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“OVIDIUS” UNIVERSITY OF CONSTANTA FACULTY OF MEDICINE MEDICINE

March 1, 2019 0 Comment

“OVIDIUS” UNIVERSITY OF CONSTANTA
FACULTY OF MEDICINE
MEDICINE (IN ENGLISH LANGUAGE)
THESIS

COORDINATOR:
DR. RAZVAN CHIRICADR LOREDANA PAZARA
GRADUATE:KHAN AHMED DAUD
CONSTANTA
2018
“OVIDIUS” UNIVERSITY OF CONSTANTA
FACULTY OF MEDICINE
MEDICINE (IN ENGLISH LANGUAGE)
Inflammation in Heart Failure

COORDINATOR(S):
DR. RAZVAN CHIRICA
DR LOREDANA PAZARA
GRADUATE:KHAN AHMED DAUD
Table of Contents
General PartPage 4
IntroductionPage 5
Anatomy of the heartPage 6-18
Physiology of the heartPage 18-30
Heart Failure& InflammationPage 30-40
Biography & References
3. personal contribution:
    – working hypothesis (objectives) 
    – your study: 
                         introduction
                         working hypothesis
                         matherials and methods 
                         results
                         discutions                         conclusions
  4. references
reguarding inflamation in hearth failure, i think you can focus on: 
a) blood tests used in heart failure- natriuretic peptides (BNP and NT proBNP), 
b) blood tests that indicates an inflamation: reactive C proteine, erythrocytes sedimentation rate, and fibrinogen
 
General Part
Introduction
On the survival scale a higher number of patients sustain the first cardiac outburst. Although technology has played its role in allowing us to understand the limitations of the heart in the form of specific and non specific mechanisms. Inflammatory cells are in tandem with certain processes initiated by the body to maintain workload and survive even after repeated abuse. However, as the heart is the central figure of the body, elements that compromise of certain changes play a negative role with other organs, gradually affecting there ability to optimise. Cardiac failure suggests many semiological patterns and signs, although in terms of markers of Acute and chronic heart failure we closely associate natriuretic peptides and free inflammatory cytokines in the blood that can be used as a pathway to predict clinical severity. This achievement is a breakthrough however we still have not established a concrete causal relationship between the disease and specific indicators hence the interest of this topic for my thesis
Our hearts bear the huge burden of keeping us alive from birth till death, and while carrying this huge task it seems to be very lenient allowing you to make mistakes during your life time, although the nature and graveness of the mistakes is reiterated by compensatory changes which could potentially lead to causes that decrease the efficiency of the heart. Nevertheless it will still try to meet the demands of your body. Ultimately, during this disruptive cycle of poor lifestyle decisions and general factors to be discussed in this review, a cascade of events occur which can be highlighted although not conclusive, by specific tests to see the health of your heart allowing physicians to take action.

Heart failure is a huge health concern which affects approximately 20 million people within Europe which primarily affects elderly individuals between 65-80 years, although 20% of patient are younger than 60 years of age. The aim of this thesis is to describe, analyse, evaluate what heart failure is, aetiologies, the types of heart failure , the features of the different types of HF , how we manage HF and importantly how we can diagnose HF by interpreting different signals the body gives us in terms of inflammatory markers which are widely used and the more specific markers used by cardiologists to determine the stage, the best treatment plans and to have an idea of the degree of severity to paint a better picture as well as allowing physicians to tailor a comprehensive plan.
This thesis will begin to explain the Anatomy and Physiology of our Heart,histopathology, the dynamics of heart failure with pharmacology in the general part. I will be writing specifically on Heart Failure and the current protocol specific for Europe. My study will comprise of patient data from Spitalul Clinic Judetean with a working sample size of over 50 patients, to be used for comparison and contrast to distinguish the role Inflammatory markers in cardiac failure. Moreover, accuracy and reliability for medical purposes as well as giving a conclusion on my views on the data gathered.

Anatomy of the Heart
Overview
50800113157000The heart is a fibro muscular organ of pyramidal shape which is enclosed within the pericardium which is a sac lined with pericardial fluid. It has a base, apex, many borders and surfaces. The heart occupies an area in the middle mediastinum where it is placed obliquely behind the sternum and the rubs which encapsulates it. It is in-between the lungs and its pleura’s.
Figure (1)
The heart is distinctly separated by a septum which separates the two muscular pumps which work concurrently, once pump follows on the the lungs, and the second pump is the oxygenated blood pumped to the body. These two pumps perform in a single organ which makes it so special. This displays its engineering and efficiency. We call these two pumps as the right and left heart pumps, within this the conduction tissues and cellular syncytium are also embedded and interlaced. Both pumps complete there unique role in their respective circulation pathways to meet the oxygen demands of the body. Anatomically they are both described as working in parallel manner.

Measuring from Base to apex, the average heart is roughly 12cm, it measures 8-9cm in its transverse diameter and 6cm antero-posteriorly. The male heart is heavier in weight compared to females. In males it weighs around 270-350g, whereas in females it weighs between 220-290g. There 4 surfaces of the heart are sternocostal (anterior), diaphragmatic (inferior) and right and left (pulmonary). The borders can be described as upper, acute or obtuse.
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The Heart is comprised of four cardiac chambers, Right and Left Atriums, Right and Left Ventricles. The Atria receive venous blood (Right atrium form IVC and left atrium from Lungs via Pulmonary Vein), They serve as weakly contracting blood reservoirs for filling of both Ventricles in diastolic phase, whereas the ventricles Figure 2 are responsible for the more powerful contraction that forces blood into its respective major arterial trunks ( Pulmonary Artery ; Aorta)
The Right heart begins at the Right Atrium where it receives venous blood from the IVC which collect blood from SVC and IVC. It also receive supply via the Coronary Sinus which is the heart own venous drainage. The blood which is knows as systemic venous blood crosses the atrium into the Right AV ( Atrioventricular Valve) via the AV orifice to enter into the Right ventricle. The right AV Valve is known as the The Tricuspid Valve (TV) and it covers the right AVO. The tricuspid valve opens to allow the passage of venous blood into the Ventricle when pressure allows it to. It closes upon contraction of the RT Ventricle to prevent backflow of blood, The RT Ventricle ejects into both Pulmonary Arteries (PA). The orifices entering the PA’s which are also guarded by the Semi Lunar Valves in this artery they are known as the Pulmonary Valves (PV), which are forced open when a pressure reaches a certain threshold this happens during Ventricular Contraction. The blood then continues through the Pulmonary circulatory bed, where it becomes oxygenated through a process of diffusion where it exchanges Carbon Dioxide for Oxygen with the help of specialized cells in the Lungs called the alveoli. The left heart begins at the Left Atrium (LA). It receives the pulmonary vein inflow of oxygenated blood, along with some coronary venous blood. Similar to the right heart, the LA contracts to fill the Left Ventricle (LV) via the left AV Orifice, which is guarded by the Atrioventricular Valve knows as the Bicuspid or Mitral Valve. Contraction of the LV increases the pressure which closes the Mitral Valve and opens the Aortic Valve(AV) Which allowing the ejection of oxygenated blood through the Aortic Sinus into the Ascending Aorta this progresses through the entire systemic arterial system, including the Coronary Arteries circulation. There is a short duration in the ejection phase of LV in comparison to the RV. Unusually there are greater changes in pressure.

The planes of the tricuspid and mitral valves are at a right angle to the plane of the septum The right atrium is positioned anteriorly and also inferior to the left atrium. The right atrium is also anterior to the left ventricle. The septal and ventricular structures are in line. The majority of the anterior ventricular muscle mass is due to the right ventricle. The inferior part of the ventricular muscle mass is located right of the left ventricle. The pulmonary orifice is located to the left and it is superior to the aortic valve. The left atrium forms the majority of the posterior facet of the heart and the muscular left ventricle and is also prominent inferiorly, where it continues to the apex. The cavity of the LV is conical and narrow and It has the most muscle in comparison to the other chambers as this is needed for powerful contraction. The ventricular orifices are more co-planar in the LV compared to the RV. The atria are situated to the right and posterior in relation to their ventricles.
Cardiac Chambers
2108200101981000Right AtriumThe RA receives deoxygenated blood from the body via the SVC and IVC and from the coronary sinus. The SVC enters the supero-posterior wall of the right atrium, alternatively the IVC and coronary sinus enter through the inferior-posterior regionBlood passes from the RA to the RV through the right Atrioventricular Orifice which is guarded by the Tricuspid valve this is closed during ventricular contraction to allow for development of pressure and prevent backflow of blood. It is positioned antero-medially.The anatomy of the RA has two spaces which are delineated. Internally there are smooth, muscular ridges called the Crista Terminalis. It begins on the roof of the RA, Figure 3 anterior to the opening of the SVC and proceeds downwards to lateral wall to the IVC. Externally we ca see the separation by the Sulcus Terminalis Cordis structure which is a shallow, vertical groove beginning form the lateral aspect of the SVC opening and the right of the IVC opening. The sinus of the vena cava is situated posterior to the crista Terminalis which drains blood from SVC and IVC.Anterior to the crista terminalis there is a space which contains walls covered by ridges called the pectinate muscles which can also found in the right auricle. This is a conical and muscular pouch that overlaps the aortic arch externally, medical to the IVC lies the opening of the coronary sinus.

