Lectures Heart Failure and Therapy
MINOR BIOMEDICAL TOPICS IN HEALTH CARE
Content
Course explanation ........................................................................................................................................................... 1
Introduction heart function .............................................................................................................................................. 2
General background on heart failure.............................................................................................................................. 12
Inherited cardiomyopathies – clinical perspectives........................................................................................................ 20
Translational studies in ischemic heart disease .............................................................................................................. 25
The Hoorn studies – diabetes and its vascular complications ........................................................................................ 35
The Engine & ENERGY studies – cardiomyopathies ........................................................................................................ 45
Cardiac aging ................................................................................................................................................................... 56
Gene regulation in the cardiovascular system................................................................................................................ 65
Basic research in atrial fibrillation................................................................................................................................... 76
Diabetes and obesity and vessel function ...................................................................................................................... 92
Pulmonary arterial hypertension – clinical aspects ...................................................................................................... 109
Diastolic heart failure .................................................................................................................................................... 118
Disease models of inherited cardiomyopathies ........................................................................................................... 131
,Course explanation
Aim of the course
This course aims to provide further insights into the pathophysiologic mechanisms, diagnostic approaches and
therapies and societal impacts of cardiovascular diseases
Goals of the course
Overview of the course
Course consists of:
- 1 group assignment (research proposal) (20% final grade)
- 2 literature discussions (recent research papers)
- 12 blocks of online lectures
- Presentation of group assignment (research proposal) (10% final grade)
- Exam (25 multiple choice questions, 5 open questions) (70% final grade)
Assignment
Project assignment: the main goals of the project assignment is to write a short research grant proposal on a heart
failure related subject
This should include the following:
- Background of the disease
- What is the overall research question that is going to be answered?
- Why is answering this question important?
- What are the research aims?
- What techniques are going to be used to answer the questions?
- What is the potential impact for patients, physicians, society if the research is successful?
- Conclusion
Literature discussions
Two papers will be discussed:
1. Basic science: Schiattarella et al. (September 15)
2. Clinical science: Puntmann et al. (September 29)
Read and try to understand each paper beforehand
1
,Introduction heart function
The right side of the heart pumps blood into the lungs (pulmonary circulation) and the left side pumps blood into the
rest of the body (the amount of blood that enters the aorta determines how much blood will be pumped into the
circulation)
- Pulmonary circulation: low pressure
- Systemic circulation: high pressure
Function of the heart
- Pumping deoxygenated blood to the lungs
- Pumping oxygenated blood to all the organs in the body
- Together with blood vessels: providing adequate perfusion of all organs & tissues of the body
The ability of the ventricle to relax is very important
What is the main determinant of cardiac output: contraction or relaxation?
It’s not only the force, but more importantly the amount of blood that can fill the ventricle (by relaxation) → heart
failure is more often a result of relaxation problems
How can heartbeats be sustained?
