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Heartbeat: Diabetes and heart failure

2017-02-16T08:40:35-08:00

In this issue of Heart, Skrtic and colleagues1 evaluated data from over 94 thousand primary care patients with type 2 diabetes (T2D) in the Clinical Practice Research Data Link to study the relationship between incident heart failure (HF) and hemoglobin A1c (HbA1c) levels at the initial diagnosis (baseline), most recent visit (updated latest) and an updated mean level. As shown in figure 1, elevations in all 3 HbA1c levels were associated with a higher hazard ratio  for HF, with the strongest association seen for the updated mean value. The authors suggest that ‘hyperglycaemia continues to be a strong risk factor of HF in persons with T2D, and the higher risk estimates for the updated mean HbA1c indicate that there is clinically significant benefit on reducing HF outcomes by implementing glycaemic control.’ They also note that the risk of HF may be underestimated by the baseline or latest...




Estimating cancer risk from invasive cardiac procedures in children

2017-02-16T08:40:35-08:00

In recent decades, survival among patients with congenital heart disease (CHD) has increased considerably, to the point that there are currently more adults than children living with CHD. With increasing life expectancy, new health concerns have come into focus, including the potentially long-term carcinogenic risks of exposure to low-dose ionising radiation (LDIR) from cardiac diagnostic and therapeutic procedures, particularly those related to cardiac catheterisation in children. Studies from non-medical contexts—atomic bomb survivors and uranium mine workers, among others—have clearly linked LDIR exposure with a higher risk of subsequent malignancy. Many organisations monitoring the use of radiation-emitting technologies—including the US National Research Council's Biological Effects of Ionizing Radiation (BEIR VII) Committee, the International Commission on Radiological Protection and the US National Council on Radiation Protection and Measurements—endorse a ‘linear no-threshold’ model for LDIR-related malignancy risk. That is, even at the lower doses typically encountered in medical settings, LDIR would be...




The long and unfinished journey of hyperglycaemia and heart failure research

2017-02-16T08:40:35-08:00

In 1972, Rubler et al1 reported the clinical and postmortem findings of a small cohort study involving 27 patients with diabetes. The vast majority of these patients (85%) had several other cardiovascular risk factors or evidence of ischaemic heart disease or valvular disease. After excluding these patients, the investigators found evidence of cardiomyopathy and heart failure in the remaining four patients with no apparent alternative cause other than diabetes. Intrigued by this somewhat puzzling finding, the authors coined the term ‘diabetic cardiomyopathy’, implying that diabetes causes heart failure independent of other established cardiovascular risk factors.

Since that early report, several much larger studies have investigated the association between diabetes and risk of heart failure and other cardiovascular conditions. For instance, in a recent study of 35 000 UK adults with prevalent type 2 diabetes without any known pre-existing cardiovascular disease, the risk of incident heart failure was 56%...




Understanding sudden death risk in tetralogy of Fallot: from bedside to bench

2017-02-16T08:40:35-08:00

Tetralogy of Fallot (TOF) is the most common and best studied of the various forms of complex congenital heart diseases. It is characterised by a malaligned ventricular septal defect (VSD), aortic over-ride, right ventricular (RV) outflow tract obstruction and resulting hypertrophy of the right ventricle. Since the era of infant surgery for the correction of congenital heart disease, the repair of TOF represents one of the great success stories in the treatment of congenital heart disease. The 30-year survival for patients with repaired TOF (rTOF) approaches 90%.1 Despite this unequivocal success, it was recognised, as early as the 1970s, that a subset of patients with TOF was dying suddenly. To a great extent, the research focus in TOF has since been to identify those few patients at risk of dying suddenly and to figure out what to do about it. Until relatively recently, the primary manner of...




