John Payne

Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial

Objective To determine whether or not radiofrequency ablation (RFA) for persistent atrial fibrillation in patients with advanced heart failure leads to improvements in cardiac function. Setting Patients were recruited from heart failure outpatient clinics in Scotland. Design and intervention Patients with advanced heart failure and severe left ventricular dysfunction were randomised to RFA (rhythm control) or continued medical treatment (rate control). Patients were followed up for a minimum of 6 months. Main outcome measure Change in left ventricular ejection fraction (LVEF) measured by cardiovascular MRI. Results 22 patients were randomised to RFA and 19 to medical treatment. In the RFA group, 50% of patients were in sinus rhythm at the end of the study (compared with none in the medical treatment group). The increase in cardiovascular magnetic resonance (CMR) LVEF in the RFA group was 4.5±11.1% compared with 2.8±6.7% in the medical treatment group (p=0.6). The RFA group had a greater increase in radionuclide LVEF (a prespecified secondary end point) than patients in the medical treatment group (+8.2±12.0% vs +1.4±5.9%; p=0.032). RFA did not improve N-terminal pro-B-type natriuretic peptide, 6 min walk distance or quality of life. The rate of serious complications related to RFA was 15%. Conclusions RFA resulted in long-term restoration of sinus rhythm in only 50% of patients. RFA did not improve CMR LVEF compared with a strategy of rate control. RFA did improve radionuclide LVEF but did not improve other secondary outcomes and was associated with a significant rate of serious complications. Clinical trials registration number NCT00292162.

Genetic Variants of Angiotensin II Receptors and Cardiovascular Risk in Hypertension

Abstract—Renin-angiotensin systems may mediate cardiovascular disease pathogenesis through a balance of actions of angiotensin II on (potentially proatherogenic) constitutive type 1 (AT1R) and (potentially antiatherogenic) inducible type 2 (AT2R) receptors. We explored such potential roles in a prospective candidate gene association study. Cardiovascular end points (fatal, nonfatal, and silent myocardial infarction and coronary artery bypass surgery/angioplasty) were documented among 2579 healthy UK men (mean age, 56.1±3.5 years; median follow-up, 10.1 years) genotyped for the AT1R1166A>C and the X chromosome located AT2R1675A>G and 3123C>A polymorphisms. Baseline characteristics, including blood pressure, were independent of genotype. The AT1R1166CC genotype was associated with relative cardiovascular risk (hazard ratio, 1.65 [1.05 to 2.59]; P =0.03) independent of blood pressure. Systolic blood pressure was associated with risk (P =0.0005), but this association was restricted to AT2R1675A allele carriers (P <0.00001), with G allele carriers protected from the risk associated with blood pressure (P =0.18). Hypertensive carriers with the AT2R1675A/3123A haplotype were at most risk, with 37.5% having an event. This is the first study to demonstrate an association of AT2R genotype with coronary risk, an effect that was confined to hypertensive subjects and supports the concept that the inducible AT2R is protective. Conversely, the AT1R1166CC genotype was associated with cardiovascular risk irrespective of blood pressure. These data are important to our understanding of the divergent role of angiotensin II acting at its receptor subtypes and coronary disease pathogenesis and for the development of future cardiovascular therapies.

Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.

Background—Inflammation following acute myocardial infarction (MI) has detrimental effects on reperfusion, myocardial remodelling, and ventricular function. Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide can detect cellular inflammation in tissues, and we therefore explored their role in acute MI in humans. Methods and Results—Sixteen patients with acute ST-segment elevation MI were recruited to undergo 3 sequential magnetic resonance scans within 5 days of admission at baseline, 24 and 48 hours following no infusion (controls; n=6) or intravenous infusion of ultrasmall superparamagnetic particles of iron oxide (n=10; 4 mg/kg). T2*-weighted multigradient-echo sequences were acquired and R2* values were calculated for specific regions of interest. In the control group, R2* values remained constant in all tissues across all scans with excellent repeatability (bias of −0.208 s−1, coefficient of repeatability of 26.96 s−1; intraclass coefficient 0.989). Consistent with uptake by the reticuloendothelial system, R2* value increased in the liver (84±49.5 to 319±70.0 s−1; P<0.001) but was unchanged in skeletal muscle (54±8.4 to 67.0±9.5 s−1; P>0.05) 24 hours after administration of ultrasmall superparamagnetic particles of iron oxide. In the myocardial infarct, R2* value increased from 41.0±12.0 s−1 (baseline) to 155±45.0 s−1 (P<0.001) and 124±35.0 s−1 (P<0.05) at 24 and 48 hours, respectively. A similar but lower magnitude response was seen in the remote myocardium, where it increased from 39±3.2 s−1 (baseline) to 80±14.9 s−1 (P<0.001) and 67.0±15.7 s−1 (P<0.05) at 24 and 48 hours, respectively. Conclusions—Following acute MI, uptake of ultrasmall superparamagnetic particles of iron oxide occurs with the infarcted and remote myocardium. This technique holds major promise as a potential method for assessing cellular myocardial inflammation and left ventricular remodelling, which may have a range of applications in patients with MI and other inflammatory cardiac conditions. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01323296.

