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By A. Sugut. Pensacola Christian College.

Psychosocial factors and quality of life in children and adolescents with implantable cardioverter-defibrillators discount minocycline online amex. Psychological functioning and disease-related quality of life in pediatric patients with an implantable cardioverter defibrillator cheap minocycline 50 mg visa. Acceptance and psychological impact of implantable defibrillators amongst adults with congenital heart disease buy generic minocycline 50mg line. Outpatient left ventricular assist device support: A destination rather than a bridge buy generic minocycline on line. Recovery of major organ function in patients awaiting heart transplantation with Thoratec ventricular assist devices. Assessment of submaximal exercise capacity in patients with left ventricular assist devices. Exercise performance in patients with end-stage heart failure after implantation of a left ventricular assist device and after heart transplantation: an outlook for permanent assisting? Change in quality of life from before to after discharge following left ventricular assist device implantation. Quality of life and psychological well-being during and after left ventricular assist device support. Comparison of functional capacity in patients with end-stage heart failure following implantation of a left ventricular assist device versus heart transplantation: Results of the experience with left ventricular assist device with exercise trial. Pediatric ventricular assist device use as a bridge to transplantation does not affect long-term quality of life. Educational and psychological interventions to improve outcomes for recipients of implantable cardioverter defibrillators and their families: a scientific statement from the American Heart Association. A randomized controlled trial of cognitive behavior therapy tailored to psychological adaptation to an implantable cardioverter defibrillator. Effect of physical training in children and adolescents with congenital heart disease. Effectiveness of a school- and community-based academic asthma health education program on use of effective asthma self-care behaviors in older school-age students. Adherence to asthma medication regimens in urban African American adolescents: Application of self-determination theory. Effect of guided self-determination youth intervention integrated into outpatient visits versus treatment as usual on glycemic control and life skills: a randomized clinical trial in adolescents with type 1 diabetes. Improving glycaemic control and life skills in adolescents with type 1 diabetes: A randomised, controlled intervention study using the Guided Self- Determination-Young method in triads of adolescents, parents and health care providers integrated into routine paediatric outpatient clinics. Comprehensive cardiac rehabilitation programme for implantable cardioverter-defibrillator patients: A randomised controlled trial. Evaluation of child and parent outcomes after a pediatric cardiac camp experience. Changes in perceived health of children with congenital heart disease after attending a special sports camp. As a result some quality-related terminology may not be familiar to the pediatric cardiologist or they may not be familiar with the specific definitions. To avoid confusion and put some terms in the clinical context of the Heart Center, the following is a brief definition list: Quality: The degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge (1). Thus, quality is about outcomes: how successful are we in treating a certain cardiac defect? Patient safety: Freedom from accidental injury (2), or avoidance, prevention, and amelioration of adverse outcomes or injuries from healthcare processes (3). Medical error: An event where a planned action is not carried out or carried out incorrectly—an “error of execution;” or an event occurring secondary to a faulty plan—an “error of planning” (2,4). James Reason (4) further dissects the anatomy of medical errors into slips, lapses, and fumbles. Swiss cheese phenomenon: Another concept popularized by Reason (4) is that most significant adverse events do not result from a single medical error. Instead they result from multiple failures of the barriers (usually policies and procedures) which were intended to protect the patient. The barriers are not perfect and the holes in the Swiss cheese represent areas where the barrier could be breached. For an error to reach the patient and cause harm, all the holes in the various Swiss cheese layers must line up. Further, most clinician scientists are trained in the traditional research model (randomized trials with treatment groups and control groups) wherein an intervention is introduced while controlling for all or most other variables and then examining the result. This chapter is intended to provide the cardiology specialist with an overview of quality- and safety-related principles. He undergoes his first stage palliation on day of life 5, with a traditional Norwood procedure and a modified Blalock–Thomas–Taussig shunt. The attending physician orders 20 mL/kg of packed red blood cells along with platelets and fresh frozen plasma for this blood type O negative patient. The critical care fellow orders 20 mL/kg of packed red blood cells (A positive) and platelets for this patient. They asked for an update on his condition but were asked to return to the waiting room. A subsequent cause analysis revealed: (1) the perceived urgency to administer the blood was used by the nurse as a reason to “skip” the double check that should occur prior to all blood product administration (an “individual failure”); and (2) the hospital and blood bank did not have a clear and well-known double-check policy (with consequences for policy violation) prior to all medication and blood product administration (a “system failure”). Examples of improved outcomes included reduced mortality following various surgical procedures, reduced patient falls, and improved liver transplant graft survival. Causal factors are often broken into subcategories such as patient factors, caregiver factors, team factors, and technology or environmental factors (8). The responses obtained to these “why” questions are used to help create a cause and effect diagram. This diagram or “fishbone diagram” can also be used to help map the process and better categorize root causes. The main factor categories contributing to the event are listed on the various “fishbone branches or ribs. Failure modes with high scores get prioritized to develop a mitigation plan and action plan to be followed if the failure happens. Recently Ashley and Armitage (11) have questioned the reliability of the mathematical scoring systems in use today which result in very different prioritization recommendations for the failure modes. They suggest that a consensus scoring system should be developed to mitigate this possibility. Sentinel events are identified by the outcome without consideration for preventability or whether there was a variation from expected care practices that caused the event. In contrast, a serious harm event starts with a deviation from best practice that results in serious harm. Therefore a serious harm event includes both the causal process and the untoward outcome. The timeline description requires interviews with all staff involved in the event along with a review of pertinent policies and procedures. Inappropriate actions are identified when there is deviation from expected practice or local or national policies/guidelines. There are multiple subcategories within the larger system or individual failure groupings. This subcategorization is intended to make it easier to find common causes for adverse events, even if the various event specifics are disparate. Individuals who possess the authority to implement the corrective actions are identified, and a timeline for implementation is established. System failures included the following: The hospital did not have a clear, consistent method and policy for double-checking blood products. Additionally, the expectations and potential consequences of violating a patient check were not clearly understood by all staff members. Individual failures include: The nurse did not perform a double check prior to blood administration to ensure the blood was intended for her patient although she knew the double check was necessary. The blood bank technician did not confirm delivering the blood product to the correct patient bed. System corrective measures include: Establish a hospital-wide policy regarding how blood products are ordered and delivered to patients. Require a mandatory double check of blood products (as well as high-risk medications) by all staff members. Provide education to staff members regarding this policy as well as providing background to why it was established.

