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1.  Descriptive epidemiology and short-term outcomes of heart failure hospitalisation in rural Haiti 
Heart (British Cardiac Society)  2016;102(2):140-146.
Objective
There is increasing attention to cardiovascular diseases in low-income countries. However, little is known about heart failure (HF) in rural areas, where most of the populations in low-income countries live. We studied HF epidemiology, care delivery and outcomes in rural Haiti.
Methods
Among adults admitted with HF to a rural Haitian tertiary care hospital during a 12-month period (2013–2014), we studied the clinical characteristics and short-term outcomes including length of stay, inhospital death and outpatient follow-up rates.
Results
HF accounted for 392/1049 (37%) admissions involving 311 individuals; over half (60%) were women. Mean age was 58.8 (SD 16.2) years for men and 48.3 (SD 18.8) years for women; 76 (41%) women were <40 years of age. Median length of stay was 10 days (first and second quartiles 7, 17), and inhospital mortality was 12% (n=37). Ninety nine (36%) of the 274 who survived their primary hospitalisation followed-up at the hospital’s outpatient clinic, and 18 (6.6%) were readmitted to the same hospital within 30 days postdischarge. Decreased known follow-up (p<0.01) and readmissions (p=0.03) were associated with increased distance between patient residence and hospital. Among the one-quarter (81) patients with echocardiograms, causes of HF included: non-ischaemic cardiomyopathy (64%), right HF (12%), hypertensive heart disease (7%) and rheumatic heart disease (5%). One-half of the women with cardiomyopathy by echocardiogram had peripartum cardiomyopathy.
Conclusions
HF is a common cause of hospitalisation in rural Haiti. Among diagnosed patients, HF is overwhelming due to non-atherosclerotic heart disease and particularly affects young adults. Implementing effective systems to improve HF diagnosis and linkage to essential outpatient care is needed to reduce long-term morbidity and mortality.
doi:10.1136/heartjnl-2015-308451
PMCID: PMC4854668  PMID: 26729609
2.  Higher Circulating Adiponectin Levels Are Associated with Increased Risk of Atrial Fibrillation in Older Adults 
Heart (British Cardiac Society)  2015;101(17):1368-1374.
Background
Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner.
Methods
We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years).
Results
During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1–76, the hazard ratio (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05–1.24), while that for HMW adiponectin was 1.17 (1.08–1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids, and inflammation, did not significantly affect these estimates.
Conclusions
The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age.
doi:10.1136/heartjnl-2014-307015
PMCID: PMC5161822  PMID: 25855796
Adiponectin; Atrial fibrillation; Aging
3.  Post-resuscitation care following out-of-hospital and in-hospital cardiac arrest 
Heart (British Cardiac Society)  2015;101(24):1943-1949.
Cardiac arrest is a leading cause of death in developed countries. Although a majority of cardiac arrest patients die during the acute event, a substantial proportion of cardiac arrest deaths occur in patients following successful resuscitation and can be attributed to the development of post-cardiac arrest syndrome. There is growing recognition that integrated post-resuscitation care, which encompasses targeted temperature management (TTM), early coronary angiography and comprehensive critical care, can improve patient outcomes. TTM has been shown to improve survival and neurological outcome in patients who remain comatose especially following out-of-hospital cardiac arrest due to ventricular arrhythmias. Early coronary angiography and revascularisation if needed may also be beneficial during the post-resuscitation phase, based on data from observational studies. In addition, resuscitated patients usually require intensive care, which includes mechanical ventilator, haemodynamic support and close monitoring of blood gases, glucose, electrolytes, seizures and other disease-specific intervention. Efforts should be taken to avoid premature withdrawal of life-supporting treatment, especially in patients treated with TTM. Given that resources and personnel needed to provide high-quality post-resuscitation care may not exist at all hospitals, professional societies have recommended regionalisation of post-resuscitation care in specialised ‘cardiac arrest centres’ as a strategy to improve cardiac arrest outcomes. Finally, evidence for post-resuscitation care following in-hospital cardiac arrest is largely extrapolated from studies in patients with out-of-hospital cardiac arrest. Future studies need to examine the effectiveness of different post-resuscitation strategies, such as TTM, in patients with in-hospital cardiac arrest.
doi:10.1136/heartjnl-2015-307450
PMCID: PMC4780335  PMID: 26385451
4.  Underuse of β-blockers in heart failure and chronic obstructive pulmonary disease 
Heart  2016;102(23):1909-1914.
