Hemodynamics, echocardiography, and biomarkers in different heart failure phenotypes

Background: Heart failure (HF) is a major health problem affecting millions of patients worldwide and is associated with impaired quality of life and poor prognosis. Different approaches including invasive and non-invasive methods can be used to provide information about the cardiac performance in HF patients. The overall aim of this thesis was to study a number of different but complementary invasive and non-invasive methods that are currently used to assess cardiac performance in different HF phenotypes, mainly in advanced HF.

Methods and results: Study I. Twenty-three patients with advanced stable chronic HF received a single 24 h levosimendan infusion. Levosimendan had the following effects (median change ± SD): a significant increase in cardiac output (+9.8 ± 21.6%; P = 0.026) and decrease in N-terminal pro-brain natriuretic peptide (-28.1 ± 16.3%, P < 0.001), estimated total peripheral resistance (-16.9 ± 18.3%, P = 0.004), and mean arterial pressure (-5.9 ± 8.2%, P = 0.007). There was no change in estimated glomerular filtration rate (+0.89 ± 14.0%, P = 0.955). No significant associations between baseline clinical and/or hemodynamic factors and the change in CO were found. Study II. Levels of soluble suppression of tumorigenicity 2 (sST2) were investigated in HF with reduced ejection fraction (HFrEF), preserved EF (HFpEF) and in healthy controls. Crude sST2 levels were higher in HFrEF compared to HFpEF and controls. sST2 was associated with the composite endpoint of death or HF hospitalization in HFpEF, adjusted hazard ratio (HR) per log increase in sST2 6.62, 95% confidence interval (CI) 1.04–42.28, p=0.046, and in HFrEF with death, heart transplant or left ventricular assist device (LVAD); 3.51, 95% CI 1.05–11.69, p=0.041. Study III. In 192 patients with hemodynamic findings indicating HF, right heart catheterization waveforms were used to measure the pulsatile and steady components of the pulmonary capillary wedge pressure (PAWP) and to assess their impact on the pulmonary arterial compliance (PAC) and pulmonary vascular resistance (PVR) relationship. PAC and PVR were hyperbolically and inversely associated. In the patient cohort with higher pulsatile PAWP component, there was a significant downward and leftward shift of the PAC-PVR curve fit. The steady PAWP component did not impact significantly on the PAC-PVR relationship. Study IV. Data from 14 LVAD patients assessed by echocardiographic ramp test was retrospectively reviewed. Adequate left ventricular (LV) unloading was defined as no more than mild mitral regurgitation, and intermittent aortic valve (AV) opening or closed AV, and reduction of LV end-diastolic diameter, and for the follow-up measurement, decreased NT-proBNP. Ramp testing resulted in final LVAD speed increase in 79% of patients and a median net change of 200 (200; 300) revolutions per minute. Speed adjustments after ramp testing resulted in improved LV unloading in additional 21% of patients who were not originally optimized. Right ventricular function did not worsen.

Conclusion: By assessing hemodynamics, echocardiography and biomarkers, it is possible to gain a better understanding of the different HF phenotypes and the underlying physiology, which may help to optimize care and introduce potential targets for therapy.

List of scientific papers

I. Najjar, E., M. Stalhberg, C. Hage, E. Ottenblad, A. Manouras, I. Haugen Lofman and L. H. Lund. (2018). Haemodynamic effects of levosimendan in advanced but stable chronic heart failure. ESC Heart Fail. 5(3): 302-308.
https://doi.org/10.1002/ehf2.12272

II. Najjar, E., U. L. Faxen, C. Hage, E. Donal, J. C. Daubert, C. Linde and L. H. Lund. (2019). ST2 in heart failure with preserved and reduced ejection fraction. Scand Cardiovasc J. 53(1): 21-27.
https://doi.org/10.1080/14017431.2019.1583363

III. Najjar, E., L. H. Lund, C. Hage, J. Johnson and A. Manouras. Left atrial pressure pulsatility attenuates pulmonary arterial compliance in heart failure. [Manuscript]

IV. Najjar, E., T. Thorvaldsen, M. Dalén, P. Svenarud, A. Hallberg Kristensen, M. J. Eriksson, E. Maret and L. H. Lund. Validation of non-invasive ramp testing for HeartMate 3. [Submitted]