Cardiac Emergencies

Regarding recent reports on the epidemiology of congenital heart diseases, left to right shunts are considered the most diagnosed impairment. This group of anomalies is characterized by the return of oxygenated blood back to the lungs for re-oxygenation, creating a physiological redundancy in the circulatory system. There is an increased venous return from the lungs through the pulmonary veins to the left atrium and ventricle. As a result, a volume overload is created on the left ventricle and decreases systemic cardiac output. The resulting physiological alterations associated with the shunt are determined by the magnitude of the anomaly and the post-infancy changes in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR).

In the fetal stage of development, shunt defects have minimal or no physiological effect since a high PVR limits blood flow to the lungs. Oxygen administration, low arterial carbon dioxide tension, nitric oxide, and other interventions or maneuvers that decrease the PVR automatically increase the left-to-right shunt at the cost of decreasing systemic output. Continued shunting damages the pulmonary vasculature, ultimately causing pulmonary hypertension and hyperplasia of the vessel walls. A reversal or discontinuation of shunting has been reported to normalize PVR.

Physiologically, right-to-left shunts are characterized by the return of deoxygenated blood from the tissues back to the body without re-oxygenation.

With the advent of technological innovations in medicine, many experts have proposed different diagnostic standards for congenital heart disease across the spectrum of patients' demography. Across the board, the consistent theme in these proposals is a multi-system diagnosis method recommending the use of physical examination, magnetic resonance imaging (MRI), echocardiography, cardiac catheterization, cardiac computed tomography (CT), and open-heart surgery. An accurate diagnosis may be difficult, especially in the adult population. However, a multidisciplinary approach involving special expertise and training may increase the chances of accurate diagnosis (Institute of Medicine, 2010).

Surgical interventions for managing congenital heart anomalies have been popular since the mid-1990s. However, advances in this care have not been widely accepted until recently. These include the development of catheter heart placement and staged palliation for hypoplastic left heart syndrome. Drug regimens developed recently also provide care options for physiological complications, including pulmonary hypertension, arrhythmia, and heart failure.

Since studies on the clinical importance of heart failure began in the early 1980s, experts have proposed multiple clinical classifications based on factors such as disease severity, pathophysiology, clinical presentation complications, and disease progression. The New York Heart Association's functional classification system is based on symptom severity. The American College of Cardiology (ACC) classification on disease progression stages from A to D (Heidenreich et al., 2022). These classifications include:

• Stage A - Patients at risk of developing heart failure
• Stage B - Patients with a structural defect but asymptomatic
• Stage C - Patients with heart failure and symptomatic
• Stage D - Patients with advanced heart failure

Although these clinical classifications provide a simple categorization of patients, they are not exactly considered for practical purposes. Heart failure is widely discussed based on left ventricular ejection fraction (LVEF) for functional and practical purposes. The LVEF below 40% is termed 'heart failure with reduced ejection fraction' or HFrEF. If the LVEF is greater than 40%, it is termed 'heart failure with mildly reduced ejection fraction.' On the other hand, patients with an LVEF greater than 50% are considered to have 'heart failure with preserved ejection fraction.' These criteria are the results of discrete LVEF considered as cut-off points used as selection criteria in clinical trials and studies evaluating the clinical efficacy of drug candidates and surgical procedures in managing heart failure (Yancy et al., 2017).

In itself, heart failure is not considered a diagnosis but a syndrome with multiple clinical presentations. Presenting symptoms relate to significant reductions in cardiac output and elevated filling pressures. In many cases, symptoms presented by patients are non-specific, and reduced ejection fraction is only identified on acute admission to the hospital. Clinically presenting with reduced ejection fraction is often considered the ultimate stage in a long process involving chronic pressure overload of the left ventricle accompanied by subacute decompensation on a background of chronic cardiovascular impairments.

Physical examination of patients presenting with heart failure requires a comprehensive assessment. Generally, the most commonly reported symptoms include shortness of breath related to positional changes (orthopnea) or exertion. Other commonly reported symptoms include fatigue, anorexia, palpitation, recurrent cough, and chest pain. The general appearance of patients with chronic heart failure may also include anxiety, diaphoresis, and malnutrition. In acute decompensated heart failure, wheezing may be noticed. In advanced stages of pulmonary congestion, frothy and blood-stained sputum may also be present.