Objective
Although β-blockers are an established therapy in heart failure (HF) guidelines, including for patients with chronic obstructive pulmonary disease (COPD), there remain concerns regarding bronchoconstriction even with cardioselective β-blockers. We wished to assess the real-life use of β-blockers for patients with HF and comorbid COPD.
Methods
We evaluated data from the Optimum Patient Care Research Database over a period of 1 year for co-prescribing of β-blockers with either an ACE inhibitor (ACEI) or angiotensin-2 receptor blocker (ARB) in patients with HF alone versus HF+COPD. Association with inhaler therapy was also evaluated.
Results
We identified 89 861 patients with COPD, 24 237 with HF and 10 853 with both conditions. In patients with HF+COPD, the mean age was 79 years; 60% were male, and 27% had prior myocardial infarction. Of patients with HF+COPD, 22% were taking a β-blocker in conjunction with either ACEI/ARB (n=2416) compared with 41% of patients with HF only (n=10 002) (adjusted OR 0.54, 95% CI 0.51 to 0.58, p<0.001). Among HF+COPD patients taking inhaled corticosteroid (ICS) with long-acting β-agonist (LABA) and long-acting muscarinic antagonist, 27% of patients were taking an ACEI/ARB with β-blockers (n=778) versus 46% taking an ACEI/ARB without β-blockers (n=1316). Corresponding figures for those patients taking ICS/LABA were 20% (n=583) versus 48% (n=1367), respectively.
Conclusions
These data indicate a substantial unmet need for patients with COPD who should be prescribed β-blockers more often for concomitant HF.
doi:10.1136/heartjnl-2016-309458
PMCID: PMC5136686  PMID: 27380949
5.  Coronary endothelial dysfunction is associated with a reduction in coronary artery compliance and an increase in wall shear stress 
Heart (British Cardiac Society)  2010;96(10):773-778.
Objective
Endothelial dysfunction is associated with arterial stiffness in large arteries. The purpose of this study was to investigate the association between coronary endothelial dysfunction, coronary artery compliance and wall shear stress in patients with early atherosclerosis.
Methods
Coronary endothelial function was assessed according to responses to intracoronary acetylcholine in 120 patients without significant coronary stenosis. Acceleration of peak velocity (ACC), which is inversely related to coronary artery compliance, was derived from coronary flow velocity spectra, and wall shear rate (WSR) was calculated. Measurements were performed at baseline and after intracoronary nitroglycerin in order to eliminate the contribution of vascular smooth muscle tone to coronary artery compliance.
Results
In all patients, heart rate significantly increased (72±1 to 77±1 bpm, p<0.01) and mean arterial pressure decreased (97±2 to 93±1 mm Hg, p<0.01) after nitroglycerin. Coronary blood flow (CBF) and resistance were not significantly changed, but the diastolic to systolic velocity ratio increased significantly (2.15±0.08 to 5.36±0.61, p<0.01). Patients with abnormal endothelial function (n=70) had a higher WSR at baseline (559±41 vs 440±26 s−1, p<0.05) and after nitroglycerin (457±41 vs 339±29 s−1, p<0.05), and a higher ACC after nitroglycerin (3.9±0.4 vs 2.8±0.4 m/s2, p<0.05) than patients with normal function (n=50).
Conclusions
The current study demonstrates that intracoronary nitroglycerin does not contribute to an increase of CBF but alters the phasic coronary flow pattern. Furthermore, early coronary atherosclerosis characterised by endothelial dysfunction is associated with a decrease in coronary artery compliance and an increase in wall shear stress. Therefore, coronary wall properties are affected early in the atherosclerosis process.
doi:10.1136/hrt.2009.187898
PMCID: PMC5120394  PMID: 20448128
6.  Imaging diagnoses and outcome in patients presenting for primary angioplasty but no obstructive coronary artery disease 
Heart  2016;102(21):1728-1734.
Objective
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1136/heartjnl-2015-309039
PMCID: PMC5099205  PMID: 27368743
7.  An unusual finding in a 57-year-old woman with new onset hypertension and a diastolic murmur 
Heart  2016;102(21):1762.
Clinical introduction
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 (figure 1).
Question
Which complication of the underlying disease is evident in figure 1, panel C? Aortic aneurysmAortic dissectionAortic thrombusCoronary artery aneurysmCoronary sinus fistula
doi:10.1136/heartjnl-2016-309661
PMCID: PMC5099207  PMID: 27411841
8.  Cost-effectiveness of implantable cardiac devices in patients with systolic heart failure 
Heart  2016;102(21):1742-1749.
