Dataset Information

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

ABSTRACT: Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables.The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (??Tpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included.The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ??Tpe and TMR. For PFD, the indices were diabetes, NYHA class, ??Tpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers.The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients.

SUBMITTER: Ramirez J

PROVIDER: S-EPMC5636125 | biostudies-other | 2017

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

Ramírez Julia J Orini Michele M Mincholé Ana A Monasterio Violeta V Cygankiewicz Iwona I Bayés de Luna Antonio A Martínez Juan Pablo JP Laguna Pablo P Pueyo Esther E

PloS one 20171011 10

<h4>Background</h4>Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables.<h4>Methods</h4>The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSI ...[more]

PMID: 29020031

Similar Datasets

Project description:Sudden cardiac death (SCD) associated with heart failure (HF) is a multifactorial problem requiring a systems level approach applied to suitable experimental animal models with features of the human disease. Here we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated HF and SCD by integrated analysis of the transcriptome, proteome and metabolome. In a guinea pig model of acquired long QT syndrome and HF/SCD, relative protein abundances from sham-operated, HYP and HF hearts were assessed using isobaric tags for relative and absolute quantification (iTRAQ), prior to liquid chromatography and tandem mass spectrometry (LC-MS/MS). Metabolites were quantified by LC-MS/MS or gas chromatography coupled to MS (GC-MS). Transcriptome profiles were obtained using DNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, cellular degeneration, inflammation and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial processes, were downregulated in HF, but not HYP. Proteins upregulated in HF are consistent with extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, downregulation of acyl-carnitines was observed in HYP, while fatty acids accumulated in HF. Levels of the tricarboxylic acid (TCA) cycle metabolite, citrate, and the potent inhibitor, 2-methylcitrate, increased upon transition from HYP to HF. Correlation of the magnitude of transcript and protein changes in HF is weak (R2=0.23), indicating that targeting transcript/proteome may reveal inform post-transcriptional gene regulation in HF. Proteome/Metabolome integration suggests metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (CPT1B) as well as TCA cycle inhibition. We present a model in which hallmarks of acute signaling in HF, including Ca2+ dysregulation and low cAMP levels, are coupled to mitochondrial metabolic and antioxidant defects, through a CREB/PGC1-alpha transcriptional axis.

Project description:Here we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig model by integrated multi-ome analysis. Relative protein abundances from sham-operated, HYP and HF hearts were assessed by iTRAQ shotgun LC-MS/MS. Metabolites were quantified by LC-MS/MS or GC-MS. Transcriptome profiles were obtained using DNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, inflammation and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial processes, were downregulated in HF, but not HYP. Proteins upregulated in HF implicate extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, downregulation of acyl-carnitines was observed in HYP, while fatty acids accumulated in HF. Correlation of transcript and protein changes in HF is weak (R2=0.23), suggesting transcript/proteome divergence may reveal post-transcriptional gene regulation in HF. Proteome/Metabolome integration suggests metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (CPT1B) as well as TCA cycle inhibition. We present a model by which acute signaling in HF, including Ca2+ dysregulation and low cAMP levels, is coupled to mitochondrial metabolic and antioxidant defects, through a CREB/PGC1 transcriptional axis. Animal Model The guinea pig model of heart failure and sudden cardiac death has been described previously. Briefly, the HF and SCD guinea pig model was produced by combining ascending aortic constriction (AC) and daily isoproterenol challenge (ACi model). Specifically, Hartley guinea pigs (~250 g; Hilltop Lab Animals) were anesthetized with 4% isoflurane in a closed box for 4min, and then intubated and ventilated with oxygen and 2% isoflurane. Ascending aortic constriction (AC) was produced by tying a suture around the ascending aorta using an 18‐gauge needle as a spacer, which was then removed. For sham operations the procedure was identical though the suture was not tied. After the procedure, bupronex (0.05 mg/kg) was administered via intramuscular injection for analgesia and animals were observed until full recovery. Isoproterenol was administered daily by intra peritoneal injection at 1 mg/kg for the first week after surgery and at 2 mg/kg for a subsequent 3 weeks. As characterized previously (1), cardiac function of ACi animal is well compensated in the first 2 weeks (HYP) but declined rapidly thereafter (HF). Hypertrophic heart was collected between 1-2 weeks post-surgery (ACi-2w), whereas failing heart was collected at 4 weeks after surgery (ACi-4w). Following retrograde perfusion with 20ml Tyrode’s solution, excised hearts were Snap-frozen in liquid N2 and stored at -80°C Experimental Design The experiment consisted of 3 treatment groups: 1) HYP (ACi-2wk), 2) HF (ACi-4wk) 3) sham-operated animals with daily administration for 4 weeks (Shami-4w). 1 heart from each group was included in an iTRAQ 4-plex experiment wherein peptides from each heart are subjected to reaction with an isobaric label. The experiment was repeated twice, yielding a total of 3 independent experiments quantifying the peptides from 9 hearts. ITRAQ reagents were shuffled among treatment groups for each experiment to minimize labeling bias.

Dataset Information

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

Publications

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure