Heart failure: clinical features and diagnosis

What Is Tetralogy Of Fallot?

Tetralogy of Fallot (TOF) is a birth defect of the heart in which four conditions are happening. One, there is a hole between the heart's pumping chambers, or the ventricles. This is called a ventricular septal defect. Two, there is some obstruction or blockage of the pulmonary valve and the pulmonary artery, which connects the heart to the lungs. This is called pulmonary stenosis. Three, the aortic valve is larger than usual, and opens from both of the heart's ventricles instead of the left ventricle only. Four, the muscle surrounding the lower right ventricle thickens more than usual. This is called ventricular hypertrophy.

In someone without TOF, the right side of the heart pumps oxygen-poor blood to the lungs, where the lungs absorb oxygen and remove carbon dioxide. This creates oxygen-rich blood that can be sent to the left side of the heart, which sends it to arteries and the rest of the body.

In TOF, blood moves across the hole in the ventricles. The blood can then move through the aorta, sending oxygen-poor blood through the body.

The most common symptom for people with TOF is that they often turn blue, which is called cyanosis. The areas of the body most likely to turn blue are the fingers, toes, and lips. This is such a prominent symptom that tetralogy of Fallot was referred to as Blue Baby Syndrome many years ago. Some parts of the body may not get as much oxygen as they should. This can result in shortness of breath.  For some people with TOF, symptoms do not occur right after birth. In some cases, cyanosis can occur months after the baby is born. Research suggests the severity of cyanosis depends on how obstructed the pulmonary artery is. Other symptoms can include clubbing of the fingers, difficulty feeding, inability to gain weight, passing out, poor development, and squatting during episodes of shortness of breath. Squatting can lead to an increase in blood flow to the lungs, allowing the body to get more oxygen. People with TOF can live with no symptoms, but some may have problems that occur over and over. This can include a leaky heart valve, an obstruction (blockage of blood leaving the right ventricle), and heart rhythm problems. The cause of TOF in most children is unknown. It is the most common heart defect in children that is present at birth, and is more commonly seen in children with Down syndrome and DiGeorge syndrome. DiGeorge syndrome is a condition where a piece of a specific chromosome (chromosome 22) is deleted. This condition causes heart defects, low calcium levels, and poor immune function. Some heart defects may be related to a person's genes or chromosomes, while others could be related to the environment. Factors which may increase risk of TOF include excessive alcohol consumption in the birthing parent, untreated diabetes of the birthing parent, a person who gives birth over the age of 40, poor nutrition during pregnancy, and Rubella or other viral illnesses during pregnancy. Diagnosis of TOF can occur either during pregnancy at a prenatal visit or right after a baby is born. During Pregnancy Tetralogy of Fallot may be diagnosed during a routine prenatal ultrasound (a tool used to view the developing embryo or fetus in utero). If the health care provider suspects TOF from the images of the ultrasound, they may order an echocardiogram to confirm the results from the ultrasound. The echocardiogram will help the healthcare provider examine blood flow and the heart's structure. After Birth Tetralogy of Fallot can be diagnosed after the baby is born if no tests are done during pregnancy. This is usually done if the baby turns blue when crying or feeding. This is called a "tet spell." The healthcare provider may also suspect TOF during a physical exam if they notice the skin has a bluish color or if they hear a heart murmur. Tetralogy of Fallot in Adults Most people are diagnosed with TOF as an infant or young child. Tetralogy of Fallot that is left untreated can be seen in adults, as they may experience certain areas of the body turning blue. Treatment options can look similar for children and adults. In TOF, the goal for treatment is to minimize symptoms and live as normal a life as possible. The most important part about living with a heart defect is to see a cardiologist (a medical doctor who specializes in the heart) regularly and seek treatment options as necessary.  Treatment options for TOF include two types of surgery: a shunt operation or a complete repair.  The shunt operation provides temporary improvement for the problem. A shunt is sewn between the aorta or a body artery and the pulmonary artery to aid in more blood flow to the lungs. The shunt is oftentimes done first until a complete repair of the heart can be done, in which case the shunt will be removed. In a complete repair, the defect in the ventricles is closed with a patch. This should relieve the obstruction of blood flow going to the lungs. Sometimes a tube with a valve in it is surgically placed between the right ventricle and the pulmonary artery, called a Rastelli repair. In some cases, patients may have both of these surgeries in their lifetime. Because there is no proven research explaining what causes TOF, there is no known way to prevent the condition. Some risk factors for TOF are related to the birthing parent's dietary habits. It is important to see a healthcare provider during pregnancy to discuss any potential risk factors. For those who do have heart surgery, physical activity exercise should be limited if shortness of breath is a recurring issue. Check with a cardiologist about physical limitations and recommendations for strenuous activities. Children diagnosed with TOF are at higher risk for endocarditis (inflammation of the lining around the heart's chamber and valves). Some children may also need to take antibiotics before certain dental procedures. This can help to prevent endocarditis. Surgery to open up the pulmonary valve can lead to complications, including a leaky pulmonary valve. Your healthcare provider may suggest another surgery to resolve this problem. Obstructed pathways can also be a problem as the person with TOF grows. Another surgery to replace the pulmonary valve may be needed later if these conditions occur. In addition to these conditions, people with TOF may experience weakened function of the right-side of the heart or an abnormal heart rhythm. Pregnant people who have had a repair for TOF should be monitored by a cardiologist for treatment options in case there are complications during pregnancy or while giving birth. Tetralogy of Fallot is rare, but it is also the most common type of heart disease at birth. If you or your child have been diagnosed with TOF you will need to consult with your doctor following surgical repair for guidelines. Even if surgical repair of the heart goes well, regular follow up with a cardiologist is recommended. The cardiologist should be someone who specializes in congenital heart defects. Even after your child becomes an adult, they will still need to follow up with a cardiologist regularly. In addition to regular follow up with a cardiologist, you may need medications and more surgeries if any complications from TOF occur.