Objective
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1136/heartjnl-2015-308883
PMCID: PMC5099208  PMID: 27411837
9.  Primary percutaneous coronary intervention for ST elevation myocardial infarction in nonagenarians 
Heart  2016;102(20):1648-1654.
Objective
To assess outcomes following primary percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI) in nonagenarian patients.
Methods
We conducted a multicentre retrospective study between 2006 and 2013 in five international high-volume centres and included consecutive all-comer nonagenarians treated with primary PCI for STEMI. There were no exclusion criteria. We enrolled 145 patients and collected demographic, clinical and procedural data. Severe clinical events and mortality at 6 months and 1 year were assessed.
Results
Cardiogenic shock was present at admission in 21%. Median (IQR) delay between symptom onset and balloon was 3.7 (2.4–5.6) hours and 60% of procedures were performed through the transradial approach. Successful revascularisation of the culprit vessel was obtained in 86% of the cases (thrombolysis in myocardial infarction flow of 2 or 3). Major or clinically relevant bleeding was observed in 4% of patients. Median left ventricular ejection fraction post PCI was 41.5% (32.0–50.0). The in-hospital mortality was 24%, with 6 months and 1-year survival rates of 61% and 53%, respectively.
Conclusions
In our study, primary PCI in nonagenarians with STEMI was achieved and feasible through a transradial approach. It is associated with a high rate of reperfusion of the infarct-related artery and 53% survival at 1 year. These results suggest that primary PCI may be offered in selected nonagenarians with acute myocardial infarction.
doi:10.1136/heartjnl-2015-308905
PMCID: PMC5099211  PMID: 27411839
10.  Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes 
Heart  2016;102(20):1671-1679.
Objective
Myocardial intracellular/extracellular structure and aortic function were assessed among hypertensive left ventricular (LV) phenotypes using cardiovascular magnetic resonance (CMR).
Methods
An observational study from consecutive tertiary hypertension clinic patients referred for CMR (1.5 T) was performed. Four LV phenotypes were defined: (1) normal with normal indexed LV mass (LVM) and LVM to volume ratio (M/V), (2) concentric remodelling with normal LVM but elevated M/V, (3) concentric LV hypertrophy (LVH) with elevated LVM but normal indexed end-diastolic volume (EDV) or (4) eccentric LVH with elevated LVM and EDV. Extracellular volume fraction was measured using T1-mapping. Circumferential strain was calculated by voxel-tracking. Aortic distensibility was derived from high-resolution aortic cines and contemporaneous blood pressure measurements.
Results
88 hypertensive patients (49±14 years, 57% men, systolic blood pressure (SBP): 167±30 mm Hg, diastolic blood pressure (DBP): 96±14 mm Hg) were compared with 29 age-matched/sex-matched controls (47±14 years, 59% men, SBP: 128±12 mm Hg, DBP: 79±10 mm Hg). LVH resulted from increased myocardial cell volume (eccentric LVH: 78±19 mL/m2 vs concentric LVH: 73±15 mL/m2 vs concentric remodelling: 55±9 mL/m2, p<0.05, respectively) and interstitial fibrosis (eccentric LVH: 33±10 mL/m2 vs concentric LVH: 30±10 mL/m2 vs concentricremodelling: 19±2 mL/m2, p<0.05, respectively). LVH had worst circumferential impairment (eccentric LVH: −12.8±4.6% vs concentric LVH: −15.5±3.1% vs concentric remodelling: –17.1±3.2%, p<0.05, respectively). Concentric remodelling was associated with reduced aortic distensibility, but not with large intracellular/interstitial expansion or myocardial dysfunction versus controls.
Conclusions
Myocardial interstitial fibrosis varies across hypertensive LV phenotypes with functional consequences. Eccentric LVH has the most fibrosis and systolic impairment. Concentric remodelling is only associated with abnormal aortic function. Understanding these differences may help tailor future antihypertensive treatments.
doi:10.1136/heartjnl-2016-309576
PMCID: PMC5099214  PMID: 27260191
11.  Marginal role for 53 common genetic variants in cardiovascular disease prediction 
Heart  2016;102(20):1640-1647.
Objective
We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed.
