Convergent approach to persistent atrial fibrillation ablation: long-term single-centre safety and efficacy.

Background: Efforts to maintain sinus rhythm in patients with persistent atrial fibrillation (PsAF) remain challenging, with suboptimal long-term outcomes. Methods: All patients undergoing convergent PsAF ablation at our centre were retrospectively analysed. The Atricure Epi-Sense® system was used to perform surgical radiofrequency ablation of the LA posterior wall followed by endocardial ablation. Results: A total of 24 patients underwent convergent PsAF ablation, and 21 (84%) of them were male with a median age of 63. Twelve (50%) patients were obese. In total, 71% of patients had a severely dilated left atrium, and the majority (63%) had preserved left ventricular function. All were longstanding persistent. Eighteen (75%) patients had an AF duration of >2 years. There were no endocardial procedure complications. At 36 months, all patients were alive with no new stroke/transient ischaemic attack (TIA). Freedom from documented AF at 3, 6, 12, 18, 24, and 36 months was 83%, 78%, 74%, 74%, 74%, and 61%, respectively. There were no major surgical complications, with five minor complications recorded comprising minor wound infection, pericarditic pain, and hernia. Conclusions: Our data suggest that convergent AF ablation is effective with excellent immediate and long-term safety outcomes in a real-world cohort of patients with a significant duration of AF and evidence of established atrial remodelling. Convergent AF ablation appears to offer a safe and effective option for those who are unlikely to benefit from existing therapeutic strategies for maintaining sinus rhythm, and further evaluation of this exciting technique is warranted. Our cohort is unique within the published literature both in terms of length of follow-up and very low rate of adverse events.

Increasing age does not affect time to appropriate therapy in primary prevention ICD/CRT-D: a competing risks analysis.

Aims: To evaluate the impact of age on the clinical outcomes in a primary prevention implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) population. Methods and Results: A retrospective, multicentre analysis of patients aged 60 years and over with primary prevention ICD/CRT-D devices implanted between 1 January 2006 and 1 November 2014 was performed. Survival to follow-up with no therapy (T1), death prior to follow-up with no therapy (T2), delivery of appropriate therapy with survival to follow-up (T3), and delivery of appropriate therapy with death prior to follow-up (T4) were measured. In total, 424 patients were eligible for inclusion in the analysis, mean follow-up of 32.6 months during which time 44 patients (10.1%) received appropriate therapy. The sub-hazard ratio (SHR) for the cumulative incidence of appropriate therapy (T3) according to age at implant was 1.00 (P = 0.851; 95% CI 0.96­1.04). The SHR for cumulative incidence of death (T2) according to age at implant was 1.06 (P < 0.001; 95% CI 1.03­1.01). Age at implant, ischaemic aetiology, baseline haemoglobin, and the presence of diabetes mellitus were predictors of all-cause mortality. Conclusion: Age has no impact on the time to appropriate therapy, but risk of death prior to therapy increases by 6% for every year increment. As the ICD population ages, the proportion who die without receiving appropriate therapy increases due to competing risks. Characterizing competing risks predictive of death independent of ICD indication would focus therapy on those with potential to benefit and reduce unnecessary exposure to ICD-related morbidity.

Clinical Predictors of Pacemaker Implantation in Patients with Syncope Receiving Implantable Loop Recorder with or without ECG Conduction Abnormalities.

BACKGROUND: Implantable loop recorders (ILR) allow prolonged cardiac rhythm monitoring and improved diagnostic yield in syncope patients. Predictive factors for pacemaker (PM) implantation in the ILR population with unexplained syncope have not been adequately investigated. In this single center, retrospective, observational study we investigated factors that predict PM implantation in this population. METHODS: We retrospectively analyzed our ILR database of patients aged over 18 years who underwent ILR implantation for unexplained syncope between January 2009 and June 2013. Patient case notes were examined for demographics, history, electrocardiogram (ECG) abnormalities, investigations, and events during follow-up. The primary end-point was the detection of a symptomatic or asymptomatic bradycardia requiring PM implantation. RESULTS: During a period of 4.5 years, 200 patients were implanted with ILR for unexplained syncope, of who n = 33 (16.5%) had clinically significant bradycardia requiring PM implantation. After multivariable analysis, history of injury secondary to syncope was found to be the strongest independent predictor for PM implantation (odds ratio [OR]:9.1; P < 0.001; 95% confidence interval [CI]: (3.26-26.81). Other significant predictors included female sex, PR interval > 200msec, and age >75 years. In patients without conduction abnormalities on the ECG, history of injury secondary to syncope was found to be the strongest independent predictor for PM implantation (OR: 8.16; P = 0.00027; 95% [CI]: (2.67-26.27). CONCLUSIONS: A history of injury secondary to syncope and female sex were independent predictive factors for bradycardia necessitating PM implantation in patients receiving an ILR for syncope with or without ECG conduction abnormalities.

