Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
2.
Heart Rhythm ; 15(6): 855-859, 2018 06.
Article in English | MEDLINE | ID: mdl-29325975

ABSTRACT

BACKGROUND: The decision to abandon or extract superfluous sterile leads is controversial. OBJECTIVE: The purpose of this study was to compare procedural outcomes and long-term survival of patients with and those without abandoned leads undergoing lead extraction (LE). METHODS: Retrospective review of all patients who had undergone transvenous LE at our institution from January 2007 to May 2016 was performed. Patients were stratified into 2 groups based on the presence (group 1) or absence (group 2) of abandoned leads. RESULTS: Among 774 patients who had undergone LE procedures, 38 (4.9%) had abandoned leads (group 1). Dwell time of the oldest extracted lead was longer in group 1 vs group 2 (7.6 ± 4.9 years vs 5.6 ± 4.4 years; P = .017), as was infection as an indication for LE (76% vs 33%; P <.001). A bailout femoral approach was more commonly required in group 1 than in group 2 (18.4% vs 6%; P = .007). Complete procedural success rates were similar (92.1% in group 1 vs 95.0% in group 2; P = .439), but there was a trend toward lower clinical success in group 1 (92.1% vs 97.4%; P = .088), primarily due to failure to remove all hardware in the setting of infection. Major procedural complication rates were similar (2.6% in group 1 vs 1.2% in group 2; P = .397), as was long-term survival (mean follow-up 2.3 ± 2.2 years). CONCLUSION: Abandoned leads at the time of LE were associated with increased procedural complexity, including a higher rate of bailout femoral extraction, and may be associated with lower clinical success. Among appropriately selected patients, consideration should be given to LE instead of abandonment.


Subject(s)
Arrhythmias, Cardiac/therapy , Defibrillators, Implantable/adverse effects , Device Removal/methods , Forecasting , Pacemaker, Artificial/adverse effects , Arrhythmias, Cardiac/mortality , Device Removal/mortality , Equipment Failure , Female , Follow-Up Studies , Georgia/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate/trends , Treatment Outcome
3.
J Magn Reson Imaging ; 47(2): 477-486, 2018 02.
Article in English | MEDLINE | ID: mdl-28556294

ABSTRACT

PURPOSE: To develop a Shared K-space (SharK) magnetic resonance imaging (MRI) sequence that combines angiographic and late gadolinium enhancement (LGE) acquisitions to improve atrial wall segmentation and scar identification, and to develop a novel visualization method that quantifies scar encirclement of pulmonary veins postablation treatment for atrial fibrillation. MATERIALS AND METHODS: A SharK sequence was developed and used at 3T to image the left atrium in 11 patients postcryoballoon ablation. The effects of sharing k-space between the angiographic and LGE acquisitions on the accuracy of scar were assessed. The left atrial wall was segmented and points about each pulmonary vein (PV) ostia were projected onto a bullseye to quantitatively compare PV encirclement. The parameters used to quantify encirclement were varied to perform a sensitivity analysis. RESULTS: Compared to using a complete set of k-space, total atrial scar differences were significant only when sharing >75% k-space (P = 0.014), and 90% sensitivity and specificity for identifying scar was achieved when sharing 50% k-space. In patients, the right PVs showed more intersubject variance in encirclement compared to the left PVs. A 100° anteroinferior portion of the left PVs was always encircled, while the superior segments of both right PVs was ablated in only 6/11 patients. CONCLUSION: A SharK sequence was developed to combine angiographic and LGE imaging for atrial wall segmentation and scar identification. The PV bullseye quantifies and localizes encirclement about the PVs. The left PVs showed a higher amount of scar encirclement and less variability compared to the right PVs. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:477-486.


Subject(s)
Atrial Fibrillation/diagnostic imaging , Contrast Media , Gadolinium , Image Enhancement/methods , Magnetic Resonance Angiography/methods , Pulmonary Veins/diagnostic imaging , Atrial Fibrillation/pathology , Female , Heart Atria/diagnostic imaging , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
4.
Congenit Heart Dis ; 12(1): 6-16, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27597140

ABSTRACT

"Frontiers in Fontan Failure" was the title of a 2015 conference sponsored by Children's Healthcare of Atlanta and Emory University School of Medicine. In what is hoped to be the first of many such gatherings, speakers and attendees gathered to discuss the problem of long-term clinical deterioration in these patients. Specific focuses included properly defining the problem and then discussing different treatment strategies, both medical and surgical. The health of the liver after Fontan palliation was a particular point of emphasis, as were quality of life and future directions.


