M. Sarah Rose

Microvascular Function Predicts Cardiovascular Events in Primary Prevention Long-Term Results From the Firefighters and Their Endothelium (FATE) Study

Background— Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men. Methods and Results— The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24). Conclusions— In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.

Atrial Pacing Periablation for Prevention of Paroxysmal Atrial Fibrillation

BACKGROUND This study tested the hypothesis that rate-adaptive atrial pacing would prevent paroxysmal atrial fibrillation (PAF) in patients with frequent PAF in the absence of symptomatic bradycardia. METHODS AND RESULTS Patients (n=97) with antiarrhythmic drug-refractory PAF received a Medtronic Thera DR pacemaker 3 months before planned AV node ablation. Patients were randomized to no pacing (n=48) or to atrial rate-adaptive pacing (n=49). After a 2-week stabilization period, patients were followed up for an additional 10 weeks. The time to first recurrence of sustained PAF, the interval between successive episodes of PAF, and the frequency of PAF were compared between the 2 groups in intention-to-treat analysis. Time to first episode of sustained PAF was similar in the no-pacing (4.2 days; 95% CI, 1.8 to 9.5) and the atrial-pacing (1.9 days; 95% CI, 0.8 to 4.6; P=NS) groups. PAF burden was lower in the no-pacing (0.24 h/d; 95% CI, 0.10 to 0.56) than in the atrial-pacing (0.67 h/d; 95% CI, 0.30 to 1.52; P=0.08) group. Paired crossover analysis in 11 patients revealed that time to first PAF was shorter during atrial pacing (1.6 days; 95% CI, 0.6 to 4.9) than with no pacing (6.0 days; 95% CI, 2.4 to 15.0; P=0.13), and PAF burden was greater during atrial pacing (1.00 h/d; 95% CI, 0.35 to 2.91) than with no pacing (0.32 h/d; 95% CI, 0.09 to 1.13; P<0.016). CONCLUSIONS Atrial rate-adaptive pacing does not prevent PAF over the short term in patients with antiarrhythmic drug-resistant PAF without symptomatic bradycardia.

The relationship between health-related quality of life and frequency of spells in patients with syncope

Chronic syncope has a wide range of symptom burden, and anecdotal data suggest substantial but variable physical and psychosocial morbidity. We hypothesized that health-related quality of life (HRQL) is impaired in syncope patients and the degree of impairment is proportional to syncope frequency. The EuroQol EQ-5D was completed by 136 patients (79 female and 57 male) with mean age 40 (SD = 17) prior to assessment. HRQL was substantially impaired in syncope patients compared to population norms in all five dimensions of health measured by the EQ-5D. In patients with six or more lifetime syncopal spells there was a significant (P < 0.001) negative relationship between the frequency of spells and overall perception of health, which was not evident in those who had a history of less than six lifetime spells. These relationships were maintained after controlling for comorbid conditions.

Randomized Crossover Comparison of DDDR Versus VDD Pacing After Atrioventricular Junction Ablation for Prevention of Atrial Fibrillation

BACKGROUND Some clinical data suggest that atrial-based pacing prevents paroxysmal atrial fibrillation (AF). This study tested the hypothesis that DDDR pacing compared with VDD pacing prevents AF after atrioventricular (AV) junction ablation. METHODS AND RESULTS Patients were randomized to DDDR pacing (n=33) or to VDD pacing (n=34) after AV junction ablation and followed every 2 months for 6 months. Patients then crossed over to the alternate pacing mode and were followed for an additional 6 months. Primary analysis included the time to first recurrence of sustained AF (duration >5 minutes), total AF burden, and the development of permanent AF. The time to first episode of AF was similar in the DDDR group (0.37 days, 95% CI 0.1 to 1.3 days) and the VDD pacing group (0.5 days, 95% CI 0.2 to 1.7 days, P=NS). AF burden increased over time in both groups (P<0.01). At the 6-month follow-up, AF burden was 6.93 h/d (95% CI 4. 37 to 10.96 h/d) in the DDDR group and 6.30 h/d (95% CI 3.99 to 9.94 h/d) in the VDD group (P=NS). Twelve (35%) patients in the DDDR group and 11 (32%) patients in the VDD group had permanent AF within 6 months of ablation. Within 1 year of follow-up, 43% of patients had permanent AF. CONCLUSIONS DDDR pacing compared with VDD pacing does not prevent paroxysmal AF over the long term in patients in the absence of antiarrhythmic drug therapy after total AV junction ablation. Many patients have permanent AF within the first year after ablation.

