Safety and Efficacy of Apixaban, Rivaroxaban, and Warfarin in End-Stage Renal Disease With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the role of direct oral anticoagulants (DOACs) in this population is limited. METHODS: Electronic databases were searched and articles comparing the safety and efficacy of warfarin with apixaban or rivaroxaban were identified. Pooled hazard ratios (HR) were computed using a random-effects model. RESULTS: A total of eight articles consisting of 30,806 patients; (rivaroxaban 2196, apixaban 2745 and warfarin 25,865) were identified. The pooled HR for major bleeding events favored apixaban over warfarin (0.53, 95% confidence interval (CI) 0.33-0.84, p = 0.008). Apixaban was similar to warfarin in terms of clinically relevant non-major bleeding (HR 1.08, 95% CI 0.64-1.84, p = 0.77) and stroke events (HR 1.09, 95% CI 0.85, 1.39, p = 0.99). There was no significant difference in the risk of major bleeding events (HR 0.95, 95% CI 0.50-1.81, p = 0.88) and stroke between rivaroxaban (HR 1.39, 95% CI, 0.59-3.29, p = 0.09) and warfarin. The combined results of major bleeding in the apixaban group were not affected by the sensitivity analysis. CONCLUSIONS: Apixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD.

Impact of Body Mass Index on COVID-19-Related In-Hospital Outcomes and Mortality.

BACKGROUND: Given the high prevalence of obesity around the globe, patients with coronavirus disease 2019 (COVID-19) are at an increased risk of devastating complications. METHODS: A retrospective cohort study was performed to determine the association of basal metabolic index (body mass index (BMI)) with the need for invasive mechanical ventilation (IMV), dialysis, upgrade to an intensive care unit (ICU) and mortality. Independent t-test and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aORs) with its 95% confidence interval (CI), respectively. RESULTS: A total of 176 consecutive patients with confirmed COVID-19 diagnosis were included. The mean age was 62.2 years, with 51% being male patients. The mean BMI for non-surviving patients was significantly higher compared to patients surviving on the seventh day of hospitalization (35 vs. 30 kg/m2, P = 0.022). Similarly, patients requiring IMV had a higher BMI (33 vs. 29, P = 0.002) compared to non-intubated patients. The unadjusted OR for patients with a higher BMI requiring IMV (56% vs. 28%, OR: 3.3, 95% CI: 1.6 - 7.0, P = 0.002) and upgrade to ICU (46% vs. 28%, OR; 2.2, 1.07 - 4.6, P = 0.04) were significantly higher compared to patients with a lower BMI. Similarly, patients with a higher BMI had higher in-hospital mortality (21% vs. 9%, OR: 3.2, 95% CI: 1.3 - 8.2, P = 0.01) compared to patients with a normal BMI. Despite a numerical advantage in the lower BMI group, there was no significant difference between the two groups in terms of the need for dialysis (5% vs. 13%, OR: 3.8, 13% vs. 4%, 1.1 - 14.1, P = 0.07). aORs controlled for baseline comorbidities and medications mirrored the overall results, except for the need to upgrade to ICU. CONCLUSIONS: In patients with confirmed COVID-19, morbid obesity serves as an independent risk factor of high in-hospital mortality and the need for IMV.

Effects of left ventricular assist device on pulmonary functions and pulmonary hemodynamics: A meta-analysis. waqasullah.dr@gmail.com.

BACKGROUND: Given current evidence, the effect of left ventricular assist device (LVAD) implantation on pulmonary function tests remains controversial. AIM: To better understand the factors contributing to the changes seen on pulmonary function testing and the correlation with pulmonary hemodynamics after LVAD implantation. METHODS: Electronic databases were queried to identify relevant articles. The summary effect size was estimated as a difference of overall means and standard deviation on a random-effects model. RESULTS: A total of four studies comprising 219 patients were included. The overall mean forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion lung capacity of carbon monoxide (DLCO) after LVAD implantation were significantly lower by 0.23 L (95%CI: 0.11-0.34, P = 00002), 0.18 L (95%CI: 0.03-0.34, P = 0.02), and 3.16 mmol/min (95%CI: 2.17-4.14, P < 0.00001), respectively. The net post-LVAD mean value of the cardiac index was significantly higher by 0.49 L/min/m2 (95%CI: 0.31-0.66, P < 0.00001) compared to pre-LVAD value. The pulmonary capillary wedge pressure and pulmonary vascular resistance were significantly reduced after LVAD implantation by 8.56 mmHg (95%CI: 3.78-13.35, P = 0.0004), and 0.83 Woods U (95%CI: 0.11-1.55, P = 0.02), respectively. There was no significant difference observed in the right atrial pressure after LVAD implantation (0.61 mmHg, 95%CI: -2.00 to 3.32, P = 0.65). Overall findings appear to be driven by studies using HeartMateII devices. CONCLUSION: LVAD implantation might be associated with a significant reduction of the spirometric measures, including FEV1, FVC, and DLCO, and an overall improvement of pulmonary hemodynamics.

