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Heartbeat: Warfarin therapy for mechanical heart valves

2017-01-13T03:45:09-08:00

Although many patients requiring long term anti-thrombotic therapy now can be treated with direct oral anticoagulants (DOACs), vitamin K antagonists, such as warfarin, remain the only treatment option in patients with mechanical heart valves (MHVs). In the future, we can expect that fewer patients will receive (MHVs), given that surgical repair often is possible in patients with mitral valve disease and a bioprosthetic valve is appropriate in older adults with aortic valve disease. However, there still is a group of younger patients in whom the benefits of long term valve durability with a MHV outweigh the risks of warfarin anticoagulation.

Management of warfarin therapy can be challenging given the need for frequent dosage adjustment to maintain adequate anticoagulation, with the international normalized ratio (INR) varying with changes in diet, physical activity, concurrent medications, patient compliance and other factors. Grzymala-Lubanski and colleagues (see page 198) examined data...




Pixels or Pixie Dust? Grading of mitral regurgitation using intensity analysis of continuous wave Doppler

2017-01-13T03:45:09-08:00

Accurate quantification of mitral regurgitation (MR) plays a critical role in clinical decision making for mitral valve disease. Doppler echocardiography has emerged as the primary method used to quantitate mitral regurgitation in clinical practice but remains challenging. Current recommendations integrate multiple Doppler-derived parameters to determine MR degree,1 mainly colour-flow jet area, vena contracta (VC) width and effective regurgitant orifice area (EROA). As is well known, each colour Doppler parameter has limitations based on technical issues or inaccurate geometric assumptions. Colour-flow jet area is semi-quantitative, while VC width reflects orifice size, not MR regurgitant volume. There are well-known limitations of these variables including sensitivity to load, gain settings (jet area) and narrow measurement range (VC). EROA is a quantitative measure that is calculated using geometric assumptions based on the proximal isovelocity surface area (PISA) method. The MR regurgitant volume is calculated by multiplying the EROA by the time...




The need for a continuing awareness of the quality of anticoagulant therapy in patients with mechanical prostheses

2017-01-13T03:45:09-08:00

The difficulties in achieving stable international normalised ratios (INRs) are a common concern in clinical practice and have been related to thromboembolic and bleeding risks in a number of clinical trials in patients with atrial fibrillation.1 The paper by Grzymala-Lubanski and colleagues fills an important gap since it provides an in-depth analysis of the clinical impact of warfarin treatment quality in the specific population of patients with mechanical heart valve prostheses, who are at particular risk of thromboembolism and bleeding.2

The time in therapeutic range (TTR) of 72% in the paper by Grzymala-Lubanski and colleagues is consistent with trials performed in atrial fibrillation. However, adherence to treatment is often better in clinical trials than in real life. In addition, this analysis was based on INR management by the Auricula network which uses a computerised dosing system allowing for good INR stability. In Sweden, TTR rates...




The search for the tipping point on when to anticoagulate patients with atrial fibrillation

2017-01-13T03:45:09-08:00

Most therapeutic interventions quickly show their real benefits in certain patient groups and absence of benefits or even harm in others. That leaves a grey zone in between that gives rise to opinions and often heated discussions on where to draw the line between indication or not. For conditions that affect large groups of patients with chronic illnesses, the drawing line may be different in primary versus secondary care settings. One of such highly disputed grey zones is on the threshold to start oral anticoagulant therapy in patients with atrial fibrillation (AF). Only scientific data can help to visualise the division line more clearly, to narrow down the grey area and to abate opinionated discussions. That is exactly what the authors of an article in this issue have tried to do.1 They report on the net clinical benefit of anticoagulation with vitamin-K antagonists (VKAs) in real-world patients...




The challenge of frailty and sarcopenia in heart failure with preserved ejection fraction

2017-01-13T03:45:09-08:00

Frailty is a clinical state in which there is an increase in an individual's vulnerability for developing increased dependency and/or mortality when exposed to stressors. Frailty is often accompanied by heart failure with preserved ejection fraction (HFpEF), and frailty is likely to affect its clinical features and outcomes. Frail patients with HFpEF are frequently associated with sarcopenia (ie, muscle loss and weakness), which is a major component of the pathophysiology of frailty. Sarcopenia is a systemic skeletal muscle disease that impairs the function of limb skeletal muscles, as well as respiratory muscles, and this results in further functional decline. In addition, sarcopenia may contribute to cardiovascular remodelling and dysfunction, leading to the development of HFpEF through several metabolic and endocrine abnormalities. Although there is no established strategy for frail patients with HFpEF, a multidisciplinary approach, including various types of muscular training and nutritional intervention, may provide beneficial effects for these patients.




