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Heartbeat: Glycaemic control and excess risk of major coronary events in type 1 diabetes

2017-10-12T07:30:15-07:00

Individuals with diabetes are known to be at increased risk of cardiovascular events. However, most studies to date have focused patients with type 2 diabetes. In this issue of Heart, Matuleviciene-Anängen and colleagues1 report the findings of a study that investigates the risk of myocardial infarction in patients with type 1 diabetes compared with matched controls in Sweden. The focus on type 1 diabetes is particularly valuable given that (unlike type 2 diabetes) its diagnosis commonly precedes the development of other potentially confounding or mediating risk factors for cardiovascular disease. With about 1500 cardiovascular events during 8 years of follow-up, the researchers show that patients with type 1 diabetes have a four times higher risk of non-fatal myocardial infarction or coronary death. The excess risk was diminished but did not disappear in those with good glycaemic control or when there was no renal dysfunction at baseline. In...




Extreme ischaemic heart disease risk in people with type 1 diabetes

2017-10-12T07:30:15-07:00

Observational studies show strong associations between diabetes and risk of ischaemic heart disease (IHD).1 Data, mainly from population-based cohorts in high-income countries, suggest that diabetes approximately doubles the risk of IHD, and this association may be doubled again in countries where healthcare resources to treat diabetes are limited.2 Diabetes associates with several known cardiovascular disease risk factors, but the persistence of this excess risk despite accounting for the effects of blood pressure, lipids and lifestyle factors (including smoking) suggests other important mediators of risk exist.1

Most large-scale observations of diabetes, glycaemic control and IHD have come from populations where type 2 diabetes predominates. In their Heart manuscript Matuleviciene Anängen and colleagues have studied IHD risk in type 1 diabetes and assessed how glycaemic control and reduced kidney function influence this risk.3 Studying these exposures in type 1 diabetes is an attractive strategy as the...




Improving postoperative outcome of congenital heart surgery in low/middle-income countries: climbing mount excellence

2017-10-12T07:30:15-07:00

Congenital cardiac defects continue to be a major cause of death and suffering in the low/middle-income countries.1 This stems from the larger burden of congenital heart defects in these countries,2 coupled with the paucity of specialised centres and the reported worse outcome of operations in the existing centres. These facts have stimulated concerted efforts to establish new sustainable centres3 and, importantly, developing strategies to improve outcome in the existing centres.

The Heart paper by Khan and colleagues4 is a welcome addition to the literature as it highlights the advantages, as well as limitations, of applying some of the recommendations of a collaborative programme developed by workers at Boston Children Hospital, and currently being applied completely, or in part, by 28 centres in low/middle-income countries.5 The authors report the effect of applying some of these recommendations, including enhancing hospital infection control...




A nationwide contemporary epidemiological portrait of valvular heart diseases

2017-10-12T07:30:15-07:00

The spectrum of valvular heart diseases (VHDs) has evolved during the past decades in the developed countries. However, there are few epidemiological data on VHD and large contemporary population-based studies are lacking. In this issue of the journal, Andell et al present the findings of a nationwide study in Sweden that includes a population of about 10 million people.1 The authors used nationwide registers to identify all patients with first diagnosis of VHD at Swedish hospitals between 2003 and 2010. The cases diagnosed in the years 2000, 2001 and 2002 were excluded, therefore allowing to estimate the incidence rates of VHDs. The incidence of each VHD was then stratified for age and sex.

Andell et al should be commended for this elegant and important study that provides a contemporary and comprehensive portrait of the epidemiology spectrum of VHD within a large European country.1 Previous epidemiology studies...




Mitral valve repair for degenerative mitral valve disease: surgical approach, patient selection and long-term outcomes

