Tilting the balance: hemidiaphragm paralysis leading to right to left cardiac shunt

Abstract

Patent foramen ovale (PFO) is a congenital abnormality present in 25%–30% of healthy adults and rarely leads to any sequelae. ^{1 2} It is associated with a left-to-right shunt which usually does not lead to any haemodynamic compromise. Occasionally, the shunt can get reversed; that is, right-to-left shunt occurs due to worsening pulmonary hypertension and can lead to persistent hypoxia. It is rare for the shunt reversal to happen in the absence of pulmonary hypertension. Here, we present an exceedingly rare case in a 61-year-old man presenting with hypoxia, was found to have shunt reversal due to unilateral diaphragmatic paralysis. He was successfully treated with PFO closure. The purpose of this report is to consider rare possibilities of PFO shunt reversal when the right-sided heart pressure is normal and to highlight that a simple chest X-ray can be a clue to the diagnosis.

Background

Unilateral diaphragmatic paralysis (UDP) is an uncommon condition found incidentally on chest X-rays done for other reasons.³ Similarly, patent foramen ovale (PFO) has no long-term detrimental effects on the body, but UDP and PFO can lead to interesting phenomena when they occur together. Distortion of the normal anatomy due to diaphragmatic paralysis can lead to right-to-left shunt (RLS) without reversal of the pressure gradient. Resulting intracardiac shunt causes severe hypoxia resistant to oxygen therapy. The diagnosis is difficult to reach due to the rarity of this condition and low index of suspicion. We are presenting a case of persistent hypoxia due to RLS due to idiopathic diaphragmatic paralysis in the absence of elevated right-sided cardiac pressure.

Case presentation

A 61-year-old otherwise healthy man was referred to the emergency room (ER) by his primary care physician (PCP) for worsening shortness of breath and hypoxia. Dyspnoea started 6 weeks before presentation and was progressive. Initially, he noticed it with exertion and later even while resting. He denied any fevers, chills, cough, sick contacts, recent travel, chest pain, palpitations, orthopnoea, paroxysmal nocturnal dyspnoea or leg swelling. He was a former smoker, smoked one to two packs a day for 10 years and quit about 30 years ago. He had alcohol abuse history in the past but had been sober for the last 2 years. He denied any illicit drug use. Medical history was significant for depression, sleep apnoea for which he underwent uvulopalatopharyngoplasty and a mechanical fall about 1 year ago.

At his PCP office, he was in moderate respiratory distress and was hypoxic with oxygen saturation in low 80s and was referred to ER of another hospital. His vitals in the ER included a temperature of 98°F, heart rate 88 beats/min, respiratory rate of 23/min and oxygen saturation (PO₂) of 85% on a 6 L nasal cannula. His physical examination showed moderate respiratory distress; otherwise, respiratory examination was negative for wheezes/ronchi/crackles. Cardiovascular examination was negative for any cardiac murmurs; the rest of the examinations were unremarkable.

Investigations

Laboratory evaluation including complete blood count and metabolic profile was unremarkable. D-dimer was 464 ng/mL (n<230 ng/mL). His ECG was unremarkable. CT chest with pulmonary embolism (PE) protocol was negative for PE but showed elevated right hemidiaphragm with right lower and middle lobe atelectasis. Chest X-ray also showed elevated right hemidiaphragm (figure 1). Non-specific left upper lobe and peripheral interstitial opacities were also seen.

Figure 1.

Chest X-ray showing elevated right hemidiaphragm.

He was initially treated as pneumonitis and atypical infection with levofloxacin and steroids. Virus respiratory panel including influenza/parainfluenza, adenovirus and respiratory syncytial viruses were negative. Due to lack of improvement and significant oxygen requirement, he was transitioned back and forth between BiPAP and high flow nasal cannula with 100% FiO₂, and antibiotics were broadened to include vancomycin and cefepime.

At this point, an echocardiogram (ECHO) was done to rule out cardiac causes of hypoxia which showed a possible intracardiac shunt. On the fifth postadmission day, he was transferred to our hospital for further evaluation.

A repeat transthoracic echo (TTE) with bubble study showed the significant passage of bubbles from right to left atrium signifying a PFO, and normal (55%–60%) ejection fraction (figure 2). The patient still required 100% FiO₂ on Bilevel Positive Airway Pressure (BiPAP) to keep his saturation above 90%. He was electively intubated for transoesophageal echo (TOE) which showed a large PFO with significant RLS and the absence of an atrial septal defect or clot in the right atrium while Doppler studies showed a flow through the PFO (figure 3). Both TEE and TOE did not show any findings suggestive of raised pulmonary or right-sided heart pressures. Right and left ventricles size and function were normal. Antibiotics and steroids were discontinued as the patient remained afebrile during this time; all his viral, fungal and bacterial serologies were negative, and interstitial infiltrates were vague and not significant enough to explain this degree of hypoxaemia. This prompted us to perform a more specific test that is right heart catheterisation (RHC) to evaluate the intracardiac pressures, which showed mean left atrial pressure of 7 mm Hg and mean right atrial pressure of 4 mm Hg. Pulmonary capillary wedge pressure was 5 mm Hg and mean pulmonary artery pressure was 14 mm Hg which ruled out pulmonary hypertension as the cause of the RLS. During the RHC, intracardiac echo (ICE) was done which confirmed the presence of PFO and the three-dimensional images showing the size measured about 12 mm (figure 4).

