Keywords pulmonary artery banding - berlin heart - LVAD - left ventricular assist device -
weaning - myocarditis in children
Introduction
Cardiomyopathy is the leading indication for transplantation in children. Ten percent
of cases of dilated cardiomyopathy are caused by acute myocarditis.[1 ] Myocarditis is an inflammation of cardiac myocytes, causing myocardial injury.[2 ] The leading cause in children is infectious etiology, today most commonly parvovirus
B 19.[3 ] Acute myocarditis can lead to borderline systolic function and arrhythmias. The
progress into inflammatory cardiomyopathy with massive dilation of the left ventricle
is possible where spontaneous recovery is not as likely anymore.[4 ]
Phosphodiesterase inhibitors like milrinone, levosimendan (Ca-sensitizers), or even
catecholamines are commonly used as first-line therapy for ionotropy.[5 ] In addition oral heart failure therapy should be initiated once the patient is beyond
the acute stage but still continues to have a compromised systolic function.[2 ]
According to Schranz et al., there is a newer and controversially discussed approach
to the treatment of severe (left-sided) heart failure, some forms of cardiomyopathy,
and myocarditis which includes the modification of the right ventricular afterload
by pulmonary banding, inducing right ventricular hypertrophy and thereby improving
the contra-lateral ventricular function by so far unknown interventricular cross-talk
mechanisms.[6 ]
[7 ]
To assess ventricular failure, today brain natriuretic peptide (BNP) values are determined
regularly. Due to the age dynamics; however, the absolute values have not been reliable.[8 ] Palm et al reinvented the BNP value by introducing the zlog value of NT-proBNP.
zlog-proBNP (the zlog-is a value as basis for the standardization of laboratory results.
It describes the standardized range [−1.96 to +1.96] of the normal reference values
according to age, size, weight etc.) levels can be interpreted as low (≤1.0), normal
(>1.0 and ≤1.96), intermediate (>1.96 and ≤ 3.0), and high (>3.0).[9 ]
[10 ] Cardiac recovery may be assessed by normalization of BNP levels even during assist
device therapy in adults.[9 ]
We present a case in which pulmonary artery (PA) banding was used to enable and support
left ventricular recovery after failed recovery by LVAD (left ventricular assist device)
implantation alone. The timely course of recovery could be monitored by BNP zlog values
in addition to echocardiography.
Case
The patient was born at term with no prior known diseases. There is no positive family
history. She presented at our department with progressive cardiomyopathy, diagnosed
in her home country (Romania) and already treated with oral anti-congestive heart
failure therapy. (i.e., ACE inhibitors [angiotensin converting enzyme], β blockers,
and antidiuretics).
The first cardiac catheter was performed 2 months after the first presentation (at
the age of 1 year) and the biopsy revealed a parvovirus B19-associated myocarditis.
The progression of the disease led to severe cardiac decompensation within the next
6 months. The BNP increased accordingly. ([Figs. 1 ] and [2 ])
Fig. 1 Absolute BNP values; arrow shows the time of PA banding; the graph shows the timeline
from the first presentation until the week after the LVAD explantation. It shows elevated
BNP values in the beginning and during the time of PA banding with a drastic drop
after surgery. (1) First BNP after presentation; (2) 6 days after LVAD implementation;
(3) 3 months after LVAD implementation; (4) PA Banding; (5) 1 day after debanding;
(6) 2 days after debanding; (7) 4 days after partial debanding; (8) 10 days after
partial debanding; (9) 3 months after partial debanding; (10) 1 day after LVAD explantation;
and (11) 1 week after LVAD explantation.
Fig. 2 zlog values; the graph shows the timeline from the first presentation until the week
after the LVAD explantation. It shows elevated zlog BNP values in the beginning and
during the time of PA banding with a drastic drop after surgery. (1) First BNP after
presentation; (2) 6 days after LVAD implementation; (3) 3 months after LVAD implementation;
(4) PA Banding; (5) 1 day after debanding; (6) 2 days after debanding; (7) 4 days
after partial debanding; (8) 10 days after partial debanding; (9) 3 months after partial
debanding; (10) 1 day after LVAD explantation; and (11) 1 week after LVAD explantation.
Therapy was first increased by milrinone and levosimendan, but when the systolic function
continued to worsen and multi-organ impairment developed, an LVAD—extracorporal assist
device was implanted at the age of 1.5 years. (i.e., Berlin heart excor, LVAD 25 ml
ventricle). Subsequently and after initial stabilization, several attempts to wean
the young patient off the Berlin Heart failed due to left ventricular enlargement
and clinical deterioration. In the meantime, Interferon therapy was implemented for
6 months while on the LVAD, however with no significant benefit.
As the right ventricle continuously showed excellent function, pulmonary banding was
deemed a potential beneficial therapy. Therefore, before deciding to list her for
transplantation and after extensive discussion with the parents, a pulmonary banding
was performed 10 months after the LVAD implementation.
The initial banding was placed with a 4 mm residual lumen (∼30% diameter) in the middle
of the pulmonary artery. It was fixated when the right ventricle had a systolic pressure
of 60 mmHg and the left ventricle 85 mmHg. The echocardiography showed good cardiac
function and a systolic gradient of 46 mm Hg over the PA banding.
