Metoprolol XL Research Articles

5150 When Few Options Exist: Graves’ Disease Treated with Potassium Iodide and Levothyroxine Block-and-Replace Therapy

Abstract Disclosure: O. Magvanjav: None. S.K. Majumdar: None. Background: In the US, methimazole and propylthiouracil are effective first-line agents for the treatment of Graves’ disease. However, side effects including liver dysfunction may limit their use. In such instances, alternative non-conventional agents such as potassium iodide (KI) may be considered. Here, we present a case of a patient with Graves’ disease successfully treated with KI, drawing on the example of similar treatment experiences in Japan. Clinical case: Our patient is a 29-year-old woman who presented with a 3-week history of palpitations accompanied by fatigue, heat intolerance, itchiness, insomnia, and unintentional weight loss. Exam was notable for tachycardia (135 bmp), elevated blood pressure (BP) (150/81 mmHg), normal temperature, slight thyromegaly, brisk reflexes, mild anxiousness, and tremulousness. She was found to have a TSH of 0.007 mIU/ml (normal: 0.270-4.200 mIU/ml), elevated free T4 of 5.19 ng/dl (normal: 0.80-1.70 ng/dL), total T3 of 330 ng/dl (normal: 72.0-153.0 ng/dl), total T4 of 12.1 ug/dl (normal: 4.5-11.7 ug/dl), and positive antibodies (TSI 443%; TRAB 5.42 IU/L). A thyroid ultrasound showed diffuse hyperemia and a 1.4 cm right lobe TR3 nodule. She had a normal baseline neutrophil count with mild eosinophilia; a baseline hepatic function panel was not obtained. She was started on methimazole 20 mg daily and metoprolol XL 50 mg daily for symptom control. One week into treatment, a hepatic function panel showed elevated liver enzyme levels: AST 70 U/L (normal: 10-35 U/L) and ALT 223 U/L (normal: 10-35 U/L); previous values from 2 years prior were normal. Repeat levels a few days later showed increasing liver enzyme levels (AST 83 U/L; ALT 268 U/L) despite decreasing thyroid hormone levels. Methimazole was stopped, and she was then seen by a gastroenterologist, who concurred with the possibility of an adverse drug reaction to methimazole. She declined definitive therapy with surgery or radioactive iodine therapy and wanted to pursue alternative and less invasive options. Drawing on a previous successful experience from Japan, we initiated her on KI (50 mg twice daily), which resulted in normalization of her thyroid hormones within two weeks of initiation. She subsequently developed hypothyroidism 2 months later, at which point we initiated block-and-replace therapy with the addition of 50 mcg of levothyroxine. Her liver enzymes normalized with normalization of thyroid hormones. Conclusions: We present a patient with symptomatic Graves’ disease who was successfully treated with KI in the setting of limited treatment options, specifically an adverse reaction to methimazole (transaminitis), and who declined both surgery and radioactive iodine. This case demonstrates that KI may be useful in Graves’ disease as either a bridge to more definitive therapy when thioamides are not tolerated, or perhaps as a treatment option for those most likely to go into remission. Presentation: 6/1/2024

Abstract 12764: Reduced EF With Mavacamten Initiation in a Patient With Atrial Fibrillation: A Case Report

