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1.  Right Ventricular-Pulmonary Arterial Coupling Predicts Outcome in Patients Referred for Pulmonary Hypertension 
Heart (British Cardiac Society)  2014;101(1):37-43.
Prognosis in pulmonary hypertension is largely determined by right ventricular (RV) function. However, uncertainty remains about what metrics of RV function might be most clinically relevant. The purpose of this study was to assess the clinical relevance of metrics of RV functional adaptation to increased afterload.
Patients referred for pulmonary hypertension (PH) underwent right heart catheterization and RV volumetric assessment within 48 hours. A RV maximum pressure (Pmax) was calculated from the RV pressure curve. The adequacy of RV systolic functional adaptation to increased afterload was estimated either by a stroke volume (SV)/end-systolic volume (ESV) ratio, a Pmax/ mean pulmonary artery pressure (mPAP) ratio, or by ejection fraction (RVEF). Diastolic function of the RV was estimated by a diastolic elastance coefficient β. Survival analysis was via Cox proportional hazard ratio and Kaplan-Meier with the primary outcome of time to death or lung transplant.
Patients (n=50; age 58±13) covered a range of mPAP (13–79 mmHg) with an average RVEF of 39±17% and ESV of 143±89 ml. Average estimates of the ratio of end-systolic ventricular to arterial elastance were 0.79±0.67 (SV/ESV) and 2.3±0.65 (Pmax/mPAP-1). Transplantation-free survival was predicted by right atrial pressure, mPAP, pulmonary vascular resistance, β, SV, ESV, SV/ESV, and RVEF but after controlling for right atrial pressure, mPAP, and SV, SV/ESV was the only independent predictor.
The adequacy of RV functional adaptation to afterload predicts survival in patients referred for pulmonary hypertension. Whether this can simply be evaluated using RV volumetric imaging will require additional confirmation.
PMCID: PMC4268056  PMID: 25214501
pulmonary hypertension; heart failure; right ventricle; pressure-volume loops; CT imaging
2.  State of the evidence: mechanical ventilation with PEEP in patients with cardiogenic shock 
Heart (British Cardiac Society)  2013;99(24):1812-1817.
The need to provide invasive mechanical ventilatory support to patients with myocardial infarction and acute left heart failure is common. Despite the large number of patients requiring mechanical ventilation in this setting, there are remarkably few data addressing the ideal mode of respiratory support in such patients. Although there is near universal acceptance regarding the use of non-invasive positive pressure ventilation in patients with acute pulmonary oedema, there is more concern with invasive positive pressure ventilation owing to its more significant haemodynamic impact. Positive end-expiratory pressure (PEEP) is almost universally applied in mechanically ventilated patients due to benefits in gas exchange, recruitment of alveolar units, counterbalance of hydrostatic forces leading to pulmonary oedema and maintenance of airway patency. The limited available clinical data suggest that a moderate level of PEEP is safe to use in severe left ventricular (LV) dysfunction and cardiogenic shock, and may provide haemodynamic benefits as well in LV failure which exhibits afterload-sensitive physiology.
PMCID: PMC4096289  PMID: 23539555
3.  Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms 
Heart  2014;100(20):1571-1576.
Elective root replacement in Marfan syndrome has improved life expectancy in affected patients. Three forms of surgery are now available: total root replacement (TRR) with a valved conduit, valve sparing root replacement (VSRR) and personalised external aortic root support (PEARS) with a macroporous mesh sleeve. TRR can be performed irrespective of aortic dimensions and a mechanical replacement valve is a secure and near certain means of correcting aortic valve regurgitation but has thromboembolic and bleeding risks. VSRR offers freedom from anticoagulation and attendant risks of bleeding but reoperation for aortic regurgitation runs at 1.3% per annum. A prospective multi-institutional study has found this to be an underestimate of the true rate of valve-related adverse events. PEARS conserves the aortic root anatomy and optimises the chance of maintaining valve function but average follow-up is under 5 years and so the long-term results are yet to be determined. Patients are on average in their 30s and so the cumulative lifetime need for reoperation, and of any valve-related complications, are consequently substantial. With lowering surgical risk of prophylactic root replacement, the threshold for intervention has reduced progressively over 30 years to 4.5 cm and so an increasing number of patients who are not destined to have a dissection are now having root replacement. In evaluation of these three forms of surgery, the number needed to treat to prevent dissection and the balance of net benefit and harm in future patients must be considered.