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Others have described alternative approaches purchase minocycline without prescription, including reconstruction of the deficient inlet septum generic minocycline 50 mg without prescription, septal myectomy discount minocycline 50mg fast delivery, and apical-aortic conduits (79 purchase minocycline 50 mg free shipping,80,81,82). It occurs in the presence of pulmonary hypertension or in association with tetralogy of Fallot with right ventricular dysfunction and pulmonary valve regurgitation or stenosis. The patch (arrow) is attached to the right side of the atrial septum and the right atrioventricular valve to avoid damage to the conduction tissue and left atrioventricular valve. However, there are limited data in pediatric patients regarding the utility and feasibility of 3-D color Doppler quantitative assessment of regurgitation in these patients. In that setting, the echocardiographer should use indirect techniques such as assessment of ventricular septal flattening or bowing, right ventricular size and function, and Doppler interrogation of the pulmonary regurgitation velocity waveforms to assess pulmonary artery diastolic pressure. Note the tear in the leaflet (white arrow) just posterior to the repaired cleft (black dashed line). The larger jet (dashed black arrow) is through the tear just posterior to the repaired cleft and central to the cleft. The smaller jet is located near the atrial septum, within the repaired cleft itself (solid black arrow). The role of cardiac catheterization for some patients is to evaluate coronary artery anatomy or for calculation of pulmonary vascular resistance. If the rPa is elevated above this level, then provocative testing in the catheterization laboratory with the use of pulmonary vasoactive 2 agents such as nitric oxide is indicated. In this select group of patients, one would consider pre- and postoperative treatment with pulmonary vasoactive agents such as bosentan, sildenafil or Flolan, and documentation via hemodynamic catheterization of a substantial improvement in rPa during this therapy. In patients older than age 40 years, regardless of symptoms, noninvasive assessment of coronary artery disease typically is performed prior to surgery. However, for women with pulmonary vascular obstructive disease and severe pulmonary artery hypertension (pulmonary artery systolic pressure >60 mm Hg), pregnancy is not advised. Preferably, this should be at centers that specialize in the care of adults with congenital heart disease. The pioneering work performed by Giancarlo Rastelli in the 1960s is but one of these accomplishments. Acknowledgments The authors acknowledge the contributions of the former authors of this chapter (Drs. Surgical management of complete atrioventricular septal defect: Association with surgical technique, age, and trisomy 21. Actuarial survival, freedom from reoperation, and other events after repair of atrioventricular septal defects. Prevalence at birth, “natural” risk and survival with atrioventricular septal defect. Prospective diagnosis of 1006 consecutive cases of congenital heart disease in the fetus. Ethnicity, sex and the incidence of congenital heart defects: a report from the National Down Syndrome Project. Asplenia syndrome: insight into embryology through an analysis of cardiac and extracardiac anomalies. Evaluation of risk factors for prediction of outcome in fetal spectrum of atrioventricular septal defects. Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart. Cleft anterior leaflet of the mitral valve with intact septa: a study of 20 cases. Atrioventricular septal defect with cor triatriatum: case report and review of the literature. Atrioventricular canal ventricular septal defect with cleft mitral valve: angiographic and echocardiographic features. Atrioventricular septal defect with intact atrial and ventricular septal structures. Evaluation of atrioventricular septal defects by three-dimensional echocardiography: benefits of navigating the third dimension. Two-dimensional versus transthoracic real-time three- dimensional echocardiography in the evaluation of the mechanisms and sites of atrioventricular valve regurgitation in a congenital heart disease population. Three-dimensional echocardiography improves the understanding of the mechanisms and site of left atrioventricular valve regurgitation in atrioventricular septal defect. Variations of atrioventricular septal defects predisposing to regurgitation and stenosis. Quantitative real-time three-dimensional echocardiography provides new insight into the mechanisms of mitral valve regurgitation post-repair of atrioventricular septal defect. Partial zone of apposition closure in atrioventricular septal defect: are papillary muscles the clue? Fixed subaortic stenosis in atrioventricular canal defect: a Doppler echocardiography study. Electrophysiologic cardiac function before and after surgery in children with atrioventricular canal. The atrioventricular conduction system in persistent common atrioventricular canal defect: correlations with electrocardiogram. Atrioventricular septal defect with balanced ventricles and malaligned atrial septum: double-outlet right atrium. Successful correction of double outlet left atrium associated with complete atrioventricular canal and l-loop double outlet right ventricle with stenosis of the pulmonary artery. Anatomic observations on complete form of persistent common atrioventricular canal with special reference to atrioventricular valves. Double-outlet right ventricle associated with persistent common atrioventricular canal. The surgical anatomy of common atrioventricular orifice associated with tetralogy of Fallot, double outlet right ventricle and complete regular transposition. Development of left atrioventricular valve regurgitation after correction of atrioventricular septal defect. Echocardiographic evaluation of atrioventricular orifice anatomy in children with atrioventricular septal defect. Morphometric analysis of unbalanced common atrioventricular canal using two-dimensional echocardiography. Predicting feasibility of biventricular repair of right- dominant unbalanced atrioventricular canal. Correction of atrioventricular septal defect: results influenced by Down syndrome? Complete atrioventricular canal associated with tetralogy of Fallot: morphologic and surgical considerations. Prevalence of left-sided obstructive lesions in patients with atrioventricular canal without Down syndrome. Atrioventricular septal defect – anatomic characteristics in patients with and without Down syndrome. Pulmonary vascular resistance in complete atrioventricular septal defect: a comparison between children with and without Down syndrome. Does Down syndrome affect prognosis of surgically managed atrioventricular canal defects? Surgical anatomy and pathology of the conduction tissues in atrioventricular defects. Surgical anatomy and management of the mitral component of atrioventricular canal defects. Efficacy of pulmonary artery banding in infants with complete atrioventricular canal. Should repair of atrioventricular septal defect be delayed until later in childhood? Determinants of early and late results of repair of atrioventricular septal (canal) defects. Anatomically sound, simplified approach to repair of “complete” atrioventricular septal defect. Simplified single patch technique for the repair of atrioventricular septal defect. Atrioventricular septal defects: lessons learned about patterns of practice and outcomes from the congenital heart surgery database of the Society of Thoracic Surgeons. Complete atrioventricular canal: comparison of modified single-patch technique with two-patch technique.

