The Drug-Induced Cardiotoxicity Website and App

Chemotherapy, antineoplastic

Collectively, antineoplastic chemotherapy, myeloablative and conditioning regimens for HSCT, alkylating chemo agents, regimens containing bleomycin, busulfan, cyclophosphamide, gemcitabine, taxanes, G-CSF, FOLFOX/FOLFIRI produce lung injury including pulmonary edema, ARDS, diffuse alveolar hemorrhage and noninfectious lung injury. See under each specific drug or agent including radiation therapy and/or TBI. In a sizable fraction of patients, identification of the causal agent is difficult. A likelihood analysis is performed relating incidence, clinical, imaging and pathologic pattern of injury and the specific drug. Toxicity in lung cancer see PMID 21283982. The risk of developing pulmonary toxicity with chemotherapy may be increased in patients with preexisting ILD or IPF (PMID 19420811, 23171837, 25316105).

Frequency - Incidence

Incidence of cardiac adverse event(s) due to the specific drug as assessed by number of reported/published cases in the literature. Red digits in stars indicate: 0 = Very rare, questionable signal · 1 = < 10 cases · 2 = 10-50 cases · 3 = 50–100 cases · 4 = 100-200 cases · 5 = >200 cases

Evidence level/grade

Evidence level for cardiac adverse event(s) due to the specific drug as estimated using Hill’s (1965), Naranjo’s (1981), and Bégaud’s (1985) criteria applied to published cases. Blue digits in stars indicate: 0 = Questionable · 1 = Low · 2 = Moderate · 3 = Robust · 4 = Definite · 5 = Unquestionable, pathognomonic

I - Myocardial dysfunction - Heart failure

I.a

Left or biventricular dysfunction/failure

II - Cardiac arrhythmia(s)/dysrhythmia(s) (AF, VT, VF, TdP) - QTc prolongation)

II.a

Cardiac arrhythmias or dysrhythmias (AF, VT, VF, TdP)

II.b

Atrial fibrillation

III - Myocardial ischemia - Coronary artery disease

III.a

Coronary artery disease (acute) - Myocardial ischemia/infarction

IV - Heart block (bundle branch-, AV-block)

IV.a

Heart block (bundle branch- or AV-)

VI - Cardiomyopathy

VI.a

Cardiomyopathy (acute, subacute, chronic)

VI.c

Takotsubo (stress) cardiomyopathy

VII - Cardiotoxicity

VII.a

Cardiotoxicity

VIII - Valvular heart disease

VIII.a

Valvular heart disease and/or dysfunction

X - Pulmonary edema - ALI/ARDS

X.a

Pulmonary edema, cardiogenic

X.b

Pulmonary edema, noncardiogenic (NCPE)

X.f

Capillary leak syndrome (CLS)

XI - Pulmonary vasculopathies

XI.a

Pulmonary arterial hypertension

XI.i

Pulmonary veno-occlusive disease

XII - Pericardial involvement

XII.b

Pericardial effusion (w/wo tamponade)

XIV - Pleural involvement

XIV.a

Pleural effusion (uni- or bilateral) (can accompany DI-LDs)

XIV.f

Pneumothorax

XIV.l

Pneumothorax, bilateral

XIV.o

Pleuroparenchymal fibroelastosis (PPFE)

XV - Chest pain

XV.a

Chest pain (acute or subacute), lone or prominent

XVI - Hemorrhage - Bleeding - Hematoma

XVI.e

Alveolar hemorrhage (AH), diffuse AH (DAH)

XXI - Mediastinal involvement/injury

XXI.a

Lymphadenopathy (intrathoracic)

XXI.c

Pneumomediastinum

XXII - Acute respiratory/cardiorespiratory failure

XXII.b

ARDS - Acute lung injury

XXIV - Interstitial lung disease - Pulmonary infiltrates - Pulmonary fibrosis

XXIV.a

Pneumonitis (interstitial lung disease/ILD)

XXIV.b

Pneumonitis (ILD), acute and/or severe (may produce the ARDS pattern)

XXIV.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

XXIV.f

Diffuse alveolar damage (DAD) (see alsoo under IIb and XVf)

XXIV.h

Pulmonary fibrosis

XXIV.j

Progression, acceleration or exacerbation of preexisting ILD/fibrosis

XXIV.k

Organizing pneumonia pattern (an area or areas of consolidation on imaging)

XXIV.m

Acute fibrinous organizing pneumonia (AFOP)

XXIV.n

Subclinical pulmonary infiltrates/ILD

XXIV.p

Rapidly progressive ILD/pulmonary fibrosis (a.k.a. Hamman-Rich syndrome)

XXIV.r

Delayed ILD, -pneumonitis, -fibrosis

XXIV.s

Lung nodule or nodules

XXIV.t

ILD with a granulomatous component

XXIV.w

Radiation recall pneumonitis

XXIV.ad

Pulmonary alveolar proteinosis (PAP) (secondary)

XXVI - Neuromuscular dysfunction

XXVI.a

Phrenic nerve injury - Hemi- or bilateral diaphragmatic paralysis

XXVIII - Large airway involvement including UAO

XXVIII.a

Angioedema (may cause UAO, asphyxia and death)

XXVIII.m

Bronchiectasis

XXIX - Small airway involvement

XXIX.a

Bronchospasm - Wheezing - Asthma

XXX - Imaging features

XXX.i

Imaging: Cavitating/cavitary lung nodule, mass or nodules (see also Iq, XIs, XIIi, XVIaa and XVIIp)

XXXIII - Histopathology (for pulmonary pathology see in ‘Pneumotox’ (a free companion App)

XXXIII.m

Path: Pulmonary veno-occlusive disease (PVOD)

XXXIII.y

Path: Acute fibrinous organizing pneumonia (AFOP-pattern)

XXXIV - Infections

XXXIV.e

Tuberculosis (pulmonary, pulmonary, extrapulmonary or disseminated). Reactivation or de novo

XXXIV.f

Opportunistic pulmonary/systemic infections

XXXIV.g

Pneumocystis jiroveci pneumonia

XXXVI - Autoimmune syndromes - Systemic reactions or conditions

XXXVI.b

Lupus - Lupus syndrome (see also Vd)

XXXVI.c

Sarcoid-like granulomatosis (endo-/extrathoracic)

XXXVI.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)

XXXVI.q

Tumor lysis syndrome (TLS)

XXXVIII - Miscellaneous - Varia

XXXVIII.k

Hypersensitivity reaction (may manifest with fever and/or skin, throat or airway involvement)

XXXVIII.n

Hiccup

XXXVIII.y

Neutropenia, agranulocytosis (w/wo infection/sepsis)