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Heartbeat: Is there any effective therapy for heart failure with preserved ejection fraction?

2018-02-12T01:00:46-08:00

Heart failure with preserved ejection fraction (HFpEF) increasingly is recognised as a cause of disabling symptoms, yet we have little data to support medical therapy for this condition. In order to objectively assess the published data on drug therapy for HFpEF, Zheng and colleagues1 performed a systematic review and meta-analysis of 25 randomised controlled trials with a total of over 18 000 patients. This analysis showed that beta-blocker therapy was associated with lower all-cause mortality compared with placebo (RR: 0.78, 95% CI 0.65 to 0.94, P=0.008). Other studied therapies, including ACE inhibitors, aldosterone receptor blockers, and mineralocorticoid receptor antagonists were not associated with lower all-cause or cardiovascular mortality (figure 1).

Figure 1

Pooled and individual estimates of relative risk (RR) and 95% CI of the primary outcome all-cause mortality for different therapies. Data are shown stratified by individual drug classes (beta-blockers, ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor...




Coronary artery variants and bicuspid aortic valve disease: gaining insight into genetic underpinnings

2018-02-12T01:00:46-08:00

Introduction

Although bicuspid aortic valve (BAV) is the most common congenital heart disease (CHD), data are limited regarding associated coronary artery variants and how they may impact clinical outcomes, and importantly how this association may inform our understanding of the genetics of aortic root and coronary embryogenesis. An increased incidence in separate left coronary ostia, left dominant systems and high take-off coronary arteries among patients with BAV has been identified particularly among type IB BAVs (without raphe).1 However, among patients with BAV and associated CHD, pathological characteristics of coronary ostia including high take-off variants arising above the sinotubular junction have not previously been described. In this edition of Heart, Koenraddt et al report novel findings of 84 postmortem heart specimens with BAV and associated CHD and observed that high take-off coronaries were common, noted in 45% of hypoplastic left ventricle specimens and 62% of specimens with...




Pharmacological strategies in heart failure with preserved ejection fraction: time for an individualised treatment strategy?

2018-02-12T01:00:46-08:00

Heart failure (with preserved ejection fraction (HFpEF) is a major global health issue. Indeed, with the ageing of the population, its prevalence is growing, affecting between 1.1% and 5.5% of the global population, and accounting for 50% of HF cases.

HFpEF: a difficult diagnosis

HFpEF is a complex clinical syndrome with a large variety of phenotypes. Its definition is not simple, with no gold standard, making the diagnosis sometimes challenging for the clinician, and explaining therefore the heterogeneity of patients included in the different studies. HFpEF is characterised by symptoms and signs of HF associated with a normal or nearly normal left ventricular ejection fraction. The definition of ‘preserved’ ejection fraction (EF) in previous clinical trials was not homogeneous, with cut-off values varying from 40% to 50%. The latest European Society of Cardiology (ESC) guidelines have chosen a cut-off value of ≥50% and have created a new category called...




Cochrane corner: interventions to improve adherence to lipid-lowering medication

2018-02-12T01:00:46-08:00

Background

High cholesterol is an important risk factor contributing to the global burden of disease. A WHO report estimated that it accounts for more than one-third of all deaths worldwide, and causes 18% of cerebrovascular disease (CVD) and 56% of ischaemic heart disease.1

The evidence that lipid-lowering drugs can reduce both lipid levels and the risk of heart attacks and strokes is well established. Lipid-lowering medications include statins, fibrates, niacin and bile acid resins. The effectiveness of statins is supported by large randomised trials and meta-analyses2 3 showing that the absolute reduction in LDL-cholesterol is linearly related to a reduction in the incidence of coronary and major vascular events.2 Statins are recommended as first-line therapy, whereas fibrates, niacin and bile acid resins are generally second-line therapy, alone or in combination with statins.4 5

Despite this evidence...




