Chimaera Infection Research Articles

Longest incubation period of Mycobacterium chimaera infection after cardiac surgery.

Mycobacterium chimaera infections have been associated with contamination of a heater-cooler unit used during cardiopulmonary bypass procedures since 2006. Mycobacterium chimaera is a slow-growing non-tuberculous mycobacterium responsible for an infection, which is difficult to treat and has often a devastating course. Until now, M. chimaera infection has been shown to occur up to 8 years after operation. We report a patient presenting with an aortic pseudoaneurysm who developed M. chimaera infection 12 years after repair of an acute type A aortic dissection with graft replacement of the ascending aorta and stent-grafting of the arch. As far as we know, this is the case with the longest incubation period of M. chimaera infection. The present experience indicates that all patients who underwent open heart procedures since 2006 with such heater-cooler unit model should be closely followed up regardless of time of index surgery.

Clinical and Multimodal Imaging Findings in Disseminated Mycobacterium Chimaera

To characterize the ophthalmic clinical and multimodal imaging findings of disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Observational case series. Four patients (8 eyes) with disseminated M.chimaera infection. Patients were evaluated with biomicroscopy, OCT and OCT angiography, fundus autofluorescence, and fluorescein and indocyanine green angiography. Clinical and multimodal imaging findings of patients with disseminated M.chimaera infection. All 4 patients were white men with a mean age of 65.5 years (range, 60-75 years) who had aortic valve or root infection, or both, with M.chimaera diagnosed by culture, gene sequencing, or both. All 4 patients demonstrated bilateral choroidal lesions on funduscopy and evidence of osteomyelitis by imaging, culture analysis, or both at the time of ocular diagnosis. Indocyanine green and OCT angiography revealed numerous additional subclinical choroidal lesions and were used to track disease response to therapy. Fluorescein angiography and fundus autofluorescence were useful in determining lesion age and activity. All patients were treated with 3- or 4-drug antimycobacterial therapy. Three underwent revision of cardiothoracic surgery with removal of infected graft. One patient went on to demonstrate progressive ocular disease that was noted before each of his surgical revisions. Two patients showed improvement in ocular and systemic disease, however one of them developed a choroidal neovascular membrane. The final patient was a single encounter whose clinical and imaging findings showed longstanding inactive disease. Ophthalmologists should be aware of the systemic and ocular findings of this rare life-threatening disease. Multimodal imaging is useful in corroborating a diagnosis of ocular M.chimaera andparticularly in evaluating patient response to therapy, because choroidal activity seems to mimic systemic activity. Treating physicians should be aware of the co-occurrence of choroiditis and osteomyelitis. Choroidalneovascular membrane can also be a late complication of this disease.

Diversity of non-tuberculous mycobacteria in heater-cooler devices: results from prospective surveillance

The international outbreak of cardiac surgery-associated Mycobacterium chimaera infections was traced back to infectious aerosols originating from contaminated water reservoirs of heater-cooler devices (HCD). In general, nontuberculous mycobacteria (NTM) frequently colonize water systems and can contaminate medical devices. Data on detection of NTM other than M. chimaera in samples gathered from HCDs are scarce. The present study summarizes prospective mycobacterial surveillance of five HCDs over more than four years. A cohort of five, in 2014 factory-new acquired, LivaNova 3T (London, UK) HCDs were prospectively followed. Until mid-April 2014 HCDs were maintained according to the manufacturer's recommendations, subsequently according to an intensified in-house protocol including exhaust air evacuation. Mycobacterial surveillance cultures consisted of monthly water samples gathered from patient and cardioplegia circuits, as well as airflow samples. Out of 441 water samples, 170 (38.6%) revealed NTM growth. The most frequently detected NTM were Mycobacterium chimaera (n=120 (67.4%)), Mycobacterium gordonae (n=35 (19.7 %)), and Mycobacterium paragordonae (n=17 (9.6%)). Growth of NTM, M. chimaera and M. paragordonae was significantly more common in water samples derived from the patient than the cardioplegia circuit of the HCD. Three (2.0%) out of 150 air samples grew NTM. Growth of NTM in HCD water samples was frequent. Diverse NTM species were detected, with M. chimaera being most common. The majority of air samples remained negative. The relevance of NTM other than M. chimaera contaminating HCDs is poorly defined, but a recent report on a HCD-associated outbreak with Mycobacterium abscessus confirms a potential threat.

