Brief report: Effect of cardiac multi-morbidity on COVID hospitalization outcomes.

BACKGROUND: The COVID-19 pandemic has stretched healthcare resources thin and led to significant morbidity and mortality. There have been no studies utilizing national data to investigate the role of cardiac risk factors on outcomes of COVID hospitalizations. The aim of this study was to examine the effect of cardiac multimorbidity on healthcare utilization and outcomes among COVID hospitalizations during the first year of the pandemic. METHODS: Using the national inpatient sample (NIS), we identified all adult hospital admissions with a primary diagnosis of COVID in 2020, using International Classification of Diseases, Tenth Revision, Clinical Modification codes (ICD010-CM). Coronary artery disease, diabetes mellitus, heart failure, peripheral vascular disease, previous stroke, and atrial fibrillation were then identified as cardiac comorbidities using ICD-10-CM codes. Multivariable logistic regression was used to evaluate the effect of cardiac multimorbidity on mortality and mechanical ventilation. RESULTS: We identified 1,005,040 primary COVID admissions in 2020. Of these admissions, 216,545 (20.6%) had CAD, 413,195 (39.4%) had DM, 176,780 (16.8%) had HF, 159,700 (15.2%) had AF, 30735 (2.9%) had PVD, and 25,155 (2.4%) had a previous stroke. When stratified by number of comorbidities, 428390 (40.8%) had 0 comorbidities, 354960 (33.8%) had 1, 161225 (15.4%) had 2, and 105465 (10.0%) had 3+ comorbidities. COVID hospitalizations with higher cardiac multimorbidity had higher mortality rates (p<0.001) higher MV rates (p<0.001). In our multivariable regression, these associations remained with increasing odds for mortality with each stepwise increase in cardiac multimorbidity (1: OR 1.48 (1.45-1.50); 2: OR 2.13 (2.09-2.17); 3+: OR 2.43 (2.38-2.48), p<0.001, all). CONCLUSIONS: Our study is the first national examination of the impact of cardiac comorbidities on COVID outcomes. A higher number of cardiac comorbidities was associated with significantly higher rates of MV and in-hospital mortality, independent of age. Future, more granular, and longitudinal studies are needed to further examine these associations.

Rationale, Design, and Methodology of the MORCOR-TURK Trial: Predictors of In-hospital MORtality in CORonary Care Patients in Turkey.

BACKGROUND: Coronary care units are sophisticated clinics established to reduce deaths due to acute cardiovascular events. Current data on coronary care unit mortality rates and predictors of mortality in Turkey are very limited. The MORtality predictors in CORonary care units in TURKey (MORCOR-TURK) trial was designed to provide information on the mortality rates and predictors in patients followed in coronary care units in Turkey. METHODS: The MORCOR-TURK trial will be a national, observational, multicenter, and noninterventional study conducted in Turkey. The study population will include coronary care unit patients from 50 centers selected from all regions in Turkey. All consecutive patients admitted to coronary care units with cardiovascular diagnoses between 1 and 30 September 2022 will be prospectively enrolled. All data will be collected at one point in time, and the current clinical practice will be evaluated (ClinicalTrials.gov number NCT05296694). In the first step of the study, admission diagnoses, demographic characteristics, basic clinical and laboratory data, and in-hospital management will be assessed. At the end of the first step, the predictors and rates of in-hospital mortality will be documented. The second step will be in cohort design, and discharged patients will be followed up till 1 year. Predictors of short- and long-term mortality will be assessed. Moreover, a new coronary care unit mortality score will be generated with data acquired from this cohort. RESULTS: The short-term outcomes of the study are planned to be shared by early 2023. CONCLUSION: The MORCOR-TURK trial will be the largest and most comprehensive study in Turkey evaluating the rates and predictors of in-hospital mortality of patients admitted to coronary care units.

Validation study on definition of cause of death in Japanese claims data.

Identifying the cause of death is important for the study of end-of-life patients using claims data in Japan. However, the validity of how cause of death is identified using claims data remains unknown. Therefore, this study aimed to verify the validity of the method used to identify the cause of death based on Japanese claims data. Our study population included patients who died at two institutions between January 1, 2018 and December 31, 2019. Claims data consisted of medical data and Diagnosis Procedure Combination (DPC) data, and five definitions developed from disease classification in each dataset were compared with death certificates. Nine causes of death, including cancer, were included in the study. The definition with the highest positive predictive values (PPVs) and sensitivities in this study was the combination of "main disease" in both medical and DPC data. For cancer, these definitions had PPVs and sensitivities of > 90%. For heart disease, these definitions had PPVs of > 50% and sensitivities of > 70%. For cerebrovascular disease, these definitions had PPVs of > 80% and sensitivities of> 70%. For other causes of death, PPVs and sensitivities were < 50% for most definitions. Based on these results, we recommend definitions with a combination of "main disease" in both medical and DPC data for cancer and cerebrovascular disease. However, a clear argument cannot be made for other causes of death because of the small sample size. Therefore, the results of this study can be used with confidence for cancer and cerebrovascular disease but should be used with caution for other causes of death.