Thus purchase minocycline 50mg without prescription, the pH of unsatisfactory cannula placement can reduce fow to the strategy selected purchase minocycline 50mg amex, whether the more alkaline alpha stat strat- brain or lower body resulting in lower venous saturation in egy or the more acidotic pH stat strategy order discount minocycline line, will infuence oxy- that cannula purchase minocycline 50mg without a prescription. However, this is logistically complicated and is blood that is added to the pump prime for neonates and rarely if ever practiced in day-to-day surgery. Therefore, it is infants will exacerbate the leftward shift induced by cooling essential that the surgeon develop the habit of constantly moni- and alkalinity. Thus, this factor also potentially raises venous toring the color of the venous return in both cannulas. It is also oxygen saturation even though there has been no change in possible by looking at the Y junction of the two cannulas to the metabolic needs of the patient until hypothermia has estimate the relative fow in each cannula. How much to adjust the minimal acceptable also be alert to notifcation by the perfusion team that there is level of venous saturation according to the volume of bank a problem with volume loss from the circuit suggesting that blood used in the prime is entirely empirical. This should always lead to an inspection of both cannulas for signs of lower Left Heart Return, Collateral Steal or higher venous saturation with subsequent repositioning. A second dangerous assumption is Because heart rate, perfusion pressure and venous saturation that only macroscopic connections between the systemic all have serious limitations as methods for monitoring the arterial and pulmonary circulations result in a signifcant adequacy of perfusion, it is critically important that accurate 184 Comprehensive Surgical Management of Congenital Heart Disease, Second Edition information is available regarding the fow rate of blood anesthetized patient who is not on bypass, it is of very little actually entering the patient’s arterial circulation through the use during bypass. In addition, hypothermia can result in using modern equipment is able to continuously monitor all vasoconstriction of peripheral vessels resulting in inadequate patient variables, including heart rate and blood pressure on signal. Baseline calibration drift The steal from internal circuits, such as flters and hemocon- and wedging against the venous wall further complicate rou- centrators, adds even greater inaccuracy to calculated rather tine use. The interaction of these perfusion variables must be The principal limitation of these devices that can measure understood by the perfusion, anesthesia and surgical team changes from baseline fow in the middle cerebral artery is and is discussed in detail later in this chapter. Slight movement of the head, for example to operation, there are multiple disadvantages to this approach suction the endotracheal tube will alter the angle and the which supplies far more substrate than is required by the reading. Disadvantages include need for a higher volume to be The minimal acceptable fow relative to baseline that will maintained in the circuit and therefore either a greater use avoid cerebral injury is unknown. They are not recom- A progressive lactic acidosis during bypass is a serious indi- mended for neonates and infants who have reduced synap- cator of a perfusion problem. Fortunately, lactate levels can tic development and where greater degrees of hypothermia now be obtained much more easily than in the past. Hypothermia per se reduces elec- it is still not a real-time monitor and may not be noted until trical activity. Near-infrared tion of circulatory arrest that is safe, the reality is that the light penetrates the skull and allows assessment of changes safe duration of circulatory arrest changes according to from baseline of the oxyhemoglobin and deoxyhemoglo- conditions, particularly brain temperature, pH and hemato- crit. Approximately 70% of the signal is from venous blood so both functional and structural endpoints, i. Although there was initial brain during circulatory arrest because of ongoing metabo- hope that the technique would allow assessment of intracel- lism (Fig. A more acidotic pH and lower temperature lular oxygenation through measurement of changes in cyto- decrease the rate of HbO2 decay, while a higher hematocrit chrome aa3 redox state, studies using cyanide suggested that raises the baseline from which the decay begins, i. It instrument is a useful real-time monitor for determining the is longest with a lower temperature, more acidotic pH and safety of a reduced fow rate under specifc bypass condi- higher hematocrit (Table 10. The duration of arrest beyond the nadir time (oxyhemoglobin nadir time) is a useful predictor of behavioral and histological injury after circulatory arrest. Prediction of safe duration of hypothermic circulatory arrest by near infrared spectroscopy. No injury is seen under 25 minutes so that if it takes 30 minutes for the signal to fat-line, 55 minutes of circulatory arrest is “safe. In the world of cardiopulmonary bypass for adults, there was considerable enthusiasm for normothermic bypass in the mid-1990s. The usual practice minutes were free of behavioral and histologic evidence of today is to use “tepid” bypass, meaning that active warming brain injury. Analogies are frequently drawn between the airline indus- try and cardiac surgery, particularly in the domain of safety. In the absence of information from instru- Decreased Infammatory Response ments, a pilot must maintain safety margins: adequate speed of Cardiopulmonary Bypass greater than stall speed and adequate altitude greater than any Among the most obvious sequelae of bypass in the neonate or possible ground elevation in the fight path. Unfortunately, young infant are whole body edema, fuid retention, pleural cardiac surgeons have limited monitoring information as effusions and ascites. Conduct of Cardiopulmonary Bypass 187 What Is the Infammatory Response to Cardiopulmonary 100 Bypass? The systemic infammatory response to bypass 90 consists of activation of multiple humoral cascades, as well 80 as activation of cellular components of blood and endothelial 70 cells throughout the body. There are multiple humoral 40 cascades which are activated during bypass includ- 30 ing the coagulation cascade, the fbrinolytic cascade, 20 the complement system and the kallikrein/bradyki- 29,30 31 10 nin cascade. Previously in 32 (a) 1981, Chenoweth and colleagues, also from the University of Alabama, Birmingham, had demon- 100 strated that there was a progressive rise in plasma 90 C3a during cardiopulmonary bypass. Both C3a and C5a are vasoactive anaphyla- 60 toxins which increase vascular permeability, release 50 histamine from muscles and cause hypertension and contraction of airway smooth muscle. C5a is rapidly 40 taken up by neutrophils, but an increase associated 30 with bypass has been demonstrated. Craddock and 20 colleagues33 have shown that complement activated 10 neutrophils sequester within the lung and increase 0 0 500 1000 1500 2000 2500 3000 3500 4000 perivascular edema. The fg- adhesion molecules, such as selectin proteins on ure illustrates percentile distribution of patients according to C3a endothelial surfaces and carbohydrate ligands levels. J Thorac Cardiovasc protein was particularly important in bypass-related vascular Surg 1983;86:845–57. White cell activation was measured by direction obser- Synthesis and release of chemoattractants, such as leukotri- vation of white cell rolling and adhesion in cerebral arterioles enes, promote further neutrophil activation and attraction. Hypothermia and the Infammatory