By coordination of contraction and relaxation of the 2-3 billion cardiomyocytes that must contract or relax in order
to have a heart rate
Excitation-contraction coupling
Contraction of the heart following electrical stimulation of cardiomyocytes (link between membrane depolarisation
and contraction) → this only happens when all cells are stimulated electrically
2
, Automation of the heart
The heart can beat independent of hormonal and neuronal input (although it
can get input which can affect the heart rate, this isn’t necessary)
Automation: the heart keeps on beating
- Spontaneous active
- Pacemaker cells (SA node) → control heart rate
Conduction through the heart
- SA (sinoatrial) node is the place where the pacemaker cells are located
- AV (atrioventricular) node (slow conduction: ~100 ms delay → so the atria and ventricles won’t contract at
the same time) conducts the electrical signal from the atria to the ventricles
- The signal travels to the Bundle of His → fast ventricular conduction
- The AV node is the only connection between the atria and ventricles, they are isolated from each other
Conduction between cardiomyocytes
Cardiomyocytes can also pass on signals, but they do it slower than the conduction system. Automation comes from
action potentials in cardiomyocytes. These cells are electrically coupled
3
MINOR BIOMEDICAL TOPICS IN HEALTH CARE
Content
Course explanation ........................................................................................................................................................... 1
Introduction heart function .............................................................................................................................................. 2
General background on heart failure.............................................................................................................................. 12
Inherited cardiomyopathies – clinical perspectives........................................................................................................ 20
Translational studies in ischemic heart disease .............................................................................................................. 25
The Hoorn studies – diabetes and its vascular complications ........................................................................................ 35
The Engine & ENERGY studies – cardiomyopathies ........................................................................................................ 45
Cardiac aging ................................................................................................................................................................... 56
Gene regulation in the cardiovascular system................................................................................................................ 65
Basic research in atrial fibrillation................................................................................................................................... 76
Diabetes and obesity and vessel function ...................................................................................................................... 92
Pulmonary arterial hypertension – clinical aspects ...................................................................................................... 109
Diastolic heart failure .................................................................................................................................................... 118
Disease models of inherited cardiomyopathies ........................................................................................................... 131
,Course explanation
Aim of the course
This course aims to provide further insights into the pathophysiologic mechanisms, diagnostic approaches and
therapies and societal impacts of cardiovascular diseases
Goals of the course
Overview of the course
Course consists of:
- 1 group assignment (research proposal) (20% final grade)
- 2 literature discussions (recent research papers)
- 12 blocks of online lectures
- Presentation of group assignment (research proposal) (10% final grade)
- Exam (25 multiple choice questions, 5 open questions) (70% final grade)
Assignment
Project assignment: the main goals of the project assignment is to write a short research grant proposal on a heart
failure related subject
This should include the following:
- Background of the disease
- What is the overall research question that is going to be answered?
- Why is answering this question important?
- What are the research aims?
- What techniques are going to be used to answer the questions?
- What is the potential impact for patients, physicians, society if the research is successful?
- Conclusion
Literature discussions
Two papers will be discussed:
1. Basic science: Schiattarella et al. (September 15)
2. Clinical science: Puntmann et al. (September 29)
Read and try to understand each paper beforehand
1
,Introduction heart function
The right side of the heart pumps blood into the lungs (pulmonary circulation) and the left side pumps blood into the
rest of the body (the amount of blood that enters the aorta determines how much blood will be pumped into the
circulation)
- Pulmonary circulation: low pressure
- Systemic circulation: high pressure
Function of the heart
- Pumping deoxygenated blood to the lungs
- Pumping oxygenated blood to all the organs in the body
- Together with blood vessels: providing adequate perfusion of all organs & tissues of the body
The ability of the ventricle to relax is very important
What is the main determinant of cardiac output: contraction or relaxation?
It’s not only the force, but more importantly the amount of blood that can fill the ventricle (by relaxation) → heart
failure is more often a result of relaxation problems
How can heartbeats be sustained?
By coordination of contraction and relaxation of the 2-3 billion cardiomyocytes that must contract or relax in order
to have a heart rate
Excitation-contraction coupling
Contraction of the heart following electrical stimulation of cardiomyocytes (link between membrane depolarisation
and contraction) → this only happens when all cells are stimulated electrically
2
, Automation of the heart
The heart can beat independent of hormonal and neuronal input (although it
can get input which can affect the heart rate, this isn’t necessary)
Automation: the heart keeps on beating
- Spontaneous active
- Pacemaker cells (SA node) → control heart rate
Conduction through the heart
- SA (sinoatrial) node is the place where the pacemaker cells are located
- AV (atrioventricular) node (slow conduction: ~100 ms delay → so the atria and ventricles won’t contract at
the same time) conducts the electrical signal from the atria to the ventricles
- The signal travels to the Bundle of His → fast ventricular conduction
- The AV node is the only connection between the atria and ventricles, they are isolated from each other
Conduction between cardiomyocytes
Cardiomyocytes can also pass on signals, but they do it slower than the conduction system. Automation comes from
action potentials in cardiomyocytes. These cells are electrically coupled
3
