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2.
JACC Case Rep ; 4(22): 1490-1495, 2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36444185

ABSTRACT

Atrial arrhythmias are common in transthyretin cardiac amyloidosis (ATTR-CA), with a prevalence of ≤80%. They are often not well tolerated. We describe 3 patients with decompensated heart failure and cardiogenic shock precipitated by atrial arrhythmias who ultimately received diagnoses of ATTR-CA. (Level of Difficulty: Intermediate.).

3.
Heart Fail Rev ; 27(3): 755-766, 2022 05.
Article in English | MEDLINE | ID: mdl-33495937

ABSTRACT

Obesity is a growing worldwide epidemic with significant economic burden that carries with it impacts on every physiologic system including the cardiovascular system. Specifically, the risk of heart failure has been shown to increase dramatically in obese individuals. The purpose of this review is to provide background on the individual burdens of heart failure and obesity, followed by exploring proposed physiologic mechanisms that interconnect these conditions, and furthermore introduce treatment strategies for weight loss focusing on bariatric surgery. Review of the existing literature on patients with obesity and heart failure who have undergone bariatric surgery is presented, compared, and contrasted.


Subject(s)
Bariatric Surgery , Heart Failure , Heart Failure/epidemiology , Heart Failure/surgery , Humans , Obesity/complications , Obesity/surgery , Weight Loss
4.
JACC Case Rep ; 3(4): 603-609, 2021 Apr.
Article in English | MEDLINE | ID: mdl-34317586

ABSTRACT

We report a unique case of delivery of inappropriate implantable cardioverter-defibrillator therapies related to a "perfect storm": presence of an integrated lead, insufficient lead slack related to right heart dilation resulting in shock coil misplacement, myocarditis with loss of R waves, and the concomitant occurrence of an incessant atrial tachycardia. (Level of Difficulty: Advanced.).

5.
Am J Cardiol ; 123(11): 1845-1852, 2019 06 01.
Article in English | MEDLINE | ID: mdl-30922540

ABSTRACT

Transcatheter aortic valve implantation (TAVI) is an acceptable treatment for severe aortic stenosis in high or intermediate risk patients. Conduction abnormalities are a known complication of TAVI. Most abnormalities occur perioperatively but can develop later. The predictors of delayed conduction abnormalities are unknown. Patients who underwent TAVI at our institution were reviewed. Patients with a pre-existing pacemaker were excluded. Baseline, in-hospital, and 30-day follow-up ECGs were reviewed. Patient and procedural characteristics were analyzed to look for predictors of acute and delayed abnormalities. Ninety-eight patients were included. All valves implanted were balloon expandable, most commonly SAPIEN S3 (78%). Thirty-seven (37.7%) patients developed abnormalities before discharge. Of these patients, 20 (57.1%) had complete resolution at 30-day follow-up. No patients with new conduction abnormalities during hospitalization had additional abnormalities at 30-day follow-up. Five (5.1%) patients developed new conduction abnormalities following discharge. Overall, 22 (22.4%) patients had conduction abnormalities at 30-day follow-up which were not present at baseline. Predilatation (p = 0.003), higher ratios of balloon (p = 0.03) or valve (p = 0.05) size to left ventricular outflow tract, and previous myocardial infarction (p = 0.034) were predictive of acute conduction abnormalities. Baseline right bundle branch block (p = 0.002), longer baseline (p <0.001) and discharge (p = 0.004) QRS duration, moderate, or severe aortic insufficiency (p = 0.002) and atrial fibrillation (p = 0.031) were predictors of new conduction abnormalities after discharge. In conclusion, most new in-hospital conduction abnormalities resolve by 30-day follow-up. In-hospital conduction abnormalities are related to technical aspects of TAVI while delayed conduction abnormalities are related to baseline conduction system disease.


Subject(s)
Aortic Valve Stenosis/surgery , Cardiac Conduction System Disease/etiology , Heart Valve Prosthesis , Postoperative Complications/etiology , Transcatheter Aortic Valve Replacement/adverse effects , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Prognosis , Prosthesis Design , Retrospective Studies , Time Factors , Treatment Outcome
6.
Eur J Radiol ; 111: 1-5, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30691659

ABSTRACT

Assessing coronary artery calcium (CAC) is a valuable tool for individualizing cardiac risk assessment. In CAC scanning, this technical report assesses the use of a true model-based iterative reconstruction algorithm using forward projected model-based iterative reconstruction ("FIRST") and assess whether FIRST allows for reduced radiation dose CAC scanning on 320-detector row computed tomography (320-CT). Here, 100 consecutive patients prospectively underwent reduced and standard dose scans. For the patients (59 ± 9 years, 61% male) stratified by Agatston categories 0, 1-10, 11-100, 101-400,> 400, agreement between reduced dose with FIRST versus standard dose with FBP was excellent at 81% (95% CI: 73-88%) with kappa 0.74 (95% CI: 0.64-0.85). Median radiation exposure was 75% lower for reduced (0.35 mSv) versus standard dose (1.37 mSv) scans. In conclusion, agreement was excellent for reduced dose with FIRST and standard dose with FBP in 320-detector row CT CAC imaging in well-established categories of cardiovascular risk. These methods make it possible to reduce radiation exposure by 75%.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Tomography, X-Ray Computed , Vascular Calcification/diagnostic imaging , Algorithms , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Radiation Dosage , Risk Assessment , Tomography, X-Ray Computed/methods
7.
Oxf Med Case Reports ; 2018(1): omx082, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29670747

