Chronotropic Incompetence

Chronotropic incompetence (CI), the inability of the heart rate to increase appropriately in response to an increase in activity or metabolic demand,1,2 occurs because of altered balance between the sympathetic and parasympathetic branches of the autonomic nervous system.3,4 Chronotropic incompetence is common in various types of cardiac disease including sick sinus syndrome, atrioventricular (AV) block, coronary artery disease, and heart failure5,6 and is also seen in patients with no structural heart disease.7–9 Chronotropic incompetence first appeared in the literature in 1975 when a high rate of cardiac events was observed in those with a decreased heart rate (HR) response during treadmill exercise test.10Although often not recognized, CI is frequently present in heart failure, which is a common reason for hospital admission and a common comorbid condition in patients admitted for noncardiac reasons. Implantable cardiac devices may allow identification of CI in patients with heart failure.2 Chronotropic incompetence has prognostic significance and impacts functional status and quality of life. Diagnosis of CI should be considered in patients with heart failure who remain symptomatic despite therapy because there are potential treatments for CI.2 Currently, gaps exist in nursing knowledge regarding the clinical significance of CI. This column provides an overview of CI and includes a case example where nursing assessment led to diagnosis and treatment in a patient with CI.During exercise, cardiac output must increase to meet the demand for increased oxygen consumption (VO2) by either an increase in stroke volume or an increase in HR.11 An athlete can increase cardiac output up to 6-fold during intense exercise,11 and cardiac output and VO2 in healthy people increase by 4 times during maximal exercise.12,13 Stroke volume seldom exceeds 50% from its resting value, therefore HR is responsible for the largest contribution to increased cardiac output.11 Heart rate increases because of decreased vagal tone at the onset of exercise, followed by an increase in sympathetic tone.11,12 During maximal exercise, there is an approximate 2.2-fold increase in HR and only a 0.3-fold increase in stroke volume.13 An increase in HR during exercise is the most important contributor to a person’s ability to do physical work,1,3 and HR rate increase during work also determines quality of life.3Heart rate response to exercise was studied by Astrand, and the maximum heart rate was shown to decrease with age.14,15 This led to the creation of the formula for the age-predicted maximal heart rate (APMHR) during maximal exercise (220 − age).16 Because the formula was developed on the basis of studies of middle-aged men, some of whom had coronary artery disease and were on β-blocker therapy, there are limitations to it; the formula may overestimate maximum HR in younger persons and women and underestimate maximum HR in older persons.17,18 An alternative formula, 208 – 0.7 (age), has been proposed for APMHR, although this formula may still underpredict maximum expected HR in older adults.17 For patients with coronary artery disease who are taking β-blockers, the formula 164 − 0.7 (age) has been proposed.19 Sex does not affect maximum predicted HR during peak exercise.17People experience decreased β-adrenergic responsiveness with age, which is one reason for the decrease in maximal achievable HR in older adults.20 During exercise, older adults appear to produce similar catecholamine levels as younger adults, but they are less responsive to them.3 This decrease in maximal HR response to exercise is the most important change in cardiac function in the aging adult and results in an age-related decline in aerobic activity.21,22 Heart rate reserve (HRR) is the difference between resting and peak heart rate. Maximal HR, but not resting HR, decreases with age, resulting in a decrease in HRR.22Chronotropic incompetence is commonly diagnosed when the HR fails to meet an arbitrary percentage, commonly 80%, of the APMHR during a graded exercise test.2,3,11 Alternatively, failure to achieve > 80% of the HRR during exercise testing has also been used.3,11 Because HRR is affected by resting HR, the formula (change in HR from rest to peak divided by the difference between APMHR and resting HR × 100) is often used to calculate the adjusted HRR.2,11 For example, to achieve 80% of HRR, a 55-year-old male with a resting HR of 65 bpm would need to achieve a peak HR of 145. Heart rate reserve measures HR dynamics rather than a static peak HR during exercise. Heart rate reserve will be reduced in patients with a very high resting HR even if peak exercise HR is normal.2With either method of determination, it is essential that patients perform a true symptom-limited stress test. Patients should achieve > 18 on the Borg scale of perceived exertion, indicating that the level of activity is very hard.2,11 Respiratory gas analysis to determine the respiratory exchange ratio (VCO2 [carbon dioxide production]/VO2) is the most objective method of measuring