Estimated glomerular filtration rate and the risk of stroke in individuals with diabetes mellitus and atrial fibrillation insight from a large contemporary population study.

BACKGROUND: Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Impaired renal function (IRF) increases the risk of stroke as well, but this finding is not consistent among all studies. Our aim was to assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels Among individuals with AF and DM. METHODS: A prospective, historical cohort study using the Clalit Health Services electronic medical records database. Among patients with AF and DM, we compared three groups according to eGFR levels: eGFR ≥ 60, between 30 and 60, and ≤ 30 (mL/min/1.73m2). RESULTS: A total of 17,567 cases were included in the final analysis; of them, 11,013 (62.7%) had eGFR ≥ 60, 4930 (28%) had eGFR between 30 and 60, and 1624 (9.24%) with eGFR ≤ 30. The incidence of stroke per 100 person-years in the three study groups was: 1.88, 2.69, and 3.34, respectively (p < 0.001). IRF was associated with increased risk of stroke in univariate analysis, but not after multivariate adjustment (Adjusted Hazard Ratio (AHR) 0.96 {95%CI; 0.74-1.25} for eGFR 30-60 and 0.96 {95%CI; 0.60-1.55} for eGFR ≤ 30). Mortality per 100 person-years was 10.78, 21.49, and 41.55, respectively (p < 0.001). IRF was associated with increased mortality risk in univariate analysis, as well as in multivariate analysis (AHR 1.08 {95%CI; 0.98-1.18} for eGFR 30-60, and 1.59 {95%CI; 1.37-1.85} for eGFR ≤ 30. CONCLUSION: In patients with NVAF and DM, IRF was not associated with an increased risk of stroke, but severe IRF (eGFR ≤ 30) was associated with increased mortality risk.

Predictors of Adverse Outcome in High-Risk Percutaneous Coronary Interventions Patients.

BACKGROUND: Identifying high-risk percutaneous coronary intervention (PCI) patients is challenging. We aimed to evaluate which high-risk patients are prone to adverse events. METHODS: We performed a retrospective study including consecutive high-risk PCIs from 2005 to 2018 in a large tertiary medical centre. Patients with unprotected left main (LM) disease, last patent coronary vessel, or 3-vessel coronary artery disease with left ventricular ejection fraction < 35% were included. A predictive 30-day major adverse cardiac events (MACE) score consisting of any myocardial infarction, all-cause death, or target-vessel revascularisation was constructed. RESULTS: From 2005 to 2018, a total of 1890 patients who underwent PCI met the predefined high-risk PCI criteria. Mortality rate was 8.8% at 30 days and 20.7% at 1 year, and 30-day MACE rate was 14.2% and 33.5% at 1 year. Predictors of short-term MACE were New York Heart Association functional class (NYHA) 4 (hazard ratio [HR] 6.65; P < 0.001), systolic blood pressure (SBP) < 90 mm Hg (HR 4.93; P < 0.001), creatinine > 1.3 mg/dL (HR 3.57; P < 0.001), hemoglobin < 11.0 g/dL (HR 3.07; P < 0.001), pulmonary artery systolic pressure > 50 mm Hg (HR 2.06; P < 0.001), atrial fibrillation (HR 1.74; P < 0.001), and LM disease (HR 2.04; P < 0.001) or last patent vessel (HR 1.70; P = 0.002). A score constructed from these parameters reached a sensitivity of 90% and a specificity of 81% with areas under the receiver operating characteristic curve of 0.92 for MACE and 0.94 with 89% sensitivity and 87% specificity for all-cause mortality. CONCLUSIONS: Specific features such as LM lesion or last patent conduit, pulmonary hypertension, atrial fibrillation, anemia, and renal failure, along with low SBP and NYHA 4, aid risk stratification and consideration of further treatment measures.

Clinical Outcomes of Patients with COVID-19 Infection and Cardiac Implantable Electronic Devices.