Risk of death following COVID-19 vaccination or positive SARS-CoV-2 test in young people in England.

Several studies have reported associations between COVID-19 vaccination and risk of cardiac diseases, especially in young people; the impact on mortality, however, remains unclear. We use national, linked electronic health data in England to assess the impact of COVID-19 vaccination and positive SARS-CoV-2 tests on the risk of cardiac and all-cause mortality in young people (12 to 29 years) using a self-controlled case series design. Here, we show there is no significant increase in cardiac or all-cause mortality in the 12 weeks following COVID-19 vaccination compared to more than 12 weeks after any dose. However, we find an increase in cardiac death in women after a first dose of non mRNA vaccines. A positive SARS-CoV-2 test is associated with increased cardiac and all-cause mortality among people vaccinated or unvaccinated at time of testing.

Cinco bilhões de pessoas estão expostas à gordura trans, que pode levar a doenças cardíacas

De acordo com um novo relatório da Organização Mundial da Saúde (OMS), cinco bilhões de pessoas em todo o mundo permanecem desprotegidas das gorduras trans prejudiciais, aumentando seu risco de doenças cardíacas e morte.

Research Note: COVID-19 Is Not an Independent Cause of Death.

The COVID-19 pandemic has had overwhelming global impacts with deleterious social, economic, and health consequences. To assess the COVID-19 death toll, researchers have estimated declines in 2020 life expectancy at birth (e0). When data are available only for COVID-19 deaths, but not for deaths from other causes, the risks of dying from COVID-19 are typically assumed to be independent of those from other causes. In this research note, we explore the soundness of this assumption using data from the United States and Brazil, the countries with the largest number of reported COVID-19 deaths. We use three methods: one estimates the difference between 2019 and 2020 life tables and therefore does not require the assumption of independence, and the other two assume independence to simulate scenarios in which COVID-19 mortality is added to 2019 death rates or is eliminated from 2020 rates. Our results reveal that COVID-19 is not independent of other causes of death. The assumption of independence can lead to either an overestimate (Brazil) or an underestimate (United States) of the decline in e0, depending on how the number of other reported causes of death changed in 2020.

Galectin-3 is an independent predictor of postoperative atrial fibrillation and survival after elective cardiac surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication after heart surgery and is associated with thromboembolic events, prolonged hospital stay, and adverse outcomes. Inflammation and fibrosis are involved in the pathogenesis of atrial fibrillation. OBJECTIVE: The purpose of this study was to assess whether galectin-3, which reflects preexisting atrial fibrosis, has the potential to predict POAF and mortality after cardiac surgery. METHODS: Four hundred seventy-five consecutive patients (mean age 67.4 ± 11.8 years; 336 (70.7%) male) undergoing elective heart surgery at the Medical University of Vienna were included in this prospective single-center cohort study. Galectin-3 plasma levels were assessed on the day before surgery. RESULTS: The 200 patients (42.1%) who developed POAF had significantly higher galectin-3 levels (9.60 ± 6.83 ng/mL vs 7.10 ± 3.54 ng/mL; P < .001). Galectin-3 significantly predicted POAF in multivariable logistic regression analysis (adjusted odds ratio per 1-SD increase 1.44; 95% confidence interval 1.15-1.81; P = .002). During a median follow-up of 4.3 years (interquartile range 3.4-5.4 years), 72 patients (15.2%) died. Galectin-3 predicted all-cause mortality in multivariable Cox regression analysis (adjusted hazard ratio per 1-SD increase 1.56; 95% confidence interval 1.16-2.09; P = .003). Patients with the highest-risk galectin-3 levels according to classification and regression tree analysis (>11.70 ng/mL) had a 3.3-fold higher risk of developing POAF and a 4.4-fold higher risk of dying than did patients with the lowest-risk levels (≤5.82 ng/mL). CONCLUSION: The profibrotic biomarker galectin-3 is an independent predictor of POAF and mortality after cardiac surgery. This finding highlights the role of the underlying arrhythmogenic substrate in the genesis of POAF. Galectin-3 may help to identify patients at risk of POAF and adverse outcome after cardiac surgery.