Graphics and statistics for cardiology: survival analysis

2017-02-16T08:40:35-08:00

Reports of data in the medical literature frequently lack information needed to assess the validity and generalisability of study results. Some recommendations and standards for reporting have been developed over the last two decades, but few are available specifically for survival data. We provide recommendations for tabular and graphical representations of survival data. We argue that data and analytic software should be made available to promote reproducible research.




Survival adjusted cancer risks attributable to radiation exposure from cardiac catheterisations in children

2017-02-16T08:40:35-08:00

Objectives

To estimate the risk of developing cancer in relation to the typical radiation doses received from a range of X-ray guided cardiac catheterisations in children, taking variable survival into account.

Methods

Radiation doses were estimated for 2749 procedures undertaken at five UK hospitals using Monte Carlo simulations. The lifetime attributable risk (LAR) of cancer incidence was estimated using models developed by the Biological Effects of Ionising Radiation committee, based on both normal life expectancy, and as a function of attained age, from 20 to 80 years, to take reduced life expectancy into account.

Results

The radiation-related risks from these procedures are dominated by lung and breast cancer (for females). Assuming normal life expectancy, central LAR estimates for cancer incidence, based on median doses, ranged from <1 in 2000 for atrial septal defect occlusions to as high as 1 in 150 for valve replacements. For a reduced life expectancy of 50 years, estimated risks are lower by a factor of around 7. For conditions with especially poor survival (age 20 years), such as hypoplastic left heart syndrome, estimated cancer risks attributable to radiation were <1 in 20 000.

Conclusions

Based on recent UK radiation dose levels, the risk of cancer following cardiac catheterisations is relatively low and strongly modified by survival and the type of procedure. The risk of breast cancer, especially following pulmonary artery angioplasty and valve replacements, is the greatest concern.




Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

2017-02-16T08:40:35-08:00

Objective

The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF).

Methods and results

Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV.

Conclusion

Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF.




Contemporary risk estimates of three HbA1c variables in relation to heart failure following diagnosis of type 2 diabetes

2017-02-16T08:40:35-08:00

Background

We evaluated the association between glycaemic control and the risk of heart failure (HF) in a contemporary cohort of persons followed after diagnosis of type 2 diabetes (T2D).

Methods and results

Persons with T2D diagnosed between 1998 and 2012 were retrieved from the Clinical Practice Research Data Link in the UK and followed from diagnosis until the event of HF, mortality, drop out from the database due to any other reason, or the end of the study on 1 July 2015. The association between each of three different haemoglobin A1C (HbA1c) metrics and HF was estimated using adjusted proportional hazard models. In the overall cohort (n=94 332), the increased risk for HF per 1% (10 mmol/mol) increase in HbA1c was 1.15 (95% CI 1.13 to 1.18) for updated mean HbA1c, and 1.06 (1.04 to 1.07) and 1.06 (1.04 to 1.08) for baseline HbA1c and updated latest HbA1c, respectively. When categorised, the hazard risk (HR) for the updated mean HbA1c in relation to HF became higher than for baseline and updated latest HbA1c above HbA1c levels of 9%, but did not differ at lower HbA1c levels. The updated latest variable showed an increased risk for HbA1c <6% (42 mmol/mol) of 1.16 (1.07 to 1.25), relative category 6–7%, while the HRs for updated mean and baseline HbA1c showed no such J-shaped pattern.

Conclusions

Hyperglycaemia is still a risk factor for HF in persons with T2D of similar magnitude as in earlier cohorts. Such a relationship exists for current glycaemic levels, at diagnosis and the overall level but the pattern differs for these variables.




Pre-procedural dual antiplatelet therapy in patients undergoing transcatheter aortic valve implantation increases risk of bleeding

2017-02-16T08:40:35-08:00

Objective

To evaluate the clinical benefit of pre-procedural antiplatelet therapy in patients undergoing transfemoral (TF) transcatheter aortic valve implantation (TAVI).

