Pulmonary hypertension in children negatively impacts clinical outcome and is not always responsive to medical therapy. An entire supplement to Heart
Coronary heart disease (CHD) caused by the narrowing of arteries that feed the heart is the single biggest killer in industrialised societies. Current treatments are palliative, failing to provide a definitive repair of the injured heart. Refractory angina, often seen in patients with occlusive pathology extending to the coronary microvasculature, also represents an unmet therapeutic need. There is hope that regenerative treatments based on gene and stem cell therapy provide a solution for patients with refractory CHD.
Therapeutic angiogenesis with molecules of the vascular endothelial growth factor (VEGF) family has been successfully tested in preclinical rodent models of myocardial and peripheral ischaemia, but clinical trials have not matched the initial promises. This discrepancy is mainly attributable to the dosage and time of delivery, due to the pathophysiological difference between the mouse heart and the human heart. This limitation called for the use of large animal models in cardiovascular research....
It is interesting to observe that details of cardiovascular anatomy become more relevant if novel therapeutic targets are on the horizon. Surgeons have always had a genuine interest in anatomy, along with close and continuous knowledge exchange with morphologists. Radiologists focus on the correlation of anatomical knowledge with various imaging techniques. However, the interventional cardiologist only began to show interest in detailed cardiovascular anatomy when novel transcatheter options became available to treat or palliate a wider range of structural cardiac defects. In the context of transcatheter therapies, some structures have really only been visualised in detail for the first time by modern imaging techniques. For the paediatric cardiologist, the detailed anatomy of the atrial and ventricular septum, the arterial duct, aortic isthmus or, in particular, the right ventricular outflow tract became obvious and relevant in consideration of device closure, stent or valve stent placement. For the adult cardiologist, advanced...
Ventricular arrhythmias remain a challenge in the care of adults with congenital heart disease (ACHD). This Heart review
The development of evidence-based guidelines in ACHD is particularly difficult for several reasons. Randomised controlled trials (RCTs) provide the foundation of data for most other cardiac guidelines; however, heterogeneity of diagnoses and physiological variations leads to relatively small populations in ACHD, which require long recruitment periods. Today, individuals also emerge from childhood surgery with a different footprint than those in prior decades, further complicating the interpretation, and relevance of past RCTs. Therefore, thorough observational studies have been crucial to the development of ACHD guidelines, and with consensus statements inform much of the ACHD literature.
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Remarkable gains in survival have led to an unprecedented number of adults with congenital heart disease. Arrhythmias collectively comprise the most common complication encountered. Recognising the unique issues and challenges involved in managing arrhythmias in adults with congenital heart disease and the consequential decisions surrounding sudden death prevention, expert societies have proposed evidence-based recommendations. On the whole, acute ventricular arrhythmias are managed according to general cardiology guidelines, while taking into consideration congenital heart disease-specific issues, such as positioning of patches or paddles according to location of the heart. Implantable cardioverter-defibrillators (ICDs) are indicated for secondary prevention in patients with sustained ventricular tachycardia or resuscitated cardiac arrest in the absence of a reversible cause. Pharmacological therapy and catheter ablation can be effective in reducing recurrent ICD shocks. Risk–benefit assessment for primary prevention ICDs is a major challenge. Although a clearer picture has emerged of the high-risk patient with tetralogy of Fallot, ICD indications for those with systemic right ventricles or univentricular hearts remain contentious. Challenges to ICD implantation include obstructed veins, conduits and baffles, atrioventricular valve disease and intracardiac shunts. In selected patients, customised systems with epicardial and/or subcutaneous coils may represent a viable solution. Alternatively, the subcutaneous ICD is an attractive option for patients in whom transvenous access is not feasible or desirable and in whom bradycardia and antitachycardia pacing features are not essential. Continued advances in risk stratification and device technologies carry the potential to further improve efficacy and safety outcomes in this growing population of patients.
Calcific diseases of the cardiovascular system, such as atherosclerotic calcification and calcific aortic valve disease, are widespread and clinically significant, causing substantial morbidity and mortality. Vascular cells, like bone cells, interact with their matrix substrate through molecular signals, and through biomechanical signals, such as traction forces transmitted from cytoskeleton to matrix. The interaction of contractile vascular cells with their matrix may be one of the most important factors controlling pathological mineralisation of the artery wall and cardiac valves. In many respects, the matricrine and matrix mechanical changes in calcific vasculopathy and valvulopathy resemble those occurring in embryonic bone development and normal bone mineralisation. The matrix proteins provide a microenvironment for propagation of crystal growth and provide mechanical cues to the cells that direct differentiation. Small contractions of the cytoskeleton may tug on integrin links to sites on matrix proteins, and thereby sense the stiffness, possibly through deformation of binding proteins causing release of differentiation factors such as products of the members of the transforming growth factor-β superfamily. Inflammation and matrix characteristics are intertwined: inflammation alters the matrix such as through matrix metalloproteinases, while matrix mechanical properties affect cellular sensitivity to inflammatory cytokines. The adhesive properties of the matrix also regulate self-organisation of vascular cells into patterns through reaction-diffusion phenomena and left-right chirality. In this review, we summarise the roles of extracellular matrix proteins and biomechanics in the development of inflammatory cardiovascular calcification.
