Relationship Between Left Ventricular Strain Assessment by Cardiac Magnetic Resonance Imaging and Response to Cardiac Resynchronization Therapy.

Although cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction, 30 to 50% patients are non-responders. In this retrospective single-centre study, 19 patients underwent cardiac MRI pre-CRT, and global left ventricular (LV) strain and late gadolinium enhancement (LGE) were measured by a blinded reader. LV reverse remodeling was independently assessed using transthoracic echocardiogram before and after CRT implant. Both LV strain and extent of LGE correlated significantly with measures of reverse LV remodeling (reduction in LV volume and improvement in LV ejection fraction). These findings suggest that CMR derived strain analysis and scar evaluation may be useful preimplant predictors of response to CRT. Larger prospective multi-center studies are needed to confirm these findings and to further evaluate the role of CMR strain imaging in guiding CRT treatment decisions.

Microvolt QRS Alternans Without Microvolt T-Wave Alternans in Human Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias.

Background Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T-wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes. Methods and Results Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12-lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128-beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signal:noise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV, P<0.01) and proportion of TWA+ studies (16% versus 46%, P<0.01) increased with rate, QRSA did not change. QRS duration was longer in QRSA+ than QRSA-negative patients (138±23 versus 113±26 ms, P<0.01). At 3.5 years follow-up, appropriate defibrillator therapy or sustained ventricular tachyarrhythmia was greater in QRSA+ than QRSA-negative patients (30% versus 8%, P=0.02) but similar in TWA+ and TWA-negative patients. Among QRSA+ patients, the event rate was greater in those without TWA (62% versus 21%, P=0.02). Multivariable Cox analysis revealed QRSA+ (hazard ratio [HR], 4.6; 95% CI, 1.5-14; P=0.009) and QRS duration >120 ms (HR, 4.1; 95% CI, 1.3-12; P=0.014) to predict events. Conclusions Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation. QRSA increases the risk of ventricular tachyarrhythmia 4-fold, which merits further study as a risk stratifier.

Quantification of abnormal QRS peaks predicts response to cardiac resynchronization therapy and tracks structural remodeling.

BACKGROUND: Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response. METHODS: Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT. RESULTS: Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ≥150ms, QRSp ≥7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ≥7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). CONCLUSIONS: Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.

Unexpected High Prevalence of Cardiovascular Disease Risk Factors and Psychiatric Disease Among Young People With Sudden Cardiac Arrest.

Background It is believed that most sudden cardiac arrests ( SCA s) in young people occur in previously healthy people with rare risk factors for sudden death. Few studies have investigated large populations with complete ascertainment. Our objective was to use multisource records to identify and classify all out-of-hospital cardiac arrests in the Greater Toronto Area (population 6.6 million) in people aged 2 to 45 years from 2009 to 2012. Methods and Results Expert reviewers employed a systematic process, with emergency medical services, in-hospital and coroner records, to adjudicate the cause of death as SCA from cardiac or noncardiac causes. We report the adjudicated etiologies, circumstances, triggers, and characteristics of the SCA cohort. Of 2937 eligible out-of-hospital cardiac arrest cases, 608 (20.7%) SCA s had an adjudicated etiology of cardiac cause (120 survivors and 488 nonsurvivors). Two thirds of these SCA patients had a history of cardiovascular disease, and over 50% had been diagnosed with ≥1 cardiovascular disease risk factor. Moreover, 20.1% of SCA s were diagnosed with psychiatric disease and 30% had central nervous system drugs prescribed. Over 30% of SCA patients had central nervous system active drugs, including drugs of abuse detected postmortem, with opioids and ethanol being detected most frequently. Potentially heritable structural cardiac diseases accounted for only 6.9% of SCA events, with acquired cardiac diseases comprising the rest. Conclusions The underlying causes of SCA , in people aged 2 to 45 years, often occur in those with previously diagnosed cardiovascular diseases, and are associated with contributory factors including prescribed medications, recreational drugs, and a concomitant psychiatric history.

Automated Quantification of Low-Amplitude Abnormal QRS Peaks From High-Resolution ECG Recordings Predicts Arrhythmic Events in Patients With Cardiomyopathy.

