Leptospirosis presenting as severe cardiogenic shock: A case report

Abstract

Background

Leptospirosis is a rare infectious illness caused by the Spirochaete Leptospira. It has a wide-varying spectrum of presentation. We present a rare case of severe cardiogenic shock secondary to leptospirosis, in the absence of its common clinical features.

Case presentation

A 36-year-old woman presented to our unit with severe cardiogenic shock and subsequent multi-organ failure. Her clinical course was characterised by ongoing pyrexia of unknown origin with concurrent cardiac failure. She was initially managed with broad-spectrum antibiotics and inotropes. Percutaneous cardiac biopsy excluded major causes of myocarditis. On day 21 after presentation, she was found to be IgM-positive for leptospirosis.

Conclusions

This is a rare case of severe cardiogenic shock secondary to leptospirosis infection. The case also highlights the importance of obtaining a thorough social history when assessing a patient with an unusual presentation, as clues can often be missed.

Background

Leptospirosis is an infectious illness spread via rodents or mammals including dogs, monkeys and wild boars. Spread can be via both direct and indirect contact, and the disease is caused by the Spirochaetes “Leptospira” with a total of 14 possible pathogenic species. ¹ The infection is most evident within tropical regions such as Sri Lanka, with an annual incidence of 14/100,000 cases, ² and has low incidence in the UK; a study in 2012 found 301 cases in the preceding five years in the UK, a significant proportion of which were acquired abroad. ³ This has been attributed to the wide spectrum of disease severity and presentation, rendering it often underreported and underdiagnosed. Risk factors, aside from endemic areas, include contact with urine of the vector, recreational or occupational activity involving water and poor hygiene. The onset of symptoms is quick and typically occurs after an incubation period of five days to two weeks. ⁴ The disease can present as either a mild, self-limiting illness or be fulminant, with multi-organ failure most commonly neurological, renal and respiratory. The mortality is variable upon the organ dysfunction, with mortality rates of 30–60% in respiratory failure, 26–36% in renal failure and variable figures in neurological failure, although neurological involvement is thought to be a predictor of mortality. ¹

Case presentation

A 36-year-old woman was referred and then retrieved from her local general hospital due to new onset severe biventricular failure. The patient presented with a one-day history of upper abdominal pain and vomiting, following recent treatment for community-acquired pneumonia. Her co-morbidities included morbid obesity (body mass index [BMI] 53), diabetes mellitus type 2, asthma, hypothyroidism, chronic back pain, depression, anxiety and previous alcohol excess and benzodiazepine dependence. She was also an ex-smoker.

Abdominal computed tomography (CT) showed no features of intra-abdominal sepsis, and subsequently her condition deteriorated over the next 24 h with an acute systemic inflammatory response syndrome, presumed to be due to an infectious process, metabolic acidosis (pH 7.27 (normal range [NR] 7.35–7.45), pO₂ 7.71 kPa (NR 10–14 kPa), pCO₂ 5.23 kPa (NR 4.5–6 kPa), base excess −8.2 mmol/L (NR −2 to 2 mmol/L), HCO₃ 18.0 mmol/L (NR 22–26 mmol/L), lactate 10.3 mmol/L (NR 0.3–0.7)) and reducing level of consciousness. She required intubation and mechanical ventilation due to progressive hypoxia and cardiogenic shock, and was commenced on noradrenaline. A transthoracic echocardiogram revealed dilated left and right ventricles with severely reduced biventricular function with an estimated left ventricular (LV) ejection fraction of 10% (Simpson’s biplane). She was referred to our cardiac intensive care unit for consideration of veno-arterial extra-corporeal membrane oxygenation support (VA-ECMO).

She was transferred to our institution conventionally and commenced on ionotropic support with milrinone (0.7 mcg/kg/min). Initial chest radiograph revealed left basal atelectasis but no focal consolidation; electrocardiogram showed sinus rhythm and Troponin T was 46 ng/L (normal range = 0–40). Levosimendan was given on day 9 for further inotropy, titrated up to 0.2 mcg/kg/min and her noradrenaline dose was subsequently weaned. Our initial transoesophageal echocardiography (TOE) showed persistence of severe LV systolic impairment (global hypokinesis, worse at inferior and septal walls) with an estimated ejection fraction of 30–35%) and severe right ventricular (RV) systolic impairment with elevated RV systolic pressures (estimated right ventricle systolic pressure 42 mmHg) and severe tricuspid regurgitation (TR). Supportive care included diuresis with loop diuretic and empirical broad-spectrum antibiotics (Ciprofloxacin, Gentamicin and Teicoplanin) with cover for atypical organisms and fungal infection (Caspofungin and Doxycycline). She was not deemed a candidate for cardiac transplant due to her high BMI of 53.3 kg/m² and premorbid neurocognitive status (low mood with suicidal ideation and agoraphobic behaviour) with lack of social and family support. Concurrently she was not considered a candidate for a mechanical assist device, since in the UK it is not considered destination therapy. CT-pulmonary angiography (CTPA) did not show pulmonary emboli and the coronary arteries were unobstructed on invasive coronary angiography.