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Melody Valve Yields Good Long-term Results, Especially With Pre-Stenting

Longer-term clinical and hemodynamic outcomes are generally positive following transcatheter pulmonary valve replacement with the Melody valve, according to a study published online May 5, 2015, ahead of print in Circulation. Endocarditis remains a concern up to 7 years after the procedure, however.

John P. Cheatham, MD, of Nationwide Children's Hospital (Columbus, OH), and colleagues looked at data from the US investigational device exemption trial for the Melody device (Medtronic), which enrolled 171 pediatric and adult patients (median age 19 years) with RV outflow tract (RVOT) conduit obstruction and/or regurgitation. The current analysis included the 148 patients who were discharged with a Melody valve in place.

As seen in prior studies, the procedure substantially reduced pulmonary regurgitation. On the discharge echocardiogram, regurgitation was absent or trivial in 140 patients and mild in 5 (the valve was not visualized in the remaining 3 patients). There was also a drop in the mean Doppler RVOT gradient from 33 to 17 mm Hg (P < .001). Even so, at discharge, the gradient was > 20 mm Hg in 33% of patients and > 25 mm Hg in 12%.

During a median follow-up of 4.5 years (range, 0.4-7 years), 4 patients died—1 from multisystem failure resulting from endocarditis/sepsis and 3 from causes not deemed related to the Melody valve (1 from respiratory and 2 from unknown causes). Estimated survival at 5 years was 98%.

Overall, 32 patients underwent RVOT reintervention, mostly for obstruction (27 patients, including 22 with stent fracture). Another 3 patients underwent reintervention for endocarditis and 2 for RV dysfunction. Eleven patients had the device explanted during follow-up.

At 5 years, 76% of patients remained free from reintervention and 92% were free from explant. Factors associated with valve reintervention included use of a homograft conduit and having a conduit angiographic:nominal diameter ratio < .65, a discharge RVOT gradient > 25 mm Hg, and preimplant moderate-to-severe regurgitation. Use of pre-stenting was tied to a lower risk of reintervention (HR 0.29; 95% CI 0.13-0.67).

During follow-up, Melody valve stent fracture occurred in 50 patients, with type II fracture—defined as a compromise of stent integrity—in 25. Freedom from any stent fracture and type II fracture at 5 years was 61% and 83%, respectively. The risk of reintervention after a diagnosis of stent fracture was greater among patients with a higher discharge RVOT gradient (HR 1.07 per mm Hg; 95% CI 1.02-1.13) and an angiographic:nominal conduit diameter ratio < .65 (HR 4.2; 95% CI 1.4-12.2).