Methods
Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up. We calculated a score from 53 CVD-related single nucleotide polymorphisms and an established CVD risk equation ‘QRISK-2’ comprising phenotypic measures. The area under the receiver operating characteristic curve (AUROC), detection rate for given false-positive rate (FPR) and net reclassification improvement (NRI) index were estimated for gene scores alone and in addition to the QRISK-2 CVD risk score. We also evaluated use of genetic information only for those at intermediate risk according to QRISK-2.
Results
The AUROC was 0.635 for QRISK-2 alone and 0.623 with addition of the gene score. The detection rate for 5% FPR improved from 11.9% to 12.0% when the gene score was added. For a 10-year CVD risk cut-off point of 10%, the NRI was 0.25% when the gene score was added to QRISK-2. Applying the genetic risk score only to those with QRISK-2 risk of 10%–<20% and prescribing statins where risk exceeded 20% suggested that genetic information could prevent one additional event for every 462 people screened.
Conclusion
The gene score produced minimal incremental population-wide utility over phenotypic risk prediction of CVD. Tailored prediction using genetic information for those at intermediate risk may have clinical utility.
doi:10.1136/heartjnl-2016-309298
PMCID: PMC5099215  PMID: 27365493
12.  Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality 
Heart  2016;102(21):1750-1756.
Objective
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.
Research design and methods
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.
Results
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.
Conclusion
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.
doi:10.1136/heartjnl-2015-309223
PMCID: PMC5099221  PMID: 27465053
13.  Risk Stratification in Patients with Pulmonary Hypertension Undergoing Transcatheter Aortic Valve Replacement 
Heart (British Cardiac Society)  2015;101(20):1656-1664.
Objective
Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS) and when the pulmonary artery pressure is particularly elevated there may be questions about the clinical benefit of TAVR. We aimed to identify clinical and hemodynamic factors associated with increased mortality after TAVR among those with moderate/severe PH.
Methods
Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) I randomized trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included and moderate/severe PH was defined as a mPAP ≥35mmHg.
Results
Increasing severity of PH was associated with progressively worse 1-year all-cause mortality: none (n=785, 18.6%), mild (n=838, 22.7%), and moderate/severe (n=557, 25.0%) (p=0.01). The increased hazard of mortality associated with moderate/severe PH was observed in females but not males (interaction p=0.03). In adjusted analyses, females with moderate/severe PH had an increased hazard of death at 1 year compared to females without PH (adjusted HR 2.14, 95% CI 1.44–3.18), whereas those with mild PH did not. Among males, there was no increased hazard of death associated with any severity of PH. In a multivariable Cox model of patients with moderate/severe PH, oxygen dependent lung disease, inability to perform a 6 minute walk, impaired renal function, and lower aortic valve mean gradient were independently associated with increased 1-year mortality (p<0.05 for all), whereas several hemodynamic indices were not. A risk score including these factors was able to identify patients with a 15% versus 59% 1-year mortality.
Conclusion
The relationship between moderate/severe PH and increased mortality after TAVR is altered by sex and clinical factors appear to be more influential in stratifying risk than hemodynamic indices. These findings may have implications for the evaluation of and treatment decisions for patients referred for TAVR with significant PH.
doi:10.1136/heartjnl-2015-308001
PMCID: PMC4620051  PMID: 26264371
aortic valve stenosis; pulmonary hypertension; transcatheter aortic valve replacement; outcomes
14.  LEFT VENTRICULAR HYPERTROPHY AFTER HYPERTENSIVE PREGNANCY DISORDERS 
Heart (British Cardiac Society)  2015;101(19):1584-1590.
Objective
Cardiac changes of hypertensive pregnancy include left ventricular hypertrophy (LVH) and diastolic dysfunction. These are thought to regress postpartum. We hypothesized that women with a history of hypertensive pregnancy would have altered left ventricular (LV) geometry and function when compared to women with only normotensive pregnancies.
Methods
In this cohort study, we analyzed echocardiograms of 2637 women who participated in the Family Blood Pressure Program (FBPP). We compared LV mass and function in women with hypertensive pregnancy compared to those with normotensive pregnancies.
Results
Women were evaluated at a mean age of 56 years: 427 (16%) had at least one hypertensive pregnancy; 2210 (84%) had normotensive pregnancies. Compared to women with normotensive pregnancies, women with hypertensive pregnancy had a greater risk of LVH (OR: 1.42, 95% CI 1.01-1.99, p=0.05), after adjusting for age, race, research network of the FBPP, education, parity, BMI, hypertension and diabetes. When duration of hypertension was taken into account, this relationship was no longer significant (OR: 1.19, CI 0.08-1.78 p=0.38). Women with hypertensive pregnancies also had greater left atrial size and lower mitral E/A ratio after adjusting for demographic variables. The prevalence of systolic dysfunction was similar between the groups.