2017-10-12T07:30:15-07:00

Mitral valve repair (MVRepair) has become the procedure of choice to correct severe degenerative mitral regurgitation (MR), due to its documented superiority to valve replacement regarding long-term survival, freedom from valve-related adverse events and preservation of left ventricular (LV) function. The refinement of MVRepair techniques has rendered almost all valves (more than 95%) amenable to repair with a 15-year freedom from reoperation of 90%. The concept of ‘centres of excellence for MVRepair’ has emerged, encouraging referring doctors to select the most experienced institutions or individual surgeons to deal with the most complex cases, based on repair volume, appropriate peri-procedural imaging and data regarding expected outcomes (repair, mortality and durability of repair). Based on the good results, operating on asymptomatic patients with severe MR is now widely accepted, prophylactically avoiding the dire consequences of chronic MR, such as LV function deterioration/enlargement, and development of atrial fibrillation and pulmonary hypertension. In reference centres, where the repair rate is over 95% for all types of disease with <1% mortality, it has become standard practice in nearly 50%–60% of all patients submitted to MVRepair. Finally, recent advances in the surgical treatment with the purpose of reducing invasiveness and surgical trauma, through partial sternotomy or mini-thoracotomy (video-assisted with or without robotics), are now being increasingly performed in 20%–30% of centres, claiming comparable results to conventional surgery. In addition, transcatheter technology, particularly the MitraClip, is evolving and treading its way in the treatment of high-risk patients with severe MR, but the results are still short of ideal.




PCSK9 inhibition and atherosclerotic cardiovascular disease prevention: does reality match the hype?

2017-10-12T07:30:15-07:00

Within this review we look at whether the potential provided by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition for prevention of atherosclerotic cardiovascular disease matches the excitement generated. Two fully human monoclonal antibodies to PCSK9 are currently licenced for clinical use both in the USA and the European Union: evolocumab and alirocumab. These reduce low-density lipoprotein cholesterol by over 50% across a range of populations and were generally found to have a safety profile comparable with placebo. The development programme for a third humanised monoclonal antibody, bococizumab, was terminated early due to the presence of neutralising antibodies reducing its efficacy over time. Results from the first cardiovascular outcomes trial, FOURIER, have demonstrated significant reductions in cardiovascular events in a population with stable cardiovascular disease over a 2-year period. The ODYSSEY OUTCOMES trial comparing alirocumab to placebo is expected to report in 2018 and provide cardiovascular outcome data in a post acute coronary syndrome population. Monoclonal antibodies have an injection burden of 12–26 injections per year. An alternative approach to reducing PCSK9 is to inhibit translation of the messenger RNA for PCSK9. The phase II ORION-1 study using inclisiran, a small interference RNA to PCSK9, suggested that two doses of inclisiran produced time averaged reductions in LDL cholesterol of 50% over 9 months. The ORION-4 cardiovascular outcome trial will assess the cardiovascular benefits of two injections per year using inclisiran. With further outcome trials expected, appropriate patient selection will be key considering the higher drug costs of these therapies.




Impact of International Quality Improvement Collaborative on Congenital Heart Surgery in Pakistan

2017-10-12T07:30:15-07:00

Background

The International Quality Improvement Collaborative (IQIC) was formed to reduce mortality and morbidity from congenital heart disease (CHD) surgeries in low/middle-income countries.

Objectives

We conducted this study to compare the postoperative outcomes of CHD surgeries at a centre in Pakistan before and after joining IQIC.

Methods

The IQIC provides guidelines targeting key drivers responsible for morbidity and mortality in postoperativepatients with CHD. We focused primarily on nurse empowerment and improving the infection control strategies at our centre. Patients with CHD who underwent surgery at this site during the period 2011–2012 (pre-IQIC) were comparedwith those getting surgery in 2013–2014 (post-IQIC). Morbidity (major infections), mortality and factors associated with them were assessed.

Results

There was a significant decrease in surgical site infections and bacterial sepsis in the post-IQIC versus pre-IQIC period (1% vs 30%, p=0.0001, respectively). A statistically insignificant decrease in the mortality rate was also noted in post-IQIC versus pre-IQIC period (6% vs 9%, p=0.17, respectively). Durations of ventilation and intensive care unit (ICU) and hospital stay were significantly reduced in the post-IQIC period. Age <1 year, malnutrition, low preoperative oxygen perfusion, Risk Adjustment for Congenital Heart Surgery score >3, major chromosomal anomalies, perfusion-related event, longer ventilation and ICU/hospital stay durations were associated with greater odds of morbidity and mortality.

Conclusion

Enrolling in the IQIC programme was associated with an improvement in the postsurgical outcomes of the CHD surgeries at our centre.




Glycaemic control and excess risk of major coronary events in persons with type 1 diabetes

2017-10-12T07:30:15-07:00

Objective

The excess risk of major coronary events (acute myocardial infarction (AMI) or death from coronary heart disease (CHD)) in individuals with type 1 diabetes (T1D) in relation to glycaemic control and renal complications is not known.

