A 24-year-old female with rheumatic heart disease presents with a 6 years history of symptoms, with an eventful pregnancy, medical management, and subsequent surgery. The history and management is ...discussed.
Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There ...is a need for a randomised controlled trial. In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement greater than or equai to 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 ...patients will also be evaluated.
This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial.
The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase AST / alanine aminotransferase ALT > 240), myopathy and rhabdomyolysis (creatine phosphokinase CPK > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine will also be excluded from the trial.
In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute's COVID-19 treatment protocol and the treating physician's clinical judgment.
All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions.
The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy).
The study will be an open-label trial.
As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data.
The institutional ethical committee has approved the study protocol (Protocol version 3.0 June 2020). Participant recruitment starting date: 28
July 2020 Participant recruitment ending date: 27
January 2021 Trial duration: 6 months TRIAL REGISTRATION: The trial has been prospectively registered in Clinical Trial Registry - India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020).
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Inflammation has been implicated in the initiation and perpetuation of non‐valvular atrial fibrillation (AF). However, there is a lack of similar data on AF in rheumatic heart disease ...(RHD). The objective of this study was to analyze the association of inflammation as measured by serum inflammatory biomarkers with AF in rheumatic mitral stenosis (Rh‐MS).
Methods
A comparative cross‐sectional analytical study was conducted on 181 Rh‐MS patients in normal sinus rhythm (NSR; n = 69), subclinical transient AF (SCAF; detected by 24‐hours Holter monitoring; n = 30) and chronic AF (n = 82). Serum hs‐CRP, IL‐6, and sCD‐40L were assessed using ELISA immunoassay and compared in all groups of Rh‐MS with or without AF.
Results
We found significantly higher serum hs‐CRP and sCD‐40L levels in the overall AF (Chronic AF + SCAF) group (hs‐CRP: 4.5 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD‐40L: 6.4 ± 4.8 vs 3.1 ± 3.4 ng/mL, P < .01) and chronic AF subgroup (hs‐CRP: 4.9 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD‐40L: 6.9 ± 5.1 vs 3.1 ± 3.4 ng/mL, P < .01) compared to patients with sinus rhythm. There was a statistically significant graded increase of serum IL‐6 level from the NSR to the SCAF (vs NSR: 6.8 ± 3.9 vs 4.0 ± 2.2 pg/mL, P = .03), and chronic AF subgroups (vs NSR: 9.3 ± 6.5 vs 4.0 ± 2.2 pg/mL, P < .01; vs SCAF: 9.3 ± 6.5 vs 6.8 ± 3.9, P = .05) of atrial fibrillation.
Conclusions
Elevated levels of serum hs‐CRP, IL‐6, and sCD‐40L were strongly associated with overall AF and also with SCAF and chronic AF in Rh‐MS patients indicating a potential role of inflammation in the pathophysiology of rheumatic AF.
Progressive increase was observed in biomarkers level in NSR, SCAF, and chronic AF.
Elevated inflammation among three groups may represent progressive stages in rheumatic AF pathophysiology.
Low‐grade inflammation is associated with AF in RHD patients.
Graded biomarkers level shows increasing AF burden with higher inflammation.
Patients can be intensively screened for prophylactic stroke preventive management.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Nature and intensity of physical activity may influence cognition, coping mechanisms and overall personality of an individual. The objective of this cross-sectional study was to compare cognition, ...coping styles and vedic personality among individuals practicing different lifestyle.
Thirty-nine healthy young adults of both gender (27.63±4.04 years) were recruited and categorized into three groups; i.e. yoga, physical activity or sedentary lifestyle groups. Participants were assessed on cognition, coping styles and Vedic personality inventory (VPI). Verbal-n-back and Stroop tasks were performed using 3 Tesla MRI scanner. Task Based Connectivity (TBC) analysis was done using CONN toolbox in SPM.
