An Analysis of Clinical Outcomes of Exploratory Pediatric Metformin Ingestions Reported to the Texas Poison Center Network From 2011 to 2021.

Background: Poison centers develop triage threshold guidelines for pediatric metformin ingestions. Our network uses 1700 mg, or 85 mg/kg. Objective: To describe the dose, clinical course, and outcomes for inadvertent metformin ingestions in children 5 years old and younger reported to our statewide poison center network. Methods: We searched the poison center database 2011 to 2021 for metformin ingestions in patients 5 years and younger. Variables included age, sex, weight, dose, symptoms, outcome, and more. We used descriptive statistics with medians and interquartile ranges (IQR) for continuous variables. Results: Of 669 cases, exposures by age were 208 (31.1%) 1 to 2 years, and 275 (41.1%) 2 years. Weight was recorded in 342 (51.1%) (median 13.5 kg; IQR: 3.7 kg), and dose in 149 (22.3%) (median 500 mg; IQR: 500 mg). Milligram/kilogram values were available for 103 (15.4%) with median 42.4 mg/kg, IQR: 39 mg/kg. Most (647, 98.5%) exposures were unintentional. Most (445/669, 66.5%) were managed at a non-healthcare facility, while 204 (30.7%) were already at or referred to a healthcare facility. Of these 204 patients, 169 (82.8%) were evaluated and treated at the emergency department and discharged. Four (2%) were admitted to critical care, and 7 (3.4%) to the ward. Medical outcomes by effect were 5 (0.7%) minor, 2 (0.3%) moderate, 253 (37.8%) none, 292 (43.6%) not followed (minimal effects possible), and no major effects or deaths. Of 20 clinical occurrences reported, vomiting was most common (8, 1.2%). Conclusion: Despite little recorded dosage information, pediatric metformin ingestions under 85 mg/kg had predominantly uneventful medical outcomes.

Snake Eyes: Coral Snake Neurotoxicity Associated With Ocular Absorption of Venom and Successful Treatment With Exotic Antivenom.

BACKGROUND: Coral snake bites from Micrurus fulvius and Micrurus tener account for < 1% of all snake bites in North America. Coral snake envenomation may cause significant neurotoxicity, including respiratory insufficiency, and its onset may be delayed up to 13 h. CASE REPORT: We present a unique patient encounter of M. tener venom exposure through the ocular mucous membranes and a small cutaneous bite, resulting in neurotoxicity. To our knowledge, this is the first reported case of systemic neurotoxicity associated with ocular contact with coral snake venom. Our patient developed rapid-onset skeletal muscle weakness, which is very uncommon for M. tener, along with cranial nerve deficits. Acquisition of antivenom was challenging, but our patient provides a rare report of resolution of suspected M. tener neurotoxicity after receiving Central American coral snake (Micrurus nigrocinctus) antivenom. Our patient subsequently developed serum sickness, a known delayed complication of antivenom. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The emergency physician should be aware that coral snake venom may be absorbed through different routes. Neurotoxicity and respiratory insufficiency may be fatal and onset may be delayed up to 13 h. North American Coral Snake Antivenom is in very limited supply, so non-Food and Drug Administration-approved alternative coral snake antivenoms may be used for patients demonstrating neurotoxicity. Emergency physicians should be proactive in contacting a toxicologist to procure antivenom, as well as consideration of adjunctive treatments, such as neostigmine. Furthermore, whole immunoglobulin G products, such as antivenom, may result in immediate and delayed reactions.

Failing the failing heart: a review of palliative care in heart failure.

Heart failure (HF) is the most common reason for hospital admission for patients older than 65 years. With an aging population and improving survival in heart failure patients, the number of people living with HF continues to grow. As this population increases, the importance of treating symptoms of fatigue, dyspnea, pain, and depression that diminish the quality of life in HF patients becomes increasingly important. Palliative care has been shown to help alleviate these symptoms and improve patients' satisfaction with the care they receive. Despite this growing body of evidence, palliative care consultation remains underutilized and is not standard practice in the management of HF. With an emphasis on communication, symptom management, and coordinated care, palliative care provides an integrated approach to support patients and families with chronic illnesses. Early communication with patients and families regarding the unpredictable nature of HF and the increased risk of sudden cardiac death enables discussions around advanced care directives, health care proxies, and deactivation of permanent pacemakers or implantable cardioverter defibrillators. Cardiologists and primary care physicians who are comfortable initiating these discussions are encouraged to do so; however, many fear destroying hope and are uncertain how to discuss end-of-life issues. Thus, in order to facilitate these discussions and establish an appropriate relationship, we recommend that patients and families be introduced to a palliative care team at the earliest appropriate time after diagnosis.