Predictability of CRP and D-Dimer levels for in-hospital outcomes and mortality of COVID-19.

BACKGROUND: Systemic inflammation elicited by a cytokine storm is considered a hallmark of coronavirus disease 2019 (COVID-19). This study aims to assess the clinical utility of the C-reactive protein (CRP) and D-Dimer levels for predicting in-hospital outcomes in COVID-19. METHODS: A retrospective cohort study was performed to determine the association of CRP and D-Dimer with the need for invasive mechanical ventilation (IMV), dialysis, upgrade to an intensive care unit (ICU) and mortality. Independent t-test and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aOR) with its 95% confidence interval (CI), respectively. RESULTS: A total of 176 patients with confirmed COVID-19 diagnosis were included. On presentation, the unadjusted odds for the need of IMV (OR 2.5, 95% CI 1.3-4.8, p = 0.012) and upgrade to ICU (OR 3.2, 95% CI 1.6-6.5, p = 0.002) were significantly higher for patients with CRP (>101 mg/dl). Similarly, the unadjusted odds of in-hospital mortality were significantly higher in patients with high CRP (>101 mg/dl) and high D-Dimer (>501 ng/ml), compared to corresponding low CRP (<100 mg/dl) and low D-Dimer (<500 ng/ml) groups on day-7 (OR 3.5, 95% CI 1.2-10.5, p = 0.03 and OR 10.0, 95% CI 1.2-77.9, p = 0.02), respectively. Both high D-Dimer (>501 ng/ml) and high CRP (>101 mg/dl) were associated with increased need for upgrade to the ICU and higher requirement for IMV on day-7 of hospitalization. A multivariate regression model mirrored the overall unadjusted trends except that adjusted odds for IMV were high in the high CRP group on day 7 (aOR 2.5, 95% CI 1.05-6.0, p = 0.04). CONCLUSION: CRP value greater than 100 mg/dL and D-dimer levels higher than 500 ng/ml during hospitalization might predict higher odds of in-hospital mortality. Higher levels at presentation might indicate impending clinical deterioration and the need for IMV.

Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis.

BACKGROUND: The utility of novel oral soluble guanylate cyclase (sGC) stimulators (vericiguat and riociguat), in patients with reduced or preserved ejection fraction heart failure (HFrEF/HFpEF) is currently unclear. AIM: To determine the efficacy and safety of sGC stimulators in HF patients. METHODS: Multiple databases were searched to identify relevant randomized controlled trials (RCTs). Data on the safety and efficacy of sGC stimulators were compared using relative risk ratio (RR) on a random effect model. RESULTS: Six RCTs, comprising 5604 patients (2801 in sGC stimulator group and 2803 placebo group) were included. The primary endpoint (a composite of cardiovascular mortality and first HF-related hospitalization) was significantly reduced in patients receiving sGC stimulators compared to placebo [RR 0.92, 95% confidence interval (CI): 0.85-0.99, P = 0.02]. The incidence of total HF-related hospitalizations were also lower in sGC group (RR 0.91, 95%CI: 0.86-0.96, P = 0.0009), however, sGC stimulators had no impact on all-cause mortality (RR 0.96, 95%CI: 0.86-1.07, P = 0.45) or cardiovascular mortality (RR 0.94, 95%CI: 0.83-1.06, P = 0.29). The overall safety endpoint (a composite of hypotension and syncope) was also similar between the two groups (RR 1.50, 95%CI: 0.93-2.42, P = 0.10). By contrast, a stratified subgroup analysis adjusted by type of sGC stimulator and HF (vericiguat vs riociguat and HFrEF vs HFpEF) showed near identical rates for all safety and efficacy endpoints between the two groups at a mean follow-up of 19 wk. For the primary composite endpoint, the number needed to treat was 35, the number needed to harm was 44. CONCLUSION: The use of vericiguat and riociguat in conjunction with standard HF therapy, shows no benefit in terms of decreasing HF-related hospitalizations or mortality.

