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1.
Am J Med ; 136(1): 12-14, 2023 01.
Article in English | MEDLINE | ID: mdl-36150512

Subject(s)
Humans , Pregnancy , Female
2.
Curr Probl Cardiol ; 47(12): 101365, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36031016

ABSTRACT

Disparities in overall outcomes for atrial fibrillation (AF) across racial and ethnic groups have been demonstrated in prior studies. We aim to evaluate in-hospital outcomes and resource utilization across 3 racial/ethnic groups with AF using contemporary data. We identified patients admitted with AF in the National Inpatient Sample registry from 2015 to 2018. ICD-10-CM codes were used to identify variables of interest. The primary outcomes were in-hospital complications and resource utilization. There were 1,250,075 AF admissions. Our sample was made up of 85.49% White, 8.12% Black, and 6.38% Hispanic patients. Black patients were younger but had a higher burden of cardiovascular comorbidities including obesity, hypertension, and chronic kidney disease. Social determinants were also less favorable in Black patients, with a higher percentage of Medicaid insurance and a high proportion of patients being in the lowest percentile for household income. Total hospital charge was highest in Hispanic patients. Despite higher rates of gastrointestinal bleed, Black patients were least likely to undergo left atrial appendage occlusion device implantation. Black and Hispanic patients were less like to undergo catheter ablation therapy. Black race was an independent predictor of mortality, stroke, mechanical ventilation, acute kidney injury, hemodynamic shock, need for vasopressor, upper gastrointestinal bleed, need for blood transfusion, total hospital charges, and length of stay when compared to other groups. Disparities exist in the risk of AF, and its management among racial and ethnic groups. Health care costs and inpatient outcomes disproportionately impact minorities in the United States.


Subject(s)
Atrial Fibrillation , Ethnicity , Humans , United States/epidemiology , Atrial Fibrillation/epidemiology , Atrial Fibrillation/therapy , Healthcare Disparities , Racial Groups , Hospitals
3.
J Clin Lipidol ; 16(3): 253-260, 2022.
Article in English | MEDLINE | ID: mdl-35260347

ABSTRACT

Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality in the US. Preeclampsia (PreE) which includes hypertension and proteinuria during pregnancy, is thought to result from placental ischemia. Risk factors for PreE parallel those for cardiovascular disease, and recent studies point to hyperlipidemia specifically, hypertriglyceridemia, as a risk factor for PreE. Current practice does not routinely include lipid testing pre-conception or during pregnancy. Professional, societal recommendations should advocate for hyperlipidemia screening, followed by appropriate management, pre-conception and during pregnancy.


Subject(s)
Hyperlipidemias , Hypertension , Pre-Eclampsia , Female , Humans , Hyperlipidemias/complications , Hyperlipidemias/epidemiology , Hypertension/complications , Placenta , Pre-Eclampsia/diagnosis , Pre-Eclampsia/epidemiology , Pre-Eclampsia/etiology , Pregnancy , Proteinuria/complications , Risk Factors
4.
Cureus ; 13(2): e13574, 2021 Feb 26.
Article in English | MEDLINE | ID: mdl-33815982

ABSTRACT

Dual antiplatelet therapy (DAPT), defined as administration of a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin, is recommended after percutaneous coronary intervention. We describe a case of a 50-year-old gentleman with intolerance to the three previously mentioned P2Y12 inhibitors following the placement of a drug-eluting stent to the left anterior descending artery. To our knowledge, based on a thorough review of the literature, this is the second case reporting a similar medical dilemma. We have discussed the multidisciplinary approach implemented to overcome this clinical challenge, which involved the use of clopidogrel with simultaneous administration of a six-day course of oral steroids.