The Right Atrium and Left Atrium are separated by the inter atrial septum which faces anterior and toward the right side. We can also identify as visible depression superior to the IVC orifice this is called the oval fossa (fossa ovalis) and has a prominent margin knows as the oval fossa border ( limbus fossa ovalis). Furthermore, openings for the venae cordis minimae are scattered beside the RA walls whose function is to gutter the myocardium into the RA.

Right VentricleThe RV is located on the left of the RA and elongates lengthwise downwards. Anatomically, it is antero-lateral to right AVO. This is why blood enters the RV from the RA in a level and frontward direction.The outflow tract of the RV is the Conus Arteriosus (infundibulum) which leads to the pulmonary trunk.

There are also multiple irregular, muscular structures found on the walls of the inflow portion of the RV called Trabeculae carneae which are mostly attached to the ventricular walls whose job is forming ridges, although Some are only attached at one end called papillary muscles. The corresponding end of the papillary muscles act as an attachment point for the chordae tendineae. The chordae tendineae connect the free edges of the cusps of the Triscupid Valve.

In the RV We have 3 papillary muscles. They are anterior, posterior and septal. The largest papillary muscle arises from the anterior ventricular wall so it is denoted as anterior. The papillary muscle arising from the ventricular wall which are also supplemented by little amounts of chordae tendineae and it can consist of two or three structures are knows as the posterior. The last papillary muscles can be absent or very small and they have chordae tendineae straight from the septal wall. There is also a septomarginal trabecula which is a moderator band which bonds the lower IV(Interventricular) Septum and the base of the anterior papillary muscle. Furthermore it also contains the right AV bundle involved in the conduction system where it continues to the anterior wall of the Right Ventricle
Tricuspid ValveThe Tricuspid Valve closes the right Atrioventricular orifice during ventricular contraction. When the RV is filling the TV opens, and the cusps line into the RV. Each cusp is secured at its base to the fibrous ring adjacent the AVO. The cusps are continuous with each other at their bases in an area called commissures. The fibrous ring therefore maintains shape of the opening. The 3 cusps are called the anterior, posterior and septal cusps, according to there location in the RV. The chordae tendineae begin from the tips of the papillary muscles, and attach to the free areas of the cusps. Each cusp is attached to chordae tendineae from two papillary muscles. These structures play an important role as a compensatory mechanism. They prevent the back flow of blood into the RA during right ventricular contraction.The contraction of the papillary muscles prevents the upside down eversion of the cusps into the RA as the pressures rises in the right ventricle.

Pulmonary ValveThe Pulmonary valve lines the opening into the pulmonary trunk located at the apex of the infundibulum. It consists of three semilunar cusps with free edges which project up into the lumen of the pulmonary trunk. There are three semilunar cusps which are denoted to as the anterior, left and right semilunar cusps. The upper part of the cusp has two parts called the nodule and the lunula. The nodule is thicker than the lunula. The cusps follow a concave shape forming curved sinuses, with the dome part of the curve facing the pulmonary trunk. Therefore, any back flow of blood post ventricular contraction consequently fills these pockets, and forces the cusps closed. This amazing mechanism prevents blood coming back into the RV
Left AtriumThe LA receives the four PV’s in its posterior upper half as this is where the inflow occurs from the pulmonary vein. The walls of this area of the atrium are smooth. The anterior half is continuous with the left auricle(pouch on top of heart),this half contains pectinate muscles. In comparison to the RA, there are no recognisable structures like the crista terminalis that divide both portions of the RA.The interatrial septum is located on the anterior wall. It has a slight depression for the foramen ovale which closed at birth, and is opposite the fossa ovalis in the RA.

1770380423037000Left VentricleThe Left Ventricle is located anterior to the LA. Blood continues from the LA through the left Atrioventricular Orifice and into the LV towards the apex. The LV is a very important chamber of the heart as it is composed of the thickest layer of myocardium. The musculature is conical shaped and lengthier than the RV. The aortic vestibular opening (outflow tract towards aorta) has smooth walls, and is located in posterior fashion to the infundibulum of the RV. Trabeculae carneae are present in the LV, Figure 4 similar in appearance to the trabeculae of the RV with muscular ridges and bridges however those in the LV are fine and delicate.Moreover larger anterior amd posterior papillary muscles with chordae tendineae are also present(larger than RV). However only two papillary muscles, known as the anterior and posterior papillary muscles, are present. There are two parts to the interventricular septum the muscular part and the membranous part. The bulk of the interventricular septum is made of the thick muscular part, although the thinner membranous part occupies the upper part of the septum.

2454910308991000244919515367000Mitral Valve (Bicuspid Valve)The Mitral valve guards guards the space of the left Atrioventricular orifice. This valve opens at the superior part of the Left Ventricle. It is a bicuspid valve with 2 cups which are the anterior and posterior cusps. These are close shut during ventricular contraction and at the commissure they are continuous with each other. At the opening they are surrounded by a fibrous ring. They have a similar cooperated purposefulness with the papillary muscles Figure 5 (MV Cusps) and chordae tendineae similar to the RV.

-62230383476500Aortic ValveThe Aortic valve closes the entrance from the LV into the Aortic arch. The aortic vestibule which is the opening where blood outflows from the left ventricle continues superiorly with the Aorta(Aortic Arch). Itshas similar structure to that of the Pulmonary artery with three semilunar cusps all with free edges projecting up into the Aortic Arch lumen. The posterior, left and right aortic sinuses are found between the semilunar cusps and the wall of the AA. The right and left coronary arteries arise from the right and left aortic sinuses. Figure 6 (MV Papillary Muscles) It has The same mechanism as the Pulmonary Valve where it prevents the back flow of blood into the LV. Moreover, the blood retreats after ventricular contraction, it fills the aortic sinuses and thus forces blood into the Coronary Arteries which originate from the left and right aortic sinuses.
Figure 7
Vascular SupplyThe Coronary sulcus is an area which separates the atria and ventricles of the heart, it contains the main trunks of the nutritional vessels of the heart knows as the coronary arteries. It supplies with interventricular and marginal branches in the interventricular sulci, which continue towards the apex. All cardiac veins empty venous blood into the coronary sinus, which is in the coronary sulcus between the left atrioventricular groove. The coronary sinus empties into the Right Atrium between the IVC opening and the right Atrioventricular orifice. 0177673000
Figure 8
Coronary Arteries
Right Coronary Artery
The Right coronary artery supplies oxygenated blood to the right atrium, right ventricle, sinoatrial node, atrioventricular node, the interatrial septum, a portion of the left atrium, the postero-inferior third of the interventricular septum, and a portion of the posterior left ventricle.The right coronary artery starts from the right aortic sinus of the ascending aorta. It continues in anteriorly fashion follows with a vertical descent in the coronary sulcus, between the right atrium and right ventricle. Inferiorly, at the heart margins, it turns posteriorly and follows in the sulcus over the diaphragmatic surface and base of the heart, on this course it gives rise to many branches. The atrial branch passes advances in the groove between the right auricle and the ascending aorta, branching off to the sinoatrial nodal branch which continues posteriorly around the superior vena cava to supply the sinoatrial node. As the right coronary artery continues to the hearts margin and continues towards the apex its gives off the right marginal branch and also a atrioventricular nodal branch as it extend over the diaphragm and the base of the heart. The last branch sits in the posterior interventricular sulcus and the name is given by the location, called the posterior interventricular branch.
Left Coronary Artery
The left CA supplies a huge chunk of the left atrium and left ventricle the remaining two thirds of the interventricular septum that is not supplied by the right cornory artery, including the atrioventricular bundle and all of its branches. The left coronary artery originates from the left aortic sinus of the ascending aorta and progresses inbetween the pulmonary trunk and the left auricle before entering the coronary sulcus pathway. The left CA artery divides into 2 terminal branches called the left anterior descending artery and the circumflex artery which is just behind the pulmonary trunk. The
LAD Branch
The left anterior descending artery advances at the left side of the pulmonary trunk and progressing diagonally towards the apex using the interventricular sulcus, diagonal branches are given from this artery on its course to the apex these branches cover the anterior surface on the left ventricle and descend in a diagonal manner.
Circumflex Branch
The circumflex artery also progresses towards the left, in the coronary sulcus, and on to the base / diaphragmatic heart surface. It ends before reaching the posterior interventricular sulcus. The left marginal artery or obtuse marginal artery rises from the circumflex artery and extends across the obtuse margin of the heart almost parallel to the diagonal artery.

-62230144145000The dispersal and distribution pattern explained for the branching of right and left coronary artery is generally the most collectively used and seen. Patients tend to have a right dominant coronary artery. This necessitates the posterior interventricular branch arising from the right CA. The right CA therefore supplies a large part of the posterior LV wall and the circumflex branch of the left CA is comparatively smaller and shorter in length. Alternatively, hearts with left dominant CA, the posterior interventricular branch arises from a large circumflex branch, and supplies most of the posterior LV wall.