Safety and Efficacy of Hydroxychloroquine in COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: During the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however, recently, the Centers for Disease Control and Prevention (CDC) has recommended against routine use of HCQ outside of study protocols citing possible adverse outcomes. METHODS: Multiple databases were searched to identify articles on COVID-19. An unadjusted odds ratio (OR) was used to calculate the safety and efficacy of HCQ on a random effect model. RESULTS: Twelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-cause mortality (OR: 2.23, 95% confidence interval (CI): 1.58 - 3.13, P value < 0.00001) were significantly higher in patients on HCQ compared to patients on control agent. The response to therapy assessed by negative repeat polymerase chain reaction (PCR) (OR: 1.83, 95% CI: 0.50 - 6.75, P = 0.36), radiological resolution (OR: 1.98, 95% CI: 0.47 - 8.36, P value = 0.36) and the need for invasive mechanical ventilation (IMV) (OR: 1.21, 95% CI: 0.34 - 4.33, P value = 0.76) were identical between the two groups. Overall, four times higher odds of net adverse events (NAEs) were observed in the HCQ group (OR: 4.59, 95% CI 1.73 - 12.20, P value = 0.02). The measures for individual safety endpoints were also numerically lower in the control arm; however, none of these values reached the level of statistical significance. CONCLUSIONS: HCQ might offer no benefits in terms of decreasing the viral load and radiological improvement in patients with COVID-19. HCQ appears to be associated with higher odds of all-cause mortality and NAEs.

Is therapeutic anticoagulation improving renal outcomes in COVID-19?

We present three patients with COVID-19 who developed acute renal failure during hospitalization and were seen to have an improvement in their kidney function after being started on therapeutic anticoagulation with heparin (Target PTT 58-93 seconds) for varying indications (atrial fibrillation, popliteal vein thrombosis and a pulmonary embolism). Their kidney functions improved significantly following anticoagulation with a clear temporal relationship between the former and latter. Anticoagulation was held for one patient due to concern of gastrointestinal bleeding and his kidney functions worsened a day after stopping anticoagulation. D-dimer levels also improved with anticoagulation but the trend of other inflammatory markers remained unpredictable.

Comparative accuracy of non-invasive imaging versus right heart catheterization for the diagnosis of pulmonary hypertension: A systematic review and meta-analysis.

BACKGROUND: Right heart catheterization (RHC) is the gold-standard in the diagnosis of pulmonary hypertension (PH) but at the cost of procedure-related complications. We sought to determine the comparative accuracy of RHC versus non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and transthoracic echocardiography (TTE). METHODS: Pulmonary hypertension was defined as a mean pulmonary artery pressure (mPAP) of>20 mmHg. Multiple databases were queried for relevant articles. Raw data were pooled using a bivariate model to calculate the measures of diagnostic accuracy and to estimate Hierarchical Summary Receiver Operating Characteristic (HSROC) on Stata 13. RESULTS: A total of 51 studies with a total patient population of 3947 were selected. The pooled sensitivity and specificity of MRI for diagnosing PH was 0.92(95% confidence interval (CI) 0.88-0.96) and 0.86 (95% CI, 0.77-0.95), respectively. The net sensitivities for CT scan and TTE were 0.79 (95% CI 0.72-0.89) and 0.85 (95% CI 0.83-0.91), respectively. The overall specificity was 0.82 (0.76-0.92) for the CT scan and 0.71 (95% CI 0.61-0.84) for TTE. The diagnostic odds ratio (DOR) for MRI was 124 (95% CI 36-433) compared to 30 (95% CI 11-78) and 24 (95% 11-38) for CT scan and TTE, respectively. Chi-squared (x2) test showed moderate heterogeneity on the test for equality of sensitivities and specificities. CONCLUSIONS: MRI has the highest sensitivity and specificity compared to CT and TTE. MRI can potentially serve as a surrogate technique to RHC for the diagnosis of PH.

Lymphocyte-to-C-Reactive Protein Ratio: A Novel Predictor of Adverse Outcomes in COVID-19.