Point-by-Point Radiofrequency Ablation Versus the Cryoballoon or a Novel Combined Approach: A Randomized Trial Comparing 3 Methods of Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation (The Cryo Versus RF Trial).

INTRODUCTION: Catheter ablation of paroxysmal AF using the Cryoballoon (CRYO) has yielded similar success rates to conventional wide encirclement using radiofrequency catheter ablation (RFCA), but randomized data are lacking. Pilot data suggested a high success rate with a combined approach (COMBINED) using wide encirclement with RFCA followed by 2 CRYO applications to each vein. We compared these 3 strategies in a randomized controlled trial. METHODS AND RESULTS: Patients undergoing first time paroxysmal AF ablation were randomized to RFCA, CRYO, or COMBINED. Patients were followed up at 3, 6, and 12 months with 7 days of ambulatory ECG monitoring. Success was defined as freedom from arrhythmia without antiarrhythmic drugs after a single procedure. A total of 237 patients were randomized. Success at 1 year was achieved in 47% in the RFCA group, 67% in the CRYO group, and 76% in the COMBINED group (P < 0.001 for RFCA vs. CRYO, P<0.001 for RFCA vs. COMBINED, and P = 0.220 for CRYO vs. COMBINED). Procedure time was 211 (IQR 174-256) minutes for RFCA compared to 167 (136-202) minutes for CRYO and 278 (243-327) minutes for COMBINED (P < 0.001 for RFCA vs. COMBINED, RFCA vs. CRYO, and CRYO vs. COMBINED groups). CONCLUSIONS: Pulmonary vein isolation for paroxysmal AF is faster with CRYO and results in a higher single procedure success rate than conventional point by point RFCA. The COMBINED approach was not superior to CRYO alone.

Predictors of new onset atrial fibrillation in patients with heart failure.

INTRODUCTION: Stroke associated with atrial fibrillation (AF) is more frequent in heart failure. It is unknown what variables predict future AF in these patients and how AF might evolve over time. We investigated this in patients with implantable cardiac defibrillators (ICD) where AF detection is optimal. METHODS: Single centre, retrospective, observational cohort study. All ischaemic cardiomyopathy patients with dual chamber, primary prevention ICD implants between Aug 2003 and Dec 2009 were screened and included if at implant, they had no known AF history. Nine variables were analysed. AF was defined as any atrial tachyarrhythmia ≥180 bpm and ≥30 s. Multivariable, binary logistic regression models were built by adding variables significant in the univariate models. Variables were retained in the final multivariate models if p<0.05. RESULTS: n=197 met the inclusion criteria (85.8% male, median age: 66.8 years). After median follow-up for 2.8 years, 44.2% developed AF. After univariate analysis, the baseline variables associated with AF after implant were age, NYHA class and renal impairment (RI, defined eGFR<60 ml/min/1.73 m2) (p<0.05). After multivariable analysis, the only variable which was associated with AF was RI (HR: 2.04 (CI: 1.10-3.79)). Two baseline variables were independently associated with all-cause mortality: RI (HR: 2.42 (1.14-5.12)) and non-white ethnicity. CONCLUSION: RI at time of implant was independently associated with both future AF and all-cause mortality during long-term follow-up. RI was a stronger predictor of AF than age. Those patients with heart failure and RI should be regularly screened for asymptomatic AF, regardless of age, to ensure that stroke prophylaxis may be initiated.

Epicardial catheter ablation for ventricular tachycardia in heparinized patients.

