.6 Gy (65.1-72.3). 27% of patients were still alive 36 months after the initiation of RT (17.3% of SFRT, 20.3% of HFRT, 33.2% of SFRT+CT, and 21.8% of HFRT+CT). After IPTW propensity weighting, the probability of death at 3 years was compared between the treatment groups and only SFRT+CT was associated with longer OS. Compared with SFRT, the hazard ratio for all-cause mortality for those treated with SFRT+CT was 0.67 (95% CI: 0.57-0.75), for HFRT was 0.86 (95% CI: 0.61-1.06), and for HFRT+CT was 0.81 (95% CI 0.61-1.06). <h3>Conclusion</h3> To our knowledge, this is the first large database propensity weighted analysis of patients with cT1-T2N1M0 NSCLC managed non-surgically with definitive radiation or chemoradiation. In this group, treatment with SFRT+CT is associated with longer OS relative to treatment with radiation alone.

Prognostic value of left atrial function in patients with severe primary mitral regurgitation undergoing mitral valve repair

Abstract Background Timing of mitral valve surgery for primary mitral regurgitation (MR) remains challenging. Since MR has a significant hemodynamic impact on the left atrium (LA), assessment of LA function may have prognostic value in these patients which is incremental to LA volume and left ventricular (LV) remodeling parameters. Purpose This study sought to investigate whether preoperative assessment of LA reservoir strain (LASr) by speckle tracking echocardiography is associated with long-term outcome in patients undergoing mitral valve repair for severe primary MR. Methods Echocardiography was performed prior to mitral valve surgery in 566 patients (age 64±12 years, 66% men) with severe primary MR. Complete clinical information was collected and the endpoint was all-cause mortality after operation. The study population was divided based on a cut-off value of LASr (22%) derived from a spline curve analysis (hazard ratio for all-cause mortality &amp;gt;1). Results Patients with LASr ≤22% (n=277) were significantly older, had more impaired renal function and were more symptomatic (NYHA functional class III to IV) compared to patients with LASr &amp;gt;22% (n=289). In terms of echocardiographic data, patients with LASr ≤22% had significantly lower LV ejection fraction and LV global longitudinal strain (LV-GLS) and significantly higher systolic pulmonary artery pressures and LA volume index compared with patients with LASr &amp;gt;22%. During a median follow-up of 95 (56 – 147) months, 129 patients (22.8%) died. Patients with LASr ≤22% experienced significantly higher mortality rates compared to patients with LASr &amp;gt;22% (log rank chi-square 35.1; p&amp;lt;0.001) (Figure). On multivariable analysis, age (hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.03 to 1.09; p&amp;lt;0.001), LV-GLS (HR: 1.08; 95% CI: 1.02 to 1.15; p=0.014) and LASr (HR: 0.96; 95% CI: 0.93 to 0.99; p=0.014) were independently associated with all-cause mortality. The addition of LASr to a clinical model (including: age, coronary artery disease, estimated glomerular filtration rate, NYHA class III-IV, atrial fibrillation, LV end-diastolic volume index, LV ejection fraction, LV-GLS, LA volume index and systolic pulmonary artery pressure) showed a significant increase in the chi-square value (chi-square differences = 6.9; p=0.011), demonstrating the incremental prognostic value of LASr in patients with primary MR. Conclusions Preoperative LASr is independently associated with all-cause mortality in patients undergoing mitral valve repair for primary MR, has incremental prognostic value over LA volume and LVEF and might therefore be helpful to guide surgical timing. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Jan Stassen has received an ESC training grant (Appehab724.011364741) Association of LASr and outcome

The impact of non-pharmacological therapies on cardiovascular outcomes in patients with refractory angina: a systematic review and meta-analysis of randomized controlled trials