BACKGROUND: Existing cardiac disease contributes to poor outcome in patients with coronavirus disease 2019 (COVID-19). Little information exists regarding COVID-19 infection in patients with a cardiac implantable electronic device (CIED). OBJECTIVES: To assess the association between CIEDs and severity of COVID-19 infection. METHODS: We performed a retrospective analysis including 13,000 patients > 18 years old with COVID-19 infection between January and December 2020. Patients with COVID-19 who had a permanent pacemaker or defibrillator were matched 1:4 based on age and sex followed by univariate and multivariate analyses. Baseline characteristics and clinical outcomes were assessed. RESULTS: Forty patients with CIED and 160 patients without CIED were included in the current analysis. Mean age was 72.6 ± 13 years, and approximately 50% were females. Majority of the patients in the study arm had a pacemaker (63%), whereas only 15 patients (37%) had a defibrillator. Patients with COVID-19 and CIED presented more often with atrial fibrillation, coronary artery disease, heart failure, hypertension, diabetes, and chronic kidney disease. They were more likely to be hospitalized in the intensive care unit (ICU) and required more ventilatory support (35% vs. 18.3%). Thirty-day mortality (22.5% vs. 13.8%) and 1-year mortality (25% vs. 15%) were higher among patients with COVID-19 and CIED. CONCLUSIONS: Patients with COVID-19 and CIED had a significantly higher prevalence of co-morbidities that were associated with increased mortality. Although, CIED by itself was not found as an independent risk factor for morbidity and mortality, it may serve as a warning for severe illness with COVID-19.

Nonobstructive coronary atherosclerosis is associated with adverse prognosis among patients diagnosed with myocardial infarction without obstructive coronary arteries.

BACKGROUND AND AIMS: The prognostic impact of nonobstructive coronary artery disease (CAD), as opposed to normal coronary arteries, on long-term outcomes of patients with myocardial infarction with no obstructive coronary arteries (MINOCA) is unclear. We aimed to address the association between nonobstructive-CAD and major adverse events (MAE) following MINOCA. METHODS: We conducted a retrospective cohort study of consecutive MINOCA patients admitted to a large referral medical center between 2005 and 2018. Patients were classified according to coronary angiography as having either normal-coronaries or nonobstructive-CAD. The primary outcome was MAE, defined as the composite of all-cause mortality and recurrent acute coronary syndrome (ACS). RESULTS: Of the 1544 MINOCA patients, 651 (42%) had normal coronaries, and 893 (58%) had CAD. The mean age was 61.2 ± 12.6 years, and 710 (46%) were females. Nonobstructive-CAD patients were older and less likely to be females, with higher rates of diabetes, hypertension, dyslipidemia, atrial fibrillation, and chronic renal-failure (p < 0.05). At a median follow-up of 7 years, MAE occurred in 203 (23%) patients and 67 (10%) patients in the nonobstructive-CAD and normal-coronaries groups, respectively (p < 0.01). In multivariable models, nonobstructive -CAD was significantly associated with long-term MAE [adjusted-hazard-ratio (aHR):1.67, 95% confidence-interval (95%CI):1.25-2.23; p < 0.001]. Other factors associated with a higher MAE-risk were older-age (aHR:1.05,95%CI:1.03-1.06; p < 0.001) and left ventricular ejection-fraction<40% (aHR:3.04,95%CI:2.03-4.57; p < 0.001), while female-sex (aHR:0.72, 95%CI: 0.56-0.94; p=0.014) and sinus rhythm at presentation (aHR:0.66, 95%CI: 0.44-0.98; p=0.041) were associated with lower MAE-risk. CONCLUSIONS: In MINOCA, nonobstructive-CAD is independently associated with a higher MAE-risk than normal-coronaries. This finding may promote risk-stratification of patients with nonobstructive-CAD-MINOCA who require tighter medical follow-up and treatment optimization.

