A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients. METHODS: In an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge. RESULTS: From October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median [IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care alone). No clinically significant differences were found between those who received adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, 4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: 0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose levels, and larger increase in creatinine and sodium levels within the first 7 days of hospital admission were each independent predictors of 28-day mortality (p < 0.05). CONCLUSION: In this study of hospitalized patients with COVID-19, while the outcomes of COVID illness severity, odds of mortality, and chance of respiratory failure were better in the Aggrenox group compared to standard of care alone, the data did not reach statistical significance to support the standard use of adjuvant Aggrenox in such patients.

Antiarrhythmic Drugs or Catheter Ablation in the Management of Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In patients with an implantable cardioverter-defibrillator (ICD), shocks are associated with increased morbidity and mortality. Therefore, we conducted this study to evaluate the efficacy and safety of antiarrhythmic drugs and catheter ablation (CA) in the treatment of ventricular tachyarrhythmias (VT) in patients with an ICD. METHODS: An electronic database search for randomized controlled trials that evaluated antiarrhythmic drugs and CA in patients with ICD was conducted. The primary outcome was recurrent VT. Secondary outcomes were ICD shocks and any deaths. Bayesian and frequentist network meta-analyses were performed to calculate hazard ratios (HRs) and 95% credible intervals (CrIs)/CIs. RESULTS: Twenty-two randomized controlled trials were identified (3828 total patients; age 64.3±11.4; 79% males). The use of amiodarone was associated with a significantly reduced rate of VT recurrence compared with control (HR=0.34 [95% CrI=0.15-0.74]; absolute risk difference=-0.23 [95% CrI=-0.23 to -0.09]; number needed to treat=4). Sotalol was associated with increased risk of VT recurrence compared with amiodarone (HR=2.88 [95% CrI=1.35-6.46]). Compared with control, amiodarone (HR=0.33 [95% CrI=0.15-0.76]; absolute risk difference=-0.17 [95% CrI=-0.32 to -0.06]; number needed to treat=6) and CA (HR=0.52 [95% CrI=0.30-0.89; absolute risk difference=-0.12 [95% CrI=-0.24 to -0.03]; number needed to treat=8) were associated with significantly reduced ICD shocks. Compared with amiodarone, sotalol was associated with significantly increased ICD shocks (HR=2.70 [95% CrI=1.17-6.71]). The rate of death was not significantly different between the competing strategies. The node-splitting method showed no inconsistency. CONCLUSIONS: Among patients with an ICD, amiodarone significantly reduced VT recurrence and ICD shocks, while CA reduced ICD shocks. Sotalol significantly increased VT recurrence and ICD shocks compared with amiodarone. The long-term side effects of amiodarone and early complications of CA should be weighed carefully according to specific patient characteristics.

Isolated myxoid degeneration of aortic valve: diagnostic dilemma.

Myxoid degeneration of the aortic valve as a cause of acute aortic valve regurgitation in young age is uncommon. We report a 39-year-old African-American man with a history of epilepsy and hypertension who presented with a 1-month history of worsening shortness of breath. He was diagnosed with acute pulmonary oedema. Transoesophageal echocardiogram showed normal ejection fraction but severe aortic valve insufficiency with small masses on the ventricular side of the right and non-coronary cusps, small vegetations cannot be ruled out but other valves were normal. Subsequent cultures were negative for endocarditis. Myocardial positron emission tomography (PET) scan was strongly suggestive of cardiac sarcoidosis. However, this diagnosis was ruled out as well when he underwent aortic valve replacement with bioprosthetic valve as he did not want to take long-term anticoagulation. Histological examination of the aortic valve showed myxoid degeneration. The patient was doing very well 1 year after the surgery.

Ibrutinib-induced cardiomyopathy.

The use of ibrutinib for the treatment of chronic lymphocytic leukemia (CLL) and other hematologic malignancies is blooming. Atrial fibrillation is a known side effect of ibrutinib but cardiomyopathy was not reported previously. We present an 88-year-old man with CLL who was admitted to the hospital with new-onset atrial fibrillation and symptomatic systolic congestive heart failure one month after ibrutinib initiation. Although ibrutinib was discontinued, the patient continues to have a low ejection fraction four months after discontinuation. Ischemic heart disease was ruled out with normal cardiac catheterization. This case highlights a possible new side effect of ibrutinib that needs to be monitored while patients receive this medication.

Pancreatic Adenocarcinoma Masquerading as Idiopathic Chronic Pancreatitis with Delayed Diagnosis.

Pancreatic cancer carries poor prognosis. Establishing the diagnosis early could help in improving outcome. We are presenting a case of pancreatic cancer with delayed diagnosis. Our 60-year-old patient underwent multiple endoscopic ultrasound-guided biopsies with no evidence of malignancy. He had normal molecular tumor biomarkers. The patient needed 8 months to receive the diagnosis and initiate the treatment. There are no specific guidelines regarding choice of tissue sampling modalities in such cases.

Seizure Associated Takotsubo Syndrome: A Rare Combination.

Takotsubo cardiomyopathy (TC) is increasingly recognized in neurocritical care population especially in postmenopausal females. We are presenting a 61-year-old African American female with past medical history of epilepsy, bipolar disorder, and hypertension who presented with multiple episodes of seizures due to noncompliance with antiepileptic medications. She was on telemetry which showed ST alarm. Electrocardiogram (ECG) was ordered and showed ST elevation in anterolateral leads and troponins were positive. Subsequently Takotsubo cardiomyopathy was diagnosed by left ventriculography findings and absence of angiographic evidence of obstructive coronary artery disease. Echocardiogram showed apical hypokinesia, ejection fraction of 40%, and systolic anterior motion of mitral valve with hyperdynamic left ventricle, in the absence of intracoronary thrombus formation in the angiogram. Electroencephalography showed evidence of generalized tonic-clonic seizure. She was treated with supportive therapy. This case illustrates importance of ECG in all patients with seizure irrespective of cardiac symptoms as TC could be the cause of Sudden Unexpected Death in Epilepsy (SUDEP) and may be underdiagnosed and so undertreated.