A Study of Vericiguat in People With Breast Cancer and Cancer Therapy-Related Cardiac Dysfunction

Inclusion Criteria:

* Age ≥ 18 years
* Biopsy proven breast cancer (stage I-IV)
* Cancer treatment related cardiac dysfunction (CTRCD), established by an absolute decrease in LVEF ≥ 10% from baseline/pre-treatment to \< 53% and attributable to prior cardiotoxic cancer treatment, per the clinical investigator.
* Able to complete an acceptable baseline CPET, in the absence of high-risk ECG findings or other inappropriate response to exercise as determined by the PI, as defined by any of the following criteria:

  * Achieving a plateau oxygen consumption, concurrent with an increase in power output;
  * A respiratory exchange ratio ≥ 1.00;
  * Attainment of maximal predicted heart rate, as defined by a peak heart rate within 10bpm of the age predicted maximal heart rate (220 - Age\[years\]); or if on a beta-blocker, 164 - (age \* 0.7)
  * Volitional exhaustion, as measured by a rating of perceived exertion (RPE) ≥ 18 on the BORG scale.
* Willing to use highly effective contraceptive measures if of child-bearing potential or if the patient's sexual partner is a woman of child-earing potential while receiving study drug and for 30 days after the last dose of study drug:

  * Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test (within 6 months prior to study enrollment) and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  * Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
  * Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the postmenopausal range for the institution
  * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation.
* Male subjects should be willing to use barrier contraception °Willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

* Systolic blood pressure \< 90 mmHg
* Concurrent or anticipated use of a long-acting nitrate or NO donor (e.g., nitroglycerin, isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal NTG patch, or molsidomine).
* Concurrent or anticipated use of a phosphodiesterase inhibitor (e.g., vardenafil, tadalafil, or sildenafil).
* Cardiac comorbidity, including any of the following:

  * Hypertrophic cardiomyopathy, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac sarcoidosis, or amyloid cardiomyopathy
  * Uncontrolled arrhythmia
  * Uncorrected congenital cardiac disease
  * Acute coronary syndrome, percutaneous coronary intervention, or coronary artery bypass graft surgery within 3 months prior to randomization.
  * Symptomatic carotid stenosis, or transient ischemic attack (TIA) or stroke within 3 months prior to randomization.
  * Cardiac transplantation
* Valvular heart disease requiring surgery or intervention
* Non-cardiac comorbidity, including any of the following:

  * eGFR \< 15ml/min/1.73m\^2 (based upon CKD-EPI, Cockroft-Gault, etc.)
  * Severe hepatic insufficiency (e.g., Child-Pugh C)
  * Severe pulmonary disease, such as requiring continuous home oxygen or interstitial lung disease
  * Other medical disorder or condition that in the opinion of the investigator would impair the subject's ability to participate or complete the study
* Subjects must not have any of the following absolute contraindications to cardiopulmonary exercise testing:

  * Acute myocardial infarction (within 30 days of any planned study procedures)
  * Unstable angina
  * Uncontrolled arrhythmias causing symptoms or hemodynamic compromise,
  * Symptomatic severe aortic stenosis
  * Recurrent syncope
  * Active endocarditis
  * Acute myocarditis or pericarditis
  * Acute pulmonary embolus or pulmonary infarction (within 3 months of any planned study procedures)
  * Thrombosis of lower extremities (within 3 months of any planned study procedures)
  * Suspected dissecting aneurysm
  * Uncontrolled asthma
  * Pulmonary edema
  * Room air desaturation at rest ≤85%
  * Respiratory failure
  * Acute noncardiopulmonary disorder that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)
  * Mental impairment leading to inability to cooperate.
* Current alcohol and/or drug abuse
* Any other condition or intercurrent illness (e.g., symptomatic weight-bearing bone metastases or limited life expectancy \< 6-9 months) that, in the opinion of the investigator, makes the participant a poor candidate for the trial