Response to Decreased Metabolic Rate Cardiopulmonary Bypass There has been little attention In contrast to the surprising lack of information regarding paid to the impact of hypothermia in reducing the infamma- the direct effect of hypothermia in reducing the systemic tory response to bypass. Not surprisingly, the amount of acti- infammatory response of bypass, there is now a large body vation of humoral cascades, including release of vasoactive of information regarding the effect of hypothermia in reduc- 37 ing metabolic rate (Fig. A study conducted 188 Comprehensive Surgical Management of Congenital Heart Disease, Second Edition 10 versus 34°C, p < 0. The number of (a) rolling leukocytes and (b) adherent leukocytes was signifcantly less at 15°C relative to 34°C. Higher bypass temperature correlates with increased white cell activation in the cerebral microcirculation. In retrospect, this appears to have been related to a failure to abolish shivering because of use of an inadequate level of anesthesia in studies that were undertaken before 1950. The effect of temperature on cerebral Hypothermia was not used in the early years of metabolism and blood fow in adults during cardiopulmonary cardiopulmonary bypass. Current day rate that occurs with hypothermia has several important con- bypass hardware is very much more reliable so that the safety sequences for the cardiac surgical team. Nevertheless, the skill and experi- Safety Margin for Acute Pump, Oxygenator, Circuit or ence of the perfusion team in dealing with an acute prob- Cannula Failure In the early years of cardiopulmonary lem must be considered. Even today, clamps can be placed bypass, hypothermia provided an important safety element. Conduct of Cardiopulmonary Bypass 189 Improved Myocardial Protection Hypothermia reduces complete cessation of bypass, i. Although local myocardial hypothermia of perfusion fow rate evolved slowly and somewhat surrep- can be attained through infusion of cold cardioplegia solu- titiously entered into clinical cardiac surgical practice. One tion, the temperature of the pump perfusate has an important of the most important reasons for the slow acceptance of effect on the rate of rewarming of the heart between car- reduced fow rate with hypothermic bypass is a consequence dioplegia infusions (Fig. Even when there is total cardiopulmonary bypass with separate caval cannulas and • Improved intracardiac exposure. Many patients tourniquets, the temperature of retrocardiac tissues in par- with congenital cardiac anomalies, particularly ticular will be determined by perfusate temperature and will those which result in cyanosis, will develop mul- affect the rate of myocardial rewarming. Although multiple tiple profuse collateral vessels which increase the infusions of cardioplegia solution are well tolerated beyond left heart return. This blood fow usually returns infancy, many studies have suggested that in the neonate and to the left atrium through the pulmonary veins, younger infant, multiple reinfusions of cardioplegia result in but when the pulmonary artery is open it will also less good myocardial protection, most likely because of myo- result in continuous back bleeding from the pulmo- cardial edema. When excellent intracardiac expo- sure is necessary, it is often important to reduce the Decreased Metabolic Rate Allows Reduced Flow Rate: amount of left heart return temporarily. This can be Advantages Although it was recognized early in the his- achieved very effectively by reducing the perfusion tory of cardiac surgery that hypothermia would allow fow rate.

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An additional concern when discussing transcatheter interventions for native coarctation is the potentially greater incidence of aortic aneurysm formation in the area of the coarctation dilation purchase minocycline no prescription. However buy minocycline 50 mg with visa, the follow-up data is limited discount 50mg minocycline visa, and the long-term outcome is uncertain discount 50mg minocycline overnight delivery, at best. Another concern with these aneurysms, particularly following an otherwise successful dilation, is that if subsequent surgery is necessary, it could be more hazardous because of the disappearance of collaterals following a hemodynamically successful dilation. As more follow-up information is gathered regarding dilation of native coarctation, this technique appears more reasonable for discrete lesions in patients over 7 to 12 months of age (102). In the larger child, primary stent therapy for native coarctation is a suitable treatment alternative to balloon angioplasty, even though aneurysms can occur with these stent implants. It has been suggested that gradual conservative expansion of these stents be performed over two or three procedures, especially in tight lesions, to reduce the incidence of dissection or aneurysm formation. If balloon angioplasty alone is performed, a balloon of the same diameter as the narrowest aortic diameter adjacent to the coarctation is prepared. A “J” or curved-tip stiff guidewire is positioned retrograde through the coarctation, around the aortic arch, and into the aortic root or occasionally into the right innominate artery. The dilation balloon catheter is passed over the wire and across the area of coarctation. The inflation may be repeated several times until the waist in the balloon or the gradient disappears. In smaller children and infants, cutting balloon angioplasty frequently adds an additional treatment alternative in patients where endovascular stent placement should be avoided. In the slightly larger patient, when the results of the dilation are not satisfactory and where larger sheaths can be introduced into the arteries, intravascular stents can be used to support the dilated segment of aorta. When stents are used, it is imperative that only stents that eventually can be dilated to the full diameter of the adult descending aorta are used. Transcatheter management of coarctation in the adult has some important differences when compared to its management in the younger child. For example, limiting factors in younger children when considering endovascular stent therapy, are the potential for injury to the arterial vessels and access sites due to the need for larger-sized hemostatic sheaths as well as the higher likelihood of developing in-stent stenosis when stents are only expanded to fairly small diameters. The goal of the interventional procedure in adults is similar to children: To achieve reduction in the gradient to less than 10 mm Hg or a 90% or greater relief of the obstruction angiographically. It has been advocated that the risk of catastrophic aortic injury during or after balloon angioplasty and/or stent placement in the adult (106,107,108) is higher than what would be expected in the younger child, especially when treating primary coarctation. Many adult patients with systemic and exercise-induced hypertension, may present with “just” a 20 to 30 mm Hg upper-to-lower limb blood pressure gradient with an angiographic discrepancy between coarcted segment and the aorta at the diaphragm of not more than 30% to 50%. To achieve an adequate result with balloon angioplasty alone, one would ideally have to expand the area to at least twice the size of the coarctation segment (91,92). However, using this as a guide would lead to significant overdilation of not only the coarcted segment, but also the adjacent “healthy” aorta. Primary stent therapy is therefore the treatment of choice in adults with primary or recurrent coarctation, as it not only avoids the need for overexpansion, but also has a lower risk of recurrence when compared to balloon angioplasty. A 34-year-old pregnant woman hospitalized during