A client on an ecg monitor begins having dysrhythmias. which electrolyte imbalances are a concern

Perspective

Arrhythmias may have little meaning if they have no prognostic significance, do not alter hemodynamics or cardiac function, and are not symptomatic. Routine screening of an asymptomatic patient is not recommended. Patients typically seek medical care for palpitations, for an arrhythmia associated with symptoms, a symptom thought due to an arrhythmia, or nonspecific symptoms that may be due to an arrhythmia. Occasionally, an asymptomatic patient is found to have an arrhythmia by an ECG, an ambulatory monitor, an exercise test, or a hospital monitor (placed for no specific reason). Arrhythmias such as ventricular premature beats and atrial fibrillation are so common that it is impractical, and unnecessary, to refer every arrhythmia to the attention of a specialist. Alternatively, with major advances in the management of several cardiac arrhythmias (using ablation and implantable devices), identifying the patient who requires such an intervention can markedly improve the outcome.

Incidence and Prevalence

Cardiac arrhythmias are relatively common in the general population; and their prevalence increases with age. They occur more frequently in elderly persons, people with a long history of smoking, patients with underlying ischemic heart disease, and patients taking certain drugs or have various systemic diseases.4 In the United States, arrhythmias are present in 12.6% of people older than 65 years of age,5 with a rate of 13.6 per 100,000 reported for the general population.6 Arrhythmias directly account for more than 36,000 deaths annually and constitute the underlying or contributing cause in almost 460,000 cases.7 The most common type of persistent arrhythmia is atrial fibrillation (AF), which affects approximately 2.6 million people.7

Little and associates8,9 found the prevalence of cardiac arrhythmias in a large population of more than 10,000 general dentistry patients to be 17.2%, and more than 4% of those were serious, potentially life-threatening cardiac arrhythmias. In two similar studies performed in health care settings, a prevalence of 15% for arrhythmias, with 1.7% to 4% considered as potentially serious, has been reported.10,11 To manage their arrhythmias, more than 500,000 people in North America have implanted pacemakers.12

General Information

Arrhythmias are abnormalities in the rate, rhythm, or both of the heartbeat. These abnormalities occur with increasing frequency as one ages. Under normal circumstances, the heartbeat is regular in its timing, and the heart rate falls into somewhat narrow limits of numbers of heartbeats per minute. The heart rate increases with exercise.

The development of abnormal rates or rhythms has many causes. Some of these causes are primary, and others are secondary. Primary causes are those that occur within the heart. Secondary causes are those that result from external forces that act on the heart indirectly to cause a change in its rate or rhythm. It is important for your physician to separate primary from secondary causes to be able to select the most appropriate form of therapy. If the arrhythmia is secondary, it is better to treat the underlying cause than simply to try to normalize the heart rhythm with drugs and ignore what has caused the change in the first place.

Some arrhythmias pose no threat to your health. Others have great implications for the development of more serious problems. Careful evaluation to figure out the cause of the arrhythmia also permits your physician to learn the significance of the arrhythmia. The identification of the occurrence of an arrhythmia is not a dire finding, but it is an indication for further investigation.

Ordinarily, we have no perception of our own heartbeat. Irregular heart rates can come to our awareness. Single extra heartbeats may feel like “the heart turning over.” Many people also notice a “racing heart” when the rate is inappropriately fast. Nonetheless, many arrhythmias occur without symptoms specific enough to alert the patient that there is abnormal heart action.

Introduction

Arrhythmias (dysrhythmias) are disorders of the electrical properties of the heart. Two major types of disorders can occur, an abnormality in the generation of an electrical impulse (abnormality in automaticity) or an abnormality in impulse conduction after generation of the impulse (abnormality in propagation). From another perspective, arrhythmias can be divided into bradyarrhythmias (slow arrhythmias) and tachyarrhythmias (rapid arrhythmias). From still another perspective, arrhythmias can be classified based on anatomical site of origin, i.e., atrial, atrioventricular (AV) junctional, or ventricular (occurring below the bifurcation of the bundle of His) (Sponner and Rosen (2001), Zipes et al (2005).

