Doses Of Metoprolol Research Articles

Abstract 4136330: It’s ‘Tachy’ To Be Fooled - Adenosine Use During Leadless Pacemaker Placement to Ensure Reliable Threshold Assessment in the Setting of Tachycardia

Introduction: Accurate assessment of pacing thresholds during permanent pacemaker implantation is critical to ensure device function and longevity. A few reports have described rate-related threshold variability during Micra TM leadless pacemaker (Medtronic Inc, Minneapolis, MN) procedures. Postulated mechanisms for this phenomenon include variable myocardial contact or micro-dislodgment, and inflammation-induced phase IV block. In this case series, we demonstrate the use of adenosine to induce transient heart block for accurate threshold assessment in patients with tachycardia during leadless pacemaker placement. Cases: A 69-year-old male with a history of atrial flutter presented with complete atrioventricular (AV) block requiring emergent transvenous pacing. A Micra placement was performed. During the procedure, the patient was tachycardic in rapid atrial flutter despite multiple doses of metoprolol. It was noted that with rapid pacing from the pacemaker at 120 pulses per minute (ppm) the threshold was ≤1V at 0.24 ms. An adequate “tug-test” was performed and at least 2 of 4 tines were noted to be fixated based on fluoroscopic motion. To confirm the capture threshold before final deployment, 12 mg of adenosine was given to induce heart block. However, at a rate of 60 ppm, there was no ventricular capture at 3V at 0.24ms. The device was repositioned and repeat threshold testing with adenosine at 60 ppm was 0.38V at 0.24ms. Pacing parameters were assessed the next day and remained stable. Similarly, a 75-year-old female with ischemic cardiomyopathy was admitted with new atrial fibrillation (AF). She then developed pauses prompting Micra placement. During initial threshold testing, she was in rapid AF despite receiving multiple doses of metoprolol. Heart block was induced with 12mg adenosine to assess the threshold at a lower pacing rate of 60 ppm. The capture threshold achieved was 0.5V at 0.24ms. Discussion: Nusbickel et al., Yoshiyama et al., and Sano et al. have reported rate dependent discrepancies in capture thresholds after Micra implantation. Our cases highlight the importance of capture threshold assessment at lower pacing rates during implantation. In patients who are tachycardic at the time of the procedure, adenosine may be useful to more reliably assess device capture threshold and determine the need for repositioning.

8621 A Challenging Case of Preoperative Management of Pheochromocytoma Presenting With Recurrent Hypotension

Abstract Disclosure: N. Shripad: None. R. Osman: None. Introduction: Pheochromocytoma is a neuroendocrine tumor that clinically manifests due to the hypersecretion of catecholamines. Preoperative management typically involves alpha- and beta-adrenergic blockade. Patients commonly present with hypertension; however, in rare cases, patients may be hypotensive due to other comorbidities, posing a challenge to preoperative management. The following is a case of management of a pheochromocytoma with recurrent preoperative hypotension before the initiation of blood pressure-lowering agents. Case: A 47-year-old female presented to the hospital with dizziness and hypotension. The patient has a history of bilateral nephrectomy with left-sided adrenalectomy secondary to left-sided renal cell cancer and is hemodialysis-dependent. A right-sided pheochromocytoma was diagnosed a year ago on a follow-up CT scan done for monitoring renal cell cancer. The diagnosis was later confirmed with a DODATE scan and, eventually, a biopsy. Normetanephrine levels were between 581-735 pg/mL (0-88 pg/mL), with normal metanephrine levels. She denies having hyperadrenergic spells. She was started on metoprolol and doxazosin the year prior to presentation; however, she self-discontinued doxazosin after experiencing dizziness and palpitations on hemodialysis days. On admission, she was afebrile with a blood pressure of 103/66 mm Hg and a heart rate of 115 BPM. After an interdisciplinary decision was made for surgical resection, she was restarted on a lower dose of doxazosin (1 mg) and metoprolol was increased to the goal heart rate. Despite fewer hypotensive episodes on a reduced dose of doxazosin, the patient remained hypotensive on hemodialysis days. Salt tablets were started post-dialysis after clearance from nephrology, and an improvement in blood pressure was noted. She underwent a right adrenalectomy without receiving saline infusion before surgery due to concerns about volume overload. She was started on stress dose steroids due to her history of left adrenalectomy. She remained stable during and following surgery and did not require any vasopressor support. Discussion: Perioperative management of pheochromocytoma can be challenging in hypotensive patients and is poorly documented. Midodrine, an alpha-1 agonist that is typically used in dialysis-induced hypotension, is contraindicated in the setting of pheochromocytoma. We opted to manage our patient with a reduced dose of doxazosin and beta-blocker initially; however, with continued hypotensive episodes, the addition of salt tablets preoperatively on dialysis days helped to alleviate the hypotension. Although our patient did not require it, a preoperative overnight albumin infusion is a viable alternative to saline to prevent volume overload. Despite the limited literature, the patient was treated successfully through an interdisciplinary approach. Presentation: 6/3/2024

