Meeting Reviews

Session I

Welcome/Program Overview/CCAS Board of Directors Inauguration

By Sana Ullah, MB, ChB, FRCA

What a difference a year makes! Last year we were in the Bahamas enjoying the beautiful weather and the company of our colleagues. This year we were in our living rooms, kitchens and bedrooms for the annual meeting. If there was one silver lining, it is that more people were able to “attend” including many more from overseas. Being able to separate the CCAS meeting from the annual SPA meeting also allowed for an extended program spread over two days. In my humble opinion, this is a good thing – a one-day meeting is not enough for the educational agenda.

The meeting was opened by the outgoing president, Dr. Wanda Miller-Hance, who thanked the previous Board of Directors and the organizers of this year’s program – Drs. Gregory Latham, James Spaeth, David Vener, Susan Nicholson, and Nina Guzzetta. She then passed the baton to the incoming President, Dr. Mark Twite, who introduced the new Board of Directors – Drs. Rania Abbasi, Laura Downey, Laura Diaz-Berenstain, David Faraoni, and Kelly Machovec – and the new Executive Committee – Drs. Luis Zabala (VP) and Viviane Nasr (Secretary-Treasurer). Dr. Susan Nicholson, the Program Chair, followed with opening comments before the sessions started.

Session I: Pediatric Cardiomyopathies

Moderators: Kelly Chilson, MD; Susan Nicholson, MD
Reviewer: Sana Ullah, MB ChB, FRCA

The first morning session on pediatric cardiomyopathies consisted of five pre-recorded lectures followed by a live panel discussion with online questions submitted by the audience.

Cardiomyopathy: The Importance of Phenotype
Dr. Shelley Miyamoto

The first talk entitled “Cardiomyopathy: The Importance of Phenotype” was presented by Dr. Shelley Miyamoto, a pediatric cardiologist and director of the Cardiomyopathy Program from Children’s Hospital Colorado. She gave an excellent broad overview of the important clinical features and clinical management of the five categories of pediatric cardiomyopathies, progressing from the least to the most common - namely, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARCV/D), left ventricular non-compaction (LVNC), restrictive cardiomyopathy, hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM).

ARVC/D is a relatively rare inherited cardiomyopathy of which the pathological hallmark is progressive fibrofatty infiltration and replacement of the right ventricular myocardium. Gene mutations in the cardiac desmosomes are implicated in the pathogenesis. Although the name implies only right ventricular involvement, growing evidence shows that the left ventricle can also be affected. It typically presents in older children or young adults as arrhythmias or features of heart failure. Cardiac MRI often shows the abnormal myocardium in advanced cases. The main clinical concerns are the risk of arrhythmias - including ventricular tachycardia, sudden death, and right heart failure. The mainstays of management include exercise restriction, antiarrhythmic medications, catheter ablation of arrhythmogenic foci, and implantable cardioverter defibrillator (ICD) placement in selected cases. Right ventricular failure may need treatment with beta-blockers, ACE-inhibitors, and diuretics.

Restrictive cardiomyopathy often presents as congestive heart failure resulting from severe diastolic dysfunction and left atrial hypertension. Echocardiography usually confirms the diagnosis with the appearance of marked bi-atrial enlargement and normal systolic function. Cardiac MRI is helpful to rule out constrictive pericarditis which may be surgically treatable. Serial cardiac catheterization may be needed to assess for progression of pulmonary hypertension. Treatment options are limited with medications to treat heart failure symptoms, ICD for arrhythmias, and ultimately, transplantation.

Prognosis is fairly abysmal with transplant-free survival of 48% at one year and 22% at five years. Perioperatively, care must be taken not to infuse intravenous fluids rapidly as this might cause a rapid rise in left atrial pressure leading to pulmonary edema. The same considerations apply to using pulmonary vasodilators, as this might lead to increased pulmonary venous return in the face of restrictive physiology.

LVNC is thought to result from the intrauterine arrest of the normal process of compaction of the myocardium, resulting in a “spongy” trabecular myocardium with deep recesses and a thin layer of normally compacted myocardium on the epicardial surface. Diagnosis is usually made by echocardiography and by MRI. The clinical features and management depend on the “sub-phenotype” which is determined by left ventricular (LV) function and the thickness of the compacted layer. Isolated LVNC has normal LV size and function with a normal thickness of the compacted layer. Most of these cases have a benign course but there is a risk of arrhythmias and intracardiac thrombus formation. There is no consensus on anticoagulation, but some authorities recommend low-dose aspirin. Other subtypes include dilated, hypertrophic, restrictive, and mixed. Management is based on the predominant physiology.