Abstract Despite advances in revascularization techniques and optimal medical management, refractory angina (RFA) represents an essential group of patients where progress has stalled, and in which therapeutic approaches remain uncertain. Numerous randomized control trials have reported clinical outcomes on a variety of treatments but to date no direct outcome comparison has been made. Our aim is to investigate and compare the outcomes of these different non-pharmacological technologies in RFA, centring on major adverse cardiac events and all-cause mortality. We performed a systematic review and meta-analysis of randomized controlled trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive search was performed of PubMed, EMBASE (Excerpta Medica database),Cochrane, ClinicalTrials.gov, Google Scholar databases of randomized controlled trials, and scientific session abstracts. Studies were deemed eligible if they met the following criteria: (1) full-length publications in peer-reviewed journals; (2) evaluated non-pharmacological therapies use in patients with no further revascularization options while on optimal medical treatment; (3) patients had ongoing angina, Canadian Cardiovascular Society class II–IV; and (4) included a placebo/control arm. We calculated risk ratios for all-cause mortality, combined MACE events. We assessed heterogeneity using χ2 and I2 tests. We analysed 3292 citations with 51 randomized control trials testing 9 therapies including angiogenic proteins, stem-cell therapy, lipoprotein apheresis, coronary sinus reducer, spinal cord stimulator, percutaneous laser revascularization, shock-wave therapy, transmyocardial laser revascularization and enhanced external counter pulsation all meeting the inclusion criteria (table 1). Our analysis identified stem cell therapy as the only therapy with a reduction in all-cause mortality (Odds ratio, 0.45; CI, 0.21–1.00) (figure 1). A corresponding reduction in major adverse cardiac events (MACE) was also seen with stem cell therapy (OR 0.48: CI 0.30–0.75) alongside patients who received angiogenic proteins (OR 0.72: CI 0.55–0.93) and cardiac shockwave therapy (OR, 0.21: CI 0.10–0.46) Improvements in secondary measures of angina symptoms or frequency were seen with stem cell therapy, angiogenic proteins, coronary sinus reducer, spinal cord stimulator, shock-wave therapy, transmyocardial laser revascularization and enhanced external counterpulsation. This is the largest meta-analysis comparing outcomes of novel technologies used in refractory angina. This suggests that stem cell therapy is the only non-pharmacological therapy for RFA associated with a reduction in mortality, MACE and anginal symptoms. We propose further larger randomized control trials, to support these findings. Funding Acknowledgement Type of funding sources: None. Table 1. Randomized control trials and outcomesFigure 1. All-cause mortality forest plot

Restrictive vs liberal blood transfusion strategy in patients with symptomatic coronary artery disease: meta-analysis from randomized controlled trials

Abstract Background Anemia is common in patients with symptomatic coronary artery disease. Observational studies investigated blood transfusion threshold in symptomatic coronary artery disease but results were conflicting. Meta-analyses evaluating transfusion threshold utilized data mainly from observational trials but no meta-analysis, to our knowledge, used data solely from randomized clinical trials. Objective The goal of our study is to evaluate efficacy and safety outcomes in anemic patients presenting with symptomatic coronary artery disease using pooled data from randomized clinical trials. Methods We queried Medline, Embase and Cochrane data bases for randomized clinical trials comparing restrictive blood transfusion (defined as transfusion when hemoglobin is less than 8 gm/dl) vs liberal blood transfusion (transfusion when hemoglobin is less than 10 gm/dl) in patients presenting with symptomatic artery disease or acute coronary syndrome. We identified 3 randomized controlled trials; MINT, CRIT and REALITY trials. Data were pooled from 3 trials. Efficacy outcomes evaluated were all-cause mortality and New or recurrent myocardial infarction. Safety outcomes were congestive heart failure at 30-day follow up. Results A total of 820 patients were included in our meta-analysis; 420 patients in restrictive blood transfusion protocol and 400 in liberal blood transfusion protocol There was no difference between two groups at 30-day follow up in all identified outcomes (all-cause mortality, new or recurrent myocardial infarction, and Congestive heart failure). 55 patients died (22/420 in restrictive group and 33/400 in liberal group). Risk ratio of all-cause mortality in restrictive group was 0.63 [95% CI (0.38–1.07), P=0.09, I2=30%]. 15/420 in restrictive group and 16/400 in liberal group had new or recurrent myocardial infarction. Risk ratio of myocardial infarction in restrictive group was 0.91 [95% CI (0.46–1.80), P=0.78, I2=0%]. 20/420 patients in restrictive group and 24/400 in liberal group had congestive heart failure with risk ratio of 0.80 [95% CI (0.19–3.37), P=0.30, I2=76%] in restrictive group. Conclusion Our meta-analysis showed similar outcomes between restrictive and liberal transfusion policies in patients presenting with symptomatic coronary artery disease of acute myocardial infarction. Our findings are consistent with available data about restricting transfusion in general population. Restricting blood transfusion might be cost-effective. Further studies are warranted to evaluate long term safety and efficacy of such approach. Funding Acknowledgement Type of funding sources: None.