The impact of mean first-year heart rate on outcomes after heart transplantation: does it make a difference?

BACKGROUND: Cardiac denervation following transplantation has a variable effect on heart rate (HR), and the consequence of this is not known. We examined the impact of first-year HR on five-yr outcomes after heart transplant. METHODS: We evaluated 544 heart transplant recipients from 1994 to 2008. Patients were divided into groups by mean first-year HR: group 1, HR < 90 (mean 85.0 ± 4.3); group 2, 90 ≤ HR < 110 (mean 97.8 ± 4.9); group 3, HR ≥ 110 (mean 111.5 ± 1.8). Endpoints included one-yr freedom from treated rejection, five-yr survival, five-yr freedom from cardiac allograft vasculopathy (CAV), and five-yr freedom from non-fatal major adverse cardiac events (NF-MACE). RESULTS: One-yr freedom from treated rejection, five-yr survival and freedom from CAV were not significantly different between groups. Five-yr freedom from NF-MACE was significantly lower in group 3 compared with group 2, 69% vs. 91%, p < 0.01, mainly due to higher prevalence of congestive heart failure (CHF) in group 3 over five yr. CONCLUSIONS: Mean first-year HR does not provide prognostic significance for one-yr freedom from treated rejection, five-yr survival or development of CAV five yr after heart transplant. These results suggest that HR post-heart transplantation does not affect long-term outcomes, but high first-year HRs may be associated with new-onset CHF.

Comparison of long-term outcomes of drug-eluting stents and bare metal stents for saphenous vein graft stenosis.

OBJECTIVE: Our aim was to compare the long-term outcomes between drug-eluting stents and bare-metal stents for saphenous vein graft stenosis. BACKGROUND: The ideal type of stent to treat saphenous vein graft stenosis has not been clearly established. Short-term randomized controlled trial results comparing drug-eluting stents with bare-metal stents for saphenous vein graft stenosis are conflicting, intermediate-term retrospective studies and meta-analyses at two years suggest no difference in outcomes, and there are no long term follow-up studies. The need for long term follow-up data has become emerged with concern over late stent thrombosis. METHODS: 246 saphenous vein graft patients undergoing stenting from August 2002-December 2008 were studied. Overall survival and event-free survival were compared by Kaplan-Meier method. Hazard ratios (HR) were calculated by Cox-proportional hazards models. RESULTS: We treated 133 patients with DES (median follow-up four years) and 113 patients with BMS (median follow-up four years) for SVG stenosis. Overall survival (77.0% ± 3.9% vs. 70.6% ± 4.6%, log-rank P = 0.60) and MACE-free survival (57.5% ± 4.6% vs. 56.8% ± 4.9, log-rank P = 0.70) were not significantly different between the DES and BMS groups. Although BMS was associated with increased risk of target lesion revascularization (TLR) (freedom from TLR 85.2% ± 3.5% vs. 90.0% ± 3.0%, HR 2.07, 95% CI 0.97-4.42, log-rank P = 0.05), there was no significant difference in the freedom from myocardial infarction (86.7% ± 3.3% vs. 88.7% ± 3.2%, log-rank P = 0.39) or target vessel revascularization (77.1% ± 4.2% vs. 76.1% ± 4.2%, log-rank P = 0.33) between the two groups. CONCLUSIONS: Although mortality is not statistically different between DES and BMS for SVG stenosis, BMS is associated with increased risk of revascularization, thus suggesting the superiority of DES over BMS in the long term.

The JUPITER trial: myth or reality?