A 50-year-old man with incidental cardiac mass

2017-01-13T03:45:09-08:00

Clinical introduction

A 50-year-old white male with a history of paroxysmal atrial fibrillation presented for transoesophageal echocardiogram prior to atrial fibrillation ablation. However, an echo lucent mass was noted (figure 1A). Colour Doppler and contrast administration showed no flow across the mass or the interatrial septum (see online s 1 and ). CT of the chest demonstrated a thin-walled, well-demarcated mass in the inferior border of the fossa ovalis protruding into the left atrium (figure 1B).

Question

Which of the following is the most likely diagnosis?

  • Atrial myxoma

  • Bronchogenic cyst

  • Cardiac angiosarcoma

  • Hydatid cyst




  • Grading of mitral regurgitation based on intensity analysis of the continuous wave Doppler signal

    2017-01-13T03:45:09-08:00

    Objectives

    Echocardiographic methods are used to quantify mitral regurgitation (MR) severity; however, their applicability, accuracy and reproducibility have been debated. We aimed to develop and validate a novel custom-made transthoracic echocardiographic method for grading MR severity based on average pixel intensity (API) analysis of the continuous wave (CW) Doppler envelope.

    Methods

    MR was assessed in 290 patients using API, colour Doppler imaging, vena contracta width (VCW) and proximal iso-velocity surface area (PISA) method. For the validation of the API method, a pulsatile in vitro cardiac phantom was used.

    Results

    Indices of MR severity, such as left ventricular and atrial dimension, pulmonary arterial pressure, significantly cosegregate with API severity (p≤0.002). The API method showed a linear correlation with colour Doppler (r=0.79), VCW (r=0.68), PISA-effective regurgitant orifice area (r=0.72) and PISA-regurgitant volume (r=0.67); p<0.001 for all. The API was significantly more applicable than VCW (95% vs 75% of all patients; p<0.001) and PISA-based methods (65%; p<0.001). Additionally, the API showed a stronger intraobserver and interobserver agreement compared with other methods. Finally, in the in vitro validation, API values showed a strong linear correlation with increasing regurgitant volumes (r=0.81; p<0.001).

    Conclusions

    We showed the clinical feasibility and in vitro validation of a novel digital quantitative echocardiographic method to grade MR severity. This method is more applicable and has less interobserver and intraobserver variability compared with current quantitative methods.




    Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis

    2017-01-13T03:45:09-08:00

    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)), respectively. 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 (5.20 to 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).




    Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia

    2017-01-13T03:45:09-08:00

    Objective

    We aimed to investigate the association of diffuse myocardial fibrosis by cardiac magnetic resonance (CMR) T1 with complex ventricular arrhythmia (ComVA) in mitral valve prolapse (MVP).

    Methods

    A retrospective analysis was performed on 41 consecutive patients with MVP referred for CMR between 2006 and 2011, and 31 healthy controls. Arrhythmia analysis was available in 23 patients with MVP with Holter/event monitors. Left ventricular (LV) septal T1 times were derived from Look-Locker sequences after administration of 0.2 mmol/kg gadopentetate dimeglumine. Late gadolinium enhancement (LGE) CMR images were available for all subjects.

    Results

    Patients with MVP had significantly shorter postcontrast T1 times when compared with controls (334±52 vs 363±58 ms; p=0.03) despite similar LV ejection fraction (LVEF) (63±7 vs 60±6%, p=0.10). In a multivariable analysis, LV end-diastolic volume, LVEF and mitral regurgitation fraction were all correlates of T1 times, with LVEF and LV end-diastolic volume being the strongest (p=0.005, p=0.008 and p=0.045, respectively; model adjusted R2=0.30). Patients with MVP with ComVA had significantly shorter postcontrast T1 times when compared with patients with MVP without ComVA (324 (296, 348) vs 354 (327, 376) ms; p=0.03) and only 5/14 (36%) had evidence of papillary muscle LGE.

    Conclusions

    MVP may be associated with diffuse LV myocardial fibrosis as suggested by reduced postcontrast T1 times. Diffuse interstitial derangement is linked to subclinical systolic dysfunction, and may contribute to ComVA in MVP-related mitral regurgitation, even in the absence of focal fibrosis.




