Pancreatic exocrine functioning after cardiac resynchronization therapy

Heart failure (HF) is a clinical syndrome resulting from any functional or
structural heart disorder, impairing ventricular filling or ejection of blood
to the systemic circulation to meet the systemic needs (1,2). Ultimately, this
leads to impairment and/or failure of target organs of which the kidney (3,4),
liver (5,6), brain (7,8) and intestines (6,9,10) have been well studied. In
contrast, the effects of the hemodynamic derangements of HF on the pancreas
have received little attention. This is surprising, given the pancreas is
particularly susceptible to ischemic injury (11-14) and congestion (15,16).
Although conclusive data are lacking, HF is thought to result in exocrine
pancreatic insufficiency (17), potentially leading to further deterioration
through maldigestion and malnutrition.

Cardiac resynchronization therapy (CRT) is an effective method to treat HF with
reduced ejection fraction (HFrEF) accompanied by ventricular dysschrony (18).
CRT improves cardiac efficiency through better temporal coordination of left
ventricular activation and contraction, resulting in increased cardiac output
and stroke work and reduced mitral regurgitation and cardiac filling pressures
(19-22). CRT exerts systemic hemodynamics leading to increased survival, lower
HF-related hospitalization and improved end-organ functioning (23,24).
Unfortunately, approximately one-third of recipients fail to respond to CRT for
a variety of reasons (25-27).

Non-response to CRT is reflected by little hemodynamic improvement and
potentially further deteriorating clinical status and end-organ function.
Ideally, CRT mitigates end-organ dysfunction through both improved perfusion
and reduced venous pressures (22,28,29). This has previously been demonstrated
through improved renal function after CRT, which has shown to be indicative of
response to therapy (22,30,31). Other organ systems also seem to respond to
therapy (32,33), yet are underreported in current scientific literature.

The rapid hemodynamic changes induced by CRT make it an interesting
intervention to study the effects of HF on the pancreas. Given the proposed
susceptibility of the (exocrine) pancreas to hemodynamic variations (11-16), it
is hypothesized favourable response to CRT is reflected by improved exocrine
pancreatic function. The aim of this study is to investigate the effect of CRT
on pancreatic exocrine functioning and to compare CRT responders and
non-responders.

Primary Objective:
1. To investigate the effect of CRT on markers of pancreatic exocrine
functioning

Secondary Objectives:
1. To compare changes in markers of pancreatic exocrine function between CRT
responders and non-responders
2. To compare the prevalence of exocrine pancreatic insufficiency between CRT
responders and non-responders
3. To investigate the association between exocrine pancreatic insufficiency at
baseline and response to CRT
4. To investigate the association between the degree of response to CRT and
changes in markers of pancreatic exocrine functioning

This is a single center, prospective observational study performed at the
University Medical Center Groningen (UMCG). A total of 60 patients referred to
our center for transvenous CRT implantation will be recruited.
The standard CRT protocol in our center consists of blood sampling,
electrocardiography, and radiographs at baseline and evaluation of response at
6 months after implantation.

Participants are burdened with non-invasive faecal sampling testing at baseline
and 6-months after CRT implantation. The present study may render important
insights into the effects of HF on the pancreas. Additionally, this study may
provide insight into the utility of pancreatic testing to identify response to
CRT.