Among the 113 patients who survived to the end of follow-up without needing reintervention, RVOT gradient had not changed from early after the procedure. Only 1 patient had more than mild pulmonary regurgitation, and nearly all patients were in NYHA class I or II.

The most noteworthy adverse event during follow-up was definite/presumed endocarditis or bloodstream infection, which occurred in 14 patients, 5 of whom underwent reintervention within 3 months of diagnosis.

Infection and endocarditis are therefore "clearly a high-priority issue for ongoing investigation and will continue to be a focal point in analyses of this technology," the authors write.

Changes in Practice, Outcomes Over Time

The performance of Melody valve implantation evolved during the conduct of the trial, which enrolled patients from January 2007 through January 2010. For example, conduit pre-stenting was not allowed during the first 35 implants. Thus, placement of a new pre-stent occurred in only 10% of the first 50 patients, with the percentage increasing to 54% of the next 50 and 42% of the final 50. Overall, pre-stenting was used in 36% of patients.

Other changes included an increase in the proportion of patients who underwent the procedure with the largest 22-mm delivery system, a decrease in use of the smallest 18-mm system, and a decline in postimplant dilation of the Melody valve.

"These differences corresponded to less complete relief of RVOT obstruction and shorter freedom from [stent fracture] and reintervention in the first 50 patients than those enrolled later," Dr. Cheatham and colleagues write.

"Because this series represents the first prospective multicenter trial, and the first experience with [transcatheter pulmonary valve replacement] in the [United States], the results in the earliest patients… reflect a naive experience," they continue. "Thus, although the data provide important insights, they are not representative of contemporary best practices, which include maximal relief of RVOT obstruction and, in most cases, implantation of one or more conduit pre-stents."

Although the study will "serve as a landmark" because of its long follow-up, they say, "the freedom-from-event analyses of this cohort almost certainly overestimate the risk of [stent fracture], reintervention, and explant relative to contemporary practice."

'Promising' Results

Editorialist Christopher J. Petit, MD, of Children's Healthcare of Atlanta (Atlanta, GA), writes, "In contrast to reports of surgically implanted pulmonary valves, this study indicates that the Melody valve remains nonstenotic and nonregurgitant up to 7 years after implantation.

"The ramifications of such promising midterm results are important," he says. The study "allows the clinician to more confidently counsel families when considering [transcatheter pulmonary valve replacement] and likewise gives our surgical colleagues good reason to implant conduits and valve prostheses compatible with future Melody utilization."

Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), told TCTMD in an email that "the most exciting part of this study is the lack of valve stenosis and insufficiency late after implantation.

"With surgically implanted valves in children, there is a very high rate of failure over the first several years, usually in the form of valvular insufficiency," he continued. "With the Melody, there is almost no rate of valve regurgitation outside of the devices that fractured early in the experience (prior to pre-stent implantation)."

Dr. Sommer explained that the use of pre-stenting has solved the problem of Melody valve stent fracture.

"If there is no recoil of the stent after deflation of the balloon, the Melody is implanted inside the stent," he said. "If there is conduit recoil, a second bare-metal stent is placed inside the first, further strengthening its resistance to external compression. This can be repeated several times until a sturdy platform is achieved for the Melody, one which will be free of external compressive forces."

Dearth of Pediatric Options

In his editorial, Dr. Petit highlights the disparity between adult and congenital valve technology.

"It is worthwhile, yet sobering, to compare the experience of a child with tetralogy of Fallot to that of an adult with acquired aortic valve disease," he writes. "In the United States, a child with pulmonary valve failure might be fortunate to be among the subset of patients with suitable anatomy for the only FDA-approved percutaneous valve option [Melody]. Even so, that child would face a certain future of regular valve replacements. On the other hand, an adult in 2015 with acquired aortic stenosis may undergo implantation of 1 of 5 [TAVR] devices in the United States, or 1 of 7 devices in Canada or Europe."

Dr. Petit questions how advancements in adult technology will eventually benefit patients with congenital heart disease, noting that despite the existence of the FDA's Humanitarian Device Exemption pathway, which is meant to "incentivize industry to manufacture devices for areas of unmet clinical need," economic obstacles remain to developing pediatric devices.