A jugular venous extension has also been reported in a few patients, including cases of paradoxical increase in jugular venous distention with respiration (Kussmal sign). On examination of cardiac signs, S3 gallop, pulsus alternans, and accentuation of P2 may be noticed. Mitral and tricuspid regurgitation have been reported to be present in cases of decompensated dilated cardiomyopathy. If there are enough physical signs to suspect heart failure, serum B-type natriuretic peptide (BNP) or N-terminal component (NT-proBNP) should be measured as definitive diagnostic examinations. Although highly sensitive, these markers are poorly specific for heart failure (Haydock & Flett, 2022).

The National Institute for Health and Care Excellence (NICE) published a detailed illustration of the steps for chronic heart failure diagnosis in 2020 (Haydock & Flett, 2022).

NICE Guideline for the Diagnosis of Suspected Heart Failure. Adapted from the National Institute for Health and Care Excellence (2018)

The overactivation of the neuronal axis, particularly the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), is implicated in the development of HFrEF. In the early stages of heart failure, this adaptive feature is required to maintain the overall contractile processes of the heart and becomes maladaptive. These include the Frank-Starling mechanism, changes in myocyte regeneration, myocardial hypertrophy, and myocardial hypercontractility (Kemp & Conte, 2012). The myocardium attempts to compensate in the face of increased wall stress by initiating eccentric remodeling, further worsening the loading condition and wall stress. A resultant decrease in cardiac output activates the RAAS, ultimately leading to salt and water retention and increased vasoconstriction (Kimeu et al., 2023).

Generally, the goal of therapy for chronic heart failure is the improvement of symptom profile and an overall decrease in mortality score. These goals have been observed to decrease the frequency of hospitalization and significantly improve the quality of life. Patients with a diagnostic classification of HFrEF should be placed on a disease management plan. Loop diuretics are considered first-line treatment agents in the management of heart failure. In cases of renal comorbidities, high doses or IV administration of diuretics may be considered. In cases of symptom improvement by other therapies, the dose of administered diuretic may need to be reduced.

It is commonplace to find literature on hypertensive crisis in CVDs described under separate headings, including hypertensive urgency, acute severe hypertension, hypertensive crisis, and malignant hypertension. In an attempt to consolidate treatment models and monitoring frameworks, these terms help clinicians distinguish clinical presentations and accurately categorize patients.

On presenting with elevated blood pressure with or without clinical evidence of end-organ damage, patients are expected to undergo a detailed medical assessment. Clinicians are expected to document and analyze information covering medical, physical, and family history, including a complete review of available medical and family records of diseases. In patients with comorbidities, a complete review of medications and history of adherence may guide the clinician in drug choice and drug use counseling. Special attention should be placed on the patient's use of recreational drugs, including cocaine, morphine, and other stimulants; herbal formulations, including St John's wort and licorice; and over-the-counter medications, including non-steroidal anti-inflammatory drugs (NSAIDs) and oral contraceptives.

A complete review of systems may help clinicians understand the extent of lifestyle choices and medication use on patients' vitals, including the review of ongoing symptoms and patients' accounts of symptom manifestation. Accurate diagnosis should commence with measuring blood pressure in both arms and observing peripheral pulsation. An observation of retinal changes is recommended in patients presenting with a likely diagnosis of malignant hypertension and severely elevated blood pressure. In women of childbearing age, it is important to consider the possibility of pregnancy and specifically exclude this before determining drug choices. The assessment of progressive end-organ damage should be considered in patients with multiple cardiovascular risk factors, including the laboratory assessment of renal function, electrolyte balance, glucose level, full blood count, and clotting factor.

Imaging can also be considered in patients with clinical presentation suggestive of neurological impairments. MRI scans and CT may be helpful for the diagnosis of malignant hypertension by providing clinical evidence for stroke or a lesion within the central nervous system. Renovascular lesions may also be examined with renal imaging, particularly in patients presenting with elevated creatinine levels.

The aim of therapy in the management of hypertension and hypertensive emergencies, as defined by the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) and AHA/ACC guidelines, is to initiate oral antihypertensive medications while monitoring for any clinical presentations as the patient responds to therapy. In modern practice, guidelines in the management of blood pressure are now pathophysiology-based, with therapy options selected based on comorbidities present and the severity of end-organ damage.