AIMS: In patients undergoing epicardial catheter ablation of ventricular tachycardia (VT), current guidelines recommend obtaining pericardial access prior to heparinization to minimize bleeding complications. Consequently, access is obtained before endocardial mapping (leading to unnecessary punctures) or during an additional procedure. We present our experience of obtaining pericardial access during the index procedure in heparinized patients. METHODS AND RESULTS: Patients undergoing catheter ablation of VT in whom pericardial access was performed after heparinization were included. Clinical and procedural data and complications were recorded. Electrocardiograms (ECGs) were analysed for published criteria suggesting an epicardial ablation target and compared with patients (matched for substrate) undergoing successful endocardial ablation. Seventeen patients (13 males, age 58 ± 16 years, 8 (47%) ischaemic) were evaluated. Pericardial access was achieved in 16 (94%), including 2 patients with prior epicardial ablation. The mean activated clotting time was 273 ± 36 s. No bleeding complications occurred. In three patients, inadvertent puncture of the right ventricle caused no adverse consequences. An epicardial ablation target was found in nine of which three (33%) had ECG criteria, suggesting an epicardial circuit. In comparison 5 of 17 patients undergoing successful endocardial ablation had at least one ECG criterion suggesting an epicardial ablation target. CONCLUSION: Obtaining pericardial access for epicardial catheter ablation for VT appears to be safe in heparinized patients. Electrocardiogram criteria suggesting an epicardial ablation target lack the sensitivity and specificity accurately to predict which patients might need epicardial ablation. Performing pericardial access in heparinized patients therefore may reduce unnecessary punctures and reduce the number of additional procedures in some patients.

Improved electrogram attenuation during ablation of paroxysmal atrial fibrillation with the Hansen robotic system.

BACKGROUND: Robotic catheter ablation aims to improve outcomes after ablation of atrial fibrillation (AF) through improved lesion quality. This study examined electrogram attenuation as a measure of efficacy in response to robotic (ROB) and manual (MAN) ablation. METHODS: Patients with paroxysmal AF undergoing ablation as part of an ongoing randomized controlled trial were studied (Clinical Trials Registration NCT01037296). Patients underwent pulmonary vein isolation using NavX (St. Jude Medical, St. Paul, MN, USA). Patients were randomized to MAN or ROB catheter ablation using a 3.5-mm irrigated-tip catheter with standardized ablation settings. Bipolar electrogram voltage was measured at 0, 5, 10, 20, and 30 seconds after ablation onset. Distance from ablation lesion to the left atrial surface on NavX were calculated. RESULTS: Similar ablation energy was delivered in ROB and MAN groups, achieving comparable rates of PV isolation (100% vs 98%). The bipolar voltages of 4,434 electrograms from 303 ablation lesions (146 ROB, 157 MAN) were measured. At 30 seconds, signal attenuation was greater in the ROB group than MAN (mean 65 ± 4% vs 55 ± 4% of baseline voltage, P < 0.01). A total of 2,064 NavX ablation lesions were assessed (906 ROB and 1,158 MAN). ROB lesions were on average 0.52 mm further inside the geometry than MAN (P < 0.0001). CONCLUSIONS: Robotic ablation results in greater signal attenuation in man. This is achieved despite manual lesions being closer to the left atrial surface. Catheter stability and constant energy delivery may be key to achieving signal attenuation, rather than increased contact force.

Increasing circulating IGFBP1 levels improves insulin sensitivity, promotes nitric oxide production, lowers blood pressure, and protects against atherosclerosis.

Low concentrations of insulin-like growth factor (IGF) binding protein-1 (IGFBP1) are associated with insulin resistance, diabetes, and cardiovascular disease. We investigated whether increasing IGFBP1 levels can prevent the development of these disorders. Metabolic and vascular phenotype were examined in response to human IGFBP1 overexpression in mice with diet-induced obesity, mice heterozygous for deletion of insulin receptors (IR(+/-)), and ApoE(-/-) mice. Direct effects of human (h)IGFBP1 on nitric oxide (NO) generation and cellular signaling were studied in isolated vessels and in human endothelial cells. IGFBP1 circulating levels were markedly suppressed in dietary-induced obese mice. Overexpression of hIGFBP1 in obese mice reduced blood pressure, improved insulin sensitivity, and increased insulin-stimulated NO generation. In nonobese IR(+/-) mice, overexpression of hIGFBP1 reduced blood pressure and improved insulin-stimulated NO generation. hIGFBP1 induced vasodilatation independently of IGF and increased endothelial NO synthase (eNOS) activity in arterial segments ex vivo, while in endothelial cells, hIGFBP1 increased eNOS Ser(1177) phosphorylation via phosphatidylinositol 3-kinase signaling. Finally, in ApoE(-/-) mice, overexpression of hIGFBP1 reduced atherosclerosis. These favorable effects of hIGFBP1 on insulin sensitivity, blood pressure, NO production, and atherosclerosis suggest that increasing IGFBP1 concentration may be a novel approach to prevent cardiovascular disease in the setting of insulin resistance and diabetes.

