Abstract
BACKGROUND: Objective tools to define the optimal time for referral for advanced therapies and to help guide escalation and de-escalation of support can improve management decisions and outcomes for patients with advanced heart failure. The current parameters have variable prognostic potential depending on the patient population being studied and often have arbitrary thresholds. METHODS: Here, a mathematical and physiological framework to define the patient-specific tipping point of myocardial energetics is defined. A novel hemodynamic parameter known as the myocardial performance score (MPS), a marker of power and efficiency, is introduced that allows for the objective assessment of the physiological tipping point. The performance of the MPS and other advanced hemodynamic parameters including aortic pulsatility index (API) and cardiac power output (CPO) in predicting myocardial energetics and the overall myocardial performance was evaluated using a validated computer simulation model of heart failure (Harvi) as well as a proof-of-concept clinical validation using a cohort of the Society for Cardiovascular Angiography and Interventions (SCAI) Stage C cardiogenic shock patients. RESULTS: Approximately 1010 discrete heart failure scenarios were modeled. API strongly correlated with the left ventricular coupling ratio (R(2) = 0.81) and the strength of association became even stronger under loaded conditions where pulmonary capillary wedge pressure (PCWP) was >20 mmHg (R(2) = 0.94). Under loaded conditions, there is a strong logarithmic relationship between MPS and mechanical efficiency (R(2) = 0.93) with a precipitous rise in potential energy (PE) and drop in mechanical efficiency with an MPS <0.5. An MPS <0.5 was able to predict a CPO <0.6 W and coupling ratio of <0.7 with sensitivity (Sn) of 87%, specificity (Sp) of 91%, positive predictive value of 81%, and negative predictive value of 94%. In a cohort of 224 patients with SCAI Stage C shock requiring milrinone initiation, a baseline MPS score of <0.5 was associated with a 35% event rate of the composite endpoint of death, left ventricular assist device, or transplant at 30 days compared with 3% for those with an MPS >1 (p < 0.001). Patients who were able to augment their MPS to >1 after milrinone infusion had a lower event rate than those with insufficient reserve (40% vs. 16%, p = 0.01). CONCLUSIONS: The MPS, which defines the patient-specific power-to-efficiency ratio and is inversely proportional to PE, represents an objective assessment of the myocardial energetic state of a patient and can be used to define the physiological tipping point for patients with advanced heart failure.