Coronary heart disease remains a significant clinical problem, and new therapies are needed especially for patients with refractory angina for whom the current therapies do not provide sufficient relief. The aim of this study was to find out if angiogenic gene therapy using new members of the vascular endothelial growth factor (VEGF) family, VEGF-B186 and VEGF-DNC, increase myocardial perfusion as measured by the positron emission tomography (PET) 15O-imaging, and whether there would be coronary steal effect to the contralateral side. Furthermore, safety of intramyocardial angiogenic adenoviral gene transfer was evaluated.
Intramyocardial adenoviral (Ad) VEGF-B186 or AdVEGF-DNC gene transfers were given endovascularly into the porcine posterolateral wall of the left ventricle (n=34). Six days later, PET 15O-imaging for myocardial perfusion and coronary angiography were performed.
AdVEGF-B186 and AdVEGF-DNC induced angiogenesis and increased total microvascular area 1.8-fold (95% CI 0.2 to 3.5) and 2.8-fold (95% CI 1.4 to 4.3), respectively. At rest, perfusion was maintained at normal levels, but at stress, relative perfusion was increased 1.4-fold (95% CI 1.1 to 1.7) for AdVEGF-B186 and 1.3-fold (95% CI 1.0 to 1.7) for AdVEGF-DNC, without causing coronary steal effect in the control area. The therapy was well tolerated and did not lead to any significant changes in laboratory safety parameters.
Both AdVEGF-B186 and AdVEGF-DNC gene transfers induced efficient angiogenesis in the myocardium resulting in an increased myocardial perfusion measured by PET. Importantly, local perfusion increase did not induce any coronary steal effect. As such, both treatments seem suitable new candidates for the induction of therapeutic angiogenesis for the treatment of refractory angina.
To determine cut-off values for a recently introduced high sensitive cardiac troponin assay (hs-cTnI) which provide similar sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for acute myocardial infarction (AMI) as known cut-off values for an hs-cTnT assay.
A prospective observational study was performed. Hs-cTnT (Roche) and hs-cTnI (Abbott) were measured in consecutive patients with symptoms suggestive of AMI. Representative measurements (obtained at least 3 h after chest pain has started) and serial measurements with a time delay between 2.5 h and 4.5 h were used to determine cut-off levels. Two independent clinicians adjudicated the final diagnosis.
1490 patients were included in the study of whom 114 (8%) received a final diagnosis of AMI. Receiver operating characteristics analysis showed no statistically significant differences in the areas under the curve between the two assays. Cut-off values for representative hs-TnI were found to be as follows: rule-out: 10 ng/L (sensitivity: 98.2%; 95% CI 95.7% to 100.0% and NPV: 99.8%; 99.5% to 100.0%); rule-in: 70 ng/L (specificity: 90.8%; 89.3% to 92.4% and PPV: 39.7%; 36.1% to 43.3%). For serial measurements we found a rule-out cut-off value of 20 ng/L (sensitivity: 94.9%; 88.0% to 100.0% and NPV: 98.7%; 96.9% to 100.0%) and rule-in cut-off values of 100 ng/L (specificity: 92.7%; 87.9% to 95.8% and PPV: 57.6%; 39.4% to 74.0%) and 300% (specificity: 93.8%; 90.4% to 97.2% and PPV: 61.3%; 51.1% to 71.5%).
Cut-off values for hs-cTnI measurements are determined which allow a similar diagnostic classification as compared with hs-cTnT. Importantly, for a rule-out paradigm this cut-off value is unmistakably lower than the upper reference limit.
A proportion of patients with suspected ST-elevation myocardial infarction (STEMI) presenting for primary percutaneous coronary intervention (PPCI) do not have obstructive coronary disease and other conditions may be responsible for their symptoms and ECG changes. In this study, we set out to determine the prevalence and aetiology of alternative diagnoses in a large PPCI cohort as determined with multimodality imaging and their outcome.