Invasive Mycobacterium abscessus Complex Infection After Cardiac Surgery: Epidemiology, Management, and Clinical Outcomes.

We recently mitigated a clonal outbreak of hospital-acquired Mycobacterium abscessus complex (MABC), which included a large cluster of adult patients who developed invasive infection after exposure to heater-cooler units during cardiac surgery. Recent studies have detailed Mycobacterium chimaera infections acquired during cardiac surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive MABC infection. We retrospectively collected clinical data on all patients who underwent cardiac surgery at our hospital and subsequently had positive cultures for MABC from 2013 through 2016. Patients with ventricular assist devices or heart transplants were excluded. We analyzed patient characteristics, antimicrobial therapy, surgical interventions, and clinical outcomes. Ten cardiac surgery patients developed invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting. Median time from presumed inoculation in the operating room to first positive culture was 53 days (interquartile range [IQR], 38-139 days). Disseminated infection was common, and the most frequent culture-positive sites were mediastinum (n = 7) and blood (n = 7). Patients received a median of 24 weeks (IQR, 5-33 weeks) of combination antimicrobial therapy that included multiple intravenous agents. Six patients required antibiotic changes due to adverse events attributed to amikacin, linezolid, or tigecycline. Eight patients underwent surgical management, and 6 patients required multiple sternal debridements. Eight patients died within 2 years of diagnosis, including 4 deaths directly attributable to MABC infection. Despite aggressive medical and surgical management, invasive MABC infection after cardiac surgery caused substantial morbidity and mortality. New treatment strategies are needed, and compliance with infection prevention guidelines remains critical.

The effect of sodium thiosulfate on the recovery of Mycobacterium chimaera from heater–cooler unit water samples

Heater-cooler units (HCUs) have been implicated in the recent global outbreak of invasive Mycobacterium chimaera infection among patients following cardiothoracic surgery. Because infected patients tend to remain asymptomatic for extended periods, detection of M.chimaera from HCUs in real time is essential to halting the ongoing M.chimaera HCU-associated outbreak. Sample collection protocols to evaluate the presence of M.chimaera offer conflicting recommendations regarding the addition of sodium thiosulfate (NaT) during the collection process. To study the effect of NaT on M.chimaera recovery and culture contamination. Seventy-six paired HCU water samples (with and without NaT) were collected, processed and cultured simultaneously into Lowenstein-Jensen slants, Middlebrook 7H10 agar plates, and mycobacterial growth indicator tubes (MGITs), and incubated at 37°C. A subset of 31 paired samples was additionally cultured on MGITs and incubated at 30°C. Of 76 samples incubated at 37°C in each of the three media, with and without NaT, M.chimaera was identified in at least one aliquot of 21 samples. The presence of NaT did not significantly increase the probability of recovering M.chimaera in a multi-variable conditional logistic model and culture contamination rates were similar between aliquots with and without NaT. In the subset of samples cultured on MGITs at both 30°C and 37°C, the presence of NaT again was not associated with M.chimaera recovery, but was significantly associated with reduced culture contamination.

