Mohammad Al-Ani

Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors in patients with type II diabetes mellitus: A meta-analysis of placebo-controlled randomized trials

BACKGROUND The impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular outcomes in patients with type II diabetes mellitus (DM) is not well established. METHODS We searched electronic databases from inception through July 2016 for randomized, placebo-controlled trials, involving SGLT-2 inhibitors. Fixed-effects summary odds ratios (OR) were constructed using Peto model. RESULTS Eighty-one trials with a total of 37,195 patients were included. The mean follow-up was 89weeks. Compared with placebo, SGLT-2 inhibitors were associated with a lower risk of all-cause mortality (OR 0.72; 95% CI 0.59-0.86; P<0.001), cardiovascular mortality (OR 0.67; 95% CI 0.53-0.84; P=0.001), and heart failure (OR 0.67; 95% CI 0.51-0.87; P=0.003), but a similar risk of myocardial infarction (OR 0.89; 95% CI 0.74-1.09; P=0.29) and stroke/transient ischemic attack (OR 1.09; 95% CI 0.87-1.37; P=0.47). The reduction in all-cause mortality was noticed with empagliflozin (OR 0.66; 95% CI 0.54-0.81; P<0.001), but not with other SGLT-2 inhibitors (ORdapagliflozin 1.37; 95% CI 0.71-2.62; P=0.35; ORcanagliflozin 0.82; 95% CI 0.41-1.68; P=0.59; ORluseogliflozin 4.6; 95% CI 0.07-284.25; P=0.47; and ORipragliflozin 4.73; 95% CI 0.08-283.14; P=0.46) (Pinteraction=0.19). Potential harm was observed with dapagliflozin on cardiovascular mortality (OR 2.15, 95% CI 0.92-5.04, P=0.08). CONCLUSIONS In patients with type II DM, SGLT-2 inhibitors appeared to reduce both all-cause and cardiovascular mortality, primarily due to reduction in the risk of heart failure. The benefit was only seen with empagliflozin. There was suggestion of potential harm with dapagliflozin, thus future trials are needed to ascertain the cardiovascular safety of other agents in this class.

Determining the Role of Thiamine Deficiency in Systolic Heart Failure: A Meta-Analysis and Systematic Review

BACKGROUND Approximately 5.7 million Americans carry the diagnosis of systolic heart failure (HF), a major health care burden. HF is a known manifestation of thiamine deficiency (TD). HF patients are at unique risk for developing TD, which may contribute to further altered cardiac function and symptoms. METHODS AND RESULTS We performed a systematic review of the literature and a meta-analysis to evaluate the prevalence of TD in HF patients, risk factors for and mechanisms of development of TD in HF population, and outcomes of thiamine supplementation in HF patients. We found 54 studies that met our selection criteria, 9 of which were suitable for meta-analysis. TD is more common in HF patients than control subjects (odds ratio 2.53, 95% confidence interval 1.65-3.87). Diuretic use, changes in dietary habits, and altered thiamine absorption and metabolism were identified as possible mechanisms of TD in HF patients. Small observational studies and randomized control trials suggest that thiamine supplementation in HF population may improve ejection fraction and reduce symptoms. CONCLUSIONS Thiamine deficiency is more prevalent in the HF population, and its supplementation may be beneficial. The therapeutic role of thiamine in HF warrants further study.

Prevalence and Overlap of Noncardiac Conditions in the Evaluation of Low-risk Acute Chest Pain Patients.

