The Corrupt Heart is the final boss, fought in Act 4. It is very powerful; its innate powers and buffs it gains throughout the fight can prove very difficult to counter. Because of its Invincible buff, it can only take 300 (200) damage per turn, rendering strategies that rely on heavy damage less effective. Additionally, it will gain incredible amounts of Strength on its fourth buff and onward, so killing it quickly is also important.
Do not use either of the first two cards in this list on a turn where The Heart buffs. It will clear the strength down debuff, then gain back the strength you made it lose from the card, essentially making you give The Heart free strength.
Any source of Weak will also be extremely valuable against both of The Heart's attacks.
Sources of damage negation such as Intangible and Buffer can be very effective against the Echo attack. Intangible is also reasonably useful against Blood Shots, as it will always lower the damage to 12 (15), whereas Buffer would only negate 1 (2) of the attacks.
Incense Burner is a source of Intangible that can reliably block Blood Shots or Echo on turn two or three, if you end the Spire Shield and Spire Spear fight with it on 3 or 4. Because the attack pattern repeats every three turns, it will activate again on turn 9 or 10, during The Heart's third use of Blood Shots or Echo. Alternatively, it also works to set the relic to 0 or 1 to block the second and fourth cycles.
Any effect that triggers on-damage or on-attack is very good against The Heart due to it triggering 12 (15) times for each Blood Shots that The Heart does. This includes:
Medical Kit can be useful against The Heart, as it will allow you to remove the many statuses it will inflict on you, but beware of its Beat of Death power, as it will trigger whenever you play any card, including curses and statuses.
Tungsten Rod or After Image can completely negate Beat of Death 1. Both of these, 2 copies of After Image, or gaining Intangible with either is necessary to negate Beat of Death 2, which is found on Ascension 19+ or applied on The Heart's second Buff action.
Mitigating the debuffs from Debilitate is important to take less damage in the first attack cycle. This includes:
Artifact, with one stack negating Vulnerable since it's applied first, and three negating all. Saving an Ancient Potion is a strong option for this strategy.
While Weak isn't a major problem if the goal is to block the first cycle, Ginger will prevent it, which means that Frail will be negated by a second stack of Artifact since it's applied third. This is notable because Panacea+ provides two stacks, and so does an Ancient Potion combined with Sacred Bark.
Clockwork Souvenir and Orange Pellets, both shop-exclusive relics, provide very reliable ways to deal with these debuffs, so checking the rightmost relic slot in shops, where such relics are always found, for these and purchasing them is a priority.
Because Vault does not affect buffs on enemies, the Invincible damage cap is not reset for the extra turn.
Trivia[]
An early version of this boss, which didn't make it past the playtesting phase around two years before it was released, used to deal 1 blockable damage per second instead of per card played.[1] This would make it the only timing-based gameplay mechanic outside of the Speed Climber Achievement and the Speedster and Lightspeed Scores.
Strength on its fourth buff and onward, so killing it quickly is also important.
Vulnerable, 2 
Weak, and 2 
Frail in that order.
4+ damage.
Weak will also be extremely valuable against both of The Heart's attacks.
