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1.
JRSM Open ; 8(9): 2054270417728230, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28904808

ABSTRACT

In end stage renal disease patients on dialysis, the use of catheter as a vascular access is associated with a significant risk of sepsis compared to an arterio-venous fistula. Our case emphasizes the importance of having high index of suspicion for unusual complications in patients presenting with possible catheter-related blood stream infection and early use of complementary tools such as trans-oesophageal echocardiography whenever applicable.

2.
J Heart Lung Transplant ; 27(10): 1102-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18926401

ABSTRACT

BACKGROUND: Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is associated with a high rate of morbidity and mortality. We sought to determine pre-operative right heart echocardiographic predictors of post-LVAD severe RV failure. METHODS: RV failure, defined as the need for inotropic support or pulmonary vasodilators for >or=14 days post-operatively, was evaluated in 33 patients (age 54 +/- 13 years) with LVADs. Preoperative RV systolic and diastolic echocardiographic parameters, including RV fractional area change, tricuspid annular motion, right atrial volume index, RV index of myocardial performance, hepatic vein Doppler velocities, tricuspid regurgitation severity, and RV systolic pressures (RVSPs) in patients with and without RV failure were compared. RESULTS: Of the 33 patients evaluated, 11 (33%) had post-LVAD RV failure (2 needed RVAD support). Patients with post-LVAD RV failure had significantly lower pre-operative tricuspid annular motion (8 +/- 4 vs 15 +/- 6 mm, p < 0.01) and higher RVSPs (60 +/- 14 vs 46 +/- 11 mm Hg, p = 0.02). In 13 patients (39%) with moderate tricuspid regurgitation, pre-operative tricuspid annular motion remained significantly reduced (6.0 +/- 0.5 vs 13.5 +/- 5.0 mm, p = 0.045). Other echocardiographic parameters were not significantly different between patients. Tricuspid annular motion of <7.5 mm provides 91% specificity and 46% sensitivity in predicting post-LVAD RV failure. CONCLUSION: Tricuspid annular motion is a predictor of post-LVAD RV failure. Using tricuspid annular motion in addition to conventional criteria may aid in early identification of patients with prolonged inotropic support or severe RV failure and allow for better pre-operative planning.


Subject(s)
Heart Transplantation/physiology , Heart-Assist Devices , Tricuspid Valve Insufficiency/physiopathology , Tricuspid Valve/physiopathology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy , Ventricular Dysfunction, Right/physiopathology , Adult , Aged , Defibrillators, Implantable , Diastole/physiology , Echocardiography, Transesophageal , Heart-Assist Devices/adverse effects , Humans , Middle Aged , Predictive Value of Tests , Retrospective Studies , Systole/physiology , Tricuspid Valve Insufficiency/surgery , Tricuspid Valve Insufficiency/therapy , Ventricular Dysfunction, Left/surgery , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/surgery
3.
Pharmacogenet Genomics ; 17(4): 277-82, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17496726

ABSTRACT

OBJECTIVES: The Arg389Gly polymorphism (Arg389Gly) in the beta1-adrenergic receptor gene (ADRB1) has been associated with improvement in left-ventricular remodeling with beta-blocker treatment. One study of risk for heart failure suggested a synergistic effect of ADRB1 Arg389Gly with the insertion/deletion polymorphism in the alpha2C-adrenergic receptor gene (ADRA2C). We tested whether the ADRA2C insertion/deletion polymorphism was associated with beta-blocker response in heart failure, either alone or in combination with the ADRB1Arg389Gly polymorphism. METHODS: Fifty-four beta-blocker naive heart failure patients underwent echocardiography before and after 5-6 months of metoprolol CR/XL therapy. Multivariant linear regression modeling was performed to assess the impact of genotypes and other variables on changes in left-ventricular function in response to metoprolol therapy. RESULTS: Deletion carriers had a significantly greater negative chronotropic response. Predictors of the end of study ejection fraction were baseline ejection fraction, deletion carrier status and Arg389Arg genotype. Patients with Arg389Arg/Del-carrier status showed the greatest ejection fraction increase with metoprolol CR/XL. Adjusting for baseline ejection fraction, final S-metoprolol plasma concentration and race, final ejection fraction in patients with this genotype combination was significantly higher than all other genotype combination groups. CONCLUSION: ADRB1 and ADRA2C polymorphisms synergistically influence the ejection fraction response to beta-blocker therapy of heart failure patients.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Heart Failure/drug therapy , Heart Failure/genetics , Polymorphism, Genetic , Receptors, Adrenergic, alpha-2/genetics , Receptors, Adrenergic, alpha-2/physiology , Receptors, Adrenergic, beta-1/genetics , Receptors, Adrenergic, beta-1/physiology , Stroke Volume/genetics , Ventricular Function, Left/drug effects , Ventricular Function, Left/genetics , Aged , Amino Acid Substitution , DNA Primers/genetics , Female , Heart Failure/physiopathology , Humans , Male , Middle Aged , Pharmacogenetics , Polymorphism, Single Nucleotide , Stroke Volume/drug effects , Stroke Volume/physiology , Ventricular Function, Left/physiology , Ventricular Remodeling/drug effects , Ventricular Remodeling/genetics , Ventricular Remodeling/physiology
4.
Pharmacogenet Genomics ; 15(4): 227-34, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15864115

