Predictors of gastrointestinal bleeding in patients following left ventricular assist device implantation: a systematic review and meta-analysis.

Aim: Our study aims to provide a more holistic understanding of the available data and predictive risk factors for gastrointestinal bleed (GIB). Materials & methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science Core Collection and calculated relative risk and meta-regression was utilized to evaluate for risk factors in order to assess the effect of covariates. Results: Our meta-analysis reported a pooled prevalence rate of GIB of 24.4%. Meta-regression analysis did not yield a statistically significant association between GIB and risk factors, including age, gender, hypertension, chronic kidney disease and diabetes. Conclusion: Studies investigating larger sample sizes are required for conclusive findings.

Postural orthostatic tachycardia syndrome: pathophysiology, management, and experimental therapies.

INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies. AREAS COVERED: In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic. EXPERT OPINION: Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

Primary and Secondary Prevention Strategies for Gastrointestinal Bleeding in Patients with Left Ventricular Assist Device: A Systematic Review and Network Meta-analysis.

Recurrent gastrointestinal bleeding (GIB) is a common complication following left ventricular assist device (LVAD) implantation. Our study aimed to estimate the comparative efficacy of different pharmacologic interventions for the prevention of GIB, through a network meta-analysis (NMA). A total of 13 observational studies comparing six strategies. Among those, 4 were for primary, and 9 were for secondary prevention of GIB. On NMA, thalidomide (Hazard ratio [HR]: 0.016, Credible interval [CrI]I: 0.00053-0.12), omega-3-fatty acid (HR:0.088, CrI: 0.026-0.77), octreotide (HR: 0.17, CrI: 0.0589-0.41) and danazol (HR:0.17, CrI: 0.059-0.41) reduced the risk of GIB. The use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker (ACEi/ARB) and digoxin were not associated with any significant reduction. Based on NMA, combining indirect treatment comparisons, thalidomide, danazol, and octreotide treatments were associated with decreased risk of recurrent GIB. Additionally, Omega 3 fatty acids were associated with a lower risk of the primary episode of GIB in the LVAD patient population.

Cardiovascular Toxicities of Immune Checkpoint Inhibitors: JACC Review Topic of the Week.

Immune checkpoint inhibitors (ICIs) have been an important therapeutic advance in the field of cancer medicine, resulting in a significant improvement in survival of patients with advanced malignancies. Recent reports provided greater insights into the incidence of cardiovascular adverse events (CVAEs) with ICI use. Myocarditis is the most common CVAE associated with ICI. Pericardial diseases, Takotsubo syndrome, arrhythmias, and vasculitis constitute other significant AEs. Physicians should be aware of these infrequent, but potentially fatal toxicities associated with ICIs as their therapeutic use becomes widespread with a myriad of approvals by the U.S. Food and Drug Administration. Management involves prompt administration of high-dose corticosteroids and discontinuation of ICIs in severe myocarditis. This review summarizes the most updated evidence on epidemiology, pathophysiological mechanisms, and management strategies of various CVAEs associated with ICIs. Highlights from recent guidelines published by National Comprehensive Cancer Network on ICI-related CV toxicities have also been incorporated.

Fish Oil and Cardiometabolic Diseases: Recent Updates and Controversies.

Fatty acids derived from fish oil are long-chain omega-3 (n-3) polyunsaturated fatty acids. The important polyunsaturated fatty acids of fish oil are eicosapentaenoic acid, and docosahexaenoic acid. For decades, there has been a debate about the use of omega-3 fatty acids and their benefits on cardiovascular health. The more recent trials including the JELIS, VITAL, STRENGTH, and ASCEND trials, addressed the paucity of data of omega-3 fatty acids on primary and secondary prevention of cardiovascular events and the risk-benefit balance of these supplements. Prior to these studies, many large randomized controlled trials have shown conflicting results on the effect of polyunsaturated fatty acids in patients with prior coronary artery disease, stroke, or major vascular events. These inconsistent results warrant a better understanding of the effects of omega-3 fatty acids on the subtypes of cardiovascular diseases, and their use in primary and secondary prevention. More recently, icosapent ethyl showed a significant reduction in cardiovascular mortality and ischemic events in patients with elevated triglyceride (TG) and established cardiovascular disease or diabetes. The REDUCE-IT trial paved the way to further reduce cardiovascular risk in patients with high TG despite being on a maximally tolerated statin. The aim of this review is to discuss these recent updates on the use of various forms of fish oil, including prescription form and supplement in cardiometabolic diseases, and their surrounding controversies.

Management of cardiac hemochromatosis.