Subject(s)
Fontan Procedure/adverse effects , Heart Defects, Congenital/surgery , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/physiopathology , Humans , Liver/physiopathology , Liver Diseases/etiology , Liver Diseases/physiopathology , Palliative Care , Quality of Life , Risk Factors , Time Factors , Treatment Failure
5.
Am J Cardiovasc Dis ; 6(3): 118-28, 2016.
Article in English | MEDLINE | ID: mdl-27679746

ABSTRACT

Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT1R) and type-2 (AT2R) receptors, which have opposing effects. AT2R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT2Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation. However, the role of endogenous VSMC AT2Rs in these events is unknown. Effect of 7-day low-dose Ang II-infusion (12 µg/kg/hr) on blood pressure was tested in 9-week-old apoE((-/-)) mice fed a low or high cholesterol diet (LCD or HCD, respectively). Cardiac output was measured by echocardiography. Immunohistochemistry was performed to localize and quantify AT2Rs and p-Ser(1177)-endothelial nitric oxide synthase (eNOS) levels in the aortic arch. PD123319 and GW-9662 were used to selectively block the AT2R and peroxisome proliferator-activated receptor-γ (PPAR-γ), respectively. Ang II infusion decreased blood pressure by 12 mmHg (P < 0.001) in LCD/apoE((-/-)) mice without altering cardiac output; a response blocked by PD123319. Although, AT2R stimulation neither activated eNOS (p-Ser(1177)-eNOS) nor changed plasma NO metabolites, it caused an ~6-fold increase in VSMC PPAR-γ levels (P < 0.001) and the AT2R-mediated hypotension was abolished by GW-9662. AT2R-mediated hypotension was also inhibited by HCD, which selectively decreased VSMC AT2R expression by ~6-fold (P < 0.01). These findings suggest a novel pathway for the Ang II/AT2R-mediated hypotensive response that involves PPAR-γ, and is down regulated by a HCD.

6.
Proc Natl Acad Sci U S A ; 113(25): 6949-54, 2016 06 21.
Article in English | MEDLINE | ID: mdl-27274047

ABSTRACT

Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in postischemic heart disease.


Subject(s)
Cell Death , Insulin-Like Growth Factor I/metabolism , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Serine Endopeptidases/metabolism , Animals , Hydrolysis , Mice , Serine Endopeptidases/genetics
7.
Cell ; 157(4): 795-807, 2014 May 08.
Article in English | MEDLINE | ID: mdl-24813607

ABSTRACT

It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.


Subject(s)
Cell Differentiation , Cell Proliferation , Heart/growth & development , Myocytes, Cardiac/cytology , Animals , Cell Separation , Male , Mice , Mice, Inbred C57BL , Myocytes, Cardiac/physiology , Triiodothyronine/metabolism
8.
Kidney Int ; 75(4): 381-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18971923

ABSTRACT

C-jun N-terminal kinase (JNK) regulates both the development of insulin resistance and inflammation. Podocytes of the widely used db/db mouse model of diabetic nephropathy lose their ability to respond to insulin as albuminuria develops, in comparison to control db/+ mice. Here we tested whether JNK inhibition or its gene deletion would prevent albuminuria in experimental diabetes. Phosphorylated/total JNK was significantly increased in vivo in glomeruli of db/db compared to db/+ mice. Treatment of podocytes isolated from these two strains of mice with tumor necrosis factor-alpha caused greater phosphorylation of JNK in those obtained from diabetic animals. When db/db mice were treated with a cell-permeable TAT-JNK inhibitor peptide, their insulin sensitivity and glycemia significantly improved compared to controls. We induced diabetes in JNK1 knockout mice with streptozotocin and found that they had significantly better insulin sensitivity compared to diabetic wild-type or JNK2 knockout mice. Albuminuria was, however, worse in all mice treated with the JNK inhibitor and in diabetic JNK2 knockout mice compared to controls. Nephrin expression was also reduced in JNK inhibitor-treated mice compared to controls. A similar degree of mesangial expansion was found in all diabetic mice. Our study shows that targeting JNK to improve systemic insulin sensitivity does not necessarily prevent diabetic nephropathy.