6537 Recurrent Graves Thyrotoxicosis After Prolonged Radioiodine-Induced Hypothyroidism

Abstract Disclosure: H.K. Deveaux: None. A. Gundeti: None. K. Mitrollari: None. A.P. Calimag: None. T. Yasmeen: None. Radioactive iodine (I-131) ablation (RAI) is one of the effective therapies for Graves’ disease (GD). Successful treatment is indicated by sustained, irreversible hypothyroidism requiring lifelong replacement for which recurrence of disease rarely develops. Recurrent hyperthyroidism is a rare development without apparent predisposition. Here, we describe a case of recurrent thyrotoxicosis after 36 years of RAI.70-year-old female PMH atrial fibrillation (AFib) on apixaban s/p cardioversion, HTN, HFpEF, Pulmonary HTN, and Graves’ Disease s/p RAI ablation 36 years ago with RAI-induced hypothyroidism. The patient was initially on levothyroxine for post-ablative hypothyroidism and stopped taking levothyroxine around 2019. NM scintigraphy done in 2019 showed an abnormal I-123 thyroid uptake and scan with the five-hour radioiodine thyroid uptake showed mildly hyperthyroid. On the thyroid scan, there is a note of a prominent pyramidal lobe with some thyroid gland asymmetry. In 2022, the patient was admitted for new-onset AFib and was noted to have subclinical hyperthyroidism with TSH 0.157, fT4 1.4, TrAb>40, and TSI 34.8. The patient was started on methimazole, which she stopped one month later. During this admission, the patient presented secondary to a mechanical fall and was found to be in AFib with a rapid ventricular rate. Her labs were significant for TSH<0.008 fT4 4.2, TrAb >40. Methimazole was restarted with maximal doses of diltiazem and metoprolol for rate control. Thyroid ultrasound demonstrated an enlarged, heterogeneous thyroid gland with increased vascularity and multiple bilateral TR3 thyroid nodules.Hyperthyroidism affects approximately 1.2% of the population. GD involves autoantibodies activating the thyrotropin receptor, increasing synthesis and release of thyroid hormone and is for 50-60% of cases with a 5-to-10-fold preference for females. RAI ablation is preferred, being inexpensive, with a cure rate approaching 100%. The incidence of transient hypothyroidism post-RAI varies from 9-17%. Retrospective studies have observed hyperthyroidism within the first 12 months post-RAI; however, some cases have seen a resurgence as late as 22 years later. Recurrent hyperthyroidism is an uncommon occurrence with various postulated aetiologies, such as inadequate dosing/incomplete ablation with residual cells remaining viable and regenerating in the setting of increased TSIiv, Marine-Lenhart syndrome (MLS), or an unclear mechanism associated with autoimmunity in the presence of TSI. Hyperthyroidism rarely recurs in GD after successful post-ablative treatment with RAI. Our case, while an uncommon presentation and underlying aetiology yet to be determined, illustrates the importance of continued surveillance, even after successful treatment.‌ Presentation: 6/3/2024