Rhythm control in patients with atrial fibrillation and heart failure: a meta-analysis of randomized controlled trials

Abstract Background Atrial fibrillation (AF) is a common arrhythmia that can promote or worsen heart failure (HF). Limited data exist to guide treatment for patients with AF with HF regarding rate versus rhythm control. Purpose To perform a meta-analysis of randomized controlled trials (RCT) in the determination of the efficacy of rhythm control as compared to rate control among patients with AF and HF. Methods Extensive search of PubMed, Cochrane Library, Ovid, EMBASE, Google scholar, and Medline was done up to October 2020. Studies were limited to RCTs comparing rhythm control in patients with atrial fibrillation and heart failure with rate control. Outcome measures include all-cause mortality and cardiovascular mortality. Statistical analysis was done using Review manager V5.3. Results A total of 9800 patients were included in the pooled analysis of the comparison of rhythm control versus rate control strategy in patients with AF and HF. All pooled analyses were done using random effects model. The pooled risk ratio for all-cause mortality of rate control vs rhythm control did not achieve significance at 1.15, with 95% CI 0.91 to 1.45, and p=0.24. There was statistically significant heterogeneity across the two studies with I2 of 54% and p=0.02 (Figure 1A). The pooled risk ratio for cardiovascular mortality in rate control strategy vs rhythm control is 1.19, with 95% CI 0.94 to 1.50, and p=0.15 (Figure 1B). Eight trials with 9987 participants reported stroke. The pooled risk ratio of stroke in rate control vs rhythm control is 1.11, with 95% CI 0.84 to 1.46, and p=0.47 (Figure 1C). The 95% CI for the pooled risk ratio cross 1.00, indicating an equivocal result. Our results do not indicate statistical heterogeneity across the studies with I2 of 28% and p=0.27. Seven trials with 8311 participants reported bleeding. The pooled risk ratio of hospitalization for bleeding in rate control vs rhythm control is 1.18, with 95% CI 0.81 to 1.73, and p=0.39 (Figure 1D). Thus, we have insufficient evidence to demonstrate whether rate or rhythm control have significantly higher or lower risk for bleeding. Four trials with 8468 participants reported hospitalization rate. The pooled risk ratio of hospitalization in rate control compared to rhythm control is 0.96, with 95% CI 0.86 to 1.07, and p=0.42 (Figure 1E). None of the studies individually showed statistically significant differences but AF–CHF showed benefit of rate control in the first year after enrolment (p=0.001) and a tendency favouring rate control (p=0.06) when the study was analysed in full length except for AF-CHF. Conclusion Among patients with AF and concomitant HF, there is no sufficient evidence between rate and rhythm control strategies in their effects to rates of mortality and major clinical outcomes; therefore, choosing an appropriate therapeutic strategy should consider individual variations such as patient preferences, comorbidities, and treatment cost. Funding Acknowledgement Type of funding sources: None. Forest Plot A–CForest Plot D–E

The Combined Prognostic Significance of Alkaline Phosphatase and Intracranial Arterial Calcifications in Hemodialysis Patients

Introduction: The prevalence of intracranial arterial calcification (ICAC) in maintenance hemodialysis (MHD) patients is about 90%, and its severity is correlated with age, hemodialysis vintage, and mineral bone disease. Elevated concentrations of calcium and phosphorus are not sufficient for medial calcification because of inhibition by pyrophosphate. Alkaline phosphatase (ALP) promotes calcification by hydrolyzing extracellular pyrophosphate. Epigenetic mechanisms involving ALP inhibition by apabetalone were investigated as a potential target for preventing vascular calcifications (VCs). This study assessed the combined impact of VCs and elevated serum ALP on mortality among chronic HD patients. Methods: VCs represented by ICAC were measured simultaneously with mineral bone disease parameters including serum ALP of MHD patients who underwent noncontrast brain computed tomography from 2015 to 2018 in our institution. Results: This retrospective study included 150 MHD patients (mean age 71.3 ± 12.1 years, 60.1% male). Of the total cohort, 12 (7.8%) had no brain calcifications and 69 (45.1%) had multiple intracranial calcifications. Considering the patients with normal ALP and no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 4.6 (95% CI: 1.7–12.7) among patients with brain calcifications and normal ALP (p = 0.003) and odds ratios for all-cause mortality of 6.1 (95% CI: 2.1–17.7) among patients with brain calcifications and elevated ALP (p= 0.001). Conclusion: We found an independent association between ICAC and the risk of death among MHD patients. The combined effect of ICAC and elevated ALP was associated with a higher odds ratio for all-cause mortality in MHD patients and may contribute to the risk stratification of these patients.

Usefulness of Diastolic Function Score as a Predictor of Long-Term Prognosis in Patients With Acute Myocardial Infarction.