5.
J Oncol Pharm Pract ; 27(7): 1799-1801, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33779370

ABSTRACT

INTRODUCTION: Trastuzumab and pertuzumab are recombinant humanized monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2). Currently, six reported cases on the use of trastuzumab in dialysis, and one on the use of pertuzumab, have been identified in the literature. This case is one of the first to describe the use of pertuzumab, and adds to currently available reports on the use of trastuzumab, in hemodialysis. CASE REPORT: A female receiving hemodialysis three times per week was diagnosed with a clinical T2N1M0, hormone receptor-negative, HER2-positive, invasive ductal carcinoma of the breast. She received six cycles of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab, with left ventricular ejection fraction (LVEF) remaining stable throughout. Following surgery, she continued dual HER2 blockade with trastuzumab and pertuzumab, after six cycles of which she was found on routine echocardiogram to have an asymptomatic decline in LVEF.Management & outcome: Following the decline in LVEF, trastuzumab and pertuzumab were held, and cardio-oncology was consulted. LVEF recovered within one month, after which she continued on single-agent trastuzumab to complete one year of HER2-directed therapy. DISCUSSION: To our knowledge, this is one of the first published cases describing the use of pertuzumab in a patient receiving hemodialysis. Though our patient did experience a reversible decline in LVEF following twelve cycles of combination trastuzumab and pertuzumab, this case demonstrates the relatively safe and effective use of pertuzumab in a patient with end-stage renal disease undergoing hemodialysis, and lends additional support to the use of trastuzumab in this particular patient population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Ventricular Function, Left , Antibodies, Monoclonal, Humanized , Female , Humans , Renal Dialysis , Stroke Volume , Trastuzumab/therapeutic use
6.
Adv Mind Body Med ; 34(1): 8-16, 2020.
Article in English | MEDLINE | ID: mdl-32277749

ABSTRACT

CONTEXT: Mortality associated with cardiovascular disease is significantly higher in African Americans compared with people of other ethnicities, with hypertension being the single most significant risk factor in this population. Underdiagnosis and undertreatment of hypertension is common. Although cardiovascular lifestyle education and self-management programs are available for the general public, many African Americans prefer to learn about health-promoting activities through interactive programs led by church ministries. OBJECTIVE: This study examined the influence of adding a faith-based protocol using creative musical expression as a catalyst for improving retention, engagement, and positive health outcomes for African Americans participating in a 1-y, lifestyle skills program for reducing cardiovascular risk factors. DESIGN: The study was a randomized, controlled trial. SETTING: The study occurred at Rodman Street Missionary Baptist Church (Pittsburgh, PA, USA). PARTICIPANTS: Participants were African Americans with at least 2 of the following medical conditions: high blood pressure, elevated cholesterol and/or triglycerides, heart attack, angina, stroke, irregular heartbeats, palpitations, shortness of breath, dizziness or fainting, diabetes, and tobacco use. INTERVENTION: Intervention and control groups both participated every other week in one 45-min structured cardiovascular risk reduction educational session over the course of 1 year. During alternative weeks, sessions comprised blood pressure checks, coupled with individualized support discussions focused on challenges and identified obstacles to adherence. In addition to the aforementioned sessions, the intervention group participated in a novel gospel music program with weekly, 45-minute vocal and instrumental sessions. OUTCOME MEASURES: Outcome measures include retention, attendance, systolic and diastolic blood pressures, weight, body mass index, hip measurement, and waist measurement as well as the Short Form-12 (SH-12) Health Survey. RESULTS: Subjects in the intervention group demonstrated a statistically significant 83.3% retention rate in the course of 1 year compared with only 54.3% for the control group (cardiovascular lifestyle education sessions alone). Six dropouts were noted in the intervention group in sharp contrast to 16 dropouts in the control group. Participants in the intervention group were 4.21 times more likely to complete the program than the control group. A significant difference was also noted for attendance, which was higher for the intervention group (21.33 sessions for the intervention group vs 17.95 sessions for the control group). Statistically significant systolic blood pressure reductions noted in both groups were sustained 6 mo postprogram conclusion. In addition, a statistically significant pre-between post-between group improvement in SF-12 Physical Component Scores was noted for intervention subjects in sharp contrast with controls who actually demonstrated worsening scores. CONCLUSIONS: The addition of a gospel music program as a catalyst for increase engagement in a sustainable, healthy lifestyle program warrants further consideration and additional study in African American churches.


Subject(s)
Cardiovascular Diseases , Healthy Lifestyle , Music , Black or African American , Cardiovascular Diseases/ethnology , Cardiovascular Diseases/prevention & control , Humans , Outcome Assessment, Health Care
7.
JACC Case Rep ; 2(7): 1056-1061, 2020 Jun 17.
Article in English | MEDLINE | ID: mdl-34317414

ABSTRACT

Scar-mediated ventricular tachycardia (VT) commonly results from ischemic heart disease. We present a case of recurrent VT, which was initially attributed to ischemic disease; however, the scar location pointed to an alternate pathology. This case demonstrates the utility of multimodality imaging in diagnosing sarcoidosis as a cause of VT. (Level of Difficulty: Intermediate.).