PMCID: PMC4215278  PMID: 24986892
4.  Cost-effectiveness of eplerenone in patients with systolic heart failure and mild symptoms 
Heart  2014;100(21):1681-1687.
In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), aldosterone blockade with eplerenone decreased mortality and hospitalisation in patients with mild symptoms (New York Heart Association class II) and chronic systolic heart failure (HF). The present study evaluated the cost-effectiveness of eplerenone in the treatment of these patients in the UK and Spain.
Methods and results
Results from the EMPHASIS-HF trial were used to develop a discrete-event simulation model estimating lifetime direct costs and effects (life years and quality-adjusted life years (QALYs) gained) of the addition of eplerenone to standard care among patients with chronic systolic HF and mild symptoms. Eplerenone plus standard care compared with standard care alone increased lifetime direct costs per patient by £4284 for the UK and €7358 for Spain, with additional quality-adjusted life expectancy of 1.22 QALYs for the UK and 1.33 QALYs for Spain. Mean lifetime costs were £3520 per QALY in the UK and €5532 per QALY in Spain. Probabilistic sensitivity analysis suggested a 100% likelihood of eplerenone being regarded as cost-effective at a willingness-to-pay threshold of £20 000 per QALY (UK) or €30 000 per QALY (Spain).
By currently accepted standards of value for money, the addition of eplerenone to optimal medical therapy for patients with chronic systolic HF and mild symptoms is likely to be cost-effective.
PMCID: PMC4215293  PMID: 24993605
Heart Failure
5.  Impact of preprocedural mitral regurgitation upon mortality after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis 
Heart  2014;100(22):1799-1803.
To identify the effects of preprocedural significant mitral regurgitation (MR) and change in MR severity upon mortality after transcatheter aortic valve implantation (TAVI) using the Edwards SAPIEN system.
A retrospective analysis of 316 consecutive patients undergoing TAVI for aortic stenosis at a single centre in the UK between March 2008 and January 2013. Patients were stratified into two groups according to severity of MR: ≥grade 3 were classed as significant and ≤grade 2 were non-significant. Change in MR severity was assessed by comparison of baseline and 30-day echocardiograms.
60 patients had significant MR prior to TAVI (19.0%). These patients were of higher perioperative risk (logistic EuroScore 28.7±16.6% vs 20.3±10.7%, p=0.004) and were more dyspnoeic (New York Heart Association class IV 20.0% vs 7.4%, p=0.014). Patients with significant preprocedural MR displayed greater 12-month and cumulative mortality (28.3% vs 20.2%, log-rank p=0.024). Significant MR was independently associated with mortality (HR 4.94 (95% CI 2.07 to 11.8), p<0.001). Of the 60 patients with significant MR only 47.1% had grade 3–4 MR at 30 days (p<0.001). Patients in whom MR improved had lower mortality than those in whom it deteriorated (log-rank p=0.05).
Significant MR is frequently seen in patients undergoing TAVI and is independently associated with increased all-cause mortality. Yet almost half also exhibit significant improvements in MR severity. Those who improve have better outcomes, and future work could focus upon identifying factors independently associated with such an improvement.
PMCID: PMC4215343  PMID: 25155800
7.  The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation 
Heart  2014;100(18):1462-1468.
We aimed to derive and validate a clinical decision rule (CDR) for suspected cardiac chest pain in the emergency department (ED). Incorporating information available at the time of first presentation, this CDR would effectively risk-stratify patients and immediately identify: (A) patients for whom hospitalisation may be safely avoided; and (B) high-risk patients, facilitating judicious use of resources.