Description of Case: A 55-year-old male with a history of paroxysmal atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM) diagnosed three years prior at an outside institution presented to clinic with exertional dyspnea. Baseline TTE confirmed HCM demonstrating an EF of 69%, mitral systolic anterior motion (SAM), left ventricular outflow tract (LVOT) obstruction, and a peak gradient exceeding 100 mmHg. Initiation of mavacamten 5mg resulted in symptom improvement and a one-month follow-up TTE demonstrating a reduced peak gradient of 74 mmHg and normal EF. However, two months after initiation the patient returned with AF with rapid ventricular response (RVR) and TTE showed a newly reduced EF of 21%. Mavacamten was stopped while home metoprolol XL was increased from 100 to 150 mg daily for rate optimization. Holter monitoring showed a 100% Afib burden with an average heart rate of 108 beats per minute. Stopping mavacamten for four weeks resulted in worsening exertional dyspnea but restoration of EF to 52% on TTE. Mavacamten was reinstated at a lower dose of 2.5 mg, resulting in symptom improvement. Monthly TTE exams over four months consistently demonstrated a normal EF without LVOT obstruction at rest. Discussion: Mavacamten, a promising drug used to treat obstructive HCM, modulates myosin to reduce myosin-actin cross-bridging. Reduction in contractility improves mitral SAM, LVOT obstruction, and symptoms. However, because mavacamten is a negative inotrope it can also precipitate reductions in EF. Generally, patients have a mild drop in EF (~5 points) after initiation. However, our patient had a significant EF drop of over 25 points likely due to both mavacamten initiation and new AF with RVR reducing systolic function. Discontinuation of mavacamten for four weeks and rate optimization likely restored EF. Dose reduced re-initiation of mavacamten resulted in long-term normal EF and improvement in symptoms. This case highlights the need for close monitoring and individualized mavacamten treatment plans. Further research is warranted to understand the interplay and long term outcomes of tachyarrhythmias and mavacamten use.

A patient with obstructive hypertrophic cardiomyopathy: a case report

Background: Hypertrophic cardiomyopathy (HCM) is a left ventricle hypertrophic condition related to genetic disorders involving the gene encoding protein from the cardiac sarcomere apparatus. The prevalence of this disease is relatively low, but various clinical presentations make underrecognized and underdiagnosed. We reported obstructive hypertrophy cardiomyopathy patients with an episode of unexplained syncope and malignant arrhythmia.Case Report: A 44 years old man came with the chief complaint of shortness of breathing. The patient felt the chief complaint since two years ago with getting worse during mild physical activity. The symptom got better during rest or slept with one pillow without complaining of dyspnea. One year ago, the patient started to feel palpitation disappear and arise with shortness of breathing. The patient got syncope two weeks ago during mild activities after a short period of breathlessness. For the vital sign, blood pressure was at 90/60 mmHg, blood pulse was 67 bpm irregular, breath frequency was 17x/min, and oxygen saturation was 99% room air. The electrocardiogram (ECG) showed atrial fibrillation with regular ventricular rate and left bundle branch block morphology of the QRS complex with Q wave at anterior precordial. The patient also checked for electrocardiography and ambulatory ECG monitoring using Holter. The patient was diagnosed with obstructive hypertrophy cardiomyopathy (OHCM), atrial fibrillation with regular ventricular rate and given Dabigatran 110 mg twice daily, metoprolol XL 12,5 mg once daily, and furosemide 10mg once daily for his medication.Conclusion: Theoretically, myectomy is the best option for this case; however, due to limited high-volume hospitals in Indonesia doing myectomy for hypertrophic obstructive cardiomyopathy, alcohol septal ablation may be an alternative option if the medication was no longer adequate to improve symptoms.

Abstract 13100: Rescue Myocardial Aging Caused a Progressive Decline in Cardiac Function and β-Adrenergic Reserve With a Selective Beta3-Adrenergic Receptor Antagonist, but Not Beta1-Adrenergic Receptor Blocker in a Murine Model