The JUPITER trial is widely hailed as a landmark trial that has the potential to dramatically change the landscape of primary prevention of cardiovascular disease. Like most trials, however, it is not without its limitations. We address some of the common myths and misunderstandings that are underscored by the JUPITER trial. First, by its intentional and ill-advised exclusion of patients with low levels of high-sensitivity C-reactive protein (hsCRP), it is not possible to assess whether baseline hsCRP modifies treatment response to statins or whether it identifies patients most likely to benefit from statin therapy. Second, by stopping the trial early, one cannot rule out the possibility that the treatment benefit was overestimated and risk was underestimated, thereby precluding a reliable estimate of benefit/risk. Finally, as a consequence of early stopping, it is not possible to reliably assess the cost-effectiveness of primary prevention with rosuvastatin. Given these limitations, the attendant societal health policy implications remain largely unknown.

Severe myeloneuropathy from acute high-dose nitrous oxide (N2O) abuse.

BACKGROUND: Myeloneuropathy from chronic exposure to nitrous oxide has been described. Nitrous oxide irreversibly alters B(12) activation, causing signs and symptoms of B(12) deficiency. OBJECTIVES: We describe a case of myeloneuropathy secondary to acute use of high-dose nitrous oxide. CASE REPORT: A 24-year-old man presented to the Emergency Department complaining of numbness and tingling of his hands and feet, as well as worsening clumsiness and gait disturbances after escalating use of nitrous oxide in the prior 2 weeks. He was found to have dysmetria, poor proprioception, decreased sensation to vibration and light touch over his extremities, and a mildly positive Romberg sign. Laboratory test values revealed a normal B(12) level but increased methylmalonic acid and homocysteine levels. The patient was admitted to the hospital and started on a course of B(12) injections. He was discharged after 3 days with daily B(12) supplementation. CONCLUSIONS: This case demonstrates myeloneuropathic changes secondary to acute high-dose nitrous oxide exposure.

Left ventricular noncompaction cardiomyopathy: updated review.

The first case of noncompaction was described in 1932 after an autopsy performed on a newborn infant with aortic atresia/coronary-ventricular fistula. Isolated noncompaction cardiomyopathy was first described in 1984. A review on selected/relevant medical literature was conducted using Pubmed from 1984 to 2013 and the pathogenesis, clinical features, and management are discussed. Left ventricular noncompaction (LVNC) is a relatively rare congenital condition that results from arrest of the normal compaction process of the myocardium during fetal development. LVNC shows variability in its genetic pattern, pathophysiologic findings, and clinical presentations. The genetic heterogeneity, phenotypical overlap, and variety in clinical presentation raised the suspicion that LVNC might just be a morphological variant of other cardiomyopathies, but the American Heart Association classifies LVNC as a primary genetic cardiomyopathy. The familiar type is common and follows a X-linked, autosomal-dominant, or mitochondrial-inheritance pattern (in children). LVNC can occur in isolation or coexist with other cardiac and/or systemic anomalies. The clinical presentations are variable ranging from asymptomatic patients to patients who develop ventricular arrhythmias, thromboembolism, heart failure, and sudden cardiac death. Increased awareness over the last 25 years and improvements in technology have increased the identification of this illness and improved the clinical outcome and prognosis. LVNC is commonly diagnosed by echocardiography. Other useful diagnostic techniques for LVNC include cardiac magnetic resonance imaging, computerized tomography, and left ventriculography. Management is symptom based and patients with symptoms have a poorer prognosis. LVNC is a genetically heterogeneous disorder which can be associated with other anomalies. Making the correct diagnosis is important because of the possible associations and the need for long-term management and screening of living relatives.

Does the United States economy affect heart failure readmissions? A single metropolitan center analysis.

