Raymond W. Sy

Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies: The SEARCH-AF study

Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be

Arrhythmia characterization and long-term outcomes in catecholaminergic polymorphic ventricular tachycardia.

AUD5,988 (€3,142;

Health care exposure and age in infective endocarditis: results of a contemporary population-based profile of 1536 patients in Australia

USD4,066) per Quality Adjusted Life Year gained and

Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands

AUD30,481 (€15,993;

Incidence and predictors of silent myocardial infarction in type 2 diabetes and the effect of fenofibrate: an analysis from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

Utility of the recovery electrocardiogram after exercise: a novel indicator for the diagnosis and genotyping of long QT syndrome?

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergically induced ventricular tachycardia (VT) associated with syncope and sudden death. OBJECTIVE This study sought to characterize arrhythmias associated with CPVT with respect to provocation by exercise and drugs, electrocardiographic characteristics, and association with long-term outcomes; and to explore the relation between age and clinical presentation. METHODS Seventy patients from 16 families were evaluated with exercise and selective adrenaline challenge, and screened for RyR2 mutations. CPVT was diagnosed in probands with symptoms and stress- or adrenaline-provoked VT, or in asymptomatic relatives with provoked VT or RyR2 mutations. Patients were followed up for recurrent syncope, VT, and sudden death. RESULTS Twenty-seven patients including 16 probands were identified (median age 35 years, 67% female). Presentation was cardiac arrest in 33% and syncope in 56%, and 11% were asymptomatic. Polymorphic or bidirectional VT was provoked with exercise in 63% and adrenaline in 82%. The initiating beat of VT was late-coupled and wide (coupling interval 418 ± 42 ms; QRSd 131 ± 17 ms), and QRS morphology suggested an outflow tract origin in 59%. During follow-up of 6.2 ± 5.7 years, 2 patients died despite an implantable cardioverter-defibrillator (ICD), 4 patients received ICD therapy for VT, and 5 patients had inappropriate therapy for supraventricular tachycardia. Patients presenting with late-onset CPVT (age > 21; n = 10) were often female (80%) and less likely to have RyR2 (Ryanodine receptor type 2) mutations (33%), and fatal events were not observed during follow-up (4.1 ± 3.6 years). CONCLUSION Ventricular arrhythmia in CPVT is often initiated from the outflow tract region. Despite β-blocker therapy and selective ICD implantation, breakthrough arrhythmias occur and may be associated with adverse outcomes.

Survivor Treatment Selection Bias and Outcomes Research A Case Study of Surgery in Infective Endocarditis

AIMS Institutional-based studies of infective endocarditis (IE) are limited by referral bias. Longitudinal population-based data were used to overcome such bias to provide a contemporary profile of IE and specifically investigate the importance of health care-associated IE and age. METHODS AND RESULTS Between 2000 and 2006, 1536 consecutive adult admissions with IE were identified in the Australian state of New South Wales using a state-wide database. The annual incidence was 4.7 per 100 000 (95% CI 4.4-4.9) being highest in patients aged between 80 and 84 years. The most frequent causative organism was Staphylococcus aureus (32%). Surgery was performed in 20% and the 6-month mortality was 18%. During the study period, the median age of patients increased from 61 to 65 years (P = 0.02), but microbiology, surgery, and mortality rates remained stable. Health care-associated IE was identified in 30% and was associated with older age, diabetes, renal impairment, heart failure, and infection with methicillin-resistant Staphylococcus aureus and enterococcus. Even after adjustment for these differences, recent health care exposure was an independent predictor of mortality (hazard ratio 1.62, 95% CI 1.34-1.96). CONCLUSION Contemporary IE contributes to health care-related infection, occurs in an increasingly elderly population, and remains a condition with unacceptably high mortality.

Development and validation of a time-dependent risk model for predicting mortality in infective endocarditis

Background— Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. Methods and Results— Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers. QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers). Mean age was 35±18 years, and resting corrected QT interval (QTc) was 466±39 ms. Abnormal resting QTc (females ≥480 ms; males ≥470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc ≥445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (n=152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc=443±47 ms), sensitivity was 0.92 and specificity was 0.82. Conclusions— A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relatives.

Repolarization dynamics during exercise discriminate between LQT1 and LQT2 genotypes.

AIMS To determine the incidence and predictors of, and effects of fenofibrate on silent myocardial infarction (MI) in a large contemporary cohort of patients with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. METHODS AND RESULTS Routine electrocardiograms taken throughout the study were assessed by Minnesota-code criteria for the presence of new Q-waves without clinical presentation and analysed with blinding to treatment allocation and clinical outcome. Of all MIs, 36.8% were silent. Being male, older age, longer diabetes duration, prior cardiovascular disease (CVD), neuropathy, higher HbA(1c), albuminuria, high serum creatinine, and insulin use all significantly predicted risk of clinical or silent MI. Fenofibrate reduced MI (clinical or silent) by 19% [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.94; P = 0.006], non-fatal clinical MI by 24% (P = 0.01), and silent MI by 16% (P = 0.16). Among those having silent MI, fenofibrate reduced subsequent clinical CVD events by 78% (HR 0.22, 95% CI 0.08-0.65; P = 0.003). CONCLUSION Silent and clinical MI have similar risk factors and increase the risk of future CVD events. Fenofibrate reduces the risk of a first MI and substantially reduces the risk of further clinical CVD events after silent MI, supporting its use in type 2 diabetes.

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital cardiac disease

BACKGROUND Exercise testing has shown modest utility in the ability to diagnose and genotype long QT syndrome (LQTS). Although numerous small studies have shown a genotype-specific repolarization response to exercise, the repolarization responses during recovery from exercise have received less focus. OBJECTIVE The purpose of this study was to characterize genotype-specific QT responses during recovery from exercise and to determine its potential as a diagnostic and genotyping tool. METHODS Seventy-five patients were age and sex matched into three groups (n = 25): LQT1, LQT2, and unaffected controls based on Schwartz score and genetic testing results. Each group underwent upright burst and gradual bicycle exercise testing while being monitored by 12-lead electrocardiogram. RESULTS LQT1 patients had significantly longer corrected QT (QTc) than LQT2 intervals during early recovery (P <.01). Control subjects showed little variation in QTc throughout the recovery period, maintaining a QTc within normal limits. Each group showed a distinct pattern of QTc adaptation during recovery. LQT1 patients began the recovery period at a QTc of 492 +/- 11 ms, after which the QTc decreased by 33 +/- 11 ms during recovery. Conversely, the LQT2 patients began recovery at its lowest mean QTc of 420 +/- 10 ms, which increased by 40 +/- 16 ms. At the end of recovery, a QTc cut-off value of 445 ms distinguished 92% of LQTS patients from unaffected controls, while a start-of-recovery QTc cut-off of 460 ms correctly identified genotype in 80% of LQT1 and 92% of LQT2 patients. CONCLUSIONS Genotype-specific differences exist in QT recovery after exercise. These differences can help to identify LQTS patients and distinguish LQT1 from LQT2 genotypes.