In two sequential prospective observational cohort studies at heterogeneous centres, we included ED patients with suspected cardiac chest pain. We recorded clinical features and drew blood on arrival. The primary outcome was major adverse cardiac events (MACE) (death, prevalent or incident acute myocardial infarction, coronary revascularisation or new coronary stenosis >50%) within 30 days. The CDR was derived by logistic regression, considering reliable (κ>0.6) univariate predictors (p<0.05) for inclusion.
In the derivation study (n=698) we derived a CDR including eight variables (high sensitivity troponin T; heart-type fatty acid binding protein; ECG ischaemia; diaphoresis observed; vomiting; pain radiation to right arm/shoulder; worsening angina; hypotension), which had a C-statistic of 0.95 (95% CI 0.93 to 0.97) implying near perfect diagnostic performance. On external validation (n=463) the CDR identified 27.0% of patients as ‘very low risk’ and potentially suitable for discharge from the ED. 0.0% of these patients had prevalent acute myocardial infarction and 1.6% developed MACE (n=2; both coronary stenoses without revascularisation). 9.9% of patients were classified as ‘high-risk’, 95.7% of whom developed MACE.
The Manchester Acute Coronary Syndromes (MACS) rule has the potential to safely reduce unnecessary hospital admissions and facilitate judicious use of high dependency resources.
PMCID: PMC4174131  PMID: 24780911
8.  Secular trends in echocardiographic left ventricular mass in the community: The Framingham Heart Study 
Heart (British Cardiac Society)  2013;99(22):1693-1698.
To investigate secular trends in echocardiographically-determined left ventricular mass (LVM).
Design, Setting and participants
Longitudinal community-based cohort study in Framingham, Massachussetts. LVM was calculated from routine echocardiography in 4,320 participants (52% women) of the Framingham Offspring cohort at examination cycles 4 (1987-91), 5 (1991-95), 6 (1995-98) and 8 (2005-08), totalling 13,971 person-observations.
Main outcome measures
Sex-specific trends in mean LVM (and its components, LV diastolic diameter [LVDD] and LV wall thickness [LVWT]), and LVM indexed to body surface area (BSA).
In men, age-adjusted LVM modestly increased from examination 4 to 8 (192 g to 198 g, P-trend=0.0005), whereas in women it decreased from 147 g at examination 4 to 140 g at examination 8 (P-trend<0.0001). The trend for increasing LVM in men tracked with an increasing LVDD (P-trend=0.0002), whereas the decline in LVM in women was accompanied by a decrease in LVWT (P-trend<0.0001). Indexing LVM to BSA abolished the increasing trend in men (P-trend=0.49), whereas the decreasing trend in women was maintained.
In our longitudinal analysis of a large community-based sample spanning two decades, we observed sex-related differences in trends in LVM, with a modest increase of LVM in men (likely attributable to increasing body size), but a decrease in women. Additional studies are warranted to elucidate the basis for these sex-related differences.
PMCID: PMC4139052  PMID: 24041649
9.  Medication, reperfusion therapy and survival in a community-based setting of hospitalised myocardial infarction 
Heart (British Cardiac Society)  2013;99(11):767-773.
To examine the survival benefit of multiple medical therapies in a large, community-based population of validated myocardial infarction (MI) events.
Retrospective observational cohort study.
Population-based sample of 30 986 definite or probable MIs in residents of four US communities aged 35–74 years randomly sampled between 1987 and 2008 as part of the Atherosclerosis Risk in Communities Surveillance Study.
Main outcome measures
All-cause mortality 30, 90 and 365 days after discharge.