Initially, she was extubated but due to agitation and neurological impairment the patient was re-intubated. She developed focal signs of left-sided facial droop, dysarthria and reduced left upper limb power. A CT scan of the brain revealed a right middle cerebral artery (MCA) territory infarct the aetiology of which was felt to be cardiac embolus. This was confirmed on subsequent TOE revealed left atrial appendage clot. The patient was continued on cardiorespiratory support and a repeat levosimendan dose was given at seven days. Repeat TOE suggested biventricular function had recovered to a limited degree. From screening blood tests and further investigation into the cause of acute heart failure, the patient was found to have biochemical evidence of hypothyroidism (thyroid stimulating hormone 12.51 mIU/L, range 0.32–5.00) and iron deficiency (iron 2.4 umol/L (NR 12.6–26), Transferrin Saturation 3% (NR 20–45%).

Further examination of the clinical presentation and social history revealed a history of mouse infestation at her home; no travel history or substance misuse was found. Atypical serology including Chlamydia psittaci, Coxiella and Leptospirosis were sent. Hepatitis screen, HIV serology, respiratory viral polymerase chain reaction, Pneumococcal and Legionella urinary antigen were all negative, as were the autoimmune (ESR, rheumatoid factor, Cardiolipin IgG and IgM antibodies, anti-cyclic citrullinated peptide antibody, Complement C3 and C4, U1RNP, SS-A/Rho, SS-B/La, centromere B, Scl-70, Jo-1, Sm proteins, anti-nuclear antibody), vasculitis (anti-neutrophil cytoplasmic antibody, immunoglobulins G, A, M and E, anti-glomerular basement membrane antibody), myositis (antibodies to Mi-2, PM/Scl, Ku, PL7, PL12, Jo-1) and myocarditis screens (Mycoplasma pneumoniae, Enterovirus, Adenovirus, Parechovirus, Human Herpes virus Type 6 and Influenza A and B).

Throughout her initial admission, she remained persistently febrile, therefore antimicrobial therapy was escalated to Meropenem and subsequently changed to Ceftazidime and Metronidazole. Continuous veno-venous haemodiafiltration with an effluent rate of 45 mL/kg/h was commenced for intravascular cooling and renal replacement therapy.

Lumbar puncture was performed which was negative for infection (clear cerebrospinal fluid, glucose 5 mmol/L, protein 0.33 g/L, white cell count < 1/cu.mm, red blood cell 420/cu.mm, no organisms on Gram stain and no growth after 48-h incubation). A percutaneous RV biopsy was also performed 11 days into her inpatient stay, which showed morphologically normal myocardium and overlying endocardium, with no significant inflammation, granuloma formation or malignancy but mainly mature adipose tissue. Congo red stain for amyloidosis and Perls stain for haemosiderin was also negative.

Due to continued raised left atrial pressures, diuresis was continued with optimisation of her medications for biventricular failure. A surgical tracheostomy was performed for ventilatory weaning and control of her agitation.

On day 21 of her admission, she was found to be Leptospirosis IgM positive. Ceftriaxone was commenced and Public Health England was notified. Further transthoracic echocardiogram showed some improvement in function, but she was still dependent on inotropic support. She was transferred back to her local hospital 30 days after her admission. Biventricular and renal function slowly improved, and she was discharged to a medical ward for ongoing neuro-rehabilitation. She currently mobilises with a frame and is able to perform activities of daily living independently

Discussion

This case has highlighted that a good clinical history is pertinent to the diagnosis of leptospirosis, on detailed questioning the patient was in fact living within squalid conditions of a rodent infested residence. If a detailed social history had not been sought, the diagnosis may have been missed. Especially given that her presentation was so unusual, with no literature on biventricular failure in leptospirosis. Furthermore, a predisposition for leptospirosis has also been reported in those who suffer with chronic alcoholism and smoking ¹ – both of which were pertinent in this patient.

There is an abundance of literature on the evidence of neurological, renal and respiratory failure subsequent to leptospirosis. Some have reported that cardiac involvement is often disguised by pulmonary haemorrhage or hepatorenal failure, ⁵ however this cannot be explained in this particular case. When cardiac findings have been reported, these have included: myocarditis, conduction system abnormalities and acute coronary arteritis and aortitis. ⁶ What is interesting about this case however is that her primary issue was that of severe cardiogenic shock – not caused by myocarditis, of which there is no literature to our knowledge, to date.

One retrospective review of autopsied leptospirosis cases demonstrated 41 of the 44 cases to have cardiovascular involvement, of which histological evidence of myocarditis was found in 100% of the cases, epicardial/endocardium involvement in 39%, valvular in 36%, coronary artery in 51% and finally aortic involvement in 56%. ⁷

Another autopsy study of 24 patients who had died from leptospirosis found that on gross examination of the heart, 45% demonstrated enlargement, 33% pericardial haemorrhage, 21% right sided dilatation and 12% biventricular dilatation with histological findings showing that 96% had myocardial inflammation. ⁵

Importantly, cardiac biopsy of the right ventricle was carried out in the case presented, and there was no evidence of myocarditis or granuloma formation – could this be the reason that the patient in our case survived? Or is the biventricular failure simply a by-product of severe sepsis and not leptospirosis specific? The pathophysiology behind cardiac involvement beyond myocarditis as the cause of cardiac failure in leptospirosis, has yet to be elucidated.