HCM, the second most common pediatric cardiomyopathy, results from the abnormal growth and arrangement of myocardial fibers, resulting in thickening of the ventricular walls. Clinical presentation is variable from an arrhythmia, syncope, or sudden death in an older child. It can also be part of a syndrome such as Noonan syndrome, inborn errors of metabolism, or neuromuscular disorders. Echocardiography usually confirms the diagnosis. HCM is also sub-categorized as “asymmetric” with thickening of the septum only, as seen in the familial type, or “symmetric” with global thickening of the LV as seen in the syndromic or metabolic conditions. Physiologically, it is characterized by restrictive physiology, diastolic dysfunction, and obstruction in the mid-cavity or the outflow tract of the left ventricle. Treatment is based on reducing the obstruction with beta-blockers or calcium channel blockers, avoiding volume depletion (important to minimize preoperative fasting), and avoiding afterload reduction. The major risk is sudden death, and these patients are often candidates for an ICD placement.

DCM is characterized by cardiac chamber enlargement and impaired systolic function of one or both ventricles. There are numerous causes, but most are idiopathic. Therefore, it is important to rule out treatable conditions such as congenital heart disease and arrhythmias. Over 80% of these patients actually present with acute decompensated heart failure with a 7% overall hospital mortality. One third of these children will die or require heart transplantation within a year of presentation. These patients have a very high perioperative risk of morbidity and mortality. However, it is more important to consider the symptoms and functional status rather than the numerical ejection fraction when assessing the perioperative risks.

Genetics and Cardiomyopathy
Dr. Juan Alejos

The next talk titled “Genetics and Cardiomyopathy” was given by Dr. Juan Alejos, Director of the pediatric heart transplant/heart failure program at UCLA Mattel Children’s Hospital. In contrast to adults, pediatric cardiomyopathies have a variable but strong genetic component; therefore, genetic testing and counselling should be an important part of the work-up of these patients. Cardiomyopathy in children has a wide and unique differential diagnosis which includes metabolic conditions and genetic syndromes.

Extracardiac abnormalities such as dysmorphic features, short stature, other congenital anomalies, and muscle diseases should prompt further evaluation of cardiomyopathy. This was laid out in the 2018 Heart Failure Society of America Guidelines on Genetic Evaluation of Cardiomyopathy which recommended that genetic testing for patients with cardiomyopathy should include the following: (1) family history of three generations, (2) genetic counselling of all patients with cardiomyopathy and their family members, and (3) clinical screening for cardiomyopathy in at-risk first-degree relatives. Dr. Alejos then described the main clinical features of the five pediatric cardiomyopathies and their associated multiple gene mutations. He pointed out that there can be variable genotypic and phenotypic heterogeneity with variable expression and gene penetrance which can affect the clinical course of the disease.

Identification of the genetic etiology can impact clinical management and make for more informed genetic counselling. There may be many “red flags” in the family history which may point to the presence of an inherited cardiomyopathy. These include cardiomyopathy or an enlarged heart, sudden cardiac death, sudden infant death syndrome, unexplained syncope, seizure disorder, pacemaker at a young age, muscle weakness/myopathy, drowning of an experienced swimmer, single vehicle car accident, “heart attack” at a young age, and multiple affected individuals in a family, particularly at a young age.

Treatment of Heart Failure in Children: Where’s the Evidence?
Dr. Shelley Miyamoto

Dr. Miyamoto returned with a talk titled “Treatment of Heart Failure in Children: Where’s the Evidence?”, which dealt with the medical treatment of heart failure in children and offered some fascinating insights into why there are important and significant differences in response to the same medications between children and adults. She outlined the challenges to drug development, which include the following: (1) the relative rarity in the incidence of pediatric heart failure versus adults; (2) often underpowered pediatric studies; (3) the multifactorial etiology of heart failure in children versus adults; (4) low market share and thus low motivation from industry; and (5) the assumption that children will respond to medical therapy in the same manner as adults.