8.
Circ Heart Fail ; 12(9): e006082, 2019 09.
Article in English | MEDLINE | ID: mdl-31514517

ABSTRACT

BACKGROUND: Women comprise approximately one-third of the advanced heart failure population but may receive fewer advanced heart failure therapies including left ventricular assist devices (LVADs). During the early pulsatile-flow device era, women had higher post-LVAD mortality and increased complications. However, knowledge about these differences in the continuous-flow device era is limited. Therefore, we sought to explore temporal trends in LVAD utilization and post-LVAD mortality by sex. METHODS AND RESULTS: Patients with LVAD implantation from 2004 to 2016 were identified using the Nationwide Inpatient Sample. Trends in LVAD utilization and post-LVAD inpatient mortality were compared by sex and device era. Although LVADs are being increasingly utilized for patients with advanced systolic heart failure, women continue to represent a smaller proportion of LVAD recipients-25.8% in 2004 to 21.9% in 2016 (P for trend, 0.91). Women had increased inpatient mortality after LVAD implantation compared with men in the pulsatile-flow era (46.9% versus 31.1%, P<0.0001) but not in the continuous-flow era (13.3% versus 12.1%, P=0.27; P for interaction=0.0002). Inpatient mortality decreased for both sexes over time after LVAD, with a sharp fall in 2008 to 2009. Female sex was independently associated with increased post-LVAD inpatient mortality beyond adjustment for demographics and risk factors during the pulsatile-flow era (odds ratio, 2.13; 95% CI, 1.45-3.10; P<0.0001) but not during the continuous-flow era (1.18; 0.93-1.48; P=0.16). CONCLUSIONS: Although utilization of LVAD therapy increased over time for both sexes, LVAD implantation remains stably lower in women, which may suggest a potential underutilization of this potentially life-saving therapy. Prospective studies are needed to confirm these findings.


Subject(s)
Health Services Misuse/trends , Heart Failure/surgery , Heart-Assist Devices/trends , Hospital Mortality/trends , Prosthesis Implantation/statistics & numerical data , Adult , Aged , Databases, Factual , Female , Health Services Misuse/statistics & numerical data , Heart Failure/epidemiology , Heart Failure/mortality , Heart-Assist Devices/statistics & numerical data , Humans , Male , Middle Aged , Prosthesis Implantation/mortality , Prosthesis Implantation/trends , Sex Factors , United States/epidemiology
9.
Eur Heart J Case Rep ; 2(2): yty029, 2018 Jun.
Article in English | MEDLINE | ID: mdl-31020112

ABSTRACT

INTRODUCTION: Primary cardiac lymphoma accounts for <2% of all primary cardiac tumours. It is uncommon in immunocompetent patients, often fatal and diagnosed at autopsy. Tumour usually involves the right heart chambers and pericardium. With advances in imaging, early diagnosis is possible and treatment including chemotherapy and surgery affords good prognosis. CASE PRESENTATION: We present a 50-year-old woman with abdominal pain and fevers for 5 days. Computed tomography of the abdomen showed splenic and renal infarcts but no mass or vegetation was noted on echocardiography. Thoracic computed tomography divulged a large left ventricular filling defect. Cardiac magnetic resonance imaging delineated a 3.5 × 4.5 cm anterobasal mass with frond-like projections and endocardial invasion without extracardiac involvement suggestive of a low-vascularity tumour. Echo-guided endomyocardial biopsy and minithoracotomy with needle biopsy were inconclusive. A sarcoid-protocol cardiac positron emission tomography-fluorodeoxyglucose scan showed focally elevated uptake in the basal anteroseptum without extracardiac uptake, supporting a malignant entity. This prompted open heart mass resection. Pathology revealed diffuse large B-cell lymphoma. DISCUSSION: Our case is a unique report of cardiac lymphoma isolated to the left ventricle. Location of the tumour and lack of specific imaging characteristics made it a diagnostic challenge. It underscores the importance of including lymphoma in the differential for intracardiac masses as it is responsive to chemotherapy. Additionally, it emphasizes the complementary role of imaging modalities and multidisciplinary team approach in diagnosis. Early diagnosis and therapy is the key to establishing successful outcomes.