Validation of a New Simple Scale to Measure Symptoms in Atrial Fibrillation The Canadian Cardiovascular Society Severity in Atrial Fibrillation Scale

Background— Atrial fibrillation (AF) is commonly associated with impaired quality of life. There is no simple validated scale to quantify the functional illness burden of AF. The Canadian Cardiovascular Society Severity in Atrial Fibrillation (CCS-SAF) scale is a bedside scale that ranges from class 0 to 4, from no effect on functional quality of life to a severe effect on life quality. This study was performed to validate the scale. Methods and Results— In 484 patients with documented AF (62.2±12.5 years of age, 67% men; 62% paroxysmal and 38% persistent/permanent), the SAF class was assessed and 2 validated quality-of-life questionnaires were administered: the SF-36 generic scale and the disease-specific AFSS (University of Toronto Atrial Fibrillation Severity Scale). There is a significant linear graded correlation between the SAF class and measures of symptom severity, physical and emotional components of quality of life, general well-being, and health care consumption related to AF. Patients with SAF class 0 had age- and sex-standardized SF-36 scores of 0.15±0.16 and −0.04±0.31 (SD units), that is, units away from the mean population score for the mental and physical summary scores, respectively. For each unit increase in SAF class, there is a 0.36 and 0.40 SD unit decrease in the SF-36 score for the physical and mental components. As the SAF class increases from 0 to 4, the symptom severity score (range, 0 to 35) increases from 4.2±5.0 to 18.4±7.8 ( P <0.0001). Conclusions— The CCS-SAF scale is a simple semiquantitative scale that closely approximates patient-reported subjective measures of quality of life in AF and may be practical for clinical use. Received August 1, 2008; accepted January 14, 2009.Background—Atrial fibrillation (AF) is commonly associated with impaired quality of life. There is no simple validated scale to quantify the functional illness burden of AF. The Canadian Cardiovascular Society Severity in Atrial Fibrillation (CCS-SAF) scale is a bedside scale that ranges from class 0 to 4, from no effect on functional quality of life to a severe effect on life quality. This study was performed to validate the scale. Methods and Results—In 484 patients with documented AF (62.2±12.5 years of age, 67% men; 62% paroxysmal and 38% persistent/permanent), the SAF class was assessed and 2 validated quality-of-life questionnaires were administered: the SF-36 generic scale and the disease-specific AFSS (University of Toronto Atrial Fibrillation Severity Scale). There is a significant linear graded correlation between the SAF class and measures of symptom severity, physical and emotional components of quality of life, general well-being, and health care consumption related to AF. Patients with SAF class 0 had age- and sex-standardized SF-36 scores of 0.15±0.16 and −0.04±0.31 (SD units), that is, units away from the mean population score for the mental and physical summary scores, respectively. For each unit increase in SAF class, there is a 0.36 and 0.40 SD unit decrease in the SF-36 score for the physical and mental components. As the SAF class increases from 0 to 4, the symptom severity score (range, 0 to 35) increases from 4.2±5.0 to 18.4±7.8 (P<0.0001). Conclusions—The CCS-SAF scale is a simple semiquantitative scale that closely approximates patient-reported subjective measures of quality of life in AF and may be practical for clinical use.

Adolescent Attachment Questionnaire: A Brief Assessment of Attachment in Adolescence.

The Adolescent Attachment Questionnaire (AAQ), a brief questionnaire to assess attachment characteristics in adolescents, was developed and validated in a large normative sample (n = 691) and a sample of 133 adolescents in psychiatric treatment. The AAQ is a self-report questionnaire consisting of 3 scales of 3 statements each, with Likert-type responses from strongly disagree to strongly agree. The Availability scale assesses the adolescents confidence in the availability and responsiveness of the attachment figure. TheGoal-Corrected Partnershipscale assesses the extent to which the adolescent considers and is empathetic to the needs and feelings of the attachment figure. The Angry Distress scale taps the amount of anger in the adolescent–parent relationship. All scales demonstrate satisfactory internal reliability and agreement between scores for adolescents (n = 91) from the normative sample who completed the AAQ twice. Adolescents in the clinical sample also completed the Adult Attachment Interview (AAI); the AAQ demonstrated high convergent validity with the AAI.