BACKGROUND: To determine the effects of the US economy on heart failure hospitalization rates. HYPOTHESIS: The recession was associated with worsening unemployment, loss of private insurance and prescription medication benefits, medication nonadherence, and ultimately increased rates of hospitalization for heart failure. METHODS: We compared hospitalization rates at a large, single, academic medical center from July 1, 2006 to February 28, 2007, a time of economic stability, and July 1, 2008 to February 28, 2009, a time of economic recession in the United States. RESULTS: Significantly fewer patients had private medical insurance during the economic recession than during the control period (36.5% vs 46%; P = 0.04). Despite this, there were no differences in the heart failure hospitalization or readmission rates, length of hospitalization, need for admission to an intensive care unit, in-hospital mortality, or use of guideline-recommended heart failure medications between the 2 study periods. CONCLUSIONS: We conclude that despite significant effects on medical insurance coverage, rates of heart failure hospitalization at our institution were not significantly affected by the recession. Additional large-scale population-based research is needed to better understand the effects of fluctuations in the US economy on heart failure hospitalization rates.

The potential effects of IGF-1 and GH on patients with chronic heart failure.

Heart failure (HF) is an important health concern with almost a quarter million deaths each year despite advances in medical therapy. Improvement of cardiac function has been shown to reduce morbidity and mortality in patients with HF. There has been recent interest in the growth hormone (GH) / insulin-like growth factor (IGF) pathway as a potential therapeutic target for patients with HF. Insulin-like growth factor 1 has been shown to augment cardiac function ex vivo and in animals. It was hypothesized that IGF-1/IGF-binding protein 3 levels might be able to provide prognostic benefits in patients with heart disease. Initial observational studies have shown significant benefits from GH supplementation including improved ejection fraction, increased exercise tolerance, and decreased New York Heart Association functional class. These results, however, were not replicated in randomized, controlled trials. Patients with advanced stages of HF might develop cachexia associated with a state of significant GH resistance. The lack of response to GH supplementation may be secondary to a deficiency in IGF-1, the effector hormone. Hypothetically, this group of patients could benefit from direct IGF-1 supplementation. Combined therapy with GH and IGF-1 is appealing; however, future trials in patients with advanced HF are warranted to prove this concept.

Pilot study of palliative care consultation in patients with advanced heart failure referred for cardiac transplantation.

BACKGROUND: Heart failure (HF) in its chronic form is an irreversible and progressive disease. Palliative care (PC) interventions have traditionally been focused on patients with advanced cancer. We performed a pilot study to assess the feasibility of implementing the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for early PC intervention in patients with advanced HF who were seeking or received potentially curative therapies. METHODS: Twenty consecutive patients with advanced HF referred to PC from the heart transplant service with stage D, New York Heart Association (NYHA) class III-IV symptoms were analyzed retrospectively in a tertiary care setting. Data were reviewed to assess the clinical impact of PC intervention. Feedback was obtained to assess satisfaction of the patients, their families, and the health care professionals. An independent assessment of the impact of the PC service in the care of each patient was performed by a cardiologist and PC physician by use of a scoring system. RESULTS: Twenty consecutive patients with HF were analyzed. PC consult was obtained for a variety of reasons. All patients complained of a high symptom burden. PC consultation resulted in a decrease in the use of opioids and increased patient satisfaction. Patients and their family members generally reported improved holistic care, continuity of care, more focused goals of care, and improved planning of treatment courses. The nonstandardized scoring system used to determine the impact of the PC service showed an average of moderate to significant impact when assessed by both a cardiologist and a PC physician. CONCLUSION: PC consultation appears to be beneficial in the treatment and quality of life of advanced HF patients, independent of their prognosis. This pilot study demonstrated feasibility and sufficient evidence of clinical benefit to warrant a larger randomized clinical trial assessing the benefit of standard involvement by PC in patients with advanced HF, independent of the patient's prognosis or treatment goals.

Chronic heart failure: current evidence, challenges to therapy, and future directions.

