A pharmaceutical composition for use in the treatment of a cardiovascular disease which is bradycardia, symptomatic sinus bradycardia, ventricular bradycardia or atrial bradycardia in order to enhance cardiac output, said pharmaceutical composition comprising: (a) the four following compounds: (i) a phosphodiesterase inhibitor or an adenosine receptor antagonist, wherein the phosphodiesterase inhibitor or adenosine receptor antagonist is theophylline, or an isotopic variant thereof; or a pharmaceutically acceptable salt, hydrate, or solvate thereof, (ii) a calcium channel blocker, wherein the calcium channel blocker is nifedipine, or an isotopic variant thereof; or a pharmaceutically acceptable salt, hydrate, or solvate thereof, (iii) a histamine Hi-receptor agonist, or a histamine H 3 -receptor antagonist, wherein the histamine Hi-receptor agonist or histamine H 3 -receptor antagonist is betahistine or betahistine dihydrochloride, or an isotopic variant thereof, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, or (iv) a β 2 -adrenoreceptor agonist, wherein the β 2 -adrenergic receptor agonist is levalbuterol, or an isotopic variant thereof; levalbuterol hydrochloride, or a pharmaceutically acceptable salt, hydrate, or solvate thereof; and (b) a pharmaceutically acceptable excipient, wherein the pharmaceutical composition is formulated in a dosage form for injectable or oral administration. (a) the four following compounds: (i) a phosphodiesterase inhibitor or an adenosine receptor antagonist, wherein the phosphodiesterase inhibitor or adenosine receptor antagonist is theophylline, or an isotopic variant thereof; or a pharmaceutically acceptable salt, hydrate, or solvate thereof, (ii) a calcium channel blocker, wherein the calcium channel blocker is nifedipine, or an isotopic variant thereof; or a pharmaceutically acceptable salt, hydrate, or solvate thereof, (iii) a histamine Hi-receptor agonist, or a histamine H 3 -receptor antagonist, wherein the histamine Hi-receptor agonist or histamine H 3 -receptor antagonist is betahistine or betahistine dihydrochloride, or an isotopic variant thereof, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, or (iv) a β 2 -adrenoreceptor agonist, wherein the β 2 -adrenergic receptor agonist is levalbuterol, or an isotopic variant thereof; levalbuterol hydrochloride, or a pharmaceutically acceptable salt, hydrate, or solvate thereof; and (i) a phosphodiesterase inhibitor or an adenosine receptor antagonist, wherein the phosphodiesterase inhibitor or adenosine receptor antagonist is theophylline, or an isotopic variant thereof; or a pharmaceutically acceptable salt, hydrate, or solvate thereof, (ii) a calcium channel blocker, wherein the calcium channel blocker is nifedipine, or an isotopic variant thereof; or a pharmaceutically acceptable salt, hydrate, or solvate thereof, (iii) a histamine Hi-receptor agonist, or a histamine H 3 -receptor antagonist, wherein the histamine Hi-receptor agonist or histamine H 3 -receptor antagonist is betahistine or betahistine dihydrochloride, or an isotopic variant thereof, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, or (iv) a β 2 -adrenoreceptor agonist, wherein the β 2 -adrenergic receptor agonist is levalbuterol, or an isotopic variant thereof; levalbuterol hydrochloride, or a pharmaceutically acceptable salt, hydrate, or solvate thereof; and (b) a pharmaceutically acceptable excipient, wherein the pharmaceutical composition is formulated in a dosage form for injectable or oral administration.