Long-term follow-up of post-cardiac surgery Mycobacterium chimaera infections: A 5-center case series

ObjectivesIn multiple countries, endovascular/disseminated Mycobacterium chimaera infections have occurred in post-cardiac surgery patients in association with contaminated, widely-distributed cardiac bypass heater-cooler devices. To contribute to long-term characterization of this recently recognized infection, we describe the clinical course of 28 patients with 3–7 years of follow-up for survivors. MethodsIdentified at five hospitals in the United States 2010–2016, post-cardiac surgery patients in the cohort had growth of Mycobacterium avium complex (MAC)/M. chimaera from a sterile site or surgical wound, or a clinically compatible febrile illness with granulomatous inflammation on biopsy. Case follow-up was conducted in May 2019. ResultsOf 28 patients, infection appeared to be localized to the sternum in four patients. Among 18 with endovascular/disseminated infection who received combination anti-mycobacterial treatment and had sufficient follow-up, 39% appeared to have controlled infection (>12 months), 56% died, and one patient is alive with relapsed bacteremia. While the number of patients is small and interpretation is limited, four (67%) of six patients who had cardiac prosthesis removal/replacement appeared to have controlled infection compared to three (25%) of 12 with retained cardiac prosthesis (p >0.14; Fisher's exact test). ConclusionsGiven poor response to treatment and potential for delayed relapses, post-cardiac surgery M. chimaera infection warrants aggressive treatment and long-term monitoring.

Brain Infection from Mycobacterium chimaera: A Case Report

We describe the first case report of pathology-proven brain infection by Mycobacterium chimaera (MC). A 35-year-old male, previously operated in 2010 of aortic valve and ascending aortic replacement, was addressed to our hospital for the acute onset of aphasia preceded by absence. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple left frontal and temporal cortical-subcortical lesions. During hospitalization the patient never presented fever and cerebrospinal fluid (CSF), PCR, FilmArray and blood tests were within normal ranges. Transesophageal echocardiography showed no cardiac abnormalities. A thorax-abdomen CT scan was performed, revealing no extracranial abnormalities, and a whole body PET-CT scan showed a high uptake of brain lesions. Considering clinical results and the suspect of a tumoural lesion, the patient underwent surgery, where a left frontal enhanced nodular lesion was removed. Pathology finally revealed it was an abscess caused by Mycobacterium chimaera. This case confirms that Mycobacterium chimaera infection spread can be very subtle and diagnosis a real challenge, particularly years after surgery. We would like to underline the importance of suspecting an atypical infection source related to a history of cardiothoracic surgery, given a non-specific MR pattern and subtle clinical and laboratory findings.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Mycobacterium chimaera Infection: A Case Report and Review of Literature

Abstract Mycobacterium chimaera (MCH) is a non-tuberculous mycobacterium commonly found in the environment. It is a member of the M. avium complex (MAC), and rarely causes infections in humans. However, invasive MCH infections have been reported associated with heater-cooler devices during cardiac surgery. Detection of MCH infections in this setting has been impeded by inadequate clinical awareness and laboratory tests. A 77-year-old man had aorta valve replacement 3 years ago. He recently presented with constitutional symptoms, including fatigue, night sweats, and 50 pounds of weight loss. PET CT showed ground-glass and nodular opacities in the lungs. Bone marrow biopsy demonstrated noncaseating granulomas. Transesophageal echocardiogram revealed severe stenosis and regurgitation of aortic valves. Despite antibiotics and heart surgery to relieve stenosis, the patient succumbed. Autopsy showed multiple small granulomas in the lung and multifocal chronic inflammation in the heart. Premortem mycobacterial cultures of aortic valves were performed, which grew MAC by DNA probe in 1 week. Subsequently, it was identified as MCH by sequencing of the ITS1/ITS2 region. The cause of death was heart failure due to MCH endocarditis. MCH infection is rare but potentially fatal if not promptly treated. Therefore, it is critical to identify patients at risk for infection. Since 2013, over 100 cases of MCH endocarditis have been reported worldwide, specifically associated with contaminated heater-cooler units during heart surgery. Characteristically, MCH infection has a long incubation period after exposure (median 17 months, range 3-72 months). Signs and symptoms are generally nonspecific and often include fatigue, fever, and weight loss. The risk of MCH infection in patients undergoing open heart surgery is low, but clinicians should be aware of the risks especially when heater-cooler units are utilized. A close follow-up over a long period may be necessary due to the long incubation period of this infection.