Pharmacogenetic Considerations in Beta-Blocker Therapy

Pharmacogenetic testing offers a promising approach to personalizing beta-blocker therapy which is used for a variety of diseases, such as heart failure, myocardial infarction and migraine prophylaxis. The genetic variability in the metabolism and response to beta-blockers such as metoprolol can significantly influence treatment outcomes. Understanding these genetic differences can help optimize therapy and minimize adverse effects. A brief summary of the current guideline and recommendations: Approximately 0.3-6.5% (depending on their ancestry) of patients are CYP2D6 poor metabolizers. CYP2D6 Poor Metabolizers have significantly decreased metabolism of metoprolol, leading to increased drug concentration and a higher risk of adverse effects. The highest dose of metoprolol that patients can tolerate may be lower in CYP2D6 poor metabolizers compared to those that are non-poor CYP2D6 metabolizers. Current evidence is insufficient to support routine clinical testing or therapeutic adjustments for other genes affecting beta-blocker pharmacodynamics, such as ADRB1, ADRB2, ADRA2C, and GRK5. Future research should consider the combined effects of multiple genetic variants (e.g., polygenic risk scores) rather than focusing solely on single-gene associations.

Impact of CYP2D6 and ADRB1 polymorphisms on heart rate of post-PCI patients treated with metoprolol.

Aim: To explore the effect of CYP2D6*10 (100C>T) and ADRB1 1165 G>C polymorphisms on heart rate of post-PCI (percutaneous coronary intervention) patients treated with metoprolol succinate sustained-release tablets. Methods: A total of 756 inpatients with metoprolol succinate sustained-release tablets were selected and the genotypes of CYP2D6*10 and ADRB1 1165G>C were detected in 319 patients using gene chip detection. The target heart rate was defined as a resting heart rate<70beats/min. Clinical data were collected. Results: A total of 319 inpatients were enrolled in the study. The mutant allele frequencies of CYP2D6 and ADRB1 were 57.21 and 69.44%, respectively. Whatever the dose of metoprolol, the heart rates were lower in patients with homozygous mutation of CYP2D6 than those with heterozygous mutation and wild-type (p<0.05). Nevertheless, this effect was not seen between different genotypes of ADRB1. Logistic regression analysis showed that the dose of metoprolol and the genotypes of CYP2D6 were predictors of heart rate<70beats/min in these patients. Further multivariate analysis indicated that patients with homozygous mutation had better control of heart rates compared with those with wild-type and heterozygous mutation of CYP2D6*10 genotypes (all: p<0.001). Conclusion:CYP2D6*10 polymorphisms were associated with the heart rate of post-PCI patients treated with metoprolol succinate sustained-release tablets.

Ageing and Polypharmacy in Mesenchymal Stromal Cells: Metabolic Impact Assessed by Hyperspectral Imaging of Autofluorescence.

The impact of age on mesenchymal stromal cell (MSC) characteristics has been well researched. However, increased age is concomitant with increased prevalence of polypharmacy. This adjustable factor may have further implications for the functionality of MSCs and the effectiveness of autologous MSC procedures. We applied hyperspectral microscopy of cell autofluorescence-a non-invasive imaging technique used to characterise cytometabolic heterogeneity-to identify changes in the autofluorescence signals of MSCs from (1) young mice, (2) old mice, (3) young mice randomised to receive polypharmacy (9-10 weeks of oral therapeutic doses of simvastatin, metoprolol, oxycodone, oxybutynin and citalopram), and (4) old mice randomised to receive polypharmacy. Principal Component Analysis and Logistic Regression Analysis were used to assess alterations in spectral and associated metabolic characteristics. Modelling demonstrated that cells from young mice receiving polypharmacy had less NAD(P)H and increased porphyrin relative to cells from old control mice, allowing for effective separation of the two groups (AUC of ROC curve > 0.94). Similarly, cells from old polypharmacy mice were accurately separated from those from young controls due to lower levels of NAD(P)H (p < 0.001) and higher porphyrin (p < 0.001), allowing for an extremely accurate logistic regression (AUC of ROC curve = 0.99). This polypharmacy regimen may have a more profound impact on MSCs than ageing, and can simultaneously reduce optical redox ratio (ORR) and increase porphyrin levels. This has implications for the use of autologous MSCs for older patients with chronic disease.

