Preload, also known as end diastolic volume, follows the Frank Starling principle where a slight increase results in an increase in cardiac output. However, if preload is significantly increased, such as exceeding 250ml, it can lead to a decrease in cardiac output.

The heart has four chambers and generates pressures of 0-25 mmHg on the right side and 0-120 mmHg on the left. The cardiac output is the product of heart rate and stroke volume, typically 5-6L per minute. The cardiac impulse is generated in the sino atrial node and conveyed to the ventricles via the atrioventricular node. Parasympathetic and sympathetic fibers project to the heart via the vagus and release acetylcholine and noradrenaline, respectively. The cardiac cycle includes mid diastole, late diastole, early systole, late systole, and early diastole. Preload is the end diastolic volume and afterload is the aortic pressure. Laplace’s law explains the rise in ventricular pressure during the ejection phase and why a dilated diseased heart will have impaired systolic function. Starling’s law states that an increase in end-diastolic volume will produce a larger stroke volume up to a point beyond which stroke volume will fall. Baroreceptor reflexes and atrial stretch receptors are involved in regulating cardiac output.

The observed ECG alterations are indicative of an ischemic injury in the lower region of the heart. The ST depressions in leads I and aVL, which are located in the lateral wall, are common reciprocal changes that occur during an inferior myocardial infarction. Typically, the right coronary artery is the most probable site of damage in cases involving lesions in the lower wall.

Understanding Acute Coronary Syndrome

Acute coronary syndrome (ACS) is a term used to describe various acute presentations of ischaemic heart disease. It includes ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina. ACS usually develops in patients with ischaemic heart disease, which is the gradual build-up of fatty plaques in the walls of the coronary arteries. This can lead to a gradual narrowing of the arteries, resulting in less blood and oxygen reaching the myocardium, causing angina. It can also lead to sudden plaque rupture, resulting in a complete occlusion of the artery and no blood or oxygen reaching the area of myocardium, causing a myocardial infarction.

There are many factors that can increase the chance of a patient developing ischaemic heart disease, including unmodifiable risk factors such as increasing age, male gender, and family history, and modifiable risk factors such as smoking, diabetes mellitus, hypertension, hypercholesterolaemia, and obesity.

The classic and most common symptom of ACS is chest pain, which is typically central or left-sided and may radiate to the jaw or left arm. Other symptoms include dyspnoea, sweating, and nausea and vomiting. Patients presenting with ACS often have very few physical signs, and the two most important investigations when assessing a patient with chest pain are an electrocardiogram (ECG) and cardiac markers such as troponin.

Once a diagnosis of ACS has been made, treatment involves preventing worsening of the presentation, revascularising the vessel if occluded, and treating pain. For patients who’ve had a STEMI, the priority of management is to reopen the blocked vessel. For patients who’ve had an NSTEMI, a risk stratification tool is used to decide upon further management. Patients who’ve had an ACS require lifelong drug therapy to help reduce the risk of a further event, which includes aspirin, a second antiplatelet if appropriate, a beta-blocker, an ACE inhibitor, and a statin.

Arteriolar constriction is facilitated by various mediators such as noradrenaline from the sympathetic nervous system, circulating catecholamines, angiotensin-2, and locally released endothelin peptide by endothelial cells. Endothelin primarily acts on ET(A) receptors to cause constriction, but it can also cause dilation by acting on ET(B) receptors.

On the other hand, the parasympathetic nervous system, nitric oxide, and prostacyclin are all responsible for facilitating arteriolar dilation, rather than constriction.

Understanding Endothelin and Its Role in Various Diseases

Endothelin is a potent vasoconstrictor and bronchoconstrictor that is secreted by the vascular endothelium. Initially, it is produced as a prohormone and later converted to ET-1 by the action of endothelin converting enzyme. Endothelin interacts with a G-protein linked to phospholipase C, leading to calcium release. This interaction is thought to be important in the pathogenesis of many diseases, including primary pulmonary hypertension, cardiac failure, hepatorenal syndrome, and Raynaud’s.

Endothelin is known to promote the release of angiotensin II, ADH, hypoxia, and mechanical shearing forces. On the other hand, it inhibits the release of nitric oxide and prostacyclin. Raised levels of endothelin are observed in primary pulmonary hypertension, myocardial infarction, heart failure, acute kidney injury, and asthma.

In recent years, endothelin antagonists have been used to treat primary pulmonary hypertension. Understanding the role of endothelin in various diseases can help in the development of new treatments and therapies.

Understanding the Cardiac Action Potential and Conduction Velocity

The cardiac action potential is a series of electrical events that occur in the heart during each heartbeat. It is responsible for the contraction of the heart muscle and the pumping of blood throughout the body. The action potential is divided into five phases, each with a specific mechanism. The first phase is rapid depolarization, which is caused by the influx of sodium ions. The second phase is early repolarization, which is caused by the efflux of potassium ions. The third phase is the plateau phase, which is caused by the slow influx of calcium ions. The fourth phase is final repolarization, which is caused by the efflux of potassium ions. The final phase is the restoration of ionic concentrations, which is achieved by the Na+/K+ ATPase pump.