10.
J Am Heart Assoc ; 6(11)2017 Oct 27.
Article in English | MEDLINE | ID: mdl-29079563

ABSTRACT

BACKGROUND: Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen-Alone (E-Alone) trial, randomization to conjugated equine estrogen-alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI-CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post-trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors. METHODS AND RESULTS: WHI-CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age-adjusted rates/1000 person-years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2-fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen-alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality. CONCLUSIONS: Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E-Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen-alone versus placebo or CVD risk factors. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611.


Subject(s)
Coronary Artery Disease/epidemiology , Estrogen Replacement Therapy/methods , Estrogens, Conjugated (USP)/administration & dosage , Vascular Calcification/epidemiology , Women's Health , Chi-Square Distribution , Computed Tomography Angiography , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Estrogen Replacement Therapy/adverse effects , Estrogen Replacement Therapy/mortality , Estrogens, Conjugated (USP)/adverse effects , Female , Humans , Incidence , Middle Aged , Multivariate Analysis , Postmenopause , Proportional Hazards Models , Risk Factors , Time Factors , Treatment Outcome , United States/epidemiology , Vascular Calcification/diagnostic imaging , Vascular Calcification/mortality
11.
BMJ Case Rep ; 20162016 Oct 04.
Article in English | MEDLINE | ID: mdl-27702930

ABSTRACT

A woman aged 22 years with a history of lupus presented in the 18th week of pregnancy with hypertensive emergency and flash pulmonary oedema. Bedside echocardiogram revealed severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 25% and pericardial effusion. Laboratories revealed hypocomplementemia, proteinuria, elevated C reactive protein and anti-DS-DNA, raising concern for a lupus flare. Cardiac MRI showed an acute intramyocardial oedematous process, consistent with lupus carditis, and further worsening of LVEF to 13%. Shared-decision-making with the patient included discussion of maternal risks of continuation of pregnancy in the setting of worsening heart function and the fetal risks of definitive treatment with cyclophosphamide for a lupus flare and the patient decided to proceed with medical termination of pregnancy. Treatment with immunosuppressants, including cyclophosphamide, and steroids, was then initiated. 2 months after discharge, cardiac MRI showed marked improvement in LVEF to 50% and the patient remains clinically free of heart failure.


Subject(s)
Lupus Erythematosus, Systemic/complications , Pregnancy Complications/etiology , Ventricular Dysfunction, Left/etiology , Cyclophosphamide/administration & dosage , Echocardiography , Female , Humans , Hypertension, Pregnancy-Induced/diagnosis , Hypertension, Pregnancy-Induced/etiology , Immunosuppressive Agents/administration & dosage , Lupus Erythematosus, Systemic/diagnosis , Magnetic Resonance Angiography , Pregnancy , Pregnancy Complications/diagnosis , Proteinuria/diagnosis , Proteinuria/etiology , Pulmonary Edema/diagnosis , Pulmonary Edema/etiology , Ventricular Dysfunction, Left/diagnosis , Young Adult
12.
J Nucl Cardiol ; 23(4): 856-84, 2016 08.
Article in English | MEDLINE | ID: mdl-27251147

ABSTRACT

With the increasing number of individuals living with a current or prior diagnosis of cancer, it is important for the cardiovascular specialist to recognize the various complications of cancer and its therapy on the cardiovascular system. This is true not only for established cancer therapies, such as anthracyclines, that have well established cardiovascular toxicities, but also for the new targeted therapies that can have "off target" effects in the heart and vessels. The purpose of this informational statement is to provide cardiologists, cardiac imaging specialists, cardio-oncologists, and oncologists an understanding of how multimodality imaging may be used in the diagnosis and management of the cardiovascular complications of cancer therapy. In addition, this document is meant to provide useful general information concerning the cardiovascular complications of cancer and cancer therapy as well as established recommendations for the monitoring of specific cardiotoxic therapies.