Methods

Individuals with T1D in the Swedish National Diabetes Registry after 1 January 1998, without a previous MI (n=33 170) and 1 64 698 controls matched on age, sex and county were followed with respect to non-fatal AMI or death from CHD. Data were censored at death due to any cause until 31 December 2011.

Results

During median follow-up of 8.3 and 8.9 years for individuals with T1D and controls, respectively, 1500 (4.5%) and 1925 (1.2%), experienced non-fatal AMI or died from CHD, adjusted HR 4.07 (95% CI 3.79 to 4.36). This excess risk increased with younger age, female sex, worse glycaemic control and severity of renal complications.

The adjusted HR in men with T1D with updated mean haemoglobin A1c (HbA1c) <6.9% (52 mmol/mol) and normoalbuminuria was 1.30 (95% CI 0.90 to 1.88) and in women 3.16 (95% CI 2.14 to 4.65). HRs increased to 10.7 (95% CI 8.0 to 14.3) and 31.8 (95% CI 23.6 to 42.8) in men and women, respectively, with HbA1c >9.7% and renal complications.

Conclusions

The excess risk of AMI in T1D is substantially lower with good glycaemic control, absence of renal complications and men compared with women. In women, the excess risk of AMI or CHD death persists even among patients with good glycaemic control and no renal complications.




Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study

2017-10-12T07:30:15-07:00

Objective

Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking.

Methods

We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified incidence of each VHD and adjusted comorbidity profiles were assessed.

Results

In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100 000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR; 24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects aged ≥65 years), but pulmonary valve disease incidence peaked in newborns. Incidences of AR, AS and MR were higher in men who were also more frequently diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women. Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic vascular disease (48.4%), whereas concomitant heart failure and atrial fibrillation were common in mitral valve disease and tricuspid regurgitation. Other common comorbidities were thoracic aortic aneurysms in AR (10.3%), autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR (10.7%) and TR (10.3%).

Conclusions

Clinically diagnosed VHD was primarily a disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs showed a range of different comorbidity profiles . Pronounced sex-specific patterns were observed for AR and MS, for which the mechanisms remain incompletely understood.




Progressive breathlessness following transcatheter aortic valve replacement

2017-10-12T07:30:15-07:00

An 84-year-old man presented urgently to the cardiology clinic with rapid onset exertional dyspnoea while walking on the flat. Five months previously, he underwent implantation of a balloon-expandable 26 mm transcatheter heart valve (SAPIEN 3, Edwards Lifesciences) for severe aortic stenosis. On clinical examination, the jugular venous pressure was elevated and a mid-late ejection systolic murmur was audible in the aortic region. ECG demonstrated sinus rhythm with a left ventricular (LV) strain pattern. Transthoracic echocardiography and cardiac CT were performed (figure 1). Figure 1

(A) Transthoracic continuous wave Doppler through the transcatheter AV. ECG-gated cardiac CT oblique reconstruction of the LV outflow tract and aortic root in mid-diastole (B) with axial reconstruction of the transcatheter AV in end-systole (inset). AT, acceleration time; AV, aortic valve; LV, left ventricular.

Question

Which aetiology best explains this presentation?

  • Pannus formation

  • Transcatheter bioprosthetic valve endocarditis

  • Patient-prosthesis mismatch

  • Transcatheter bioprosthetic valve leaflet thrombosis

  • Structural valve degeneration




  • Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy

    2017-10-12T07:30:15-07:00

    Objective

    To explore the genetic landscape of a well selected dilated cardiomyopathy (DCM) cohort, assessing the possible relation between different genotypes and left ventricular reverse remodelling (LVRR).

    Methods

    A cohort of 152 patients with DCM from the Heart Muscle Disease Registry of Trieste has been studied by next-generation sequencing (NGS). Patients were grouped into different ‘gene-clusters’ with functionally homogeneous genetic backgrounds. LVRR was defined by left ventricular ejection fraction normalisation or increase ≥10% associated with normalisation in indexed left ventricular end-diastolic diameter or relative decrease ≥10% at 24 months follow-up.