Heart failure (HF) is a complex syndrome characterized by the inability of the heart to maintain a normal cardiac output without elevated intracardiac filling pressures, resulting in signs of pulmonary and peripheral edema and symptoms of dyspnea and fatigue. Central to the management of HF is a multifaceted pharmacological intervention to abate the harmful counter-regulatory effects of neurohormonal activation and avid salt and water retention. Whereas up to 40 years ago HF was managed with diuretics and leaf of digitalis, the cornerstones of therapy for HF patients with systolic dysfunction now include ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers), ß-adrenoceptor antagonists (ß-blockers), and aldosterone antagonists, which have significantly improved survival. However, with the increasing number of beneficial therapies, there are challenges to implementing all of them. Specific cardiomyopathies also merit specific considerations with respect to treatment, and - unfortunately - there is no therapy for HF with preserved left ventricular ejection fraction that has been shown to improve survival. Although mortality has improved in HF, the biggest challenge to treatment lies in addressing the morbidity of this disease, which is now the most common reason for hospital admission in our aged population. As such, there are many therapies that may serve to improve the quality of life of HF patients. Future HF treatment regimens may include direct cellular therapy via hormone and cytokine signaling or cardiac regeneration through growth factors or cell therapy.

Case of fulminant giant-cell myocarditis associated with polymyositis, treated with a biventricular assist device and subsequent heart transplantation.

Giant-cell myocarditis is an autoimmune myocarditis that rapidly progresses to heart failure, and is often associated ventricular tachycardia. We describe an otherwise healthy patient who was acutely ill with decompensated heart failure and ventricular tachycardia associated with rash and polymyositis, who then developed cardiogenic shock and multiorgan failure due to giant-cell myocarditis.

Update on the safety of testosterone therapy in cardiac disease.

INTRODUCTION: Testosterone has been used for decades in the treatment of men with hypogonadism and women with low libido. More recently, it has been used in patient populations with cardiac disease and, in particular, in those patients with heart failure. The benefits of testosterone supplementation have been demonstrated in the literature, but there is also concern that testosterone supplementation may not be benign, especially when administered to achieve supraphysiological levels, e.g., to improve athletic performance. AREAS COVERED: This review seeks to address the link between testosterone levels and cardiac disease while discussing the safety concerns of testosterone supplementation in clinical practice. Randomized controlled trials, systematic reviews and meta-analyses that were obtained through a literature search of the Medline database are discussed in this paper. EXPERT OPINION: Ultimately, the definitive role of testosterone in cardiovascular disease remains contentious, but testosterone may have niche roles in certain conditions, such as advanced heart failure and cardiac cachexia. Testosterone has been used safely, and we believe may continue to be used safely, in men with cardiac disease when achieving physiological levels, with adequate monitoring of prostate specific antigen and hematocrit levels during the course of treatment per established clinical guidelines. Testosterone might exert beneficial effects on physical capacity and functioning as well as overall outcomes in patients with chronic heart failure.

Myths and truths of growth hormone and testosterone therapy in heart failure.

Heart failure is a chronic clinical syndrome with very poor prognosis. Despite being on optimal medical therapy, many patients still experience debilitating symptoms and poor quality of life. In recent years, there has been a great interest in anabolic hormone replacement therapy - namely, growth hormone and testosterone - as an adjunctive therapy in patients with advanced heart failure. It has been observed that low levels of growth hormone and testosterone have been associated with increased mortality and morbidity in patients with heart failure. Animal studies and clinical trials have shown promising clinical improvement with hormonal supplementation. Growth hormone has been shown to increase ventricular wall mass, decrease wall stress, increase cardiac contractility, and reduce peripheral vascular resistance, all of which might help to enhance cardiac function, resulting in improvement in clinical symptoms. Likewise, testosterone has been shown to improve hemodynamic parameters via reduction in peripheral vascular resistance and increased coronary blood flow through vasodilation, thereby improving functional and symptomatic status. To date, growth hormone and testosterone therapy have shown some positive benefits, albeit with some concerns over adverse effects. However, large randomized controlled trials are still needed to assess the long-term safety and efficacy.

Prognostic value of E/E' ratio in patients with unoperated severe aortic stenosis.