Conduction velocity is the speed at which the electrical signal travels through the heart. The speed varies depending on the location of the signal. Atrial conduction spreads along ordinary atrial myocardial fibers at a speed of 1 m/sec. AV node conduction is much slower, at 0.05 m/sec. Ventricular conduction is the fastest in the heart, achieved by the large diameter of the Purkinje fibers, which can achieve velocities of 2-4 m/sec. This allows for a rapid and coordinated contraction of the ventricles, which is essential for the proper functioning of the heart. Understanding the cardiac action potential and conduction velocity is crucial for diagnosing and treating heart conditions.

The equation used to calculate systemic vascular resistance is SVR = MAP / CO. For example, if the mean arterial pressure (MAP) is 140 mmHg and the cardiac output (CO) is 4 mL/min, then the SVR would be 35 mmHg⋅min⋅mL-1. Although the theoretical equation for SVR is more complex, it is often simplified by assuming that central venous pressure (CVP) is negligible. However, in reality, MAP is typically measured directly or indirectly using arterial pressure measurements. The equation for calculating MAP at rest is MAP = diastolic pressure + 1/3(pulse pressure), where pulse pressure is calculated as systolic pressure minus diastolic pressure.

Cardiovascular physiology involves the study of the functions and processes of the heart and blood vessels. One important measure of heart function is the left ventricular ejection fraction, which is calculated by dividing the stroke volume (the amount of blood pumped out of the left ventricle with each heartbeat) by the end diastolic LV volume (the amount of blood in the left ventricle at the end of diastole) and multiplying by 100%. Another key measure is cardiac output, which is the amount of blood pumped by the heart per minute and is calculated by multiplying stroke volume by heart rate.

Pulse pressure is another important measure of cardiovascular function, which is the difference between systolic pressure (the highest pressure in the arteries during a heartbeat) and diastolic pressure (the lowest pressure in the arteries between heartbeats). Factors that can increase pulse pressure include a less compliant aorta (which can occur with age) and increased stroke volume.

Finally, systemic vascular resistance is a measure of the resistance to blood flow in the systemic circulation and is calculated by dividing mean arterial pressure (the average pressure in the arteries during a heartbeat) by cardiac output. Understanding these measures of cardiovascular function is important for diagnosing and treating cardiovascular diseases.

Understanding Atherosclerosis and its Complications

Atherosclerosis is a complex process that occurs over several years. It begins with endothelial dysfunction triggered by factors such as smoking, hypertension, and hyperglycemia. This leads to changes in the endothelium, including inflammation, oxidation, proliferation, and reduced nitric oxide bioavailability. As a result, low-density lipoprotein (LDL) particles infiltrate the subendothelial space, and monocytes migrate from the blood and differentiate into macrophages. These macrophages then phagocytose oxidized LDL, slowly turning into large ‘foam cells’. Smooth muscle proliferation and migration from the tunica media into the intima result in the formation of a fibrous capsule covering the fatty plaque.

Once a plaque has formed, it can cause several complications. For example, it can form a physical blockage in the lumen of the coronary artery, leading to reduced blood flow and oxygen to the myocardium, resulting in angina. Alternatively, the plaque may rupture, potentially causing a complete occlusion of the coronary artery and resulting in a myocardial infarction. It is essential to understand the process of atherosclerosis and its complications to prevent and manage cardiovascular diseases effectively.

Pericarditis is inflammation of the pericardium, a sac surrounding the heart. It can be caused by various factors, including viral infections. The typical symptom of pericarditis is central chest pain that is relieved by sitting up or leaning forward. ST-segment depression on a 12-lead ECG is not a sign of pericarditis, but rather a sign of subendocardial tissue ischemia. A pansystolic cardiac murmur heard on auscultation is also not associated with pericarditis, as it is caused by valve defects. Additionally, pericarditis is not typically associated with bradycardia, but rather tachycardia.

Acute Pericarditis: Causes, Features, Investigations, and Management

Acute pericarditis is a possible diagnosis for patients presenting with chest pain. The condition is characterized by chest pain, which may be pleuritic and relieved by sitting forwards. Other symptoms include non-productive cough, dyspnoea, and flu-like symptoms. Tachypnoea and tachycardia may also be present, along with a pericardial rub.

The causes of acute pericarditis include viral infections, tuberculosis, uraemia, trauma, post-myocardial infarction, Dressler’s syndrome, connective tissue disease, hypothyroidism, and malignancy.

Investigations for acute pericarditis include ECG changes, which are often global/widespread, as opposed to the ‘territories’ seen in ischaemic events. The ECG may show ‘saddle-shaped’ ST elevation and PR depression, which is the most specific ECG marker for pericarditis. All patients with suspected acute pericarditis should have transthoracic echocardiography.

Management of acute pericarditis involves treating the underlying cause. A combination of NSAIDs and colchicine is now generally used as first-line treatment for patients with acute idiopathic or viral pericarditis.