Temporal Patterns of Paroxysmal Atrial Fibrillation Following DDDR Pacemaker Implantation

Paroxysmal atrial fibrillation (AF) episodes have been reported to be randomly distributed. However, because patients are not always symptomatic, it has been difficult to study temporal patterns of AF. Newer implantable pulse generators have data-logging capabilities that permit the detection and analysis of temporal patterns of AF. This study tested the hypothesis that AF episodes occur in clusters over time and that these episodes are not randomly distributed in individual patients. The date and time of 582 episodes of AF were recorded from the data logs of 16 patients with a Medtronic Thera DR followed 6 weeks and 6 and 12 months after pulse generator implant. The probability of AF recurrence and the interevent intervals between successive episodes of AF were fitted to monoexponential and Weibull distributions. A Weibull distribution best described the nonrandom distribution of AF for 67% of follow-up visits. Temporal clustering of AF (interevent intervals <24 hours) declined during follow-up (95 +/- 10%, 90 +/- 11%, and 74 +/- 28% at the 6-week and 6- and 12-month visits, respectively; p <0.05). The average duration of an episode of AF tended to increase over time (0.31 hour, 95% confidence intervals [CI] 0.17 to 0.58 hours; 0.36 hours, 95% CI 0. 17 to 0.78 hours; 0.65 hours, 95% CI 0.29 to 1.45 hours [p = 0.07] at the 6-week and 6- and 12-month visits, respectively). Paroxysmal AF recurrence is nonrandomly distributed over the long term in many patients. The temporal patterns of AF change over time after pacemaker implantation. This has implications for the selection of study end points in AF clinical trials.

Age-dependent effect of β-blockers in preventing vasovagal syncope.

Background—&bgr;-blockers have little effectiveness in preventing vasovagal syncope in unselected populations, but they might be effective in older patients. We determined whether &bgr;-blockers prevent vasovagal syncope in an age-related fashion. Methods and Results—Two populations were studied. A proportional hazards analysis was performed on an observational cohort study of 153 patients with vasovagal syncope, 52 of whom received &bgr;-blockers. A multivariable proportional hazards model stratified by center was performed on 208 participants in the randomized Prevention of Syncope Trial (POST), examining the interaction between age group and treatment with metoprolol. Age-specific hazard ratios were estimated for both studies and combined using the inverse variance meta-analytic method. In the cohort study, the hazard ratio for syncope if treated with &bgr;-blockers was 1.54 (95% CI, 0.78–3.05) for patients aged <42 years and 0.48 (95% CI, 0.12–1.92) for patients aged ≥42 years. In POST, the proportional hazards model showed interactions between age and treatment effect (P=0.026). The hazard ratio for patients aged ≥42 years who received metoprolol was 0.53 (95% CI, 0.25–1.10); in patients aged <42 years, the hazard ratio was 1.62 (95% CI, 0.85–3.10). A pooled analysis of both studies yielded an estimate of the hazard ratio of 1.58 (CI, 1.00–2.31) for patients aged <42 years, and the hazard ratio was 0.52 (CI, 0.27–1.01) for patients aged ≥42 years. The 2 age groups differed significantly in response to &bgr;-blockers (P=0.007). Conclusions—&bgr;-blocker treatment may suppress vasovagal syncope in middle-aged patients aged >42 years.

Distribution of Patients′ Paroxysmal Atrial Tachyarrhythmia Episodes: Implications for Detection of Treatment Efficacy

Distribution of Paroxysmal Atrial Tachyarrhythmia Episodes. Introduction: Clinical trials of treatments for paroxysmal atrial tachyarrhythmia (pAT) often compare different treatment groups using the time to first episode recurrence. This approach assumes that the time to the first recurrence is representative of all times between successive episodes in a given patient. We subjected this assumption to an empiric test.

The relationship between chinook conditions and women's illness-related behaviours

The objective of this study was to (1) to describe the relationship between chinook conditions and illness related behaviour in women, aged 20–49 years, and (2) to examine the possibility of the existence of subgroups of chinook-sensitive women. At present no empirical evidence is available regarding a relationship between chinook conditions and illness related behaviours. This study comprises the secondary analysis of a large survery of various health and health-related factors of urban women aged 20–49 years, carried out in 1985–1986 in Calgary. The interview date was used to link behaviours to chinook conditions. We found no evidence of a significant relationship between the behaviours investigated and chinook conditions in the general population. However, the data strongly supported the concept of chinook sensitivity. Women with a history of chronic health problems were more likely to visit a health care professional on chinook days than healthy women and women in the subgroup aged less than 35 years cut down their usual daily activities during chinook conditions. Women with a history of recurring migraine headaches were less likely to take prescription medication on chinook days, and women with a history of emotional disorders were more likely to have higher scores on the accident scale and to report bursts of energy or excitement during chinook days. More research is needed to identify subgroups of susceptible persons, as well as to determine whether chinook sensitive persons are equally susceptible to weather changer of other types.