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at least 14 days and up to 21 days (total antibiotic course), depending on the severity of clinical presentation and response to treatment. The prognosis for early-treated disseminated LC is favourable, with complete recovery occurring in most patients treated with antibiotics.484,487 Although LC may resolve spontaneously, antibiotic therapy shortens the disease duration and prevents further complications.

9.5.3 Chagas disease

Chagas disease (CD) is a systemic disorder caused by the protozoan parasite T. cruzi, which is transmitted through a haematophagous triatomine insect vector in endemic areas, such as Latin America, and can be transmitted transplacentally, by infected blood, or even orally through ingestion of contaminated food and drinks. Current migration has made CD a global disease, and congenital transmission has become relevant in non-endemic areas, including Europe.

9.5.3.1 Presentation

Acutely infected individuals remain asymptomatic or show mild and non-specific symptoms. Intense direct tissue parasitism may result in AM in less than 5% of cases. Chagas disease may evolve into CMP in 20%–30% of cases. Common findings in patients with Chagas CMP include brady- or tachyarrhythmias, dilated ventricles with regional (mainly inferior, inferolateral, or apical) or global systolic dysfunction, and thromboembolism.

9.5.3.2 Diagnosis

Diagnosis of CD requires a high clinical suspicion. Polymerase chain reaction testing is the most sensitive test in acute infection while, for diagnosing chronic CD, the combination of two serological tests with antigens that detect different antibodies against T. cruzi is preferable. Multimodality imaging is able to support the diagnosis, as often apical aneurysms with and without thrombi can be detected by CMR.488

9.5.3.3 Therapy

Eradication of the parasite is a target in early phases, and anti-parasitic treatment should be provided as soon as possible, following detection of an acute infection. In the BENEFIT (Benznidazole Evaluation for Interrupting Trypanosomiasis) trial, 2854 patients with Chagas CMP were randomized to either benznidazole or placebo for 80 days. Benznidazole significantly reduced serum parasite detection, but there was no significant reduction in clinical cardiac deterioration at 5 years.489 Therefore, anti-trypanosomal treatment should not be routinely used in adult patients with chronic CMP, but it can be considered in early and mild forms490,491 (see Table 12). Patients with Chagas CMP should be treated according to HF guidelines. Chagas disease is associated with high morbidity and mortality, with an annual rate of cardiovascular death of 6%.492 In this population, the benefit of ICD in primary and secondary prevention is controversial, since observational studies did not demonstrate a mortality benefit compared with amiodarone.493 However, a systematic review and meta-analysis showed that, in patients with previous VT, appropriate ICD interventions and electric storms were frequent, occurring at a rate of 25% and 9% per year, respectively, with an overall mortality of 9% per year.494 A case-based decision is warranted. 9.6 Drug- or vaccine-induced myocarditis

9.6.1. Drug-induced myocarditis 9.6.1.1. Immune checkpoint inhibitor-induced myocarditis Immune checkpoint inhibitors have revolutionized cancer treatment and are approved in multiple cancer types. These agents are monoclonal antibodies blocking specific molecules that inhibit the immune response—CTLA-4 (cytotoxic T-lymphocyte antigen 4), PD-1 (programmed cell death protein 1) and its ligand PD-L1 (programmed death ligand 1), and LAG-3 (lymphocyte activation gene 3)—strongly enhancing T-cell responses against cancer. By activating the immune system, ICIs may induce immune-related adverse events, which can affect any organ. Myocarditis is one of the most feared complications,495–497 although rare, as it affects approximately 1% of treated patients, within the first weeks following the initiation of therapy.495 Since a growing number of patients are eligible for ICI treatment, the absolute number of cases is increasing. One of the largest case series, including 122 patients with ICI-associated myocarditis, recorded early onset after treatment initiation (median 30 days), and up to 50% mortality.496 A systematic analysis of the World Health Organization (WHO) pharmacovigilance database confirmed a high mortality rate up to 33%.498 The main risk factor for ICI-induced AM is combination therapy with two types of ICI, such as an anti-CTLA-4, e.g. ipilimumab, combined with an anti-PD-1, e.g. nivolumab.499 This complication affects mostly men495 and older patients (median age 65 years) with more comorbidities.28,495 Furthermore, if ICIs are combined with other cancer therapies, their toxicity aggravates.

9.6.1.1.1 Presentation. Immune checkpoint inhibitor-induced myo-

carditis is especially arrhythmogenic, including a risk of conduction disorders, and HF with reduced EF occurs in about half of patients.500 Myocarditis is frequently associated with peripheral myositis, which, when associated with respiratory failure, can negatively affect survival.

9.6.1.1.2 Diagnosis. When suspected, rapid diagnostic triage is

needed.495–497 Early diagnosis is extremely important, usually including laboratory tests and multimodality imaging (Section 5). The detection of a coexisting CAD in older patients should not refrain from further work-up for myocarditis (Table 4). In inconclusive cases an EMB can be necessary. For more details, see the 2022 ESC cardio-oncology guidelines.501

9.6.1.1.3 Therapy. After diagnosis, immediate discontinuation of ICI

and early (within the first 24 h) initiation of corticosteroids is warranted. Up to 50% of patients will be refractory to corticosteroids. In this situation, second-line immunosuppression treatments are necessary (see Table 12).502 In a prospective registry, the combination of ruxolitinib and high doses of abatacept, and screening for concurrent respiratory muscle failure, was associated with improved survival.502 Long-term cardiovascular effects of ICIs become more and more relevant since a growing number of cancer patients are exposed to this therapy.503,504 Rechallenge with an ICI has to be considered following a multidisciplinary team discussion, based on factors such as the severity of the myocarditis, cancer prognosis, oncology treatment options, and patient preference.504,505 Details are given in the 2022 ESC guidelines for cardio-oncology.501

ESC Guidelines                                                                                                                                                                                          4005

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