Background: Cardiac aging (CA) leads to the progressive decline in cardiac function- increasing risk for heart failure (HF) and cardiac mortality. Both down-regulation of β 1 -adrenergic receptors (AR) and up-regulation of a newly-described inhibitory pathway mediated by β 3 -AR may play a crucial role in the development of CA. β-AR blockers are a mainstay in the therapy of several cardiovascular diseases, including HF. However the therapeutic effects of different β blockers in CA are unknown. We tested the hypothesis that up-regulation of cardiac β 3 -AR with enhanced negative inotropic actions, rather than the desensitization of β 1 -AR, is the critical determinant of the dysfunctional β-AR regulation that occurs in CA. Thus, β 3 -AR antagonists (β 3 ANT), but not β 1 Blockade, may reverse the progression of age-associated deficits in LV myocyte functional performance. Methods: LV myocyte basal and isoproterenol (ISO)-stimulated functional and [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses were compared in 4 groups (7/group) of wild-type (WT) mice: 1) YWT , young (Y, 6 mo); 2) Aβ 3 ANT , aged (A, 26 mo) treated with β 3 ANT (L-748,337, 10 -7 M/kg/day, mini-pump) for 12 weeks (W);3) Aβ 1 Blockade , metoprolol XL (1.5 mg/kg/day, po), a selective β 1 blocker was given for 12 W and 4) AWT , aged sham control. Results: Compared with YWT, AWT myocytes had about 30% decreases in basal cell contraction (dL/dt max , 85.9 vs 122.3 μm/s) and relaxation (dR/dt max , 69.4 vs 99.2 μm/s) with reduced the peak [Ca 2+ ] iT (0.17 vs 0.21). ISO (10 -8 M)-stimulated increases in dL/dt max (33% vs 69%), dR/dt max (31% vs 62%) and [Ca 2+ ] iT (15% vs 34%) also significantly reduced. In Aβ 1 Blockade group, metoprolol therapy failed to improve basal dL/dt max (86.3 μm/s), dR/dt max (68.9 μm/s) and [Ca 2+ ] iT (0.18). ISO-stimulated increases in dL/dt max (34%), dR/dt max (35%) and [Ca 2+ ] iT (17%) remained attenuated. By contrary, Aβ 3 ANT myocytes showed normal basal cell contraction (131.0 μm/s), relaxation (101.9 μm/s) and [Ca 2+ ] iT (0.21) with preserved ISO-stimulated increases in dL/dt max (68%), dR/dt max (59%) and [Ca 2+ ] iT (32%). Conclusions: Chronic β 3 -AR antagonist, but not β 1 -AR blocker leads to the preservation of myocyte function, [Ca 2+ ] iT , and β-adrenergic responsiveness in a murine model of cardiac aging.

SAT-501 Thyrotoxicosis with Pre-Ventricular Complexes Resulting in Thyroid Storm and Cardiac Arrest

Background: Ventricular arrythmias are a rare, often lethal complication of thyrotoxicosis. We describe a patient with uncontrolled hyperthyroidism and pre-ventricular complexes (PVCs) who presented with ventricular tachyarrhythmia cardiac arrest and was successfully resuscitated. Clinical Case: A 64 year old woman was diagnosed with thyrotoxicosis secondary to Graves’ disease [TSH < 0.01 (0.40 – 4.5 mcIU/mL) and free T4 of 2.8 (0.8 – 1.8 ng/dL)] 1 year ago in the setting of a 6 month history of weight loss, palpitations, tremors, and a large goiter. She was started on methimazole and metoprolol XL and was intermittently compliant. During follow-up evaluation she complained of light headedness, developed agonal breathing, and became pulseless. Chest compressions were initiated. She regained spontaneous rhythm after receiving 1 shock with an Automated Electronic Defibrillator (AED). She was transferred to the Emergency Room (ER) and intubated for altered mental status.Emergent CT Angiography and bedside echocardiogram showed no pulmonary embolism and normal biventricular function. Troponin T high sensitivity assay was negative and electrolytes were normal. Repeat thyroid function tests showed TSH <0.01, Free T4 of 5.6 and free T3 of 14.5 (2.0 – 4.4 pg/mL). She was started on propylthiouracil, glucocorticoids, potassium iodide and treated for thyroid storm. EKG in the ER showed sinus tachycardia with no ischemic ST changes but PVCs and fusion complexes were noted. These were also present on EKG at the time of her initial diagnosis of hyperthyroidism. EKGs prior to the diagnosis of hyperthyroidism showed normal sinus rhythm.Cardiac arrest was attributed to thyrotoxicosis as there was no infectious nidus and no evidence of structural cardiac disease. The AED rhythm strips could not be obtained but she was presumed to have an appropriately shockable ventricular tachyarrhythmia such as ventricular tachycardia (VT) or ventricular fibrillation (VF).Her thyroid hormone levels declined appropriately over the course of the hospitalization and PVCs were no longer noted on telemetry and daily EKGs. She was discharged on methimazole which she took consistently. She underwent RAI ablation several months after discharge. Conclusion: Failure to achieve rapid euthyroidism in thyrotoxicosis is associated with increased cardiovascular morbidity and mortality (1). Most arrythmias associated with thyrotoxicosis are supraventricular and ventricular arrythmias are a rare sequela (2). This is one of the few cases reported of antecedent PVCs being noted on EKG. The PVCs resolved with anti-thyroid medications.

