The time course of natriuretic hormones as plasma markers of myocardial recovery in heart transplant candidates during ventricular assist device support reveals differences among device types

Milting, Hendrik; Banayosy, Aly El; Kassner, Astrid; Fey, O.; Sarnowski, Peter; Arusoglu, Latif; Thieleczek, Rolf; Brinkmann, Thomas; Kleesiek, Knut; Körfer, Reiner

doi:10.1016/s1053-2498(01)00289-3

Cited by 60 publications

(33 citation statements)

References 22 publications

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“…39,40 Meanwhile, the status of NPs in relation to mechanical support has been investigated in a few studies of adult populations. 5,37,[41][42][43][44] The present study has shown a significant decrease in serum NP concentration during Excor support in children; this coincides with a decrease in LVEDD ( Figure 2). After 1 week, LVEDD remained stable, whereas levels of NPs showed further down-regulation on Day 30 as compared with 1 week after Excor implantation (Figures 1 and 2).…”

Section: Discussionsupporting

confidence: 72%

“…5 In adult patients with heart failure the concentration of natriuretic peptides (NPs) correlates with the degree of ventricular dysfunction and is a strong, independent predictor of mortality. 6 -11 In adults, plasma neurohormone levels seem to correlate with the morphologic improvement during mechanical circulatory support (MCS), 12,13 but little is known about remodeling after severe myocardial destruction and MCS in children.…”

mentioning

confidence: 99%

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Biomarker Responses During Mid-term Mechanical Cardiac Support in Children

Heise¹,

Lemmer²,

Weng³

et al. 2008

The Journal of Heart and Lung Transplantation

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Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

Biomarker Responses During Mid-term Mechanical Cardiac Support in Children

Heise¹,

Lemmer²,

Weng³

et al. 2008

The Journal of Heart and Lung Transplantation

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“…Consequently, an inverse relationship between SERCA and BNP in failing myocardium has been reported previously by us and others. 20,21 Likewise, BNP expression has been shown to decrease 18,22 and SERCA expression to recover 23 during mechanical support in LVAD-treated patients. However, to the best of our knowledge, we are the first to investigate and demonstrate a direct causal relationship between BNP levels and SERCA expression in the myocardium.…”

Section: Discussionmentioning

confidence: 99%

“…LVAD treatment, which is targeted at mechanically unloading the failing heart, has been reported to induce reverse remodeling of the heart 17 and thus may cause downregulation of myocardial BNP expression and upregulation of SERCA2a. 18 We therefore analyzed BNP and SERCA2a mRNA expression levels in sequential myocardial biopsies obtained at the times of device implantation and transplantation and for both genes assessed relative changes in expression between implantation and transplantation ( Figure 8). The response of individual patient BNP expression levels to LVAD treatment was variable ( Figure 8A).…”

Section: Relationship Between Bnp and Serca2a Expression In Human Myomentioning

confidence: 99%

Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca ²⁺ ATPase Expression

et al. 2006

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Background— In heart failure (HF), ventricular myocardium expresses brain natriuretic peptide (BNP). Despite the association of elevated serum levels with poor prognosis, BNP release is considered beneficial because of its antihypertrophic, vasodilating, and diuretic properties. However, there is evidence that BNP-mediated signaling may adversely influence cardiac remodeling, with further impairment of calcium homeostasis. Methods and Results— We studied the effects of BNP on preload-dependent myocardial sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a) expression. In rabbit isolated muscle strips stretched to high preload and shortening isotonically over 6 hours, the SERCA/glyceraldehyde phosphate dehydrogenase mRNA ratio was enhanced by 168% (n=8) compared with unloaded preparations (n=8; P <0.001). Recombinant human BNP at a concentration typically found in end-stage HF patients (350 pg/mL) abolished SERCA upregulation by stretch (n=9; P <0.0001 versus BNP free). Inhibition of cyclic guanosine 3′,5′ monophosphate (cGMP)–phosphodiesterase-5 mimicked this effect, whereas inhibition of cGMP-dependent protein kinase restored preload-dependent SERCA upregulation in the presence of recombinant human BNP. Furthermore, in myocardium from human end-stage HF patients undergoing cardiac transplantation (n=15), BNP expression was inversely correlated with SERCA levels. Moreover, among 23 patients treated with left ventricular assist devices, significant SERCA2a recovery occurred in those downregulating BNP. Conclusions— Our data indicate that preload stimulates SERCA expression. BNP antagonizes this mechanism via guanylyl cyclase-A, cGMP, and cGMP-dependent protein kinase. This novel action of BNP to uncouple preload-dependent SERCA expression may adversely affect contractility in patients with HF.