Vascular insulin-like growth factor-I resistance and diet-induced obesity.

Obesity and type 2 diabetes mellitus are characterized by insulin resistance, reduced bioavailability of the antiatherosclerotic signaling molecule nitric oxide (NO), and accelerated atherosclerosis. IGF-I, the principal growth-stimulating peptide, which shares many of the effects of insulin, may, like insulin, also be involved in metabolic and vascular homeostasis. We examined the effects of IGF-I on NO bioavailability and the effect of obesity/type 2 diabetes mellitus on IGF-I actions at a whole-body level and in the vasculature. In aortic rings IGF-I blunted phenylephrine-mediated vasoconstriction and relaxed rings preconstricted with phenylephrine, an effect blocked by N(G)-monomethyl L-arginine. IGF-I increased NO synthase activity to an extent similar to that seen with insulin and in-vivo IGF-I led to serine phosphorylation of endothelial NO synthase (eNOS). Mice rendered obese using a high-fat diet were less sensitive to the glucose-lowering effects of insulin and IGF-I. IGF-I increased aortic phospho-eNOS levels in lean mice, an effect that was blunted in obese mice. eNOS activity in aortae of lean mice increased 1.6-fold in response to IGF-I compared with obese mice. IGF-I-mediated vasorelaxation was blunted in obese mice. These data demonstrate that IGF-I increases eNOS phosphorylation in-vivo, increases eNOS activity, and leads to NO-dependent relaxation of conduit vessels. Obesity is associated with resistance to IGF-I at a whole-body level and in the endothelium. Vascular IGF-I resistance may represent a novel therapeutic target to prevent or slow the accelerated vasculopathy seen in humans with obesity or type 2 diabetes mellitus.

Effect of endothelium-specific insulin resistance on endothelial function in vivo.

OBJECTIVE: Insulin resistance is an independent risk factor for the development of cardiovascular atherosclerosis. A key step in the development of atherosclerosis is endothelial dysfunction, manifest by a reduction in bioactivity of nitric oxide (NO). Insulin resistance is associated with endothelial dysfunction; however, the mechanistic relationship between these abnormalities and the role of impaired endothelial insulin signaling versus global insulin resistance remains unclear. RESEARCH DESIGN AND METHODS: To examine the effects of insulin resistance specific to the endothelium, we generated a transgenic mouse with endothelium-targeted overexpression of a dominant-negative mutant human insulin receptor (ESMIRO). This receptor has a mutation (Ala-Thr(1134)) in its tyrosine kinase domain that disrupts insulin signaling. Humans with the Thr(1134) mutation are insulin resistant. We performed metabolic and vascular characterization of this model. RESULTS: ESMIRO mice had preserved glucose homeostasis and were normotensive. They had significant endothelial dysfunction as evidenced by blunted aortic vasorelaxant responses to acetylcholine (ACh) and calcium ionophore. Furthermore, the vascular action of insulin was lost in ESMIRO mice, and insulin-induced endothelial NO synthase (eNOS) phosphorylation was blunted. Despite this phenotype, ESMIRO mice demonstrate similar levels of eNOS mRNA and protein expression to wild type. ACh-induced relaxation was normalized by the superoxide dismutase mimetic, Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride. Endothelial cells of ESMIRO mice showed increased superoxide generation and increased mRNA expression of the NADPH oxidase isoforms Nox2 and Nox4. CONCLUSIONS: Selective endothelial insulin resistance is sufficient to induce a reduction in NO bioavailability and endothelial dysfunction that is secondary to increased generation of reactive oxygen species. This arises independent of a significant metabolic phenotype.

The role of IGF-I and its binding proteins in the development of type 2 diabetes and cardiovascular disease.