As plasma membrane ion channel activity is the basis for the electrophysiological properties of the heart, drugs (and other modalities) used in treating arrhythmias have direct or indirect effects on ion channels. Integrated activity of several ion channels is responsible for action potentials of cells and therefore changes in ion channel activity can lead to alterations in (1) automaticity (the ability to spontaneously generate an action potential), (2) duration of the entire action potential, or (3) length of the refractory period of the cell. As the coordinated efforts of all cells make up the overall electrical activity of the heart, the summation of action potentials from all cells of the heart is responsible for the overall normal or abnormal cardiac rhythm. Ultimately, the pump function of the heart depends on this coordinated electrical activity.

Disorders of cell ion channel activity can occur through such events as ischemia, congestive heart failure, drug therapy, fibrosis and scarring, or imbalance between sympathetic and parasympathetic nerve stimulation of the heart.

Introduction

Arrhythmias, or abnormal heart rhythms, remain a major cause of morbidity and mortality in the United States (Goldberger et al., 2011). Arrhythmias are categorized as slow (bradyarrhythmias) versus fast (tachyarrhythmias), and as originating in the atria or nodes (supraventricular) versus ventricles or lower conduction system (ventricular). Bradyarrhythmias, including sinus node disease and heart block, lead to more than a hundred thousand pacemaker implants in the United States and approximately half a million worldwide each year (Brunner et al., 2004). Atrial fibrillation, an irregularly irregular supraventricular tachyarrhythmia, affects over two million people in the United States, often requires systemic anticoagulation due to the increased risk of stroke, and usually requires pharmacological therapy or invasive procedures to either control the ventricular rate or maintain sinus rhythm (Kannel and Benjamin, 2008). Ventricular tachyarrhythmias, including ventricular tachycardia and ventricular fibrillation, lead to sudden cardiac death (SCD), defined as death from cardiac causes within an hour of symptom onset. Between 200,000 and 450,000 people annually die from SCD in the United States; this exceeds the mortality of all cancers combined (Goldberger et al., 2011; Smith and Cain, 2006). Pharmacological therapies do not effectively prevent SCD in those at high risk (Echt et al., 1991). Implantable cardioverter defibrillators (ICDs) are effective, but their use is associated with procedural complications, limited battery life, infections, premature device and lead failure, inappropriate shocks, limitations to quality of life, and cost (Tung et al., 2008). In addition, many ICDs must be placed to prevent one sudden death, and most sudden deaths occur in individuals not identified as being at high risk (Myerburg et al., 2009).

Mutations in the genes that control cardiac electrical activity cause inherited arrhythmia syndromes such as long-QT syndrome and Brugada syndrome, and are characterized by both atrial and ventricular arrhythmias (Priori, 2010; Priori and Napolitano, 2004). While rare, they have led to research that has greatly enhanced our understanding of arrhythmia mechanisms. Mutations in structural heart genes cause inherited cardiomyopathies such as arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and familial dilated cardiomyopathy, and are also associated with arrhythmias and sudden death (Elliott et al., 2000). The vast majority of atrial and ventricular arrhythmias, however, occur in the setting of structural heart disease that results from coronary artery disease with myocardial ischemia or infarction, viral infections leading to cardiomyopathy, valve disease, hypertension, endocrine and metabolic disorders, and the use of substances toxic to the myocardium (Goldberger et al., 2011; Myerburg, 2002; Smith and Cain, 2006). While these do not have a simple genetic etiology, the prognosis and response of these disorders to therapy is likely influenced by genomic factors.

For patients with either inherited syndromes or structural heart disease, clinical predictors of the onset and/or severity of arrhythmias have been disappointing (Spooner, 2009). Similarly, the response to pharmacological and device therapy is variable and often unpredictable. In this chapter, we will discuss the development and use of personalized and genomic predictors to define the population at risk for arrhythmias and the efficacy of potential therapies. We will begin with inherited arrhythmia syndromes and proceed to the more complex arrhythmias associated with structural heart disease. Finally, we will summarize the current state of clinical genetic testing.

Summary in the Context of Patient Perspectives for Personalizing Medicine

The treatment of arrhythmia has been a controversial subject for many years. The 2006 and 2011 ACC/AHA/ESC guidelines have helped health practitioners evaluate and manage treatments. Currently, there is no section which considers Chinese medicine as a possible non-pharmaceutical treatment for any type of arrhythmia.

Current studies present novel methods for determining the cause and course of arrhythmia at the genetic level. Some studies conclude that general results are fit for guiding the treatments for all, while others point out specific cultural and racial differences on the genetic level which complicate generalizations. Integrative cardiovascular Chinese medicine focuses more on prevention, which mostly means attempting to provide early solutions which may help to delay or divert away from more aggressive forms of therapy if possible.