Conclusions
A history of hypertensive pregnancy is associated with LVH after adjusting for risk factors; this might be explained by longer duration of hypertension. This finding supports current guidelines recommending surveillance of women following a hypertensive pregnancy, and sets the stage for longitudinal echocardiographic studies to further elucidate progression of LV geometry and function after pregnancy.
doi:10.1136/heartjnl-2015-308098
PMCID: PMC4568146  PMID: 26243788
Hypertension; Pregnancy; Left ventricular hypertrophy; Women; Diastolic function
15.  Improvements in ECG accuracy for diagnosis of left ventricular hypertrophy in obesity 
Heart  2016;102(19):1566-1572.
Objectives
The electrocardiogram (ECG) is the most commonly used tool to screen for left ventricular hypertrophy (LVH), and yet current diagnostic criteria are insensitive in modern increasingly overweight society. We propose a simple adjustment to improve diagnostic accuracy in different body weights and improve the sensitivity of this universally available technique.
Methods
Overall, 1295 participants were included—821 with a wide range of body mass index (BMI 17.1–53.3 kg/m2) initially underwent cardiac magnetic resonance evaluation of anatomical left ventricular (LV) axis, LV mass and 12-lead surface ECG in order to generate an adjustment factor applied to the Sokolow–Lyon criteria. This factor was then validated in a second cohort (n=520, BMI 15.9–63.2 kg/m2).
Results
When matched for LV mass, the combination of leftward anatomical axis deviation and increased BMI resulted in a reduction of the Sokolow–Lyon index, by 4 mm in overweight and 8 mm in obesity. After adjusting for this in the initial cohort, the sensitivity of the Sokolow–Lyon index increased (overweight: 12.8% to 30.8%, obese: 3.1% to 27.2%) approaching that seen in normal weight (37.8%). Similar results were achieved in the validation cohort (specificity increased in overweight: 8.3% to 39.1%, obese: 9.4% to 25.0%) again approaching normal weight (39.0%). Importantly, specificity remained excellent (>93.1%).
Conclusions
Adjusting the Sokolow–Lyon index for BMI (overweight +4 mm, obesity +8 mm) improves the diagnostic accuracy for detecting LVH. As the ECG, worldwide, remains the most widely used screening tool for LVH, implementing these findings should translate into significant clinical benefit.
doi:10.1136/heartjnl-2015-309201
PMCID: PMC5037604  PMID: 27486142
16.  Obesity and sudden death: visceral response? 
Heart (British Cardiac Society)  2014;101(3):165-166.
doi:10.1136/heartjnl-2014-306921
PMCID: PMC5018826  PMID: 25502517
17.  Midlife blood pressure predicts future diastolic dysfunction independently of blood pressure 
Heart  2016;102(17):1380-1387.
Objectives
High blood pressure (BP) is associated with diastolic dysfunction, but the consequence of elevated BP over the adult life course on diastolic function is unknown. We hypothesised that high BP in earlier adulthood would be associated with impaired diastolic function independent of current BP.
Methods
Participants in the Medical Research Council National Survey of Health and Development birth cohort (n=1653) underwent investigations including echocardiography at age 60–64 years. The relationships between adult BP, antihypertensive treatment (HTT) and echocardiographic measures of diastolic function were assessed using adjusted regression models.
Results
Increased systolic BP (SBP) at ages 36, 43 and 53 years was predictive of increased E/e′ and increased left atrial volume. These effects were only partially explained by SBP at 60–64 years and increased left ventricular mass. HTT was also associated with poorer diastolic function after adjustment for SBP at 60–64 years. Faster rates of increase in SBP in midlife were also associated with increased poorer diastolic function.
Conclusions
High SBP in midlife is associated with poorer diastolic function at age 60–64 years. Early identification of individuals with high BP or rapid rises in BP may be important for prevention of impaired cardiac function in later life.
doi:10.1136/heartjnl-2015-308836
PMCID: PMC4998951  PMID: 27056972
18.  Efficacy of cardiac rehabilitation after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension 
Heart  2016;102(17):1403-1409.
Objective
To determine safety and efficacy of cardiac rehabilitation (CR) initiated immediately following balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) who presented with continuing exercise intolerance and symptoms on effort even after a course of BPA; 2–8 sessions/patient.