    Results

    A pathogenic disease-related gene variant was identified in 57% of patients: 28 (18%) TTN; 7 (5%) LMNA; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18 (12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features were similar throughout the different genotypes. A significant relationship was found between gene cluster subgroups and LVRR, with a lower rate of LVRR in structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p<0.05 vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare variants were independently and inversely associated with LVRR when adjusted for clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011).

    Conclusions

    NGS confirmed a high genetic diagnostic yield in DCM. A specific ‘gene-clusters’ classification based on functional similarities in different genes might be helpful in the clinical management of genetically determined DCM. In this study, structural cytoskeleton Z-disk gene rare variants were independently associated with a lower rate of LVRR at follow-up.




    Nitric oxide synthase inhibition restores orthostatic tolerance in young vasovagal syncope patients

    2017-10-12T07:30:15-07:00

    Objective

    Syncope is sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). We previously demonstrated impaired post-synaptic adrenergic responsiveness in young VVS patients was reversed by blocking nitric oxide synthase (NOS). We hypothesised that nitric oxide may account for reduced orthostatic tolerance in young recurrent VVS patients.

    Methods

    We recorded haemodynamics in supine VVS and healthy volunteers (aged 15–27 years), challenged with graded lower body negative pressure (LBNP) (–15, –30, –45 mm Hg each for 5 min, then –60 mm Hg for a maximum of 50 min) with and without NOS inhibitor NG-monomethyl-L-arginine acetate (L-NMMA). Saline plus phenylephrine (Saline+PE) was used as volume and pressor control for L-NMMA.

    Results

    Controls endured 25.9±4.0 min of LBNP during Saline+PE compared with 11.6±1.4 min for fainters (p<0.001). After L-NMMA, control subjects endured 24.8±3.2 min compared with 22.6±1.6 min for fainters. Mean arterial pressure decreased more in VVS patients during LBNP with Saline+PE (p<0.001) which was reversed by L-NMMA; cardiac output decreased similarly in controls and VVS patients and was unaffected by L-NMMA. Total peripheral resistance increased for controls but decreased for VVS during Saline+PE (p<0.001) but was similar following L-NMMA. Splanchnic vascular resistance increased during LBNP in controls, but decreased in VVS patients following Saline+PE which L-NMMA restored.

    Conclusions

    We conclude that arterial vasoconstriction is impaired in young VVS patients, which is corrected by NOS inhibition. The data suggest that both pre- and post-synaptic arterial vasoconstriction may be affected by nitric oxide.




    One-year costs of bilateral or single internal mammary grafts in the Arterial Revascularisation Trial

    2017-10-12T07:30:15-07:00

    Objective

    Coronary artery bypass grafting (CABG) using bilateral internal mammary arteries (BIMA) may improve survival over CABG using single internal mammary arteries (SIMA), but may be surgically more complex (and therefore costly) and associated with impaired sternal wound healing. We report, for the first time, a detailed comparison of healthcare resource use and costs over 12 months, as part of the Arterial Revascularisation (ART) Trial.

    Methods

    3102 patients in 28 hospitals in seven countries were randomised to CABG surgery using BIMA (n=1548) or SIMA (n=1554). Detailed resource use data were collected covering surgery, the initial hospital episode, and for 12 months post randomisation. Using UK unit costs, total costs were calculated and compared between trial arms and for subgroups.

    Results

    Patients randomised to BIMA spent 20 min longer in theatre (95% CI 15 to 25, p<0.001) and also required more treatment for sternal wound problems. Mean (SD) total costs per patient at 12 months were £13 839 (£10 534) for BIMA and £12 717 (£9719) for SIMA (mean cost difference £1122, 95% CI £407 to £1838, p=0.002). No tests for interaction between subgroups and treatment allocation were significant.

    Conclusions

    At 12 months from randomisation, mean costs were approximately 9% higher in BIMA than SIMA patients, primarily due to longer time in theatre and in-hospital stay, and slightly higher costs related to sternal wound problems during follow-up. Follow-up to the primary trial endpoint of 10 years will reveal whether longer-term differences emerge in graft patency or in overall survival.

    Trial registration number

    Controlled-trials.com (ISRCTN46552265).




    Frequency of chest pain in primary care, diagnostic tests performed and final diagnoses

    2017-10-12T07:30:15-07:00

    Objective

    Observational study of patients with chest pain in primary care: determination of incidence, referral rate, diagnostic tests and (agreement between) working and final diagnoses.

