A 55-year-old female patient presented to our facility with dyspnea in the setting of bacteremia. During the course of her hospital stay, she was diagnosed with two rare entities that were contributing to her symptoms: severe pulmonary hypertension related to a prior liver transplant, and coronary cameral fistulae. There is little data available to describe appropriate therapy for either of these two diagnoses. The patient described was successfully treated with medical therapy, including oral phosphodiesterase-5 inhibitor. We present the diagnostic work up of this patient and a brief review of the literature.
Dyspnea is a common complaint among hospitalized patients. The workup is often multi-disciplinary, and the etiology of the complaint is often multifactorial. In a patient with not one, but two, unusual causes of dyspnea and elevated troponin-I, ample opportunity for discussion of treatment options exists. However, complex issues do not always require complex solutions. Following a thorough work-up, the patient was ultimately treated conservatively with good results.
A 55-year-old female presented to our hospital in transfer from an outlying facility with complaints of fever, chills, and dyspnea. Her medical and surgical history include liver transplant at age 40 for primary biliary cirrhosis, hypertension, and pericardial effusion of unknown etiology with pericardial window two years prior to presentation. Prior to admission, her medication regimen consisted of sirolimus, cyclosporine, metolazone, verapamil, furosemide, and potassium chloride. She is a life-long non-smoker and does not use alcohol or illicit drugs.
During initial evaluation, the patient was diagnosed with Eschericia coli bacteremia and an associated urinary tract infection. An initial electrocardiogram at the outlying facility was noted to be abnormal, and a Troponin-I was drawn. Troponin-I was elevated at 1.80 ng/mL (reference range 0.0-0.30 ng/mL). A transthoracic echocardiogram was performed, and elevated right heart pressures were noted. At this point, the decision was made to transfer the patient to our facility, which has cardiac catheterization facilities. Right and left heart catheterizations were performed to assess for pulmonary hypertension, constrictive pericarditis, and non-ST elevation myocardial infarction (NSTEMI).
Right heart catheterization revealed a mean right atrial pressure of 19 mmHg, right ventricular pressure of 123/12 mmHg, pulmonary artery pressure of 117/49 mmHg, pulmonary capillary wedge pressure of 17 mmHg, and pulmonary vascular resistance of 2323 dyn·second/cm5. Arterial pressure ranged from 123/84 mmHg to 139/83 mmHg. Femoral artery saturation was 83%, right atrial saturation was 34%, and pulmonary artery saturation was 36%. All saturations were drawn on room air. A vasodilatory challenge was done with adenosine infusion, without improvement in pulmonary pressures. No signs of constrictive pericarditis or cardiomyopathy were noted.
Left heart catheterization revealed mild, non-obstructive coronary artery disease, particularly in the circumflex and right coronary arteries. Left ventricular end diastolic pressure (LVEDP) was 11 mmHg. Additionally, coronary cameral fistulae were noted. Multiple, small fistulae were noted from both left-sided septal perforator branches of the left anterior descending artery (Figure 1) and septal branches of the posterior descending artery (Figure 2), with clear connections to the left ventricle. Despite their small size, fistulae were numerous enough that a left ventriculogram could be seen with injection of either the left main coronary artery or the right coronary artery.
Pulmonary hypertension in the setting of liver transplant and coronary cameral fistulae are both rare entities. Coronary fistulae with communication to the cardiac chambers have incidence of between 0.08-0.3% in patients undergoing routine diagnostic left heart catheterization.1-3 Of these, approximately 90% communicate with the right-sided chambers of the heart.3-4 Additionally, only about 5% of all coronary cameral fistulae originate from both coronary arteries3, making our finding extremely rare. Fistulae of this variety are often discovered incidentally in the course of evaluation for other cardiac issues. Occasionally, patients will experience angina related to the fistulae. Given the lack of significant coronary artery disease in our patient, we believe the additional insult of bacteremia in the setting of coronary cameral fistulae likely resulted in a type two myocardial infarction.
Coronary cameral fistulae with communication to the right-sided heart chambers might have explained the elevated right heart pressures and dyspnea. However, in this case, the coronaries are in communication with the left ventricle, leaving us to search for another explanation for the patient’s severe pulmonary hypertension. Another explanation is severe pulmonary hypertension related to her status as a liver transplant recipient.