Abstract 18718: Differential Effects of Nebivolol and Metoprolol on Oxidative Stress Markers and Circulating Progenitor Cells

Background: Unlike traditional beta-blockers, nebivolol activates nitric oxide (NO) release via partial agonist activity at beta-2/3 receptors. We hypothesized that this property of nebivolol compared to metoprolol would improve oxidative stress (OS) and mobilize progenitor cells (PCs) that are known to be enhanced by NO, and ultimately contribute to improved vascular health. Methods: Thirty-two hypertensive subjects (age 54±10 years, 57% male, 83% African American) were randomized in a double-blind, cross-over study to receive either nebivolol or metoprolol for 3 months each. Of the 32 subjects randomized, 30 subjects successfully completed the trial. Two subjects did not complete the study due to serious adverse events. Nebivolol was titrated from 5mg to 20mg daily (mean 12mg) and metoprolol XL from 50mg to 200mg daily (mean 123mg). All other hypertensive therapy was kept constant. Measurements were made at baseline and on each drug after 3 and 6 months. OS was estimated from plasma levels of glutathione that reflects increased oxidative stress at lower levels. Circulating PCs were measured using flow cytometry for CD34+ and CD34+/CD133+ positive cells in mononuclear cell pools (CD45med). Arterial stiffness was measured as pulse wave velocity and augmentation index using the Sphygmacor device. Results: Compared to baseline, both nebivolol and metoprolol significantly and equally lowered systolic and diastolic BP (p&lt;0.01). Nebivolol, but not metoprolol significantly increased the glutathione level (from 1.08 to 1.50μM; p=0.04). Both nebivolol and metoprolol significantly increased circulating numbers of CD34+/CD133+ PCs compared to baseline by 28% and 18%, respectively (p=0.02, for both). Neither nebivolol nor metoprolol significantly changed indices of arterial stiffness. Conclusion: Beta adrenergic antagonists increase circulating levels of PCs indicating improved regenerative capacity. Nebivolol, but not metoprolol, reduces oxidative stress, measured as plasma glutathione. The lack of translation of these effects on arterial stiffness may be secondary to the short duration of therapy in a treated population.

Abstract P333: Heart Rate Control in Patients With Chronic Atrial Fibrillation and Heart Failure