Figure 8
Some the blood supply of the AVN and SAN has another variation they are supplied by the right Coronary Artery, moreover branches from the circumflex branch of the left Coronary Artery also occasionally supply them.

Cardiac VeinsThe coronary sinus receives deoxygenated blood from the great, middle, small and posterior cardiac veins.

Great Cardiac Vein
Originates at the apex, then proceedes upwards on the anterior interventricular sulcus, where it’s related to the path of left anterior descending artery, then continues left towards the coronary sulcus, and extends onto the diaphragmatic surface. It now related to the circumflex branch of the left Coronary artery furthermore it continues along the coronary sulcus, it gradually expands to form the coronary sinus, which terminates in the Right Atrium.

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Middle Cardiac Vein (posterior interventricular vein)
Originates near the apex, and ascends in the posterior interventricular sulcus towards the coronary sinus. It is associated with the posterior interventricular branch of the right or left CA during its course depending on variation.

Small Cardiac Vein
Originates between the RA and RV at bottom ant section of sulcus. It proceeds in this groove onto diaphragmatic surface until terminating at coronary sinus at its atrial end. Figure 9 It accompanies the marginal branch of the right CA along the acute margin. The right marginal vein enters the RA directly if it does not join the small cardiac vein.

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Posterior Cardiac Vein
Lies on the posterior surface of the LV, left of the middle cardiac vein. It either links the great cardiac vein or terminates at the coronary sinus.

Anterior Cardiac Veins (anterior veins of the RV)
Arise on the anterior surface of the RV. They cross the coronary sulcus and enter the anterior wall of the RA. The right marginal vein could be included in this group if it does not enter the small cardiac vein. They drain the anterior portion of the RV.

Venae Cordis Minimae
They drain directly into the cardiac chambers, and are abundant in the RA and RV. Occasionally they drain LA, Figure 10 but rarely the LV. They are the smallest group of veins
Major Blood Vessels
Pulmonary TrunkThe pulmonary trunk is enclosed by the visceral layer of serous pericardium, and is associated with the Ascending Aorta in a common sheath. It begins from the Right Ventricle at the Conus Arteriosu, anterior to the aortic orifice. Ascends, posteriorly to the left. Initially, positioned anteriorly and then to the left of the Ascending aorta. The pulmonary trunk divides into the right and left Pulmonary Arteries level to the T5/T6, opposed to the left sternum border, posterior to the third left costal cartilage. The left Pulmonary Artery passes inferiorly to the aortic arch, and anteriorly to the descending aorta to enter the left lung. The right Pulmonary Artery passes to the right, posterior to the ascending aorta and the Superior Vena cava to enter the right lung.

Ascending AortaAs explained up the ascending aorta is covered by the visceral layer of serous pericardium, organised with the pulmonary trunk in a common sheath. It begins in the aortic orifice at the base of the Left ventricle level with the lower edge of the third left costal cartilage, posterior to the left half of the sternum and moves superiorly, anterior, to the right, proceeding to the level of the 2nd right costal cartilage and becomes the arch of the aorta when it enters the superior mediastinum. Three small protrusions or bulges can be seen at a point superior to where the Aortic arch arises from the Left Ventricle. They are opposite the semilunar cusps of the aortic valve, and represent the right, left and posterior aortic sinuses. The right and left Coronary arteries develop from their corresponding aortic sinuses.

Cardiac Conduction System
It is the system that initiates the impulse which follows a pathway to coordinate the contraction of the atrial and ventricular muscles. Formed by nodes and extensive networks of specialised muscle cells(nodes, fibres and bundles). The SAN, AVN, AV Bundle and its respective right and left bundle branches with there purkinje fibres are the four main and integral constituents of the conduction system that is vital to sustain life. The impulse pathway that is generated by automaticity and excitation causes a unidirectional contraction is throughout the pathway. Large branches of the system are insulated and unable to conduct impulse from the myocardium by connective tissue to provide efficiency by doing this it helps prevent excessive unnecessary stimulation and contraction of the cardiac muscle fibres.The SAN is signified to as the cardiac pacemaker. Impulses begin at this collection of cells located in the superior end of the crista terminalis in the Right Atrium. The electrical signals generated spread across the atria, which causes them to contract, this continued impulse of excitation in the atria stimulate the AVN which is located near the opening of the coronary sinus. near the attachment of the septal cusp of the Tricuspid, within the atrioventricular septum. This collection of specialised cells relays and conveys the excitatory impulse to the ventricular musculature. In a timely manner and a specific framework. A bundle that is a continuation of AVN is called the atrioventricular bundle. It passes along the membranous part of the interventricular septum, and divides into the right and left bundles.RBB proceeds on the right of the interventricular septum towards the apex of the RV. It enters the septomarginal trabecula to reach the base of the anterior papillary muscle. It then splits and continues to form the purkinje fibres. These fibres are spread across the ventricle to supply its musculature, including the papillary muscles.LBBB follows to the left of the interventricular septum, and descends to the apex of the LV. It gives off branches along its course, and terminates as the purkinje fibres, these fibres spread electrical impulses throughout the ventricle.

Innervation
The initiation of the cardiac cycle is myogenic beginning in the sinoatrial node. The autonomic nerves affect the nodal tissues, their extensions, on coronary vessels and also on the atrial and ventricular musculature. The autonomic nerves control the rate and force and ouput. The cardiac branches of the vagus are parasympathetic and they have both afferent and efferent fibres. The same is true for the sympathetic branches, apart from the superior cervical sympathetic ganglion. This is totally efferent. Sympathetic fibres accelerating the heart and dilate the coronary arteries. The vagal fibres slow the heart and constrict the coronary arteries. The preganglionic cardiac sympathetic axons begin from neurones that are situated in the interomediolateral segment of the upper five thoracic spinal segments. They may either synapse at the upper thoracic sympathetic ganglia or they rise to synapse in the cervical ganglia. The sympathetic cardiac nerves are formed by the postganglionic fibres.
The preganglionic cardiac parasympathetic axons begin from neuornes in the dorsal vagal nucleus or in close proximity to the nucleus ambiguous. They continue as vagal branches and synapse in the cardiac plexus and also the atrial walls. The intrinsic cardiac neurones are only found in the atria and interatrial septum. They are mostly in the subepicardial connective tissue which is located near the sinoatrial node and the atrioventricular node. The intrinsic ganglia form complex circuits for the local neuronal control of the heart.
Cardiac plexus
The autonomic nerves together produce a mixed cardiac plexus. It has two parts: the superficial part, which is located between the aortic arch and the pulmonary trunk, and the deep part. This is located between the aortic arch and the tracheal bifurcation. . It is produced by the cardiac branches of the cervical and upper thoracic sympathetic ganglia, the vagus nerve and recurrent laryngeal nerve. Branches from the right half of the deep part continue anterior to and posterior to the right pulmonary artery. The anterior ones supply some filaments to the right anterior pulmonary artery and then they form part of the right coronary plexus. The ones that are behind supply some filaments to the right atrium and continue to the left coronary plexus. The left half is linked to the superficial cardiac plexus. It supplies filaments to the left atrium and left pulmonary plexus. The cardiac plexus has many extensions. The plexuses have with them ganglion cells. The ganglion cells are found in the atrial tissue and along the supply of branches of the plexus. Their axons are postganglionic parasympathetic. Passing through the cardiac plexus are the cholinergic and adrenergic fibres. These are mostly located in the sinoatrial node and atrioventricular nodes. Adrenergic fibres supply the coronary arteries and cardiac veins. There is a plexus of nerves that have cholinesterase, adnrenergic transmitters and neuropeptide Y in the subendocardial parts of all the chambers and in the cusps also.
Physiology of the Heart
The human heart is comprised of 2 distinguished pumps divided into the right and left heart. The right heart receives blood from the Vena cava which is deoxygenated blood collected from peripheral organs and pumps it through to the lungs. Alternatively, The left heart receives oxygenated blood from the lungs and pumps it back to the peripheral organs. Both pumps works in tandem and have an atrium and ventricle respectively. The atria functions as a primary pump and fills the stronger ventricles capable of pushing blood out of the heart with more force and a higher pressure, which is responsible for propelling through a very tentative environment of blood vessels. Moreover the heart also has a unique conduction mechanism that maintains its own rhythmicity and transmits action potentials through the heart muscles 1
Cardiac Muscle Physiology
The three muscle types in the heart are atrial muscle, ventricular muscle, conductive muscle and specialised excitatory fibres. The atrial and ventricular types of muscle contract in a similar way to normal skeletal muscle but with a longer contraction length. The contraction of the conductive muscle and specialised excitatory fibres are less in intensity as they have a limited amount of contractile fibrils, however
24555455080000 they display automaticity. This means they exhibit automatic rhythmical electrical discharges therefore forming there own action potentials which propagates through the heart this ultimately allows the heart to beat in a regular rhythm.