Figure 2.

Transoesophageal echo showing a tunnel-shaped patent foramen ovale.

Figure 3.

Doppler flow through the patent foramen ovale.

Figure 4.

Three-dimensional view of patent foramen ovale.

Treatment

A 12 mm occluder device was placed in and follow-up imaging with ICE showed no residual shunt.

Outcome and follow-up

Follow-up TTE after the procedure showed well-seated atrial septal occluder (ASO) device with no evidence of PFO. Patient’s oxygen requirement decreased radically after the procedure, and he was extubated the next day. He was weaned down to room air the same day and was transferred to the general medical floor. He did well post procedure and was discharged 3 days later. At his follow-up clinical appointment after a month, he was doing well doing his usual activities without any respiratory distress.

Discussion

Hypoxaemia is defined as the reduced PO₂ in the blood while hypoxia means reduced tissue oxygenation. Most common causes of hypoxaemia include hypoventilation, for example, opioid overdose, ventilation-perfusion (V/Q) mismatch, for example, PE, decreased inspired oxygen tension, for example, high altitude, diffusion impairment, for example, pulmonary fibrosis and RLS. All of the causes mentioned above for hypoxaemia improve with supplemental oxygen, at least to some extent except RLS. RLS should always be a consideration when there is virtually no response to supplemental oxygen therapy.⁴

RLS can also be defined as the extreme form of V/Q mismatch as there is no perfusion in the presence of normal ventilation. RLS exists when blood from the right side of heart bypasses the standard circuitry and reaches the left side of the heart without getting oxygenated. RLS can be anatomical or physiological. The most common anatomical intracardiac cause of RLS is PFO.^{3 5} PFO is asymptomatic in most conditions as the defect is flap like and the left atrial pressure is 5–10 mm Hg higher than the right atrium, and the atrial septum is essentially closed.

RLS in PFO can occur in the presence of elevated right-sided cardiac pressure such as in severe pulmonary hypertension due to obstructive sleep apnoea, PE and chronic lung diseases. Interestingly, RLS in PFO can also occur in scuba divers possibly due to the reversal of pressure differential between the left and right atrium. Although causation is still debated, PFO has been associated with cryptogenic ischaemic stroke, migraine and fat embolism. RLS through PFO can result in hypoxia resistant to oxygenation due to venous admixture in the left atrium. RLS through PFO in the absence of elevated right-sided cardiac pressure has been previously reported due to right pneumonectomy, aortic root enlargement, abdominal surgery but very rarely with diaphragmatic paralysis.^6–8

We did a comprehensive literature search and found only 12 cases reported previously with UDP associated RLS via PFO. The characteristics of these studies are shown in table 1. All of these patients were above the age of 50, and 8/12 (66%) patients were above the age of 60 indicating that PFO by itself is benign and it is the diaphragm paralysis later in life which triggers the hypoxia. Although the duration of hypoxia or dyspnoea was not mentioned in all cases, where it was said it was present for at least a few weeks duration. Precipitating cause for UDP in most cases was unknown (idiopathic UDP); however, in some cases, the definite reason was coronary artery bypass graft surgery, hepatic metastasis or arthrodesis of the lumbar spine. All these patients had normal right-sided heart pressures and successful recovery with the intervention.

Table 1.

Previously reported cases of unilateral hemidiaphragm paralysis-induced right-to-left shunt