In summary, acute pericarditis is a possible diagnosis for patients presenting with chest pain. The condition is characterized by chest pain, which may be pleuritic and relieved by sitting forwards, along with other symptoms. The causes of acute pericarditis are varied, and investigations include ECG changes and transthoracic echocardiography. Management involves treating the underlying cause and using a combination of NSAIDs and colchicine as first-line treatment.

In the treatment of heart failure, medications are used to improve the heart’s ability to pump blood effectively. Beta blockers, such as bisoprolol, are commonly prescribed to slow the heart rate and improve filling. The first-line drugs for heart failure are beta blockers and ACE inhibitors. Therefore, the patient in question will be prescribed an ACE inhibitor, such as ramipril, as the second drug. Ramipril works by reducing venous resistance, making it easier for the heart to pump blood out, and lowering arterial pressures, which increases the heart’s pre-load.

Carvedilol is not the correct choice for this patient. Although it can be used in heart failure, the patient is already taking a beta blocker, and adding another drug from the same class could cause symptomatic bradycardia or hypotension.

Digoxin is not the appropriate choice either. While it can be used in heart failure, it should only be initiated by a specialist.

Sacubitril-valsartan is also not the right choice for this patient. Although it is becoming more commonly used in heart failure patients, it should only be prescribed by a specialist after first and second-line treatment options have been exhausted.

Chronic heart failure can be managed through drug treatment, according to updated guidelines issued by NICE in 2018. While loop diuretics are useful in managing fluid overload, they do not reduce mortality in the long term. The first-line treatment for all patients is a combination of an ACE-inhibitor and a beta-blocker, with clinical judgement used to determine which one to start first. Aldosterone antagonists are recommended as second-line treatment, but potassium levels should be monitored as both ACE inhibitors and aldosterone antagonists can cause hyperkalaemia. Third-line treatment should be initiated by a specialist and may include ivabradine, sacubitril-valsartan, hydralazine in combination with nitrate, digoxin, and cardiac resynchronisation therapy. Other treatments include annual influenzae and one-off pneumococcal vaccines. Those with asplenia, splenic dysfunction, or chronic kidney disease may require a booster every 5 years.

ECG changes indicating hypokalaemia include ST-segment depression, along with other signs such as small or absent P waves, tall tented T waves, and broad bizarre QRS complexes. On the other hand, hyperkalaemia can be identified through ECG signs such as a long PR interval and a sine wave pattern, as well as tall tented T waves and broad bizarre QRS complexes. Prolongation of the PR interval may be seen in both hypokalaemia and hyperkalaemia, while a short PR interval suggests pre-excitation or an AV nodal rhythm. Patients with hypokalaemia may present with symptoms such as fatigue, muscle weakness, myalgia, muscle cramps, constipation, hyporeflexia, and in rare cases, paralysis. It is worth noting that abnormalities in serum potassium levels are often discovered incidentally.

Hypokalaemia, a condition characterized by low levels of potassium in the blood, can be detected through ECG features. These include the presence of U waves, small or absent T waves (which may occasionally be inverted), a prolonged PR interval, ST depression, and a long QT interval. The ECG image provided shows typical U waves and a borderline PR interval. To remember these features, one user suggests the following rhyme: In Hypokalaemia, U have no Pot and no T, but a long PR and a long QT.

The patient with osteoarthritis is likely taking NSAIDs, which can diminish the effectiveness of ACE inhibitors in controlling hypertension. Additionally, NSAIDs can worsen the hyperkalemic effects of ACE inhibitors, contributing to the patient’s uncontrolled blood pressure. It is important to note that alcohol can also exacerbate the hypotensive effects of ACE inhibitors. Nitrates, on the other hand, are useful in managing hypertension.

Angiotensin-converting enzyme (ACE) inhibitors are commonly used as the first-line treatment for hypertension and heart failure in younger patients. However, they may not be as effective in treating hypertensive Afro-Caribbean patients. ACE inhibitors are also used to treat diabetic nephropathy and prevent ischaemic heart disease. These drugs work by inhibiting the conversion of angiotensin I to angiotensin II and are metabolized in the liver.

While ACE inhibitors are generally well-tolerated, they can cause side effects such as cough, angioedema, hyperkalaemia, and first-dose hypotension. Patients with certain conditions, such as renovascular disease, aortic stenosis, or hereditary or idiopathic angioedema, should use ACE inhibitors with caution or avoid them altogether. Pregnant and breastfeeding women should also avoid these drugs.

Patients taking high-dose diuretics may be at increased risk of hypotension when using ACE inhibitors. Therefore, it is important to monitor urea and electrolyte levels before and after starting treatment, as well as any changes in creatinine and potassium levels. Acceptable changes include a 30% increase in serum creatinine from baseline and an increase in potassium up to 5.5 mmol/l. Patients with undiagnosed bilateral renal artery stenosis may experience significant renal impairment when using ACE inhibitors.

The current NICE guidelines recommend using a flow chart to manage hypertension, with ACE inhibitors as the first-line treatment for patients under 55 years old. However, individual patient factors and comorbidities should be taken into account when deciding on the best treatment plan.