The influence of sex on the treatment of postural tachycardia syndrome in children.

There are differences in postural tachycardia syndrome (POTS) incidence and manifestations in children between the sexes. However, there is limited evidence on how the gender affects the prognosis of POTS in children. This study is aimed at exploring the differences between the sexes regarding the prognosis of children with POTS. A retrospective study was conducted on children (n = 53; aged 6-14 years) who were diagnosed with POTS. All the POTS patients were given health education and autonomic function training, their water and salt intake was increased (oral rehydration salt III, 250 mL, Bid), and they were administered oral metoprolol (1 mg/kg per day) for 3 months. The prognosis was defined by the head-up tilt test results after treatment. It was observed that male and female children exhibited different trends in POTS prognosis. Further, the sex showed a stable independent effect on prognostic in children with POTS. To elaborate, females had a 503% increased risk of poor prognosis compared to males. We hence hypothesize that there is an association between the sex and the POTS prognosis in children. Female patients have a significantly higher risk of poor prognosis compared to males. A slight increase in the dose of oral rehydration salt could help lower the risk of poor prognosis in children with POTS. A higher absorption of total metoprolol, lower local concentrations, and slower metabolic excretion are documented in research in female POTS patients during treatment. It is recommended that the optimal dose of metoprolol should be lowered in female children undergoing treatment, to limit the risk of poor prognosis.

Role of enteral metoprolol tartrate on hemodynamics and clinical outcomes of septic shock patients of various pretargeted heart rate groups

Introduction Although septic shock mortality has decreased lately due to better identification and timely application of therapies. Research has continued for 20 years, but no therapies have been discovered yet to change sepsis’s course once it is infected. Objective The aim of this study was to evaluate the effect of enteral metoprolol tartrate on hemodynamics and clinical outcomes in patients with septic shock grouped into various pretargeted heart rate (HR) groups. Methods Septic shock patients (n=90) were randomly assigned directly after the resuscitation into 3 groups (30 in each). Then, treatment with metoprolol tartrate was started. The dose of metoprolol was 25-150 mg every 12 h and increased gradually to reach the pretargeted HR group range; group A (HR = 60-70 beats/min), group B (HR = 71-80 beats/min), and group C (HR = 81-90 beats/min). Metoprolol was continued to maintain the targeted HR till either discharge form intensive care unit (ICU) or death. The primary outcomes measured were mean arterial pressure (MAP), mixed venous oxygen saturation (SvO2), serum lactate, and sequential organ failure assessment (SOFA) score. Results After 1 day, group A (60-70 beats/min) had a significantly higher MAP (61.73±6.39 mmHg) than group B (51.33±7.76 mmHg) and group C (52.0±7.14 mmHg) (P &lt; 0.001). After 3 days, group A had a significantly improved SvO2, lower serum lactate, and lower SOFA score than the other groups (all P &lt; 0.05). When compared with groups B and C, group A had decreased norepinephrine (NE) requirements (P &lt; 0.001) and shorter ICU stay (P = 0.001). Conclusion Targeting HR between 60-70 beats/min using metoprolol tartrate, when compared with higher targets in septic shock after hemodynamic stabilization, was not associated with profound hypotension but also with earlier improved MAP, tissue perfusion measured as SvO2 and serum lactate, and organ failure measured as the SOFA score. It also showed decreased Norepinephrine requirements and a shorter ICU stay, but with no 28-day mortality benefit.