Methods

OCEAN (Optimized transCathEter vAlvular interveNtion)-TAVI is a prospective, multicentre, observational cohort registry, enrolling 749 patients who underwent TAVI from October 2013 to August 2015 in Japan. We identified 540 patients (median age 85 years, 68.1% female) undergoing TF-TAVI; of these, 80 had no pre-procedural antiplatelet therapy and 460 had antiplatelet therapy. The endpoints were any bleeding (life-threatening, major, and minor bleeding) and thrombotic events (stroke, myocardial infarction, and valve thrombosis) during hospitalisation.

Results

Patients with dual antiplatelet therapy (DAPT) had a significantly higher incidence of any bleeding than those with single antiplatelet therapy (SAPT) (36.5% vs 27.5%, p=0.049) and no antiplatelet therapy (36.5% vs 21.3%, p=0.010). Patients without pre-procedural antiplatelet therapy did not experience an increased risk of thrombotic events. In multivariable logistic regression analysis, DAPT before TF-TAVI significantly increased any bleeding compared with SAPT (OR 2.05, 95% CI 1.16 to 3.65) and no antiplatelet therapy (OR 2.30, 95% CI 1.08 to 4.90).

Conclusions

The current study demonstrated that DAPT before TF-TAVI increased the risk of bleeding compared with single or no antiplatelet therapy. Lower intensity antiplatelet therapy was not associated with thrombotic events. In modern practice, it might be reasonable to perform TAVI using single or no pre-procedural antiplatelet therapy with an expectation of no increase of adverse events.

Trial registration number

UMIN-ID; 000020423; Results.




Postoperative dyspnoea

2017-02-16T08:40:35-08:00

Clinical introduction

A man in his 50s presented with abscessed aortic valve methicillin-sensitive Staphylococcus aureus endocarditis, received intravenous antibiotics and underwent bioprosthetic aortic valve replacement with removal of all infected tissues. He returned 18 days later with severe dyspnoea, subjective fever and bilateral lower extremity oedema. Physical examination revealed tachypnoea and tachycardia without fever, prominent neck CV waves visible at 90°, left parasternal heave, 3/6 holosystolic murmur across the precordium, lung rales and severe peripheral oedema. C reactive protein was 211 mg/L (normal <8 mg/L). Blood cultures were obtained. ECG showed sinus tachycardia and right axis deviation. Transthoracic echocardiogram (TTE) parasternal zoomed short-axis systolic frame (figure 1A, B), apical four-chamber systolic frame (figure 1C) and subcostal continuous wave (CW) Doppler (figure 1D), are shown.

Question

Given the clinical presentation and TTE findings, what is the diagnosis?

  • Severe tricuspid regurgitation due to extension of endocarditis

  • Aortic valve obstruction resulting in severe pulmonary hypertension

  • Acquired Gerbode defect

  • Aortic valve dehiscence with severe paraprosthetic regurgitation




  • Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial

    2017-02-16T08:40:35-08:00

    Objective

    The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablation was elimination of electrical activity inside pulmonary veins. We present the results of the 5-year follow-up.

    Methods

    This pre-specified 5-year follow-up included assessment of any AF and symptomatic AF burden by one 7-day Holter recording and quality of life (QoL) assessment, using SF-36 questionnaire physical and mental component scores. Analysis was intention-to-treat. Imputation was used to compensate for missing Holter data.

    Results

    245 of 294 patients (83%) randomised to RFA (n=125) or AAD (n=120) attended the 5-year follow-up, 227 with Holter recording. Use of class I or III AAD was more frequent in AAD group (N=61 vs 13, p<0.001). More patients in the RFA group were free from AF (126/146 (86%) vs 105/148 (71%), p=0.001, relative risk (RR) 0.82; 95% CI 0.73 to 0.93) and symptomatic AF (137/146 (94%) vs 126/148 (85%), p=0.015, 2 test, RR 0.91; 95% CI 0.84 to 0.98) in 7-day Holter recording. AF burden was significantly lower in the RFA group (any AF: p=0.003; symptomatic AF: p=0.02). QoL scores did not differ between randomisation groups. QoL scores remained improved from baseline (both components p<0.001), and did not differ from 2-year scores.