Iron-overload syndromes may be hereditary or acquired. Patients may be asymptomatic early in the disease. Once heart failure develops, there is rapid deterioration. Cardiac hemochromatosis is characterized by a dilated cardiomyopathy with dilated ventricles, reduced ejection fraction, and reduced fractional shortening. Deposition of iron may occur in the entire cardiac conduction system, especially the atrioventricular node. Cardiac hemochromatosis should be considered in any patient with unexplained heart failure. Screening for systemic iron overload with serum ferritin and transferin saturation should be performed. If these tests are consistent with iron overload, further noninvasive and histologic confirmation is indicated to confirm organ involvement with iron overload. Cardiac magnetic resonance imaging is superior to other diagnostic tests since it can quantitatively assess myocardial iron load. Therapeutic phlebotomy is the therapy of choice in nonanemic patients with cardiac hemochromatosis. Therapeutic phlebotomy should be started in men with serum ferritin levels of 300 µg/l or more and in women with serum ferritin levels of 200 µg/l or more. Therapeutic phlebotomy consists of removing 1 unit of blood (450 to 500 ml) weekly until the serum ferritin level is 10 to 20 µg/l and maintenance of the serum ferritin level at 50 µg/l or lower thereafter by periodic removal of blood. Phlebotomy is not a treatment option in patients with anemia (secondary iron-overload disorders) nor in patients with severe congestive heart failure. In these patients, the treatment of choice is iron chelation therapy.

Cardiovascular Abnormalities in Carbon Monoxide Poisoning.

Acute carbon monoxide (CO) poisoning is the most common cause of poisoning and poisoning-related death in the United States. It manifests as broad spectrum of symptoms ranging from mild headache, nausea, and fatigue to dizziness, syncope, coma, seizures resulting in cardiovascular collapse, respiratory failure, and death. Cardiovascular complications of CO poisoning has been well reported and include myocardial stunning, left ventricular dysfunction, pulmonary edema, and arrhythmias. Acute myocardial ischemia has also been reported from increased thrombogenicity due to CO poisoning. Myocardial toxicity from CO exposure is associated with increased short-term and long-term mortality. Carboxyhemoglobin (COHb) levels do not correlate well with the clinical severity of CO poisoning. Supplemental oxygen remains the cornerstone of therapy for CO poisoning. Hyperbaric oxygen therapy increases CO elimination and has been used with wide variability in patients with evidence of neurological and myocardial injury from CO poisoning, but its benefit in limiting or reversing cardiac injury is unknown. We present a comprehensive review of literature on cardiovascular manifestations of CO poisoning and propose a diagnostic algorithm for managing patients with CO poisoning.

Cardiovascular benefits and safety of non-insulin medications used in the treatment of type 2 diabetes mellitus.

Diabetes mellitus is a growing in exponential proportions. If the current growth trend continues, it may result in every third adult in the United States having diabetes mellitus by 2050, and every 10th adult worldwide. Type 2 diabetes mellitus (T2DM) confers a 2- to 3-fold increased risk of cardiovascular (CV) events compared with non-diabetic patients, and CV mortality is responsible for around 80% mortality in this population. Patients with T2DM can have other features of insulin resistance-metabolic syndrome like hypertension, lipid abnormalities, and obesity which are all associated with increased CV disease and stroke risk even in the absence of T2DM. The management of a T2DM calls for employing a holistic risk factor control approach. Metformin is the first line therapy for T2DM and has been shown to have cardiovascular beneficial effects. Intense debate regarding the risk of myocardial infarction with rosiglitazone led to regulatory agencies necessitating cardiovascular outcome trials with upcoming anti-diabetic medications. Glucagon like peptide-1 agonists and sodium glucose co-transporter-2 inhibitors have shown promising CV safety and additional CV benefit in recent clinical trials. These drugs have favorable effects on traditional CV risk factors. The findings from these studies further support that fact that CV risk factor control plays an important role in reducing morbidity and mortality in T2DM patients. This review article will discuss briefly the cardiovascular safety and benefits of the oral medications which are currently being used for T2DM and will then discuss in detail about the newer medications being investigated for the treatment of T2DM.

New oral anticoagulants in patients with cancer: current state of evidence.

