Cardiac hypertrophy is a predictor of survival in patients undergoing allogeneic stem cell transplantation

Daniel Finke (Heidelberg)1, J.-P. Lange (Heidelberg)1, S. Romann (Heidelberg)1, M. Heckmann (Heidelberg)1, H. Hund (Heidelberg)1, P. Dreger (Heidelberg)2, N. Frey (Heidelberg)1, T. Luft (Heidelberg)2, L. H. Lehmann (Heidelberg)1

1Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland; 2Universitätsklinikum Heidelberg Klinik für Hämatologie und Onkologie Heidelberg, Deutschland

 

The cardiological assessment of patients before planned allogeneic stem cell transplantation (alloSCT) relies mainly on echocardiography. The left ventricular ejection fraction (LVEF) is the most relevant parameter to decide on cardiac limitations of the oncological therapy.

To evaluate a prognostic effect of further echocardiographic parameters, we retrospectively collected and analyzed echocardiographic and epidemiologic data from 599 patients who underwent alloSCT at the Heidelberg University Hospital between March 2002 and June 2018. These patients were assessed by echocardiography at median 27 days prior to alloSCT. 

In terms of LVEF, the commonly used cutoff of LVEF ≤ 50%, did not discriminate patients in non-relapse mortality (NRM) (log-rank test, p < 0.46). In turn, patients with LVEF ≤ 40% before alloSCT had a significantly lower NRM (log-rank test, p < 0.01). We evaluated the prognostic value of other echocardiographic parameters, in comparison to cardiovascular risk factors such as smoking status, hyperlipidemia, diabetes and arterial hypertension (aHT). History of prior cardiac diseases and increased posterior wall thickness (PW) ≥ 10mm correlated in univariable Cox regression with reduced 5-year all-cause mortality (ACM) (logistic regression, p = 0.016) as well as a reduced LVEF ≤ 40% (logistic regression, p = 0.003). Both, LVEF and PW, were independent predictors in a multivariate analysis (LVEF ≤ 40%: p = 0.007; PW: p = 0.016). 

High-intensity myeloablative conditioning (MAC) prior to alloSCT could potentially associate with more cardiac complications than reduced intensity conditioning (RIC). Therefore, we selected patients who received RIC (n = 478) and used shorter time periods of NRM (one and two years) after alloSCT as endpoints in logistic regression analyses. In these patients, cardiac hypertrophy was again a predictor for mortality (posterior wall and hypertrophic septum), in contrast to LVEF (logistic regression, PW: p = 0.007, LVEF ≤ 40%, p = 0.08, Septum ≥11mm: p = 0.02). In addition, cardiovascular risk factors (aHT and obesity (BMI > 30 kg/m2)) were significantly associated with 2 year NRM (logistic regression, aHT: p = 0.01, BMI: 0.02) but not with ACM (logistic regression, aHT: p = 0.3, BMI: p = 0.3), suggesting a role of cardiovascular risk factors in mortality of cancer patients, independently of cancer-progression.

In conclusion, longterm overall survival after alloSCT is substantially worse in patients with LVEF ≤ 40%. Arterial hypertension and cardiac hypertrophy adversely affect non-relapse mortality up to two years after transplantation.

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