From 2009 to 2012, 5238 patients with suspected STEMI were referred for consideration of PPCI. Patients who underwent angiography but had no culprit artery for revascularisation and no previous history of coronary artery disease were included in the study. Troponin values, imaging findings and all-cause mortality were obtained from hospital and national databases.
A total of 575 (13.0%) patients with a mean age of 58±15 years (69% men) fulfilled the inclusion criteria. A specific diagnosis based on imaging was made in 237 patients (41.2%) including cardiomyopathies (n=104, 18%), myopericarditis (n=48, 8.4%), myocardial infarction/other coronary abnormality (n=27, 4.9%) and severe valve disease (n=23, 4%). Pulmonary embolism and type A aortic dissection were identified in seven (1.2%) and four (0.7%) cases respectively. A total of 40 (7.0%) patients died over a mean follow-up of 42.6 months.
A variety of cardiac and non-cardiac conditions are prevalent in patients presenting with suspected STEMI but culprit-free angiogram, some of which may have adverse outcomes. Further imaging of such patients could thus be useful to help in appropriate management and follow-up.
To morphometrically characterise the region of adjacent descending aorta (DAo) and left pulmonary artery (LPA) regarding the transcatheter creation of the reverse Potts shunt.
Retrospective review of the invasive haemodynamic data and measurements of the vessel diameters, distances and angles based on the thoracic CT of children with idiopathic pulmonary arterial hypertension (PAH) with pulmonary-to-systemic systolic pressure ratio ≥0.5. Forty-eight CT scans from 47 patients were analysed. Independent of the PAH severity, the diameters of DAo and LPA, and the area of tightest contact between these vessels were very similar in patients with either infrasystemic or isosystemic/suprasystemic PAH. For total population, the tightest contact area (mean±SD, 51.8±31.9 mm2, range 12.5–177.7 mm2) had an elliptic shape stretched along the DAo length and LPA width. The shortest mean DAo-LPA distance was 1.7±0.8 mm (range 1–5 mm). Only one patient, from the suprasystemic PAH group, had the DAo-LPA distance >4 mm. None had lung tissue identified between these two vessels, while in four patients (8.3%) the prominent bronchial artery was seen coursing exactly between the LPA and DAo. The difference of prevalence of the bronchial arteries between two vessels in patients with either infrasystemic PAH or isosystemic/suprasystemic PAH did not reach statistical significance.
Children with idiopathic PAH showed no complicating anatomic or morphometric parameters of the region with adjacent DAo and LPA, which potentially determine the planning of the transcatheter creation of Potts shunt. It holds promises for standardisation of the procedure in the future.
To evaluate the cost-effectiveness of implantable cardioverter defibrillators (ICDs), cardiac resynchronisation therapy pacemakers (CRT-Ps) and combination therapy (CRT-D) in patients with heart failure with reduced ejection fraction based on a range of clinical characteristics.
Individual patient data from 13 randomised trials were used to inform a decision analytical model. A series of regression equations were used to predict baseline all-cause mortality, hospitalisation rates and health-related quality of life and device-related treatment effects. Clinical variables used in these equations were age, QRS duration, New York Heart Association (NYHA) class, ischaemic aetiology and left bundle branch block (LBBB). A UK National Health Service perspective and a lifetime time horizon were used. Benefits were expressed as quality-adjusted life-years (QALYs). Results were reported for 24 subgroups based on LBBB status, QRS duration and NYHA class.
At a threshold of £30 000 per QALY gained, CRT-D was cost-effective in 10 of the 24 subgroups including all LBBB morphology patients with NYHA I/II/III. ICD is cost-effective for all non-NYHA IV patients with QRS duration <120 ms and for NYHA I/II non-LBBB morphology patients with QRS duration between 120 ms and 149 ms. CRT-P was also cost-effective in all NYHA III/IV patients with QRS duration >120 ms. Device therapy is cost-effective in most patient groups with LBBB at a threshold of £20 000 per QALY gained. Results were robust to altering key model parameters.
At a threshold of £30 000 per QALY gained, CRT-D is cost-effective in a far wider group than previously recommended in the UK. In some subgroups ICD and CRT-P remain the cost-effective choice.
Experimental evidence has shown potential cardioprotective actions of phosphodiesterase type-5 inhibitors (PDE5is). We investigated whether PDE5i use in patients with type 2 diabetes, with high-attendant cardiovascular risk, was associated with altered mortality in a retrospective cohort study.
Between January 2007 and May 2015, 5956 men aged 40–89 years diagnosed with type 2 diabetes before 2007 were identified from anonymised electronic health records of 42 general practices in Cheshire, UK, and were followed for 7.5 years. HRs from multivariable survival (accelerated failure time, Weibull) models were used to describe the association between on-demand PDE5i use and all-cause mortality.