Methods
Forty-one consecutive patients with inoperable CTEPH who underwent their final BPA with improved resting mean pulmonary arterial pressure of 24.7±5.5 mm Hg and who suffered remaining exercise intolerance were prospectively studied. Participants were divided into two groups just after the final BPA (6.8±2.3 days): patients with (CR group, n=17) or without (non-CR group, n=24) participation in a 12-week CR of 1-week inhospital training followed by an 11-week outpatient programme. Cardiopulmonary exercise testing, haemodynamics, and quality of life (QOL) were assessed before and after CR.
Results
No significant between-group differences were found for any baseline characteristics. At week 12, peak oxygen uptake (VO2), per cent predicted peak VO2 (70.7±9.4% to 78.2±12.8%, p<0.01), peak workload, and oxygen pulse significantly improved in the CR group compared with the non-CR group, with a tendency towards improvement in mental health-related QOL. Quadriceps strength and heart failure (HF) symptoms (WHO functional class, 2.2–1.8, p=0.01) significantly improved within the CR group. During the CR, no patient experienced adverse events or deterioration of right-sided HF or haemodynamics as confirmed via catheterisation.
Conclusions
The combination of BPA and subsequent CR is a new treatment strategy for inoperable CTEPH to improve exercise capacity to near-normal levels and HF symptoms, with a good safety profile.
doi:10.1136/heartjnl-2015-309230
PMCID: PMC5013094  PMID: 27220694
19.  The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan 
Heart  2016;102(17):1342-1347.
Inhibition of neurohumoural pathways such as the renin angiotensin aldosterone and sympathetic nervous systems is central to the understanding and treatment of heart failure (HF). Conversely, until recently, potentially beneficial augmentation of neurohumoural systems such as the natriuretic peptides has had limited therapeutic success. Administration of synthetic natriuretic peptides has not improved outcomes in acute HF but modulation of the natriuretic system through inhibition of the enzyme that degrades natriuretic (and other vasoactive) peptides, neprilysin, has proven to be successful. After initial failures with neprilysin inhibition alone or dual neprilysin-angiotensin converting enzyme (ACE) inhibition, the Prospective comparison of angiotensin receptor neprilysin inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) trial demonstrated that morbidity and mortality can be improved with the angiotensin receptor blocker neprilysin inhibitor sacubitril/valsartan (formerly LCZ696). In comparison to the ACE inhibitor enalapril, sacubitril/valsartan reduced the occurrence of the primary end point (cardiovascular death or hospitalisation for HF) by 20% with a 16% reduction in all-cause mortality. These findings suggest that sacubitril/valsartan should replace an ACE inhibitor or angiotensin receptor blocker as the foundation of treatment of symptomatic patients (NYHA II–IV) with HF and a reduced ejection fraction. This review will explore the background to neprilysin inhibition in HF, the results of the PARADIGM-HF trial and offer guidance on how to use sacubitril/valsartan in clinical practice.
doi:10.1136/heartjnl-2014-306775
PMCID: PMC5013095  PMID: 27207980
20.  Cardiac rehabilitation delivery model for low-resource settings 
Heart  2016;102(18):1449-1455.
Objective
Cardiovascular disease is a global epidemic, which is largely preventable. Cardiac rehabilitation (CR) is demonstrated to be cost-effective and efficacious in high-income countries. CR could represent an important approach to mitigate the epidemic of cardiovascular disease in lower-resource settings. The purpose of this consensus statement was to review low-cost approaches to delivering the core components of CR, to propose a testable model of CR which could feasibly be delivered in middle-income countries.
Methods
A literature review regarding delivery of each core CR component, namely: (1) lifestyle risk factor management (ie, physical activity, diet, tobacco and mental health), (2) medical risk factor management (eg, lipid control, blood pressure control), (3) education for self-management and (4) return to work, in low-resource settings was undertaken. Recommendations were developed based on identified articles, using a modified GRADE approach where evidence in a low-resource setting was available, or consensus where evidence was not.
Results
Available data on cost of CR delivery in low-resource settings suggests it is not feasible to deliver CR in low-resource settings as is delivered in high-resource ones. Strategies which can be implemented to deliver all of the core CR components in low-resource settings were summarised in practice recommendations, and approaches to patient assessment proffered. It is suggested that CR be adapted by delivery by non-physician healthcare workers, in non-clinical settings.