her 24th week gestation with severe systemic hypertension. Fluoroscopy time was minimized and appropriate radiation protection measure were taken. This not only identifies areas with medial and intimal disruption as could relate from a previous attempt at balloon angioplasty, but it also allows to clearly define the extension of the abnormal vessel wall, thereby allowing to choose a stent that is of sufficient length to cover the full length of the abnormal vasculature. Some institutions advocate pre-expansion of the coarcted segment as a means of testing aortic wall compliance prior to stent implantation. However, this has the disadvantage of potentially extending a intimal-medial tar into healthy vasculature that subsequently may not be covered during stent placement, therefore potentially acting as a “nidus” for aneurysm formation, especially at the areas immediately adjacent to the placed stent. In adults with very “tight” coarctation, it may be beneficial to expand the aorta not to the full intended diameter in a single procedure, but instead adopting a staged approach where the stent is dilated over two or three sessions up to its desired final diameter, thereby allowing the aorta to heal in between interventional procedures, with a reduced risk of catastrophic aortic wall injury. However, even with a very careful and considerate approach, the risks of treating adult coarctation cannot be fully eliminated and therefore whenever possible, the availability of an approved covered stent variety as a primary or rescue intervention could potentially enhance the safety of these procedures (Fig. Covered stents have also been successfully used to exclude aortic aneurysms at the site of (re)coarctation (Fig. It is important to minimize the potential risk of aneurysm formation and other vascular complications after transcatheter therapy of (re)coarctation. The freshly injured vessel wall should be protected from any hypertensive strain and as such, at least temporary placement of the patient on antihypertensive medications such a beta-receptor blockers (even in the normotensive patient), may potentially reduce the incidence of early vascular complications after transcatheter therapy. During follow-up, it is important to investigate for the potential development of aneurysms at the site of interventional therapy, which can occur even after stent therapy. Rehabilitation of (Branch) Pulmonary Artery Stenosis Transcatheter therapy of all varieties of branch pulmonary artery stenoses is a widely accepted standard procedure, in large part because most of these lesions are not amenable to surgical repair. However, rehabilitation of branch pulmonary artery stenoses can be one of the most challenging tasks in congenital pediatric patients. Transcatheter therapy has to strive to achieve the optimum possible outcome, which sometimes requires repeated and staged procedures to achieve some improvement for an individual complex patient. The treatment modalities available include the use of cutting balloons, standard balloon angioplasty, or the placement of endovascular stents. A 23-year-old male who underwent GoreTex patch augmentation earlier in life and subsequently developed recoarctation with a 22 mm Hg peak systolic gradient and an associated posterior aneurysm. The individual success of treating these lesions is sometimes difficult to assess, but in patients with a biventricular circulation a reduction in the right ventricular to systemic pressure ratio is a good indicator for a successful outcome. Individual pressure gradients to branch pulmonary arteries may be less meaningful, and in fact angiographically significant branch pulmonary artery stenoses can be associated with surprisingly low-pressure gradients, especially for isolated lesions and in the presence of significant pulmonary insufficiency. The angiographic appearance of the vessel before and after transcatheter intervention is equally important, and while one should strive to aim to achieve a “normal” vessel diameter, frequently the percentage of improvement in the anatomic measured stenosis is a good outcome parameter. Rotational angiography with 3-D reconstruction is a new tool that is in particular suited for patients that require complex pulmonary artery rehabilitation. The 3-D reconstructions allow to visualize the complete pulmonary artery tree and the best angulations can be chosen to profile individual lesions P. This not only provides better imaging of individual lesions, but may also lead to a reduction in the overall amount of contrast needed, especially in patients who require multilevel pulmonary artery rehabilitation. The amount of contrast for individual rotational angiographies can be further reduced by using rapid right ventricular pacing during the rotational acquisition. The image can be rotated until the lesion is best profiled and the allowable angles are displayed (**) which then allows the operator to choose the same angulations for two-dimensional acquisitions. While standard balloon angioplasty can be performed using a normal balloon-over-the-wire technique, it is frequently helpful to place long sheaths toward the area of intended interventional therapy to facilitate simultaneous therapies of adjacent lesions, balloon exchanges, and subsequent placement of stents if required (Fig. In many patients, especially in adults, placements of long sheaths from a femoral venous approach may be difficult. Internal jugular venous or transhepatic approaches offer the advantages of eliminating some of the double-S-curves that have to be traversed from a femoral venous approach, while also requiring a shorter sheath length and allowing improved “pushability” of the catheter. Standard balloon angioplasty alone rarely achieves a sustainable long-term improvement to an individual stenosis and as such is usually only performed in situations where other forms of transcatheter treatment are not available or where the size of the patient or vessel prevents the use of endovascular stents that can be expanded to adult size. No absolute rules exist for determining the correct balloon size; however, it appears that the balloon should preferably be larger than two times the diameter of the stenotic segment while avoiding exceeding a diameter of three times the actual narrowing. However, when using standard balloon angioplasty “overdilation” of a vessel is frequently required to achieve an adequate outcome. In very resistant stenoses, the use of high-pressure balloons should be employed, rather than exceeding the size of the dilation balloons. Cutting balloon angioplasty is available for maximum diameters of up to 8 mm and is a suitable alternative to endovascular stenting especially in small distal pulmonary arteries (109,110). It is frequently beneficial to “score” very tight stenoses and can be followed either by standard balloon angioplasty or endovascular stent placement if required. In a randomized multicenter trial, Bergersen and colleagues demonstrated for cutting balloon angioplasty to be more effective to treat resistant pulmonary artery stenosis when compared to sole high- pressure balloon angioplasty (111). Standard balloon angioplasty of pulmonary branch stenosis has not been highly successful at correcting the lesions and many of the vessels that initially are dilated satisfactorily reconstrict immediately (recoil) with the deflation of the balloon or, if not immediately, a short time later. The true success rate at achieving a vessel of normal diameter with no gradient is less than 20%; at the same time, there is a definite morbidity and even mortality for the procedure. It is not possible to determine in advance which case will be successful, so the procedure is often performed as a therapeutic trial.