Compared with non-users, men who are prescribed PDE5is (n=1359) experienced lower percentage of deaths during follow-up (19.1% vs 23.8%) and lower risk of all-cause mortality (unadjusted HR=0.69 (95% CI: 0.64 to 0.79); p<0.001)). The reduction in risk of mortality (HR=0.54 (0.36 to 0.80); p=0.002) remained after adjusting for age, estimated glomerular filtration rate, smoking status, prior cerebrovascular accident (CVA) hypertension, prior myocardial infarction (MI), systolic blood pressure, use of statin, metformin, aspirin and β-blocker medication. PDE5i users had lower rates of incident MI (incidence rate ratio (0.62 (0.49 to 0.80), p<0.0001) with lower mortality (25.7% vs 40.1% deaths; age-adjusted HR=0.60 (0.54 to 0.69); p=0.001) compared with non-users within this subgroup.
In a population of men with type 2 diabetes, use of PDE5is was associated with lower risk of overall mortality and mortality in those with a history of acute MI.
The purpose of this study was to analyse the association between resting heart rate (RHR) and type 2 diabetes and hypertension in Korean adults.
A total of 5124 participants, who participated in the exercise programme at the National Health Promotion Center between 2007 and 2010 (male=904, female=4220) were analysed in this study. Anthropometrics, body mass index (BMI), blood pressure (BP) and RHR were measured, and blood samples were collected after fasting for at least 12 hours.
To investigate the association between RHR and metabolic parameters, participants were divided into quartiles. Participants in the fourth quartile (RHR >80 beats per minute (bpm) showed significantly higher systolic and diastolic BP and glucose compared with participants in the first quartile (RHR <69 bpm). When logistic regression analyses were performed, participants in the fourth quartile of RHR had 2.76 times (95% CI 2.03 to 3.77; absolute risk (AR): 12.1% (166/1371)) higher odds of type 2 diabetes and 1.27 times (95% CI 1.04 to 1.55; AR: 22.2% (304/1371)) higher odds of hypertension compared with those in the first quartile of RHR (type 2 diabetes AR: 5.3% (71/1346); hypertension AR: 18.9% (254/1346)). Multiple regression analyses showed that both BMI and RHR were significantly associated with glucose and mean arterial pressure.
RHR is significantly associated with type 2 diabetes and hypertension independent of age, gender, BMI, smoking, drinking and family history of disease. RHR in combination with BMI, and multiple linear regression analyses emphasise the importance of the association of RHR with type 2 diabetes and hypertension in Korean adults.
A 57-year-old woman presented to our clinic with breathlessness brought on while walking uphill. She had been recently diagnosed with systemic hypertension. There was no known family history of cardiac disease, or prior smoking habit. On examination, pulse was 73 bpm and blood pressure 155/73 mm Hg, which was asymmetrical in her arms. Auscultation revealed a readily audible early diastolic murmur in the aortic area and bilateral subclavian bruits. ECG showed sinus rhythm with no abnormality. Transthoracic echocardiography demonstrated mild-to-moderate aortic regurgitation, and normal left ventricular size and function. The ascending aorta was mildly dilated (41 mm), with para-aortic thickening noted. Owing to the abnormal appearance of the aortic wall, cardiac MRI, and subsequently 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan was performed (
Which complication of the underlying disease is evident in Aortic aneurysm Aortic dissection Aortic thrombus Coronary artery aneurysm Coronary sinus fistula
Coronary artery aneurysm
Coronary sinus fistula
Learning objectives Understanding the process of stress echo service development and the influencing factors. Learning the requirements of a stress echo service. Acknowledging the recommendations and guidelines underpinning a stress echo service.
Understanding the process of stress echo service development and the influencing factors.
Learning the requirements of a stress echo service.
Acknowledging the recommendations and guidelines underpinning a stress echo service.
Stress echocardiography (SE) is well established in the assessment of ischaemic heart disease (IHD),
To the Editor,
Goorden et al aim to establish the optimal threshold to rule out myocardial infarction using a high-sensitivity cardiac troponin I assay. They report that a cardiac troponin I concentration <10 ng/L or a change of <20 ng/L on serial testing had a negative predictive value for the diagnosis of myocardial infarction of 99.8% and 98.7%, respectively.
First, the authors compared diagnostic sensitivity and specificity to identify thresholds for cardiac troponin I with similar diagnostic performance to the reference standard. When used in conjunction with a separate rule-in threshold, we believe the optimal threshold to rule out myocardial infarction should prioritise sensitivity alone to ensure a...