Subject(s)
Antineoplastic Agents/adverse effects , Cardiac Imaging Techniques/methods , Heart Diseases/diagnostic imaging , Heart Diseases/etiology , Multimodal Imaging/methods , Radiation Injuries/diagnostic imaging , Radiotherapy/adverse effects , Evidence-Based Medicine , Humans , Radiation Injuries/etiology , Tomography, Emission-Computed/methods
15.
Tex Heart Inst J ; 41(1): 70-2, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24512406

ABSTRACT

We describe the case of a previously healthy 22-year-old man who presented with anginal chest pain and was diagnosed with a non-ST-elevation myocardial infarction. For 3 weeks, he had been ingesting the dietary supplements Jack3d® (principal ingredient, 1,3-dimethylamylamine) and Phenorex™ (principal ingredient, Citrus aurantium) daily, before undertaking physical activity. Coronary angiograms revealed a proximal left anterior descending coronary artery thrombus with distal embolization. A combined medical regimen led to resolution of the thrombus. Three months later, the patient was asymptomatic with no evidence of ischemia. The primary ingredients in the sympathomimetic supplements taken by our patient are controversial in the medical community and have been individually associated with adverse cardiac events. There are no safety data on their simultaneous use. We discuss other reports of adverse effects associated with these supplements and recommend that the relevant safety guidelines be revised.


Subject(s)
Amines/adverse effects , Citrus , Coronary Thrombosis/chemically induced , Dietary Supplements/adverse effects , Myocardial Infarction/chemically induced , Plant Extracts/adverse effects , Angina Pectoris/chemically induced , Coronary Angiography , Coronary Thrombosis/diagnosis , Coronary Thrombosis/drug therapy , Eptifibatide , Humans , Male , Myocardial Infarction/diagnosis , Myocardial Infarction/drug therapy , Peptides/therapeutic use , Phytotherapy , Plants, Medicinal , Platelet Aggregation Inhibitors/therapeutic use , Time Factors , Treatment Outcome , Young Adult
16.
Menopause ; 21(7): 702-10, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24473535

ABSTRACT

OBJECTIVE: This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. METHODS: We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. RESULTS: In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. CONCLUSIONS: The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.


Subject(s)
Calcinosis/blood , Coronary Artery Disease/blood , Osteoprotegerin/blood , Postmenopause/blood , RANK Ligand/blood , Receptor Activator of Nuclear Factor-kappa B/blood , Triglycerides/blood , Biomarkers/blood , Calcinosis/physiopathology , Coronary Artery Disease/physiopathology , Female , Humans , Middle Aged , Predictive Value of Tests , Risk Factors
18.
Clin Cardiol ; 32(11): E55-7, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19816867

ABSTRACT

Right to left shunting through a patent foramen ovale (PFO) or atrial septal defect (ASD) can cause platypnea-orthodeoxia even in a setting of normal pulmonary artery pressures. However, the late onset of symptoms despite the congenital origin of the anatomical defects is not well understood. We report a case series of patients presenting with dyspnea and orthodeoxia who developed right to left shunting as a result of associated anatomical changes that occur with aging such as tortuosity and elongation of the aorta. We propose that these acquired anatomical changes can favor right to left shunting in the setting of congenital abnormalities, therefore explaining the late onset of symptoms.


Subject(s)
Aorta/pathology , Diaphragm/pathology , Dyspnea/etiology , Foramen Ovale, Patent/complications , Heart Septal Defects, Atrial/complications , Hypoxia/etiology , Paralysis/complications , Age Factors , Aged , Aging , Aorta/physiopathology , Cardiac Catheterization/instrumentation , Diaphragm/physiopathology , Dyspnea/pathology , Dyspnea/physiopathology , Echocardiography, Transesophageal , Female , Foramen Ovale, Patent/diagnostic imaging , Foramen Ovale, Patent/physiopathology , Heart Septal Defects, Atrial/diagnostic imaging , Heart Septal Defects, Atrial/physiopathology , Heart Septal Defects, Atrial/therapy , Hemodynamics , Humans , Hypoxia/pathology , Hypoxia/physiopathology , Magnetic Resonance Imaging , Male , Paralysis/pathology , Paralysis/physiopathology , Risk Factors , Septal Occluder Device , Severity of Illness Index , Treatment Outcome
19.
Circ Heart Fail ; 1(3): 153-60, 2008 Sep.
Article in English | MEDLINE | ID: mdl-19727407