Figure 10(1)

Action potentials within cardiac muscle
There are special membranes within the intercalated discs In the cardiac muscle that are specific for cardiac muscle tissue. These cell membranes combine with other cell membranes of the cardiac muscle forming communication junction which facilitate in the rapid diffusion of ions. These are called gap junctions. The ions can move easily into the intracellular fluid allowing movement of action potential from one cardiac muscle cell to another. This is why we say they are a syncytium. However, Action potentials can only be conducted by the atrioventricular bundle allowing atria to contract before the ventricles enabling extra time for ventricular filling.

2796540762000Action potentials has an average 105 millivolts, this rises from approximately from -85 to +20 during every cardiac cycle. The first phase is where the initial spike occurs which lasts 0.2 seconds, following by a rapid repolarization stage, lastly the plateau phase allows for prolonging ventricular contract to make the whole cycle more efficient. The action potentials are propagated Figure 11(2)
by fast sodium and slow calcium channels. The sodium channels facilitate the influx of sodium ions to enter from the extracellular environment. These channels close after a small amount of time and repolarization starts. On the other hand the slow calcium channels open slowly but remain open for longer periods, and this facilitates large influxes of calcium and sodium ions into the cardiac muscle fibres. This is where the extended period of depolarization occurs and cause the plateau, furthermore when the action potential starts there is also a marked decrease in the permeability of potassium ions, so outflow decreases during the plateau phase of the action potential therefore this prevent the voltage from returning to normal. This happens at the end of 0.2 seconds and the sodium and calcium influx stops. Now at this moment in time the membrane permeability increases back to normal and potassium outflow finally occurs causing the action potential to halt.
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Excitation contraction coupling is a phenomenon when the changes in action potentials causes the myofibrils in the muscles to contract. The way this works is when the action potential passes along the membrane of the transverse tubule and reaches the internal aspect of the cardiac muscle fibre. The calcium ions are released into the sarcoplasm from the sarcoplasmic reticulum because the action potentials act on the membranes of the longitudinal sarcoplasmic reticulum. The calcium ions in the myofibrils initiates a response from actin and myosin causing a muscular contraction. 2
(a)there is a long plateau phase due to the influx of calcium ions. The extended refractory period allow the cell Figure 12 (3)
to fully contract before another electrical event can occur.

(b)The action potential for heart muscle is compared to that of the skeletal muscle
Calcium enters the cell and activates ryanodine receptor channels ( calcium release channels)
Calcium ions have the ability to also diffuse into the sarcoplasm from the T Tubules. These calcium ions now interact with troponin forming cross bridges allowing muscle contraction.

11
Furthermore, Calcium ions have the ability to enter the sarcoplasm from the T Tubules. Calcium used the voltage gated calcium channels in the membrane of the T tubule to enter the sarcoplasm and this in turn activated the calcium release channels via the ryanodine receptor channels. Calcium enters the sarcoplasm, which interact with troponin resulting in formation of cross bridges and contract of the muscle. The cardiac muscle doesn’t have ample amount of calcium to induce on its own to cause a full muscle contraction, hence the role of the T tubules is very important. In addition to that the contraction strength is proportional to the calcium ions concentration in the extracellular fluid, the same is the case with the T tubule network. As soon as the plateau phase of the cardiac muscle fibre completes, there is a block on the calcium ions from entering into the muscle fibre.
The remaining calcium ions that are in the sarcoplasm are rapidly transported back in to the sarcoplasmic reticulum and the extracellular fluid space. The ATPase pump facilitates the movement of calcium to the sarcoplasmic reticulum. (12)

The cardiac muscle contract for the period the action potential lasts. It ends milliseconds after the termination of the action potential. The duration of muscle contracts is 0.2 seconds in atrial muscle and 0.3 seconds in ventricular muscle. (13)
The Cardiac Cycle

Figure 13 (4) Initially, both the atria and ventricles are relaxed (diastole). The P wave represents depolarization of the atria and is followed by atrial contraction (systole). Atrial systole extends until the QRS complex, at which point, the atria relax. The QRS complex represents depolarization of the ventricles and is followed by ventricular contraction. The T wave represents the repolarization of the ventricles and marks the beginning of ventricular relaxation.
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Figure 14 (5) The cardiac cycle begins with atrial systole and progresses to ventricular systole, atrial diastole, and ventricular diastole, when the cycle begins again.

The events that occurs from the commencement of one heart beat to the start of the next is know as one full cardiac cycle. This cycle is activated by a spontaneous action potential which is generated in the sinoatrial node. This action potential travels swiftly through the atrium and is conducted by the atrioventricular bundle and the impulse is transferred to the ventricles and contraction occurs. Each cycle is activated by an action potential generated in the SAN. The conduction system is such that a delay of more than 0.1 seconds occurs during the passage of the impulse from the atria to the ventricles. The ensures the atria contracts before the ventricles and also more blood is pumped into the ventricles and this is required as the ventricles provide the major source for delivering blood through the bodies circulatory system whether to the lungs or to the body.
Systole and Diastole
Systole is simply defined as the contraction period of the cardiac cycle this is when the heart fills with blood and contraction occurs. Diastole is used when the heart is in relaxation this is the stage where the myocardium is not contracting and the heart is filling with blood. An easy way the find out roughly, the duration of the cardiac cycle we do a reciprocal of the heart rate. If a person’s heart beat is 80bpm, the duration of the cardiac cycle 60/80 which is 0.75 seconds for 1 beat. Alternatively, when the heart rate increases the length of the cardiac cycle decreases as it is inversely proportional, during this time the action potential and diastole phase also decreases in duration and systole stay the same. In conclusion an increased rate hinders the filling of the heart.

Figure 15 (6) A Wiggers diagram, showing the cardiac cycle events occuring in the left ventricle. In the atrial pressure plot: wave “a” corresponds to atrial contraction, wave “c” corresponds to an increase in pressure from the mitral valve bulging into the atrium after closure, and wave “v” corresponds to passive atrial filling. In the electrocardiogram: wave “P” corresponds to atrial depolarization, waves “QRS” correspond to ventricular depolarization, and wave “T” corresponds to ventricular repolarization. In the phonocardiogram: The sound labeled 1st contributes to the S1 heart sound and is the reverberation of blood from the sudden closure of the mitral valve (left A-V valve) and the sound labeled “2nd” contributes to the S2 heart sound and is the reverberation of blood from the sudden closure of the aortic valve.

Function of the AtriaThe atria has a continuous flow of blood from the Great veins ( Superior & Inferior Vena Cava & Pulmonary Veins). While the atria are still relaxing more than 75% of blood is able to flow directly into the ventricles, before the atria contract. Atrial contraction compensates for the remaining 25% of blood filling into the ventricles. Although, the heart can continue to function under most conditions, even without this extra 20% effectiveness, because it is capable of pumping 300-400% more blood than what is essential for the resting body. If the atria fail to function, adverse effects will only be noticed in a body not at rest, as the demands will increase for more blood volume required for adequate perfusion.
Transition Period
Wiggers Diagram Pressure explanation: The a wave occurs due to atrial contraction with the right atrial pressure increases around 4-6mm Hg and the left atrial pressure increases between 7-8mm Hg. The c wave represents the ventricles on the verge of contracting and there AVV slight backflow of blood to the atria. This increasing pressure in the ventricles causes the AVV (bicuspid and tricuspid) to bulge backwards. The v wave around the end of the ventricular contraction. This is the slow flow of blood into the atria from the veins whilst AVV closed during the contraction and disappears when ventricular contraction has finished. Diastole occurs and ventricles fill rapidly with blood and the cycle repeats.

Function of the Ventricles
During diastole, the ventricles fill with blood. During systole, both AVV close, this results in blood accumulation in both atria. The rapid filling period of the ventricles occurs immediately after systole whereby the ventricular pressure drops to their diastolic value. The increased pressure in the atria force the AVV open, allowing blood to pass rapidly into the ventricles.

The period of rapid filling occurs in the first 1/3 of diastole, with a small amount in the 2/3 which is mainly blood emptying into the atria from the great veins which directly enters the ventricles. In the final third of diastole and then the atria contract to push the remaining 25% as explained in the previous page.

Ventricular Emptying : 3 Phases;
Isovolumic Contraction period, Ejection period, Isovolumic Contraction period
The period of isovolumic contraction is the stage after ventricular contraction begins. The ventricular pressure rises rapidly, which lead to the closure of the AVV. An extra 0.02-0.03 seconds is needed to increase the pressure in the ventricles to push the semilunar valves open against the pressure in the aorta and the pulmonary arteries. In this period, ventricular contraction occurs however this is no emptying in this period. This increases the cardiac muscle tension but no shortening of the muscle fibres occurs.