The ageing heart: the systemic and coronary circulation

2018-02-12T01:00:46-08:00

Most cardiovascular disease (CVD) occurs in patients over the age of 60. However, most evidence-based current cardiovascular guidelines lack evidence in an older population, due to the under-representation of older patients in randomised trials. Blood pressure rises with age due to increasing arterial stiffness, and stricter control results in improved outcomes. Myocardial ischaemia is also more common with increasing age, due to a combination of coronary artery disease and myocardial changes. However, despite higher rates of adverse outcomes, older patients are offered guideline-based therapy less frequently. Frailty is an independent predictor of mortality in adults over the age of 60, yet remains poorly assessed; slow gait speed is a key marker for the development of frailty and for adverse outcomes following intervention. Few trials have assessed frailty independent of age; however, there is evidence that non-frail older patients derive significant benefit from therapy, highlighting the urgent need to include frailty as a measure in clinical trials of treatment in CVD.

In this review, the authors appraise the literature in regard to the cardiovascular changes with ageing, specifically in relation to the systemic and coronary circulation and with a particular emphasis on frailty and its implication in the evaluation and treatment of CVD.




Heart failure with preserved ejection fraction: controversies, challenges and future directions

2018-02-12T01:00:46-08:00

Heart failure with preserved ejection fraction (HFpEF) comprises almost half of the population burden of HF. Because HFpEF likely includes a range of cardiac and non-cardiac abnormalities, typically in elderly patients, obtaining an accurate diagnosis may be challenging, not least due to the existence of multiple HFpEF mimics and a newly identified subset of patients with HFpEF and normal plasma natriuretic peptide concentrations. The lack of effective treatment for these patients represents a major unmet clinical need. Heterogeneity within the patient population has triggered debate over the aetiology and pathophysiology of HFpEF, and the neutrality of randomised clinical trials suggests that we do not fully understand the syndrome(s). Dysregulated nitric oxide–cyclic guanosine monophosphate–protein kinase G signalling, driven by comorbidities and ageing, may be the fundamental abnormality in HFpEF, resulting in a systemic inflammatory state and microvascular endothelial dysfunction. Novel informatics platforms are also being used to classify HFpEF into subphenotypes, based on statistically clustered clinical and biological characteristics: whether such subclassification will lead to more targeted therapies remains to be seen. In this review, we summarise current concepts and controversies, and highlight the diagnostic and therapeutic challenges in clinical practice. Novel treatments and disease management strategies are discussed, and the large gaps in our knowledge identified.




Coronary anatomy in children with bicuspid aortic valves and associated congenital heart disease

2018-02-12T01:00:46-08:00

Objective

In patients with bicuspid aortic valve (BAV), coronary anatomy is variable. High take-off coronary arteries have been described, but data are scarce, especially when associated with complex congenital heart disease (CHD). The purpose of this study was to describe coronary patterns in these patients.

Methods

In 84 postmortem heart specimens with BAV and associated CHD, position and height of the coronary ostia were studied and related to BAV morphology.

Results

High take-off right (RCA) and left coronary arteries (LCA) were observed in 23% and 37% of hearts, respectively, most frequently in hearts with hypoplastic left ventricle (HLV) and outflow tract anomalies. In HLV, high take-off was observed in 18/40 (45%) more frequently of LCA (n=14) than RCA (n=6). In hearts with aortic hypoplasia, 8/13 (62%) had high take-off LCA and 6/13 (46%) high take-off RCA. High take-off was seen 19 times in 22 specimens with perimembranous ventricular septal defect (RCA 8, LCA 11). High take-off was associated with type 1A BAV (raphe between right and left coronary leaflets), more outspoken for the RCA. Separate ostia of left anterior descending coronary artery and left circumflex coronary artery were seen in four hearts (5%), not related to specific BAV morphology.

Conclusion

High take-off coronary arteries, especially the LCA, occur more frequently in BAV with associated CHD than reported in normal hearts and isolated BAV. Outflow tract defects and HLV are associated with type 1A BAV and high take-off coronary arteries. Although it is unclear whether these findings in infants with detrimental outcome can be related to surviving adults, clinical awareness of variations in coronary anatomy is warranted.




Prognostic value of galectin-3 in adults with congenital heart disease

2018-02-12T01:00:46-08:00

Objective

Galectin-3 is an emerging biomarker for risk stratification in patients with heart failure. This study aims to investigate the release of galectin-3 and its association with cardiovascular events in patients with adult congenital heart disease (ACHD).

