Calum J. Redpath

The Short QT Syndrome : Proposed Diagnostic Criteria

OBJECTIVES We aimed to develop diagnostic criteria for the short QT syndrome (SQTS) to facilitate clinical evaluation of suspected cases. BACKGROUND The SQTS is a cardiac channelopathy associated with atrial fibrillation and sudden cardiac death. Ten years after its original description, a consensus regarding an appropriate QT interval cutoff and specific diagnostic criteria have yet to be established. METHODS The MEDLINE database was searched for all reported cases of SQTS in the English language, and all relevant data were extracted. The distribution of QT intervals and electrocardiographic (ECG) features in affected cases were analyzed and compared to data derived from ECG analysis from general population studies. RESULTS A total of 61 reported cases of SQTS were identified. Index events, including sudden cardiac death, aborted cardiac arrest, syncope, and/or atrial fibrillation occurred in 35 of 61 (57.4%) cases. The cohort was predominantly male (75.4%) and had a mean QT(c) value of 306.7 ms with values ranging from 248 to 381 ms in symptomatic cases. In reference to the ECG characteristics of the general population, and in consideration of clinical presentation, family history, and genetic findings, a highly sensitive diagnostic scoring system was developed. CONCLUSIONS Based on a comprehensive review of 61 reported cases of the SQTS, formal diagnostic criteria have been proposed that will facilitate diagnostic evaluation in suspected cases of SQTS. Diagnostic criteria may lead to a greater recognition of this condition and provoke screening of at-risk family members.

Clinical ResearchHeart Rhythm DisorderThe Short QT Syndrome: Proposed Diagnostic Criteria

OBJECTIVES We aimed to develop diagnostic criteria for the short QT syndrome (SQTS) to facilitate clinical evaluation of suspected cases. BACKGROUND The SQTS is a cardiac channelopathy associated with atrial fibrillation and sudden cardiac death. Ten years after its original description, a consensus regarding an appropriate QT interval cutoff and specific diagnostic criteria have yet to be established. METHODS The MEDLINE database was searched for all reported cases of SQTS in the English language, and all relevant data were extracted. The distribution of QT intervals and electrocardiographic (ECG) features in affected cases were analyzed and compared to data derived from ECG analysis from general population studies. RESULTS A total of 61 reported cases of SQTS were identified. Index events, including sudden cardiac death, aborted cardiac arrest, syncope, and/or atrial fibrillation occurred in 35 of 61 (57.4%) cases. The cohort was predominantly male (75.4%) and had a mean QT(c) value of 306.7 ms with values ranging from 248 to 381 ms in symptomatic cases. In reference to the ECG characteristics of the general population, and in consideration of clinical presentation, family history, and genetic findings, a highly sensitive diagnostic scoring system was developed. CONCLUSIONS Based on a comprehensive review of 61 reported cases of the SQTS, formal diagnostic criteria have been proposed that will facilitate diagnostic evaluation in suspected cases of SQTS. Diagnostic criteria may lead to a greater recognition of this condition and provoke screening of at-risk family members.

Atrioesophageal Fistula in the Era of Atrial Fibrillation Ablation: A Review

The purpose of this review is to understand the epidemiology, clinical features, etiopathogenesis, and management of atrioesophageal fistula (AEF) after atrial fibrillation (AF) ablation. The incidence of AEF after AF ablation is 0.015%-0.04%. The principal clinical features include fever, dysphagia, upper gastrointestinal bleeding, sepsis, and embolic strokes. The close proximity of the esophagus to the posterior left atrial wall is responsible for esophageal injury during ablation. Prophylactic proton pump inhibitors, esophageal temperature monitoring, visualization of the esophagus during catheter ablation, esophageal protection devices, and avoidance of energy delivery in close proximity to the esophagus play an important role in preventing esophageal injury. Early surgical repair or esophageal stenting are the mainstay of treatment. Eliminating esophageal injury during AF ablation is of utmost importance in preventing AEF. A high index of suspicion and early intervention is necessary to prevent fatal outcomes.

Prevalence of Cardiac Sarcoidosis in Patients Presenting with Monomorphic Ventricular Tachycardia

Sarcoidosis is a granulomatous disease of unknown etiology, which involves the heart in 5–25% of cases. Although ventricular tachycardia (VT) has been reported as the first presentation of sarcoidosis, its prevalence has not previously been investigated. In this prospective study, we sought to systematically investigate the prevalence of cardiac sarcoidosis (CS) in patients presenting with monomorphic VT (MMVT) and no previous history of sarcoidosis.

Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging in the Diagnosis of Cardiac Implantable Electronic Device InfectionCLINICAL PERSPECTIVE: A Systematic Review and Meta-Analysis

Background— The use of cardiac implantable electronic devices (CIED) is increasing, and their associated infections result in significant morbidity and mortality. The introduction of better cardiac imaging techniques could be useful for diagnosing this condition and guiding therapy. Our objective was to systematically assess the diagnostic accuracy of Fluor-18-fluorodeoxyglucose positron emission tomography and computed tomography, labeled leukocyte scintigraphy (LS), and Gallium-67 citrate scintigraphy for the diagnosis of CIED infection. Methods and Results— A systematic review of the literature and meta-analysis on the use of all 3 modalities in CIED infection were conducted. Pooled sensitivity, specificity, and summary receiver operating characteristic curves of each imaging modalities were determined. The literature search identified 2493 articles. A total of 13 articles (11 studies for 18F-FDG PET-CT and 2 for LS), met the inclusion criteria. No studies for 67Ga citrate scintigraphy met the inclusion criteria. The pooled sensitivity of 18F-FDG PET-CT for the diagnosis of CIED infection was 87% (95% CI, 82%–91%) and pooled specificity was 94% (95% CI, 88%–98%). The summary receiver operating characteristic curve analysis demonstrated good overall accuracy, with an area under the curve of 0.935. There were insufficient data to do a meta-analysis for LS, but both studies reported sensitivity above 90% and specificity of 100%. Conclusions— Both 18F-FDG PET-CT and LS yield high sensitivity, specificity, and accuracy, and thus seem to be useful for the diagnosis of CIED infection, based on robust data for 18F-FDG PET-CT but limited data for LS. When available,18F-FDG PET-CT may be preferred.

Mitochondrial Hyperfusion during Oxidative Stress Is Coupled to a Dysregulation in Calcium Handling within a C2C12 Cell Model

Atrial Fibrillation is the most common sustained cardiac arrhythmia worldwide harming millions of people every year. Atrial Fibrillation (AF) abruptly induces rapid conduction between atrial myocytes which is associated with oxidative stress and abnormal calcium handling. Unfortunately this new equilibrium promotes perpetuation of the arrhythmia. Recently, in addition to being the major source of oxidative stress within cells, mitochondria have been observed to fuse, forming mitochondrial networks and attach to intracellular calcium stores in response to cellular stress. We sought to identify a potential role for rapid stimulation, oxidative stress and mitochondrial hyperfusion in acute changes to myocyte calcium handling. In addition we hoped to link altered calcium handling to increased sarcoplasmic reticulum (SR)-mitochondrial contacts, the so-called mitochondrial associated membrane (MAM). We selected the C2C12 murine myotube model as it has previously been successfully used to investigate mitochondrial dynamics and has a myofibrillar system similar to atrial myocytes. We observed that rapid stimulation of C2C12 cells resulted in mitochondrial hyperfusion and increased mitochondrial colocalisation with calcium stores. Inhibition of mitochondrial fission by transfection of mutant DRP1K38E resulted in similar effects on mitochondrial fusion, SR colocalisation and altered calcium handling. Interestingly the effects of ‘forced fusion’ were reversed by co-incubation with the reducing agent N-Acetyl cysteine (NAC). Subsequently we demonstrated that oxidative stress resulted in similar reversible increases in mitochondrial fusion, SR-colocalisation and altered calcium handling. Finally, we believe we have identified that myocyte calcium handling is reliant on baseline levels of reactive oxygen species as co-incubation with NAC both reversed and retarded myocyte response to caffeine induced calcium release and re-uptake. Based on these results we conclude that the coordinate regulation of mitochondrial fusion and MAM contacts may form a point source for stress-induced arrhythmogenesis. We believe that the MAM merits further investigation as a therapeutic target in AF-induced remodelling.

Rapid genetic testing facilitating the diagnosis of short QT syndrome

Short QT syndrome (SQTS) is a rare genetic disease with a risk of sudden cardiac death. The present report describes syncope in a young man that resulted in a motor vehicle accident. An electrocardiogram and initial investigations were unremarkable, but treadmill testing showed a lack of adaptation of the QT interval, which has been described in SQTS. To evaluate the possible diagnosis of SQTS, DNA sequencing of genes known to be associated with SQTS was performed and identified a novel mutation in the KCNH2 gene. Consequently, the patient was diagnosed with SQTS and the recommendation of implantable cardioverter defibrillator implantation was accepted by the patient before discharge from the hospital.

