Autonomic Cardiovascular Control After Heart Transplantation

• Conditions: Heart Transplant Recipients

• Registration Number: NCT01759966
• Lead Sponsor: Oslo University Hospital

Brief Summary

The purpose of this prospective study is to investigate denervation (ie. surgical cutting of autonomic nerves) and re-innervation (ie. growth of autonomic nerves) in heart transplant recipients. More specifically, we focus on:

1. The physiological consequences of denervation, in particular its consequences for clinical symptoms, orthostatic tolerance (ie. the ability to stand upright) and exercise capacity. We hypothesize that denervation has negative consequences for all these factors.

2. The pathological consequences of denervation and reinnervation, in particular its association to acute rejection and coronary artery disease (cardiac allograft vasculopathy, CAV). We hypothesize that reinnervation protects against acute rejection and development of CAV

3. Donor and recipient factors associated with the reinnervation process. We hypothesize that characteristics of the surgical procedure (such as aorta cross-clamp time) as well as the rehabilitation process of the recipient (such as physical activity) impacts on the reinnervation process.

Detailed Description

Heart transplantation is annually offered to more than 3500 patients worldwide. In Norway, the number is approximately 30/year, and all transplants are carried out at one single hospital (Oslo University Hospital, Rikshospitalet).

Normally, the heart function is intimately controlled by the autonomic nervous system (ANS), but all nervous connections are lost during the surgical transplantation procedure, and the transplanted heart thus becomes denervated. In time, regrowth of nerves may cause partial reinnervation of the new heart.

Some evidence suggests that reinnervation improves exercise capacity and reduces episodes of acute rejections and the development of cardiac allograft vasculopathy. The purpose of this study is further to investigate the changes over time with respect to all parts of the autonomic nervous system (the sympathetic, parasympathetic and sensoric part), and the associated physiological and pathological consequences.

The study may provide knowledge which ultimately could help us improve health and quality of live for heart transplant recipients.

Study Timeline

• Study First Submitted: 2012-12-28
• Study First Submitted QC: 2012-12-28
• Study Start: 2013-01
• Study First Posted: 2013-01-03
• Primary Completion: 2016-03
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-10
• Last Update Posted: 2018-04-11
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Acute rejections	1 year	The frequency of acute rejections episodes and time to first rejection (combined time/event outcome), as assessed by analyses of heart biopsy specimens
Cardiac allograft vasculopathy	1 year	Indications of cardiac allograft vasculopathy (CAV), assessed by intravascular ultrasound (IVUS) during coronary catheterization.

Secondary Outcome Measures

Name	Time	Method
General immune activity	6 months, 1, 2 and 3 years	The blood levels of cytokines and other markers of immune function, as well as whole blood gene expression.
MetaIodoBenzylGuanidin-scan	1 and 3 years	The degree of sympathetic cardiac reinnervation as assessed by the scintigraphic method MetaIodoBenzylGuanidin-scan
Ambulant blood pressure recording	1, 2 and 3 years	24 hours ambulant blood pressure recordings
Cardiac catheterization	1, 2 and 3 years	Routine data from surveillance cardiac catheterization procedures, such as pressure recordings, angiograms and biopsy assessments
Acute rejections	2 and 3 years	Cf. above
Activity recordings	6 months, 1, 2 and 3 years	Number of steps/day during 7 consecutive days, assessed by an accelerometer
Clinical symptoms	6 months, 1, 2 and 3 years	Validated questionnaires assessing: symptoms of autonomic dysfunction, quality of life, pain, fatigue, anxiety, depression and sleep problems.
Cardiac allograft vasculopathy	3 years	Cf. above
Hormonal levels	6 months, 1, 2 and 3 years	The levels of catecholamines, cortisol and other hormones influenced by autonomic nervous activity in blood, urine and saliva
Pain threshold	6 months, 1, 2 and 3 years	Assessment of pain sensitivity by means of an algometer. Anatomically well-defined "trigger-points" are subjected to increasing pressure; the patients alert at the point where the pressure is perceived to be painful
Autonomic cardiovascular responses	6 months, 1, 2 and 3 years	Autonomic cardiovascular responses (such as changes in blood pressures, heart rate, cardiac output, total peripheral resistance and heart rate variability) during head-up tilt-test, valsalva maneuver and isometric exercise
Exercise capacity	1, 2 and 3 years	Cardio-pulmonary responses to a standardized exercise tolerance test (treadmill), such as maximal oxygen consumption(maxVO2), heart rate increase, blood pressure increase, etc.
Echocardiographic indices	1, 2 and 3 years	Echocardiographic indices of cardiac function, such as as systolic and diastolic velocities of the ventricular myocardium based on Tissue Doppler Imaging

Trial Locations

Locations (1)

Dept. of Cardiology, Oslo University Hospital; 🇳🇴 Oslo, Norway