Surprisingly, there is a lack of published guidelines for the management of pediatric heart failure since 2014. The 2014 guidelines did not contain any Level A recommendations which arise from multiple randomized trials. In fact, 70% of the recommendations were based on expert consensus rather than evidence from published studies. A study published in 2010 demonstrated that medical treatment was more advantageous versus no medical treatment; however, there was no survival benefit when comparing older medical therapy versus more recent types of medical therapy. This is in complete contrast to adults who have 94% transplant-free survival two years after the diagnosis of DCM versus 50% transplant-free survival in children after diagnosis of DCM.

The question then becomes, “Do children respond to adult-based medical therapy differently?” In all likelihood, the answer is “yes” for the following reasons: (1) children have not seen the same improvements in survival with advancement in medical therapy, (2) even though the clinical phenotype of pediatric heart failure is similar, there may be different adaptive responses, and (3) there is increasing evidence to suggest there are molecular differences in the failing pediatric myocardium which cause a different response to the same medications used in adults.

Dr. Miyamoto discussed two studies which support these assertions. The first study discussed was the “Carvedilol for Children and Adolescents with Heart Failure Trial”, a randomized trial published in 2007. The aim of the trial was to determine if the beneficial effects of carvedilol, a non-selective beta-blocker, seen in adults were replicated in children. Rather surprisingly, there was no difference between the treatment and placebo groups. In fact, about half of the patients in both the treatment and placebo groups actually improved over the course of the study.

Research from Dr. Miyamoto’s lab has demonstrated a difference between beta-1 and beta-2 receptor adaptation and down-regulation in response to carvedilol and metoprolol, a selective beta-blocker, in the cardiac tissue from children versus adults. She speculates that a selective beta-blocker may have a more beneficial clinical effect in children versus a non-selective beta-blocker. An additional example of the differential response to medical therapy in pediatric patients versus adults is illustrated by the use of milrinone in pediatric heart failure. Milrinone use in pediatric patients has significant benefit and is a long-term therapy for chronic heart failure. Conversely, the PROMISE trial published in 1991 demonstrated an increase in mortality with use of milrinone in adults.

The concluding remarks touched upon the following: 1) outcomes in pediatric patients with heart failure are worse than adults, 2) there is little evidence to support the current treatment modalities of pediatric heart failure, 3) the failing pediatric myocardium has different characteristics and, thus, responds differently to medical therapy as compared to the adult failing myocardium, and 4) treatment of pediatric heart failure should be tailored more specifically.

Surgical Interventions - For Whom and How?
Dr. Katsuhide Maeda

The next presentation was entitled “Surgical Interventions – For Whom and How?” and was presented by Dr. Katsuhide Maeda, Surgical Director of mechanical circulatory support at Children’s Hospital of Philadelphia. The presentation focused on the surgical options for children with heart failure but did not include orthotopic heart transplantation. These options are used mainly as a bridge to transplantation. This is an area of rapid growth with the increasingly common use of various types of mechanical circulatory support (MCS) beyond extracorporeal membrane oxygenation (ECMO).

Dr. Maeda began with a discussion of the novel idea of pulmonary artery banding (PAB) as a bridge to transplantation or potential recovery in patients with dilated cardiomyopathy. This was first reported in the literature in 2007 in a case report that detailed the use of PAB in a 2-month-old infant with DCM as a means to retrain the ventricle in preparation for future surgery. Surprisingly, it was noted that the ejection fraction improved from 13% to 66%, and the patient was removed from the transplant list.

Although the exact cause of the beneficial effect of the PAB is still under debate, some hypothesize that there may be a realignment of the ventricular septum and a reduction in mitral regurgitation. A subsequent study was published by the same group in 2013 detailing their single-center experience with the use of pulmonary arterial banding in 12 patients with DCM. There were significant improvements in left ventricular ejection fraction from 14% to 47% and decreased levels of brain natriuretic peptide. Eight patients were subsequently de-banded. Although there were no in-hospital deaths, two of the de-banded patients with LVNC died six months post pulmonary artery banding.

Unfortunately, the European success could not be replicated in a multi-center US study published in 2020. Out of 14 patients, only six had successful outcomes (recovery or transplant). Clearly, more work needs to be done to define the place of pulmonary artery banding as a viable strategy for heart failure.