Background: Left ventricular diastolic function (LVDF) evaluation using a combination of several echocardiographic parameters is an important predictor of adverse events in patients with acute myocardial infarction (AMI). To date, the clinical impact of each individual LVDF marker is well-known, but the clinical significance of the sum of the abnormal diastolic function markers and the long-term clinical outcome are not well-known. This study aimed to investigate the usefulness of LVDF score in predicting clinical outcomes of patients with AMI.Methods: LVDF scores were measured in a 2,030 patients with AMI who underwent successful percutaneous coronary intervention from 2012 to 2015. Four LVDF parameters (septal e′ ≥ 7 cm/s, septal E/e′ ≤ 15, TR velocity ≤ 2.8 m/s, and LAVI ≤ 34 ml/m2) were used for LVDF scoring. The presence of each abnormal LVDF parameter was scored as 1, and the total LVDF score ranged from 0 to 4. Mortality and hospitalization due to heart failure (HHF) in relation to LVDF score were evaluated. To compare the predictive ability of LVDF scores and left ventricular ejection fraction (LVEF) for mortality and HHF, receiver operating characteristic (ROC) curve and landmark analyses were performed.Results: Over the 3-year clinical follow-up, all-cause mortality occurred in 278 patients (13.7%), while 91 patients (4.5%) developed HHF. All-cause mortality and HHF significantly increased as LVDF scores increased (all-cause mortality–LVDF score 0: 2.3%, score 1: 8.8%, score 2: 16.7%, score 3: 31.8%, and score 4: 44.5%, p < 0.001; HHF–LVDF score 0: 0.6%, score 1: 1.8%, score 2: 6.3%, score 3: 10.3%, and score 4: 18.2%, p < 0.001). In multivariate analysis, a higher LVDF score was associated with significantly higher adjusted hazard ratios for all-cause mortality and HHF. In landmark analysis, LVDF score was a better predictor of long-term mortality than LVEF (area under the ROC curve: 0.739 vs. 0.640, p < 0.001).Conclusion: The present study demonstrated that LVDF score was a significant predictor of mortality and HHF in patients with AMI. LVDF scores are useful for risk stratification of patients with AMI; therefore, careful monitoring and management should be performed for patients with AMI with higher LVDF scores.

1034All-cause mortality in Australia: impact of social isolation and living alone

Abstract Background The prevalence of social isolation (SI), living alone (LA) and loneliness among older people in Australia is 17%, 25% and 19% respectively. In a meta-analysis of 70 prospective studies undertaken by Holt-Lunstad et al (2015)1 they found, after controlling for covariates, a 29% increased all-cause mortality for SI, 32% for LA, and 26% for loneliness. But how accurate is this evidence for Australia considering that the meta-analysis only included three Australian studies; all only reporting on LA, and only one reported a significant effect of LA on total mortality. Methods We conducted a record linkage study in NSW using the Social Economic and Environmental Factors sub-study questionnaire data (n = 60,399) from the 45 and Up Study (n = 267,153) and death registrations (Centre for Health Record Linkage). Overall, 20% were SI and 18% were LA. Univariate and multivariable generalised linear models were used to estimate crude and adjusted 7-year all-cause mortality rate ratios (MRR). Results Crude MRR were 28% higher for SI and 98% higher for LA. When adjusted by age and sex they were still significantly higher (28% and 23% respectively). However, when controlled for covariates, SI was 9% higher [AdjRR(95%CI):1.09(1.01-1.18)] and LA had no effect on mortality [AdjRR(95%CI):1.05(0.94-1.18)]. Conclusions As was the case for the Australian studies used in the meta-analysis we found no association between LA and all-cause mortality. We did however find a small significant effect for SI. Key messages Applying the overall meta-analysis results to Australia overestimates the effect of SI and LA on increased all-cause mortality.

Diagnostic and Prognostic Performance of Aortic Valve Calcium Score with Cardiac CT for Aortic Stenosis: A Meta-Analysis.

To evaluate the diagnostic and prognostic performance of the aortic valve calcium score (AVCS) with the Agatston method using CT in aortic stenosis (AS) and to assess mean AVCS according to AS severity. In this meta-analysis, PubMed, Embase, and Cochrane were searched from January 1, 1980, to December 31, 2020, for studies reporting sensitivity and specificity of AVCS using CT for severe AS, mean AVCS in severe and nonsevere AS, and/or hazard ratios for all-cause mortality in AS. Data were pooled using random effect models and meta-analysis software. Twelve studies (six diagnostic, three prognostic, and 10 reporting mean AVCS by AS severity) were included for analysis. A total of 4101 patients (2255 with severe AS) were described in these 12 studies. Pooled sensitivity and specificity were 82% (95% CI: 80, 84) and 78% (95% CI: 75, 81), respectively. Pooled mean AVCS were 3219 (95% CI: 2795, 3643) for severe AS, compared with 1252 (95% CI: 863, 1640) for nonsevere AS, 1808 (95% CI: 1163, 2452) for moderate AS, and 584 (95% CI: 309, 859) for mild AS. Pooled hazard ratio for AVCS as a binary threshold to predict mortality was 2.11 (95% CI: 1.11, 4.12). AVCS had moderate to high sensitivity and specificity for identifying severe AS and was also a useful prognostic imaging marker in AS. Mean AVCS categorized by AS severity may help guide clinical management.Keywords CT, Aortic Valve, Valves, Meta-Analysis© RSNA, 2021.