No	Reference	Age/sex	Presentation and duration	Precipitating cause	CT to r/o PE	RHC	Intervention and result
1	Fabris et al, 12	66/F	Refractory hypoxaemia for weeks	Idiopathic unilateral phrenic nerve palsy	No PE	MRAP: 3 MPP: 12	Successful closure
2	Benito-González et al, 13	75/M	Dyspnoea on exertion	Arthrodesis of thoracolumbar spine	No PE	Normal	Successful closure
3	Charbonnel et al,14	84/F	Severe hypoxaemia	Idiopathic unilateral phrenic nerve palsy	Small PE	–	–
4	Maholic et al, 15	84/F	Hypoxia	GBS 1 month earlier	No PE	PA: 22/5, RA: 5	Successful closure
5	Darchis et al,16	79/F	Dyspnoea for 3 weeks	Hepatomegaly from metastasis	Small PE	MRA: 4	Successful closure
6	Darchis et al, 16	61/F	Hypoxaemia	Phrenic nerve injury from CABG surgery	–	MRA: five with no right-to-left pressure gradient	Successful closure
7	Darchis et al, 16	84 Y/F	Dyspnoea for 3 weeks	–	Small PE	Cath done but values not mentioned	Successful closure
8	Lopez Gaston et al,17	75/M	Dyspnoea × 7 weeks	–	No PE	Cath done	Successful closure
9	Ghamade et al,18	79/F	Hypoxaemia for 6 weeks	Oophorectomy and bladder suspension	No PE	MPA: 21, MRA: seven with no gradient	Successful closure
10	Cordero et al, 19	57/M	Dyspnoea 1 month	Idiopathic unilateral phrenic nerve palsy	No PE	Normal pressures	Successful closure
11	Murray et al, 20	72/M	Dyspnoea 3 months	Idiopathic unilateral phrenic nerve palsy	No PE	Normal Pressure	Successful closure
12	Ibrahim et al,21	59/F	Dyspnoea	Idiopathic unilateral phrenic nerve palsy	No PE	Normal Pressure	Successful closure
13	This case	61/M	Dyspnoea	Idiopathic unilateral phrenic nerve palsy	No PE	Normal Pressure	Successful closure

CABG, coronary artery bypass grafting; GBS, Guillian-Barre syndrome; MPA, mean pulmonary artery; MPP, mean pulmonary pressure; MRA, mean right atrial; MRAP, mean right atrial pressure; PA, pulmonary artery; PE, pulmonary embolism; RA, right atrial; RHC, right heart catheterisation.

The mechanism of RLS in the absence of an interatrial pressure gradient was first described by Zanchetta et al as the ‘flow phenomena’.⁹ Right atrium can be divided into an anterior and posterior portion according to embryological development. Superior vena cava (SVC) opens in anterior portion and blood flows downward, and forward, inferior vena cava (IVC) opens up into the posterior portion, and blood flows upwards and backwards to avoid turbulence by creating a pattern of rotation. Right-sided diaphragmatic paralysis results in the shift of mediastinum, which alters the relative position of the atrial septum and IVC and the blood coming from IVC is directed towards foramen ovale creating RLS in the absence of interatrial pressure gradient. A similar mechanism has been proposed for RLS due to pneumonectomy, and aortic root enlargement.

The most common aetiology for UDP is idiopathic, but other reasons should also be considered such as cardiac surgery, cervical cord compression and pneumonia. As in our patient, detailed workup was done for the possible causes of diaphragmatic paralysis including CT of the cervical and thoracic spine and was found to be negative. An old chest X-ray from 4 years ago did not show right-sided diaphragmatic elevation. Further inquiry regarding any traumatic events in the past revealed that he did have a fall about a year ago for which a CT head and cervical cord was done and were found to be unremarkable. No chest X-ray was done at that visit, and he did not recall any respiratory problems after the fall.

In patients with severe hypoxia unresponsive to oxygen therapy and with normal lung parenchyma, intracardiac shunt should always be a consideration and workup should include transthoracic ECHO with bubble study, and if PFO is found it should be followed by TOE. TOE helps to measure the accurate anatomy of PFO, for example, size, length and also helps exclude other possible causes of shunt such as eustachian valve and atrial septal aneurysm.^{10 11} Cardiac catheterisation should follow TOE as it helps to rule out increased right-sided cardiac pressure as the cause of RLS. A step down in oxygen saturation from pulmonary veins into left atrium is also another clue for RLS, and which is due to deoxygenated blood coming in from the IVC and SVC mixing with oxygenated blood coming in from pulmonary veins in the left atrium. The diagnosis can be further consolidated by the occlusion test of the atrial defect with the help of the balloon tip catheter which brings up the oxygen saturation in the left atrium to normal.⁴ In such circumstances, closure of PFO through percutaneous transcatheter intervention is an indication and hypoxia generally improves after closure. There have been calls to address the diaphragmatic paralysis as it is the underlying cause for the decompensation in patients who had asymptomatic PFO for decades.

Recurrence of RLS is uncommon after closure, and the procedure is generally tolerated well. Our patient’s oxygenation improved after the closure of PFO.

Learning points.

• Right-to-left shunt via patent foramen ovale (PFO) can occur due to various causes that either increase the right atrial pressure, reduce the left atrial pressure or facilitate the inferior vena cava flow to be directed to the PFO.

• In rare instances, new diaphragmatic paralysis in the background of asymptomatic PFO can cause significant hypoxaemia which poses a diagnostic challenge due to the novelty of this condition.

• Pulmonologists and cardiologists need to be aware of this rare phenomena as the condition can be life threatening if not diagnosed on time but if managed appropriately has a good prognosis.