Metoprolol versus diltiazem in the emergency department for atrial fibrillation with rapid ventricular response

BackgroundAtrial fibrillation (Afib) is the most commonly treated arrhythmia in the Emergency Department (ED). Multiple guidelines recommend the use of intravenous (IV) beta-blocking (BB) agents or nondihydropyridine calcium channel blockers (Non-DHP CCB) as first line agents for heart rate control. Data regarding optimal first line selection between the agents is lacking. ObjectivesThe primary objective was to determine whether a clinically significant difference exists in achieving rate control and time to rate control between use of IV metoprolol or diltiazem. MethodsThis was a dual center, retrospective, cohort, chart review of patients presenting to the ED from January 1, 2015 to March 1, 2020, who received either IV bolus doses of metoprolol or diltiazem for Afib with RVR. Inclusion criteria: ≥18 years of age, received a bolus dose(s) of IV metoprolol or diltiazem for management in the ED, and ECG confirmed diagnosis of Afib based on ICD 9/10 codes. ResultsAnalyzed 305 patients with 99 patients in the metoprolol group and 206 patients in the diltiazem group. The primary outcome of time to HR ​< ​110 bpm was not statistically significant between metoprolol and diltiazem groups. Rates of adverse events including bradycardia and hypotension were not significantly different. ConclusionThere was no significant difference in the time to adequate heart rate control following administration of IV metoprolol or diltiazem for the treatment of atrial fibrillation with rapid ventricular response.

A Systematic Review of Weight-Based Metoprolol for Acute Atrial Fibrillation with Rapid Ventricular Rate.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in the emergency department (ED) and when patients present in acute AF with rapid ventricular rate (RVR), it can result in significant morbidity and mortality. Primary treatment modalities are aimed at rate control with the two most common agents being intravenous metoprolol and diltiazem. Some evidence suggests that diltiazem may be more effective at controlling rate in these patients; however, the dosing strategies, pharmacologic differences, and study designs may play a role in the observation of these differences. The purpose of this article is to review the evidence for using weight-based metoprolol in the treatment of AF with RVR. The vast majority of studies comparing metoprolol and diltiazem for the treatment of acute AF with RVR compare a flat dose of metoprolol to a weight-based dose of diltiazem. Following a comprehensive review, only two studies have compared a weight-based dosing strategy of intravenous (IV) metoprolol versus IV diltiazem for this disease state. Overall, the two studies only contained 94 patients and failed to meet power. Beyond differing dosing strategies, differences in pharmacokinetics between the two medications (like the onset of action and metabolism) could have played a role in the differences observed in the studies. Further studies are warranted to provide better guidance on which agent should be used in the treatment of acute AF with RVR.

Absent Right Coronary Artery in an Active Young Female

Absent Right Coronary Artery in an Active Young Female

Evaluation of the Effect of Metoprolol Dosage on Fat Graft Survival.

The aim of this study was to evaluate the effect of different metoprolol doses on fat graft survival. A total of 10 Sprague-Dawley rats were used in the study. The dorsal regions of the rats were separated into four quadrants: right and left cranial, and right and left caudal. Each quadrant was determined as a separate group. Fat grafts were harvested from the groin areas and incubated in 5ml solutions containing 0.9% sodium chloride (control group), 1mg/mL metoprolol (Group 1), 2mg/mL metoprolol (Group 2), and 3mg/mL metoprolol (Group 3), respectively. The fat grafts were then placed in pockets dissected in each of the 4 dorsal quadrants. After 3 months all the rats were euthanized. The fat grafts were removed together with the surrounding area to which they had passed. Histopathological examination was made with hematoxylin and eosin (HE) and Masson Trichrome staining, and immunohistochemical examination with fibroblast growth factor-2 and perilipin staining. In the examinations made with HE and Masson Trichrome staining, the scores of Group 2 and Group 3 were determined to be significantly higher than those of the control group (p<0.05). The Group 3 scores were significantly higher than those of Group 1 (p<0.05). In the examinations made with fibroblast growth factor-2 staining, the scores of Group 2 and Group 3 were determined to be significantly higher than those of the control group (p<0.05). The Group 3 scores were significantly higher than those of Group 1 and Group 2 (p<0.05). In the examinations made with perilipin staining, the scores in Groups 1, 2, and 3 were higher than those of the control group (p<0.05). Although metoprolol has previously been shown to prolong the survival of fat grafts, the results of this study demonstrated immunohistochemically that as the metoprolol dose increased, so the quality and vitality of fat graft also increased. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intravenous metoprolol versus diltiazem for atrial fibrillation with concomitant heart failure