BACKGROUND: Cardiomyopathy patients are at risk of sudden death, typically from scar-related abnormalities of electrical activation that promote ventricular tachyarrhythmias. Abnormal intra-QRS peaks may provide a measure of altered activation. We hypothesized that quantification of such QRS peaks (QRSp) in high-resolution ECGs would predict arrhythmic events in implantable cardioverter-defibrillator (ICD)-eligible cardiomyopathy patients. METHODS AND RESULTS: Ninety-nine patients with ischemic or non-ischemic dilated cardiomyopathy undergoing prophylactic ICD implantation were prospectively enrolled (age 62±11 years, left ventricular ejection fraction 27±7%). High-resolution (1024 Hz) digital 12-lead ECGs were recorded during intrinsic rhythm. QRSp was quantified for each precordial lead as the total number of low-amplitude deflections that deviated from their respective naive QRS template. The primary end point of arrhythmic events was defined as appropriate ICD therapy or sustained ventricular tachyarrhythmias. After a median follow-up of 24 (15-43) months, 20 (20%) patients had arrhythmic events. Both QRSp and QRS duration were greater in those with arrhythmic events (both P<0.001) and this was consistent for QRSp for both cardiomyopathy types. In a multivariable Cox regression model that included age, left ventricular ejection fraction, QRS duration, and QRSp, only QRSp was an independent predictor of arrhythmic events (hazard ratio, 2.1; P<0.001). Receiver operating characteristic analysis revealed that a QRSp ≥2.25 identified arrhythmic events with greater sensitivity (100% versus 70%, P<0.05) and negative predictive value (100% versus 89%, P<0.05) than QRS duration ≥120 ms. CONCLUSIONS: QRSp measured from high-resolution digital 12-lead ECGs independently predicts ventricular tachyarrhythmias in ICD-eligible cardiomyopathy patients. This novel QRS morphology index has the potential to improve sudden death risk stratification and patient selection for prophylactic ICD therapy.

"Presumed cardiac" arrest in children and young adults: A misnomer?

AIM: To use a novel methodology to assess the incidence and specific causes of Out-of-Hospital Cardiac Arrest (OHCA) within a young urban cohort. METHODS: All EMS attended OHCA patients in a large urban area, between 2009 and 2012, aged 2-45 years, treated or untreated, who died or survived, and that were designated as "no obvious cause" etiology by trained data abstractors were included. Using multisource (medical and coroner) records, an expert panel adjudicated the causes of the OHCAs as: confirmed cardiac causes, confirmed non- cardiac causes, and other causes. RESULTS: Of a total of 1993 cases EMS designated as "no obvious cause", only 29.9% (595/1993) were due to confirmed cardiac causes; the rest were due to other causes (non-cardiac etiologies): confirmed drug overdose (n=624), trauma (n=108), cancer (n=69), complex chronic care (n=65) and non-cardiac acute illness - mostly vascular, infectious, and metabolic (n=376). The annual incidence rate of "no obvious cause" OHCAs after initial field classification was 12.97/100,000 pt. years (95% CI 12.40, 13.50), compared to 3.87/100,000 pt. years (95% CI 3.56, 4.18) for the confirmed cardiac OHCAs after adjudication. The predominant underlying etiologies of confirmed cardiac OHCAs were coronary heart disease and structural heart disease. CONCLUSIONS: In young adults with OHCA, confirmed cardiac causes were responsible in a minority of cases, and they differed in presentation from those with confirmed non- cardiac causes. Establishing rigorous case ascertainment strategies with linkage to multiple data sources will facilitate a more reliable evaluation of the causes of these events.

Pseudo-ventricular tachycardia mimicking malignant arrhythmia in a patient with rapid atrial fibrillation.

Artifacts can simulate arrhythmias such as atrial flutter, atrial fibrillation, and ventricular tachycardia. A case of pseudo-ventricular tachycardia is outlined in a patient with newly diagnosed atrial fibrillation, which made the diagnosis a special challenge. Characteristic signs of pseudo-ventricular tachycardia are described. This case reinforces the importance of recognizing artifacts to avoid unnecessary interventions, especially in the telemetry and critical care units.

Lack of difference in T wave variability between patients at risk of sudden cardiac death and healthy subjects.

BACKGROUND: T wave variability (Tvar) is a proposed method to predict sudden cardiac death (SCD). The purpose of this trial was to evaluate the reproducibility of Tvar measurements over time and demonstrate a difference in Tvar between patient populations at risk for ventricular arrhythmias and healthy subjects. METHODS: Sixty subjects were enrolled in into 3 groups: healthy subjects (Population I), patients at high risk of SCD (Population II), and patients with a recent ventricular tachyarrhythmia event (Population III). Recording and analysis of T wave amplitude variance (TAV) as a measure of Tvar was performed at baseline and 3 months. RESULTS: TAV could not be interpreted in 12 of 43 patients in Populations II and III due to PVCs or noise. No subject had a TAV value suggestive of high risk of SCD as per a previously defined cutoff of >59 µV. Median (range) values of TAV in µV at baseline for Populations I, II and III were 26 (15-39), 21 (13-43), and 24 (18-41), respectively (p = 0.39). TAV was reproducible within population's from baseline to 3 months (p = 0.27, 0.53, 0.17 for Populations I, II and III, respectively). There was no significant difference between TAV values of high risk patients and healthy subjects. CONCLUSION: Tvar was reproducible primarily in patients with left ventricular dysfunction. However, the role of Tvar as a risk stratifying tool remains inconclusive.