Background. Heart rate (HR) control is one of the main goals in management of patients with chronic atrial fibrillation (AF). However, rate control can be challenging in patients with heart failure (HF). The goal of our study was to determine if aggressive heart rate control in patients with both chronic AF and HF results in better exercise tolerance and/or quality of life (QOL) as compared to the “usual” care. Methods. This was a single center interventional study at VA Loma Linda Healthcare System using patients as their own controls. Patients with chronic AF and LVEF ≤ 40% were recruited. Intervention consisted of increasing doses of Metoprolol XL to achieve target resting heart rate less than 70 bpm. Clinical data was collected at baseline (“usual care”) and at follow-up (3 months) and included HR data, 6-minute walk test, QOL questionnaire (Minnesota Living with Heart Failure), and brain natriuretic peptide (BNP) levels. Paired t-test was performed to evaluate statistically significant change in these clinical measures. The study had 80% power to detect clinically significant improvement in 6-minute walk test (50 meters). Results. 20 patients were recruited with an average follow-up of 98 days. Mean age was 66 years and all the patients were male with an average LVEF of 30 ± 8% and NYHA class of II-III. Average resting HR was 94 ± 14 bpm at baseline and 85 ± 12 bpm after the intervention. Average Metoprolol XL dose at the end of the study was 121mg with the average increase of the dose during the study of 59 mg. Further increases of Metoprolol doses to achieve target HR were not tolerated by the patients. Conclusion. In this small group of patients with chronic AF and HF aggressive HR control was difficult due to patient intolerance of increasing doses of beta-blockade and was not associated with better exercise tolerance, better QOL or improved HF based on BNP measurement. Further studies are needed to establish guidelines for target HR in patients with chronic AF who also have significant HF. Clinical parameter Baseline Follow-up p-value 6-min walk test (meters) 326 ± 83 330 ± 86 0.47 QOL score 42.5 ± 19 38 ± 21 &gt;0.5 BNP 242 ± 306 279 ± 395 &gt;0.5 NYHA class 2.4 ± 0.7 2.2 ± 0.7 0.009

Effect of fixed dose combinations of metoprolol and amlodipine in essential hypertension: MARS – A randomized controlled trial

Aim. To compare two strengths of a fixed drug combination (FDC) containing metoprolol XL and amlodipine (metoprolol/amlodipine 50/5; and metoprolol/amlodipine 25/2.5) with its components in hypertension. Methods. We conducted this multicentre, randomized, open-label, trial in Indian patients with hypertension (140–180 mmHg/90–114 mmHg) in 11 centres from nine cities. Eligible patients (n = 402) were randomized into one of five treatment groups (metoprolol XL 50 mg + amlodipine 5 mg, metoprolol XL 25 mg + amlodipine 2.5 mg, metoprolol XL 50 mg, metoprolol XL 25 mg or amlodipine 5 mg) and treated for 8 weeks with five follow-up visits to record blood pressure (BP) and clinical status. Results. At baseline, treatment groups were well balanced; mean ± SD BP was 154.87 ± 11.91/96.63 ± 6.97 mmHg. The greatest reduction in BP from baseline to 8 weeks was seen in the high-dose FDC group (23.61/14.91 mmHg; p < 0.001). The remaining 4 groups too demonstrated a significant reduction (p < 0.001): low-dose FDC − 22.29/ − 14.66; metoprolol 50, − 23.17/ − 13.37; metoprolol 25, − 18.41/ − 12.50 and amlodipine 5, − 23.01/ − 13.08. BP reductions by FDCs, however, were not statistically superior to monotherapies. Responder rates (sitting diastolic BP < 90 mmHg or reduction ≥ 10 mmHg) were 93% in the high-dose FDC group and 97% in the low-dose FDC group, and control rates (sitting BP < 140/90 mmHg) were 66% and 58%, respectively. These rates were higher than that seen in individual components. There were no reports of serious adverse events related to study medications. One each from the low-dose FDC and metoprolol 25 mg group discontinued because of adverse events. Conclusions. FDCs of metoprolol and amlodipine are effective and safe in mild to moderate hypertension.

Efficacy and Tolerability of a Fixed-Dose Combination of Metoprolol Extended Release/Amlodipine in Patients with Mild-to-Moderate Hypertension

Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure. The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications. This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90-109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg). Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5 mg fixed-dose combination or losartan 50 mg plus amlodipine 5 mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks' therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p < 0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population. Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.

Antihypertensive efficacy of metoprolol XL/Low dose chlorthalidone (6.25 mg) combination: a randomized, comparative study in Indian patients with mild-to-moderate essential hypertension

ObjectiveHigh blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.MethodsTotal 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.ResultsThe study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na+, K+, Cl-)and fasting blood sugar, evident across the treatment groups.ConclusionChlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.