PurposeAtrial fibrillation (Afib) with rapid ventricular response (RVR) is acutely treated with intravenous push (IVP) metoprolol (MET) or diltiazem (DIL). In heart failure (HF) patients, diltiazem is not recommended due to negative inotropic effects. Studies comparing the treatment of atrial fibrillation often exclude HF. Hirschy et al. evaluated HF patients with concomitant Afib with RVR who received IVP metoprolol or diltiazem to determine their effectiveness and safety. They found similar safety and effectiveness outcomes between the two groups. MethodsThis retrospective, IRB-approved study evaluated patients presenting to the emergency center (EC) with Afib with RVR and HF from January 1, 2018 to July 31, 2021. Included patients were 18 years of age or older, received IVP metoprolol or diltiazem in the EC, and had a recorded baseline ejection fraction (EF). The primary effectiveness outcome was successful heart rate (HR) control 30 min after treatment with either IVP metoprolol or diltiazem, which was defined as HR <100 beats per minute (bpm). Secondary effectiveness outcomes included HR control 60 min post-IVP and at EC discharge or transfer and HR reduction >20% at 30 min after IVP, 60 min after IVP, and at time of discharge or transfer. Other secondary outcomes included the time to adequate HR control, the total dose of IVP metoprolol or diltiazem given, any additional rate-controlling agents given, and crossover between metoprolol and diltiazem. Safety outcomes included bradycardia, hypotension, shortness of breath, increased oxygen requirements, change in EF, acute kidney injury or renal replacement therapy. ResultsOf 2580 evaluated, 193 patients were included (134 DIL vs. 59 MET) with age 73.3 ± 12.2 years, 63% female. The average EF was 48.2 ± 14.2% and 30% of patients had heart failure with reduced ejection fraction (HFrEF) while 64% had heart failure with preserved ejection fraction (HFpEF). Effective heart rate control 30 min post-IVP was not different between the two groups (55% DIL vs. 41% MET, p = 0.063). DIL effectively controlled HR quicker than MET (13 [9, 125] DIL vs. 27 [5, 50] MET, min, p = 0.009). DIL resulted in greater HR reductions at 30 min (33.2 ± 25.4 DIL vs. 19.7 ± 19.7 MET, bpm, p < 0.001) and at 60 min (31 ± 23.5 DIL vs. 19.6 ± 19.1 MET, bpm, p = 0.002). DIL also more frequently resulted in a HR reduction of 20% or greater at 30 min (63% DIL vs. 27% MET, p < 0.001), 60 min post-IVP (59% DIL vs. 41% MET, p = 0.019), and at time of patient discharge or transfer from the EC (70% DIL vs. 49% MET, p = 0.005). No differences in safety outcomes were identified. ConclusionAcute management of patients with Afib with RVR and HF is challenging. While successful rate control at 30 min was not significantly different between diltiazem and metoprolol, IVP diltiazem reduced HR more quickly and reduced HR by 20% or greater more frequently than IVP metoprolol with no safety outcome differences. Further studies are needed to evaluate diltiazem's safety in patients with Afib and HF.

Baroreflex sensitivity predicts therapeutic effects of metoprolol on pediatric postural orthostatic tachycardia syndrome.