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 (GLP-1) treatment leads to short-term improvements in myocardial function in ischemic and nonischemic cardiomyopathy. It is unknown whether GLP-1 improves survival when administered over a longer time period. Spontaneously hypertensive, heart failure-prone (SHHF) rats progress to advanced heart failure and death over a 15-month period. The authors sought to determine whether a continuous infusion of GLP-1 would reduce mortality in this model. METHODS AND RESULTS: At 9 months of age, 50 SHHF rats were randomized to receive a 3-month, continuous infusion of either GLP-1 or saline. Metabolic parameters were measured and cardiac ultrasounds performed at study initiation and completion of treatment. Surviving rats were euthanized at 12 months. Hearts were perfused in an isolated, isovolumic heart preparation, and Tunel staining of myocardial samples was performed. Baseline metabolic and cardiac functional parameters were comparable. GLP-1-treated SHHF rats had greater survival (72% versus 44%, P=0.008) at 12 months of age. In addition, GLP-1 treatment led to higher plasma insulin, lower plasma triglycerides, and preserved left ventricular (LV) function. GLP-1-treated rats demonstrated decreased myocyte apoptosis by Tunel staining as well as reduced caspase-3 activation. No increase in p-BAD expression was seen. In isolated hearts, the LV systolic pressure and LV-developed pressure were greater in the GLP-1 group. Myocardial glucose uptake was also increased in GLP-1-treated SHHF rats. CONCLUSIONS: Chronic GLP-1 treatment prolongs survival in obese SHHF rats. This is associated with preserved LV function and LV mass index, increased myocardial glucose uptake, and reduced myocyte apoptosis.


Subject(s)
Glucagon-Like Peptide 1/administration & dosage , Heart Failure/drug therapy , Incretins/administration & dosage , Ventricular Function, Left/drug effects , Animals , Disease Models, Animal , Heart Failure/mortality , Heart Failure/physiopathology , Infusions, Intravenous , Prone Position , Rats , Rats, Inbred SHR , Survival Rate/trends , Systole , Treatment Outcome , Ventricular Function, Left/physiology
20.
J Am Coll Cardiol ; 47(9): 1871-81, 2006 May 02.
Article in English | MEDLINE | ID: mdl-16682315

ABSTRACT

OBJECTIVES: Given that adverse effects of chronic sympathetic activation are mediated by all three adrenergic receptor subtypes (beta1, beta2, alpha1), we examined the effects of standard doses of carvedilol and metoprolol succinate (metoprolol controlled release/extended release [CR/XL]) on hemodynamics, myocardial metabolism, and regional organ perfusion. BACKGROUND: Both beta1 selective and combined adrenergic blockade reduce morbidity and mortality in heart failure. Whether there are advantages of one class over the other remains controversial, even in the wake of the Carvedilol Or Metoprolol European Trial (COMET). Similarly, the mechanistic basis for the relative differences is incompletely understood. METHODS: Thirty-three conscious, chronically instrumented dogs with pacing-induced (240 min(-1) for 4 weeks) dilated cardiomyopathy (DCM) were randomized to carvedilol (25 mg twice daily, Coreg, Glaxo Smith Kline, Research Triangle, North Carolina) or metoprolol succinate (100 mg qd, Toprol XL, Astra Zeneca, Wilmington, Delaware). Left ventricular and systemic hemodynamics, myocardial substrate uptake, and norepinephrine spillover were measured before and after three days of treatment. Regional (renal, hepatic, skeletal muscle) blood flows were measured using neutron-activated microspheres. RESULTS: Both agents had comparable heart rate effects. However, carvedilol-treated dogs showed significantly greater increases in stroke volume and cardiac output and decreases in left ventricular end-diastolic pressure and systemic vascular resistance. Carvedilol increased renal, hepatic, and skeletal muscle blood flow. Carvedilol increased myocardial glucose uptake and suppressed norepinephrine and glucagon. Carvedilol antagonized the response to exogenous norepinephrine to a greater extent than metoprolol CR/XL. CONCLUSIONS: At doses inducing comparable heart rate reductions, short-term treatment with carvedilol had superior hemodynamic and metabolic effects compared with metoprolol CR/XL. These data suggest important advantages of blocking all three adrenergic receptor subtypes in DCM.


Subject(s)
Adrenergic Antagonists/therapeutic use , Carbazoles/therapeutic use , Cardiomyopathy, Dilated/drug therapy , Hemodynamics/drug effects , Metoprolol/analogs & derivatives , Myocardium/metabolism , Propanolamines/therapeutic use , Ventricular Function, Left/drug effects , Adrenergic beta-Agonists/pharmacology , Animals , Cardiomyopathy, Dilated/metabolism , Cardiomyopathy, Dilated/physiopathology , Carvedilol , Dogs , Heart Rate/drug effects , Isoproterenol/pharmacology , Metoprolol/therapeutic use , Regional Blood Flow/drug effects
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