BACKGROUND When patients present to the emergency department with a complaint concerning for heart disease, this often becomes the primary focus of their evaluation. While patients with noncardiac causes of chest pain outnumber those with cardiac causes, noncardiac etiologies are frequently overlooked. We investigated symptoms and noncardiac conditions in a cohort of patients with chest pain at low risk of cardiac disease. METHODS We analyzed data from a prospective registry of patients who were evaluated in our chest pain evaluation center. Registry participants completed standardized and validated instruments for depression (by Patient Health Questionnaire PHQ-9), anxiety (by Generalized Anxiety Disorder GAD-7), and Gastroesophageal Reflux Disorder (GERD; by GERD Symptom Frequency Questionnaire). Chest pain characteristics were recorded; severity was reported on a 10-point scale. RESULTS A total of 195 patients were included in the investigation. Using the instruments noted above, the prevalence of depression was 34%, anxiety was 30%, and GERD was 44%, each of at least moderate severity. 32.5% of patients had 2 or more conditions. The median for the severity of angina was 7/10 and the number of episodes over the preceding week was 2, respectively. Severity of angina was associated with PHQ-9 (r = 0.238; P < 0.001) and GAD-7 (r = 0.283; P < 0.001) scores. The number of angina episodes over the prior week correlated with GERD Symptom Frequency Questionnaire (r = 0.256; P < 0.001) and PHQ-9 (r = 0.175; P = 0.019) scores. No correlation was observed between any of the scores and body mass index, smoking tobacco, diabetes mellitus, hypertension, or hyperlipidemia. CONCLUSION In our cohort of low-risk acute chest pain patients, depression, anxiety, and GERD were common, substantial overlap was observed. The severity of these noncardiac causes of chest pain causes correlated with the self-reported severity and frequency of angina, but weakly. These conditions should be part of a comprehensive plan of care for chest pain management.

The prevalence of isolated growth hormone deficiency among children of short stature in Jordan and its relationship with consanguinity

The prevalence of isolated growth hormone deficiency (IGHD) among short‐statured children in Jordan, where consanguineous marriage (CM) is common, is unknown. No studies have investigated the relationship between degrees of consanguinity and IGHD. This study aimed to determine the prevalence of IGHD among short‐statured children referred to a university hospital in Jordan and its relationship with different degrees of consanguinity.

Serpins, Viruses, and the Virome: New Directions in Therapy

Serine protease inhibitors, termed serpins, regulate myriad physiological processes in the mammalian body from thrombotic and thrombolytic pathways to inflammation, angiogenesis, hormone transport, and hypertension. The large percentage of serpins among the plasma proteins in the circulating blood as in the case of plasminogen activators, the functional redundancy of serpins, and also the debilitating serpinopathies of antithrombin III (SERPINC1), neuroserpin (SERPINI1), and alpha-1 antitrypsin (SERPINA1) provide evidence of the importance of serpins and their widespread impact in normal physiological homeostasis. Inflammation, also termed innate immunity, interacts closely with and both regulates and is regulated by thrombotic and thrombolytic serine proteases. Activation of the coagulation proteases is, in turn, controlled by serpins. Apoptosis is also modulated by serpins with cross-class inhibitory activity for cysteine and serine proteases. Excessive inflammation and cell death processes are now recognized as interacting with the thrombotic and thrombolytic proteases. Viruses have evolved to communicate and control these processes by encoding their own serpins, which confer on them the ability to evade host immune defenses. This chapter provides an introduction to the viral serpins derived from poxvirus origins that have been shown not only to be essential for successful viral infection but, in some cases, as for Serp-1 and Serp-2, to have the potential to mitigate inflammatory disease in animal models. Serp-1 has in fact been successfully tested in a small phase 2A clinical trial in unstable angina patients with coronary stent implants. A tandem discussion of mammalian serpins with actions similar to those of the viral serpins is also presented to emphasize potential evolutionary relationships between viral and mammalian serpins. The anti-inflammatory serpins hold the potential to be effective in disease states such as atheroma, sepsis, cancer, and wound healing given that these conditions are all associated with aberrant inflammatory responses and with dysregulation of thrombotic, thrombolytic, and apoptotic protease cascades. The capacity of viral serpins to provide antiviral protection by modulating the virome as well as possible therapeutic effects of serpin metabolites in inflammation will also be discussed. In summary, viral serpins have evolved over many millions of years and provide a unique and highly potent reservoir for both the study of serpin modulation of inflammatory responses and for new therapeutic approaches to inflammatory and even infectious diseases.

Advancements in pharmacotherapy for angina

ABSTRACT Introduction: Angina pectoris is the most prevalent symptomatic manifestation of ischemic heart disease, frequently leads to a poor quality of life, and is a major cause of medical resource consumption. Since the early descriptions of nitrite and nitrate in the 19th century, there has been considerable advancement in the pharmacologic management of angina. Areas covered: Management of chronic angina is often challenging for clinicians. Despite introduction of several pharmacological agents in last few decades, a significant proportion of patients continue to experience symptoms (i.e., refractory angina) with subsequent disability. For the purpose of this review, we searched PubMed and Cochrane databases from inception to August 2016 for the most clinically relevant publications that guide current practice in angina therapy and its development. In this article, we briefly review the pathophysiology of angina and mechanism-based classification of current therapy. This is followed by evidence-based insight into the traditional and novel pharmacotherapeutic agents, highlighting their clinical usefulness. Expert opinion: Considering the wide array of available therapies with different mechanism efficacy and limiting factors, a personalized approach is essential, particularly for patients with refractory angina. Ongoing research with novel pharmacologic modalities is likely to provide new options for management of angina.