Myocardial Injury Secondary to ICD Shocks: Insights from Patients with Lead Fracture

Patients who receive appropriate implantable cardioverter defibrillator (ICD) shocks have a subsequent adverse prognosis. Most data suggest that patients with inappropriate ICD shocks also have a subsequent adverse prognosis, although this is more controversial. The shocks may be an epiphenomenon, that is, a marker of underlying disease progression; however, it cannot be excluded that shocks cause direct myocardial damage. This latter question is difficult to clarify as the arrhythmia provoking the shock can also cause troponin release. Inappropriate shocks secondary to lead fracture are an ideal situation to examine this question; any troponin release in an otherwise well and hemodynamically stable patient, is likely due directly to the shocks.

Greater response to cardiac resynchronization therapy in patients with true complete left bundle branch block: a PREDICT substudy

AIMS Cardiac resynchronization therapy (CRT) benefits patients with heart failure and a wide QRS complex. Still, one-third derive no clinical benefit and a majority of patients demonstrate no objective improvement of left ventricular (LV) function. Left bundle branch block (LBBB) is a strong predictor of response to CRT. We evaluated whether absence of electrocardiogram (ECG) markers of residual left bundle (LB) conduction in guideline-defined LBBB predicted a greater response to CRT. METHODS AND RESULTS An r wave ≥1 mm in lead V1 (r-V1) and/or a q wave ≥1 mm in lead aVL (q-aVL) was used to identify patients with residual LB conduction. Forty patients with a wide QRS were prospectively enrolled and subdivided into three groups: complete LBBB (cLBBB), LBBB without r-V1 or q-aVL (n = 12); LBBB with residual LB conduction (rLBBB), LBBB with r-V1 and/or q-aVL (n = 15); and non-specific intraventricular conduction delay (IVCD), (n = 13). Following CRT: mean change in left ventricular ejection fraction was 11.9 ± 11.9% in cLBBB, 3.8 ± 5.4% in rLBBB (P= 0.045), and 2.5 ± 4.4% in IVCD (P= 0.02 cLBBB vs. IVCD); mean reduction in left ventricular end-systolic volume was 26.4 ± 39.2% in cLBBB, 14.3 ± 22.9% in rLBBB (P= 0.35), and 5.6 ± 17.3% in IVCD (P= 0.11 cLBBB vs. IVCD); mean change in native QRS duration was -8.0 ± 11.0 ms in cLBBB, -0.8 ± 8.24 ms in rLBBB (P= 0.07), and 0.15 ± 8.0 ms in IVCD (P= 0.048 cLBBB vs. IVCD). CONCLUSION In patients with guideline-defined LBBB, the absence of ECG markers of residual LB conduction was predictive of a greater improvement in LV function with CRT.

In-hospital mortality in 13,263 survivors of out-of-hospital cardiac arrest in Canada

BACKGROUND There is a substantial mortality rate in patients admitted alive after out-of-hospital cardiac arrest. The primary objective of our study was to examine trends in in-hospital survival in out-of-hospital cardiac arrest survivors in Canada between 1994 and 2004. The secondary objective was to examine predictors of in-hospital survival in these patients. METHODS Data on hospital admissions from April 1, 1994, to March 31, 2004, were obtained from the Health Person-oriented Information Database, maintained by Statistics Canada. We included all patients with a primary diagnosis of cardiac arrest who survived to hospital admission. We assessed survival to hospital discharge in all patients admitted alive. RESULTS In Canada, 13,263 patients survived community arrest between 1994 and 2004. The annual incidence of hospital admission after out-of-hospital cardiac arrest decreased by 33%, from 5.37 per 100,000 in 1994 to 3.63 per 100,000 in 2004 (P < .0001 for trend). Subsequently, 5,045 patients (38.03%) survived to hospital discharge. The survival rate did not change during the duration of the study. Invasive coronary artery disease management was associated with a greatly increased chance of survival (odds ratio 21.98, 95% CI 17.62-27.42). Also male gender, heart failure, and acute myocardial ischemia were independent positive predictors of survival to hospital discharge; greater age and comorbidities were negative predictors of survival. Finally, there were significant interprovincial variations in survival rates. CONCLUSIONS Our study, the largest of its kind, has 4 main findings. Firstly, between 1993 and 2004, there was a significant and steady decline in admission rates after community cardiac arrest. Second, there was no change in the in-hospital survival rates. Thirdly, invasive management of coronary artery disease was associated with a greatly improved chance of survival, and finally, there were important regional variations in survival rates.