    Net clinical benefit of warfarin in individuals with atrial fibrillation across stroke risk and across primary and secondary care

    2017-01-13T03:45:09-08:00

    Objective

    To investigate net clinical benefit (NCB) of warfarin in individuals with atrial fibrillation (AF) across stroke risk and across primary and secondary care.

    Methods

    We conducted a linked electronic health record cohort study of 70 206 individuals with initial record of diagnosis of AF in primary (n=29 568) or secondary care (n=40 638) in England (1998–2010). We defined stroke risk according to the CHA2DS2-VASc score, and followed individuals over a median 2.2 years for 7005 ischaemic strokes (IS) and for 906 haemorrhagic strokes (HS). We calculated incidence rates (IRs) and 95% CIs per 100 person-years (PYs) (IR (95% CI)/100 PY) of IS and HS, with and without use of warfarin, and the NCB (ie, number of IS avoided) per 100 PYs of warfarin use (NCB (95% CI)/100 PY).

    Results

    Compared with individuals with initial record of diagnosis in secondary care, those in primary care had lower scores of IS risk (CHA2DS2-VASc≤2: 30.8% vs 20.6%), and lower overall incidence of IS (IR (95% CI)/100 PY: 2.3 (2.2 to 2.4) vs 4.3 (4.2 to 4.4), p value=0.00); however among individuals with CHA2DS2-VASc=0, 1 or 2 there were no differences in IS rate between those with initial record of diagnosis in primary care or secondary care (IR (95% CI)/100 PY: 0.2 (0.1 to 0.3) vs 0.3 (0.2 to 0.5), p value=0.16), (IR (95% CI)/100 PY: 0.6 (0.4 to 0.7) vs 0.7 (0.6 to 0.9), p value=0.08) and (IR (95% CI)/100 PY: 1.1 (1.00 to 1.3) vs 1.4 (1.2 to 1.6), p value=0.05), respectively. For CHA2DS2-VASc=0, 1 and 2, IRs of IS with versus without warfarin were (IR (95% CI)/100 PY: 0.4 (0.2 to 0.8) vs 0.2 (0.1 to 0.3), p value=0.16), (IR (95% CI)/100 PY: 0.4 (0.3 to 0.7) vs 0.7 (0.6 to 0.8), p value=0.03) and (IR (95% CI)/100 PY: 0.8 (0.7 to 1.0) vs 1.4 (1.3 to 1.6), p value=0.00), respectively. We found a significant positive NCB of warfarin from CHA2DS2-VASc≥2 in men (NCB (95% CI)/100 PY: 0.5 (0.1 to 0.9)) and from CHA2DS2-VASc≥3 in women (NCB (95% CI)/100 PY: 1.5 (1.1 to 1.9)).

    Conclusions

    CHA2DS2-VASc accurately stratifies IS risk in individuals with AF across both primary and secondary care. However, the incidence rate of ischaemic stroke at CHA2DS2-VASc=1 are lower than previously reported, which may change the decision to start anticoagulation with warfarin in these individuals.




    The impact of moderate distance recreational running and ageing on cardiac physiology

    2017-01-13T03:45:09-08:00

    Objective

    Exercise-induced cardiac dysfunction and corollary biomarker release have been documented following long-distance running events. To what degree these processes occur during shorter distance running events is unknown.

    Methods

    72 healthy recreational runners (54% male/46% female) recruited by age (group 1 (18–20 years old, N=19); group 2 (45–50 years old, N=27); group 3 (70–75 years old, N=26)) were studied with echocardiography and biochemical profiling during participation in a 10 km running race.

    Results

    Despite age-dependent baseline differences in ventricular size and diastolic tissue velocities, there were no significant within group or across group decrements in ventricular systolic or diastolic function following race completion. Postrace increases in cardiac troponin-I (cTnI), B-type natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) were common and demonstrated distinct age dependent profiles. Specifically, BNP increases were most pronounced among older runners (group 3: 16±22 pg/mL, p=0.001), hs-CRP increased only among younger runners (group 1: 1.5±2.7 mg/L, p=0.03) and cTnI increased in both younger (group 1: 0.01±0.02 ng/mL, p=0.028) and older (group 3: 0.01±0.01 ng/mL, p=0.007) runners, but not middle aged runners (group 2: 0.00±0.00 ng/mL, p=0.57).

    Conclusions

    Moderate distance recreational running leads to distinct age-dependent biomarker release but is not associated with cardiac fatigue, a proposed stimulus for pathologic cardiac remodelling that has been observed following longer distance running events.