Methods

In this prospective cohort study, 602 consecutive patients with ACHD who routinely visited the outpatient clinic were enrolled between 2011 and 2013. Galectin-3 was measured in thaw serum by batch analysis. The association between galectin-3 and a primary endpoint of all-cause mortality, heart failure, hospitalisation, arrhythmia, thromboembolic events and cardiac interventions was investigated using multivariable Cox models. Reference values and reproducibility were established by duplicate galectin-3 measurements in 143 healthy controls.

Results

Galectin-3 was measured in 591 (98%) patients (median age 33 (25–41) years, 58% male, 90% New York Heart Association (NYHA) class I). Median galectin-3 was 12.7 (range 4.2–45.7) ng/mL and was elevated in 7% of patients. Galectin-3 positively correlated with age, cardiac medication use, NYHA class, loss of sinus rhythm, cardiac dysfunction and N-terminal pro-B-type natriuretic peptide (NT-proBNP). During a median follow-up of 4.4 (IQR 3.9–4.8) years, the primary endpoint occurred in 195 patients (33%). Galectin-3 was significantly associated with the primary endpoint in the univariable analysis (HR per twofold higher value 2.05; 95% CI 1.44 to 2.93, p<0.001). This association was negated after adjustment for NT-proBNP (HR 1.04; 95% CI 0.72 to 1.49, p=0.848).

Conclusions

Galectin-3 is significantly associated with functional capacity, cardiac function and adverse cardiovascular events in patients with ACHD. Nevertheless, the additive value of galectin-3 to a more conventional risk marker such as NT-proBNP seems to be limited.




Retrospective UK multicentre study of the pregnancy outcomes of women with a Fontan repair

2018-02-12T01:00:46-08:00

Background

The population of women of childbearing age palliated with a Fontan repair is increasing. The aim of this study was to describe the progress of pregnancy and its outcome in a cohort of patients with a Fontan circulation in the UK.

Methods

A retrospective study of women with a Fontan circulation delivering between January 2005 and November 2016 in 10 specialist adult congenital heart disease centres in the UK.

Results

50 women had 124 pregnancies, resulting in 68 (54.8%) miscarriages, 2 terminations of pregnancy, 1 intrauterine death (at 30 weeks), 53 (42.7%) live births and 4 neonatal deaths. Cardiac complications in pregnancies with a live birth included heart failure (n=7, 13.5%), arrhythmia (n=6, 11.3%) and pulmonary embolism (n=1, 1.9%). Very low baseline maternal oxygen saturations at first obstetric review were associated with miscarriage. All eight women with saturations of less than 85% miscarried, compared with 60 of 116 (51.7%) who had baseline saturations of ≥85% (p=0.008). Obstetric and neonatal complications were common: preterm delivery (n=39, 72.2%), small for gestational age (<10th percentile, n=30, 55.6%; <5th centile, n=19, 35.2%) and postpartum haemorrhage (n=23, 42.6%). There were no maternal deaths in the study period.

Conclusion

Women with a Fontan circulation have a high rate of miscarriage and, even if pregnancy progresses to a viable gestational age, a high rate of obstetric and neonatal complications.




Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

2018-02-12T01:00:46-08:00

Background

Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality.

Methods

We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI.

Results

We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo.

Conclusion

The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group.




Cost-effectiveness of a risk-stratified approach to cardiac resynchronisation therapy defibrillators (high versus low) at the time of generator change

2018-02-12T01:00:46-08:00

Objective

Responders to cardiac resynchronisation therapy whose device has a defibrillator component and who do not receive a therapy in the lifetime of the first generator have a very low incidence of appropriate therapy after box change. We investigated the cost implications of using a risk stratification tool at the time of generator change resulting in these patients being reimplanted with a resynchronisation pacemaker.

Methods

A decision tree was created using previously published data which had demonstrated an annualised appropriate defibrillator therapy risk of 2.33%. Costs were calculated at National Health Service (NHS) national tariff rates (2016–2017). EQ-5D utility values were applied to device reimplantations, admissions and mortality data, which were then used to estimate quality-adjusted life-years (QALYs) over 5 years.