Pre-hospital cardiac arrest in acute coronary syndromes: insights from the global registry of acute coronary events and the canadian registry of acute coronary events.

OBJECTIVES: Cardiac arrest in acute coronary syndromes (ACS) is associated with high morbidity and mortality. We examined the clinical characteristics, contemporary management patterns and outcomes of ACS patients with pre-hospital cardiac arrest. METHODS: The Global Registry of Acute Coronary Events and the Canadian Registry of Acute Coronary Events enrolled 14,010 ACS patients in 1999-2008. We compared the clinical characteristics, in-hospital treatment and outcomes between patients with and without pre-hospital cardiac arrest. RESULTS: Overall, 206 (1.4%) patients had cardiac arrest prior to hospital presentation. ACS patients with pre-hospital cardiac arrest were less frequently treated with aspirin, ß-blocker, angiotensin-converting enzyme inhibitors, and statins within the first 24 h of presentation, but the use of cardiac procedures was similar compared to the group without cardiac arrest. Patients with pre-hospital cardiac arrest had significantly higher rates of in-hospital adverse events. Factors independently associated with pre-hospital cardiac arrest included male gender, current smoker status, tachycardia, higher Killip class and ST-segment deviation. CONCLUSION: ACS patients with pre-hospital cardiac arrest continue to have more in-hospital complications and higher mortality. Their use of evidence-based medical therapies was lower but the use of cardiac procedures was similar compared to the group without cardiac arrest. Better utilization of evidence-based therapies in these patients may translate into improved outcomes.

Three-dimensional localization versus fluoroscopically only guided ablations: a meta-analysis.

OBJECTIVES: Data regarding efficacy and safety of three-dimensional localization systems (3D) are limited. We performed a meta-analysis of randomized trials comparing combined fluoroscopy- and 3D guided to fluoroscopically-only guided procedures. DESIGN: A systematic search was performed using multiple databases between 1990 and 2010. Outcomes were acute and long-term success, ablation, procedure and fluoroscopic times, radiation dose (RD), and complications. RESULTS: Thirteen studies involving 1292 patients were identified. 3D were tested against fluoroscopic guidance in 666 patients for supraventricular tachycardia (SVT), atrial flutter (AFL), atrial fibrillation (AF), and ventricular tachycardia (VT). Acute and long-term freedom from arrhythmia was not significantly different between 3D and control for AFL (acute success, 97% vs. 93%, p = 0.57; chronic success, 93% vs. 96%, p = 0.90) or for SVT (acute success, 94% vs. 100%, p = 0.36; chronic success, 88% vs. 88%, p = 0.80). A shorter fluoroscopic time was achieved with 3D in AFL (p < 0.001) and in SVT (p = 0.002). RD was significantly less for both AFL (p = 0.002) and SVT (p = 0.01). Ablation and procedure time and complications were not statistically different. CONCLUSIONS: Success, procedure time, and complications were similar between fluoroscopy- and 3D-guided ablations. Fluoroscopic time and RD were significantly reduced for ablation of AFL and SVT with 3D.

Mexiletine as an adjunctive therapy to amiodarone reduces the frequency of ventricular tachyarrhythmia events in patients with an implantable defibrillator.

The most effective pharmacological management of frequent ventricular tachyarrhythmia events in patients with an implantable defibrillator who failed or did not tolerate amiodarone is unknown. The aim of this retrospective cohort study was to assess the efficacy and tolerability of mexiletine in such patients. The patients served as self-controls. The number of treated ventricular tachyarrhythmia episodes (primary outcome); mortality, shocks from the defibrillator, and electrical storm events (secondary outcomes) during mexiletine therapy was compared with a matched duration of observation just before initiating mexiletine in 29 patients who were treated with a median dose of 300 mg/d of mexiletine and were followed for a median of 12 months. None of the patients had to stop mexiletine due to side effect. There was a significant reduction in the incidence of ventricular tachycardia/fibrillation episodes (median 2 vs. 12 events, P = 0.001) and shocks (median 0 vs. 2 events, P = 0.003) in the first 3 months of treatment, but long-term efficacy was only observed among patients who continued amiodarone therapy. In conclusion, mexiletine, when added to amiodarone in case of amiodarone inefficacy, reduces ventricular tachycardia/fibrillation events and appropriate therapies in patients with an implantable cardioverter defibrillator. A randomized trial should validate the efficacy and safety of mexiletine as an adjunctive therapy to amiodarone.

Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database.

BACKGROUND: Sex differences in the use and outcomes of implantable cardioverter-defibrillators (ICDs) have not been fully studied. OBJECTIVE: To examine potential sex differences in ICD implantation and device outcomes. DESIGN: Health payer-mandated, prospective study of patients referred for ICD implantation, with comprehensive, longitudinal follow-up for complications, deaths, and device outcomes. SETTING: 18 ICD implantation and follow-up centers in Ontario, Canada. PATIENTS: 6021 patients (4733 men) referred for ICD implantation from February 2007 to July 2010. MEASUREMENTS: Multivariate-adjusted ICD implantation rate, complications up to day 45, multivariate-adjusted complications, device outcomes (including appropriate shocks and therapies), and deaths occurring during 1-year follow-up. RESULTS: Rates of ICD implantation were similar in men and women (relative risk, 0.99 [95% CI, 0.97 to 1.02]; P = 0.60). However, women were significantly more likely to experience major complications by 45 days (odds ratio, 1.78 [CI, 1.24 to 2.58]; P = 0.002) and 1 year (hazard ratio [HR], 1.91 [CI, 1.48 to 2.47]; P < 0.001) after implantation. Occurrence of any major or minor complication was also increased in women at both 45-day follow-up (odds ratio, 1.50 [CI, 1.12 to 2.00]; P = 0.006) and 1-year follow-up (HR, 1.55 [CI, 1.25 to 1.93]; P < 0.001). After implantation, women were less likely than men to receive appropriate ICD shock (HR, 0.69 [CI, 0.51 to 0.93]; P = 0.015) or appropriate therapy via shock or antitachycardia pacing (HR, 0.73 [CI, 0.59 to 0.90]; P = 0.003). Total mortality among defibrillator recipients did not differ between men and women (HR, 1.00 [CI, 0.64 to 1.55]; P = 0.99). LIMITATION: The differential effects of sex on prereferral events were not examined. CONCLUSION: Although ICD implantation rates were similar after referral to an electrophysiologist, women who underwent ICD implantation had greater risks for complications and were less likely to experience appropriate ICD-delivered therapies than men. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Ontario Ministry of Health and Long-Term Care.

Complications of variant angina: a case report.

The case of a patient with Prinzmetal's angina causing syncope due to atrioventricular block, and later causing death, is presented. Electrocardiogram during the episodes demonstrate multiple coronary artery involvement. Detection and differential diagnosis of ST-segment elevation during paced rhythm is discussed.

Electrogram-based optimal atrioventricular and interventricular delays of cardiac resynchronization change individually during exercise.

BACKGROUND: Limited data suggest that optimal atrioventricular (AV) and interventricular (VV) delays are different at rest than during exercise in patients with heart failure. We assessed the feasibility and reproducibility of an electrogram-based method of optimization called QuickOpt at rest and during exercise. METHODS: Patients with a St Jude Medical cardiac resynchronization therapy implantable cardioverter-defibrillator were subjected to a graded treadmill test, and QuickOpt was repeatedly measured prior to, during, and after the exercise. RESULTS: Twenty-four patients (16 males, aged 67.4 ± 7.7 years) participated. At rest, delays (in ms) were 110.4 ± 20.1 for sensed AV delay and -70 (LV pacing first) to +20 (RV pacing first) for VV delay. The changes in QuickOpt-derived delays at rest were not significant despite change in body position. During exercise, QuickOpt-derived AV delays did not change in 11 patients, were shorter during peak exercise in 8 patients, and were longer in 3 patients (average value during peak exercise was 126.5 ± 15.8 ms, P = 0.04 compared to baseline). The QuickOpt-derived VV delay gradually shifted toward earlier right ventricular pacing during exercise in 19 patients, while no changes were seen in 3 patients, and a shift occurred toward earlier left ventricular pacing in 2 patients (average value during peak exercise was -30.7 ± 22.2; P = 0.001 compared to baseline). There was no correlation between changes in the QuickOpt-derived AV and VV delays and heart rate. CONCLUSIONS: The application of electrogram-based algorithm is feasible both at rest and during exercise. The results are reproducible. QuickOpt-derived AV and VV delays individually change during exercise.