ObjectiveTo determine if the baseline baroreflex sensitivity (BRS) could be a useful predictor for the metoprolol therapeutic efficacy on postural orthostatic tachycardia syndrome (POTS) in children.MethodsIn this retrospective case-control study, 54 children suffering from POTS treated with metoprolol were recruited from the pediatric department of Peking University First Hospital. After 2–3 months of metoprolol treatment, all subjects were divided into responders and non-responders based on whether the symptom score (SS) was decreased by over 50% after metoprolol treatment at the follow-up. The baseline demographic parameters and the supine BRS during the head-up tilt test (HUTT) obtained by Finapres Medical System (FMS) were compared between the two groups. The value of BRS to predict the effectiveness of POTS was analyzed by a receiver-operating characteristic (ROC) curve.ResultsThe age, sex, height, weight, body mass index (BMI), course of the disease, baseline SS, medication time, metoprolol dose, and follow-up time of the subjects were not statistically different between the responders and non-responders (P > 0.05). The decline in symptom scores (ΔSS) of the responders was more obvious than that of the non-responders (P < 0.01). The supine BRS, BRS at maximum HR, supine heart rate (HR), and maximum HR were different between responders and non-responders (P < 0.01, P = 0.022, P < 0.01, P = 0.047). The binary multivariable analysis showed that baseline supine BRS was significantly associated with the response to metoprolol therapy [OR: 2.079, 95% CI: (1.077, 4.015), P = 0.029]. According to the ROC curve, the area under the curve (AUC) of baseline BRS was 0.912 (95% CI, 0.840–0.984), with a cut-off value of 8.045 ms/mmHg, yielding a sensitivity and specificity of 75.8% and 95.2%, respectively, in predicting the effectiveness of POTS.ConclusionThe baseline supine BRS level > 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized β-adrenoceptor blocker use in pediatric patients suffering from POTS.

Abstract P027: Yamaguchi Syndrome Presenting With Atrial Fibrillation And Heart Failure Diagnosed With Contrast Echocardiography

Yamaguchi syndrome or apical hypertrophic cardiomyopathy (ApHCM), is a rare variant of hypertrophic cardiomyopathy (HCM), prevalence of about 3% among HCM population in the United States. Generally considered a benign condition but can be potentially life-threatening. A 84 year old female with history of mitral regurgitation with mitra-clip, paroxysmal atrial fibrillation (pAF) presented to ED with dyspnea and leg swelling. She was tachypneic with bibasilar rales, jugular venous distention. BNP 1,086 pg/l with cardiomegaly and pulmonary edema on chest x-ray. She was managed for acute decompensated cardiac failure (NYHA class III) using IV furosemide with symptom improvement. EKG revealed AF with abnormal deep T-wave inversion most prominent in precordial leads (V4-V6). Contrast echocardiogram revealed ApHCM, missed on prior echocardiograms. Patient’s dose of metoprolol was doubled, and outpatient follow-up was scheduled. Conclusion: ApHCM commonly presents with heart failure symptoms, chest pain, palpitation, or syncope. Undiagnosed/untreated ApHCM can lead to complications including diastolic dysfunction, left atrial enlargement causing atrial fibrillation, apical clots formation with subsequent thromboembolism, ventricular wall aneurysm, arrhythmias, and myocardial infarction. In our case, contrast echocardiogram was able to diagnose ApHCM. A presentation of heart failure symptoms at NYHA class II or higher is a known predictor of poor prognosis in patients with ApHCM. Missing diagnosis on normal echocardiogram without use of ultrasound contrast is very common. Diagnosing with proper use of modality can help to improve outcomes in these patients.

Leveraging large observational studies to discover genetic determinants of drug concentrations: A proof‐of‐concept study

Large, observational genetic studies are commonly used to identify genetic factors associated with diseases and disease‐related traits. Such cohorts have not been commonly used to identify genetic predictors of drug dosing or concentrations, perhaps because of the heterogeneity in drug dosing and formulation, and the random timing of blood sampling. We hypothesized that large sample sizes relative to traditional pharmacokinetic studies would compensate for this variability and enable the identification of pharmacogenetic predictors of drug concentrations. We performed a cross‐sectional, proof‐of‐concept association study to replicate the well‐established association between metoprolol concentrations and CYP2D6 genotype‐inferred metabolizer phenotypes in participants from the Montreal Heart Institute Hospital Cohort undergoing metoprolol therapy. Plasma concentrations of metoprolol and α‐hydroxymetoprolol (α‐OH‐metoprolol) were measured in samples collected randomly regarding the previous metoprolol dose. A total of 999 individuals were included. The metoprolol daily dose ranged from 6.25 to 400 mg (mean 84.3 ± 57.1 mg). CYP2D6‐inferred phenotype was significantly associated with both metoprolol and α‐OH‐metoprolol in unadjusted and adjusted models (all p < 10−14). Models for metoprolol daily dose showed consistent results. Our study suggests that randomly drawn blood samples from biobanks can serve as a new approach to discover genetic associations related to drug concentrations and dosing, with potentially broader implications for genomewide association studies on the pharmacogenomics of drug metabolism.

