Trace elements in patients with aortic valve sclerosis

Background: Aortic valve sclerosis (AVSc) is defined as the thickening and calcification of aortic valve cusps, in the absence of obstruction of ventricular outflow. AVSc is linked with a clear imbalance in some trace elements. Aims: The objective of this study was to investigate the relationship between AVSc and serum levels of iron (Fe), zinc (Zn), selenium (Se), and copper (Cu). Additionally, this research aimed to explore the clinical significance of human serum zinc, selenium, copper, and iron concentrations as a potential new biomarker for AVSc patients and to clarify the pathophysiological role in individuals at risk of developing AVSc. Patients and methods: The study included 40 subjects with AVSc (25% male and 75% female) who were compared with a healthy control group with the same gender ratio. AVSc was based on comprehensive echocardiographic assessments. Blood samples were taken and Zn and Cu concentrations were determined through the use of atomic absorption spectroscopy. Se was measured using an inductively coupled plasma mass spectrometry device and Fe was measured using a Beckman Coulter instrument. Results: There was a significant difference in the prevalence of diabetes, blood pressure levels, and body mass index between the patients and the healthy subjects ( p < 0.05). The differences between the serum Fe, Se, and Cu levels of the AVSc patients and the healthy subjects ( p > 0.05) were recorded. The serum Zn of AVSc patients when compared was significantly lower compared with that of the control group ( p < 0.01). Conclusion: Patients with AVSc had an imbalance in some of the trace elements in their blood. The patient group’s valves had higher serum Cu levels and lower serum Se, Zn, and Fe concentrations compared with the healthy group’s valves. In the valve patients as compared, AVSc had a high prevalence of obesity, hypertension, and diabetes.

Leading 20 drug–drug interactions, polypharmacy, and analysis of the nature of risk factors due to QT interval prolonging drug use and potentially inappropriate psychotropic use in elderly psychiatry outpatients

Background: Psychotropic medications extend corrected QT (QTc) period in the electrocardiogram (ECG). Psychiatric patients exposed to ⩾1 psychotropic medication(s) represent a group with marked probability of drug-activated QTc-prolongation. Prolonged QTc interval in elderly patients (age > 60 years) is connected to greater risk of all-cause and coronary heart disease deaths. This study aimed at investigating pattern of utilization of QTc-interval protracting medications, QT-extending drug interactions, and prevalence of QTc-interval extending hazard factors in elderly patients. Methods: This was a cross-sectional, prospective study at the Psychiatry OPD at All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India from 1 October 2017 to 30 August 2019 employing the pertinent prescriptions. Results: A total of 832 elderly patients (age 60 years or more) visiting the Psychiatry OPD during the aforementioned study duration were investigated. About 420 (50.5%) patients were males while 412 (49.5%) were females. Of the 832 patients, 588 (70.7%) were using interacting agents with capacity to produce TdP. Almost 1152 interacting torsadogenic medication pairs were unraveled. As per AzCERT/CredibleMeds Classification, 1016 (48.8%), 724 (34.8%), and 248 (12%) agents with potential to interact were identified with ‘known’, ‘possible’, and ‘conditional risk of TdP’, respectively. The common interacting medications belonged to antidepressant (288), proton pump inhibitor (364), antipsychotic (340), antinausea (184), antimicrobial (156), and H2 receptor antagonist (60) therapeutic categories. The all-inclusive frequency of potentially inappropriate psychotropic (PIP) agents administered was 62% (1343/2166) with Beers Criteria 2019, and 46% (997/2166) with STOPP Criteria 2015. Conclusion: Many geriatric patients were administered drugs and drug combinations with heightened proclivity toward QT-interval prolongation. Furthermore, reliable evidence-based online drug knowledge resources, such as AzCERT/CredibleMeds Drug Lists, Medscape Drug Interactions Checker, Epocrates Online Interaction Check, and Drugs.com Drug Interactions Checker, can facilitate clinical professionals in selecting drugs for psychiatric patients. A wise choice of medications is imperative to preclude serious adverse sequelae. Therefore, we need to exigently embrace precautionary safety means, be vigilant, and forestall QT-extension and TdP in clinical environments.

Epidemiology of infective endocarditis before versus after change of international guidelines: a systematic review