Subject(s)
Albuminuria/drug therapy , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Insulin Resistance , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Animals , Genotype , Hyperglycemia/drug therapy , Insulin/pharmacology , Membrane Proteins/analysis , Mice , Mice, Knockout , Protein Kinase Inhibitors/pharmacology
9.
Curr Diabetes Rev ; 4(1): 10-7, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18220690

ABSTRACT

Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD). Although the pathogenesis of DN is multifactorial, local inflammatory stress may result from both the metabolic and hemodynamic derangements observed in DN. Inflammatory markers such as Interleukin-18 and Tumor Necrosis Factor (TNF)-alpha are increased in the serum of patients with diabetes and DN. This occurs at a very early stage of disease, and correlates with the degree of albuminuria. Recent data suggest that standard pharmacologic interventions for DN, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists, may have anti-inflammatory properties that are independent of their hemodynamic effect. Although inflammation is traditionally thought of as a process resulting in macrophage infiltration, current scientific progress has lead to the novel idea that even cells distant from the blood stream, such as podocytes, can produce cytokines and can express molecules that are part of the co-stimulatory pathway. A strong translational research effort is currently aimed at defining the role of such molecules in cells other than lymphocytes and macrophages. Experimental animal models have recently provided evidence that some acute phase markers of inflammation such as intracellular cell adhesion molecule-1 (ICAM-1), TNF-alpha and Monocytes Chemoattractant Protein-1 (MCP-1) may have a causative role in the development of DN. Here, we review the current evidence supporting the role of inflammation in the early phases of clinical and experimental DN. A complete understanding of inflammatory pathways activated in DN may lead to the discovery of earlier and more reliable markers of DN than albuminuria and the identification of novel therapeutic targets.


Subject(s)
Diabetic Nephropathies/physiopathology , Inflammation/physiopathology , Animals , Biomarkers/blood , Cytokines/blood , Cytokines/physiology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/metabolism , Endothelium, Vascular/physiopathology , Hemodynamics , Humans , Insulin Resistance , Kidney Failure, Chronic/physiopathology , Kidney Glomerulus/physiopathology
10.
Curr Hypertens Rep ; 9(4): 284-90, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17686378

ABSTRACT

Amlodipine is a highly effective and safe antihypertensive dihydropyridine calcium channel blocker. It is even more effective when used in combination with other antihypertensive medications, including hydrochlorothiazide. When antihypertensive calcium channel blockers were first introduced, evidence in the laboratory that they had some natriuretic properties was adduced to suggest that they would be "the diuretics of the 1990s." This turned out not to be the case. Because of its clinical efficacy, amlodipine is frequently used in fixed-dose combination products, but it is not likely to replace hydrochlorothiazide.


Subject(s)
Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Calcium Channel Blockers/therapeutic use , Diuretics/therapeutic use , Drug Therapy, Combination , Humans , Hypertension/physiopathology , Randomized Controlled Trials as Topic
11.
Curr Cardiol Rep ; 8(6): 418-24, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17059793

ABSTRACT

Nondrug therapy of hypertension really does work but requires strong motivation by both patient and physician. In addition to global health benefits, prescription of weight loss, exercise, moderation of salt and alcohol intake, Dietary Approach to Stop Hypertension (DASH) eating plan, and tobacco avoidance can decrease the risk for normotensive and prehypertensive patients of developing fixed hypertension. Initiating and maintaining a healthy lifestyle may be sufficient to avoid pharmacologic therapy for some patients and is a valuable adjunct to drug therapy for most. Blood pressure lowering can be achieved by weight reduction (5-20 mm Hg/10 kg), DASH eating plan (8-14 mm Hg), dietary sodium reduction (2-8 mm Hg), increased physical activity (4-9 mm Hg), and moderation of alcohol consumption (2-4 mm Hg). Combination of two or more modalities may have an additive benefit. Cessation of tobacco abuse not only has global health benefits, but may reduce blood pressure.


Subject(s)
Alcohol Drinking , Diet, Sodium-Restricted , Exercise , Hypertension/therapy , Potassium, Dietary/administration & dosage , Smoking Cessation , Weight Loss , Humans , Hypertension/diet therapy , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...