Patients with insulin resistance and type 2 diabetes have an excessive risk of cardiovascular disease (CVD); this increased risk is not fully explained by traditional risk factors such as hypertension and dyslipidaemias. There is now compelling evidence to suggest that abnormalities of insulin-like growth factor-I (IGF-I) and one of its binding proteins, insulin-like growth factor-binding protein-1 (IGFBP-1), occur in insulin-resistant states and may be significant factors in the pathophysiology of CVD. We reviewed articles and relevant bibliographies following a systematic search of MEDLINE for English language articles between 1966 and the present, using an initial search strategy combining the MeSH terms: IGF, diabetes and CVD. Our aim was first to review the role of IGF-I in vascular homeostasis and to explore the mechanisms by which it may exert its effects. We also present an overview of the physiology of the IGF-binding proteins, and finally, we sought to summarize the evidence to date describing the changes in the insulin/IGF-I/IGFBP-1 axis that occur in type 2 diabetes and CVD; in particular, we have focused on the potential vasculoprotective effects of both IGF-I and IGFBP-1. We conclude that this system represents an interesting and novel therapeutic target in the prevention of CVD in type 2 diabetes.

Insulin resistance and endothelial cell dysfunction: studies in mammalian models.

Type 2 diabetes and obesity are major risk factors for the development of cardiovascular atherosclerosis. Resistance to the metabolic effects of insulin on its traditional target tissues (muscle, liver and adipose tissue) is a central pathogenic feature of these disorders. However, the role of insulin resistance in non-canonical tissues, such as the endothelium, is less clear. Several large studies support a role for insulin resistance in the development of premature cardiovascular atherosclerosis independent of type 2 diabetes and obesity. A key step in the initiation and progression of atherosclerosis is a reduction in the bioactivity of endothelial cell-derived nitric oxide. Nitric oxide is a signalling molecule which has a portfolio of potential antiatherosclerotic effects. The presence of insulin receptors on endothelial cells is well documented, and the endothelium has now emerged as a potentially important target tissue for insulin, with insulin-stimulated production of nitric oxide a feature of the action of insulin on endothelial cells. The role of insulin resistance at the level of the endothelial cell in vascular pathophysiology is unclear. A number of studies in humans and gene-modified mice have demonstrated a close association between insulin resistance and nitric oxide bioactivity. In this review, we discuss the link between insulin resistance and endothelial cell function in humans and demonstrate the complimentary information provided by murine models of obesity and insulin resistance in our understanding of the vasculopathy associated with type 2 diabetes and obesity.

Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species.

Insulin resistance is well established as an independent risk factor for the development of type 2 diabetes and cardiovascular atherosclerosis. Most studies have examined atherogenesis in models of severe insulin resistance or diabetes. However, by the time of diagnosis, individuals with type 2 diabetes already demonstrate a significant atheroma burden. Furthermore, recent studies suggest that, even in adolescence, insulin resistance is a progressive disorder that increases cardiovascular risk. In the present report, we studied early mechanisms of reduction in the bioavailability of the antiatheroscerotic molecule nitric oxide (NO) in very mild insulin resistance. Mice with haploinsufficiency for the insulin receptor (IRKO) are a model of mild insulin resistance with preserved glycemic control. We previously demonstrated that 2-mo-old (Young) IRKO mice have preserved vasorelaxation responses to ACh. This remained the case at 4 mo of age. However, by 6 mo, despite no significant deterioration in glucose homeostasis (Adult), IRKO mice had marked blunting of ACh-mediated vasorelaxation [IRKO maximum contraction response (E(max)) 66 +/- 5% vs. wild type 87 +/- 4%, P < 0.01]. Despite the endothelial dysfunction demonstrated, aortic endothelial nitric oxide synthase (eNOS) mRNA levels were similar in Adult IRKO and wild-type mice, and, interestingly, aortic eNOS protein levels were increased, suggesting a compensatory upregulation in the IRKO. We then examined the potential role of reactive oxygen species in mediating early endothelial dysfunction. The superoxide dismutase mimetic Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) restored ACh relaxation responses in the Adult IRKO (E(max) to ACh with MnTMPyP 85 +/- 5%). Dihydroethidium fluorescence of aortas and isolated coronary microvascular endothelial cells confirmed a substantial increase in endothelium-derived reactive oxygen species in IRKO mice. These data demonstrate that mild insulin resistance is a potent substrate for accelerated endothelial dysfunction and support a role for endothelial cell superoxide production as a mechanism underlying the early reduction in NO bioavailability.