Conclusions
Advocacy to achieve political commitment for broad delivery of adapted CR services in low-resource settings is needed.
doi:10.1136/heartjnl-2015-309209
PMCID: PMC5013107  PMID: 27181874
21.  Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure 
Heart  2016;102(18):1464-1471.
Background
QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood.
Methods
We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies.
Results
Compared with whites, Asian patients with HF were younger (62 vs 74 years, p<0.001), had smaller body size (height 163 vs 171 cm, weight 70 vs 80 kg, both p<0.001) and had more severely impaired EF (EF was <30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104 ms, p<0.001). Lower EF was associated with longer QRSd (p<0.001), with a steeper association among Asians than whites (pinteraction<0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for ≤120 ms was 40% and for >120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity.
Conclusion
We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study.
doi:10.1136/heartjnl-2015-309212
PMCID: PMC5013108  PMID: 27402805
ECG/electrocardiogram
22.  Predicting mortality after acute coronary syndromes in people with chronic obstructive pulmonary disease 
Heart  2016;102(18):1442-1448.
Objective
To assess the accuracy of Global Registry of Acute Coronary Events (GRACE) scores in predicting mortality at 6 months for people with chronic obstructive pulmonary disease (COPD) and to investigate how it might be improved.
Methods
Data were obtained on 481 849 patients with acute coronary syndrome admitted to UK hospitals between January 2003 and June 2013 from the Myocardial Ischaemia National Audit Project (MINAP) database. We compared risk of death between patients with COPD and those without COPD at 6 months, adjusting for predicted risk of death. We then assessed whether several modifications improved the accuracy of the GRACE score for people with COPD.
Results
The risk of death after adjusting for GRACE score predicted that risk of death was higher for patients with COPD than that for other patients (RR 1.29, 95% CI 1.28 to 1.33). Adding smoking into the GRACE score model did not improve accuracy for patients with COPD. Either adding COPD into the model (relative risk (RR) 1.00, 0.94 to 1.02) or multiplying the GRACE score by 1.3 resulted in better performance (RR 0.99, 0.96 to 1.01).
Conclusions
GRACE scores underestimate risk of death for people with COPD. A more accurate prediction of risk of death can be obtained by adding COPD into the GRACE score equation, or by multiplying the GRACE score predicted risk of death by 1.3 for people with COPD. This means that one third of patients with COPD currently classified as low risk should be classified as moderate risk, and could be considered for more aggressive early treatment after non-ST-segment elevation myocardial infarction or unstable angina.
doi:10.1136/heartjnl-2016-309359
PMCID: PMC5013109  PMID: 27177534
23.  Prognostic Utility of Novel Biomarkers of Cardiovascular Stress in Patients with Aortic Stenosis Undergoing Valve Replacement 
Heart (British Cardiac Society)  2015;101(17):1382-1388.
Objective
In heart failure populations without aortic stenosis (AS), the prognostic utility of multiple biomarkers in addition to clinical factors has been demonstrated. We aimed to determine whether multiple biomarkers of cardiovascular stress are associated with mortality in patients with AS undergoing aortic valve replacement (AVR) independent of clinical factors.
Methods
From a prospective registry of patients with AS, 345 participants who were referred for and treated with AVR (transcatheter [n=183] or surgical [n=162]) were included. Eight biomarkers were measured on blood samples obtained prior to AVR: growth differentiation factor 15 (GDF15), soluble ST2 (sST2), amino-terminal pro-B-type natriuretic peptide (NTproBNP), galectin-3, high sensitivity cardiac troponin T, myeloperoxidase, high sensitivity C-reactive protein, and monocyte chemotactic protein-1. Biomarkers were evaluated based on median value (high versus low) in a Cox proportional hazards model for all-cause mortality and a parsimonious group of biomarkers selected. Mean follow-up was 1.9±1.2 years; 91 patients died.
Results
Three biomarkers (GDF15, sST2, and NTproBNP) were retained in the model. One-year mortality was 5%, 12%, 18%, and 33% for patients with 0 (n=79), 1 (n=96), 2 (n=87), and 3 (n=83) biomarkers elevated, respectively (p<0.001). After adjustment for the Society of Thoracic Surgeons (STS) risk score, a greater number of elevated biomarkers was associated with increased mortality (referent: 0 elevated): 1 elevated (HR 1.47, 95% CI 0.60–3.63, p=0.40), 2 elevated (HR 2.89, 95% CI 1.24–6.74, p=0.014), and 3 elevated (HR 4.59, 95% CI 1.97–10.71, p<0.001). Among patients at intermediate or high surgical risk (STS score ≥4), 1- and 2-year mortality rates were 34% and 43% for patients with 3 biomarkers elevated versus 4% and 4% for patients with 0 biomarkers elevated. When added to the STS score, the number of biomarkers elevated provided a category-free net reclassification improvement of 64% at 1 year (p<0.001). The association between a greater number of elevated biomarkers and increased mortality after valve replacement was similar in the transcatheter and surgical AVR populations.
Conclusions
These findings demonstrate the potential utility of multiple biomarkers to aid in risk stratification of patients with AS. Further studies are needed to evaluate their utility in clinical decision making in specific AS populations.
doi:10.1136/heartjnl-2015-307742
PMCID: PMC4598053  PMID: 26037104
aortic valve stenosis; biomarkers; transcatheter aortic valve replacement; surgical aortic valve replacement; risk stratification
24.  Midlife blood pressure predicts future diastolic dysfunction independently of blood pressure 
Heart (British Cardiac Society)  2016;102(17):1380-1387.
Objectives
High blood pressure (BP) is associated with diastolic dysfunction, but the consequence of elevated BP over the adult life course on diastolic function is unknown. We hypothesised that high BP in earlier adulthood would be associated with impaired diastolic function independent of current BP.
Methods
Participants in the Medical Research Council National Survey of Health and Development birth cohort (n=1653) underwent investigations including echocardiography at age 60–64 years. The relationships between adult BP, antihypertensive treatment (HTT) and echocardiographic measures of diastolic function were assessed using adjusted regression models.
Results
Increased systolic BP (SBP) at ages 36, 43 and 53 years was predictive of increased E/e′ and increased left atrial volume. These effects were only partially explained by SBP at 60–64 years and increased left ventricular mass. HTT was also associated with poorer diastolic function after adjustment for SBP at 60–64 years. Faster rates of increase in SBP in midlife were also associated with increased poorer diastolic function.
Conclusions
High SBP in midlife is associated with poorer diastolic function at age 60–64 years. Early identification of individuals with high BP or rapid rises in BP may be important for prevention of impaired cardiac function in later life.
doi:10.1136/heartjnl-2015-308836
PMCID: PMC4998951  PMID: 27056972
25.  Relationship of plasma neuropeptide Y with angiographic, electrocardiographic and coronary physiology indices of reperfusion during ST elevation myocardial infarction 
Heart (British Cardiac Society)  2013;99(16):1198-1203.
Objectives
The co-transmitter neuropeptide Y (NPY) is released during high levels of sympathetic stimulation and is a potent vasoconstrictor. We defined the release profile of plasma NPY during acute ST elevation myocardial infarction, and tested the hypothesis that levels correlate with reperfusion measures after treatment with primary percutaneous coronary intervention (PPCI).
Design
Prospective observational study.
Setting
University hospital heart centre.
Patients
64 patients (62.6±11.7 years-old, 73% male) presenting throughout the 24-h cycle of clinical activity with ST elevation myocardial infarction.
Interventions
PPCI.
Main outcome measures
NPY was measured (ELISA) in peripheral blood taken before and immediately after PPCI and at 6, 24 and 48 h post-PPCI. Reperfusion was assessed by angiographic criteria, ST segment resolution, invasive measurement of coronary flow reserve and the index of microcirculatory resistance.
Results
Plasma NPY levels were highest before PPCI (17.4 (8.8–42.2) pg/ml, median (IQR)) and dropped significantly post-PPCI (12.4 (6.5–26.7) pg/ml, p<0.0001) and after 6 h (9.0 (2.6–21.5) pg/ml, p=0.008). Patients with admission NPY levels above the median were significantly more hypertensive and tachycardic and were more likely to have diabetes mellitus. Patients with angiographic no-reflow (less than thrombolysis in myocardial infarction 3 flow and myocardial blush grade >2, n=16) or no electrocardiographic ST resolution (<70%, n=30) following PPCI had significantly higher plasma NPY levels. Patients with a coronary flow reserve <1.5 or index of microcirculatory resistance >33 also had significantly higher plasma NPY levels pre-PPCI and post-PPCI.
Conclusions
Plasma NPY levels correlate with indices of reperfusion and coronary microvascular resistance.
doi:10.1136/heartjnl-2012-303443
PMCID: PMC4976801  PMID: 23403409

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