The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) order 50 mg minocycline with mastercard. Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome order minocycline 50 mg line. Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q effective 50mg minocycline. Protein-tyrosine phosphatase buy minocycline discount, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. Phenotypic and genotypic characterisation of Noonan-like/multiple giant cell lesion syndrome. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Novel copy-number variants in a population-based investigation of classic heterotaxy. Infants of diabetic mothers are at increased risk for the oculo-auriculo-vertebral sequence: A case-based and case-control approach. A mouse model of human congenital heart disease: high incidence of diverse cardiac anomalies and ventricular noncompaction produced by heterozygous Nkx2–5 homeodomain missense mutation. Temporal variability in birth prevalence of congenital heart defects as recorded by a general birth defects registry. Total is more than the sum of the parts: phenotyping the heart in cardiovascular genetics clinics. A population-based study of extra-cardiac anomalies in children with congenital cardiac malformations. Goodwin Introduction The structure and function of the myocardium undergoes dramatic changes during fetal life and in postnatal maturation to adulthood. The postnatal period is marked by extensive physiologic and metabolic remodeling with dynamic changes as the fetal heart adapts to birth and converts to adult function (1). These processes are regulated by a number of hormones, neurotransmitters, growth factors, and mechanical forces. The coronary circulation is tightly coordinated with myocardial growth to ensure an adequate supply of oxygen and metabolic substrates. A complete understanding of the physiologic processes that regulate myocardial structure and function is a necessary prerequisite to understand the pathogenesis of congenital and acquired heart disease. While Chapter 1 in this volume provides a comprehensive discussion of the molecular and genetic determinants of heart development, this chapter describes the developmental and postnatal changes in cardiac structure, metabolic regulation, excitation– contraction (E-C) coupling, and growth/regeneration. Postnatal changes in hemodynamic load, autonomic innervation, and hormonal status are summarized. The effects of these changes on myocardial systolic and diastolic dysfunction are also discussed. The majority of studies on developmental changes in myocardial structure and function has been performed in zebrafish, chick embryos, and rodents, with some additional data taken from higher mammals and humans. While the process of E-C coupling is very similar, there is significant spatiotemporal variability in structural development among the different model species. Unless otherwise noted, the majority of the developmental changes described in this chapter will focus on data from rodent models and humans. Myocardial Structure The heart begins functioning as a simple tube composed of only cardiac myocytes and endocardial cells. However, it quickly becomes a complex organ comprising multiple cell types that can be grouped into conducting, supporting, and functional cells (Fig. The cellular constituents of the heart include cardiac myocytes, cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells. The sinoatrial nodes are specialized myocytes responsible for action potential generation. The conducting cells, also derived from cardiac myocytes are mainly Purkinje fibers. While cardiac myocytes are responsible for the mechanical function of the heart, they comprise only ∼30% of the total number of cells. Cardiac fibroblasts predominate in conferring structural integrity to the heart (5). Cardiac Fibroblasts and the Extracellular Matrix The cardiac fibroblast is the most abundant cell type present within the postnatal mature heart. Cardiac fibroblasts are derived from different cell lineages at different developmental stages. Fibroblasts also arise from the differentiation of bone marrow–derived circulating fibrocytes (6). In the neonatal and adult heart, cardiac fibroblasts arise from resident cells via epithelial–mesenchymal transformation and from bone marrow–derived cells (7). Thus, cardiac fibroblasts from the neonatal period are distinct from those in the adult myocardium and are also different from the ones that populate the heart following acute injury or chronic hemodynamic overload (8). During development, fibroblasts secrete a number of growth factors that promote cardiac myocyte proliferation. Matrix deposition during this period establishes a functionally competent ventricle, which provides structural stability necessary for transitioning from fetal to postnatal life (9). Elastic fibers are present in close association to collagen and are responsible for maintaining normal elasticity of the cellular framework. The endothelial cell layers line the surface of the endocardium (top) and is supported by a layer of dense extracellular matrix (collagens, elastins, fibronectin, proteoglycans) secreted by interstitial cardiac fibroblasts (pink). The Purkinje fibers (green) are specialized cardiac muscle fibers located within this matrix that are responsible for electrical impulse propagation from the atrioventricular node to the ventricular myocardium. Cardiac myocytes are organized in myofibers and are electromechanically coupled by intercalated discs. Small blood vessels and capillaries are located adjacent to myofibers to provide nutrients, deliver oxygenated blood, and remove metabolic by-products. Cardiac fibroblasts become enmeshed in this network, which allows them to contract the endomysial collagen, exerting mechanical force on the myocytes. In the adult myocardium, this network includes the epimysium that surrounds large groups of muscle fibers, the perimysium arising from the epimysium that surrounds smaller groups of muscle fibers and the endomysium, which tethers individual fibers to each other and the adjacent vasculature (Fig. In addition to acting as scaffolding for cells and vessels, the collagen network also coordinates the transmission of force generated by myocytes, serving as a viscoelastic medium facilitating compression and recoil properties of the tissue (12). Cardiac fibroblasts are regulated by mechanical and molecular signals during cardiac development. Basement Membrane A specialized area of the matrix termed the basement membrane or basal lamina surrounds all cells in the myocardium except cardiac fibroblasts. An intact basement membrane is necessary for normal cardiac growth and maturation and plays an important role in postnatal cardiac myocyte sarcomerogenesis via activation of integrin-mediated signaling (14). Perlecan is expressed at high levels throughout embryogenesis in the heart and required to ensure mechanical stability until cell–cell contacts have formed and matured (16). Cardiac Myocytes Cardiac myocytes are derived from two waves of anterior splanchnic mesoderm known as the primary heart field, which forms the primary heart tube. Cardiac myocytes have two major mechanistic functions: Force generation by myofibrils in response to E-C coupling and force transmission across cell bundles mediated by the integration of electromechanical signals at the intercalated disc. Plasma Membrane The plasma membrane (or sarcolemma) is the region of the cell that contains ion pumps, channels, and exchangers that contribute to action potential propagation, as well as maintenance of proper ionic and chemical gradients. The flow of ions controlled by these proteins is essential for proper myocyte function and directly regulates cellular contraction and relaxation. Numerous G-protein–coupled receptors, cytokine receptors, and growth factor receptors are located on the plasma membrane and are responsible for transducing changes in the local neurohormonal milieu into intracellular signals that regulate cell growth and function. In the rodent heart, the low digitalis affinity α1 isoform predominates through all phases of development, while there is a postnatal transition from the neonatal α3 isoform to the adult α2 isoform that occurs within the second week of postnatal life (19). B: The interstitial connective tissue consisting of perimysial and endomysial components presents a honeycomb shape. The perimysium (thick arrow) surrounds groups of cardiomyocytes, and the endomysium (thin arrow) surrounds each cardiomyocyte. C: The endomysium (arrow) supports and connects individual cardiomyocyte fascicles. D: At higher magnification, collagen fibers show interconnections on the surface of cardiomyocytes. Three-dimensional architecture of cardiomyocytes and connective tissue in human heart revealed by scanning electron microscopy. This exchanger is bidirectional and capable of moving 2+ Ca in either direction across the sarcolemma.