Mycobacterium chimaera encephalitis following cardiac surgery in three adult immunocompetent patients: first detailed neuropathological report

Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management

Epidemiology, Clinical Presentation, Diagnosis and Treatment of Infections Caused by Mycobacterium chimaera

The recognition, correct diagnosis and adequate clinical management of infections caused by atypical mycobacteria are challenging tasks in clinical practice. Invasive infections caused by Mycobacterium chimaera, a member of the Mycobacterium avium-intracellulare complex, have been increasingly reported over the past few years. Most infections occurred in patients who had undergone open-chest cardiothoracic surgery. Epidemiological and molecular studies showed that transmission of M. chimaera occurred through intraoperative aerosols derived from contaminated heater-cooler units, i. e. devices that are used to enable the extracardiac circuit in cardiothoracic surgery. Thus far, approximately 120 patient cases have been reported worldwide. The latency between exposure and onset of clinical symptoms may comprise several years. Clinical manifestations of M. chimaera infections include not only endocarditis and implant-associated infections, but also non-cardiac entities such as sarcoidosis-like symptoms, vertebral osteomyelitis and chorioretinitis. The pathogen can be detected in blood culture vials and in surgically obtained specimens from affected tissues, if specific microbiological tests for detection of mycobacteria are employed. There are no simple-to-use screening tests and a high clinical index of suspicion is thus mandatory in patients with previous exposure and compatible signs and symptoms. The successful treatment of M. chimaera infections requires the removal of infected devices and prolonged combination therapy with antimycobacterial drugs. This review summarises the clinical relevance, epidemiology, symptomatology, diagnosis and treatment of infections caused by M. chimaera, with a specific focus on pneumological aspects.

Rapid detection of invasive Mycobacterium chimaera disease via a novel plasma-based next-generation sequencing test

BackgroundThere is an ongoing outbreak of Mycobacterium chimaera infections among patients exposed to contaminated heater-cooler devices used during cardiac surgery. Recognition of M. chimaera infection is hampered by its long latency and non-specific symptoms. Standard diagnostic methods using acid-fast bacilli (AFB) culture often require invasive sampling, have low sensitivity, and can take weeks to result. We describe the performance of a plasma-based next-generation sequencing test (plasma NGS) for the diagnosis of M. chimaera infection.MethodsWe conducted a retrospective study of 10 patients with a history of cardiac surgery who developed invasive M. chimaera infection and underwent testing by plasma NGS between February 2017 and April 2018.ResultsPlasma NGS detected M. chimaera in 9 of 10 patients (90%) with invasive disease in a median of 4 days from specimen collection, including all 8 patients with disseminated infection. In 7 of these 9 cases (78%), plasma NGS was the first test to provide microbiologic confirmation of M. chimaera infection. In contrast, AFB cultures required a median of 20 days to turn positive, and the median time for confirmation of M. chimaera was 41 days. Of 24 AFB blood cultures obtained in this cohort, only 4 (17%) were positive. Invasive procedures were performed in 90% of cases, and in 5 patients (50%), mycobacterial growth was achieved only by culture of these deep sites.ConclusionsPlasma NGS can accurately detect M. chimaera noninvasively and significantly faster than AFB culture, making it a promising new diagnostic tool.

MULTIMODAL IMAGING OF CHOROIDAL LESIONS IN DISSEMINATED MYCOBACTERIUM CHIMAERA INFECTION AFTER CARDIOTHORACIC SURGERY.

