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Quality of Warfarin Control and Events in Patients with Mechanical Heart Valves

Grzymala-Lubanski et al report a retrospective non-randomized multicenter cohort study of patients with mechanical heart valves to assess the relationship between the quality and intensity of warfarin therapy and outcomes (thrombosis/bleeding/death). Measures of better quality control were associated with a lower rate of adverse events. Higher intensity anticoagulation was associated with increased rates of bleeding and death.

Two editorials are available here and here.

Abstract

Objectives

To study the impact of time in therapeutic range (TTR) and international normalised ratio (INR)variability on the risk of thromboembolic events, major
bleeding complications and death after mechanical heart valve (MHV)implantation. Additionally, the importance of different target INR levels was elucidated.

Methods

A retrospective, non-randomised multicentre cohort study including all patients with mechanical heart valve (MVH) prosthesis registered in the Swedish
National Quality Registry Auricula from 2006 to 2011. Data were merged with the Swedish National Patient Registry, SWEDEHEART and Cause of Death Registry.

Results

In total 4687 ordination periods,corresponding to 18 022 patient-years on warfarin, were included. High INR variability (above mean ≥0.40) or lower TTR (≤70%) was associated with a higher risk of bleeding (rate per 100 years 4.33 (95% CI 3.87 to 4.82) vs 2.08 (1.78 to 2.41); HR 2.15 (1.75 to 2.61) and
5.13 (4.51 to 5.82) vs 2.30 (2.03 to 2.60); HR 2.43 (2.02 to 2.89)), espectively. High variability and low TTR combined was associated with an even higher risk of bleedings (rate per 100 years 4.12 (95% CI 3.68 to 4.51) vs 2.02 (1.71 to 2.30); HR 2.16 (1.71 to 2.58) and 4.99 (4.38 to 5.52) vs 2.36 (2.06 to 2.60); HR 2.38 (2.05 to 2.85)) compared with the best group. Higher treatment intensity (mean INR 2.8–3.2 vs 2.2–2.7) was associated with higher rate of bleedings (2.92 (2.39 to 3.47) vs 2.48 (2.21 to 2.77); HR 1.29 (1.06 to 1.58)), death (3.36 (2.79 to 4.02) vs 1.89 (1.64 to 2.17), HR 1.65 (1.31 to 2.06)) and
complications in total (6.61 (5.74 to 7.46) vs 5.65 (5.20to 6.06); HR 1.24 (1.06 to 1.41)) after adjustment for MHV position, age and comorbidity.

Conclusions

A high warfarin treatment quality improves outcome after MHV implantation, both
measured with TTR and INR variability. No benefit was found with higher treatment intensity (mean INR 2.8–3.2 vs 2.2–2.7).

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Journal Club 4 February 2015

Paper

Surgical Treatment of Moderate Ischemic Mitral Regurgitation

Presenter

AL

Summary

Background

Ischemic mitral regurgitation is associated with increased mortality and morbidity.
For surgical patients with moderate regurgitation, the benefits of adding mitralvalve
repair to coronary-artery bypass grafting (CABG) are uncertain.

Methods

We randomly assigned 301 patients with moderate ischemic mitral regurgitation to
CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end
point was the left ventricular end-systolic volume index (LVESVI), a measure of left
ventricular remodeling, at 1 year. This end point was assessed with the use of a
Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank.

Results

At 1 year, the mean LVESVI among surviving patients was 46.1±22.4 ml per square
meter of body-surface area in the CABG-alone group and 49.6±31.5 ml per square meter
in the combined-procedure group (mean change from baseline, −9.4 and −9.3 ml per
square meter, respectively). The rate of death was 6.7% in the combined-procedure
group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90;
95% confidence interval, 0.38 to 2.12; P = 0.81). The rank-based assessment of LVESVI
at 1 year (incorporating deaths) showed no significant between-group difference
(z score, 0.50; P = 0.61). The addition of mitral-valve repair was associated with a longer
bypass time (P<0.001), a longer hospital stay after surgery (P = 0.002), and more neurologic
events (P = 0.03). Moderate or severe mitral regurgitation was less common in the
combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001).
There were no significant between-group differences in major adverse cardiac or cerebrovascular
events, deaths, readmissions, functional status, or quality of life at 1 year.

Conclusions

In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve
repair to CABG did not result in a higher degree of left ventricular reverse remodeling.
Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral
regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did
not show a clinically meaningful advantage of adding mitral-valve repair to CABG.
Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation
translates into a net clinical benefit.

Supplementary Material

Editorial

Valvular Heart Disease Guidelines (ACC/AHA)

The ACC/AHA guidelines for management of patients with valvular heart disease is available here.

Journal Club 18 September 2013

September 18, 2013 Leave a comment

Paper

Dabigatran versus Warfarin in Patients with Mechanical Heart Valves

Presenter

LAM

Summary

Background

Dabigatran is an oral direct thrombin inhibitor that has been shown to be an effective
alternative to warfarin in patients with atrial fibrillation. We evaluated the use
of dabigatran in patients with mechanical heart valves.

Methods

In this phase 2 dose-validation study, we studied two populations of patients: those
who had undergone aortic- or mitral-valve replacement within the past 7 days and
those who had undergone such replacement at least 3 months earlier. Patients were
randomly assigned in a 2:1 ratio to receive either dabigatran or warfarin. The selection
of the initial dabigatran dose (150, 220, or 300 mg twice daily) was based on
kidney function. Doses were adjusted to obtain a trough plasma level of at least
50 ng per milliliter. The warfarin dose was adjusted to obtain an international normalized
ratio of 2 to 3 or 2.5 to 3.5 on the basis of thromboembolic risk. The primary end
point was the trough plasma level of dabigatran.