We used unadjusted and propensity score (PS) adjusted models to examine the relationship between medical therapy use and mortality. In unadjusted models, each medication and procedure was inversely associated with 30-day mortality. After PS adjustment, the crude survival benefits were attenuated for all therapies except for intravenous tissue plasminogen activator therapy (IV-tPA) and stent use. After inclusion of other therapies received during the event in regression models, risk ratio effect estimates (RR; (95% CI)) were attenuated for aspirin (0.66; (0.58 to 0.76) to 0.91 (0.80 to 1.03)), non-aspirin antiplatelets (0.74; (0.59 to 0.92) to 0.92 (0.72 to 1.18)), IV-tPA (0.50; (0.41 to 0.62) to 0.65 (0.52 to 0.80)) and stents (0.53 (0.40 to 0.69) to 0.68 (0.49 to 0.94)). Effect estimates remained stable for all other therapies and were similar for 90- and 365-day mortality endpoints.
We observed inverse associations between receipt of six medications and procedures for MI and all-cause mortality at 30, 90 and 365 days after adjustment for PS. The mortality benefits observed in this population-based setting are consistent with those reported in clinical trials.
PMCID: PMC4118665  PMID: 23456567
10.  Amlodipine – Not a Significant Contributor to Clopidogrel Non-Response? 
Heart (British Cardiac Society)  2013;99(7):437-439.
PMCID: PMC4064296  PMID: 23315611
11.  Safety of serial MRI in patients with implantable cardioverter defibrillators 
Heart (British Cardiac Society)  2011;97(22):1852-1856.
While patients with cardiac implantable electronic devices could benefit from magnetic resonance (MR) imaging, the presence of such devices has been designated as an absolute contraindication to MR. Although scanning algorithms are proposed for cardiac implantable electronic devices, their safety remains uncertain. To address this issue, the safety of serial cardiac MR scans was evaluated in patients with implantable cardioverter defibrillators (ICDs).
Three serial cardiac MR scans were prospectively performed at 1.5 T on 10 patients (9 men) of median age 56 years (range 51–68) with ICDs. ICD interrogation was performed before and after the MR scan and at a follow-up of median 370 days (range 274–723). Image quality was also assessed.
In all patients MR scanning occurred without complications. There were no differences between preand post-MR pacing capture threshold, pacing lead or high voltage lead impedance, or battery voltage values. During follow-up there were no occurrences of ICD dysfunction. Although most patients had image artifacts, the studies were generally diagnostic regarding left ventricular function and wall motion. Delayed enhancement imaging was of good quality for inferior wall and inferolateral infarcts, but ICD artifacts often affected the imaging of anterior wall infarcts.
Serial MR scans at 1.5 T in patients with ICDs, when carefully performed in a monitored setting, have no adverse effects on either patient or device. When required, single or multiple MR scans at 1.5 T may therefore be considered for clinical diagnostic purposes in these patients.
PMCID: PMC3994993  PMID: 21873440
12.  Long-chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese in Japan and United States whites – population-based prospective cohort study 
Heart (British Cardiac Society)  2013;100(7):569-573.
To determine whether serum levels of long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in incidence rate of coronary artery calcification (CAC) between Japanese in Japan and U.S. whites.
In a population-based prospective-cohort study, 214 Japanese and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS) = 0 were reexamined for CAC in 2007–2010. Among these, 175 Japanese and 113 whites participated in the follow-up exam. Incident cases were defined as participants with CCS ≥ 10 at follow-up. A relative risk regression analysis was used to model incidence rate ratio between Japanese and whites. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline.
Mean (standard deviation) serum percentage of LCn3PUFA was > 100% higher in Japanese than in whites (9.08 (2.49) versus 3.84 (1.79), respectively, p<0.01). Japanese had a significantly lower incidence rate of CAC compared to whites (0.9 versus 2.9/100 person-years, respectively, p < 0.01). Incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% confidence interval (CI) 0.150, 0.690: p<0.01). After adjusting for age, systolic-blood pressure, low-density-lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant: 0.262 (95% CI: 0.094, 0.731, p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376 (95% CI: 0.090, 1.572, p=0.18).
LCn3PUFAs significantly contributed to the difference in CAC incidence between Japanese and white men.
PMCID: PMC3949146  PMID: 24352736
long-chain n-3 fatty acids; coronary artery calcification; prospective cohort study; incidence; risk factors
13.  Palpitations in a 64 year old man 
Heart (British Cardiac Society)  2013;100(2):167-168.
PMCID: PMC3960282  PMID: 24281755
14.  Low-density lipoprotein and aortic stenosis 
Heart (British Cardiac Society)  2008;94(9):1111-1112.
PMCID: PMC3951852  PMID: 18703687
15.  Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery 
Heart  2013;100(6):456-464.
Current European and American guidelines recommend the perioperative initiation of a course of β-blockers in those at risk of cardiac events undergoing high- or intermediate-risk surgery or vascular surgery. The Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of trials, the bedrock of evidence for this, are no longer secure. We therefore conducted a meta-analysis of randomised controlled trials of β-blockade on perioperative mortality, non-fatal myocardial infarction, stroke and hypotension in non-cardiac surgery using the secure data.
The randomised controlled trials of initiation of β-blockers before non-cardiac surgery were examined. Primary outcome was all-cause mortality at 30 days or at discharge. The DECREASE trials were separately analysed.
Nine secure trials totalling 10 529 patients, 291 of whom died, met the criteria. Initiation of a course of β-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04). The DECREASE family of studies substantially contradict the meta-analysis of the secure trials on the effect of mortality (p=0.05 for divergence). In the secure trials, β-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001) but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001). These results were dominated by one large trial.
Guideline bodies should retract their recommendations based on fictitious data without further delay. This should not be blocked by dispute over allocation of blame. The well-conducted trials indicate a statistically significant 27% increase in mortality from the initiation of perioperative β-blockade that guidelines currently recommend. Any remaining enthusiasts might best channel their energy into a further randomised trial which should be designed carefully and conducted honestly.
PMCID: PMC3932762  PMID: 23904357
16.  Associations of vitamin D, parathyroid hormone and calcium with cardiovascular risk factors in US adolescents 
Heart (British Cardiac Society)  2010;97(4):315-320.
To examine independent associations of serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium with a range of cardiovascular risk factors in adolescents.
Cross-sectional population-based study.
A nationally representative sample of the US adolescent population.
Healthy adolescents (aged 12–19) participating in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2006. Numbers varied between 740 and 5609 for given exposure and outcome associations.
Main outcome measures
Systolic blood pressure (SBP), diastolic blood pressure (DBP), lipids (triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)), fasting insulin and glucose, postload glucose and glycohaemoglobin (HbA1c).
25(OH)D was inversely associated with SBP (−0.068 standard deviations (SD), 95% CI −0.118 to −0.018), and positively associated with HDL-C (0.101; 0.040 to 0.162) and HbA1c (0.073; 0.021 to 0.125) after adjustment for gender, age, ethnicity, socioeconomic status and waist circumference. In adjusted models, PTH was inversely associated with triglycerides (−0.115; −0.188 to −0.042) and LDL-C (−0.133; −0.207 to −0.060). In adjusted models, calcium was positively associated with fasting insulin (0.110; 0.060 to 0.160), postload glucose (0.116; 0.000 to 0.232), HbA1c (0.079; 0.035 to 0.123), triglycerides (0.182; 0.122 to 0.242), HDL-C (0.049; 0.010 to 0.088) and LDL-C (0.137; 0.080 to 0.195). The associations of each exposure with risk factors remained after mutual adjustment for each other.
Higher calcium levels might be a more important predictor of increased cardiovascular risk in adolescents than lower 25(OH)D levels or PTH levels, but the findings require replication in additional studies and examination in prospective studies.
PMCID: PMC3931194  PMID: 21193684
17.  Preeclampsia and maternal placental syndromes: An indicator of a predisposition or cause of long-term cardiovascular disease? 
Heart (British Cardiac Society)  2012;98(15):1109-1111.
PMCID: PMC3925666  PMID: 22698857
Hypertension; Pregnancy induced; Placenta Diseases; Heart failure; Arrhythmias; cardiac
18.  Bile acids induce arrhythmias: old metabolite, new tricks 
Heart (British Cardiac Society)  2013;99(22):1629-1630.
PMCID: PMC3913276  PMID: 23969477
19.  Smoking water-pipe, chewing nass, and prevalence of heart disease – A cross-sectional analysis of baseline data from the Golestan Cohort Study, Iran 
Heart (British Cardiac Society)  2012;99(4):272-278.
Water-pipe and smokeless tobacco use have been associated with several adverse health outcomes. However, little information is available on the association between water-pipe use and heart disease (HD). Therefore, we investigated the association of smoking water-pipe and chewing nass (a mixture of tobacco, lime, and ash) with prevalent HD.
Cross-sectional study.
Baseline data (collected in 2004–2008) from a prospective population-based study in Golestan Province, Iran.
50,045 residents of Golestan (40–75 years old; 42.4% male).
Main outcome measures
ORs and 95% CIs from multivariate logistic regression models for the association of water-pipe and nass use with HD prevalence.
A total of 3051 (6.1%) participants reported a history of HD, and 525 (1.1%) and 3726 (7.5%) reported ever water-pipe or nass use, respectively. Heavy water-pipe smoking was significantly associated with HD prevalence (highest level of cumulative use versus never use, OR= 3.75; 95% CI 1.52 – 9.22; P for trend= 0.04). This association persisted when using different cutoff points, when restricting HD to those taking nitrate compound medications, and among never cigarette smokers. There was no significant association between nass use and HD prevalence (highest category of use versus never use, OR= 0.91; 95% CI 0.69 – 1.20).
Our study suggests a significant association between HD and heavy water-pipe smoking. Although the existing evidence suggesting similar biological consequences of water-pipe and cigarette smoking make this association plausible, results of our study were based on a modest number of water-pipe users and need to be replicated in further studies.
PMCID: PMC3671096  PMID: 23257174
hookah; ischemic heart disease; nass; tobacco; water-pipe
20.  Multiple cardiovascular risk factors in Kenya: evidence from a Health and Demographic Surveillance System using the WHO STEPwise Approach to Chronic Disease Risk Factor Surveillance 
Heart (British Cardiac Society)  2013;99(18):1323-1329.
To describe the distribution of cardiovascular risk factors in western Kenya using a Health and Demographic Surveillance System (HDSS).
Population-based survey of residents in an HDSS
Webuye Division in Bungoma East District, Western Province of Kenya
4037 adults ≥18 years of age
Home-based survey using the World Health Organization STEPwise approach to chronic disease risk factor surveillance
Main outcome measures
Self-report of high blood pressure, high blood sugar, tobacco use, alcohol use, physical activity and fruit/vegetable intake
The median age of the population was 35 years (IQR: 26–50). Less than 6% of the population reported high blood pressure or blood sugar. Tobacco and alcohol use were reported in 7% and 16% of the population, respectively. The majority of the population (93%) was physically active. The average number of days per week that participants reported intake of fruits (3.1 +/− 0.1) or vegetables (1.6 +/− 0.1) was low. In multiple logistic regression analyses, women were more likely to report a history of high blood pressure (OR 2.72, 95% CI 1.9–3.9), less likely to report using tobacco (OR 0.08, 95% CI 0.06–0.11), less likely to report alcohol use (OR 0.18, 95% CI 0.15–0.21) or eat ≥5 servings per day of fruits or vegetables (OR 0.87, 95% CI 0.76–0.99) compared to men.
The most common cardiovascular risk factors in peri-urban western Kenya are tobacco use, alcohol use and inadequate intake of fruits and vegetables. Our data reveal locally-relevant sub-group differences that could inform future prevention efforts.
PMCID: PMC3898037  PMID: 23872588
cardiovascular diseases; risk factors; Kenya; demography; sub-Saharan Africa
21.  Future applications of contrast echocardiography 
Heart (British Cardiac Society)  2012;98(3):10.1136/heartjnl-2011-300737.