    Methods

    118 general practitioners (GPs) in the Netherlands and Belgium recorded all patient contacts during 2weeks. Furthermore, patients presenting with chest pain were registered extensively. A follow-up form was filled in after 30 days.

    Results

    22 294 patient contacts were registered. In 281 (1.26%), chest pain was a reason for consulting the GP (mean age for men 54.4/women 53 years). In this cohort of 281 patients, in 38.1% of patients, acute coronary syndrome (ACS) was suspected at least temporarily during consultation, 40.2% of patients were referred to secondary care and 512 diagnostic tests were performed by GPs and consulted specialists. Musculoskeletal pain was the most frequent working (26.1%) and final diagnoses (33.1%). Potentially life-threatening diseases as final diagnosis (such as myocardial infarction) accounted for 8.4% of all chest pain cases. In 23.1% of cases, a major difference between working and final diagnoses was found, in 0.7% a severe disease was initially missed by the GP.

    Conclusion

    Chest pain was present in 281 patients (1.26% of all consultations). Final diagnoses were mostly non-life-threatening. Nevertheless, in 8.4% of patients with chest pain, life-threatening underlying causes were identified. This seems reflected in the magnitude and wide variety of diagnostic tests performed in these patients by GPs and specialists, in the (safe) overestimation of life-threatening diseases by GPs at initial assessment and in the high referral rate we found.




    How to interpret an echocardiography report (for the non-imager)?

    2017-10-12T07:30:15-07:00

    Learning objectives

  • To be able to interpret findings from an echocardiographic study in a systematic manner.

  • To be able to appreciate relative clinical value of various echocardiographic findings in different clinical scenarios and recognise those directly impacting clinical decision making.

  • To be able to integrate echocardiographic findings with those of clinical examination and other investigations.

  • To be able to integrate echocardiography in the overall patient care.

  • Introduction

    Echocardiography is the most widely used cardiac imaging modality. Its ability to permit comprehensive assessment of cardiac structure and function combined with its safety, wide availability and ease of application render it indispensable in the management of most patients with a suspected or known cardiac illness. It is therefore not surprising that the use of echocardiography, when performed for appropriate clinical indications, has been shown to be associated with decreased odds of in-hospital mortality.




    Phosphodiesterase-5 inhibitors as novel cardioprotective agents: have we reached threshold for large-scale clinical trials?

    2017-10-12T07:30:15-07:00

    To the Editor

    We read with great interest the compelling findings of Andersson et al demonstrating strong association between on-demand use of phosphodiesterase-5 (PDE5) inhibitors (PDE5is) and a reduction in cardiovascular mortality and heart failure hospitalisation in patients followed up following their first myocardial infarction (MI). We previously reported in Heart a similarly strong association between PDE5i use and reduced mortality in a cohort of patients with type 2 diabetes and attendant high cardiovascular risk.1 In our study, we showed that the association was stronger in patients with prior MI, supporting a cardioprotective action, although we were unable to draw conclusions about underlying mechanisms of protection.

    As the authors concede, and in similarity to our study, the observational nature of their work and the presence of unmeasured confounding factors (eg, marital status, physical activity, diposable income and educational attainment) make it impossible to establish concrete conclusions. Even so,...




    The results of a pharmacoeconomic study: incremental cost-effectiveness ratio versus net monetary benefit

    2017-10-12T07:30:15-07:00

    To the Editor

    The article by Wouters and colleagues1 presents an exhaustive overview on how quality-adjusted life years (QALYs) can be used in cost-effectiveness analysis. In this framework, the authors also mention the incremental cost-effectiveness ratio (ICER), which is the parameter typically used to express the results of a cost-effectiveness study. The article, however, does not discuss the net monetary benefit (NMB), which is another parameter used to express the results of a cost-effectiveness study.

    The incremental cost (C) and the incremental effectiveness (E) are the two main parameters of pharmacoeconomics and cost-effectiveness analysis, along with the willingness-to-pay threshold (). The decision rule (eg, in the case of a favourable pharmacoeconomic result) is (C/E) < (equation 1), if based on the ICER, or (Ex–C) > 0 (equation 2), if based on the NMB. Likewise, an unfavourable pharmacoeconomic result is when (C/E) > or when...