There were no significant differences in the cognitive domains across the groups. The planning (p=0.03) and acceptance domain (p=0.03) of the Brief COPE scale showed difference across the groups. Post-hoc analysis revealed that planning and acceptance scores were distinctly higher in the physical activity group, however, there was no difference between physical activity group and yoga practitioners. Similarly, in the VPI, Sattva (p=0.003), Rajas (p=0.05) and Tamas (p=0.01) were different across the groups, and the post hoc analysis showed superiority in Sattva scores in Yoga group, meanwhile, both Rajas and Tamas were higher in the physical activity group. Yoga practitioners preferentially recruited left Superior Frontal Gyrus in relation to the physically active group and precuneus in relation to the sedentary lifestyle group.
The study revealed that yoga practitioners had a distinct higher sattva guna and preferentially recruited brain areas associated with self-regulation and inhibitory control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims : The utility of beta-blocker therapy in infants with heart failure (HF) due to significant left-to-right shunt lesions is not known. The study aimed to assess the efficacy and safety of ...propranolol in infants with HF due to moderate-to-large ventricular septal defect (VSD).
Methods : The prospective randomized trial included 80 infants with HF and moderate-to-large VSD, randomly allocated to receive either conventional therapy alone (n = 40) or propranolol plus conventional therapy (n = 40). The primary endpoint was a composite of all-cause mortality, hospitalization for HF and/or chest infection, and referral for surgery. The secondary clinical outcomes were the individual components of the composite endpoint. In addition, the patients were followed up to detect safety outcomes, for example, bronchospasm, bradyarrhythmia, and worsening HF symptoms.
Results : The addition of propranolol therapy to the conventional medications did not result in significant improvement in the primary composite endpoint (32.50% vs. 52.50%; P = 0.07). There was a trend toward improvement, but the study is underpowered for this important question. However, propranolol therapy significantly decreased the risk of hospitalization (12.50% vs. 32.50%; P = 0.03) and worsening of Ross HF class (5.41% vs. 28.21%; P = 0.01) as compared to conventional therapy (estimated number needed to treat = 5). Propranolol did not result in any significant safety concerns in these infants except bronchospasm in an infant.
Conclusions : Propranolol therapy in infants with significant left-to-right shunt may prevent worsening in HF symptoms and hospitalization and is well tolerated. However, it does not reduce mortality or need for surgery.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Late-onset atrial fibrillation (LOAF) after valve surgery for degenerative mitral valve disease often with underlying mitral valve prolapse is a known phenomenon. However, there is no similar ...data for postoperative rheumatic heart disease (RHD) patients. We sought to assess the incidence and predictors of LOAF during postoperative follow-up in RHD patients.
Methods
This single-center retrospective case–control study included a total of 384 RHD patients with normal sinus rhythm (NSR) who underwent rheumatic valve surgery between 1st July 2008 and 30th June 2013. Patients detected with
de novo
persistent atrial fibrillation (AF) after 2 months of valve surgery were diagnosed as having LOAF. Presurgical demographic and echocardiographic parameters were compared between the LOAF and NSR groups to identify risk factors for LOAF.
Results
The incidence of
de novo
LOAF after rheumatic valve surgery was 9.63% at an average of 2.67 ± 1.32 years follow-up. Age ≥ 32 years OR 2.4 (95% CI 1.2–5.1);
P
= 0.01 and left atrial (LA) size ≥ 51 mm OR 5.9 (95% CI 2.8–12.4);
P
< 0.0001 were the most significant and independent predictors of LOAF. Moreover, significant mitral valve disease was associated with a higher risk of LOAF than significant aortic valve disease (
P
= 0.037). LA size ≥ 51 mm at surgery showed a fair discriminative power AUC = 0.75; sensitivity = 68%, specificity = 70% to identify patients at high risk for LOAF.
Conclusions
Late-onset AF develops in almost a tenth of the RHD patients postoperatively following corrective valve surgery. Preoperative LA size can be used to identify patients at high risk for LOAF.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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