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Aortic Waveform Analysis to Individualize Treatment in Heart Failure.

ABSTRACT: Afterload reduction is a cornerstone in the management of patients with heart failure (HF) and reduced ejection fraction. However, arterial load and the effect of HF therapies on afterload might vary between individuals. Tailoring vasoactive medicines to patients with HF based upon better understanding of arterial afterload may enable better individualization of therapy.Subjects with HF and reduced ejection fraction underwent aggressive titration of vasoactive HF therapies with assessment of central aortic waveforms analyzed using pulse wave, wave separation, and arterial reservoir models. Clinical response to treatment was assessed using the 6-minute walk test distance, which increased in 25 subjects and decreased or remained unchanged in 13. Subjects with improvement on therapy displayed higher aortic pressure wave pulsatility (central pulse pressure [PP], reflected pressure wave, and reservoir pressure) at study entry compared with subjects without improvement (all P<0.05). Parameters derived by the arterial analysis methods were strongly correlated with one another and displayed similar ability to predict improvement. Aortic pressure pulsatility significantly decreased in subjects with functional improvement, whereas no change was observed in patients without functional improvement (P for interaction <0.05). These differences in arterial load at baseline and on therapy were not apparent from conventional brachial artery cuff pressure assessments.Increased aortic pressure wave pulsatility and greater decrease in pulsatility on treatment are associated with functional improvement in patients with HF and reduced ejection fraction receiving aggressive vasodilator titration. These differences are not identifiable using brachial cuff pressures. Central aortic waveform analysis may enable better individualization of vasoactive therapies in chronic HF and reduced ejection fraction.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00588692.

SUBMITTER: Wohlfahrt P

PROVIDER: S-EPMC5308883 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Aortic Waveform Analysis to Individualize Treatment in Heart Failure.

Wohlfahrt Peter P Melenovsky Vojtech V Redfield Margaret M MM Olson Thomas P TP Lin Grace G Abdelmoneim Sahar S SS Hametner Bernhard B Wassertheurer Siegfried S Borlaug Barry A BA

Circulation. Heart failure 20170201 2

<h4>Background</h4>Afterload reduction is a cornerstone in the management of patients with heart failure (HF) and reduced ejection fraction. However, arterial load and the effect of HF therapies on afterload might vary between individuals. Tailoring vasoactive medicines to patients with HF based upon better understanding of arterial afterload may enable better individualization of therapy.<h4>Methods and results</h4>Subjects with HF and reduced ejection fraction underwent aggressive titration of ...[more]

PMID: 28159826

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Project description:Study objectivesTo compare the frequency of achieving a therapeutic serum digoxin concentration (SDC), defined as 0.5-0.9 ng/ml, by using a simplified nomogram to individualize digoxin dosing with standard dosing practices in patients with heart failure, and to characterize the relationship between genetic polymorphisms of the ABCB1 gene and SDC.DesignProspective study with a historical control group.SettingOutpatient care center of an urban academic medical center.PatientsA total of 131 adults with heart failure due to left ventricular dysfunction who were treated with digoxin.InterventionDigoxin doses were determined either by the dosing nomogram (65 patients) or standard care (SC; 66 patients) by using historical controls who were randomly selected from a list of SDCs obtained from laboratory records and who had their digoxin doses determined by standard dosing practices.Measurements and main resultsThe primary end point was the proportion of patients achieving a steady-state SDC of 0.5-0.9 ng/ml; secondary end points were mean SDC and proportion of patients achieving a steady-state SDC lower than 1.0 ng/ml. Postdistributive steady-state SDCs were measured 2-4 weeks after digoxin dosage adjustment or initiation. Therapeutic SDCs were achieved with similar frequency in both groups (38.7% in the nomogram group vs 34.5% in the SC group, p=0.65); however, more patients in the nomogram group had SDCs lower than 1.0 ng/ml than in the SC group (85.0% vs 44.9%, p<0.001). Mean daily digoxin doses were lower in the nomogram group (149 ± 67 μg vs 177 ± 74 μg, p=0.02), resulting in lower mean SDCs compared with those in the SC group (0.52 ± 0.30 ng/ml vs 1.12 ± 0.58 ng/ml, p<0.001). Patients in the pharmacogenetic substudy provided blood samples for genotyping of three common ABCB1 single nucleotide polymorphisms: C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642). SDCs were not significantly associated with ABCB1 genotypes.ConclusionOur simplified digoxin dosing nomogram resulted in lower SDCs compared with standard dosing practices but achieved therapeutic SDCs with similar frequency. A greater proportion of patients dosed according to our nomogram had SDCs lower than 1.0 ng/ml, consistent with consensus guidelines. Genetic polymorphisms of the ABCB1 gene were not associated with SDC.