The accuracy of 8-hour ambulatory blood pressure monitoring, adjusted to seasons.

Ambulatory blood pressure monitoring (ABPM) is considered the most reliable and accurate measurement of blood pressure (BP). However, the use of ABPM has some limitations, which make it difficult to complete for the entire 24 h. We aimed to establish in which part of the day BP measurements are in highest correlation with full ABPM (over 24 h) results. We performed a retrospective cross-sectional study which included 3113 full ABPM. Each ABPM was divided into 6- and 8-hour segments, and mean BP in each time segment was calculated. Linear mix models for describing BP by BP in each time segment were performed. A total of 3113 ABPM measurements carried out on 2676 patients (mean age 57.78 ± 14.74) were included in the study. Linear mix models demonstrated significant association between mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) in full ABPM, and SBP and DBP between 2-10 PM, respectively (SBP: ß = 0.902, p < 0.001; DBP: ß = 0.839, p < 0.001), adjusted for gender, age, season, and relevant interactions. This section had higher coefficient correlations than other sections which were examined. The study findings indicate high correlation between BP between 2-10 PM, and BP in full-ABPM, by each season. This time segment may be ideal for short-term BP monitoring as an initial screening test and for patients who are unable to complete full ABPM. However, since this time segment does not include nighttime hours, there is a risk of underdiagnosis of non-dipper.

Primary Central Nervous System Lymphoma: Clinical Characteristics, Treatment Options and Therapeutic Outcome in 36 Patients. A Single Center Experience.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials. OBJECTIVES: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center. METHODS: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019. RESULTS: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively. CONCLUSIONS: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

Comparison of Transcatheter Aortic Valve Implantation Devices in Aortic Stenosis: A Network Meta-Analysis of 42,105 Patients.

Background: In recent years, trans-catheter aortic valve implantation (TAVI) has emerged as an excellent alternative to surgical aortic valve replacement (SAVR). Currently, there are several approved devices on the market, yet comparisons among them are scarce. We aimed to compare the various devices via a network meta-analysis. Methods: We performed a network meta-analysis including randomized controlled trials (RCTs) and propensity-matched studies that provide comparisons of either a single TAVI with SAVR or two different TAVI devices and report clinical outcomes. Results: We included 12 RCT and 13 propensity-matched studies comprising 42,105 patients, among whom 27,134 underwent TAVI using various valve systems (Sapien & Sapien XT, Sapien 3, Corvalve, Evolut & Evolut Pro, Acurate Neo, Portico). The mean follow-up time was 23.4 months. Sapien 3 was superior over SAVR in the reduction of all-cause mortality (OR = 0.53; 95%CrI 0.31-0.91), while no significant difference existed between other devices and SAVR. Aortic regurgitation was more frequent among TAVI devices compared to SAVR. There was no significant difference between the various THVs and SAVR in cardiovascular mortality, myocardial infarction, NYHA class III-IV, and endocarditis. Conclusions: Newer generation TAVI devices, especially Sapien 3 and Evolut R/Pro are associated with improved outcomes compared to SAVR and other devices of the older generation.

Aspirin with Low-Dose Ticagrelor or with Low-Dose Rivaroxaban for Secondary Prevention: A Cost per Outcome Analysis.

INTRODUCTION: Secondary prevention of cardiovascular events among patients with diagnosed cardiovascular disease and high ischemic risk poses a significant challenge in clinical practice. The combinations of aspirin with low-dose (LD) ticagrelor or LD rivaroxaban have shown superiority in preventing major adverse cardiovascular events (MACE) compared with aspirin treatment alone. The comparative value for money of these two regimens remains unexplored. METHODS: We analyzed each regimen's annual cost needed to treat (CNT) by multiplying the annualized number needed to treat (aNNT) by the annual cost of each drug. The aNNTs were based on outcome data from PEGASUS TIMI-54 and COMPASS trials. Scenario analyses were performed to overcome variances in terms of population risk. Costs were calculated as 75% of US National Average Drug Acquisition Cost (NADAC), extracted in January 2022. The primary outcome was defined as CNT to prevent one MACE across the two regimens. Secondary value analysis was performed for myocardial infarction (MI), stroke, and cardiovascular death as separate outcomes. RESULTS: The aNNTs to prevent MACE with LD ticagrelor and with LD rivaroxaban were 229 [95% confidence interval (CI) 141-734] and 147 (95% CI 104-252), respectively. At an annual cost of US$3726 versus US$4533, the corresponding CNTs were US$853,254 (95% CI 525,366-2,734,884) with LD ticagrelor and US$666,351 (95% CI 471,432-1,142,316) with LD rivaroxaban. CONCLUSION: Combining aspirin with LD rivaroxaban provides better value for money than with LD ticagrelor for secondary prevention of MACE.

Loss of left ventricular rotation is a significant determinant of functional mitral regurgitation.

AIM: To evaluate insufficient rotational movement of the left ventricle (LV) as a potential novel mechanism for functional regurgitation of the mitral valve (FMR). METHODS AND RESULTS: We compared reference subjects and patients with LV dysfunction (LVD, ejection fraction EF < 50%) with and without FMR (regurgitant volume RVol>10 ml). Subjects without structural mitral valve pathology undergoing cardiac MRI were evaluated. Delayed enhancement, global LV remodeling parameters, systolic twist and torsion were measured (using manual and novel automated cardiac MRI tissue-tracking). The study included 117 subjects with mean ± SD age 50.4 ± 17.8 years, of which 30.8% were female. Compared to subjects with LVD without FMR (n = 31), those with FMR (n = 37) had similar clinical characteristics, diagnoses, delayed enhancement, EF, and longitudinal strain. Subjects with FMR had significantly larger left ventricles (EDVi:136.6 ± 41.8 vs 97.5 ± 26.2 ml/m, p < 0.0001) with wider separation between papillary muscles (21.1 ± 7.6 vs 17.2 ± 5.7 mm, p = 0.023). Notably, they had lower apical (p < 0.0001) but not basal rotation and lower peak systolic twist (3.1 ± 2.4° vs 5.5 ± 2.5°, p < 0.0001) and torsion (0.56 ± 0.38°/cm vs 0.88 ± 0.52°/cm, p = 0.004). In a multivariate model for RVol including age, gender, twist, LV end-diastolic volume, sphericity index and separation between papillary muscles, only gender, volume and twist were significant. Twist was the most powerful correlate (beta -2.23, CI -3.26 to -1.23 p < 0.001). In patients with FMR, peak systolic twist negatively correlates with RVol (r = -0.73, p < 0.0001). CONCLUSION: Reduced rotational systolic LV motion is significantly and independently associated with RVol among patients with FMR, suggesting a novel pathophysiological mechanism and a potential therapeutic target.

Incidence and Clinical Outcomes of Pacing Induced Cardiomyopathy in Patients With Normal Left Ventricular Systolic Function and Atrioventricular Block.

Patients with preserved left ventricular (LV) ejection function (EF) and atrioventricular block (AVB) who are anticipated for high-burden of right ventricular (RV) pacing possess a risk to develop pacing-induced cardiomyopathy (PIC) and adverse clinical outcomes. Hence, the aim of the study is to evaluate the incidence, predictors, and clinical outcomes of RV PIC in patients with preserved LVEF, AVB, and high-burden of RV pacing. One thousand and thirteen patients with second or third-degree AVB underwent first time pacemaker implantation between January 2002 and August 2016. A total of 203 patients with a newly implanted pacemaker, normal baseline LVEF, and high burden of RV pacing were included in the present study. Follow-up echocardiography was examined for a new decrease in LVEF of 10% or higher. Alternative causes for cardiomyopathy were ruled out. Patient characteristics, echocardiographic measurements, device clinic data, mortality, and hospitalizations for heart failure were collected and compared between the PIC and the non-PIC groups. Fifty-one patients (25%) developed LV dysfunction with 22 patients (11%), showing LVEF < 40%. During a mean follow-up of 49.2 months, the risk of heart failure hospitalization or all-cause mortality was significantly higher in the PIC group versus non-PIC group (35.3% vs 19.1%, p = 0.009). In conclusion the incidence of PIC in patients with normal LVEF and AVB, who are anticipated for high-burden of RV pacing is high. PIC in patients with a previously normal LV function is associated with unfavorable long-term clinical outcomes, including higher rates of heart failure hospitalizations and all-cause mortality.