Once the LV Pressure has risen of 80 mm Hg and RV pressure rises over 8mm Hg the semilunar valves open. Blood immediately starts to pour out of the ventricles Ejection period is split into 3 parts. 1st part is rapid ejection 70% of blood is ejected during this period. The other 30% is ejected in the next two thirds in the phase of slow ejection
1994535182372000Once systole is finished, the ventricles relax, causing pressures in the Right & Left ventricles to decrease back to normal and the increased pressure in aorta in pulmonary artery cause the blood to be pushed back into the ventricles. When pressure is reached below a certain point then both SMV close preventing any re-entry. The ventricular muscles relaxes for an additional 0.03-0.06 seconds, and the ventricular volume remains the same during this period of isovolumic relaxation. The intraventricular pressures decline to their diastolic levels and AVV open again to begin filling and another cycle of ventricular pumping.

The end diastolic volume is defined as the the volume of blood in the ventricles which fill during diastole. Which is approximately 110-120 ml(EDV) During systole when the ventricles empty, their volume decreases by approximately 70 ml(Stroke volume output) leaving a residual of about 40-50ml(ESV) after contraction. The end systolic volume equates to the volume of blood remaining in each ventricle after systole, The ejection fraction{(70(SV)/110 or 120(EDF)}is the SV/EDF which normally equals to around 60%.Figure 16 (7) Although this can change and stroke volume output can change by more than 100% leaving a ESV OF 10-20ML, and also EDV Can also be 150-180ml. This all depends on blood going in and amount ejected.

After stronger heart contractions, the end systolic volume may be as little as 10-20 ml. When a large quantity of blood fill the ventricles during diastole, the end diastolic volume could be as much as 150-180 ml. The stroke volume output could double if the end systolic volume decreases and the end diastolic volume increases.
Preload and Afterload
Preload is the degree of tension on the cardiac muscle when contraction begins. It is the end diastolic pressure when the ventricle has filled. Preload is the volume of blood in the ventricles at the end of diastole. CVP is central venous pressure and provides an indirect measure of the EDV in the right ventricle.  PAOP is pulmonary artery occlusion pressure provides an indirect measure of the EDV in the left ventricle.

Afterload is the contractile force or the pressure the ventricle must exert to open the semilunar valves.  Vessels which are distally located to the ventricles exert a pressure due to vasoconstriction or vasodilation, causing the valves to be closed, hence to open the valves a certain pressure within the ventricles must be acquired and we call this afterload. Which is represented by systemic (svr) and pulmonary vascular resistance respectively, That volume is measured as the pressure that it exerts on the walls of the ventricles in mmHg. (14)
Rhythmical Excitation of the Heart
2108200154178000The heart has a unique ability to produce electrical impulses in a rhythm and conduct these in a timely fashion to other parts of the organ who receive and transmit this signal from the SAN to the AVN. This SAN is responsible for the contraction of the atria 1/6 Seconds before the ventricles which allow optimised filling of the ventricles in the meantime, furthermore the hearts conduction system enables contraction of the ventricle all at the same time within a syncytium to produce a certain pressure in the ventricles to prime expulsion. The internodal pathways act as a mediator to conduct the transmission of the SAN impulse to the AVN. A slight delay occurs at the AVN Before ventricular signal processing to the AV bundle and through to the left and right Purkinje fibres, before conducting the cardiac impulse to the whole ventricle instantaneously.

Sinoatrial Node
The SAN is an ellipsoid strip of specialised cardiac muscle measuring 15mm long, 3mm wide, and 1mm thick. The SAN node fibres measure 3-5 micrometres in diameter. There are no contractile muscle filaments in the SAN.
These fibres connect with the atrial muscle This allowing any action potential generated in the SAN to quickly spread into the atrial muscle wall. Figure 17 (8)
The resting membrane potential is less negative in the SAN is -55mV and in the ventricular muscle fibre it is -90mV. so only the slow sodium-calcium channels can open and initiate the action potential. The SAN action potential is slower to develop compared to the ventricular muscle action potential. The return of the potential to its negative state after the action potential occurs slowly as well.

Self excitation of sinus node fibres
A high concentration of sodium ions is present in the extracellular fluid and some sodium channels are also open, therefore there is a influx. Hence in-between heart beats we have a slow rise of the resting membrane potential. This becomes more positive with concurrent beats. When we reach the potentials threshold of -40Mv there is an activation of the sodium-calcium channels allow for an action potential. Self excitation is due to the calcium and sodium ions inward leak. The depolarization of the sodium-calcium channels is deactivated within 150ms of opening and also by potassium gates that open, after the end of an action potential the potassium channels close. There are intermodal pathways connecting the atrial muscle fibres with the ends of the sinus node fibres allowing conduction and passage of action potential. The anterior , middle and posterior intermodal pathways bend inside the atrial walls and end in the AV node which allows for increase conduction passage. (15)(16)
Atrioventricular Node
The cardiac impulse has a short block in the form of the AV node which prevent the conductive travel from the atria to the ventricles to quickly. This delay is important, as it allows for blood to empty into the ventricles from the atria before the ventricular contraction occurs. The AV node is situated in the posterior wall of the right atrium just behind the tricuspid valve. The impulse reached the AVN from the SAN using the intermodal pathways in around 0.03 seconds. Following a delay of 0.09 seconds. This follows with the impulse entering the AV bundle and passes into the ventricles with a further delay 0.04 seconds. Causing a total delay of 0.13 seconds excluding the conduction delay of AVN upon signal receive from SAN.

The AVN is in the RA posterior wall behind the TVa. The impulse reaches the AVN from the SAN via the internodal pathways in approximately 0.03 seconds. The AVN then sets a delay of 0.09 seconds, before the impulse enters the penetrating portion of the atrioventricular bundle, where it passes into the ventricles. This penetrating atrioventricular bundle is composed of numerous small fascicles, which pass through the fibrous tissue separating the atria from the ventricles, and sets a further delay of 0.04 seconds. The total delay of the AVN and atrioventricular bundle system is about 0.13 seconds, with the additional conduction delay from the SAN to the AVN of 0.03 seconds, equalling 0.16 seconds. There is resistance to the conduction because of the decrease number of gap junctions between cells in the conduction pathways of the AV node and AV Bundle fibres. (15)(16)
Purkinje Fibres
The cardiac impulse is transmitted to the ventricles via the purkinje fibres. These begin at the AV node and follow through the AV bundle and line the ventricles.
Most of the purkinje fibres are bigger than ventricular muscle fibres and transmit large action potentials at 1.5 to 4.0 metres per seconds. This is 150 times quicker than AV node fibres and 6 times quicker than ventricular muscle fibres.. This rapid transmission of action potential allows almost spontaneous transmission of the cardiac impulse throughout the entire ventricular muscle tissue. This rapid transmission generated by a high permeability of the gap junctions at the intercalated discs between the cells the make up the purkinje fibres. This ions can therefore easily diffuse rapidly between cells, creating a greater velocity of transmission. The purkinje fibres do not contract. The atrioventricular bundle prevents re entry action potential to go back into the atria from ventricles therefore it ensures forward conduction to the ventricles. (15)(16)
“The continuous fibrous barrier which separates the atrial muscles and ventricular muscles, serve as an insulator to avert passage of cardiac impulses between atrial and ventricular muscle through any other direction besides forwards through the atrioventricular bundle.”(18)
Right & Left bundle branches
The AV bundle passes through the fibrous tissue that delineates the atria and the ventricles. The terminating portion of this bundle passes in the ventricular septum for 1.5cm following the direction of the apex. This is where the bundle bifurcates into the left and right bundle branch situated near the endocardium. The right bundle branch and left occupy there corresponding sides of the IV septum. This branch continue and towards the apex they bifurcate again and again into smaller branches. They sweep around the ventricular chamber and ventricular walls on each side and carry onto the base of the heart. The purkinje fibres infiltrate 30% of the wall of the ventricles and coexist with the cardiac muscle. The duration of the impulse travels is 0.03 seconds from the beginning of the bundle branch to end of the purkinje fibres, which indicates a very rapid spread.The cardiac muscle envelops the heart in spiral fashion with fibrous septa. The impulse travels from the purkinje fibres to the ventricular muscle by the specialized ventricular muscle fibres. There is also a decrease in the travelling velocity of conduction from 0.5metres per second to approximately 0.3. This is due to the fibrous septa that angulated toward the surface along spiral so it need extra 0.03 seconds to travel from the endocardia to the epicardial surface of the ventricles respectively. 0.06 Seconds is the total time for the travel from start to finish in ventricular muscle fibres. (19)
The Sinus node sends 70-80 impulses per minute. The AV node can discharge at a rate of 40 per minute. The purkinje fibres can discharge at 15 to 40 time per minute. The reason why the sinus is node as a pacemaker is because it discharges at a higher rate than the AV node and purkinje fibres. Therefore when the pacemaker discharges it causes the other two to discharge, so the self excitation of the AV node and purkinje fibres is bypassed by faster rhythmical discharge of the sinus node hence the name pacemaker. Ectopic pacemakers is when it is not the sinus node, and prevents the heart from pumping efficiently because its due to abnormal order of contractions. The AV node becomes the pacemaker if Sinus node block happens and then purkinje fibres if the AV node is blocked causing some ventricular contractions.
Parasympathetic and Sympathetic Stimulation
Acetylcholine reduces rate of rhythm from sinus node as well as AV junctional fibres excitability, also reduces impulse transmission to ventricles, a little bit of Vagus stimulation can reduce the heart rate by up to half. Acetylcholine is released in response to parasympathetic nerve stimulation. If the vagal stimulation is strong enough it can induce a complete stop and ventricular escape rhythms take over at 15-40bpm. Potassium ion permeability on the membrane of the fibre increases also with Acetylcholine release causing hyperpolarization and change in the membrane potential from 65 to -75 mV. (20)
Sympathetic stimulation increase rate of sinus node discharge. The force of contraction and of the atrial and ventricular muscle increases and so does the heart rate. The sympathetic nerves stimulation allow the release of norepinephrine from the Sympathetic nerve endings stimulating Beta – 1 adrenergic receptors which causes effect on the heart rate. The resting membrane potential becomes more positive as the Sinus nodal permeability to Na and Ca increase, therefore self excitation increases. Furthermore, increased ion permeability in the AV node and bundles leads to a swifter conduction of impulse from atria to ventricles. This increased contractility is due to the new permeability situation of the calcium ions
The Electrocardiogram
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The cardiac impulse that travels along the heart can also be recorded across the surface of the body. These electrical signals can be picked up by electrodes on different parts of the chest wall to form some data that we can use to check the function of the heart this is called an Electrocardiogram or ECG/EKG.