Effectiveness of new oral anticoagulants (NOAC) in patients with cancer is not clearly defined. There remain concerns of doubtful benefit and chances of potential harm with newer agents. In this meta-analysis, we evaluated the efficacy and safety of NOAC in patients with cancer. PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched from January 01, 2001 through February 28, 2013. Randomized controlled trials reporting efficacy and safety data of NOACs (rivaroxaban, dabigatran, and apixaban) with control (low-molecular-weight heparin/vitamin K antagonists/placebo) for patients with cancer were included. Primary efficacy outcome was venous thromboembolism (VTE) or VTE-related death, and primary safety outcome was clinically relevant bleeding. We used random-effects models. Six trials randomized 19,832 patients, and 1197 patients had cancer. Risk of VTE or VTE-related death was not significantly different with NOAC versus control [odds ratio (OR), 0.80; 95% confidence interval (CI), 0.39-1.65] in patients with cancer. Separate analysis for individual effects showed similar results for rivaroxaban (OR, 1.08; 95% CI, 0.60-1.94) and dabigatran (OR, 0.91; 95% CI, 0.21-3.91). Clinically relevant bleeding was not higher with NOAC compared with control (OR, 1.49; 95% CI, 0.82-2.71); individual effect of rivaroxaban showed similar results. No statistically significant difference of efficacy and safety with NOAC was found between patients with and without cancer. Rivaroxaban might be equally effective and safe as vitamin K antagonist in patients with cancer. Dabigatran is as effective as comparator; however, safety profile of dabigatran is unknown. Randomized trials of new anticoagulants specific to the cancer population are necessary, and NOAC also need to be evaluated against low-molecular-weight heparin.

Umeclidinium for treating COPD: an evaluation of pharmacologic properties, safety and clinical use.

INTRODUCTION: Umeclidinium (UMEC) is a long-acting inhaled antagonist of muscarinic cholinergic receptors. The FDA approved UMEC for maintenance treatment of chronic obstructive pulmonary disease (COPD) in 2013 and it became available for commercial use as a single agent in 2014. After tiotropium, this is the only other once daily LAMA available for COPD patients. AREAS COVERED: In this article, we have comprehensively reviewed the pharmacokinetic properties and analyzed the currently available randomized controlled trials on the efficacy and safety profile of UMEC. We have discussed the current clinical application of UMEC and its future implication. EXPERT OPINION: UMEC is the newer long-acting antimuscarinic agent (LAMA) that has demonstrated significant improvement in lung function and improved the quality of life in moderate-to-severe COPD patients. It is suitable for once daily dosing, has low anticholinergic side effects and is well tolerated. Overall, it is a safe, effective and convenient LAMA for maintenance therapy in COPD patients.

Hyperkalemia among hospitalized patients and association between duration of hyperkalemia and outcomes.

INTRODUCTION: The aim of the study was to investigate predictors of mortality in patients hospitalized with hyperkalemia. MATERIAL AND METHODS: Data among hospitalized patients with hyperkalemia (serum potassium ≥ 5.1 mEq/l) were collected. Patients with end-stage renal disease on dialysis were excluded. RESULTS: Of 15,608 hospitalizations, 451 (2.9%) episodes of hyperkalemia occurred in 408 patients. In patients with hyperkalemia, chronic kidney disease, hypertension, diabetes, coronary artery disease and heart failure were common comorbidities. Acute kidney injury (AKI) and metabolic acidosis were common metabolic abnormalities, and 359 patients (88%) were on at least one drug associated with hyperkalemia. Mean duration to resolution of hyperkalemia was 12 ±9.9 h. Nonsteroidal anti-inflammatory drugs (HR = 1.59), highest potassium level (HR = 0.61), tissue necrosis (HR = 0.61), metabolic acidosis (HR = 0.77), and AKI (HR = 0.77) were significant independent determinants of duration prior to hyperkalemia resolution. Tissue necrosis (OR = 4.55), potassium supplementation (OR = 5.46), metabolic acidosis (OR = 4.84), use of calcium gluconate for treatment of hyperkalemia (OR = 4.62), AKI (OR = 3.89), and prolonged duration of hyperkalemia (OR = 1.06) were significant independent predictors of in-hospital mortality. CONCLUSIONS: Tissue necrosis, potassium supplementation, metabolic acidosis, calcium gluconate for treatment of hyperkalemia, AKI and prolonged duration of hyperkalemia are independent predictors of in-hospital mortality.

The meaning of hypokalemia in heart failure.

Maintenance of normal potassium (K(+)) homeostasis has become an increasingly important limiting factor in the therapy of heart failure (HF). With the application of loop diuretics and digoxin, hypokalemia has become a frequent and feared side effect of treatment. Low serum K(+) in HF may be also a marker of increased neurohormonal activity and disease progression. To gain the maximum benefit from treatment, we need to individualize drug use and carefully monitor electrolytes. Symptomatic HF patients (New York Heart Association class III-IV) should be prescribed the lowest dose of diuretic necessary to maintain euvolemia. Mild hypokalemia may be corrected by the use of aldosterone receptor antagonists such as spironolactone or eplerenone. However, a more severe hypokalemia should preferably be corrected using K(+) supplement. Serum K levels should be frequently checked and maintained between 4.0 and 5.5 mEq/l (mmol/l).

Association of warfarin use with valvular and vascular calcification: a review.