Prevalence of left ventricular hypertrabeculation/noncompaction among patients with congenital dyserythropoietic anemia Type 1 (CDA1).

BACKGROUND: Congenital dyserythropoietic anemia type 1 (CDA1) is a rare autosomal recessive disease characterized by macrocytic anemia, ineffective erythropoiesis, and secondary hemochromatosis. Left-ventricular noncompaction (LVNC) is a cardiomyopathy that is commonly attributed to intrauterine arrest of normal compaction during the endomyocardial morphogenesis. LV hypertrabeculation/noncompaction (LVHT/NC) morphology, however, might exist in various hemoglobinopathies. Our primary objective was to determine whether the pattern of LVHT/NC is more prevalent among patients with CDA1, in comparison to subjects without CDA1, and to find potential risk factors for LVHT/NC among these patients. Our secondary objective was to evaluate the clinical implication of LVHT/NC. METHODS: We retrospectively assessed 32 CDA1 patients (median age 17.5, range 6-61) that underwent routine assessment of iron overload by cardiac magnetic resonance. Number and distribution of noncompacted LV segments were assessed in CDA1 patients and compared to 64 age- and gender-matched patients without CDA1. The ratio of noncompacted to compacted myocardium (NC/C ratio) in end-diastole was calculated for each of the three long-axis views. NC/C ratio > 2.3 was considered diagnostic for LVHT/NC. RESULTS: In multivariate analysis, the presence of CDA1 was independently associated with NC/C ratio > 2.3, a feature of LVHT/NC (adjusted OR = 11.46, 95%CI = 2.6-50.68, p = .001). CDA1 was strongly associated with increased number of myocardial segments exhibiting LVHT/NC pattern. Cardiac volumes and ejection fraction were preserved without clinical adverse events in long term follow-up. CONCLUSIONS: CDA1 patients have a higher prevalence of LVHT/NC than normal individuals, independent of myocardial iron overload and without effect on ejection fraction or clinical outcome.

Correction to: Once episiotomy, always episiotomy?

The original article can be found online.

Once episiotomy, always episiotomy?

OBJECTIVE: To investigate the association between episiotomy and perineal damage in the subsequent delivery. STUDY DESIGN: A retrospective cohort study was conducted, comparing outcome of subsequent singleton deliveries of women with and without episiotomy in their first (index) delivery. Deliveries occurred between the years 1991-2015 in a tertiary medical center. Traumatic vaginal tears, multiple pregnancies, and cesarean deliveries (CD) in the index pregnancy were excluded from the analysis. Multiple logistic regression models were used to control for confounders. RESULTS: During the study period, 43,066 women met the inclusion criteria; of them, 50.4% (n = 21,711) had subsequent delivery after episiotomy and 49.6% (n = 21,355) had subsequent delivery without episiotomy in the index pregnancy. Patients with episiotomy in the index birth higher rates of subsequent episiotomy (17.5 vs. 3.1%; P < 0.001; OR 1.9; 95% CI). In addition, the rates of the first and second degree perineal tears as well as the third and fourth degree perineal tears were significantly higher in patients following episiotomy (33.6 vs. 17.8%; P < 0.001, and 0.2 vs. 0.1%; P = 0.002, respectively). Nevertheless, there was no significant difference at the rates of CD and instrumental deliveries, between the groups. While adjusting for maternal age, ethnicity, birth weight, and vacuum delivery-the previous episiotomy was noted as an independent risk factor for recurrent episiotomy in the subsequent delivery (adjusted OR 6.7; 95% CI 6.2-7.3, P < 0.001). The results remained significant for term (adjusted OR 6.8; 95% CI 6.2-7.4, P < 0.001) as well as preterm deliveries (adjusted OR 4.5; 95% CI 3.3-6.3, P < 0.001) in two different models. CONCLUSION: Episiotomy is an independent risk factor for recurrent episiotomy in the subsequent delivery.