Differential Effects of Carvedilol and Metoprolol Succinate on Plasma Norepinephrine Release and Peak Exercise Heart Rate in Subjects With Chronic Heart Failure

Dosing equivalency of carvedilol and metoprolol remains a debate. Degree of beta 1-blockade is best assessed by blunting of the exercise-induced heart rate. Accordingly, the authors have investigated dosing equivalency by examining baseline and peak exercise heart rates and norepinephrine levels in subjects with chronic heart failure treated with carvedilol or metoprolol. Thirty-seven subjects treated with carvedilol (32.9 +/- 3.5 mg; n = 23) or metoprolol succinate (XL) (96.4 +/- 15.9 mg; n = 14) referred for cardiopulmonary exercise testing were studied prospectively. Carvedilol versus metoprolol XL subjects did not differ with respect to baseline heart rate (73 +/- 2 vs 70 +/- 3 bpm), or baseline plasma norepinephrine levels (597.5 +/- 78.3 vs 602.1 +/- 69.6 pg/mL), P = NS. However, despite similar peak exercise norepinephrine levels (2735.8 +/- 320.1 vs 2403.1 +/- 371.6 pg/mL), heart rate at peak exercise was higher in subjects receiving carvedilol (135 +/- 4 bpm) than those receiving metoprolol XL (117 +/- 6 bpm), P = 0.02. Similar norepinephrine release and more complete beta 1-blockade is observed in well-matched subjects with chronic heart failure treated with a mean daily dose of metoprolol XL 96.4 mg compared with carvedilol 32.9 mg.

Effect of Beta Blockers (Carvedilol or Metoprolol XL) in Patients With Transposition of Great Arteries and Dysfunction of the Systemic Right Ventricle

Effect of Beta Blockers (Carvedilol or Metoprolol XL) in Patients With Transposition of Great Arteries and Dysfunction of the Systemic Right Ventricle

Effect of Beta Blockers ( Carvedilol or Metoprolol XL) in Patients With Transposition of Great Arteries and Dysfunction of the Systemic Right Ventricle

This study evaluated the effects of beta blockers (carvedilol and metoprolol XL) on New York Heart Association functional class and systemic right ventricular (RV) function in patients with complete transposition of the great arteries who had systemic RV dysfunction late after atrial inflow correction. A significant improvement in New York Heart Association functional class was found after 4 months of therapy with beta blockers. Functional recovery was significant mostly in those patients with pacemakers who received higher maintenance doses of carvedilol. RV end-diastolic area was significantly greater in untreated patients at the end of the follow-up period, whereas it was unchanged in treated patients. In conclusion, beta blockers prevent RV remodeling, with a concomitant improvement in exercise tolerance in patients with complete transposition of the great arteries and systemic RV dysfunction.

Sustained Restoration of Autonomic Balance With Long- but Not Short-Acting Metoprolol in Patients With Heart Failure

Background The purpose of this study was to compare the effects of immediate-release (IR) metoprolol and extended-release (XL) metoprolol on measures of heart rate variability in chronic systolic heart failure patients. Methods and Results Thirteen metoprolol-treated heart failure patients were randomized to a 2-way crossover study of equal daily doses of metoprolol IR and metoprolol XL, each administered for 3 weeks. After each 3-week interval, patients underwent 24-hour Holter and ambulatory blood pressure monitoring. Over the entire 24-hour period, the ratio of high to total variability (normalized measure of parasympathetic activity) was significantly greater ( P < .05), the ratio of low to total variability (normalized measure of sympathetic activity) was significantly lower ( P < .05), and the ratio of high to low variability (index of parasympathetic to sympathetic balance) was greater ( P < .08) for metoprolol XL compared with metoprolol IR. Over the entire 24-hour period, both systolic and diastolic blood pressure were significantly lower for metoprolol XL compared with metoprolol IR ( P < .0001, and .0005, respectively). Conclusion These data suggest that with twice daily dosing, metoprolol IR is inferior to metoprolol XL in its effects on heart rate variability, autonomic balance, and blood pressure in patients with heart failure.