Vitamin K is required for the activity of various biologically active proteins in our body. Apart from clotting factors, vitamin K-dependent proteins include regulatory proteins like protein C, protein S, protein Z, osteocalcin, growth arrest-specific gene 6 protein, and matrix Gla protein. Glutamic acid residues in matrix Gla protein are γ-carboxylated by vitamin K-dependent γ-carboxylase, which enables it to inhibit calcification. Warfarin, being a vitamin K antagonist, inhibits this process, and has been associated with calcification in various animal and human studies. Though no specific guidelines are currently available to prevent or treat this less-recognized side effect, discontinuing warfarin and using an alternative anticoagulant seems to be a reasonable option. Newer anticoagulants such as dabigatran and rivaroxaban offer promise as future therapeutic options in such cases. Drugs including statins, alendronate, osteoprotegerin, and vitamin K are currently under study as therapies to prevent or treat warfarin-associated calcification. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Treatment of stable angina pectoris.

Management of stable angina pectoris includes antianginal medications, medications to prevent progression of atherosclerosis, and aggressive treatment of causative risk factors. Antianginal medications commonly used include nitrates, beta-blockers, calcium channel blockers, and ranolazine. Antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors are used in patients with these problems to prevent progression of atherosclerosis and/or premature cardiovascular death. Aggressive risk factor control with diet; exercise; treatment of diabetes, hypertension, and dyslipidemia; and strategies to stop smoking and reduce weight should be a part of treatment strategy in all patients. Patients with stable angina who have symptoms refractory to medical treatment usually require coronary angiography, followed by either percutaneous or surgical revascularization. Recent mechanical techniques for the treatment of refractory angina include transmyocardial laser revascularization, enhanced external counterpulsation, and spinal cord stimulation.

Peripheral arterial disease in women.

Peripheral arterial disease (PAD) is chronic arterial occlusive disease of the lower extremities caused by atherosclerosis whose prevalence increases with age. Only one-half of women with PAD are symptomatic. Symptomatic and asymptomatic women with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Modifiable risk factors that predispose women to PAD include active cigarette smoking, passive smoking, diabetes mellitus, hypertension, dyslipidemia, increased plasma homocysteine levels and hypothyroidism. With regard to management, women who smoke should be encouraged to quit and referred to a smoking cessation program. Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism require treatment. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in women with PAD and hypercholesterolemia. Anti-platelet drugs such as aspirin or especially clopidogrel, angiotensin-converting enzyme inhibitors and statins should be given to all women with PAD. Beta blockers are recommended if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided as it is ineffective. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery in women are (1) incapacitating claudication interfering with work or lifestyle; and (2) limb salvage in women with limb-threatening ischemia as manifested by rest pain, non-healing ulcers, and/or infection or gangrene. Future research includes investigation of mechanisms underlying why women have a higher risk of graft failure and major amputation.

Management of peripheral arterial disease of the lower extremities.

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in patients with peripheral arterial disease (PAD) of the lower extremities. Statins decrease the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all persons with PAD. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in persons interfering with work or lifestyle, (2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene, and (3) vasculogenic impotence.

Peripheral arterial disease.

Peripheral arterial disease (PAD) in the elderly can be: 1) asymptomatic, 2) associated with intermittent claudication, or 3) cause critical limb ischemia. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease (CAD). Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism should be treated, and smoking should be stopped. Statins reduce the incidence of intermittent claudication and increase exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs (eg, aspirin, clopidogrel, angiotensin-converting enzyme [ACE] inhibitors, statins) should be given to all persons with PAD. Beta blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol lengthen exercise time until leg pain develops. Chelation therapy has no scientific basis and should be avoided. Revascularization or amputation may be indicated in some cases.

Peripheral arterial disease in the elderly.

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in elderly patients with peripheral arterial disease (PAD) of the lower extremities. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all elderly patients with PAD without contraindications to these drugs. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in patients interfering with work or lifestyle; (2) limb salvage in patients with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and (3) vasculogenic impotence.

Drug treatment of peripheral arterial disease in the elderly.

Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication or may be associated with critical limb ischaemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality and mortality from CAD. Smoking should be stopped and hypertension, diabetes mellitus, dyslipidaemia and hypothyroidism treated. HMG-CoA reductase inhibitors (statins) reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolaemia. Antiplatelet drugs such as aspirin or clopidogrel (especially the latter), ACE inhibitors and statins should be given to all persons with PAD. beta-Adrenoceptor antagonists should be given if CAD is present. The phosphodiesterase type 3 inhibitor cilostazol improves exercise time until intermittent claudication. Chelation therapy should be avoided. Correct implementation of medical therapy significantly reduces the excess mortality associated with PAD. In addition, medical therapy may result in significant improvements in walking ability that may obviate the need for lower extremity angioplasty with stenting and bypass surgery.