To explore morphologic characteristics of choroidal lesions in patients with disseminated Mycobacterium chimaera infection subsequent to open-heart surgery. Nine patients (18 eyes) with systemic M. chimaera infection were reviewed. Activity of choroidal lesions were evaluated using biomicroscopy, fundus autofluorescence, enhanced depth imaging optical coherence tomography, fluorescein angiography/indocyanine green angiography, and optical coherence tomography angiography. Relationships of choroidal findings to systemic disease activity were sought. All 9 male patients, aged between 49 and 66 years, were diagnosed with endocarditis and/or aortic graft infection. Mean follow-up was 17.6 months. Four patients had only inactive lesions (mild disease). In all five patients (10 eyes) with progressive ocular disease, indocyanine green angiography was superior to other tests for revealing new lesions and active lesions correlated with hyporeflective choroidal areas on enhanced depth imaging optical coherence tomography. One eye with a large choroidal granuloma developed choroidal neovascularization. Optical coherence tomography angiography showed areas with reduced perfusion at the inner choroid. All 5 patients with progressive ocular disease had evidence of systemic disease activity within ±6 weeks' duration. Choroidal manifestation of disseminated M. chimaera infection indicates systemic disease activity. Multimodal imaging is suitable to recognize progressive ocular disease. We propose ophthalmologic screening examinations for patients with M. chimaera infection.

Use of Nano- SIMS at the single cell-level to evaluate drug penetration into mycobacterial biofilms

Non-tuberculous mycobacteria (NTMs), such as Mycobacterium abscessus and chimaera, can cause high mortality and morbidity amongst patients who are immunocompromised or have chronic lung diseases, such as cystic fibrosis. Mycobacterial biofilms can form in the alveolar walls of such patients following inhalation from environmental reservoirs. Recently, pathogenic strains have been isolated from shower heads and hospital air conditioning units. Biofilms are notoriously difficult to eradicate and are associated with the development of increased antimicrobial resistance (AMR). Treatment for M. abscessus and chimaera infections often requires 2–3 antibiotics over 2 years. The question we want to address is whether the increased AMR and treatment time in NTM biofilm formation is due to lack of antibiotic penetration, resulting in non-therapeutic and AMR-generative levels, or the development of phenotypic and/or genetic resistance. In this project we will use Nano-SIMS (nano-scale secondary ion mass spectrometry) to measure penetration of the antibiotic bedaquiline (BDQ), used to treat NTM infections, into individual cells of NTM biofilms (M. abscessus and M. chimaera). Nano-SIMS maps the relative abundance of different ions down to the nano-scale and can be used to measure in profile through the biofilm. In addition, the minimum inhibitory concentration (MIC) and minimum duration for killing (MDK) of BDK will be measured to determine antibiotic susceptibility in biofilms and a planktonic growth control. Understanding the AMR generation and prolonged treatment in NTM biofilms could lead to improved mortality and morbidity. The development of novel treatment strategies could enhance treatment efficacy, reduce treatment duration and AMR development.

Genomic Analysis of Cardiac Surgery–Associated Mycobacterium chimaera Infections, United States

A surgical heater–cooler unit has been implicated as the source for Mycobacterium chimaera infections among cardiac surgery patients in several countries. We isolated M. chimaera from heater–cooler units and patient infections in the United States. Whole-genome sequencing corroborated a risk for these units acting as a reservoir for this pathogen.

Where Are They Now? An Update on the First Australian Case of Mycobacterium chimaera Infection Following Cardiac Surgery

Where Are They Now? An Update on the First Australian Case of Mycobacterium chimaera Infection Following Cardiac Surgery

Mycobacterium chimaera in heater-cooler units: new technical approach for treatment, cleaning and disinfection protocol.

Mycobacterium chimaera infections have mainly been associated with the heater-cooler unit (HCU) and, ultimately, linked to contaminated aerosols in the operation room. The contamination status of HCUs seems to be influenced by the maintenance, therefore, according to the manufacturer's recommendations, peracetic acid (Puristeril) was introduced to increase HCU cleaning and disinfection protocol maintenance. Aerosol dispersion from Puristeril during maintenance can cause adverse effects to nearby workers. We aim to describe our technique to reduce the impact of Puristeril on operating room staff and to limit dispersion of its aerosol in the environment by performing the cleaning procedure through a closed circuit.