    Conclusions

    At 5 years, the occurrence and burden of any AF and symptomatic AF were significantly lower in the RFA group than in the AAD group. Improved QoL scores observed after 2 years persisted after 5 years without between-group differences.

    Trial registration number

    NCT00133211; Results.




    Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip

    2017-02-16T08:40:35-08:00

    Background

    Apart from several established clinical risk factors for atrial fibrillation (AF), a number of biomarkers have also been identified as potential risk factors for AF. None of these have so far been adopted in clinical practice.

    Objective

    To use a novel custom-made proteomics chip to discover new prognostic biomarkers for AF risk.

    Methods

    In two independent community-based cohorts (Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (978 participants without AF, mean age 70.1 years, 50% women, median follow-up 10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n=725, mean age 77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85 proteins showed a call rate >70% in both cohorts.

    Results

    Thirteen proteins were related to incident AF in PIVUS (148 events) using a false discovery rate of 5%. Of those, five were replicated in ULSAM at nominal multivariable p value (123 events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23 were also associated with AF after adjusting for established AF risk factors. In a prespecified secondary analysis pooling the two data sets, T-cell immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also significantly related to incident AF in addition to the aforementioned five proteins (Bonferroni-adjustment). The addition of NT-pro-BNP to a model with established risk factors increased the C-statistic from 0.605 to 0.676 (p<0.0001).

    Conclusions

    Using a novel proteomics approach, we confirmed the previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be of importance in the development of AF.




    Cardiorespiratory fitness and exercise-induced ST segment depression in assessing the risk of sudden cardiac death in men

    2017-02-16T08:40:35-08:00

    Objective

    The aim of this study was to investigate whether information on both cardiorespiratory fitness (CRF) and exercise-induced ST segment depression improves the prediction of sudden cardiac death (SCD) in men.

    Methods

    The study was based on a population sample of 2328 men aged 42–60 years, who were followed up for on average 19 years. CRF was assessed with maximal exercise test using respiratory gas analysis, expressed in metabolic equivalents (METs) and dichotomised at eight METs. Exercise-induced ST segment depression was defined as 1 mm ST segment depression in ECG.

    Results

    Altogether 165 SCDs occurred during the follow-up. Men with low CRF (<8 METs) and exercise-induced ST segment depression had 4.8-fold (95% CI 2.9 to 7.9) higher risk of SCD than men with high CRF and without exercise-induced ST segment depression (p=0.013 for interaction) after adjustment for other cardiovascular risk factors. Men with high CRF and exercise-induced ST segment depression did not have a statistically significantly higher risk of SCD (HR 1.9, 95% CI 0.9 to 3.8) than men with high CRF and without exercise-induced ST segment depression.

    Conclusions

    The combination of low CRF and exercise-induced ST segment depression was associated with a markedly increased risk of SCD in men.




    Mitochondrial disease and the heart

    2017-02-16T08:40:35-08:00

    Learning objectives

  • Become familiar with the spectrum of cardiac involvement in mitochondrial diseases (MDs).

  • Recognise the clinical features of cardiac involvement in MDs.

  • Understand the current strategy for management of MDs.

  • Introduction

    Mitochondrial diseases (MDs) include a wide range of clinical entities involving tissues that have high energy requirements such as heart, muscle, kidney and the endocrine system1 (figure 1). Defects in mitochondrial DNA (mtDNA) mutations are the most common cause of MDs in adults.2 3 However, the nuclear gene defects are increasingly recognised as a cause of disease.4 Although the true prevalence of cardiac involvement in MD is unknown, cardiovascular involvement presents specific clinical issues that require systematic evaluation. In addition, in some MD-related mutations (eg, m.3243A.G) cardiac disease is the most common cause of early death.5 Hence, cardiologists are...