PMCID: PMC3856916  PMID: 22199019
22.  Speckle myocardial imaging modalities for early detection of myocardial impairment in isolated left ventricular non-compaction 
Heart (British Cardiac Society)  2009;96(6):10.1136/hrt.2009.182170.
To examine the hypothesis that speckle myocardial imaging (SMI) modalities, including longitudinal, radial and circumferential systolic (s) and diastolic (d) myocardial velocity imaging, displacement (D), strain rate (SR) and strain (S), as well as left ventricular (LV) rotation/torsion are sensitive for detecting early myocardial dysfunction in isolated LV non-compaction (iLVNC).
Design and results
Twenty patients with iLVNC diagnosed by cardiac magnetic resonance (15) or echocardiography (5) were included. Patients were divided into two groups: ejection fraction (EF)>50% (n=10) and EF≤50% (n=10). Standard measures of systolic and diastolic function including pulsed wave tissue Doppler Imaging (PWTDI) were obtained. Longitudinal, radial and circumferential SMI, and LV rotation/torsion were compared with values for 20 age/sex-matched controls. EF, PWTDI E′, E/E′ and all of the SMI modalities were significantly abnormal for patients with EF≤50% compared with controls. In contrast, EF and PWTDI E′, E/E′ were not significantly different between controls and patients with iLVNC (EF>50%). However, SMI-derived longitudinal sS, sSR, sD and radial sS, as well as LV rotation/torsion values, were all reduced in iLVNC (EF>50%) compared with controls. Measurements with the highest discriminating power between iLVNC (EF>50%) and controls were longitudinal sS mean of the six apical segments (area under the curve (AUC)=0.94), sS global average (AUC=0.94), LV rotation apical mean (AUC=0.94); LV torsion (AUC=0.93) LV torsion rate (AUC=0.94).
LV SMI values are reduced in patients with iLVNC, even those with normal EF and PWTDI. The most accurate SMI modalities to discriminate between patients and controls are longitudinal sS mean of the six apical segments, LV apical rotation or LV torsion rate.
PMCID: PMC3835601  PMID: 19966109
23.  Low-dose nesiritide in human anterior myocardial infarction suppresses aldosterone and preserves ventricular function and structure: a proof of concept study 
Heart (British Cardiac Society)  2009;95(16):10.1136/hrt.2008.153916.
B-type natriuretic peptide (BNP, nesiritide) has anti-fibrotic, anti-hypertrophic, anti-inflammatory, vasodilating, lusitropic and aldosterone-inhibiting properties but conventional doses of BNP cause hypotension, limiting its use in heart failure.
To determine whether infusion of low-dose BNP within 24 h of successful reperfusion for anterior acute myocardial infarction (AMI) would prevent adverse left ventricular (LV) remodelling and suppress aldosterone.
A translational proof-of-concept study was carried out to determine tolerability and biological activity of intravenous BNP at 0.003 and 0.006 mg/kg/min, without bolus started within 24 h of successful reperfusion for anterior AMI. 24 patients with first anterior wall ST elevation AMI and successful revascularisation were randomly assigned to receive 0.003 (n = 12) or 0.006 (n = 12) mg/kg/min of IV BNP for 72 h in addition to standard care during hospitalisation for anterior AMI.
Baseline characteristics, drugs and peak cardiac biomarkers for myocardial damage were similar between both groups. Infusion of BNP at 0.006 mg/kg/min resulted in greater biological activity than infusion at 0.003 mg/kg/min as measured by higher mean (SEM) plasma cGMP levels (8.6 (1) vs 5.5 (1) pmol/ml, p,0.05) and suppression of plasma aldosterone (8.0 (2) to 4.6 (1) ng/ dl, p,0.05), which was not seen in the 0.003 mg/kg/min group. LV ejection fraction (LVEF) improved significantly from baseline to 1 month (40 (4)% to 54 (5)%, p,0.05) in the 0.006 group but not in the 0.003 group. Infusion of BNP at 0.006 mg/kg/min was associated with a decrease of LV end-systolic volume index (61 (9) to 43 (8) ml/m2, p,0.05) at 1 month, which was not seen in the 0.003 group. No drug-related serious adverse events occurred in either group.