A comparative analysis of the results from 4 trials of β-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS

BackgroundRecent large randomized, controlled trials (BEST [β-blocker Evaluation of Survival Trial], CIBIS-II [Cardiac Insufficiency Bisoprolol Trial II], COPERNICUS [Carvedilol Prospective Randomized Cumulative Survival Study], and MERIT-HF [Metoprolol Randomized Intervention Trial in Congestive Heart Failure]) have addressed the usefulness of β-blockade in the treatment of advanced heart failure. CIBIS-II, COPERNICUS, and MERIT-HF have shown that β-blocker treatment with bisoprolol, carvedilol, and metoprolol XL, respectively, reduce mortality in advanced heart failure patients, whereas BEST found a statistically nonsignificant trend toward reduced mortality with bucindolol. We conducted a post hoc analysis to determine whether the response to β-blockade in BEST could be related to differences in the clinical and demographic characteristics of the study populations. We generated a sample from BEST to resemble the patient cohorts studied in CIBIS-II and MERIT-HF to find out whether the response to β-blocker therapy was similar to that reported in the other trials. These findings are further compared with COPERNICUS, which entered patients with more severe heart failure. MethodsTo achieve conformity with the entry criteria for CIBIS-II and MERIT-HF, the BEST study population was adjusted to exclude patients with systolic blood pressure <100 mm Hg, heart rate <60 bpm, and age >80 years (exclusion criteria employed in those trials). The BEST comparison subgroup (BCG) was further modified to more closely reflect the racial demographics reported for patients enrolled in CIBIS-II and MERIT-HF. The association of β-blocker therapy with overall survival and survival free of cardiac death, sudden cardiac death, and progressive pump failure in the BCG was assessed. ResultsIn the BCG subgroup, bucindolol treatment was associated with significantly lower risk of death from all causes (hazard ratio (HR)=0.77 [95% CI=0.65, 0.92]), cardiovascular death (HR=0.71 [0.58, 0.86]), sudden death (HR=0.77 [0.59, 0.999]), and pump failure death (HR=0.64 [0.45, 0.91]). ConclusionsAlthough not excluding the possibility of differences resulting from chance alone or to different properties among β-blockers, this study suggests the possibility that different heart failure population subgroups may have different responses to β-blocker therapy.

Improvement of exercise capacity and left ventricular diastolic function with metoprolol XL after acute myocardial infarction

Background Left ventricular (LV) diastolic function predicts and correlates with exercise capacity. β-Blockers improve exercise capacity and LV diastolic function in patients with severe LV systolic dysfunction in dilated cardiomyopathy. However, information on the effect of metoprolol XL on exercise capacity in relation to LV diastolic function in patients with mild to moderate LV systolic dysfunction after acute myocardial infarction is limited. Methods In a randomized, double-blind, placebo-controlled study of 77 patients, a subgroup of 59 patients with mild to moderate LV systolic dysfunction after acute myocardial infarction were given metoprolol XL (n = 29) or placebo (n = 30). The effects of metoprolol XL on exercise capacity in relation to effects on LV diastolic filling were studied. Two-dimensional Doppler echocardiography and maximal symptom limited bicycle test were performed on days 5 through 7 and after 3 months. Results Maximal exercise capacity increased in the metoprolol XL group (124 ± 30 W vs 135 ± 29 W) compared with placebo (125 ± 31 W vs 126 ± 34 W) (P <.01). E/A ratio decreased, A peak velocity increased, reverse pulmonary flow decreased, and deceleration time was significantly prolonged in the metoprolol XL group. A significant correlation was found between the changes of deceleration time (metoprolol XL: ρ = 0.69, P <.0001; placebo: ρ = 0.31, P = not significant) and A peak velocity (metoprolol XL: ρ = 0.71, P <.0001; placebo: ρ = –0.15, not significant) in relation to changes of exercise capacity. Conclusion Metoprolol XL increases exercise capacity after 3 months, and this change seems related to improvement of LV diastolic filling after acute myocardial infarction. (Am Heart J 2000;140:e2.)