BACKGROUND: Systemic inflammation elicited by a cytokine storm is considered a hallmark of coronavirus disease 2019 (COVID-19). This study aims to assess the validity and clinical utility of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR), typically used for gastric carcinoma prognostication, versus the neutrophil-to-lymphocyte ratio (NLR) for predicting in-hospital outcomes in COVID-19. METHODS: A retrospective cohort study was performed to determine the association of LCR and NLR with the need for invasive mechanical ventilation (IMV), dialysis, upgrade to an intensive care unit (ICU) and mortality. Independent t-test and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aORs) with its 95% confidence interval (CI), respectively. RESULTS: The mean age for NLR patients was 63.6 versus 61.6, and for LCR groups, it was 62.6 versus 63.7 years, respectively. The baseline comorbidities across all groups were comparable except that the higher LCR group had female predominance. The mean NLR was significantly higher for patients who died during hospitalization (19 vs. 7, P ≤ 0.001) and those requiring IMV (12 vs. 7, P = 0.01). Compared to alive patients, a significantly lower mean LCR was observed in patients who did not survive hospitalization (1,011 vs. 632, P = 0.04). For patients with a higher NLR (> 10), the unadjusted odds of mortality (odds ratios (ORs) 11.0, 3.6 - 33.0, P < 0.0001) and need for IMV (OR 3.3, 95% CI 1.4 - 7.7, P = 0.008) were significantly higher compared to patients with lower NLR. By contrast, for patients with lower LCR (< 100), the odds of in-hospital all-cause mortality were significantly higher compared to patients with a higher LCR (OR 0.2, 0.06 - 0.47, P = 0.001). The aORs controlled for baseline comorbidities and medications mirrored the overall results, indicating a genuinely significant correlation between these biomarkers and outcomes. CONCLUSIONS: A high NLR and decreased LCR value predict higher odds of in-hospital mortality. A high LCR at presentation might indicate impending clinical deterioration and the need for IMV.

COVID-19 Complicated by Acute Pulmonary Embolism and Right-Sided Heart Failure.

A patient with coronavirus disease-2019 (COVID-19) developed sudden shortness of breath and hypoxia. She received a diagnosis of massive pulmonary embolism complicated by right-sided heart failure, which was successfully managed conservatively. This case marks the first report of COVID-19-induced pulmonary embolism in association with acute heart failure. (Level of Difficulty: Beginner.).

Atrial fibrillation: a leading cause of heart failure-related hospitalizations; a dual epidemic.

BACKGROUND: Atrial fibrillation (AF), and heart failure (HF) are a major cardiovascular epidemic over the last decade. The prevalence and rehospitalization of heart failure are on rising edge, and many factors are responsible for these re-exacerbations of heart failure. In this study, we sought to determine an association of a risk factor for frequent rehospitalization of heart failure at our institute. We aimed to find the re-admission rate, heart rate, and rhythm of heart failure exacerbation. METHODS: We performed a single-center retrospective study at the Abington Hospital - Jefferson health and 418 patients having a history of heart failure, and AF were selected. The heart failure readmission rate (days), heart rate, and rhythm were analyzed. RESULTS: The mean age of the included population was 82.8 years SD ± 9.2. About 53% had AF with a mean heart rate 90 SD ± 21 bpm, and 47% had normal sinus rhythm (NSR) with a mean heart rate of 78 ± 16 bpm on re-admission. This difference was statistically significant (p=0.02). The mean re-admission rate for atrial fibrillation was 27.49 days SD ± 18.97, compared to 32.68 SD ± 20.26 days for NSR, statistically significant (p=0.007) and the Pearson Chi-square was also significant P = 0.006. CONCLUSION: There is a significantly increased rate of re-admission in heart failure patients with atrial fibrillation with a rapid ventricular rate. Efforts should be taken to keep the patient in NSR or controlled AF to minimize the rehospitalization rate, and this, in turn, reduces the financial burden on patients and institutes.

ST-Segment Elevation Myocardial Infaction Alert During the Night Shift, A Misfortune for the Patient or an Overstatement?