peak exercise.2,3,11 A ratio of < 1.05 indicates a submaximal effort.2,11 Wilkoff and Miller23 developed a chronotropic index that adjusts for age, physical fitness, and resting HR for patients undergoing a submaximal stress test.No formulas are accurate in patients with atrial fibrillation, AV block, or sinoatrial node dysfunction, nor do any formulas account for medications that lower HR.3,11,12 Patients with atrial fibrillation have both higher resting and peak exercise HR24; this increase in HR may be compensatory for lack of atrial kick.25,26 Standard definitions of CI are not adequate in heart failure because patients with heart failure already have a mismatch between cardiac output and metabolic demand.2,12 A proposed formula for determining expected HR in patients with heart failure with reduced ejection fraction (HFrEF) is 119 + 0.5 (resting HR) − 0.5 (age) − either 0 (treadmill) or 5 (bike).27 Most studies have used the traditional formula for APMHR of 220 − age, so a cutoff value for other formulas is not known.2The prevalence of CI varies by patient population and is difficult to determine because of inconsistencies in definitions.11 In a study of patients with a permanent pacemaker, 40% had evidence of CI27; in patients with sick sinus syndrome, reported prevalence has ranged from 28% to 57%.28 Reported prevalence of CI in heart failure patients ranges from 25% to 70%.3 Witte et al29 reported that 43% of HF patients had CI when the criterion of < 80% of APMHR was used, compared with 72% when using < 80% of age-predicted HRR (APHRR).When 62% of APHRR was used for patients taking β-blockers, only 22% of heart failure patients met the criteria for CI.30 In one study, CI in patients with heart failure ranged from 24% in patients with a peak VO2 of > 20 mL/kg/min to 72% in patients with a peak VO2 of < 14 mL/kg/min.31 The prevalence of CI is similar in patients with heart failure with reduced and preserved ejection fraction and is 3 times the rate of persons with no heart disease.32 Chronotropic incompetence in atrial fibrillation secondary to inadequate conduction via the AV node may be as high as 60%.33Chronic overstimulation of the sympathetic nervous system in HFrEF leads to downregulation and decreased sensitivity of the β-1 receptors, with a 50% or more reduction in β-adrenergic receptor density and a weakened responsiveness to β-adrenergic stimuli.12,34,35 This downregulation and decreased sensitivity of the β-1 receptors is thought to be the primary mechanism of CI in patients with heart failure.34–36 Sinoatrial node remodeling has also been observed in patients with heart failure and may contribute to CI.37 As heart failure advances, exercise capacity decreases and CI increases.11 Chronotropic incompetence in heart failure is associated with decreased functional capacity and survival rates, although causation has not been proven.38,39 It has been proposed that CI may be the result of, rather than the cause of, reduced exercise capacity in patients with heart failure.2,12,40β-Blockers may produce a pharmacological-induced CI, which can mask intrinsic chronotropic disease.29 β-Blockers reduce HR at rest and during peak exercise by 16% to 25% in healthy patients41 but do not appear to have a significant impact on the rate of CI or be a major cause.8 Patients with heart failure on a β-blocker are more likely to have CI, although the percentage is reduced when the criterion of < 62% of APMHR is used.30 In several large studies, β-blocker therapy has been associated with CI in patients with heart failure,29,42,43 independent of dose.44 However, not all studies have confirmed this. In one study, there was no difference in peak VO2 between patients taking or not taking β-blocker therapy, nor was there a difference in the rate of CI between those taking a high versus a low dose of β-blocker therapy.44 However, those with CI on a β-blocker had a lower peak VO2 and worse heart failure functional class compared with those with no CI on a β-blocker.44 Another study showed patients with heart failure with and without CI to be equally likely to be on β-blocker therapy, with no difference in β-blocker dose between those with CI and those without.31 The cessation of β-blockers in patients with heart failure results in an increased peak heart rate but not the normalization of chronotropic response to exercise, giving support to the idea that impaired chronotropic response in heart failure is an intrinsic component of the disease.45 β-Blockers may lose their impact on CI as heart failure severity worsens.31Dyspnea and fatigue are hallmark manifestations of heart failure. The gold standard for assessment of functional capacity in heart failure is the cardiopulmonary exercise test with measurement of peak VO2.46 In patients with heart failure, there is a linear relationship between HR and peak VO2,46 with evidence of a further reduction in peak VO2 by 12% to 23% in patients with CI.29,31,38 Heart rate reserve is also reduced in heart failure because of a higher resting HR,47,48 and HRR correlates to peak oxygen consumption.32 