The normal electrocardiogram has a P wave, a QRS complex and a T wave recording The P wave represents electrical potentials generated during atrial depolarisation just before atrial contraction this usually lasts about 0.08 – 0.10 seconds. The Figure 18 (9)
302069517208500QRS complex represents potentials generated during ventricular depolarisation,
before ventricular contraction this normally lasts 0.06 to 0.10 seconds. The T wave represents potentials generated as the ventricles recover from their depolarisation state. This usually occurs in 0.25-0.35 seconds after depolarisation. The T wave is the repolarisation wave and lasts longer than the P wave and the QRS wave.

The voltage of the P wave is between 0.1-0.3 mV. The QRS complex is around 1-1.5 mV from the top of the R wave to the bottom of the
S wave. The T wave voltage is between 0.2-0.3 mV. Figure 19 (10)
The P-Q interval is the period between the beginning of the P wave, and the beginning of the QRS complex. It represents the beginning of excitation of the atria, and beginning of excitation of the ventricles.
This normally lasts about 0.16 seconds. It is sometimes referred to as the P-R interval if the Q wave is absent. The Q-T interval lasts about 0.35 seconds. It starts at the beginning of the Q (or R) wave to the end of the T wave. It represents the contraction of the ventricles.

The HR can be determined from the ECG. If the interval between two successive beats from the time calibration line is 1 second, then the HR is 60 bpm. It is usually estimated by counting the number of large squares between two successive R intervals. (20)

Figure 20 (11)
Precordial Leads
Six chest leads are connected at different points on the anterior chest wall. These leads are recorded one at a time on the ECG and are known as leads V1, V2, V3, V4, V5 and V6. Each chest lead records the electrical potential of the cardiac muscle beneath the electrode.

In V1 and V2, the QRS complexes recorded are mostly negative because the chest electrode in these leads are closer to the base of the heart. The base of the heart is in the direction of electronegativity during most of ventricular depolarisation. In V4-V6, the QRS complexes are mainly positive because of the chest electrode in these leads being closer to the apex, which is the direction of positivity during the depolarisation
Heart Failure
The hearts inability to maintain an adequate cardiac output to provide for the demands of the body is known as cardiac failure. This can be a result of a structural or a functional disorder.

Aetiology ;Left Ventricular Failure
(1)Volume Overload: Aortic regurgitation, Mitral regurgitation, Patent ductus arteriosus(2)Pressure Overload: Systemic hypertension, Aortic stenosis
(3)Myocardial diseases: Ischaemic heart diseases, dilated cardiomyopathy; idiopathic, myocarditis, peripartum cardiomyopathy, diabetes mellitus, haemachromatosis, sarcoidosis, scleroderma, and alcohol
(4)Restrictive and hypertrophic cardiomyopathy
Right Ventricular Failure
(1)Volume Overload: Atrial septal defect, tricuspid regurgitation
(2)Pressure overload: Pulmonary hypertension, Pulmonary stenosis
(3)Myocardial diseases: Cardiomyopathy secondary to left ventricular failure.

Types of Heart Failure Classification
(1)Acute versus chronic heart failure
Acute heart failure: heart failure that develops suddenly in hours or days in a patient that was previously symptomatic.

Chronic heart failure: heart failure that develops gradually where a variety of compensatory changes can occur in early phase to improve cardiac function. This adaptive mechanism allows the patients to adjust and tolerate not only the anatomic abnormality but also a reduction in cardiac output with ease.

(2)Left versus right and biventricular heart
left sided heart failure: is characterized by a reduction in the effective left ventricular output for a given pulmonary, venous or left atrial pressure. An acute increase in left atrial pressure may cause pulmonary congestion or pulmonary oedema, however chronic increase in left atrial pressure results in reflex pulmonary vasoconstriction which safeguards a patient from pulmonary oedema but increases pulmonary hypertension as a compensatory mechanism. The causes of left heart failure are IHD, systemic hypertension, mitral and aortic valve diseases and cardiomyopathies.

Right sided heart failure: is characterized by reduction in right ventricular output for any given right atrial pressure. The increase right atrial pressure is manifested as an increased JVP and as hepatic congestion. The Causes of right heart failure are; secondary to left heart failure, chronic lunge disease causing cor pulmonale, pulmonary embolism or pulmonary hypertension, tricuspid and pulmonary valve disease, ASD, VSD, right ventricular cardiomyopathy.

Biventricular or congestive heart failure is when both sides of the heart are involved therefore features are present of both left and right side heart failure, most patient with right heart failure is due to pre-existing left heart failure
(3) Forward versus backward failure
In a variety of patient with cardiac failure predominant issue is an inadequate cardiac output that leads to decreased perfusion of vital organs leading to ischaemia of these organs called forward failure. Ischaemia of brain causes mental confusion, of skeletal muscles leads to weakness, of kidneys causes sodium and water retention leading to heart failure. Backward failure presents with features of stasis or damming of blood into venous system such as lung congestion in left heart failure, and congestion of liver, spleen and other areas in right heart failure.

(4) Systolic versus diastolic failure
In majority of patient’s heart failure is due to combined systolic and diastolic dysfunction. However, isolated systolic or diastolic dysfunction may be present. In systolic failure heart failure may develop as a result of impaired myocardial contraction (systolic dysfunction). The most common cause is systolic ventricular dysfunction in ischaemic heart disease usually proceeding from myocardial infarction, in this case the left ventricle is usually dilated and fails to contract normally resulting in symptoms of predominantly forward failure. Impaired ventricular relaxation causes poor ventricular filling therefore it is a diastolic dysfunction. Left ventricular hypertrophy as a result of hypertension and coronary artery disease is the most common cause, moreover hypertrophic restrictive cardiomyopathy. Diabetes and pericardial disease also have an effect. It is common in the elderly, women, and patients with history of HT (SOB can be caused by HT)
(5) Low versus high cardiac output failure
Low cardiac output at rest or during physical exertion in common in patients with congenital, valvular , rheumatic, hypertensive, coronary and cardiomyopathic diseases. Low output failure presents with systemic vasoconstriction such as pallor, cold/cyanotic extremities with a low pulse pressure. Whereas anaemia, beriberi, thyrotoxicosis and Paget’s disease of the bean could lead to or precipitate heart failure. The extremities are usually warm, flushed and pulse pressure is wide or normal.
Chronic Heart Failure
CHF is the gradual development of heart failure. A variety of compensatory changes take place in the early phase to improve cardiac function. These adaptive mechanisms allow the patient to deal with reduction in cardiac output with less stress on heart and to tolerate with anatomic abnormality. However these compensatory mechanisms fail to improve cardiac function as the disease progresses. Overt cardiac failure development is prevented by these adaptive changed even though there is impaired cardiac function. The changes include and increased heart rate, hypertrophy of cardiac muscles and dilation of heart chambers. Acute HF is more symptomatic due to the time required to develop compensatory changes.
-58420000Figure 21 https://www.wikidoc.org/index.php/Congestive_heart_failure_pathophysiologyDecreased heart function, causes reduced output leading to diminished filling of arterial tree, causing ischaemia of the organs and as the heart fails to pump the whole blood coming to it, this results in damming of blood back into the venous system, causing congested organs and functions inadequate. Majority of patients have a combination of both factors which causes the HF.

Features Of Left Heart Failure
Congestion causes most symptoms of lung congestion due to damming of blood
SOB (Dyspnoea), this progresses with increasing severity. Exertional dyspnoea > Orthopnoea > Paroxysmal Nocturnal Dyspnoea > Dyspnoea at rest > pulmonary oedema.
Exertional dyspnoea
Exertional dyspnoea leads to increased venous return and relative normal right heart transmits this in pulmonary circulation. However in LHF the blood isn’t pumped properly into systemic circulation resulting in damming of blood in the pulmonary veins, producing pulmonary venous congestions. The next process is the congestion stimulates fine nerve endings around the terminal of the alveoli which gives a sensation of breathlessness. Although when exercise is stopped venous return decreases and congestion subsides with a relief in dyspnoea.