The associations between air quality and the number of hospital admissions for acute pain and sickle-cell disease in an urban environment.

The clinical severity of sickle-cell disease (SCD) is dependent on genetic and environmental variables. Environmental factors have been poorly studied. We have investigated possible links between air pollution and acute pain in SCD. We retrospectively studied the numbers of daily admissions with acute sickle-cell pain to King's College Hospital, London, in relation to local daily air quality measurements. We analysed 1047 admissions over 1400 d (1st January 1998-31st October 2001). Time series analysis was performed using the cross-correlation function (CCF). CCF showed a significant association between increased numbers of admissions and low levels of nitric oxide (NO), low levels of carbon monoxide (CO) and high levels of ozone (O(3)). There was no association with sulphur dioxide (SO(2)), nitrogen dioxide or PM(10) (dust). The significant results were further examined using quartile analysis. This confirmed that high levels of O(3) and low levels of CO were associated with increased numbers of hospital admissions. Low NO levels were also associated with increased admissions but did not reach statistical significance on quartile analysis. Our study suggests air quality has a significant effect on acute pain in SCD and that patients should be counselled accordingly. The potential beneficial effect of CO and NO is intriguing and requires further investigation.

Asymmetric dimethylarginine and reduced nitric oxide bioavailability in young Black African men.

Black Africans have a higher incidence of cardiovascular disease than white Europeans. We explored potential mechanisms of this excess risk by assessing endothelium function, inflammatory status (C-reactive protein), oxidative stress (isoprostane-F2alpha), and plasma asymmetrical dimethyl arginine (ADMA; an endogenous competitive inhibitor of NO synthase) in each ethnic group. Thirty healthy black Africans and 28 well-matched white European male subjects were studied (mean age+/-SE: 32.2+/-0.9 and 29.2+/-1.2 years, respectively; P=0.07). High-resolution ultrasound was used to assess vascular function in the brachial artery by measuring flow mediated dilatation ([percentage of change]; endothelium-dependent function) and glyceryltrinitrate dilatation ([percentage of change]; endothelium-independent function). Blood pressure, fasting lipids, glucose, and estimated glomerular filtration rate levels were similar in both groups. There was no difference in C-reactive protein (black Africans: 0.8+/-0.1 mg/L; white Europeans: 0.6+/-0.1 mg/L; P=0.22), isoprostane-F2alpha (black Africans: 42.9+/-1.5 pg/mL; white Europeans: 39.2+/-1.5 pg/mL; P=0.23), and leptin (black Africans: 64.1+/-10.2 ng/mL; white Europeans: 47.8+/-9.8 ng/mL; P=0.37) levels between the 2 ethnic groups. However, compared with white Europeans, plasma ADMA levels were significantly higher in black Africans (0.34+/-0.02 micromol/L and 0.25+/-0.03 micromol/L; P=0.03). There was no difference in the percentage of glyceryltrinitrate dilatation (P=0.7), but the percentage of flow-mediated dilatation was significantly lower in black Africans (black Africans: 5.2+/-0.3; white Europeans: 6.3+/-0.4; P=0.02). In a stepwise multiple regression model, ADMA level was the only independent determinant of flow-mediated dilatation (P=0.02). In turn, race was the only independent determinant of ADMA levels (P=0.03). Our findings indicate that circulating ADMA levels are significantly higher in healthy black African males than in white European males. This may contribute to the lower NO bioavailability and higher incidence of cardiovascular disease seen in black Africans.

Windy weather and low humidity are associated with an increased number of hospital admissions for acute pain and sickle cell disease in an urban environment with a maritime temperate climate.

Sickle cell disease (SCD) is characterised by intermittent episodes of acute severe pain, related to vaso-occlusion. Environmental factors are thought to play an important role, and studies in tropical countries have suggested that cold and rainy seasons are associated with increased episodes of acute pain. We have studied retrospectively the number of admissions with acute pain and SCD to King's College Hospital, London, together with daily meteorological records collected locally. Data from 1400 d and 1047 separate admissions were analysed. Increased admissions were significantly associated with increased wind speed and low humidity, but showed no relationship to temperature, rainfall or barometric pressure. The strongest effect was for (maximum wind speed)/humidity, with 464 admissions on days in the lowest two quartiles of this parameter and 582 in the highest quartiles. The effect of high wind and low humidity is likely to be related to skin cooling.