CONCLUSIONS

The intensivist must have a keen awareness of patterns, mechanisms, precipitants, and treatment of cardiac arrhythmias. The intensivist must remember that all antiarrhythmic therapies (pharmacologic and nonpharmacologic) have the potential for adverse effects. Reducing and eliminating arrhythmia precipitants may be safer and more effective than dramatic interventions. Antiarrhythmic drugs should be chosen carefully and the patient monitored closely. Direct current cardioversion should be used aggressively when the situation is emergent, cautiously when elective, and eschewed when futile. Ablation is effective therapy for most supraventricular tachycardias, idiopathic ventricular tachycardia, and bundle branch reentry and may be used as adjuvant therapy for patients with frequent appropriate ICD shocks. ICDs are the therapy of choice for primary and secondary prevention in patients with structural heart disease. Consultation with a cardiac electrophysiologist should be considered a routine part of the critical care physician's armamentarium.

KEY POINTS

Intensivists managing arrhythmias must have expertise in electrocardiography, pharmacokinetics, pharmacodynamics, and bedside clinical acumen.

All antiarrhythmic therapies (pharmacologic and nonpharmacologic) have the potential for adverse effects.

Patients in an intensive care setting frequently have active arrhythmia precipitants. They include hypoxemia, excess circulating catecholamines, congestive heart failure, fever (sepsis), pulmonary emboli, electrolyte, and other metabolic disturbances. Reducing or eliminating arrhythmia precipitants may be safer and more effective than dramatic antiarrhythmic interventions.

Direct current cardioversion of tachyarrhythmias should be used aggressively when emergent (angina pectoris, congestive heart failure, hypotension), cautiously when elective, and eschewed when futile. The critical care physician must carefully weigh the risks and benefits of direct current cardioversion for each patient.

Left ventricular dysfunction is the most important predictor of cardiac mortality in patients with ventricular arrhythmias. Long-term management of sustained ventricular arrhythmias in the setting of structural heart disease is usually best accomplished with an implantable cardioverter-defibrillator.

Diagnosis and management of complex arrhythmias may be facilitated by consultation with a cardiac electrophysiologist.

Ablation of cardiac arrhythmias often is now first-line elective therapy for most supraventricular tachycardias and some ventricular tachycardias.

Data and electrograms stored in permanent pacemakers and ICDs can easily be assessed to help the intensivist determine the patient's past history and the frequency, rate, and duration of arrhythmias.

Antiarrhythmic drugs can raise pacing and defibrillator thresholds and change supraventricular tachycardia and supraventricular tachycardia rates, necessitating device reprogramming

Nonsustained Ventricular Tachycardia

Nonsustained ventricular tachycardia is a common arrhythmia and although of prognostic importance when linked to heart disease, management is empiric rather than of proven advantage. As a rule, it reflects transient electrolyte disturbance, especially hypokalemia, in the immediate postoperative period. When nonsustained ventricular tachycardia persists after potassium repletion, patients should be examined for evidence of ventricular dysfunction, myocardial infarction, and acute ischemia. Persistent arrhythmias in patients with ejection fractions less than 40% and coronary artery disease are indications for an electrophysiologic study, looking for inducible sustained ventricular tachycardia.28 Patients with inducible sustained ventricular tachycardia are candidates for implantable cardioverter-defibrillators.