72 h infusion of low BNP at the time of anterior AMI is well tolerated and biologically active. Patients treated with low-dose BNP had improved LVEF and smaller LV end-systolic volume at 1 month.
PMCID: PMC3835541  PMID: 19447837
24.  Changes in HDL cholesterol and cardiovascular outcomes after lipid modification therapy 
Heart (British Cardiac Society)  2012;98(10):780-785.
Lipid modification therapy (LMT) produces cardiovascular benefits principally through reductions in low density lipoprotein cholesterol (LDL-C). While recent evidence, using data from 454 participants in the Framingham Offspring Study (FOS), has suggested that increases in high density lipoprotein cholesterol (HDL-C) are also associated with a reduction in cardiovascular outcomes, independently of changes in LDL-C, replication of this finding is important. We therefore present further results using data from the EPIC Norfolk (UK) and Rotterdam (Netherlands) prospective cohort studies.
A total of 1,148 participants, 446 from the EPIC-Norfolk and 702 from the Rotterdam study were assessed for lipids before and after starting LMT. Subsequent risk of cardiovascular events, ascertained through linkage with mortality records and hospital databases, was investigated using Cox Proportional hazards regression. Random effects meta-analysis was used to combine results across studies.
Based on combined data from the EPIC-Norfolk and Rotterdam studies there was some evidence that change in HDL-C resulting from LMT was associated with reduced cardiovascular risk (hazard ratio per pooled SD (= 0. 34 mmol/l) increase = 0.74, 95% CI 0.56-0.99, adjusted for age, sex, and baseline HDL-C). However, this association was attenuated and was not (statistically) significant with further adjustments for non-HDL-C and for cigarette smoking history, prevalent diabetes, SBP, BMI, use of antihypertensive medication, previous MI, prevalent angina, previous stroke (0.92, 0.70-1.20).
Following adjustment for conventional non-lipid CVD risk factors, this study provides no evidence to support a significant benefit from increasing HDL-C independent of the effect of lowering non-HDL-C.
PMCID: PMC3773905  PMID: 22447463
Lipids; Lipoproteins; HDL; Atherosclerosis; Myocardial infarction
25.  Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study 
Heart (British Cardiac Society)  2010;96(24):1985-1989.
The value of a family history for coronary heart disease (CHD) in addition to established cardiovascular risk factors in predicting an individual’s risk of CHD is unclear. In the EPIC-Norfolk cohort, we tested whether adding family history of premature CHD in first degree relatives improves risk prediction compared to the Framingham risk score (FRS) alone.
Methods and Results
This study comprised 10,288 men and 12,553 women aged 40 to 79 years participating in the EPIC-Norfolk cohort who where followed for an average of 10.9 ± 2.1 years (mean ± SD). We computed the Framingham risk score as well as a modified score taking into account family history of premature CHD. A family history of CHD was indeed associated with an increased risk of future CHD, independent of established risk factors (FRS-adjusted hazard ratio of 1.74 (95%CI 1.56-1.95) for family history of premature CHD). However, adding family history of CHD to the Framingham risk score resulted in a negative net reclassification of 2%. In the subgroup of individuals estimated to be at intermediate risk, family history of premature CHD resulted in an increase in net reclassification of 2%. The sensitivity increased with 0.4 % and the specificity decreased 0.8%.
Although family history of CHD was an independent risk factor of future CHD, its use did not improve classification of individuals into clinically relevant risk categories based on the FRS. Among study participants at intermediate risk of CHD, adding family history of premature CHD resulted in, at best, a modest improvement in reclassification of individuals into a more accurate risk category.
PMCID: PMC3773915  PMID: 20962344

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