Morphine in Acute Pulmonary Oedema Treatment

Purpose of ReviewWe will review the pharmacodynamics and clinical outcomes of morphine therapy for pulmonary oedema.Recent FindingsBoth animal and human studies demonstrate that morphine has vasodilatory properties. The effect on pulmonary hemodynamics seems to be neutral and possibly adverse on ventilation. Morphine, along with furosemide and nitrates, is routinely used to treat cardiogenic pulmonary oedema. Clinical data on the safety and efficacy of morphine for cardiogenic pulmonary oedema are scarce; however, morphine use has been correlated with increased rates of ICU admission and mechanical ventilation. European and American heart failure guidelines do not recommend routine use of morphine for cardiogenic pulmonary oedema.SummaryMorphine is of questionable benefit and may be harmful in treatment of acute pulmonary oedema. Clinical guidelines do not encourage routine use of morphine for pulmonary oedema; other medications for anxiolysis and vasodilation may be preferable.

UTILITY OF THE DIAMOND-FORRESTER CLASSIFICATION IN STRATIFYING ACUTE CHEST PAIN IN AN ACADEMIC CHEST PAIN CENTER

The Diamond-Forrester (DF) model has been used for 30 years to risk stratify acute chest pain in the ED and has been considered highly predictive of significant CAD. We used this model to triage acute chest pain patients for evaluation in a stand alone chest pain evaluation center (CPEC) and report

Predictors of Early and Late Heart Failure Post-orthotopic Liver Transplantation

Background: Amiodarone is associated with heart block in patients with atrial fibrillation and heart failure. The safety of amiodarone use in patients with amyloid is unknown. We sought to identify the prevalence of heart block in patients with amyloid and heart failure who received amiodarone and compare them to those without amyloid in elderly patients. Methods: We searched Explorys (Explorys Inc, Cleveland, Ohio), a database that aggregates electronic health records of 45 million patients from 23 integrated health systems in the United States. We included patients who are at least 55 years of age who have heart failure and atrial fibrillation and receive amiodarone therapy. We compared those to age adjusted controls with heart failure and atrial fibrillation without amyloidosis. Results: We identified 640 patients with amyloid and 87280 patients without amyloid. Prevalence of block was higher in patients with amyloid on amiodarone (43.8% vs 30.0%, p!0.0001). When adjusted for age, odds ratio of block was as follows: 55-59 (1.9 [1.4-2.5], p50.0017), 60-64 (1.8 [1.42.4], p50.0002), 65-69 (2.1 [1.7-2.5], p!0.0001), 70-74 (1.2 [0.9-1.6], p50.31), 7579 (1.5 [1.3-1.8], p50.0001), 80-84 (1.2 [1.0-1.5], p50.09), 85-89 (1.3 [1.0-1.8], p50.052), and 90+ (1.2 [0.9-1.7], p50.25), figure. Conclusion: Elderly patients

Pericardial mass in a patient with rheumatoid arthritis

A 65-year-old man presented with long-standing rheumatoid arthritis (RA), severe fatigue and mild arthritis of metacarpophalaneal joints. Physical examination revealed S3, II/IV decrescendo diastolic murmur and 2+ LL oedema. Anticyclic citrullinated peptide antibodies were >250 units. Echocardiogram showed an 8 cm pericardial mass with no atrial or ventricular collapse and mild to moderate aortic regurgitation. Cardiac MRI defined the mass as a heterogeneous entity attached to the right, anterior and inferior heart borders, with compression on right cardiac structures and the left ventricle. CT-guided biopsy demonstrated fibrinous material without granulomas or infection. Fatigue did not improve on immunosuppression with low-dose prednisone and leflunamide. Cardiac tamponade was confirmed by heart catheterisation and the mass was surgically excised with partial pericardiectomy. The patient had a dramatic improvement and, 4 years later, he remains asymptomatic cardiac wise. This case highlights the clinical significance of pericardial disease in RA and its response to therapy.