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Pulmonary, Critical Care, and Sleep Pearls |

A 43-Year-Old Man With Daytime Sleepiness and a Heart Murmur FREE TO VIEW

Christian M. Horvath, MD; Stephan Zbinden, MD; Sebastian R. Ott, MD; Anne-Kathrin Brill, MD
Author and Funding Information

aDepartment of Pulmonary Medicine, University Hospital and University of Bern, Bern, Switzerland

bDepartment of Cardiology, University Hospital and University of Bern, Bern, Switzerland

CORRESPONDENCE TO: Christian M. Horvath, MD, Department of Pulmonary Medicine, University Hospital and University of Bern, Freiburgstrasse 4, CH-3010 Bern, Switzerland


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(4):e117-e120. doi:10.1016/j.chest.2016.03.039
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Published online

A 43-year-old man was referred to our tertiary sleep center for the initiation of sleep apnea treatment. A prior diagnostic overnight polysomnography (Fig 1) had revealed an apnea-hypopnea index (AHI) of 22/h of sleep. The apneas were predominantly central (central AHI, 18.2/h; obstructive AHI, 3.8/h), more pronounced in the supine position (AHI supine, 36.6/h; AHI nonsupine, 11/h) and during non-rapid eye movement (non-REM) sleep (REM, 15.8/h; non-REM, 23.5/h). A continuous positive airway pressure (CPAP) trial in an outpatient setting had failed, as the fixed CPAP of 11 cm H2O was not tolerated by the patient because of a feeling of lightheadedness when wearing the mask. At referral, the patient complained about falling asleep in front of the computer in the afternoons despite regular bedtimes and 7 to 8 h of sleep per night. His Epworth Sleepiness Scale score was 11. He had no significant past history including cardiopulmonary disease. He was not taking any medication but had noticed a slow decline in general physical performance in the last year, with dyspnea (New York Heart Association class I) after running distances of 1 to 2 km. He had never experienced syncope. His family history was unremarkable.

Figures in this Article

The patient was afebrile; BMI, 26 kg/m2; neck circumference, 41 cm; Mallampati score, II to III. Vital signs were within normal limits. Physical examination revealed a grade 1 to 2 systolic murmur on the left lower sternal border with augmentation during inspiration. Pulmonary examination yielded unremarkable results.

Figure 1
Figure Jump LinkFigure 1 A 5-min polysomnographic recording during stage N1 and N1 non-rapid eye movement sleep shows a pattern of cyclic central apneas followed by hyperpneas (Hunter-Cheyne-Stokes respiration) with cycle lengths of 45 to 50 s causing oxygen desaturations.Grahic Jump Location

Laboratory tests, including hemogram, blood chemistry, thyroid-stimulating hormone, vitamins, and ferritin, produced normal results. Brain MRI did not show any abnormalities. Pulmonary function test results were normal, including diffusion capacity; the 6-min walking test result was within normal limits; and there were no signs of desaturation. A CT scan of the thorax showed normal lung parenchyma. The ECG revealed T-inversions (V1-V6) and an epsilon wave (Fig 2). Echocardiography (Fig 3, Video 1) showed a severely dilated right ventricle with impaired function, with a normal left ventricular ejection fraction of 60%. Cardiac MRI confirmed severe impaired right ventricle function (right ventricular ejection fraction, 22%) and showed pronounced late gadolinium enhancement (Fig 4).

Figure 2
Figure Jump LinkFigure 2 Electrocardiogram of V2 with an epsilon wave, T-wave inversions, and ventricular extrasystoles. The open headed arrows indicate epsilon waves.Grahic Jump Location
Figure 3
Figure Jump LinkFigure 3 Echocardiographic four-chamber view showing an enlarged right ventricle and right atrium. There are no hints of hypertrophic cardiac muscle. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.Grahic Jump Location
Figure 4
Figure Jump LinkFigure 4 Cardiac MRI showing enlarged right ventricle; the arrows indicate fibrosis of the right ventricle. See Figure 3 legend for expansion of abbreviations.Grahic Jump Location

What is the diagnosis?

Diagnosis: Arrhythmogenic right ventricular cardiomyopathy causing central sleep apnea

The diagnosis of arrhythmogenic right ventricular cardiomyopathy (AVRC) was made on the basis of the pathognomonic findings of the ECG (epsilon wave, T-inversions), the echocardiography, and the cardiac MRI. A task force revised the diagnostic criteria in 2010, combining diagnostic criteria from six categories. The patient fulfilled three major criteria (two ECG findings, right ventricular ejection fraction < 40%).

AVRC is a mainly autosomal dominant inherited genetic disorder with a variable course. The prevalence is estimated at 1:2,000 (ratio of prevalence among men and women, 2.5:1) with up to 50% of cases being familial. Most often AVRC is diagnosed in adolescence, but patients can be asymptomatic for a long time (into adulthood), as in this case. Pathophysiologically, it is thought that a loss of desmosomal integrity within the intercalated disk proteins of the myocytes affects gap junctions and sodium channels. Ventricular flutter or polymorphic ventricular tachycardia can already occur at this stage of the disease. In the course of the disease, a progressive loss of myocytes occurs followed by fibro-fatty replacement of the myocardium, which then leads to enlargement of the heart and loss of contractility.

Most patients with AVRC present with palpitations; dizziness; cardiac arrhythmias, mainly atrial or ventricular tachyarrhythmia with a left bundle branch block image; or aborted sudden cardiac death. Furthermore, ARVC can result in sudden cardiac death in younger and middle-aged adults. Physical examination is normal in about 50% of patients, but can reveal tricuspid regurgitation murmurs or a fixed splitting of S2, and signs of predominantly right heart failure.