The mainstays of MCS are ECMO and various types of ventricular assist devices (VADs). Until 2004, ECMO was the only MCS option available in end-stage pediatric heart failure. Since then, several alternative options have become available. This includes the Berlin Excor, which can be used in very small infants; paracorporeal continuous-flow devices such as the PediMag; and intra-corporeal continuous flow devices such as the HeartMate 3 and the Heartware HVAD, which are used in older children, adolescents and adults. As experience with all these devices accumulates, Dr. Maeda very succinctly summarized the take-home points:

ECMO, although a necessary option in many circumstances, especially with concomitant pulmonary failure, is the least favored MCS option as it is associated with a higher wait-list mortality and worse post-transplant outcomes. In a recent study from 2016, the use of ECMO was associated with a much worse 30-day survival after heart transplant when compared with post-VAD transplant (79% vs 96% survival). The main conclusion seems to be to avoid ECMO as a support strategy if at all possible and instead consider using a VAD at an earlier stage of the patient’s illness.

The use of VADs as a bridge to transplantation has steadily increased over the past 15 years from 12% in 2005 to 32% in 2019.

VADs are increasingly utilized in younger patients.

The use of the left VAD has steadily increased over the past 15 years and, interestingly, the use of biventricular VADs have decreased over the same time period. Other significant trends include the increased use of paracorporeal continuous flow devices, a marked decrease in the use of paracorporeal pulsatile devices (mainly Berlin Excor), and an increase in the use of intracorporeal continuous flow devices such as the Heartmate 2 and 3 and Heartware HVAD.

Another key finding has been the reduction in pre-transplant risk factors with the use of VADs, such as hepatic and renal dysfunction, ventilator dependence, and decreased functional status.

All of these beneficial effects have translated into much better post-transplant outcomes.

Anesthetic Considerations
Dr. Katherine Taylor

The final talk, “Anesthetic Considerations”, was given by Dr. Katherine Taylor, an anesthesiologist from the Hospital for Sick Kids in Toronto, Canada. This was a useful review of the main clinical considerations in the perioperative anesthetic management of the various cardiomyopathies.

These patients are at high risk for complications in the perioperative period. Dr. Taylor stressed that there is no ideal “recipe” for these patients and emphasized the “do what you do best approach” based on a clear and detailed understanding of the underlying pathophysiology of each particular type of cardiomyopathy. She illustrated these principles by using left ventricular (LV) pressure-volume (PV) loops to demonstrate maintenance of hemodynamic stability. In dilated cardiomyopathy the PV loop is shifted far to the right, emphasizing that these patients are very dependent on an adequate preload.

In addition, increases in systemic vascular resistance or further decreases in contractility are poorly tolerated due to the already reduced ejection fraction. Conversely, patients with HCM are benefited from a certain degree of negative inotropy and a higher systemic vascular resistance with a slower heart rate. Patients with restrictive cardiomyopathy have a relatively fixed stroke volume and thus do not tolerate extreme bradycardia or tachycardia. Additionally, pulmonary vasodilators may lead to an acute increase in pulmonary venous return and precipitate pulmonary edema. The management of LVNC will depend on the particular sub-phenotype. ARVC/D patients are at a high risk of arrhythmias and measures must be in place to prevent and treat these, such as placing defibrillator pads and avoiding excessive sympathetic stimulation.

The talk was concluded by a brief discussion of the management of the VAD patient presenting for surgery. The main considerations include providing an adequate preload to the device by maintaining volume status, maintaining RV function, and minimizing increases in pulmonary vascular resistance; as well as maintaining appropriate afterload, in particular by avoiding large increases in systemic vascular resistance.

These pre-recorded lectures were rounded off with a live Q&A session with all of the speakers. Some interesting questions asked during the discussion are listed here.

Should all patients with cardiomyopathy be screened for skeletal muscle disease as this may impact long-term outcomes? The answer depends on clinical suspicion, history and physical, family history, etc. Checking a CK was suggested as a first step followed by muscle biopsy if strong clinical suspicion.
Why is there an increase in the use of continuous-flow devices versus pulsatile devices? It was explained that this may be due to lower complication rates - particularly stroke, increased patient mobility, and ability to discharge out of the hospital. The MCS device options for patients under 15 kg are limited but the PumpKin trial of the Jarvik 2015 device may lead to better options for smaller children.
There were several questions regarding specific drug therapies for RV support and pulmonary hypertension as well as the ideal agent for blood pressure control after surgery. The answer was, unfortunately, there is very little evidence to show which are the best treatments and medications for these clinical conditions; many treatments are essentially institution dependent.