FAILURE TO CONSIDER FUTURE ATRIAL FIBRILLATION RATE CONTROL NEEDS AFTER PRESENTATION TO THE EMERGENCY DEPARTMENT WITH RAPID RATE

Atrial fibrillation (AF) usually presents to the emergency room (ED) with a rapid ventricular rate, which commonly, but not always, is symptomatic. Rate control is usually easily managed with diltiazem (DTZ) and beta blockers (BBs), typically metoprolol (MTP). Sinus rhythm is frequently restored within 48 hours by means of spontaneous conversion, electrical cardioversion, or medications. However, AF recurs within one year in 60-80% of these subjects. There are little data describing doses of DTZ and MTP used for AF rate control at discharge. A retrospective study of 576 patients presenting with acute AF were evaluated for admission and discharge rate control medications (RCMs). For the 319 (68%) patients with a ventricular rate ≥110bpm the admission and discharge dose of MTP was 61mg and 63mg and DTZ was 195mg and 204mg, respectively. Those who remained in AF had a modest increase in the two medications compared to the patients who converted to sinus rhythm. Current guidelines recommend DTZ up to 300 to 400mg and MTP up to 300mg for rate control for select patients. Concerns about high doses of MTP are mitigated by the MERIT-HF Trial demonstrating improved mortality and symptoms with doses of MTP up to 200mg demonstrating the safety and efficacy of MTP in high risk patients. Lack of follow-up of future AF recurrences is a limitation of the study. For those patients with acute AF and a heart rate (HR) &gt;110bpm, a minimal increase in RCMs for those in AF at discharge was noted.

Pharmacokinetics and pharmacodynamics of oral and intravenous metoprolol tartrate in clinically healthy horses.

Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04mg/kg) and PO (6mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics were modeled using a 3-compartment model and non-linear least squares regression. Median (range) MET concentration was 110 (40.1-197) ng/ml collected 1min (0.0167h) after a bolus IV administration. Maximum concentration (Cmax ) after PO administration was 2135 (1590-4170) ng/ml at 0.5 (0.25-0.5) hours. Oral bioavailability was 54% (17-100%). Median apparent volume of distribution was 0.39 (0.17-0.58) l/kg, clearance was 12.63 (11.41-18.94) ml/kg/min, and elimination half-life was 21.1 (7.46-34.36) minutes. No clinically relevant effects of IV or PO metoprolol were noted on cardiac rhythm or NIBP. Sweating was the most common side effect. The metoprolol doses used in this study achieve plasma concentrations reported to achieve ß-blockade in humans.

A Case of High Dose Metoprolol Poisoning; Case Report and Literature Review

β-Blockers are prescribed by physicians for many medical reasons (hypertension, long-term prophylaxis of angina pectoris, myocardial infarction, stable heart failure treatment, cardiac arrhythmias, etc.). Although cases of β-blocker poisoning have a low rate of 0.9% among all poisoning cases, they have a high mortality rate. In β-blocker poisoning with high lipid solubility; seizures, respiratory depression, coma, resistant bradycardia-hypotension and shock may occur. Metoprolol, a type of β-blocker, is a selective β1-adrenoceptor antagonist with sympathomimetic effect. It is also reported that metoprolol is the 2nd most commonly prescribed β-blocker after bisoprolol all over the world. This article aims to present a case who took high-dose metoprolol for suicidal purposes and to examine metoprolol poisoning and its treatment in the light of current literature.

A Case of High Dose Metoprolol Poisoning; Case Report and Literature Review

A Case of High Dose Metoprolol Poisoning; Case Report and Literature Review