Prognostic Implications of a Modified Seattle Heart Failure Model Score following Transcatheter Aortic Valve Replacement

Background: The Seattle heart failure model (SHFM) score is a well-known risk predictor of mortality in patients with heart failure. We validated this score in patients receiving transcatheter aortic valve replacement (TAVR) and aimed to generate further risk discrimination by adding invasive hemodynamics parameters. Methods: Patients who underwent TAVR at our institute between 2015 and 2020 were included and followed for 2 years from index discharge. Patients were randomly assigned to the derivation cohort or the validation cohort. In the derivation cohort, the original SHFM score was modified by adding baseline hemodynamics parameters to evaluate the primary outcomes: 2-year incidence of mortality or readmission from heart failure. The model performance of the modified SHFM score was evaluated in the validation cohort. Results: A total of 217 patients (median age: 86 (83, 88) years old, 64 (29%) men) were included. From the derivation cohort (N = 108), a novel modified SHFM score was constructed: 6 × (original SHFM score <88.1%) + 5 × (pulmonary capillary wedge pressure > 14 mmHg) + 4 × (cardiac index < 2.26 L/min/m2), which had an improved discrimination compared with the original model (area under the curve: 0.887 versus 0.679, p = 0.014). In the validation cohort (N = 109), the modified SHFM score showed accurate predictive discrimination of the 2-year cumulative incidence of the primary endpoint into three groups (a low score group with 0–5 points, 3%; an intermediate score group with 6–10 points, 12%; and a high score group with 11–15 points, 43%, p < 0.001). Conclusion: A modified SHFM score consisting of the original SHFM score and invasive hemodynamics parameters predicted mortality and morbidity following TAVR. Evaluation of the external validity of this score in other cohorts needs further investigation.

Rodent General Anesthesia Suitable for Measurement of Experimental Invasive Hemodynamics

In cases of experimentally performed invasive rodent cardiovascular measurements, selected general anesthesia for a non-recovery procedure and its proper pain control plays a fundamental role in obtaining good data recordings. Rodent anesthesia is challenging for several reasons including high metabolic rate with elevated possibility of hypothermia and hypoglycemia during the procedure, large body surface area to adjust drug medication and anticipate drug clearance. In this review article, suitable analgesia, and anesthesia to collect rodent hemodynamics is discussed with examples of commonly used methods and anesthetic combinations to assess rodent hemodynamics. In case of injectable anesthesia, hemodynamic parameters should be measured when HR and mean arterial pressure (MAP) becomes stable. If re-injection is necessary, re-evaluation of HR and MAP is crucial for data integrity. Likewise, to safeguard data quality, longitudinal collection of HRs, HR variability, MAP and body temperature should be provided. For this reason, creation of a rodent hemodynamic anesthesia protocol might be necessary. In many cases, to refine surgical anesthetic protocol suitable for hemodynamic study, pilot experiments might be required to find the correct dose, and to probe for adequacy and duration of anesthesia, anticipating technical and procedural problems. Additionally, ensuring repeatability of the hemodynamic exam, selected experimental anesthetics should not be extensively metabolized. If metabolized, the effects on central and peripheral hemodynamics (HR, pre, afterload and contractility) should be well-known and documented.

Need for Speed: The Importance of Physiological Strain Rates in Determining Myocardial Stiffness

The heart is viscoelastic, meaning its compliance is inversely proportional to the speed at which it stretches. During diastolic filling, the left ventricle rapidly expands at rates where viscoelastic forces impact ventricular compliance. In heart disease, myocardial viscoelasticity is often increased and can directly impede diastolic filling to reduce cardiac output. Thus, treatments that reduce myocardial viscoelasticity may provide benefit in heart failure, particularly for patients with diastolic heart failure. Yet, many experimental techniques either cannot or do not characterize myocardial viscoelasticity, and our understanding of the molecular regulators of viscoelasticity and its impact on cardiac performance is lacking. Much of this may stem from a reliance on techniques that either do not interrogate viscoelasticity (i.e., use non-physiological rates of strain) or techniques that compromise elements that contribute to viscoelasticity (i.e., skinned or permeabilized muscle preparations that compromise cytoskeletal integrity). Clinically, cardiac viscoelastic characterization is challenging, requiring the addition of strain-rate modulation during invasive hemodynamics. Despite these challenges, data continues to emerge demonstrating a meaningful contribution of viscoelasticity to cardiac physiology and pathology, and thus innovative approaches to characterize viscoelasticity stand to illuminate fundamental properties of myocardial mechanics and facilitate the development of novel therapeutic strategies.