Changes in mortality in a non-industrialized Portugal: Coimbra Municipal Cemetery records (1861-1914) and identified osteological collections.

OBJECTIVE: To investigate if there were changes in mortality knowing that industrialization was a slow and late process in Portugal. MATERIALS: The biographic information (1) of the individuals buried at the Coimbra Municipal Cemetery, considering three quinquennia: 1861-1865 (n = 1111, 18.3%), 1870-1974 (n = 2602, 42.7%), 1910-1914 (n = 2374, 39.0%), related to the periods before, during and at the end of the second industrialization and (2) of the Coimbra identified osteological collections (CIOC, N = 1796) composed of individuals who were born and died in the city. METHODS: Excel databases with the biographic information were analyzed with SPSS. RESULTS: Data from the cemetery show statistically significant differences between sexes and age-at-death mortalities. Non-adult mortality (higher in the age range from 1 to 7 years) has decreased over time which has increased mean age-at-death. The main adult occupations are domestic work (females) and craft activities (males). Child labor is common after the age of 14. The main causes of death (in both cemetery and CIOC records) were infections, respiratory diseases, heart disease, and malignant neoplasm. Among the communicable diseases, tuberculosis accounted for the highest number of deaths. The identified individuals have lesions compatible with tuberculosis and sinusitis while malignant neoplasms are more difficult to identify. The high prevalence of heart disease can overshadow other causes of death. CONCLUSIONS: In the absence of industrialization, tuberculosis, heart disease, and malignant neoplasms increased over time, while respiratory diseases decreased. SIGNIFICANCE: Mortality profile changed between 1861-1864 and 1910-1914 in Coimbra. LIMITATIONS: The causes of death were studied, but not all diseases. SUGGESTIONS FOR FURTHER RESEARCH: Study of other cemetery records for further comparison.

The risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders with cobalt-chrome-containing total hip arthroplasty implants : an analysis of the National Joint Registry.

AIMS: A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database. METHODS: Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. RESULTS: There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes. CONCLUSION: CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J 2022;104-B(3):359-367.

Serum selenium concentrations and risk of all-cause and heart disease mortality among individuals with type 2 diabetes.

BACKGROUND: The impact of selenium status on the long-term health of people with type 2 diabetes (T2D) remains unclear. OBJECTIVES: To prospectively examine the association of serum selenium concentrations with all-cause and heart disease mortality among individuals with T2D. METHODS: This analysis included 3199 adults with T2D from the third NHANES (NHANES III) and NHANES (2003-2004, 2011-2014). Mortality from heart disease and all causes was linked to National Death Index mortality data. Cox proportional hazard models were used to estimate HRs and 95% CIs. RESULTS: The median (IQR) concentration of serum selenium was 127.0 (115.0, 139.1) µg/L. During an average 12.6-y follow-up, 1693 deaths were documented, including 425 heart disease deaths. Compared with participants in the lowest quartile of selenium, the multivariate-adjusted HRs (95% CIs) for participants in the highest quartile were 0.69 (0.54, 0.89) for all-cause mortality (P-trend = 0.002) and 0.66 (0.45, 0.99) for heart disease mortality (P-trend = 0.03). In addition, a linear dose-response relation between serum selenium (range: 89-182 µg/L) and mortality was observed. For per-unit increment in natural log-transformed serum selenium, there was a 64% lower risk of all-cause mortality and a 66% lower risk of heart disease mortality (both P < 0.05). Similar results were observed when stratifying by age, sex, race, smoking status, BMI, physical activity, diabetes duration, and HbA1c concentrations. CONCLUSIONS: Our study suggested that higher selenium concentration was associated with lower all-cause and heart disease mortality among individuals with T2D. More studies are needed to confirm these findings.

Total knee replacement in osteoarthritis patients on reducing the risk of major adverse cardiac events: a 18-year retrospective cohort study.