Chronotropic incompetence is thought to be the major limiting factor in exercise capacity in patients with heart failure with reduced ejection fraction.3,35 Exertional dyspnea is the primary symptom of CI.12The relationship between CI and increased cardiovascular and all-cause mortality has been known for more than 40 years.49 Multiple studies have confirmed abnormal HR response to exercise as an independent risk for acute coronary events and mortality.50,51 The Framingham Offspring Study followed men for a mean of 7.7 years and found inability to achieve target HR and a lower chronotropic response index (implying the presence of CI) demonstrated risk for a higher incidence of all-cause mortality and coronary events; this risk persisted after adjustment for ST segment changes and other cardiovascular risk factors.52,53 An abnormal HR response during exercise is a greater predictor of cardiac events than ischemic ST segment depression on an electrocardiogram (ECG).54 Chronotropic incompetence in the presence of ischemia has a worse prognosis than ischemia alone.50,51,55 Chronotropic incompetence is a prognostic indicator for adverse events in patients with no heart disease,52 in patients with coronary artery disease,30 and in patients with heart failure.39 However, CI does not appear to be an independent predictor of survival in patients with heart failure.56,57 An increase in resting HR decreases HRR3 and is also associated with increased risk of cardiovascular and sudden death in healthy persons6 and in patients with known cardiovascular disease.58β-Blockers have the potential to interfere with an improvement in functional status through their impact on chronotropic response as well metabolic changes in skeletal muscle.59 However, there is evidence that β-blockers do not alter peak VO2 or exercise time.44 Patients with heart failure taking β-blockers have demonstrated the ability to exercise longer, with a decrease in exertional dyspnea.60 Although the presence of CI in heart failure is linked to poor outcomes, the reduced HR from β-blockers has a paradoxically positive effect on survival.2 The greater the resting HR reduction from β-blocker therapy in heart failure, the greater the mortality benefit.61 β-Blockers appear to reduce the hazard associated with CI. Hung et al43 showed that patients taking a β-blocker who reached 65% of APMHR had similar mortality risk as those not taking a β-blocker who reached 85% of APMHR. However, β-blockers have not demonstrated the same effect in patients with heart failure with preserved ejection fraction (HFpEF). In a study evaluating nebivolol in HFpEF, patients exhibited no improvement in exercise tolerance despite the favorable effects of the drug on diastolic dysfunction.62Ivabradine selectively inhibits the sinoatrial node,63 lowering HR without lowering blood pressure. One small study showed the beneficial effects of ivabradine combined with low-dose bisoprolol on chronotropic reserve.64 Another study showed ivabradine in combination with carvedilol improved exercise capacity and quality of life, whereas carvedilol alone did not achieve these outcomes.65 The impact of ivabradine on chronotropic response is uncertain.2Exercise training improves chronotropic function in healthy persons, decreasing resting HR, decreasing submaximal HR, and resulting in a more rapid decline in postexercise HR.66,67 Exercise training is the intervention that most consistently improves HR response to exercise68 in patients with HFrEF, increasing peak exercise HR by 5% to 10% while contributing to increased cardiac output and peak VO2.66,67 Several studies have demonstrated that exercise training in patients with HFrEF increases peak exercise HR, contributing to increased cardiac output and peak VO2.66 Exercise positively affects neurohormonal activation and autonomic balance,68,69 decreases sympathetic drive, increases vagal stimulation, improves baroreceptor sensitivity, and improves HR variability.8 Exercise training also improves exercise tolerance and quality of life.68Rate-adaptive pacing is another potential strategy to improve CI and has been demonstrated to enhance functional capacity in various patient groups with CI.70 The goal of rate-adaptive pacing is improved HR response to exercise and increased metabolic demand.68 Less information is known about rate adaptive pacing in heart failure.3 There is some evidence that patients with HFrEF and severe CI may benefit from rate-adaptive pacing.71 In one study of patients with CI with an implantable cardiac resynchronization device, rate-adaptive pacing with dual chamber rate adaptive (DDDR) mode was associated with increased peak exercise HR, increased exercise time, and peak VO2.71 However, rate-adaptive pacing has not been proven beneficial in all patients with HFrEF and CI.72 Although up to 30% of patients with HFpEF have CI, less is known about the benefit of rate-adaptive pacing in this patient population.44,48,71 With any rate-adaptive pacing strategy, it is important to consider the difference between atrial and ventricular pacing. Atrial pacing