Results

At 5 years, the incremental cost of replacing a resynchronisation defibrillator device with a second resynchronisation defibrillator versus resynchronisation pacemaker was £5045 per patient. Incremental QALY gained was 0.0165 (defibrillator vs pacemaker), resulting in an incremental cost-effectiveness ratio (ICER) of £305 712 per QALYs gained. Probabilistic sensitivity analysis resulted in an ICER of £313 612 (defibrillator vs pacemaker). For reimplantation of all patients with a defibrillator rather than a pacemaker to yield an ICER of less than £30 000 per QALY gained (current NHS cut-off for approval of treatment), the annual arrhythmic event rate would need to be 9.3%. The budget impact of selective replacement was a saving of £2 133 985 per year.

Conclusions

Implanting low-risk patients with a resynchronisation defibrillator with the same device at the time of generator change is not cost-effective by current NHS criteria. Further research is required to understand the impact of these findings on individual patients at the time of generator change.




Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study

2018-02-12T01:00:46-08:00

Objective

Vital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study.

Methods

The ARIC Study is a predominately biracial cohort of men and women, aged 45–64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores.

Results

Through 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20).

Conclusions

Among participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.




Randomised controlled trial of two advanced and extended cardiac rehabilitation programmes

2018-02-12T01:00:46-08:00

Objective

The OPTICARE (OPTImal CArdiac REhabilitation) randomised controlled trial compared two advanced and extended cardiac rehabilitation (CR) programmes to standard CR for patients with acute coronary syndrome (ACS). These programmes were designed to stimulate permanent adoption of a heart-healthy lifestyle. The primary outcome was the SCORE (Systematic COronary Risk Evaluation) 10-year cardiovascular mortality risk function at 18 months follow-up.

Methods

In total, 914 patients with ACS (age, 57 years; 81% men) were randomised to: (1) 3 months standard CR (CR-only); (2) standard CR including three additional face-to-face active lifestyle counselling sessions and extended with three group fitness training and general lifestyle counselling sessions in the first 9 months after standard CR (CR+F); or (3) standard CR extended for 9 months with five to six telephone general lifestyle counselling sessions (CR+T).

Results

In an intention-to-treat analysis, we found no difference in the SCORE risk function at 18 months between CR+F and CR-only (3.30% vs 3.47%; p=0.48), or CR+T and CR-only (3.02% vs 3.47%; p=0.39). In a per-protocol analysis, two of three modifiable SCORE parameters favoured CR+F over CR-only: current smoking (13.4% vs 21.3%; p<0.001) and total cholesterol (3.9 vs 4.3 mmol/L; p<0.001). The smoking rate was also lower in CR+T compared with the CR-only (12.9% vs 21.3%; p<0.05).

Conclusions

Extending CR with extra behavioural counselling (group sessions or individual telephone sessions) does not confer additional benefits with respect to SCORE parameters. Patients largely reach target levels for modifiable risk factors with few hospital readmissions already following standard CR.

Trial registration number

ClinicalTrials.gov NCT01395095; results.




Wrist mass in a 93-year-old woman

2018-02-12T01:00:46-08:00

Clinical introduction

A 93-year-old woman presented electively for transaortic valve implantation (TAVI), for severe aortic stenosis. She had a history of hypertension and hypothyroidism, and she was taking clopidogrel, antihypertensives and levothyroxine. In preparation for her TAVI procedure she underwent coronary angiography 4 months previously. Her coronary angiogram revealed severe three vessel disease, however, the consensus from the multidisciplinary team meeting, at that time, was to manage the coronary disease medically. Physical examination revealed a large, non-tender swelling on the volar aspect of her wrist (figure 1). The swelling had progressively enlarged in size over the preceding 4 months. Duplex ultrasonography was performed, but was technically difficult. Turbulent bidirectional flow was seen within the wrist swelling, however the connecting tract from which the flow originated was not adequately visualised. The greyscale ultrasound is shown (figure 1).