OBJECTIVES: Osteoarthritis (OA) is a common degenerative joint disease, and total knee replacement (TKR) is a successful surgical intervention for knee OA treatment. However, the risks of mortality and major cardiovascular events (MACEs) in patients receiving TKR remain unclear. This study investigated the risks of mortality and MACEs in knee OA patients who received TKR. METHODS: For this population-based cohort study, the Longitudinal Health Insurance Database 2000 was used. Two million individuals with knee OA defined by ICD-9-CM codes who received physical therapy between 1999 and 2017 were selected. For propensity score matching (PSM), we considered the year of knee OA diagnosis, demographics, comorbidities, co-medications, and knee OA-related hyaluronic acid or physical therapy at baseline. After PSM, regression analyses were performed to assess the association of mortality or MACEs with TKR and non-TKR individuals. RESULTS: We identified patients (n = 189,708) with a new diagnosis of knee OA between 2000 and 2017. In total, 10,314 propensity-score-paired TKR and non-TKR individuals were selected. The PSM cohort algorithm revealed that the risk of mortality or MACEs was lower in the TKR group (adjusted hazard ratio: 0.791; 95% confidence interval: 0.755-0.830) than in the non-TKR group. CONCLUSIONS: Patients with knee OA who received TKR had decreased risks of mortality and MACEs than those who did not receive TKR. Moreover, the TKR group received a reduced dosage of nonsteroidal anti-inflammatory drugs at the 1-year follow-up.

Circumstances surrounding end-of-life in pediatric patients pre- and post-heart transplant: a report from the Pediatric Heart Transplant Society.

BACKGROUND: Although mortality has decreased considerably in pediatric heart transplantation, waitlist and post-transplant death rates remain notable. End-of-life focused research in this population, however, is very limited. This Pediatric Heart Transplant Society study aimed to describe the circumstances surrounding death of pediatric heart transplant patients. METHODS: A retrospective analysis of the multi-institutional, international, Pediatric Heart Transplant Society registry was conducted. Descriptive statistics and univariate analyses were performed to 1) describe end-of-life in pediatric pre- and post-heart transplant patients and 2) examine associations between location of death and technological interventions at end-of-life with demographic and disease factors. RESULTS: Of 9217 patients (0-18 years) enrolled in the registry between 1993 and 2018, 2804 (30%) deaths occurred; 1310 while awaiting heart transplant and 1494 post-heart transplant. The majority of waitlist deaths (89%) occurred in the hospital, primarily in ICU (74%) with most receiving mechanical ventilation (77%). Fewer post-transplant deaths occurred in the hospital (22%). Out-of-hospital death was associated with older patient age (p < .01). CONCLUSIONS: ICU deaths with high use of technological interventions at end-of-life were common, particularly in patients awaiting heart transplant. In this high mortality population, findings raise challenging considerations for clinicians, families, and policy makers on how to balance quality of life amidst high risk for hospital-based death.

ECG pathology and its association with death in critically ill COVID-19 patients, a cohort study.

BACKGROUND: We investigated the prevalence of ECG abnormalities and their association with mortality, organ dysfunction and cardiac biomarkers in a cohort of COVID-19 patients admitted to the intensive care unit (ICU). METHODS: This cohort study included patients with COVID-19 admitted to the ICU of a tertiary hospital in Sweden. ECG, clinical data and laboratory findings during ICU stay were extracted from medical records and ECGs obtained near ICU admission were reviewed by two independent physicians. RESULTS: Eighty patients had an acceptable ECG near ICU-admission. In the entire cohort 30-day mortality was 28%. Compared to patients with normal ECG, among whom 30-day mortality was 16%, patients with ECG fulfilling criteria for prior myocardial infarction had higher mortality, 63%, odds ratio (OR) 9.61 (95% confidence interval (CI) 2.02-55.6) adjusted for Simplified Acute Physiology Score 3 and patients with ST-T abnormalities had 50% mortality and OR 6.05 (95% CI 1.82-21.3) in univariable analysis. Both prior myocardial infarction pattern and ST-T pathology were associated with need for vasoactive treatment and higher peak plasma levels of troponin-I, NT-pro-BNP (N-terminal pro-Brain Natriuretic Peptide), and lactate during ICU stay compared to patients with normal ECG. CONCLUSION: ECG with prior myocardial infarction pattern or acute ST-T pathology at ICU admission is associated with death, need for vasoactive treatment and higher levels of biomarkers of cardiac damage and strain in severely ill COVID-19 patients, and should alert clinicians to a poor prognosis.

SGLT-2 inhibitors and cardiorenal outcomes in patients with or without type 2 diabetes: a meta-analysis of 11 CVOTs.