    Incidence and risk of heart failure in systemic lupus erythematosus

    2017-01-13T03:45:09-08:00

    Background

    Although case series suggest a higher burden of cardiovascular risk factors in patients with systemic lupus erythematosus (SLE) compared with the general population, the association between SLE and heart failure (HF) remains undefined. We sought to investigate the incidence and risk of HF in patients with SLE.

    Methods

    In April 2016, we performed a retrospective cohort analysis using the Explorys platform, which provides aggregated electronic medical record data from 26 major integrated healthcare systems across the USA from 1999 to present. Demographic and regression analyses were performed to assess the impact of SLE on HF incidence.

    Results

    Among 45 284 540 individuals in the database, we identified 95 400 (0.21%) with SLE and 98 900 (0.22%) with a new diagnosis of HF between May 2015 and April 2016. HF incidence was markedly higher in the SLE group compared with controls (0.97% vs 0.22%, relative risk (RR): 4.6 (95% CI 4.3 to 4.9)), as were other cardiovascular risk factors. In regression analysis, SLE was an independent predictor of HF (adjusted OR: 3.17 (2.63 to 3.83), p<0.0001). RR of HF was highest in young males with SLE (65.2 (35.3 to 120.5) for age 20–24), with an overall trend of increasing absolute risk but decreasing RR with advancing age in both sexes. Renal involvement in SLE correlated with earlier and higher incidence of HF.

    Conclusions

    The findings of this study suggest that patients with SLE have significantly higher risk of developing HF and a worse cardiovascular risk profile compared with the general population. These results need to be confirmed by prospective studies.




    Recurrent pre-eclampsia and subsequent cardiovascular risk

    2017-01-13T03:45:09-08:00

    Objective

    To determine the association between recurrent pre-eclampsia and long-term cardiovascular hospitalisation.

    Methods

    This study identified cardiovascular hospitalisations up to 25 years after pregnancy for all women who delivered between 1989 and 2013 in Québec, Canada. Exposures included recurrent and non-recurrent pre-eclampsia in women with two deliveries or more (N=606 820), and pre-eclampsia in women with only one delivery (N=501 761). Incidence, timing and risk of cardiovascular complications were calculated using accelerated failure time models adjusted for age, pre-existing disease, socioeconomic deprivation and period. Outcomes included a range of cardiovascular hospitalisations and procedures.

    Results

    Women with recurrent pre-eclampsia had higher incidence of cardiovascular hospitalisation (281.4 per 1000) than women with non-recurrent (167.7 per 1000) or no pre-eclampsia (72.6 per 1000). Mean time to cardiovascular hospitalisation was 10.5 years for recurrent, 11.6 years for non-recurrent and 12.7 years for no pre-eclampsia, a difference of 17.3% for recurrent and 8.7% for non-recurrent relative to no pre-eclampsia. Compared with no pre-eclampsia, recurrent pre-eclampsia was associated with 2 times the risk of heart disease (95% CI 1.69 to 2.29) and 3 times the risk of cerebrovascular disease (95% CI 2.25 to 4.05). Pre-eclampsia in women with one delivery was associated with 3 times greater risk of cardiovascular hospitalisation compared with no pre-eclampsia in women with two deliveries or more (95% CI 2.96 to 3.25).

    Conclusions

    Recurrent pre-eclampsia is associated with higher risk of future cardiovascular hospitalisation compared with no pre-eclampsia, and significantly shorter time to first cardiovascular event. Cardiovascular screening should be performed earlier for women with recurrent pre-eclampsia.




    Valvular heart disease and pregnancy part II: management of prosthetic valves

    2017-01-13T03:45:09-08:00

    Learning objectives

  • To recognise the maternal, fetal and neonatal risks of pregnancy in women with prosthetic heart valves.

  • To review anticoagulation strategies for women with mechanical heart valves during pregnancy.

  • To understand the principles of management in pregnant women with prosthetic heart valves.

  • Introduction

    Prosthetic heart valves (PHV) have been used to treat patients with both congenital and acquired valve lesions since the first surgical replacement in 1960.1 The two principal types of PHV are the mechanical prostheses and the tissue or bioprostheses. Advances in surgical technique, valve design and anticoagulation have improved overall outcomes since their introduction.2 Worldwide, there is an increasing prevalence of rheumatic heart disease, with more young women being considered for surgical treatment.3 4 There are also increasing numbers of women with congenital heart disease reaching childbearing age, some of whom...