Physician Variability in Management of Emergency Department Patients with Chest Pain.

INTRODUCTION: Chest pain is a common emergency department (ED) presentation accounting for 8-10 million visits per year in the United States. Physician-level factors such as risk tolerance are predictive of admission rates. The recent advent of accelerated diagnostic pathways and ED observation units may have an impact in reducing variation in admission rates on the individual physician level. METHODS: We conducted a single-institution retrospective observational study of ED patients with a diagnosis of chest pain as determined by diagnostic code from our hospital administrative database. We included ED visits from 2012 and 2013. Patients with an elevated troponin or an electrocardiogram (ECG) demonstrating an ST elevation myocardial infarction were excluded. Patients were divided into two groups: "admission" (this included observation and inpatients) and "discharged." We stratified physicians by age, gender, residency location, and years since medical school. We controlled for patient- and hospital-related factors including age, gender, race, insurance status, daily ED volume, and lab values. RESULTS: Of 4,577 patients with documented dispositions, 3,252 (70.9%) were either admitted to the hospital or into observation (in an ED observation unit or in the hospital), while 1,333 (29.1%) were discharged. Median number of patients per physician was 132 (interquartile range 89-172). Average admission rate was 73.7±9.5% ranging from 54% to 96%. Of the 3,252 admissions, 2,638 (81.1%) were to observation. There was significant variation in the admission rate at the individual physician level with adjusted odds ratio ranging from 0.42 to 5.8 as compared to the average admission. Among physicians' characteristics, years elapsed since finishing medical school demonstrated a trend towards association with a higher admission probability. CONCLUSION: There is substantial variation among physicians in the management of patients presenting with chest pain, with physician experience playing a role.

Short- and long-term mortality due to sepsis in patients with rheumatoid arthritis.

Severe infections and sepsis are common among patients with rheumatoid arthritis (RA) and are associated with increased morbidity and mortality risks. To determine whether RA is an independent risk factor for short- and long-term mortality in patients admitted to an Intensive Care Unit (ICU) with sepsis. A retrospective age- and sex-matched cohort study, based on data of the SEPSIS-ISR Registry, an ongoing study that collects data on all patients admitted with the diagnosis of sepsis to the ICUs of 7 large hospitals during the period 2002-2012. The primary outcomes of the study were the 30-day and 3-years survival rates. A total of 124 RA patients and 248 non-RA patients (mean age 71 years; 64.5% female) were included. Primary site of infection as well as pathogens distributions were similar between the two groups. Severe sepsis and septic shock were diagnosed in 92% vs. 84% (p = 0.03) and 50% versus 39% (p = 0.06) of the RA patients and non-RA, respectively. 30-day survival rates were similar between groups, whereas 3-year survival rate in 30-day survivors was significantly lower among RA patients (34.9%) compared to non-RA patients (55.7%) (p = 0.01). In multivariate Cox proportional hazards regression, RA was found to be a significant independent risk factor for 3-year mortality in 30-day survivors (hazard ratio 1.63 95% confidence interval 1.03-1.63; p = 0.04). RA is an independent risk factor for 3-year mortality, but not short-term mortality following ICU admission with sepsis.