ABSTRACT

A 61-year-old man, who had undergone coronary artery bypass surgery 10 years earlier, presented with a non-ST segment elevation myocardial infarction. He was treated with medical therapy and taken to the Cardiac Catheterization Laboratory. A left heart catheterization demonstrated an ostial stenosis in the left internal mammary artery graft, which was felt to be the culprit lesion. This was successfully repaired with a drug eluting stent. This case is presented as an unusual location for a de novo coronary stenosis. The pathophysiology of these lesions is not well understood.

8.
Oxf Med Case Reports ; 2018(1): omx080, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29345690

ABSTRACT

Approved in 1989 for the management of treatment-resistant schizophrenia, Clozapine is a last-line atypical antipsychotic drug used with increasing frequency. In addition to its well-known side effect of agranulocytosis, this drug also carries with it rare but serious adverse cardiovascular risk of myocarditis. We present a patient on Clozapine who was admitted to the cardiology service with chest pain, ST segment elevations and elevated troponin concerning for acute myocardial infarction. Evaluation with imaging revealed decreased left ventricular function, however, no coronary artery disease was present on catheterization; findings consistent with a diagnosis of myocarditis. Subsequent discontinuation of the patient's Clozapine and initiation of brief supportive medical therapy resulted in full recovery of systolic left ventricular function. Given the potential cardiovascular mortality risk, it is important for physicians on cardiology services caring for psychiatric patients to be aware of the presentation of symptoms, diagnostic findings and management of Clozapine induced myocarditis.

9.
J Cardiovasc Pharmacol Ther ; 22(6): 529-537, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28403647

ABSTRACT

An as-yet limited body of evidence suggests that calcium-regulating endocrine hormones-in particular, parathyroid hormone-related peptide (PTHrP)-may have unappreciated cardioprotective effects. The current review focuses on the concept that PTHrP may, via modulation of classic cardioprotective signaling pathways, provide a novel strategy to attenuate myocardial ischemia-reperfusion injury.


Subject(s)
Biomimetic Materials/therapeutic use , Cardiotonic Agents/therapeutic use , Parathyroid Hormone-Related Protein/therapeutic use , Animals , Biomimetic Materials/pharmacology , Cardiotonic Agents/pharmacology , Humans , Myocardial Infarction/physiopathology , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/prevention & control , Parathyroid Hormone-Related Protein/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiology
10.
J Endocrinol ; 216(3): 315-29, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23197743

ABSTRACT

Limited information is available on the role of MAPK phosphatase 1 (MKP1) signaling in osteoblasts. We have recently reported distinct roles for MKP1 during osteoblast proliferation, differentiation, and skeletal responsiveness to parathyroid hormone (PTH). As MKP1 regulates the phosphorylation status of MAPKs, we investigated the involvement of P-ERK and P-p38 MAPKs in MKP1 knockout (KO) early and mature osteoblasts with respect to mineralization and PTH response. Calvarial osteoblasts from 9-14-week-old WT and MKP1 KO male and female mice were examined. Western blot analysis revealed downregulation and sustained expressions of P-ERK and P-p38 with PTH treatment in differentiated osteoblasts derived from KO males and females respectively. Exposure of early osteoblasts to p38 inhibitor, SB203580 (S), markedly inhibited mineralization in WT and KO osteoblasts from both genders as determined by von Kossa assay. In osteoblasts from males, ERK inhibitor U0126 (U), not p38 inhibitor (S), prevented the inhibitory effects of PTH on mineralization in early or mature osteoblasts. In osteoblasts from KO females, PTH sustained mineralization in early osteoblasts and decreased mineralization in mature cells. This effect of PTH was attenuated by S in early osteoblasts and by U in mature KO cells. Changes in matrix Gla protein expression with PTH in KO osteoblasts did not correlate with mineralization, indicative of MKP1-dependent additional mechanisms essential for PTH action on osteoblast mineralization. We conclude that PTH regulation of osteoblast mineralization in female mice is maturation stage specific and involves MKP1 modulation of P-ERK and P-p38 MAPKs.