BACKGROUND: It has been suggested that sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduce the cardiorenal risk in patients with type 2 diabetes (T2D). The purpose of this study is to provide an update of all large cardiovascular outcome trials (CVOTs) with SGLT-2 inhibitors to assess their cardiorenal efficacy in patients with and without T2D. METHODS: An electronic search up to 30 September 2021 was conducted in PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. to determine eligible trials. We included CVOTs comparing any SGLT-2 inhibitor with placebo, reporting desired cardiovascular or renal outcomes and with a follow-up duration of at least 6 months. RESULTS: Eleven CVOTs, with data from five SGLT-2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin) and 77,541 participants, were included. In the overall analysis, the risk of the composite CV mortality or hospitalization for heart failure (HF) was reduced by 23% (HR = 0.77, 95% CI 0.73-0.82, P < 0.001) compared with placebo, with not significant heterogeneity (I2 = 26%, P = 0.20), and irrespective of the presence of T2D (P for interaction = 0.81) and age (> 65 vs ≤ 65 years, P for interaction = 0.78). The risk of CV mortality, total mortality and hospitalization for HF was significantly reduced by 16%, 13%, and 32%, respectively; similarly, the risk of the composite renal outcome was reduced by 35% (HR = 0.65, 95% CI 0.56-0.75), with moderate heterogeneity (I2 = 32%). In the analysis of 6 CVOTs reporting the data, the risk of major cardiovascular events (MACE) was reduced by 12%, with low heterogeneity (I2 = 21.2%, P = 0.19) and irrespective of the presence of established CV disease at baseline (P for interaction = 0.46). CONCLUSIONS: Therapy with SGLT-2 inhibitors in patients with cardiometabolic and renal diseases results in a sustained to moderate reduction of the composite CV death or hospitalization for HF, robust reduction of HF and renal outcomes, moderate reduction of CV mortality, total mortality and MACE.

Secondary organic aerosol association with cardiorespiratory disease mortality in the United States.

Fine particle pollution, PM2.5, is associated with increased risk of death from cardiorespiratory diseases. A multidecadal shift in the United States (U.S.) PM2.5 composition towards organic aerosol as well as advances in predictive algorithms for secondary organic aerosol (SOA) allows for novel examinations of the role of PM2.5 components on mortality. Here we show SOA is strongly associated with county-level cardiorespiratory death rates in the U.S. independent of the total PM2.5 mass association with the largest associations located in the southeastern U.S. Compared to PM2.5, county-level variability in SOA across the U.S. is associated with 3.5× greater per capita county-level cardiorespiratory mortality. On a per mass basis, SOA is associated with a 6.5× higher rate of mortality than PM2.5, and biogenic and anthropogenic carbon sources both play a role in the overall SOA association with mortality. Our results suggest reducing the health impacts of PM2.5 requires consideration of SOA.

Electrical Storm as an Independent Mortality Risk in Patients with Preserved or Moderately Reduced Left Ventricular Function.

Electrical storm (ES), defined by 3 or more occurrences of ventricular arrhythmias within 24 hours, has been shown to be associated with an increased risk of mortality; however, detailed information remains lacking. We aimed to examine the incidence and determinants of ES and its impact on mortality in patients enrolled in the nationwide implantable cardioverter-defibrillator (ICD) registry.We studied 1,256 patients (age 65 ± 12 years) who had structural heart disease with an ICD. The patients were classified into reduced ejection fraction (EF < 35%; 657 (52%) patients) and preserved or moderately reduced EF (EF ≥ 35%; 599 (48%) patients).ES occurred in 49 (7%) and 36 (6%) patients in the EF < 35% and EF ≥ 35% groups (log-rank P = 0.297) during the median follow-up of 2.3 years. ICD with resynchronization therapy was associated with a lower incidence of ES in patients with EF < 35%. Non-ischemic heart disease and diuretics were associated with ES in patients with EF ≥ 35%. During the follow-up, 10/49 (20%) patients with ES and 80/608 patients (13%) without ES died in patients with EF < 35%, while 7/36 (19%) patients with ES and 38/563 patients (7%) without ES died in those with EF ≥ 35%. We have created 4 Cox multivariate models. All models showed approximately 2-fold higher hazard ratios in patients with EF ≥ 35% compared to EF < 35%.Our study showed that the determinants of ES differed between EF < 35% and EF ≥ 35%. The impact of ES for mortality was numerically higher in EF ≥ 35% than in EF < 35%, although a significant interaction was not detected.

Treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by skin and visceral fibrosis, vascular hyperreactivity and obliterative vasculopathy. Some of its complications such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and heart involvement can be life-threatening and are associated with a high mortality and a poor prognosis. Many clinical trials were carried out in order to improve the survival and prognosis of SSc patients. The management of SSc is based on the frequent and regular assessment of the potential organ damage, and if present, the establishment of graduated pharmacological therapeutic strategies, associated with non-pharmacological procedures. Several randomized clinical trials have showed significant positive outcomes regarding some specific involvements. Many advances have been made, especially in the field of targeted therapies and personalized medicine, based on specific characteristics of the patient and the SSc.