Cardiac effects of anabolic steroids

Anabolic steroid abuse in athletes has been associated with a wide range of adverse conditions, including hypogonadism, testicular atrophy, impaired spermatogenesis, gynaecomastia, and psychiatric disturbance. But what effect does steroid abuse have on the cardiovascular system?

Variation in bradykinin receptor genes increases the cardiovascular risk associated with hypertension

AIMS The contribution of kinins to the beneficial effects of angiotensin I converting enzyme (ACE) inhibition in cardiovascular risk reduction remains unclear. The genes for the kinin inducible B1 receptor (B(1)R) and constitutive B2 receptor (B(2)R) contain functional variants: the B(1)R-699C (rather than G) and the B(2)R(-9) (rather than +9) alleles are associated with greater mRNA expression and the B(2)R(-9) allele with reduced left ventricular hypertrophic responses. We tested whether these gene variants influenced hypertensive coronary risk in a large prospective study. METHODS AND RESULTS Two thousand, seven hundred and six previously healthy UK men (mean age at recruitment 56 years; median follow-up 10.8 years) were genotyped for the kinin receptor variants. The coronary risk attributable to systolic hypertension (SBP>/=160 mmHg) was significantly higher only in B(1)R-699GG homozygotes (HR 2.14 [1.42-3.22]; P<0.0001) and B(2)R(+9,+9) individuals (HR 3.51 [1.69-7.28]; P=0.001) but not in B(1)R-699C allele carriers (HR 0.82 [0.28-2.42]; P=0.76) or in B(2)R(-9,-9) homozygotes (HR 1.25 [0.51-3.04]; P=0.63). CONCLUSIONS Common variation in the genes for the kinin B(1)and B(2)receptors influences prospective hypertensive coronary risk. These are the first reported human data to suggest a role for the B(1)R in human coronary vascular disease, and the first prospective study to demonstrate a similar role for the B(2)R.

Bone structure and geometry in young men: the influence of smoking, alcohol intake and physical activity.

BACKGROUND The development of osteoporosis is influenced by peak bone mass attained in youth - the influence of lifestyle factors upon which is poorly described, especially amongst males. We sought to address this issue in a large scale study. METHODS Hip bone mineral density (dual X-ray absorptiometry, DXA), bone microarchitecture (calcaneal quantitative ultrasound, QUS) and femoral geometry (magnetic resonance imaging, MRI) were characterised in 723 healthy male military recruits (mean ± S.E. age 19.92 ± 0.09 years [range 16-18 years], height 177.67 ± 0.24 cm, weight 73.17 ± 0.37 kg) on entry to UK Army training. Association was sought with prior physical activity, smoking status and alcohol intake. RESULTS DXA measures were made in 651, MRI measures in 650, and QUS measures in 572 recruits. Increasing levels of weight-bearing physical activity enhanced periostial bone apposition, increases in both total hip and femoral neck bone mineral density (BMD; p ≤ 0.0001 in both cases), and cortical [p<0.0001] and periostial bone volumes [p=0.016]. Smoking habit was associated with preserved bone geometry, but worse BMD [p=0.0001] and QUS characteristics [p ≤ 0.0005]. Moderate alcohol consumption was associated with greater BMD [p ≤ 0.015]. CONCLUSIONS Whilst exercise (and perhaps moderate alcohol intake) is beneficial to bone morphometry, smoking is detrimental to bone mineral density in young males notable for the likely short duration of smoking to influence skeletal properties. However, differences in socio-economic status, lifestyle and related environmental factors may to some extent confound our results.