OBJECTIVES: The aim of this study was to evaluate the value of clinical and echo-Doppler parameters for the prognosis of unoperated severe aortic stenosis (AS). BACKGROUND: Approximately one-third of severe, symptomatic AS patients are denied surgery. Risk stratification of unoperated AS is important to determine eligibility for percutaneous aortic valve replacement, an evolving treatment option for AS patients deemed suboptimal for surgical aortic valve replacement. METHODS: We retrospectively compared clinical and echo-Doppler parameters between survivors and nonsurvivors of 125 patients with unoperated severe AS. RESULTS: The 1-year survival rate was 62.4%. In univariate analysis, survivors compared with nonsurvivors were younger (80.0 ± 10.9 years vs. 84.9 ± 11.1 years, p = 0.02), had a greater left ventricular ejection fraction (LVEF) (55 ± 15% vs. 50 ± 16%, p = 0.042), a higher left ventricular stroke volume (63 ± 19 ml vs. 56 ± 13 ml, p = 0.015), a lower E/E' ratio (12.19 ± 5.7 vs. 16.87 ± 7.43, p < 0.001), and a lower prevalence of E/E' > 15 (20% vs. 55%, p < 0.001). Symptomatic status was nonsignificantly different between survivors and nonsurvivors. In patients with an LVEF ≥ 50%, the subgroup with E/E' ≤ 15 and with E/E' > 15 had a 73.8% and 47.8% 1-year survival rate, respectively (p = 0.027). In the patients with an LVEF < 50%, the patients with E/E' ≤ 15 and those with E/E' > 15 demonstrated a 70.6% and 22.3% 1-year survival rate, respectively (p = 0.003). In multivariate analysis, significant predictors of mortality were E/E' > 15 and a combination of E/E' > 15 and B-type natriuretic peptide > 300 ng/ml: adjusted mortality risk 2.34 (95% confidence interval (CI) 1.27 to 4.33, p = 0.0072) and 2.59 (95% CI 1.21 to 5.55, p = 0.014), respectively. CONCLUSIONS: The E/E' ratio is the single most predictive clinical and echo-Doppler parameter in the assessment of overall prognosis in patients with unoperated severe AS. LVEF was a significant predictor of survival only in the univariate analysis. B-type natriuretic peptide alone was not a predictor of prognosis in the study population. However, the combination of E/E' and B-type natriuretic peptide is even more predictive of the 1-year prognosis.

Statins in acute coronary syndromes: do the guideline recommendations match the evidence?

On the basis of the evidence obtained from observational studies, randomized controlled trials and their meta-analyses, current guidelines recommend initiating high-dose statin therapy pre-discharge regardless of the baseline low-density lipoprotein (LDL) level in patients with acute coronary syndromes (ACS). Careful review of the evidence indicates that early initiation of high-dose statin therapy reduces recurrent ischemia and may reduce revascularization, but does not confer benefit in terms of hard clinical outcomes such as death or myocardial infarction in any of the randomized controlled trials, and may be associated with increased liver and muscle-related adverse outcomes leading to increased withdrawal and suboptimal long-term adherence. A mortality benefit is apparent in pooled analyses of randomized controlled trials only at long-term (24-month) but not short-term (4-month) follow-up. The critical role of the timing of initiation of therapy (early vs. late) on the benefit-risk profile of statin treatment has not been systematically assessed. It is unclear whether the clinical benefits are attributable to lipid-lowering or lipid-lowering-independent effects. Finally, an optimal LDL threshold for initiating treatment or target LDL level for treatment in ACS remains yet to be defined. On the basis of these observations, and despite a compelling pathophysiologic rationale, the justification for current Class I, Level of Evidence: A recommendation for statin therapy in patients with ACS remains open to question.

Value of medical therapy in patients >80 years of age with heart failure and preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (EF) has a high prevalence in the geriatric population, and this cohort may be at risk of complications caused by polypharmacy. Effects of commonly used cardiac medications on long-term survival of patients >80 years with HF and preserved left ventricular EF were assessed. One hundred forty-two patients were evaluated. During a 5-year follow-up, 98 patients died (69%). There were no significant differences in baseline parameters in patients who died compared with those who survived at 5 years. None of the drug therapies appeared to make a significant difference in long-term survival, including beta blockers (p = 0.89), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (p = 0.91), calcium channel blockers (p = 0.69), diuretics (p = 0.30), digoxin (p = 0.22), and statins (p = 0.32). In conclusion, based on the present data, it appears that use of certain common cardiac medications may not be associated with a significant effect on long-term survival in octogenarians with HF and preserved EF.