Two mechanisms of pulmonary hypertension following liver transplant have been proposed. The literature suggests that in these cases, pulmonary hypertension was pre-existing and unmasked by liver transplant and subsequent relief of co-existing hepatopulmonary syndrome (HPS).5 HPS results in dilatation of intrapulmonary vasculature, therefore masking elevated pulmonary pressures.5-6 In prior studies, pulmonary hypertension developed from 1 month up to 11 years post liver transplant.7 In contrast, one study notes that in five patients without antecedent HPS, pulmonary hypertension developed later than in those with antecedent HPS.7 In the case presented here, pulmonary hypertension was diagnosed 15 years after liver transplantation. To the authors’ knowledge, no studies exist to evaluate right heart hemodynamic changes in liver failure patients status post liver transplant over the long term.
The question of causation between liver transplant and development of pulmonary hypertension must be raised. We cannot exclude the possibility that the patient described has idiopathic pulmonary hypertension with coincident history of liver transplantation. We also explored the possibility of the patient’s antirejection regimen being responsible. Both cyclosporine and sirolimus have been studied as drugs that actually help to reverse pulmonary hypertension.8-9 Work-up for secondary causes of pulmonary hypertension in this patient is ongoing at this time.
Further research is needed to define treatment of coronary cameral fistulae. While some patients may need surgical treatment, others may benefit from medical therapy. An additional option of percutaneous closure of coronary fistulas does exist for patients with symptoms of angina, but in this case, use of a closure device is limited by the small size of the fistulae.10 The logical follow-up question is then: what medical therapy is the most beneficial? There are no guidelines at this time to recommend specific therapy. The authors believe that medical therapy with beta-blockers to reduce myocardial oxygen demand is reasonable. With regards to her low femoral artery saturation, this patient’s hypoxemia is likely due to her pulmonary hypertension. The coronary cameral fistulae create a left-to-left shunt, which would not induce hypoxemia. For this patient, who remained without symptoms suggestive of angina after resolution of her acute illness, conservative medical therapy of the coronary cameral fistulae was deemed appropriate. A case report by Padfield supports this approach.3
Pulmonary hypertension is a well-known disease, with several classes of medications available for treatment. Pulmonary hypertension presenting in a patient with liver transplant, however, is not well described. Oxygen therapy to maintain oxygen saturation greater than 90% is generally considered to be beneficial in all types of pulmonary hypertension, to prevent the vasoconstriction that accompanies hypoxemia.11 In the case presented here, the patient declined further treatment with intravenous or intramuscular therapies. She was initiated on a trial of oral phosphodiesterase-5 inhibitor, and has thus far done well.
This manuscript received a double-blind peer review from members of the Cath Lab Digest Editorial Board.
Disclosure: The authors report no conflicts of interest regarding the content herein.
The authors can be contacted via Mallory Balmer-Swain, DO, at firstname.lastname@example.org.
- Hashmi ZA, Yoon PD, Smaroff, GG, Cardone JC. Coronary cameral fistula: Left anterior descending artery to left ventricle. J Card Surg. 2010 May; 25: 343-345.
- Yamanaka O, Hobbs RE. Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. Cathet Cardiovasc Diagn. 1990 Sep; 21: 28-40.
- Padfield GJ. A case of coronary cameral fistula. Eur J Echocardiogr. 2009 Jul; 10: 718-720.
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- Aucejo F, Miller,C, Vogt D, Eghtesad B, Nakagawa S, Stoller JK. Pulmonary hypertension after liver transplantation in patients with antecedant hepatopulmonary syndrome: A report of 2 cases and review of the literature. Liver Transpl. 2006 Aug; 12: 1278-1282.
- Martinez-Palli G, Barberà JA, Taura P, Cirera I, Visa J, Rodriguez-Roisin R. Severe portopulmonary hypertension after liver transplantation in a patient with preexisting hepatopulmonary syndrome. J Hepatol. 1999 Dec; 31: 1075-1079.
- Koch DG, Caplan M, Reuben A. Pulmonary hypertension after liver transplantation: Case presentation and review of the literature. Liver Transpl. 2009 Apr; 15: 407-412.
- Koulmann N, Novel-Chaté V, Peinnequin A, Chapot R, Serrurier B, Simler N, Richard H, Ventura-Clapier R, Bigard X. Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle hypertrophy. Am J Respir Crit Care Med. 2006 Sep 15; 174: 699-705.
- Houssaini A, Abid S, Mouraret N, Wan F, Rideau D, Saker M, Marcos E, Tissot C, Dubois-Rande J, Amsellem V, Adnot S. Rapamycin reverses pulmonary artery smooth muscle cell proliferation in pulmonary hypertension. Am J Respir Cell Mol Biol. 2013 May; 48: 568-577.
- Qureshi SA, Tynan M. Catheter closure of coronary artery fistulas. J Interv Cardiol. 2001 Jun; 14: 299-307.
- McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol. 2009; 53: 1573-1619.