In uncomplicated acute severe hypertension, NICE guidelines recommend a same-day assessment for patients presenting with a blood pressure of equal or higher than 180/120 mmHg and clinical features suggesting acute end organ damage. NICE also recommends a repeat blood pressure measurement within a week for patients presenting with severe hypertension without evidence of end-organ damage. While assessing for signs suggestive of end-organ damage, clinicians are advised to identify and address confounding factors such as pain and distress, particularly in patients presenting to the emergency department for the first time on account of elevated blood pressure. Directly observed therapies (DOT) and biochemical testing may be initiated in cases of suspected non-adherence. Blood pressure lowering should be targeted over days to weeks rather than hours, with preference given to oral therapy over IV medication.

In uncomplicated malignant hypertension, oral therapies are the first choice of management except in cases of progressive end organ damage or evident emergency comorbidities. Oral therapies have been demonstrated to gradually reduce mean arterial blood pressure without the risk of a sudden decline in pressure or complications of the renal, cerebral, and myocardial framework. Continued blood pressure monitoring over the first few hours of presentation is considered beneficial to ensure strategic lowering of blood pressure. The recommendations on the choice of first-line medications for malignant hypertension are not definitive. However, clinicians may consider calcium channel blockers, such as amlodipine or long-acting nifedipine formulations. Calcium channel blockers like amlodipine take longer to achieve steady-state concentration, leading to a longer time to achieve the desired blood pressure-lowering effect (Kulkarni et al., 2023).

Clinicians are advised to avoid prescribing repeat doses of these medications within a few hours unless there is clinical evidence suggesting ongoing end-of-organ damage. Atenolol and other beta-blockers may also be considered if there is little or no evidence of cardiovascular complications, including pheochromocytoma. These medications may be switched to first-line agents if clinical evidence suggests end-organ damage. Alpha-blockers such as doxazosin may also be considered in some patients.

The most widely regarded submission and guidelines on managing cardiac arrhythmia in modern medicine are based largely on the Vaughan-Williams classification system. This system broadly classifies antiarrhythmic drugs commonly used today based on ionic channel involvement and physiological effects on sinus node function, action potential, and AV conduction.

Class I medications are sodium channel blockers. Lidocaine, quinidine, and flecainide trigger a series of ion exchanges, ultimately resulting in the blockade of the sodium channels. They block the rapid inward sodium current, causing cardiac depolarization and conduction and repolarization prolongation. On automaticity, class I drugs reportedly affect action potential and refractory period duration (Larson et al., 2022). Class II medications (beta-blockers) blunt sympathetic activity and reduce the rate of initial depolarization of the action potential. In effect, this action mitigates automaticity and negates conduction velocity. Clinical submissions on the beneficial effects of beta-blockers in arrhythmia have linked these drugs to a significant reduction in the risk of sudden cardiac death (Al-Gobari et al., 2013). Class II medications are also generally considered in hybrid therapy options, combining pharmacotherapy with implantable cardiac defibrillators (Puljević et al., 2014).

Class III medications block the delayed rectifier potassium channel, leading to prolonged repolarization. Amiodarone is widely considered the flagship member of this class with its wide usage in the many studies on its pharmacological effects. It inhibits the calcium and sodium channels in the SA and AV nodes and Purkinje's fibers, prolonging the action potential duration and effective refractory period (Baquero et al., 2011). Calcium channel blockers (class IV medications) inhibit calcium reentry in the SA and AV nodes. The range of action these agents have on the cardiovascular systems is still the subject of many clinical studies today. These medications have also been reported to decrease diastolic depolarization, activity potential inclination, and sufficiency by blocking the calcium channels. They are considered drugs of choice in the management of violent supraventricular tachycardia and atrial fibrillation typical sinus rhythm (Wolff-Parkinson-White Disorder).

Other antiarrhythmic drugs in the Vaughan-William classification, such as adenosine and atropine, act by variable mechanisms. Adenosine particularly acts on specialized conduction tissues in the AV and SA nodes, reducing automaticity in a series of actions that culminate in the reduction of repetitive and paroxysmal monomorphic ventricular tachycardia (Lerman et al., 2014). Digoxin acts by inhibiting the sodium–potassium pump (Na+/K+ ATPase) by raising intracellular calcium levels and enhancing contractility by increasing vagal tone at the level of the AV node. Both actions affect physiological and mechanical changes, lowering conduction velocity and increasing the effective refractory period (Larson et al., 2022). In modern medicine, the use of digoxin in active cardiac emergency cases has been limited to advanced heart failure and refractory atrial fibrillation due to the associated risk of arrhythmia-related mortality linked to its use.