Introduction: All major international guidelines for the management of infective endocarditis (IE) have undergone major revisions, recommending antibiotic prophylaxis (AP) restriction to high-risk patients or foregoing AP completely. We performed a systematic review to investigate the effect of these guideline changes on the global incidence of IE. Methods: Electronic database searches were performed using Ovid Medline, EMBASE and Web of Science. Studies were included if they compared the incidence of IE prior to and following any change in international guideline recommendations. Relevant studies fulfilling the predefined search criteria were categorized according to their inclusion of either adult or pediatric patients. Incidence of IE, causative microorganisms and AP prescription rates were compared following international guideline updates. Results: Sixteen studies were included, reporting over 1.3 million cases of IE. The crude incidence of IE following guideline updates has increased globally. Adjusted incidence increased in one study after European guideline updates, while North American rates did not increase. Cases of IE with a causative pathogen identified ranged from 62% to 91%. Rates of streptococcal IE varied across adult and pediatric populations, while the relative proportion of staphylococcal IE increased (range pre-guidelines 16–24.8%, range post-guidelines 26–43%). AP prescription trends were reduced in both moderate and high-risk patients following guideline updates. Discussion: The restriction of AP to only high-risk patients has not resulted in an increase in the incidence of streptococcal IE in North American populations. The evidence of the impact of AP restriction on IE incidence is still unclear for other populations. Future population-based studies with adjusted incidence of IE, AP prescription rates and accurate pathogen identification are required to delineate findings further in these other regions.

Vasopressin antagonism in heart failure: a review of the hemodynamic studies and major clinical trials

For decades, plasma arginine vasopressin (AVP) levels have been known to be elevated in patients with congestive heart failure (HF). Excessive AVP signaling at either or both the V1a and V2 receptors could contribute to the pathophysiology of HF by several mechanisms. V1a activation could cause vasoconstriction and/or direct myocardial hypertrophy as intracellular signaling pathways are closely related to those for angiotensin II. V2 activation could cause fluid retention and hyponatremia. A hemodynamic study with the pure V2 antagonist tolvaptan (TV) showed minimal hemodynamic effects. Compared with furosemide in another study, the renal and neurohormonal effects of TV were favorable. Several clinical trials with TV as adjunctive therapy in acute HF have shown beneficial effects on fluid balance and dyspnea, with no worsening of renal function or neurohormonal stimulation. Two smaller studies, one in acute and one in chronic HF, have shown comparable clinical and more favorable renal and neurohormonal effects of TV compared with loop diuretics. However, long-term treatment with TV did not alter outcomes in acute HF. No data are available other than single-dose studies of an intravenous pure V1a antagonist, which showed a vasodilating effect if plasma AVP levels were elevated. One hemodynamic study and one short-duration clinical trial with the balanced intravenous V1a/V2 antagonist conivaptan (CV) showed hemodynamic and clinical effects largely similar to those with TV in similar studies. A new orally effective balanced V1/V2 antagonist (pecavaptan) is currently undergoing phase II study as both adjunctive and alternative therapy during and after hospitalization for acute HF. The purpose of this review is to summarize what we have learned from the clinical experience with TV and CV, and to suggest implications of these findings for future work with newer agents.

The role of directional atherectomy in critical-limb ischemia

Background: Our aim was to review the current literature of the use of directional atherectomy (DA) in the treatment of lower extremity critical-limb ischemia. Methods: A search for relevant literature was performed in PubMed and PubMed Central on 16 April 2020, sorted by best match. Three searches across two databases were performed. Articles were included that contained clinical and procedural data of DA interventions in lower extremity critical-limb ischemia patients. All studies that were systematic reviews were excluded. Results: Eleven papers were included in this review. Papers were examined under several parameters: primary patency and secondary patency, limb salvage/amputation, technical/procedural success, complications/periprocedural events, and mean lesion length. Primary and secondary patency rates ranged from 56.3% to 95.0% and 76.4% to 100%, respectively. Limb salvage rates ranged from 69% to 100%. Lesion lengths were highly varied, representing a broad population, ranging from 30 ± 33 mm to 142.4 ± 107.9 mm. Conclusions: DA may be a useful tool in the treatment of lower extremity critical-limb ischemia.

De-risking primary prevention: role of imaging

Atherosclerotic cardiovascular disease (ASCVD) is a common disease among the general population, and includes four major areas: (1) coronary heart disease (CHD), manifested by stable angina, unstable angina, myocardial infarction (MI), heart failure, and coronary death; (2) cerebrovascular disease, manifested by transient ischemia attack and stroke; (3) peripheral vascular disease, manifested by claudication and critical limb ischemia; and (4) aortic atherosclerosis and aortic aneurysm (thoracic and abdominal). CHD remains the leading cause of death for both men and women in the United States. So, it is imperative to identify people at risk of CHD and provide appropriate medical treatment or intervention to prevent serious complications and outcomes including sudden cardiac death. Coronary artery calcification (CAC) is a marker of subclinical coronary artery disease. Therefore, coronary artery calcium score is an important screening method for Coronary artery disease (CAD). In this article, we performed a comprehensive review of current literatures and studies assessing the prognostic value of CAC for future cardiovascular disease (CVD) events. We searched PubMed, MEDLINE, Google Scholar, and Cochrane library. We also reviewed the 2018 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the assessment of CVD risk. A CAC score of zero corresponds to very low CVD event rates (∼1% per year) and hence a potent negative risk marker. This has been referred to as the ‘power of zero’ and affords the lowest risk of any method of risk calculation. It is now indicated in the 2018 ACC/AHA Cholesterol guidelines to be used to avoid statins for 5–10 years after a score of zero, and then re-assess the patient.