Project description:ImportanceData are lacking on the effect of a renin-angiotensin system (RAS) inhibitor prescribed after transcatheter aortic valve replacement (TAVR). Treatment with a RAS inhibitor may reverse left ventricular remodeling and improve function.ObjectiveTo investigate the association of prescription of a RAS inhibitor and outcomes after TAVR.Design, setting, and participantsRetrospective cohort study of TAVR procedures performed in the United States (using the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry) between July 2014 and January 2016 that were linked to Medicare claims data (final date of follow-up: March 31, 2017). To account for differences in demographics, echocardiographic findings, and in-hospital complications, 1:1 propensity matching was performed.ExposuresInitial hospital discharge prescription of a RAS inhibitor after TAVR.Main outcomes and measuresPrimary outcomes were all-cause death and readmission due to heart failure at 1 year after discharge, which were considered separately. The secondary outcome was health status assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ; score range: 0-100, with a higher score indicating less symptom burden and better quality of life; a small effect size was defined as 5 points) at 1 year.ResultsAmong 21 312 patients who underwent TAVR at 417 US sites, 8468 patients (39.7%) were prescribed a RAS inhibitor at hospital discharge. After propensity matching, 15 896 patients were included (mean [SD] age, 82.4 [6.8] years; 48.1% were women; mean [SD] left ventricular ejection fraction [LVEF], 51.9% [11.5%]). Patients with a prescription for a RAS inhibitor vs those with no prescription had lower mortality rates at 1 year (12.5% vs 14.9%, respectively; absolute risk difference [ARD], -2.4% [95% CI, -3.5% to -1.4%]; hazard ratio [HR], 0.82 [95% CI, 0.76 to 0.90]) and lower heart failure readmission rates at 1 year (12.0% vs 13.8%; ARD, -1.8% [95% CI, -2.8% to -0.7%]; HR, 0.86 [95% CI, 0.79 to 0.95]). When stratified by LVEF, having a prescription for a RAS inhibitor vs no prescription was associated with lower 1-year mortality among patients with preserved LVEF (11.1% vs 13.9%, respectively; ARD, -2.81% [95% CI, -3.95% to -1.67%]; HR, 0.78 [95% CI, 0.71 to 0.86]), but not among those with reduced LVEF (18.8% vs 19.5%; ARD, -0.68% [95% CI, -3.52% to 2.20%]; HR, 0.95 [95% CI, 0.81 to 1.12]) (P = .04 for interaction). Of 15 896 matched patients, 4837 (30.4%) were included in the KCCQ score analysis and improvements at 1 year were greater in patients with a prescription for a RAS inhibitor vs those with no prescription (median, 33.3 [interquartile range, 14.2 to 51.0] vs 31.3 [interquartile range, 13.5 to 51.1], respectively; difference in improvement, 2.10 [95% CI, 0.10 to 4.06]; P < .001), but the effect size was not clinically meaningful.Conclusions and relevanceAmong patients who underwent TAVR, receiving a prescription for a RAS inhibitor at hospital discharge compared with no prescription was significantly associated with a lower risk of mortality and heart failure readmission. However, due to potential selection bias, this finding requires further investigation in randomized trials.

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Aortic Waveform Analysis to Individualize Treatment in Heart Failure.

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Aortic Waveform Analysis to Individualize Treatment in Heart Failure.

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