Within 48 hours the patient however developed a ventricular tachycardia and had to
be resuscitated. The right heart then showed significant dilatation on echocardiography
in the performed echocardiography with poor contraction and the gradient over the
pulmonary artery banding (PAB) was 20 mmHg only. Apparently, the initial banding was
too tight and the indication for partial debanding to relieve the right ventricle
was given. The PA banding was released operatively to an 8 mm lumen (∼50% diameter)
and the RV (right ventricle) function recovered rapidly. Echocardiographic follow-up
showed a maximal gradient of approximately 25 mm Hg. Subsequently, the cardiac function
improved further and 6 days after surgery the catecholamine support could be terminated.
Over the next weeks, the left ventricular function improved constantly, the LVIDD
(left ventricular internal dimension in diastole) slowly recovered and 3 months later
the LVAD could be weaned. ([Fig. 3 ])
Fig. 3 LVIDD in mm; arrow shows the time of PA banding: (1) first presentation; (2) first
heart catheter; (3) start decompensation; (4) 4 days before LVAD implantation; (5)
1 day after LVAD implantation, (6) 2.5 months after LVAD implantation, (7) 7 months
after LVAD implantation, (8) 3 days after partial debanding, (9) 2 weeks after partial
debanding, (10) 3 months after partial debanding, (11) 4 days LVAD explantation, (12)
1 month after LVAD explantation, (13) 6 months after LVAD explantation, (14) 1 year
after LVAD explantation, (15) 2 years after LVAD explantation, (16) 3 years after
LVAD explantation, and (17) 3.5 years after LVAD explantation.
In addition, the BNP decreased after the partial debanding ([Figs. 1 ] and [2 ]) After LVAD explanation, the heart failure treatment could be reduced to β blockers
and ace inhibitors while the diuretic treatment was terminated. During the follow-up
care now for the past 4 years, the function of the left ventricle is normalized, the
patient showed no clinical heart failure signs and everyday life can be managed well.
Discussion
It is well known that children with myocarditis have a better outcome than those with
an (early) onset of dilative cardiomyopathy.[4 ] Twenty-three percent of patients with severe myocarditis in the United States need
mechanical circulatory support (MCS) via extracorporeal membrane oxygenation (ECMO)
or ventricular assist device (VAD) in the early phase of the disease. If chronic heart
failure precedes the acute inflammatory phase, transplantation is often necessary.[11 ]
The waiting times for an organ in countries such as the United States are significantly
shorter (median time of 32 days) as compared with Germany where a mean waiting time
is more than 1 year.[4 ]
[12 ] In Europe in general and especially in Germany there is a shortage of organs due
to regulatory effects which makes the MCS support more relevant for many children
with acute and severe heart failure.[13 ]
[14 ] Longer waiting periods on MCS inadvertently offer the possibility that some of these
patients can be weaned off the MCS with satisfying results.[15 ]
Due to longer waiting times on the transplant list, it may be relevant and necessary
to evaluate other treatment options, which is the reason why PAB comes into play.
As described in the work by Schranz et al., heart transplantation (Htx) seems like
the only lifesaving option for children with dilated cardiomyopathy.[7 ] New treatment options can be achieved by paradigm-shifting traditional heart failure
therapies like modifying right ventricular afterload which then leads to a secondary
RV hypertrophy and a postulated ventricular crosstalk and subsequent improvement in
the left ventricular function. This can be achieved by PAB in young children.
In an initial case report by Schranz et al., an approximately 2-month-old patient
with idiopathic dilated cardiomyopathy showed significant improvements after a PAB
was performed. The left ventricular diameter decreased from 40 to 31 mm and the BNP
levels decreased to normal values 6 weeks after the performance.[16 ]
In a subsequent retrospective single-center observational study by Schranz et al.,
12 children were observed after PAB was placed in patients with severe cardiomyopathy
which showed improvement of the left ventricular function by ventricular crosstalk.[17 ]
As indicated earlier, one of the theories behind this treatment strategy is due to
a postulated inter-ventricular crosstalk the left ventricle can be improved, which
makes the function of the right ventricle crucial in this method.[7 ]
Ventricular arrhythmias are one of the possible complications that can appear after
PA banding.[18 ]
In general, MCS support reduces the mortality on the waiting list for transplants.
However, according to a report by Euromacs, only 51% of children were transplanted
after being 24 months on MCS support. Due to this limitation further treatment options
remain important.[19 ] In the analysis of pedimacs, 55% of children developed acute right-sided heart failure
after LVAD implantation.[20 ] Therefore, an excellent function of the RV is crucial when considering PA banding
for LV (left ventricle) failure. Acute right ventricular failure is one of the main
complications of LVAD implantation which would disqualify PAB as a treatment option.
Regular follow-ups on the right ventricular function are therefore necessary and usually
RV function improves over time.[21 ]
There are animal studies that support this approach; 4-month-old sheep with doxorubicin-induced
cardiomyopathy showed significant improvement in the LV functional diameters 3 months
after PA banding.[22 ] In one of the first human case series the improvement was observed after 6 months
and in neonates even after 2 to 6 weeks.[6 ]
[16 ]
So far there is little evidence or even research regarding the possibility of PA banding
for children on MCS support. Our case also shows the applicability also for this group
of patients. However, a close monitoring of the right ventricle is necessary. This
can be achieved by additional measurement of BNP levels. In our case, the zlog values
stayed over 3 until banding was performed, which then caused a drop below 3 which
correlates with a normal to intermediate risk. This classifies the explanation as
a success.
Conclusion
This case may illustrate that in selected patients PA banding with subsequent training
of the right ventricle may also be applied in patients on left ventricular assist
devices for severe LV heart failure enabling weaning off mechanical support over time.