Orthopnoea means breathlessness on lying flat. Mechanism of action is because of redistribution of fluid from tissues into the plasma. Approximately ½ of litre of blood pooled in the leg veins during standing is returned to effective circulation therefore venous return and hence workload is increased. This doesn’t help the poor function of the heart so lung congestion and dyspnoea develop. Hydrostatic pressure helps drainage of upper lungs zones into the left atrium to continue respiration even though lower zones are congested. On lying flat hydrostatic effect is lost so the whole lung becomes congested and patient becomes breathless.

Paroxysmal nocturnal dyspnoea is a sudden episode of breathlessness at night during sleep.

Venous return increases on lying flight and reduces hydrostatic effect in pulmonary veins. Depression of nervous system during sleep leads to reduced awareness of pulmonary congestion therefore when it become of high degree the patient becomes severely breathless. During sleep the sympathetic system is also depressed which is responsible for cardiac rate. The reduced heart rate leads to pooling of blood in pulmonary vessels resulting in pulmonary congestion. The patient wakes up with intense breathlessness which often produces feeling of suffocation. The patients sits upright and it relieves slowly and the attack subsides spontaneously in around half an hour.

Pulmonary Oedema develops in severe left heart failure and is characterized by persistent severe breathlessness of sudden onset. In addition, there is profuse sweating and skin becomes cold and cyanosed. Expectoration of watery, frothy and often blood stained sputum.
Acute cardiac failure after myocardial infarction, myocarditis and acute valvular regurgitation usually present with pulmonary oedema in previously asymptomatic patients.

Reduced cardiac output also causes fatigue and weakness due reduced blood flow to the skeletal muscle and CNS. Nocturia happens due to exertion of fluid retained during the day and increased renal perfusion in the recumbent portion at night. Chronic non-productive cough may also happen and is generally worse in recumbent position.

On Examination
Inspection: may have bulging of precordium due to cardiomegaly, generally no cardiomegaly in acute heart failure, diastolic heart failure, constrictive pericarditis and restrictive cardiomyopathy.

Palpation: Apex beats is displaced and heaving in character, if there is left ventricular hypertrophy.

Auscultation: Gallop-rhythm: tachycardia with 3rd or 4th heart sound is called gallop-rhythm
Basal crepitation are heard, and rhonchi may be due to bronchospasm. In pulmonary oedema loud crepitation are heard all over the lungs. And signs of a loud P2 denoting pulmonary hypertension may be present. Systolic murmurs due to functional mitral regurgitation as a result of ventricular and annular dilation.

On General physical examination:
Pallor, coldness of extremities, cyanosis of digits, distension of peripheral veins due to vasoconstriction as a result of increased adrenergic activity. Wasting that results from anorexia due to hepatic and intestinal congestion and mesenteric hypo perfusion called cardiac cachexia. Tachycardia, reduced pulse pressure and pulsus alternans may be present. Diastolic BP may be slightly elevated due to increased adrenergic activity. Fever may be present. Always examine for features of aetiology of heart failure such as hypo or hyperthyroidism.
Features Of Right Heart Failure
Tissue congestion : tissue congestion results from inability of the heart to empty properly, showing the following features;
Cerebral: headache, insomnia, restlessness
Pulmonary: cough, dyspnoea
Portal: anorexia, nausea & vomiting
Pain in right hypochondrium due to hepatic congestion which stretches the hepatic capsule
This stretching of hepatic capsule stimulates pain receptors and produces pain.

Renal : Oliguria and nocturiaPeripheral oedema of feet in ambulatory and sacral oedema in bed bound patient
On Examination
Raised JVP – +ve hepato-jugular reflux, Tender Hepatomegaly due to congestion. Dependant Pitting oedema, massive amounts of fluid can cause ascites or pleural effusion.

Evidence of heart disease : signs of right ventricular or biventricular cardiomegaly. Right ventricular gallop rhythm. Functional tricuspid regurgitation die to right ventricular dilatation. Cardiac cachexia.

Framingham Criteria for diagnosis of CCF
Major criteria : paroxysmal nocturnal dyspnoea, neck vein distention, crepitation’s, cardiomegaly, acute pulmonary oedema, S3 Gallop, Increased venous pressure (;16), positive hepatojugular reflex.

Minor criteria : pedal oedema, night cough, dyspnoea on exertion, hepatomegaly, pleural effusion, tachycardia, vital capacity reduced by one third from normal.

Investigations
ECG: right or left ventricular hypertrophy, myocardial ischaemia or infarction, arrhythmia
X-ray chest: Hilar congestion, bat wings appearance in acute pulmonary oedema (opacities tend to spread in a butterfly manner from the hilum. Also “Kerley B lines” in pulmonary oedema. The periphery is usually clear)
Cardiomegaly, evidence of Pulmonary HT, pleural effusion, pneumonia as a precipitating factor may be evident.
C-Reactive Protein: Produced in the liver and when inflammation is happening in the body Opsonin; xes complement and facilitates phagocytosis.?Measured clinically as a nonspecific c sign of ongoing in inflammation. CRP is a more sensitive and accurate reflection of the acute phase response than the ESR.ESR may be normal while CRP is elevated. CRP returns to normal more quickly than ESR in response to therapy. CRP level falls quickly because of its short half-life (4 to 7 hours) (25)( USMLE 1ST AID)
Erythrocyte Sedimentation Rate : An increase in erythrocyte sedimentation rate provides information about the inflammatory aetiology of heart failure. Products of in inflammation (eg, brinogen) coat RBCs and cause aggregation. The denser RBC aggregates fall at a faster rate within a pipette tube. Often co-tested with CRP levels. Normally reduced in heart failure. When there is inflammation in the body, the red blood cells stick together more than normal and fall to the bottom of the test tube more quickly. This means that more of them fall to the bottom of the test tube in 1 hour than when there is no inflammation. Your ESR may be higher than normal if you have a disease or problem that is causing inflammation, such as:
Arthritis Autoimmune disease (a disease that causes your body to attack your own tissues, like lupus)Infectio,CancerThe ESR is also higher during pregnancy or if you have kidney or thyroid disease. Your healthcare provider will use the result of your ESR test, the history of your illness, your physical exam, and any other tests you may have had to arrive at a diagnosis.

Some diseases cause inflammation but do not raise the ESR, so a normal result does not always mean that you do not have a medical problem.

A low ESR is usually not a problem. However, your ESR may be lower than normal if you have: 
A disease or condition that increases red blood cell production,A disease or condition that increases white blood cell production,Sickle cell anemia (abnormal red blood cells)
If you are being treated for an inflammatory disease, an ESR that is going down is a good sign that your body is responding to the treatment.

Fibrinogen also called Factor 1 is a blood plasma protein which is synthesised wihin the liver and it is one of the many (13) coagulation factors that is responsible for normal blood clotting where it takes place in the coagulation cascade. Coagulation factor; promotes endothelial repair; correlates with ESR (USMLE 1ST AID)
Serum B-Type Natriuretic Peptide (BNP) : Present in ventricle, it is elevated when ventricular filling pressures are high, it is quite sensitive more than 70% in patients with symptomatic heart failure but less specific in older patients, women and patients with COPD.

This marker is useful with patents with breathlessness or peripheral oedema (22)
Plasma endothelin – 1 concentration: for estimation of ejection fraction and wall motion abnormality.

Exercise tolerance test: when myocardial ischaemia is suspected cause of left ventricular dysfunction.

Myocardial bipsy to identify the cause of dilated cardiomyopathy but rarely performed.

Cardiac enzymes is to detect MI if suspected.

Urea ; Creatinine may be abnormal due to decrease renal perfusion
Echocardiography is a useful tool for diagnosis and cause of heart failure it can easily highlight; valvular diseases, systolic or diastolic impairment of left or right ventricle, cardiomyopathy, intracardiac thrombus, ejection fraction, and within the region motion abnormalities in ischaemic heart disease.

Management of Chronic Heart Failure
The strategy of treatment is split into 3 areas which need to be attended to;
1.Correction of the primary underlying cause (Ischaemia, valvular heart disease, thyrotoxicosis, hypothyroidism, high cardiac output states, arrhythmias, drug induced myocardial depression, acute myocarditis may respond to immunosuppressive drugs ; corticosteroids, treatment of hypertension and pericardial disease.

2.Elimination of precipitating cause (anemia, infection such as pneumonia, MI, UTI or RTI, reccurent pulmonary emboli, hypoxemia, arrhythmias, pregnancy, HT, physical, dietary, fluid and emotial excess.

3.Control of congestive heart failure.