6.3 Personalization of therapy

For certain (inherited) arrhythmia syndromes, an increased understanding of underlying mechanisms has paved the way for more effective tailored antiarrhythmic therapies. Examples include the use of flecainide for CPVT based on its combined Na+-channel and RyR2-stabilizing effects, Class I drugs with high affinity for INa,late for patients with long-QT syndrome type-3, and quinidine for Brugada syndrome and idiopathic VF (Thomas et al., 2019; Kryshtal et al., 2021). Conversely, for complex acquired arrhythmias such as AF, the choice of AAD is at present largely determined by safety concerns or practical considerations (e.g., differences in approval or availability of oral formulations). Of note, considerable deviation from guideline recommendations has been reported for AAD use in AF patients (Chiang et al., 2013; Field et al., 2021), which may negatively affect antiarrhythmic efficacy and patient outcomes. Accumulating data suggest that AAD therapy can be tailored, e.g., based on clinical characteristics, to improve therapeutic efficacy. For example, non-recommended use of β-blockers in patients with vagal AF is associated with AF progression (De Vos et al., 2008). Similarly, Class I AADs appear to be less effective in obesity-related AF (Ornelas-Loredo et al., 2020). Pharmacogenetic information may also help to guide the choice of AADs. For example, the presence of genetic variants at chromosome 4q25 (near PITX2), might help to decide between Class I and Class III AADs, at least in the absence of strong acquired AF-promoting risk factors such as obstructive sleep apnea (Goyal et al., 2014). Similarly, the therapeutic effect size of the β-blocker bucindolol against new-onset AF in HF patients may depend on the presence of polymorphisms in β1 and α2c-adrenoceptors, as well as the duration of AF and HF (Piccini et al., 2019). In general, several preclinical studies have identified specific cellular and molecular mechanisms involved in different types of AF (e.g., paroxysmal, long-standing persistent or post-operative AF) (Heijman et al., 2014b, 2020), as well as revealing distinct components of proarrhythmic atrial remodeling by different AF-promoting risk factors such as HF, sleep apnea and obesity (Molina et al., 2018; Lebek et al., 2020; Scott et al., 2021). These insights may facilitate future risk factor-based tailoring of AAD therapy. Finally, there is a growing interest in true patient-specific therapy based on individual AF mechanisms, e.g., identified using detailed invasive or non-invasive electrical mapping, patient-specific induced pluripotent stem cell-derived cardiomyocytes, or personalized computer models based on cardiac magnetic resonance imaging (for structural properties) and electrocardiographic information (for functional properties) (Wu et al., 2019; Trayanova et al., 2020; Heijman et al., 2021c). In theory, such an approach would be expected to significantly improve rhythm control success, although targeted AF ablation based on patient-specific mapping information has so far not been able to systematically outperform standard pulmonary vein isolation (Cluckey et al., 2019). Similarly, initial proof-of-concept studies have shown that simulation-guided AF therapy (mainly focusing on catheter ablation) based on personalized computer models is feasible, but randomized clinical trials establishing that simulation-guided therapy is superior to routine clinical care are lacking (Heijman et al., 2021c). Moreover, given the number of patients with AF and the efforts involved in some of these mechanistic approaches to personalized AF therapy, a judicious selection of suitable patients and comprehensive cost-effectiveness studies will be required for the integration of these approaches in standard clinical care.

Class II: Propranolol, Nadolol, Atenolol, Esmolol

The mechanisms by which β blockade modifies cardiac arrhythmias are complex. The predominant effect is competitive inhibition of catecholamine binding at cardiac receptors, which reduces both normal and abnormal automaticity and slows AV node conduction. However, direct membrane effects may also occur, including prolonging the duration of the action potential and ERPs, as well as increasing the threshold for VF. These direct cellular actions are most pronounced during chronic administration of moderate to high doses.

Class II agents are used to treat a diverse spectrum of arrhythmias in children. They are often effective in catecholamine-mediated tachycardias from either abnormal automaticity or triggered activity at both the atrial and ventricular levels. They are less useful for reentry tachycardias but often prove effective if they suppress premature beats that serve as the initiating event for the reentry circuit. Additionally, some forms of reentry SVT may be effectively treated by β blockade if the AV node is a necessary part of the circuit and can be sufficiently slowed to prevent rapid conduction.

Propranolol is the prototype β blocker. It is nonselective and affects both B1 (cardiac) and B2 (bronchial and blood vessel) receptors. Propranolol is available for oral administration in both solution and tablet form. Important limitations include its B2 blockade properties, which can aggravate reactive airway disease, and its B1 blockade, which may further depress ventricular function in patients with poor contractility. Nadolol is likewise a nonselective β blocker that differs from propranolol in requiring less frequent dosing, as well having reduced penetration across the blood–brain barrier.

Atenolol is a cardioselective β blocker, although some cross-reactivity with B2 receptors can still occur at high doses. It has low central nervous system penetration and maintains effectiveness with oral administration only once or twice a day. For most arrhythmias that respond to propranolol, atenolol can be equally effective. There is one report suggesting lower efficacy with atenolol while treating long QT syndrome, although this experience has not been replicated in other studies. Esmolol is an intravenous B1 selective agent that is unique in its rapid onset and short duration of action, thus lending itself well to emergency management of arrhythmias.