Title : Management conundrum of right ventricular failure in a mixed connective tissue disease overlap syndrome of systemic lupus erythematosus and systemic sclerosis
Abstract:
A 36-year-old woman with a significant history of Group 1 pulmonary arterial hypertension
(PAH) with secondary to mixed connective tissue disease overlap syndrome (systemic lupus
erythematosus and systemic sclerosis), presented with a one-week history of fever, nonproductive
cough, and gastrointestinal symptoms including diarrhoea, nausea, vomiting, and
abdominal pain. She also reported worsening shortness of breath and orthopnoea. She has
severe group 1 PAH which was complicated by right ventricular failure. Her previous right
heart catherisation in Dec 2021 showed a mean pulmonary arterial pressure (MPAP) of 59
mmHg. Her previous transthoracic echocardiogram in February 2025 showed normal left
ventricular ejection fraction of 55%, flattened interventricular septum consistent with right
ventricular pressure and volume overload, severely dilated right ventricle with moderate right
ventricular hypertrophy and moderately impaired right ventricular function. She was initiated
on triple therapy with sildenafil, macitentan and selexipag. She was not a candidate for home
pump with epoprostenol infusion due to poor social and family support. With regards to the
management of her complex connective tissue disease which was diagnosed in 2017, she was
maintained on a baseline prednisolone 20mg OM, hydroxychloroquine 200mg 5x/week,
azathioprine 50mg OM dose and tacrolimus 0.5mg OM dose.
On examination, she was febrile (40.1°C), tachycardic (HR 120 bpm), and hypotensive (BP
79/53) mmHg, requiring initiation of norepinephrine at 0.1 mcg/kg/min. She also developed
hypoxia, with an initial saturation of 77% on room air which subsequently improved to 90%
after being initiated on high-flow nasal cannula (60 L/min, 60% FiO2).
Her ABG showed severe type 1 respiratory failure with P/F ratio of 62. Her bedside
echocardiogram showed evidence of right ventricle volume and pressure overload - dilated
right ventricle, D-shaped septum as well reduced left ventricular ejection fraction ?LVEF.
Her COVID test retuned positive. Electrocardiogram done showed old T wave inversions in
lead II, III, AVF, V2-V5, no electrical alternans and no low QRS voltages. Chest X-ray taken
in AP film showed faint patchy airspace opacities in the right lower zone. Procalcitonin was
7.50 ug/L and C reactive protein was 85.0 mg/L. Troponin levels were 67 to 70 ng/dL, serum
lactate peaked at 1.5 mmol/L. Her sodium was 134 mmol/L, potassium 4.0mmol/L, creatinine
106 umol/L, urea 11.6 mmol/L and bicarbonate 10 mmol/L. Her liver function test was
normal.
The patient was admitted to outbreak intensive care unit (OICU) for isolation of COVID
infection. She was diagnosed to have mixed septic and cardiogenic shock, driven by a severe
COVID-19 infection with concurrent RV volume overload complicated by Type 1
respiratory failure. She was treated for a possible superimposed bacterial pneumonia with a
course of IV Benzylpenicillin, and IV Ceftazidime, alongside a 2-day course of Remdesivir
and 3 days of IV Dexamethasone for COVID-19. A multiplex pneumonia panel was positive
for Streptococcus pneumoniae, Respiratory Syncytial Virus (RSV), and Staphylococcus
aureus (though with doubtful significance). Her care was subsequently transferred to cardiac
intensive care unit for further management for RV failure. RAI team was also consulted
regularly for the titration of immunosuppressants. Tacrolimus and azathioprine were initially
held off in view of acute infection with haemodynamic instability.
Her vasopressor was switched from noradrenaline to vasopressin 1.8U/hour as it was deemed
to have less pulmonary vasoconstriction effect. Continuous iv furosemide infusion of
5mg/hour was started for treatment of right ventricular volume overload. Good diuretic
response was achieved with urine output of 2-3mL/kg/hour was achieved. Inhaled iloprost,
which is a potent pulmonary vasodilator, was started with aim to reduce right ventricular
afterload. IV milrinone 0.125mcg/kg/min was initiated as a short acting inodilator and its
positive inotropy effect. Her oxygenation remained stable with HFNC 60L/95% and was
subsequently weaned to nasal prongs needing 1-2L/min oxygen. There was a plan for trial of
intravenous epoprostenol with a right heart catheterisation prior should her condition
continue to deteriorate. She was transferred to general ward then eventually discharged home
with PO sildenafil and ambrisentan with plan to consider initiation of sotatercept in the
outpatient setting.
Conclusion
Connective tissue disease-related pulmonary hypertension (CTD-PH) is a leading cause of
morbidity and mortality in patients with systemic sclerosis, lupus, and other connective tissue
diseases (CTDs). In this condition, the prognosis is principally determined by the
development of right ventricular failure (RVF).[1] The prevalence of PH varies by CTD
subtype, with systemic sclerosis conferring the highest risk.
Right ventricular dysfunction in CTD-PH results from a combination of factors including
increased afterload, maladaptive remodelling, and impaired contractility, leading to distinct
haemodynamic phenotypes that require specific and individualised management.[1-2]
Diagnosis and risk stratification of patients with CTD-PH, require a multimodal approach,
including clinical assessment for signs of RVF, serial echocardiography to evaluate cardiac
structure and function, and right heart catheterization for definitive haemodynamic
measurement.[1-3] Successful treatment hinges on a dual understanding: identifying the
specific connective tissue disease and defining the right ventricular phenotype (e.g., dilated,
hypertrophic, or failing), as this directly informs therapeutic choices
Effective management rests on addressing four central pillars: preload optimization,
contractility augmentation, afterload reduction, and treatment of the underlying CTD. [2][4-
6]. Preload optimization is achieved with cautious use of loop diuretics (e.g., furosemide,
bumetanide, torsemide), with thiazide diuretics considered for refractory volume overload.[4-
5] For our patient, we chose low dose continuous furosemide therapy for gentle and controlled
fluid removal. Ultrafiltration is another good option for controlled diuresis if response to
pharmacological therapy is inadequate.[4] Pharmacologic therapies for afterload reduction are
central in CTD-PH with RVF. Inhaled vasodilators (nitric oxide, prostacyclin analogues) may
be used acutely in decompensated RVF.[4] Our patient was started on inhaled iloprost (a
prostacyclin analogue) for pulmonary vasodilation for right ventricle afterload reduction. She
was later restarted on macitentan, an FDA-approved endothelin receptor antagonist for
pulmonary arterial hypertension (PAH, WHO Group I), which is commonly used in CTDPH.[
4][8-9]. Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) and soluble guanylate cyclase
stimulators (riociguat) are also effective in reducing pulmonary vascular resistance and
improving RV function
Multidisciplinary care and referral to pulmonary hypertension centers of excellence are
recommended for complex cases and for advanced therapies.