Figure 1

The panel on the left shows the swelling on the volar aspect of the wrist. The panel on the right shows the grey scale ultrasound image of the swelling at the wrist.

Question 

What is the next most appropriate management step?

  • Antibiotics and drainage

  • Urgent ultrasound guided thrombin injection

  • Non-emergent vascular surgery

  • Conservative management, with observation and follow-up

  • Ultrasound guided compression




  • Early days in congenital heart surgery in the UK: the Peacock Club

    2018-02-12T01:00:46-08:00

    Dr Campbell: two lectures with contradictory conclusions

    Dr Maurice Campbell (1891–1973) was from 1936 the first Secretary of the British Cardiac Society, and in 1938 he was the first editor of the British Heart Journal, but it was as a general physician that he went on 3 September 1939 to Orpington, Kent, with a contingent of 87 nurses, to set up an outpost hospital away from the London bombing for the duration of the Second World War. In January 1946 after his return, he gave one of the standard lunchtime lectures to the staff and clinical students on the subject of congenital heart disease. In keeping with a practice which persisted until my time as a student in the 1960s, a transcript appeared in Guy’s Hospital Gazette soon after. Dr Campbell opened by saying ‘Sometimes this seems a dull subject because of the lack of treatment for this condition, so...




    Rotational atherectomy: re-emergence of an old technique

    2018-02-12T01:00:46-08:00

    Learning objectives

  • Understand the incidence, pathophysiology and treatment options for human coronary arterial calcification.

  • Understand the different imaging options for determining the extent of coronary vascular calcification and their role in planning treatment.

  • Understand the role and limitations of rotational atherectomy in the management of obstructive calcific coronary disease.

  • Introduction

    The generation of mineralised matrix within arterial conduits is common (see Figure 1). About 10%–20% of atherosclerotic vessels contain architecturally complete trabecular bone with fully formed marrow cavities with haematopoietic cells and vascular sinusoids. Although it is recognised that bone formation and arterial vessel calcification have common biochemical pathways, this so-called vascular calcification is a complex and incompletely understood phenomenon, which has proved difficult to prevent and treat.1 The process of extraskeletal ossification is not unlike embryonic ossification pathways which can be triggered by a variety of metabolic, inflammatory and genetic factors....




    Is traumatic intracranial haemorrhage a specific risk factor for atrial fibrillation?

    2018-02-12T01:00:46-08:00

    To the Editor: We read the study of Wei-Shiang Lin et al1 with a great interest. In their large-scale retrospective cohort study, they found that traumatic intracranial haemorrhage was associated with an increased risk of atrial fibrillation (AF) and hypothesised that inflammation and/or secondary cardiac insult due to the traumatic brain injury (TBI) may cause AF. Nevertheless, several points should be discussed. First, it is well known that  acute inflammation is related to AF in trauma patients. The risk of new-onset AF is reasonably expected to occur at the acute phase following the trauma. This has already been demonstrated to occur during the days following cardiac surgery or onset of septic shock.2 In the same way, cardiac insult occurs during the very early phase of TBI and the consecutive cardiac systolic dysfunction was reported to be reversible within the first week after the trauma.3 From...




    Authors reply

    2018-02-12T01:00:46-08:00

    To the Editor: We thank Dr Launey et al for their constructive comments regarding our recent report.1 We also greatly appreciate their shared interests in traumatic intracranial haemorrhage (ICH) and the subsequent incidence of atrial fibrillation (AF).

    Dr Launey and colleagues concerned about the acute effects of inflammation on the onset of AF.2 In our study, the mean follow-up period was 4.36 (SD 3.41) and 5.35 (SD 3.19) years in traumatic ICH group and control group, respectively. Interestingly, the mean follow-up period of the onset of AF was 2.94 years (SD 2.64) in traumatic ICH group, which is significantly less than 3.57 (SD 2.67) years in control group (p<0.001). Although acute inflammation plays a role on the onset of AF,3 4 our study along with previous evidence indicate the chronic persistent inflammation, which occurs after traumatic brain injury (TBI), contributes the development of AF.1 5 This...