endothelin-1 and Aortic-Coarctation

Coarctation of the aorta is associated with increased risk for hypertension in adulthood, despite successful repair. The intrinsic mechanisms underscoring hypertension and left ventricular performance in these patients, however, remains to be determined. Our objective was to evaluate left ventricular performance by means of echocardiographic and biochemical parameters at midterm follow-up in normotensive children who have had undergone successful surgical or catheter interventional treatment of coarctation with a residual gradient of less than 20 mmHg at rest. We studied prospectively 14 patients with native aortic coarctation who underwent surgery or balloon angioplasty, the cohort made up of equal numbers of boys and girls, and having a mean age of 8.5 plus or minus 4 years. We also studied 30 age-matched healthy subjects, measuring mitral inflow pulsed wave signals, isovolumic relaxation and contraction times, myocardial performance index parameters, and levels of B-type natriuretic peptide and endothelin-1 in both groups. We found no differences in systolic blood pressure at rest between the patients and their controls. The ventricular septal diastolic dimensions, left ventricular posterior wall dimensions, mitral valve E wave, deceleration time, isovolumic relaxation time, isovolumic contraction time and myocardial performance index were all significantly increased in the patients. Levels of plasma B-type natriuretic peptide and endothelin-1 were also significantly higher in the patients when compared to the control group. We conclude that aortic coarctation is a chronic disease characterized by persistency of myocardial and vascular alterations. The elevated levels of plasma b-type natriuretic peptide and endothelin-1 may be indicative of late onset hypertension after successful treatment of native coarctation in early childhood.

Topics: Adolescent; Angioplasty, Balloon; Aortic Coarctation; Biomarkers; Blood Pressure Determination; Cardiac Catheterization; Cardiac Surgical Procedures; Child; Diastole; Echocardiography, Doppler; Endothelin-1; Endothelium, Vascular; Female; Follow-Up Studies; Heart Function Tests; Humans; Hypertrophy, Left Ventricular; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Observer Variation; Probability; Prospective Studies; Time Factors; Treatment Outcome

Patients undergoing surgical repair of aortic coarctation have a 50% risk of pathologic left ventricular remodeling (increased left ventricular mass or relative wall thickness). Endothelin 1, ST2, galectin 3, norepinephrine and B-natriuretic peptide are biomarkers that have been associated with pathologic LV change in adult populations but their predictive value following pediatric coarctation repair are not known.. Biomarker levels at coarctation repair will predict persistent left ventricular remodeling at 1-year follow up.. Prospective, cohort study of 27 patients' age 2 days-12 years with coarctation of the aorta undergoing surgical repair. Echocardiograms were performed preoperation, postoperation, and at 1-year follow-up. Plasma biomarker levels were measured at the peri-operative time points. Association between biomarker concentrations and echocardiographic parameters was assessed.. Neither left ventricular mass index nor relative wall thickness varied from pre-op to post-op. At pre-op, relative wall thickness was elevated in 52% and left ventricular mass index was elevated in 22%; at follow-up, relative wall thickness was elevated in 13% and left ventricular mass index was elevated in 8%. Presence of residual coarctation did not predict left ventricular remodeling (AUC 0.59; P > .05). Multivariable receiver operating characteristic curve combining pre-op ST2 and endothelin 1 demonstrated significant predictive ability for late pathologic left ventricular remodeling (AUC 0.85; P = .02).. Persistent left ventricular hypertrophy and abnormal relative wall thickness at intermediate-term follow-up was rare compared to previous studies. A model combining pre-op endothelin 1 and ST2 level demonstrated reasonable accuracy at predicting persistent abnormalities in this cohort. Larger studies will be needed to validate this finding and further explore the mechanism of persistent left ventricular remodeling in this population.

Topics: Adolescent; Aortic Coarctation; Biomarkers; Cardiac Surgical Procedures; Child; Child, Preschool; Endothelin-1; Female; Humans; Hypertrophy, Left Ventricular; Infant; Infant, Newborn; Interleukin-1 Receptor-Like 1 Protein; Male; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

Use of balloon angioplasty or stent implantation has been reported to be effective in relieving coarctation of the aorta. However, restenosis frequently occurs after balloon angioplasty for native aortic coarctation in small infants, and sometimes develops after stent implantation because of vessel growth. The causes of restenosis remain uncertain. The purpose of this study was to assess the histologic differences in vascular responses to angioplasty using conventional balloon, radiofrequency thermal balloon (RFTB), or stent for experimental aortic coarctation.. The authors surgically created an aortic coarctation model using 14 puppies. Angioplasty using conventional balloon, RFTB, or stent was performed 1 month after the initial operation. At the acute or chronic phase after angioplasty, the animals were killed and histologic studies were performed.. More vascular injuries were noted in the specimens from animals undergoing conventional angioplasty than in those with RFTB or stent. However, neointimal hyperplasia was seen more often after RFTB or stent because of the proliferation of smooth muscle cells from the tunica media, caused by secretion of growth factors. Apoptosis reached a peak 1-2 weeks after angioplasty, regardless of the type of intervention.. The authors conclude that angioplasty with RFTB or stent can provide relatively small injuries in the vessel wall for aortic coarctation, but care must be taken to prevent restenosis caused by intimal hyperplasia, because neointima hyperplasia is more frequent after RFTB or stent.

Topics: Angioplasty, Balloon; Animals; Aortic Coarctation; Apoptosis; Dogs; Endothelin-1; Recurrence; Stents; Tunica Intima

Topics: Adolescent; Aortic Coarctation; Catheterization; Child; Child, Preschool; Endothelin-1; Humans; Infant

Chronic pressure overload is known to increase cardiac mass and expression levels of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs. Although mechanical stretching of cardiac myocytes could cause these changes, humoral factor(s) secondary to pressure overload may also be involved. To dissociate humoral effects from the effects of mechanical loading on cardiac hypertrophic responses, we examined expression of ANP and BNP at both mRNA and protein levels and proportions of myosin isoforms in transplanted cervical hearts that were mechanically unloaded under conditions with or without hypertension by aortic coarctation. Seven days after transplantation, cardiac atrophy that usually occurs in transplanted hearts without hypertension by coarctation was prevented in the transplanted hearts with hypertension by coarctation. The levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts with relative to those without hypertension by coarctation. The plasma level of angiotensin II was higher in rats with than without hypertension by coarctation. Plasma endothelin-1 levels were not significantly different between the two groups. In addition, levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts without hypertension relative to those in the in situ hearts. The proportion of the V3 myosin isoform was also increased in the transplanted hearts without hypertension relative to the in situ hearts. These results indicate that humoral factor(s) secondary to the pressure overload produced by aortic coarctation enhanced the cardiac hypertrophic response and elevated the levels of mRNAs encoding these embryonic markers. Moreover, our findings regarding ANP and BNP expression in the transplanted hearts provide additional evidence that the fetal genes are reexpressed during the process of cardiac atrophy as well as in cardiac hypertrophy.

Topics: Angiotensin II; Animals; Aortic Coarctation; Atrial Natriuretic Factor; Atrophy; Blood Pressure; Body Weight; Cardiomegaly; Endothelin-1; Heart Rate; Heart Transplantation; Hypertension; Male; Myosins; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred Lew; RNA, Messenger; Transcription, Genetic; Transplantation, Heterotopic; Transplantation, Isogeneic