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“…19 Recent reports of the neurohormonal changes in patients implanted with an LVAD have suggested that BNP concentration falls to a steady state between 30 and 60 days after implantation; this early fall in BNP concentration is proposed to be indicative of the recovery of native ventricular function. 20,21 A previous retrospective study also reported that maximal improvement in myocyte diameter and collagen deposition had occurred after 40 days of LVAD support 19 and that structural reverse remodeling had peaked and was complete within 60 days of implantation. 22 In our cohort, changes in postimplantation BNP concentration occurred over a similar time course to those documented by other investigators, and they achieved a steady state by 60 days after implantation, despite LVAD support being provided for much longer.…”

Section: Discussionmentioning

confidence: 96%

Serum Brain Natriuretic Peptide Concentration 60 Days After Surgery as a Predictor of Long-Term Prognosis in Patients Implanted With a Left Ventricular Assist Device: Erratum

2016

ASAIO Journal

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Mechanical circulatory support by a left ventricular assist device (LVAD) is used to bridge patients with advanced heart failure to transplant or as a definitive treatment. We retrospectively sought predictors of long-term outcome in a cohort of 83 patients who had undergone LVAD treatment. We subjected perioperative clinical data of patients to statistical analysis to establish parameters associated with all-cause mortality, and the cutoff values, sensitivity, and specificity of those that had a statistically significant relation with survival. Mean follow-up was 717 days (standard deviation, 334 days; range, 17-1,592 days). Fourteen patients (16.8%) died, but nine (10.8%) were weaned from support. Serum brain natriuretic peptide (BNP) concentration measured 60 days after implantation was significantly associated with all-cause mortality. The optimal BNP cutoff value to predict death during LVAD support was 322 pg/ml, with a sensitivity of 71.4% and specificity of 79.8%. Two-year survival was 92.0% in those with 60 days serum BNP concentration <322 pg/ml compared with 70.5% in those in whom it was ≥322 pg/ml (p = 0.003). The relation between BNP and survival likely reflects recovery of native myocardial function and improvements in global health and should assist clinicians in the on-going management of long-term LVAD therapy. ASAIO Journal 2015; 61:373-378.

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The time course of natriuretic hormones as plasma markers of myocardial recovery in heart transplant candidates during ventricular assist device support reveals differences among device types

Cited by 60 publications

References 22 publications

Biomarker Responses During Mid-term Mechanical Cardiac Support in Children

Biomarker Responses During Mid-term Mechanical Cardiac Support in Children

Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca ²⁺ ATPase Expression

Serum Brain Natriuretic Peptide Concentration 60 Days After Surgery as a Predictor of Long-Term Prognosis in Patients Implanted With a Left Ventricular Assist Device: Erratum

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The time course of natriuretic hormones as plasma markers of myocardial recovery in heart transplant candidates during ventricular assist device support reveals differences among device types

Cited by 60 publications

References 22 publications

Biomarker Responses During Mid-term Mechanical Cardiac Support in Children

Biomarker Responses During Mid-term Mechanical Cardiac Support in Children

Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca 2+ ATPase Expression

Serum Brain Natriuretic Peptide Concentration 60 Days After Surgery as a Predictor of Long-Term Prognosis in Patients Implanted With a Left Ventricular Assist Device: Erratum

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Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca ²⁺ ATPase Expression