(1)Reduction of cardiac workload involving physical and emotional rest, bed-rest for 1-2 weeks in symptomatic cardiac failure. Small frequent meals, reduce in weight by restricting calorie intake, prescribe vasodilators. (2) control of excessive retention of salt and water by advising a low salt diet and increase excretion of fluids via use of diuretic drugs. (3) Enhancement of myocardial contractility by advising on use of digitalis and concurrently dopamine/dobutamine.

Drugs Management
Diuretics : Loop Diuretics ( Furosemide), Potassium Sparing Diuretics ( Spironolactone) ; Thiazide Diuretics (Metalazone)
Mild diuretics can be managed by spironolactone and oral thiazide, this prevent the development of hypokalaemia, however thiazide diuretics in ineffective when GFR is below 30ml/min. Spironolactone is a specific inhibitor of aldosterone and this is increase in cardiac failure so hence why we combine its with thiazide or furosemide.
When heart failure reaches a severe stage we need to increase diuretic effect in this case furosemide is amazing. Acutely it should be given intravenously because proper absorption may not happen due to gut congestion. We can give a dose range of 20-320mg daily in 2 or more divided doses. However in severe renal insufficiency larger doses of furosemide up to 500mg may need to be given for effect. Metalazone maintains its activity even in renal insufficiency so it is combined with furosemide in refractory oedema.
Excessive diuretic therapy may lead to hyponatremia, hypokalaemia, hyperglycaemia, hyperuricemia and pre renal azotemiaVasodilators : Reduce preload and afterload therefore improve cardiac function
ACE Inhibitors(captopril), Angiotensin II Receptor antagonists(Losartan,Valsartan) Hydralazine, Nitrates, NesiritideACE prevent salt and water retention as angiotensin II stimulates aldosterone and causes salt and water retention. Inhibits peripheral arterial and venous vasoconstriction. Inhibiting action of sympathetic system improving cardiac function preload and afterload.

Long acting Nitrates such as isosorbide dinitrate 20-80mg orally 3 times daily is moderately effective, this is effective in relieving shortness of breath in mild to moderate cardiac failure but have little effect on cardiac output.

Neseretide in a recombinant form of Human BNP and is a potent vasodilator that reduces ventricular filling pressure and improve cardiac output. It is used mainly in decompensated heart failure and is more effective than IV nitroglycerine.
Digitalis (digoxin) is a positive intotropic agent (increasing the force of cardiac contraction) by competitive inhibition of sodium-potassium AT-pase which results in high intracellular sodium exchanges for extracellular calcium. High intracellular levels of calcium ions allow increased binding of contractile proteins actin and myosin, enhancing the force of cardiac contraction it is the first line therapy in patients with HF associated with AF, it can also be used in severe heart failure that has not responded to treatment with a diuretic and an ace inhibitor.
Complications of Heart Failure
Uraemia: Diuretic therapy, low cardiac output and treatment with vasodilators or dopamine may improve renal perfusion.

Hypokalaemia: Diuretic therapy, Hyperaldosternism (activation of the renin-angiotensin system and impaired aldosterone metabolism due to hepatic congestion)
Hyponatremia: Diuretic therapy and inappropriate water retention
Impaired Liver Function: Hepatic congestion and poor hepatic perfusion, abnormal liver function tests, mild jaundice and potentially anticoagulants
Thromboembolism: Deep vein thrombosis and pulmonary embolism ( low cardiac output, immobility), systemic emboli (intracardiac thrombus e.g. mitral stenosis), LV aneurysm and arrhythmias such as in atrial fibrillation.

Arrhythmias: Underlying heart disease, electrolyte changes, increased circulating catecholamine’s and drugs adverse effect such as in digoxin toxicity.

Special Part
Introduction
On the survival scale a higher number of patients sustain the first cardiac outburst. Although technology has played its role in allowing us to understand the limitations of the heart in the form of specific and non specific mechanisms. Inflammatory cells are in tandem with certain processes initiated by the body to maintain workload and survive even after repeated abuse. However, as the heart is the central figure of the body, elements that compromise of certain changes play a negative role with other organs, gradually affecting there ability to optimise. Cardiac failure suggests many semiological patterns and signs, although in terms of markers of Acute and chronic heart failure we closely associate natriuretic peptides and free inflammatory cytokines, as well as ESR,CRP and clotting factors such as fibrinogen (Factor 1) in the blood that can be used as a pathway to predict clinical severity. This achievement is a breakthrough however we still have not established a concrete causal relationship between the disease and specific indicators hence the interest of this topic for my thesis
Our hearts bear the huge burden of keeping us alive from birth till death, and while carrying this huge task it seems to be very lenient allowing you to make mistakes during your life time, although the nature and graveness of the mistakes is reiterated by compensatory changes which could potentially lead to causes that decrease the efficiency of the heart. Nevertheless it will still try to meet the demands of your body. Ultimately, during this disruptive cycle of poor lifestyle decisions and general factors to be discussed in this review, a cascade of events occur which can be highlighted although not conclusive, by specific tests to see the health of your heart allowing physicians to take action.

Heart failure is a huge health concern which affects approximately 20 million people within Europe which primarily affects elderly individuals between 65-80 years, although 20% of patient are younger than 60 years of age.
My study will comprise of patient data from Spitalul Clinic Judetean in the department of Cardiology from 1st January 2018 – 1st March 2018 for heart failure. I had a working sample size of over 50 patients (Male and Female), to be used for comparison and contrast to distinguish the role Inflammatory markers in cardiac failure as well as there class of Heart failure. The including criteria was to have signs and symptoms of heart failure, based on NYHA classification. The excluding criteria was: to be hospitalized for other disease, and not for heart failure.

Hypothesis & Objectives
The objective of this study is to identify the inflammatory markers in heart failure and to see if they are a genuine way of predicting severity or not. The specific inflammatory I will be using we be C-reactive protein, Erythrocyte sedimentation rate and also data for fibrinogen will be analysed. I want this study to clearly give me an indicator on the casual relationship between CRP, ESR and Fibrinogen and if any correlation is present. I also understand that there are variables which I will not be able to control such as medication given to patient which could skew the data. However, I predict that with males and female there will be a marked raise in inflammatory markers and that will vary with the stage of heart failure. To follow a standardised measure of degree of heart failure my objective system and patient class system made by the New York Heart association will be used for every patient and that will be compared against the values of the 3 inflammatory markers gathered for each patient it this study to make sure the validity and intent of my study is reliable to achieve a clear distinction. I will present my multiple findings and make a conclusion after presentation of the data.

Materials and Methods
As discussed in my introduction a sample size of 51 patients was taken from 1st January 2018 – 1st march 2018. Data collection including Erythrocyte Sedimentation Rate, C-Reactive Protein and Fibrinogen. Furthermore, a scale ranging from Class I to Class 4 depending on the degree of the physical activity tolerated, symptoms are rest, and level of discomfort, fatigue, palpitation and dyspnoea after ordinary physical activity or in some cases discomfort at rest was recorded. In addition to this another scale rated to alphabetic letters (A,B,C,D) was for the objective assessment to rate the degree of severity of cardiovascular disease and appearance of symptoms. The letter A being no objective evidence of cardiovascular disease and the letter D being severe limitation and objective evidence of severe progressed cardiovascular diseases with symptoms at rest.

Classes of Heart Failure
Class Patient Symptoms
I No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).

II Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).

III Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.

IV Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. (21)
Class Objective Assessment
A No objective evidence of cardiovascular disease. No symptoms and no limitation in ordinary physical activity.

B Objective evidence of minimal cardiovascular disease. Mild symptoms and slight limitation during ordinary activity. Comfortable at rest.

C Objective evidence of moderately severe cardiovascular disease. Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest.

D Objective evidence of severe cardiovascular disease. Severe limitations. Experiences symptoms even while at rest. (22)
Doctors usually classify patients’ heart failure according to the severity of their symptoms. The table below describes the most commonly used classification system, the New York Heart Association (NYHA) Functional Classification (22). It places patients in one of four categories based on how much they are limited during physical activity.

Key
Normal Values:
CRP
Risk of developing cardiovascular disease;
CRP: Low Risk ;1.0mg/L, Average Risk 1.0-3.0mg/L, High Risk ;3.0mg/L(23)
Normal Concetration of CRP in healthy adults is between 0.8mg/L – 3.0mg/L(24)
Normal levels increase with aging. Higher levels are found in late pregnant women, mild inflammation and viral infections (10–40 mg/L), active inflammation, bacterial infection (40–200 mg/L), severe bacterial infections and burns (;200 mg/L). (26)
ESR
Women under age 50 should have an ESR under 20 mm/hr.

Men under age 50 should have an ESR under 15 mm/hrWomen over age 50 should have an ESR under 30 mm/hr.

Men over age 50 should have an ESR under 20 mm/hr.

(27)
Fibrinogen
150-400 mg/dl
Main Criteria used for my study were:
Age Distribution
Sex Distribution
CRP Levels
ESR Levels
Fibrinogen Levels
Heart Failure NYHA Class I, II, III, IV
Heart Failure NYHA Class Objective Assessment A, B, C, D
Results
                       
                         discutions                         conclusions ( control of values underlying other pathologies)
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