"Thus, in 2015, the congenital heart disease community continues to lag behind the adult cardiac world, where advancements and modifications can be more quickly studied and implemented," he says. "The current study demonstrates the value of transcatheter valve implantation for treatment of congenital heart disease. One hopes that the Melody valve, despite its incredible success and durability, becomes the first of many transcatheter options for children with valve failure."

Sources:1. Cheatham JP, Hellenbrand WE, Zahn EM, et al. Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replacement in the US Melody valve investigational device exemption trial. Circulation. 2015;Epub ahead of print.2. Petit CJ. Pediatric transcatheter valve replacement: guests at our own table [editorial]? Circulation. 2015;Epub ahead of print.

Potentially Fatal Complication Found In Heart Valve Put In Children

(Updated)

Pediatric cardiac surgeons at Boston Children's Hospital are warning the medical community about a potentially fatal problem in children and young adults who received a bioprosthetic valve manufactured by Sorin. The surgeons initially became concerned when a young asymptomatic patient died suddenly after her valve underwent rapid calcification, only 7 months after a routine followup echocardiogram found no signs of blockage.

"Congenital aortic valve diseases are one of the more common heart defects that we see," said Pedro J. Del Nido, the chair of cardiac surgery at BCH. Surgeons prefer whenever possible to repair the native valve in the hope that by the time it needs replacement the children will be old enough to receive an adult valve." Valve replacement is never ideal. Mechanical valves are highly durable but require lifelong anticoagulation. Bioprosthetic valves, which are made from animal tissue, don't require anticoagulation, but are less durable and eventually need to be replaced. When a repaired valve deteriorates, or the child is not a suitable candidate for repair, adult valves may be implanted. BCH performs about 60-80 aortic valve surgeries each year, said del Nido.

In recent years surgeons at BCH and elsewhere started using the Sorin Mitroflow valve, which is made from bovine tissue, in the aortic position. (In children the valve has primarily been used to replace the pulmonary valve. No excess problems have been associated with this usage.) Following the death last year of the patient, who received the Mitroflow in 2011, doctors at BCH began an intense surveillance of all 18 patients at their institution who had received the Mitroflow valve in the aortic position. They found 4 additional cases of rapid calcification (three patients had their valves replaced with a mechanical valve; the other is being watched closely).

"The rapid failures that we're reporting have only been reported with the Mitroflow," said del Nido. "We expect all bioprosthetic valves to fail eventually. The difference now is the speed of the deterioration, in two to three years instead of the 6 years that we would expect." Typically, he said, patients are followed on a yearly basis. "But the speed of deterioration is so rapid that you won't catch this problem early on." BCH is now recommending that children with the Mitroflow valve be followed every 4 to 6 months so they can be caught before a problem occurs.

The American Society of Echocardiography forwarded a letter to its members from del Nido and James Lock, the chair of the cardiology department at BCH. The BCH doctors have also notified the FDA and the manufacturer of Mitroflow, the Sorin Group.

John Osborne, a cardiologist in Texas, first notified me about this news and provided the following perspective:

This is a pediatric/young adult population with congenital and genetic forms of valve disease that had aortic valve replacement with this particular bioprothetic valve. While calcification and resultant prosthetic valve dysfunction-- especially bioprosthetic valve stenosis-- is a known complication of bioprosthetic valves, particularly in the young, the time course and hyperacute onset of this complication is what is so unusual. This process of degeneration and resultant dysfunction of bioprosthetic valves is usually fairly slow occurring over years, or at most months, and is easily identified by echocardiography so that the valve can be electively replaced prior to critical failure. In addition, these patients usually have symptoms to trigger an evaluation of the valve.

What the esteemed pediatric cardiothoracic and cardiology groups at Boston Children's Hospital describe is a highly unusual situation where the valves appear to be working normally, then suddenly (over weeks, apparently - the accompanying graph in the letter describes this well ) the valves become abruptly calcified and stenotic while the patients have NO symptoms to indicate prosthetic valve dysfunction. This scenario has resulted in at least one death. I have never heard of a similar problem of hyperacute calcification and failure in bioprosthetic valves which makes this biologically interesting and very concerning for the physicians and their patients with the Mitroflow valve in the aortic position.

Update-- Following the publication of the above story one of my readers sent the following tweet, containing links to studies suggesting that a similar pattern of early calcification may take place in some elderly patients who get the Mitroflow:

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