Mycobacterium chimaera infections following cardiac surgery in Italy: results from a National Survey Endorsed by the Italian Society of Cardiac Surgery.

A global outbreak of Mycobacterium chimaera infections following cardiac surgery and linked to contaminated heater-cooler units (HCUs) is currently ongoing. Neither the status of this outbreak in Italy nor the mitigation strategies adopted by adult cardiac surgery units (ACSUs) are currently known. In 2017, the Italian Society of Cardiac Surgery launched a national survey among the Italian ACSU to shed some light on this issue. In Italy, there are 90 ACSUs across 20 regions. From May to November 2017, these ACSUs were surveyed collecting data on patients diagnosed with MC infections, ACSU workload, HCU models in use and control measures adopted in the operatory room. The response rate was 87.8%. The median number of cardiac procedures at each ACSU was 450/year [interquartile range (IQR) 350-650 procedures/year], and nationally, the number of procedures/year exceeded 40k. In Italy, seven patients with M. chimaera infections following cardiac procedures have been reported since 2015: all had aortic or valvular surgery as the first procedure; the median latency between the first operation and the infection was 2 years (IQR 2-3.25). Mortality for patients requiring redo cardiac surgery was 50%. M. chimaera infections risk was 0.4-1 patient every 1000 cardiac procedures. The most common HCU model in Italy is the 3T HCU (70.9%). The most common control measures adopted included implementing new HCU disinfection protocols, using sterile or filtrated water in the HCU and displacing HCU fans away from the patient: HCU replacement and microbiology testing were instead infrequent. In Italy, the risk of contracting M. chimaera infections and the mortality reported are in line with other European countries, but significant heterogeneity exists on the mitigation strategies adopted to prevent further M. chimaera inoculations, suggesting the development of national guidelines.

Successful treatment of healthcare-associated Mycobacterium chimaera prosthetic infective endocarditis: the first Spanish case report.

BackgroundSince 2011, several cases of health care-related disseminated Mycobacterium chimaera infection outbreaks have been reported subsequent to cardiac surgery. Diagnosis is difficult and the prognosis is extremely poor despite long-term antibiotic treatment and surgery.Case summaryWe report a Spanish case of M. chimaera infective endocarditis (IE) with disseminated infection. The patient was treated with long-term antibiotic therapy, valve replacement, and the novel use of interferon-gamma as adjuvant therapy. In addition, [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) was used in combination with computed tomography (CT) to facilitate the diagnosis as well as to determine the duration of antibiotics and success of treatment.DiscussionDiagnosing M. chimaera IE is difficult and requires a high index of clinical suspicion. Controlling the infection is even more difficult. Interferon-g used adjuvant to surgery and antibiotic therapy could be useful in achieving this goal. Given that the appropriate duration of antibiotics is unknown, FDG PET/CT could also be a valuable tool for determining when antibiotic therapy can be withdrawn.

Cluster of invasive Mycobacteria chimaera infections following cardiac surgery demonstrating novel clinical features and risks of aortic valve replacement.

There is a global outbreak of infections due to Mycobacterium chimaera associated with cardiac surgery. The most serious infections involve prosthetic material implantation, and all have followed surgical procedures involving cardiopulmonary bypass. We describe a cluster of four cases following cardiac surgery at a tertiary referral centre in Sydney, Australia. We report novel clinical findings, including haemolysis and kidney rupture possibly related to immune reconstitution inflammatory syndrome. The positive effect of corticosteroids on haemodynamic function in two cases and the failure of currently recommended antimicrobial therapy to sterilise prosthetic valve material in the absence of surgery despite months of treatment are also critically examined. Positron emission tomography was positive in two cases despite normal transoesophageal echocardiograms. The proportion of cases with M. chimaera infection after aortic valve replacement (4/890, 0.45%; 95% confidence interval 0.18-1.15%) was significantly higher than after all other cardiothoracic surgical procedures (0/2433, 0%; 95% confidence interval 0-0.16%).