The dawn of the four-drug era? SGLT2 inhibition in heart failure with reduced ejection fraction

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic drug with salutary effects on glucose control, body weight, and blood pressure. Emerging evidence now indicates that these drugs may have a beneficial effect on outcomes in heart failure with reduced ejection fraction (HFrEF). Post-approval cardiovascular outcomes data for three of these agents (canagliflozin, empagliflozin, and dapagliflozin) showed an unexpected improvement in cardiovascular endpoints, including heart failure hospitalization and mortality, among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease or risk factors. These studies were followed by a placebo controlled trial of dapagliflozin in patients with HFrEF both with and without T2DM, showing a reduction in all-cause mortality comparable to current guideline-directed HFrEF medical therapies such as angiotensin-converting enzyme inhibitors and beta-blockers. In this review, we discuss the current landscape of evidence, safety and adverse effects, and proposed mechanisms of action for use of these agents for patients with HFrEF. The United States (US) and European guidelines are reviewed, as are the current US federally approved indications for each SGLT2 inhibitor. Use of these agents in clinical practice may be limited by an uncertain insurance environment, especially in patients without T2DM. Finally, we discuss practical considerations for the cardiovascular clinician, including within-class differences of the SGLT2 inhibitors currently available on the US market (217/300).

Impact of body mass index on 90-day warfarin requirements: a retrospective chart review

Background: Rates of obesity continue to rise worldwide as evidenced in the 2017 Centers for Disease Control and Prevention (CDC) report that indicated over 35% of United States (US) citizens are obese, with Louisiana ranked as the fifth most obese state in America. Since large clinical trials tend to exclude obese patients, health care providers are faced with concerns of under- or overdosing these patients on warfarin. Methods: This retrospective chart review evaluated patients who reported to a community anticoagulation clinic for warfarin management between 1 June 2017 and 30 September 2017. Along with baseline demographics, chronic use of drugs that have clinically significant interactions with warfarin, social activity such as tobacco use and alcohol consumption, were collected. Body mass indexes (BMI) were collected and categorized according to the World Health Organization definitions as follows: Normal (BMI 18–24.9 kg/m2), Overweight (25–29.9 kg/m2), Obesity Class I (30–34.9 kg/m2), Obesity Class II (35–39.9 kg/m2), Obesity Class III (⩾40 kg/m2). The primary outcome was the mean 90-day warfarin dose required to maintain “intermediate control” or “good control” of international normalized ratio (INR), stratified by BMI classifications. The secondary outcome was the time in therapeutic range (TTR) stratified by BMI classifications. Results: A total of 433 patient encounters were included in this study. There was a total of 43 encounters in the Normal BMI category, 111 Overweight encounters, 135 Obesity Class I encounters, 45 Obesity Class II encounters, and 99 Obesity Class III encounters. Approximately 63% of the study population were male, and over 90% the patients were African American. The Obesity Class I and Obesity Class II class required an average of 11.47 mg and 17.10 mg more warfarin, respectively, to maintain a therapeutic INR when compared with the Normal BMI category. These findings were statistically significant with p values of 0.007 and <0.001, respectively. Additionally, upon comparing the Overweight BMI category with the Obesity Class II category, there was a mean warfarin dose difference of 11.22 mg ( p = 0.010) more in Obesity Class II encounters to maintain a therapeutic INR. In the secondary analysis of TTR, Overweight category encounters had the highest TTR, whereas encounters in the Normal BMI category had the lowest TTR. Conclusion: As BMI increases, there is an increased chronic warfarin requirement to maintain “intermediate control” or “good control” of INR between 2 and 3 in an ambulatory care setting.

Sodium glucose cotransporter (SGLT)-2 inhibitors alleviate the renal stress responsible for sympathetic activation

This review focuses on the pathogenic role of sodium glucose cotransporter (SGLT)-2 in the development of renal dysfunction and heart failure in patients with diabetes, by emphasizing the concept of reno-cardiac syndrome (kidney injury worsens cardiac condition) and by substantiating the deleterious effect of sympathetic overdrive in this context. Furthermore, the review proposes a mechanistic hypothesis to explain the benefits of SGLT2 inhibitors, specifically that SGLT-2 inhibitors reduce sympathetic activation at the renal level. To illustrate this point, several examples from both animal experiments and clinical observations are introduced. The bidirectional interaction of the heart and kidney were deeply implicated as an exacerbator of heart failure and renal failure without diabetes. Renal cortical ischemia and abnormal glucose metabolism of tubular epithelial cells are likely to exist as common pathologies in nondiabetic heart failure patients. It is no wonder why SGLT-2 inhibitors are specifically being studied even in the absence of diabetes, both for heart failure and also for renal failure.