allows maintenance of normal ventricular synchrony, whereas right ventricular pacing results in ventricular dyssynchrony.72 Consistent right ventricular pacing is associated with an increase in adverse events.73 Patient selection is important when considering rate-adaptive pacing as a strategy for treating CI.2 Most current studies are evaluating the effect of rate-adaptive pacing on exercise capacity in patients with heart failure.2A 66-year-old previously healthy and active woman presented to her primary care physician with reports of progressive dyspnea, orthopnea, fatigue, and lower extremity edema. An echo-cardiogram demonstrated severe mitral regurgitation. Following further testing, she underwent a mitral valve repair that was complicated with surgical re-exploration and hematoma extraction, postoperative bilateral thoracentesis, development of atrial fibrillation, and a reduction in left ventricular ejection fraction (LVEF) from 55% to 60% preoperatively to 25% to 30% postoperatively. Approximately 6 weeks after the initial surgery, she developed profound heart failure. Reevaluation demonstrated a failed mitral valve repair and endocarditis. She underwent repeat surgery with mitral valve replacement. Four months after the first surgery, she had an improvement in her LVEF to 45% to 50% and was beginning to feel hopeful that she might get back to her preoperative state.Approximately 5 months after her initial surgery, the patient began feeling fatigued and noted a new cough. Physical examination did not demonstrate any evidence of heart failure. However, due to the complexity of her case, a full evaluation of the prosthetic valve was completed with no evidence of prosthetic valve failure or endocarditis. It was noted during one visit at the heart failure clinic that her recorded vital signs at home included heart rates below 50 bpm. An ECG demonstrated sinus bradycardia with no ectopy or irregularity. Her β-blocker was decreased, and she was instructed not to take the β-blocker for heart rates less than 50 bpm. She continued to decline despite full recovery of her LVEF to 55% to 60%. Pulmonary evaluation demonstrated moderate restrictive lung disease thought to be secondary to her multiple surgical procedures. The β-blocker was ultimately stopped because of lack of resolution of bradycardia. She reported continued fatigue and extreme shortness of breath with any activity but was comfortable at rest. Her husband described her as “a limp rag doll.” Off β-blockers, she continued to have heart rates below 60 bpm with activity. During a session of outpatient cardiac rehabilitation, she was found to have profound shortness of breath with minimal activity; because of the patient’s symptoms and continued inappropriate HR response to activity, the nurse in cardiac rehabilitation notified her cardiologist and she was admitted to the cardiac care unit (CCU) for symptomatic heart failure.The patient was treated with intravenous diuretics for 24 hours with no improvement in symptoms with exertion. During the patient’s CCU stay, the nurse practitioner providing continuity care in the heart failure clinic observed persistence of symptoms and inappropriate HR response during the documentation of attempted phase I cardiac rehabilitation sessions. No other abnormalities were found during the diagnostic workup. When the patient was discharged, the nurse practitioner ordered an ambulatory monitor to evaluate the HR, cardiac rhythm, and symptoms during the patient’s activities of daily living. The results of ambulatory monitoring revealed an average resting HR of 52, with a maximum achieved HR with activity of 70 bpm. Electrophysiology was consulted, and a DDDR pacemaker was implanted. Post-implantation device interrogation revealed consistent rate-adaptive atrial pacing; the patient experienced complete resolution of symptoms of fatigue and shortness of breath. She was able to return to and complete phase II cardiac rehabilitation, during which objective evidence in improvement in functional capacity was observed to be consistent with subjective improvement.Chronotropic incompetence is common in various types of heart disease, has prognostic significance, reduces functional capacity, and decreases quality of life. However, patients are not routinely evaluated for CI in clinical practice. Nurses should consider CI especially in heart failure patients who continue to have symptoms of activity intolerance despite optimal medical management. Although formal stress testing may not be performed during a hospitalization, nurses have an opportunity to evaluate HR response to activity when performing phase I cardiac rehabilitation or progressive mobility. Additionally, implantable devices in heart failure patients should be interrogated to determine if there is an identifiable contributing cause to the patient’s symptoms. Device interrogation may identify arrhythmia, inappropriate or inadequate pacing, or evidence of CI. The results of nursing advocacy when CI is suspected can lead to appropriate diagnostics and subsequent potential treatment.