Results

The trial was terminated prematurely after the enrollment of 252 patients because
of an excess of thromboembolic and bleeding events among patients in the dabigatran
group. In the as-treated analysis, dose adjustment or discontinuation of
dabigatran was required in 52 of 162 patients (32%). Ischemic or unspecified stroke
occurred in 9 patients (5%) in the dabigatran group and in no patients in the warfarin
group; major bleeding occurred in 7 patients (4%) and 2 patients (2%), respectively.
All patients with major bleeding had pericardial bleeding.

Conclusions

The use of dabigatran in patients with mechanical heart valves was associated with
increased rates of thromboembolic and bleeding complications, as compared with
warfarin, thus showing no benefit and an excess risk.

Further Material

The editorial is here. The supplementary appendix is here

Journal Club 13 February 2013

Paper

Genetic Associations with Valvular Calcification and Aortic Stenosis

Presenter

CC

Summary

Background

Limited information is available regarding genetic contributions to valvular calcification,
which is an important precursor of clinical valve disease.

Methods

We determined genomewide associations with the presence of aortic-valve calcification
(among 6942 participants) and mitral annular calcification (among 3795 participants),
as detected by computed tomographic (CT) scanning; the study population
for this analysis included persons of white European ancestry from three cohorts
participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology
consortium (discovery population). Findings were replicated in independent
cohorts of persons with either CT-detected valvular calcification or clinical aortic
stenosis.

Results

One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance
for the presence of aortic-valve calcification (odds ratio per allele, 2.05;
P = 9.0×10-10), a finding that was replicated in additional white European, African-
American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically
determined Lp(a) levels, as predicted by LPA genotype, were also associated with
aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses,
LPA genotype was associated with incident aortic stenosis (hazard ratio per allele,
1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard
ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident
aortic stenosis was also replicated in an independent Danish cohort. Two SNPs
(rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide
significance for mitral annular calcification (P = 1.5×10-8 and P = 1.8×10-8,
respectively), but the findings were not replicated consistently.

Conclusions

Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aorticvalve
calcification across multiple ethnic groups and with incident clinical aortic
stenosis.

Journal Club 26 September 2012

September 26, 2012 Leave a comment

Article

Outcome of Patients With Aortic Stenosis,
Small Valve Area, and Low-Flow, Low-Gradient Despite Preserved Left Ventricular Ejection Fraction

Presenter

SP on behalf of AC

Summary

Objectives

The aim of this case match study was to compare the outcome of patients with paradoxical low-flow (left ventricular
ejection fraction [LVEF] 50% but stroke volume index 35 ml/m2), low-gradient (mean gradient [MG]
40 mm Hg), a priori severe (aortic valve area [AVA] 1.0 cm2) aortic stenosis (AS) (PLG-SAS group) with that
of patients with a severe AS (AVA 1.0 cm2) and consistent high-gradient (MG 40 mm Hg) (HG-SAS group)
and with that of patients with a moderate AS (AVA 1.0 cm2 and MG 40 mm Hg) (MAS group).
Background In patients with preserved LVEF, a discordance between the AVA (in the severe range) and the gradient (in the
moderate range) raises uncertainty with regard to the actual severity of the stenosis and thus the therapeutic
management of the patient.

Methods

In a prospective cohort of AS patients with LVEF 50%, we identified 187 patients in the PLG-SAS group. These
patients were retrospectively matched: 1) according to the gradient, with 187 patients with MAS; and 2) according
to the AVA, with 187 patients with HG-SAS.

Results

Patients with PLG-SAS had reduced overall survival (1-year: 89  2%; 5-year: 64  4%) compared with patients
with HG-SAS (1-year: 96  1%; 5-year: 82  3%) or MAS (1-year: 96  1%; 5-year: 81  3%). After adjustment
for other risk factors, patients with PLG-SAS had a 1.71-fold increase in overall mortality and a 2.09-fold increase
in cardiovascular mortality compared with the 2 other groups. Aortic valve replacement was significantly
associated with improved survival in the HG-SAS group (hazard ratio: 0.18; p  0.001) and in the PLG-SAS group
(hazard ratio: 0.50; p  0.04) but not in the MAS group.

Conclusions

Prognosis of patients with paradoxical low-flow, low-gradient severe AS was definitely worse than those with
high-gradient severe AS or those with moderate AS. The finding of a low gradient cannot exclude the presence of
a severe stenosis in a patient with a small AVA and preserved LVEF and should mandatorily prompt further
investigation.

Anticoagulation for pregnant women with prosthetic mechanical heart valves

The management of the pregnant patient with valvular heart disease and in particular mechanical prosthetic valve(s) is a complex and specialized discipline. There are only limited cohorts to guide management.

De Santo present a the outcomes of a low dose oral anticoagulant regimen  in the setting of mechanical aortic valve prosthesis and pre-operative counselling in young women planning on pregnancy. This is a small study (understandably) and highly selective group.

A very useful editorial discussed the paper in the overall context. The  following  graphic is an excerpt.

Anticoagulation regimens for pregnant women with mechanical prosthetic heart valves