Treatment options are limited to heart failure- and antiarrhythmic medical treatment, restriction of strenuous exercise, and implantation of a cardioverter defibrillator, but there is no curative treatment available. In selected cases heart transplantation can be an option.

Central sleep apnea (CSA) is not a typical initial manifestation of AVRC, but CSA is often related to congestive heart failure, neurologic disease, end-stage renal failure, or medication (eg, opioid analgesics). CSA is rarely idiopathic and therefore evaluation of underlying causes is strongly recommended in patients who do not have conditions that sufficiently explain the presence of central sleep apnea or Hunter-Cheyne-Stokes respiration. CSA in patients with congestive heart failure can be explained by a prolonged circulation time, low cardiac output, and stimulation of pulmonary J-receptors by pulmonary edema due to left heart failure. CSA is seen primarily in patients with left ventricular systolic heart failure and not isolated right ventricular heart failure, as in this patient, but has been described in patients with right heart failure due to primary pulmonary hypertension. In AVRC, the dilated right ventricle with severely impaired function can cause low-output cardiac failure with reduced pulmonary blood flow, thereby increasing circulation time. The dilated right ventricle can also impair left ventricular diastole function, due to interventricular interactions. Also, replacement of cardiac myocytes by fatty tissue can affect the left ventricle and thereby cause biventricular heart failure.

Treatment options for CSA in patients with heart failure focus on treatment of the underlying disease with improvement of cardiac function. Treatment with CPAP or adaptive servoventilation has been shown to be able to normalize sleep-disordered breathing, but there are minimal to no data on the treatment of obstructive or central sleep apnea in patients with AVRC. Problems with positive airway pressure can occur, if the acute reduction of the right ventricular preload by positive airway pressure reduces cardiac output. This may explain the dizziness and intolerance of CPAP in this patient. Adequately powered studies showing improved survival with CPAP or adaptive servoventilation are still missing. In fact, the SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servoventilation in Patients With Heart Failure) trial showed an increased risk for sudden cardiac events if CSA is corrected by adaptive servoventilation in patients with heart failure and a reduced left ventricular ejection fraction. Therefore, treatment of CSA in patients with heart failure has become more complicated. Remaining treatment options for symptomatic patients include carefully titrated CPAP, nocturnal oxygen, or positional therapy. Some case reports and case series mention a positive impact of theophylline or acetazolamide on sleep-disordered breathing in these patients, but sufficiently powered trials are missing and theophylline should be avoided because of its proarrhythmogenic potential in patients with cardiac rhythm diseases. Optimal treatment of obstructive sleep apnea in patients with AVRC also remains unknown, but patients should probably be treated since obstructive apneas increase the sympathetic tone, which might promote arrhythmias. As mandibular advancement devices do no not alter cardiac physiology as CPAP does, they might be favorable in this population.

Clinical Course

In this case, the patient’s initial symptom was daytime sleepiness leading to a diagnosis of central sleep apnea. Many patients with AVCR are asymptomatic for a long time, and physical examination can produce normal results. This might explain why this patient was not diagnosed until he was examined after the sleep study. The gentle heart murmur could have been overheard or may not yet have been present in prior examinations. After confirmation of the diagnosis of AVRC, the patient was started on heart failure treatment with an angiotensin-converting enzyme inhibitor, spironolactone, and antiarrhythmic medication with sotalol. The Holter ECG showed episodes of sustained ventricular tachycardia, and thus a primary prophylactic implantable cardioverter-defibrillator (ICD) was placed. The patient was instructed to stop strenuous physical activity. An evaluation for heart transplantation was initiated, and the patient and his family were offered genetic counseling. Along with the treatment of the underlying heart failure, a trial of adaptive servoventilation for CSA was initiated before the results of the SERVE-HF study were available. Adaptive servoventilation could suppress the AHI sufficiently to 2.4/h, but the patient did not tolerate it. We then recommended positional therapy, but this did not change sleep quality or daytime symptoms. Nocturnal oxygen was offered as alternative treatment. Since the patient’s subjective sleep quality was better without oxygen, he declined further oxygen therapy.

  • 1.

    Central sleep apnea is rarely idiopathic, and screening for an underlying cause is recommended.

  • 2.

    The main treatment option for central sleep apnea in patients with heart failure is optimal heart failure treatment. For symptomatic patients a careful CPAP titration, nocturnal oxygen, or positional therapy can be considered.

  • 3.

    The clinical course of ARVC is quite variable. Treatment options are limited, but early diagnosis and ICD implantation in selected patients improve outcome. Adaptive servoventilation should not be used at the current time in these patients.

  • 4.

    Relatives should undergo genetic testing and counseling.

Financial/nonfinancial disclosures: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Additional information: The Video can be found in the Multimedia section of the online article.


Figures

Figure Jump LinkFigure 1 A 5-min polysomnographic recording during stage N1 and N1 non-rapid eye movement sleep shows a pattern of cyclic central apneas followed by hyperpneas (Hunter-Cheyne-Stokes respiration) with cycle lengths of 45 to 50 s causing oxygen desaturations.Grahic Jump Location
Figure Jump LinkFigure 2 Electrocardiogram of V2 with an epsilon wave, T-wave inversions, and ventricular extrasystoles. The open headed arrows indicate epsilon waves.Grahic Jump Location
Figure Jump LinkFigure 3 Echocardiographic four-chamber view showing an enlarged right ventricle and right atrium. There are no hints of hypertrophic cardiac muscle. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.Grahic Jump Location
Figure Jump LinkFigure 4 Cardiac MRI showing enlarged right ventricle; the arrows indicate fibrosis of the right ventricle. See Figure 3 legend for expansion of abbreviations.Grahic Jump Location

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