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The major determinants of intra-and interindividual variability in insulin absorption include site of administration generic minocycline 50mg fast delivery, type of insulin order minocycline in united states online, and dose of insulin purchase minocycline 50mg amex. The site of insulin administration determines the rate of absorption discount minocycline 50mg overnight delivery; however, it does not infuence the extent of absorption. The abdomen is the preferred site as the rate of absorption is faster and less variable as compared to the thigh and arm. Other determinants of insulin absorption from injection site include sub- cutaneous blood and lymph fow and the frst-pass catabolism (proteases in subcutaneous tissue). Larger doses of insulin administered as a single injection have a greater vari- ability in absorption as compared to smaller doses of insulin. The mechanisms for recurrent hypoglycemia include absolute insulin def- ciency, impaired regulation of glucagon secretion, and autonomic failure. The second-line of defense against hypoglycemia is appropriate glucagon secretion. In addition, autonomic neuropathy due to long-standing diabetes also impairs glucagon secretion and predisposes for neuroglycopenia. Predominant abnormality in glucose profle of the index patient is fasting hyperglycemia. Fasting hyperglycemia may occur as a result of early morn- ing hypoglycemia (Somogyi phenomenon) or hyperglycemia (dawn phenomenon). Therefore, 0300–0400h blood glucose estimation is recom- mended to differentiate between them. Fasting hyperglycemia due to Somogyi phenomenon requires reduction in insulin doses, whereas exag- gerated dawn phenomenon needs an increase in insulin doses. The index patient had 0300h blood glucose of 60 mg/dl suggestive of Somogyi phe- nomenon as a cause for the fasting hyperglycemia; hence, the dose of glargine was reduced. If target blood pressure is not achieved within 3–6 months, pharmacological inter- vention should be considered. Annual comprehensive foot examination is recommended at the onset of puberty or at age ≥10 years, whichever is earlier, once the duration of diabe- tes is ≥5 years. Annual screening for diabetic retinopathy is recommended at the onset of puberty or at age ≥10 years, whichever is earlier, once the duration of diabetes is ≥3 years. The index child has duration of diabetes of 5 years but does not have any pubertal sign; therefore, he should be screened at the age of 10 years. Onset and progression of puberty is associated with development and wors- ening of diabetic retinopathy. Intensive insulin therapy is associated with initial worsening of diabetic reti- nopathy followed by slow progression of the disease. Therefore, periodic fundus examination should be performed after initiation of intensive insulin therapy. Limited joint mobility correlates with diabetic microvascular complications particularly diabetic retinopathy (Fig. The presence of ketoacidosis in a diabetic patient with blood glucose <250 mg/dl is termed as euglycemic diabetic ketoacidosis. Hourly monitoring of blood glucose is recommended for initial 24h to titrate the rate of insulin infusion. When blood glucose level is reduced to <200 mg/dl, 5% dextrose infusion should be added to prevent hypoglycemia, and the dose of insulin infu- sion is to be reduced. Arterial pH and serum anion gap should be monitored every four to six hours, and with effective treatment, arterial pH increases and serum anion gap progressively decreases. The presence of hypokalemia at presenta- tion suggests severe depletion of body stores of potassium, and hypokalemia may worsen after insulin infusion therapy. Failure to respond to therapy suggests inadequate fuid replacement, suboptimal insulin therapy, occult infection, or other causes of metabolic acidosis (lactic acidosis or uremia). Ketone bodies (acetone, acetoacetate, and β-hydroxybutyrate), being lipophilic, accumulate in adipose tissue. In the index case, calculated serum osmolality was 295 mOsm/Kg; there was no electrolyte abnormality and acidosis was mild. Therefore, alternative causes for altered sensorium should be actively sought in the index patient including men- ingitis, cortical vein thrombosis, stroke, and rhinocerebral mucormycosis. The index patient was evaluated and was found to have concur- rent pyogenic meningitis. This is because of relatively lower portal concentration of insulin is required to suppress hepatic glucose output (fasting hyperglycemia) as com- pared to inhibition of ketosis. Patients with diabetes are predisposed for certain infections which include emphysematous pyelonephritis, emphysematous cholecystitis, malignant otitis externa, rhino–orbito–cerebral mucormycosis, and liver abscess. The increased risk for these infections in patient with diabetes is due to glucotoxicity-mediated lazy leukocyte syndrome and impaired humoral and cellular immunity (Fig. Increased prevalence of childhood obesity as a result of sedentary lifestyle and consumption of calorie-dense food predisposes for the early development of diabetes. Biochemistry revealed fasting plasma glucose of 190 mg/dl, postpran- dial glucose 220 mg/dl, and HbA1c 8. He 12 Diabetes in the Young 415 should be carefully examined for other features of insulin resistance (double chin, skin tags, and central obesity), hypertension, and xanthelasmas. The index patient was advised to follow lifestyle modifcation and was initiated on metformin 1 g twice a day after meals. The monogenic forms of diabetes are rare and contribute only 1–2 % of individuals with diabetes. During adolescence and early adulthood, these individuals have normal fasting plasma glucose, but have hyperglycemia during oral glucose tolerance test. The important differentiating features between the two disorders are summarized in the table given below. Therefore, glucokinase is a key enzyme which regulates the rate of entry of glucose into the glycolytic pathway and its subsequent metabolism in β-cell. The most affected individuals are asymptomatic and are detected during screening (e. How do hepatocyte nuclear transcription factors regulate insulin secretion and glucose metabolism? Hepatocyte nuclear transcription factors are expressed not only in the liver but also in the pancreatic β-cells and urogenital tissues. These proteins regu- late tissue-specifc gene expression and thereby determine growth and development, as well as facilitate metabolic signaling in these organs. During embryogenesis, these transcription factors act in concert to promote islet devel- opment and regulate the expression of insulin gene, and genes-encoding pro- teins which are linked to insulin secretion. Diabetes is prevalent in approximately 60 % of individuals and occurs at an early age. These individuals are often diagnosed to have type 2 diabetes and started on oral antidiabetic drugs; however, most of these individual will require insulin within a few years. Exogenous insulin therapy results in decreased expression of β-cell autoantigens and may activate Treg cells and inhibit autoreactive T cells, thereby delaying the ongoing immunoinfamma- tory destruction of β-cells. Preservation of residual β-cell function helps to pre- vent wide swings in blood glucose and decrease the risk of hypoglycemia. Sulfonylureas are to be avoided as these drugs enhance the expression of autoan- tigens in β-cells and hasten the immunoinfammatory process. Metformin can be used in some patients who have features of insulin resistance, particularly in obese individuals. The alkaloids linamarin and lotaustralin present in cassava produce cyanide compounds which are detoxifed by sulfur-containing amino acids. These amino acids are defcient in individuals with malnutrition; therefore, accumulation of cyanogens result in chronic pancre- atitis. Increased secretion of a putative peptide termed as pancreatic stone protein has also been suggested for the development of pancreatic calcifcation. Microvascular complications are common; however, macrovascular complica- tions are rare. This dichotomy is possibly due to lack of hypertension and ath- erogenic lipid profle. Despite severe hyperglycemia, ketosis is less common because of the presence of residual β-cell function, loss of α-cell function (decreased glucagon), reduced availability of non-esterifed fatty acids due to lack of subcutaneous fat, and carnitine defciency associated with malnutrition.

Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease order minocycline online now. Assessment of operability of congenital cardiac shunts with increased pulmonary vascular resistance generic minocycline 50mg overnight delivery. Clinical applications of inhaled nitric oxide in children with pulmonary hypertension purchase 50 mg minocycline with mastercard. Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass order minocycline 50 mg otc. Pulmonary vascular bed in children with complete atrioventricular septal defect: relation between structural and hemodynamic abnormalities. Pulmonary arterial hypertension and congenital heart disease: targeted therapies and operability. Pulmonary vascular disease with congenital heart lesions: pathologic features and causes. Measurement, interpretation and use of haemodynamic parameters in pulmonary hypertension associated with congenital cardiac disease. Late results after correction of ventricular septal defect with severe pulmonary hypertension. Measured versus estimated oxygen consumption in ventilated patients with congenital heart disease: the validity of predictive equations. Validity of the LaFarge equation for estimation of oxygen consumption in ventilated children with congenital heart disease younger than 3 years–a revisit. The pulmonary vascular response to oxygen and its influence on operative results in children with ventricular septal defect. Assessment and follow-up of patients with ventricular septal defect and elevated pulmonary vascular resistance. Late results (30 to 35 years) after operative closure of isolated ventricular septal defect from 1954 to 1960. Inhaled nitric oxide to test the vasodilator capacity of the pulmonary vascular bed in children with long-standing pulmonary hypertension and congenital heart disease. Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing. Long-term outcome of patients operated for large ventricular septal defects with increased pulmonary vascular resistance. Repair of congenital heart disease with associated pulmonary hypertension in children: what are the minimal investigative procedures? Assessment of operability of patients with pulmonary arterial hypertension associated with congenital heart disease. Correlations of lung morphology, pulmonary vascular resistance, and outcome in children with congenital heart disease. Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening. Circulating endothelial cells: a new candidate biomarker of irreversible pulmonary hypertension secondary to congenital heart disease. Evaluating operability in adults with congenital heart disease and the role of pretreatment with targeted pulmonary arterial hypertension therapy. Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups. Eisenmenger syndrome a clinical perspective in a new therapeutic era of pulmonary arterial hypertension. Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome. Determinants of survival and length of survival in adults with Eisenmenger syndrome. Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart. B-type natriuretic peptide concentrations in contemporary Eisenmenger syndrome patients: predictive value and response to disease targeting therapy. Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome. Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Improved survival among patients with Eisenmenger syndrome receiving advanced therapy for pulmonary arterial hypertension. Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: does the beneficial effect persist? Pulmonary arterial hypertension in adults with congenital heart disease: distinct differences from other causes of pulmonary arterial hypertension and management implications. What limits cardiac performance during exercise in normal subjects and in healthy Fontan patients? Clinical outcomes and improved survival in patients with protein-losing enteropathy after the Fontan operation. Pulmonary vasodilation therapy with sildenafil citrate in a patient with plastic bronchitis after the Fontan procedure for hypoplastic left heart syndrome. Performance of cavopulmonary palliation at elevated altitude: midterm outcomes and risk factors for failure. Nitric oxide synthase expression by pulmonary arteries: a predictive marker of Fontan procedure outcome? Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure. Moderate altitude is not associated with adverse postoperative outcomes for patients undergoing bidirectional cavopulmonary anastomosis and Fontan operation: a comparative study among Denver, Edmonton, and Toronto. Living at altitude adversely affects survival among patients with a Fontan procedure. Moving on up: is it safe for patients to relocate to higher altitude following the fontan procedure? Predictors of sildenafil effects on exercise capacity in adolescents and adults with Fontan circulation. Midterm results of sildenafil therapy in two complex patients with elevated pulmonary artery pressure after cavopulmonary connection. Sildenafil and ventriculo-arterial coupling in Fontan- palliated patients: a noninvasive echocardiographic assessment. Successful management of plastic bronchitis in a child post Fontan: case report and literature review. Modulation of pulmonary vascular resistance as a target for therapeutic interventions in Fontan patients: focus on phosphodiesterase inhibitors. Impact of sildenafil on echocardiographic indices of myocardial performance after the Fontan operation. Sildenafil increases systemic saturation and reduces pulmonary artery pressure in patients with failing fontan physiology. Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients. Bosentan induces clinical, exercise and hemodynamic improvement in a pre-transplant patient with plastic bronchitis after Fontan operation. Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups. Screen for portopulmonary hypertension, especially in liver transplant candidates. The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat. Systemic plasma vascular endothelial growth factor levels as a marker for increased angiogenesis during the single ventricle surgical pathway. The role of oxidative stress in the development of pulmonary arteriovenous malformations after cavopulmonary anastomosis.

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