Subject(s)
Calcification, Physiologic/physiology , Dual Specificity Phosphatase 1/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Osteoblasts/metabolism , Parathyroid Hormone/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Butadienes/pharmacology , Calcification, Physiologic/drug effects , Cell Differentiation/drug effects , Down-Regulation , Dual Specificity Phosphatase 1/genetics , Enzyme Inhibitors/pharmacology , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Female , Imidazoles/pharmacology , Male , Mice , Mice, Knockout , Nitriles/pharmacology , Osteoblasts/drug effects , Phosphorylation/drug effects , Phosphorylation/physiology , Pyridines/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
11.
J Endocrinol ; 211(2): 145-56, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21852324

ABSTRACT

Parathyroid hormone (PTH) signaling via PTH 1 receptor (PTH1R) involves mitogen-activated protein kinase (MAPK) pathways. MAPK phosphatase 1 (MKP1) dephosphorylates and inactivates MAPKs in osteoblasts, the bone-forming cells. We previously showed that PTH1R activation in differentiated osteoblasts upregulates MKP1 and downregulates pERK1/2-MAPK and cyclin D1. In this study, we evaluated the skeletal phenotype of Mkp1 knockout (KO) mice and the effects of PTH in vivo and in vitro. Microcomputed tomography analysis of proximal tibiae and distal femora from 12-week-old Mkp1 KO female mice revealed osteopenic phenotype with significant reduction (8-46%) in bone parameters compared with wild-type (WT) controls. Histomorphometric analysis showed decreased trabecular bone area in KO females. Levels of serum osteocalcin (OCN) were lower and serum tartrate-resistant acid phosphatase 5b (TRAP5b) was higher in KO animals. Treatment of neonatal mice with hPTH (1-34) for 3 weeks showed attenuated anabolic responses in the distal femora of KO mice compared with WT mice. Primary osteoblasts derived from KO mice displayed delayed differentiation determined by alkaline phosphatase activity, and reduced expressions of Ocn and Runx2 genes associated with osteoblast maturation and function. Cells from KO females exhibited attenuated PTH response in mineralized nodule formation in vitro. Remarkably, this observation was correlated with decreased PTH response of matrix Gla protein expression. Expressions of pERK1/2 and cyclin D1 were inhibited dramatically by PTH in differentiated osteoblasts from WT mice but much less in osteoblasts from Mkp1 KO mice. In conclusion, MKP1 is important for bone homeostasis, osteoblast differentiation and skeletal responsiveness to PTH.


Subject(s)
Bone and Bones/metabolism , Dual Specificity Phosphatase 1/metabolism , Osteoblasts/metabolism , Parathyroid Hormone/pharmacology , Acid Phosphatase/blood , Animals , Animals, Newborn , Blotting, Western , Bone and Bones/anatomy & histology , Bone and Bones/drug effects , Cell Differentiation/drug effects , Cell Line , Cells, Cultured , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Cyclin D1/genetics , Cyclin D1/metabolism , Dual Specificity Phosphatase 1/genetics , Female , Gene Expression/drug effects , Isoenzymes/blood , Male , Mice , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Osteoblasts/cytology , Osteoblasts/drug effects , Osteocalcin/blood , Osteocalcin/genetics , Osteocalcin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tartrate-Resistant Acid Phosphatase , X-Ray Microtomography
12.
J Endocrinol ; 207(3): 355-65, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20929987

ABSTRACT

Phosphorylation, internalization, and desensitization of G protein-coupled receptors, such as the parathyroid hormone (PTH) and PTH-related peptide (PTHrP) receptor (PTH1R), are well characterized and known to regulate the cellular responsiveness in vitro. However, the role of PTH1R receptor phosphorylation in bone formation and osteoblast functions has not yet been elucidated. In previous studies, we demonstrated impaired internalization and sustained cAMP stimulation of a phosphorylation-deficient (pd) PTH1R in vitro, and exaggerated cAMP and calcemic responses to s.c. PTH infusion in pdPTH1R knock-in mouse model. In this study, we examined the impact of impaired PTH1R phosphorylation on the skeletal phenotype of mice maintained on normal, low, and high calcium diets. The low calcium diet moderately reduced (P<0.05) bone volume and trabecular number, and increased trabecular spacing in both wild-type (WT) and pd mice. The effects, however, seem to be less pronounced in the female pd compared to WT mice. In primary calvarial osteoblasts isolated from 2-week-old pd or WT mice, PTH and PTHrP decreased phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2), a member of mitogen-activated protein kinase, and cyclin D1, a G1/S phase cyclin, in vitro. In contrast to WT osteoblasts, down-regulation of cyclin D1 was sustained for longer periods of time in osteoblasts isolated from the pd mice. Our results suggest that adaptive responses of intracellular signaling pathways in the pd mice may be important for maintaining bone homeostasis.


Subject(s)
Bone and Bones/metabolism , Osteoblasts/metabolism , Receptor, Parathyroid Hormone, Type 1/metabolism , Adaptation, Physiological , Animals , Calcium, Dietary/metabolism , Cyclin D1/analysis , Down-Regulation , Female , Gene Knock-In Techniques , Male , Mice , Mice, Mutant Strains , Mitogen-Activated Protein Kinases/analysis , Phenotype , Phosphorylation
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