ABSTRACT

OBJECTIVE: Large variability exists in the improvement in left ventricular (LV) function from beta-blocker treatment. We hypothesized that polymorphisms at codon 389 (Arg389Gly) and 49 (Ser49Gly) in the beta1-adrenergic receptor (AR) gene were associated with LV reverse remodeling changes in response to beta-blocker therapy among heart failure patients. METHODS: We prospectively enrolled 61 beta-blocker naive patients with systolic heart failure. Patients underwent baseline echocardiography followed by metoprolol CR/XL. The dose was doubled on a biweekly basis up to 200 mg/day or attainment of maximum tolerated dose. Echocardiography was repeated after the patient received the target or highest tolerated dose for 3 months. RESULTS: Among patients with the Arg389Arg genotype, ejection fraction (EF) increased from 23+/-5 to 29+/-10 (P=0.008). Gly389 carriers did not demonstrate any significant change in EF (22+/-9 to 23+/-11; P=0.45). There was a significant between-group difference in EF by genotype (P=0.04). The Arg389Arg genotype was also associated with significantly greater reductions in LV end-diastolic and end-systolic diameters compared to Gly389 carriers. Patients with the Gly49 variant also had a significantly greater reduction in LV end-diastolic diameter compared to Ser49 homozygotes. Multiple regression analysis modeling revealed that the codon 389 polymorphism was a significant predictor of an improvement in EF and both codon 49 and 389 polymorphisms were significant predictors of final LV end-diastolic diameter. CONCLUSIONS: Heart failure patients with the Arg389Arg genotype and Gly49 carriers had greater improvements in LV remodeling from beta-blocker treatment.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Heart Failure/drug therapy , Heart Failure/genetics , Polymorphism, Genetic , Receptors, Adrenergic, beta-1/genetics , Codon , Echocardiography , Female , Genotype , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heterozygote , Homozygote , Humans , Male , Maximum Tolerated Dose , Middle Aged , Pharmacogenetics , Receptors, Adrenergic/metabolism , Regression Analysis , Systole , Time Factors , Ventricular Remodeling
5.
Clin Pharmacol Ther ; 77(3): 127-37, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15735607

ABSTRACT

OBJECTIVE: beta-Blockers require careful initiation and titration when used in patients with heart failure. Some patients tolerate beta-blocker therapy initiation without difficulty, whereas in other patients this period presents clinical challenges. We tested the hypothesis that polymorphisms at codons 389 (Arg389Gly) and 49 (Ser49Gly) of the beta(1)-adrenergic receptor would be associated with differences in initial tolerability of beta-blocker therapy in patients with heart failure. We also tested whether polymorphisms in the beta(2)-adrenergic receptor, G-protein alpha s subunit (G(s)alpha), and cytochrome P450 (CYP) 2D6 genes or S-metoprolol plasma concentrations were associated with beta-blocker tolerability. METHODS: Sixty-one beta-blocker-naive patients with systolic heart failure were prospectively enrolled. Patients began taking 12.5 to 25 mg metoprolol controlled release/extended release with titration every 2 weeks (as tolerated) to 200 mg/d or the maximum tolerated dose over a period of 8 to 10 weeks. Decompensation was the composite of death, heart failure hospitalization, increase in other heart failure medications, or need to discontinue metoprolol. End points were assessed during the titration period. RESULTS: The overall rate of decompensation was not different between the codon 49 or 389 genotypes. However, a significantly greater percentage of patients with the Gly389 variant required increases in heart failure medications as compared with Arg389 homozygotes (48% versus 14%, respectively; P = .006). Similarly, patients with the Ser49 homozygous genotype were significantly more likely to require increases in concomitant heart failure therapy as compared with Gly49 carriers (41% versus 11%, respectively; P = .03). Neither CYP2D6 genotypes nor metoprolol pharmacokinetics differed between patients with and those without a decompensation event. There was no association between the beta(2)-adrenergic receptor or G(s)alpha polymorphisms with decompensated heart failure. CONCLUSIONS: Patients with the Gly389 variant and Ser49Ser genotype were significantly more likely to require increases in heart failure medications during beta-blocker titration and thus may require more frequent follow-up during titration.


Subject(s)
Heart Failure/drug therapy , Metoprolol/administration & dosage , Polymorphism, Genetic/drug effects , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/genetics , Cytochrome P-450 CYP2D6/drug effects , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/metabolism , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Drug Administration Schedule , Drug Resistance/drug effects , Drug Resistance/genetics , Exercise Tolerance/drug effects , Exercise Tolerance/genetics , GTP-Binding Protein alpha Subunits, Gs/drug effects , GTP-Binding Protein alpha Subunits, Gs/genetics , Genotype , Heart Failure/diagnosis , Humans , Male , Metoprolol/pharmacokinetics , Metoprolol/therapeutic use , Middle Aged , Pharmacogenetics/methods , Phenotype , Polymorphism, Genetic/genetics , Polymorphism, Genetic/physiology , Receptors, Adrenergic, beta/physiology , Time and Motion Studies , Treatment Outcome
6.
Am J Cardiol ; 94(4): 535-8, 2004 Aug 15.
Article in English | MEDLINE | ID: mdl-15325950

ABSTRACT

This study sought to determine the influence of gender and/or race on the hemodynamic response to dobutamine during dobutamine stress echocardiography. Blood pressure response patterns differed by gender and race, and completion of testing was often limited because of adverse events, namely, hypertension. Gender and racial differences in blood pressure response merit consideration as potential contributors to the suboptimal response in dobutamine stress testing.


Subject(s)
Echocardiography, Stress/statistics & numerical data , Ethnicity/statistics & numerical data , Hemodynamics/drug effects , Adult , Aged , Aged, 80 and over , Blood Pressure/drug effects , Dobutamine/administration & dosage , Dobutamine/adverse effects , Dose-Response Relationship, Drug , Electrocardiography/drug effects , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Rate/drug effects , Humans , Infusions, Intravenous , Male , Mathematical Computing , Middle Aged , Prospective Studies , Reference Values
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