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The Drug-Induced Cardiotoxicity Website and App

Immune checkpoint inhibitors (ICI) - ICI combinatorial Rx

Specialities: Cardiology - Cardiovascular medicine · Intensive care medicine · Oncology · Thoracic oncology

The manifold possible adverse effects from ICI in varied organs must be checked in every patient receiving these medications. AEs tend to occur with higher frequency with combo theray than when these agent are taken in isolation. Anti CTLA-4, anti-CD52, anti-PD1, anti-PDL-1 antibodies (PMID 23714523, 24904570, 25776466). For review of pulmonary and nonpulmonary AEs, and management guidelines see under PMID 26371282, 29442540. Can be fatal (PMID: 29735504). For review see PMID 32158597.

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
I.c

Heart failure (biventricular, congestive)
I.d

Cardiovascular collapse - Cardiogenic shock - Hypotension

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

II.a

Cardiac arrhythmias or dysrhythmias (AF, VT, VF, TdP)
II.m

Sudden cardiac death

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-)

V - Myocarditis

V.a

Myocarditis (can be fulminant)
V.e

Necrotizing myocarditis (w/o evidence for CAD)

VI - Cardiomyopathy

VI.c

Takotsubo (stress) cardiomyopathy

VII - Cardiotoxicity

VII.a

Cardiotoxicity

X - Pulmonary edema - ALI/ARDS

X.a

Pulmonary edema, cardiogenic

XI - Pulmonary vasculopathies

XI.a

Pulmonary arterial hypertension

XII - Pericardial involvement

XII.b

Pericardial effusion (w/wo tamponade)

XIII - Thrombosis - Embolism

XIII.a

Pulmonary embolism - Venous thrombosis/thromboembolism

XIV - Pleural involvement

XIV.a

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

Serositis - Polyserositis

XV - Chest pain

XV.e

Pleuritis (can cause chest pain)

XVI - Hemorrhage - Bleeding - Hematoma

XVI.h

Coagulopathy

XXI - Mediastinal involvement/injury

XXI.a

Lymphadenopathy (intrathoracic)

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.d

Acute eosinophilic pneumonia (AEP)
XXIV.e

Relapsing or migrating pneumonitis/pneumonia (see also Id)
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.p

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

Delayed ILD, -pneumonitis, -fibrosis
XXIV.w

Radiation recall pneumonitis
XXIV.ac

Chronic pneumonitis
XXIV.ae

Shrinking lung syndrome

XXIX - Small airway involvement

XXIX.a

Bronchospasm - Wheezing - Asthma
XXIX.i

Exacerbation or deterioration of preexisting COPD

XXX - Imaging features

XXX.h

Imaging: Avid pleural uptake on PET-scan

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

XXXIII.f

Path: Myocardial vasculitis

XXXVI - Autoimmune syndromes - Systemic reactions or conditions

XXXVI.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)
XXXVI.q

Tumor lysis syndrome (TLS)
XXXVI.v

Temporal arteritis (Horton’s)