BACKGROUND: Conflicting data exist regarding the outcomes of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) based on intervention timings. It is believed that short staffing at night hours may lead to a lapse in the delivery of effective, efficient and timely medical intervention. METHODS: A retrospective single-center study was performed, and a total of 436 patients were randomized into two groups. Group A had 279 patients who had the heart catheterization done during the daytime (between 6 am and 6 pm), while group B had 157 patients who had the same intervention performed at night (between 6 pm and 6 am). RESULTS: Door to balloon (DTB) time during the day was about 16 min shorter than the DTB time at night (81.29 ± 3.26 vs. 97.30 ± 8.54) with no statistical difference (P = 0.051). The mean troponin rise during the day was 1.94 ± 10.60 SEM (95% confidence interval (CI): -22.70 to 18.90) higher than night troponin levels (71.75 ± 7.18 vs. 69.80 ± 7.18), but P value was 0.85. The left ventricular ejection fraction (LVEF) fall for daytime was 0.93% vs. 0.90% for night time patients (P = 0.94). CONCLUSION: There is no significant difference in the mean DTB time, the rise in troponin, fall in LVEF, readmission rates, or mortality, and hence no negative effects on patient outcomes based on the patient's time of presentation between the two groups.

Gitelman Syndrome: A Rare Cause of Seizure Disorder and a Systematic Review.

Gitelman syndrome is one of the few inherited causes of metabolic alkalosis due to salt losing tubulopathy. It is caused by tubular defects at the level of distal convoluted tubules, mimicking a thiazide-like tumor. It usually presents in late childhood or in teenage as nonspecific weakness, fatigability, polyuria, and polydipsia but very rarely with seizures. It is classically associated with hypokalemia, hypomagnesemia, hypocalciuria, hyperreninemia, and hyperaldosteronism. However, less frequently, it can present with normal magnesium levels. It is even rarer to find normomagnesemic patients of GS who develop seizures as the main complication since hypomagnesemia is considered the principal etiology of abnormal foci of seizure-related brain activity in GS cases. Interestingly, patients with GS are oftentimes diagnosed during pregnancy when the classic electrolyte pattern consistent with GS is noticed. Our case presents GS with normal serum magnesium in a patient, with seizures being the main clinical presentation. We also did a comprehensive literature review of 122 reported cases to show the prevalence of normal magnesium in GS cases and an overview of clinical and biochemical variability in GS. We suggest that further studies and in-depth analysis are required to understand the pathophysiology of seizures in GS patients with both normal and low magnesium levels.

Association of Parent and Offspring Religiosity With Offspring Suicide Ideation and Attempts.

Importance: Previous studies have shown an inverse association between offspring religiosity and suicidal ideation/attempts, but the association of parent religiosity on offspring suicidal ideation/attempts has not been examined. Objective: To examine associations of parent and offspring religiosity with suicide ideation and attempts in offspring. Design, Setting, and Participants: The study is based on offspring (generation 3) from a 3-generation family study at New York State Psychiatric Institute and Columbia University, in which generations 2 and 3 were defined as being at high risk or low risk for major depressive disorder because of the presence or absence of major depressive disorder in generation 1. The association between suicidal behaviors (ideation/attempts) and parent and offspring religiosity in generation 3 offspring aged 6 to 18 years (214 offspring from 112 nuclear families) was examined. Main Outcomes and Measures: Parents' psychiatric diagnoses and suicidal behaviors were assessed with the Schedule for Affective Disorders and Schizophrenia, and offspring were independently assessed using the child version. Two measures of religiosity were assessed: religious importance and religious attendance. Logistic regressions in the framework of generalized estimation equations were performed to analyze offspring suicidal behaviors while adjusting for sibling correlation and offspring age, sex, and familial depression risk status. Results: Of 214 offspring, 112 (52.3%) were girls. Offspring religious importance was associated with a lower risk for suicidal behavior in girls (odds ratio [OR], 0.48; 95% CI, 0.33-0.70) but not in boys (OR, 1.15; 95% CI, 0.74-1.80) (religiosity by sex interaction, P = .05). Religious attendance was associated with a lower risk for suicidal behavior in girls (OR, 0.64; 95% CI, 0.49-0.84) but not boys (OR, 0.94; 95% CI, 0.69-1.27) (religiosity by sex interaction, P = .17). Parent religious importance was associated with a lower risk for offspring suicidal behavior (OR, 0.61; 95% CI, 0.41-0.91) but not parent religious attendance. When parent and offspring religious importance were considered simultaneously, we found a lower risk associated with parental religious importance (OR, 0.61; 95% CI, 0.39-0.96) independent of offspring importance. These associations were independent of parental depression, marital status, and parental suicide ideation. Conclusions and Relevance: In this study, parental belief in religious importance was associated with lower risk for suicidal behavior in offspring independent of an offspring's own belief about religious importance and other known parental factors, such as parental depression, suicidal behavior, and divorce.