Logically, preventing ACS episodes rather than treating them would be beneficial. However, no definite imaging or laboratory modalities exist to accurately monitor potential plaque ruptures or predict the timing of a rupture. Risk factor identification and modification, proper patient evaluation, and the optimal management of CAD are considered the best approaches in evaluating and monitoring patients at risk of ACS. Differentiating between STEMI, NSTEMI, and unstable angina is considered an important aspect of ACS evaluation. The AHA guideline prescribes an ECG within 10 minutes of presentation for patients presenting to the emergency department with complaints suggestive of ACS (Zègre-Hemsey et al., 2019).

If STEMI is eventually confirmed, the cath lab should be immediately activated. The biological role of cardiac enzymes such as troponin makes them important biomarkers in assessing NSTEMI and myocardial infarction cases. Chest X-ray imaging may provide useful clinical information in diagnosing causes other than myocardial infarction in patients with a primary complaint of chest pain suggestive of pneumothorax and pneumonia. Blood work such as complete blood count and liver function tests can also help clinicians accurately evaluate patients presenting with chest pain patterns consistent with intraabdominal pathology. Based on multiple analysis reports of confirmed ACS diagnosis, chest pain is considered the most classic symptom presentation in patients at a high risk of ACS.

Often described as 'crushing or pressure-like,' ACS-related chest pain, as described in multiple clinical studies, radiates to the jaw and left arm. In many cases, chest complaints are often complicated with other symptoms, such as breathing difficulties, epigastric pain, nausea, dizziness, diaphoresis, and general body weakness. Females, patients with multiple comorbidities, and aging adults may present with other vague symptoms that might complicate the accurate evaluation of ACS. Physical examination may reveal general distress and suboptimal heart sounds (galop and murmurs), although heart sounds may be perfectly normal in many cases. Lung examination may be normal, or crackles suggestive of congestive heart failure (CHF) may be heard. In cases of CHF complications, bilateral leg edema may be present.

In all its presentations, the underlying pathophysiology of ACS is the reduction in flow rate to parts of the heart musculature secondary to plaque rupture and formation of thrombus. Vasospasms with or without atherosclerosis may also be implicated in ACS. In atherosclerosis, the multiplication of smooth muscles within fatty streaks creates complicated plaques. With the progression of coronary plaques, arteries narrow until blood flow is significantly impeded, and ACS results. New reports from ACS studies in animal models have described the auto-immune-mediated inflammatory stage of atherosclerosis as another trigger of plaque formation. In these models, cells of the medium-sized and large arteries, including leukocytes, smooth muscle cells, and endothelial cells, are impaired by systemic immune-mediated inflammation. The occurrence plays an important role in mediating all stages of atherosclerosis, from initiation to plaque formation and rupture stages, as described in ACS.

The exposure of the endothelium to thrombogenic substances, including platelets and clotting factors, has also been linked to the formation of thrombus preceding the impedance of blood flow in large and medium-sized vessels (Anderson & Morrow, 2017). Platelet binding on the exposed endothelial surface occurs via glycoprotein (GP) IIb/IIIa receptors on the platelet membrane, linking other platelets to other activated platelets with fibrinogen. In the same vein, activated monocytes release metalloproteinases and tissue factors interacting with the vulnerable plaque. These series of activation and cross-linkages activate the clotting cascade that eventually leads to thrombus formation. In partially occluded vessels, unstable angina or NSTEMI may occur. STEMI is mostly linked with complete occlusion of the vessels. In animal models of ACS and clinical studies, it appears the degree of occlusion and timing of presentation directly dictates the severity of myocardial damage (Anderson & Morrow, 2017).

In August 2023, the ESC released the current reference treatment guideline for managing ACS. Developed by the task force on the management of ACS of the ESC, this guideline exhaustively described recommendations for pre-clinical care and emergency care for patients with complaints consistent with an ongoing myocardial infarction and unstable angina.