Cardiovascular magnetic resonance activity in the United Kingdom: a survey on behalf of the british society of cardiovascular magnetic resonance

BackgroundThe indications, complexity and capabilities of cardiovascular magnetic resonance (CMR) have rapidly expanded. Whether actual service provision and training have developed in parallel is unknown.MethodsWe undertook a systematic telephone and postal survey of all public hospitals on behalf of the British Society of Cardiovascular Magnetic Resonance to identify all CMR providers within the United Kingdom.ResultsOf the 60 CMR centres identified, 88% responded to a detailed questionnaire. Services are led by cardiologists and radiologists in equal proportion, though the majority of current trainees are cardiologists. The mean number of CMR scans performed annually per centre increased by 44% over two years. This trend was consistent across centres of different scanning volumes. The commonest indication for CMR was assessment of heart failure and cardiomyopathy (39%), followed by coronary artery disease and congenital heart disease. There was striking geographical variation in CMR availability, numbers of scans performed, and distribution of trainees. Centres without on site scanning capability refer very few patients for CMR. Just over half of centres had a formal training programme, and few performed regular audit.ConclusionThe number of CMR scans performed in the UK has increased dramatically in just two years. Trainees are mainly located in large volume centres and enrolled in cardiology as opposed to radiology training programmes.

Thoratec CentriMag for Temporary Treatment of Refractory Cardiogenic Shock or Severe Cardiopulmonary Insufficiency: A Systematic Literature Review and Meta-Analysis of Observational Studies

The aim of the study was to systematically evaluate effect of CentriMag heart pump (Thoratec Corporation) as temporary ventricular assist device (VAD) and part of extracorporeal membrane oxygenation (ECMO) system on outcomes in patients with cardiac or cardiac-respiratory failure. A systematic search was conducted in five databases for the period 2003 to 2012. Fifty-three publications with data for 999 patients, supported with CentriMag, were included. In 72% studies, CentriMag was used as a VAD and in 25% as part of ECMO circuit. Mean duration of VAD support was 25.0 days in precardiotomy group, 10.9 days in postcardiac surgery cardiogenic shock group, 8.8 days in post-transplant graft failure and rejection group, and 16.0 days in post-LVAD placement right ventricular failure group. Survival on support was 82% (95% CI 70–92) for VAD support in precardiotomy cardiogenic shock indication, 63% (95% CI 46–78) in VAD support in postcardiac surgery cardiogenic shock indication, 62% (95% CI 46–76) in VAD support in post-transplant graft rejection or failure indication, and 83% (95% CI 73–92) in VAD support in post-LVAD placement right ventricular failure indication. CentriMag is an effective technology for temporary support of patients with cardiac and cardiorespiratory failure.

The Impact of ACE Genotype on Serum ACE Activity in a Black South African Male Population

The strong association between the angiotensin I‐converting enzyme (ACE) gene I/D polymorphism with serum ACE activity appears lacking in Nigerians and Kenyans, but has not previously been well assessed in others of African origin. This study addressed this issue in an ethnically well defined black South African population. A putative association for the A22982G ACE gene variant, a QTL likely to impact on serum ACE activity, was also sought.

Electrocardiographic (ECG) criteria for determining left ventricular mass in young healthy men; data from the LARGE Heart study

BackgroundDoubts remain over the use of the ECG in identifying those with increased left ventricular (LV) mass. This is especially so in young individuals, despite their high prevalence of ECG criteria for LV hypertrophy. We performed a study using cardiovascular magnetic resonance (CMR), which provides an in vivo non-invasive gold standard method of measuring LV mass, allowing accurate assessment of electrocardiography as a tool for defining LV hypertrophy in the young.Methods and resultsStandard 12-lead ECGs were obtained from 101 Caucasian male army recruits aged (mean ± SEM) 19.7 ± 0.2 years. LV mass was measured using CMR. LV mass indexed to body surface area demonstrated no significant correlation with the Cornell Amplitude criteria or Cornell Product for LV hypertrophy. Moderate correlations were seen with the Sokolow-Lyon Amplitude (0.28) and Sokolow-Lyon Product (0.284). Defining LV hypertrophy as a body surface area indexed left ventricular mass of 93 g/m2, calculated sensitivities [and specificities] were as follows; 38.7% [74.3%] for the Sokolow-Lyon criteria, 43.4% [61.4%] for the Sokolow-Lyon Product, 19.4% [91.4%] for Cornell Amplitude, and 22.6% [85.7%] for Cornell Product. These values are substantially less than those reported for older age groups.ConclusionECG criteria for LV hypertrophy may have little value in determining LV mass or the presence of LV hypertrophy in young fit males.