Electrophysiologic Scar Substrate in Relation to VT: Noninvasive High-Resolution Mapping and Risk Assessment with ECGI.

BACKGROUND: Ischemic cardiomyopathy (ICM) can provide the substrate for ventricular tachycardia (VT). OBJECTIVE: To map noninvasively with high resolution the electrophysiologic (EP) scar substrate, identify its relationship to reentry circuits during VT, and stratify VT risk in ICM patients. METHODS: Noninvasive high-resolution epicardial mapping with electrocardiographic imaging (ECGI) was performed in 32 ICM patients (17 with clinical VT, 15 without VT). Abnormal scar EP substrate was determined based on electrogram (EGM) amplitude (as percentage of maximal peak-to-peak voltage over the entire ventricular epicardium; total scar [TS] < 30%; dense scar [DS] < 15%), fractionation, and presence of late potentials (LPs). Scar burden was defined as the ratio of the scar size to the total epicardial surface area. The VT activation pattern was mapped and correlated with the EP substrate to identify components of the reentry circuit. RESULTS: Patients with VT had higher scar burden (TS: 51.0 ± 9.3% vs 36.5 ± 5.4%, P < 0.05; DS: 29.5 ± 7.3% vs 16.8 ± 6.8%, P < 0.05) with lower normalized unipolar EGM voltage (TS: 0.107 ± 0.027 vs 0.153 ± 0.031, P < 0.05; DS: 0.073 ± 0.023 vs 0.098 ± 0.026, P < 0.05), greater prevalence of fractionated EGMs (TS: 44.1 ± 10.6% vs 26.8 ± 6.3%, P < 0.05; DS: 50.8 ± 10.8% vs 30.9 ± 7.0%, P < 0.05), and LPs (TS: 26.8 ± 10.7% vs 15.8 ± 5.3, P < 0.05). VTs were mapped in eight patients; the reentry circuits were closely related to the EP substrate. CONCLUSIONS: ECGI noninvasively identified scar EP substrate that underlies abnormal conduction in ICM patients. It identified regions within the scar that aligned with critical elements of the reentry circuit during VT. ECGI can potentially be used for VT risk stratification in ICM patients.

Electrophysiologic substrate in congenital Long QT syndrome: noninvasive mapping with electrocardiographic imaging (ECGI).

BACKGROUND: Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. METHODS AND RESULTS: Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation-recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation-recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P<0.05). CONCLUSIONS: LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification.

Noninvasive mapping of ventricular activation in patients with transplanted hearts.

This is the first reported study of ventricular activation patterns after cardiac transplantation, using electrocardiographic imaging (ECGI), a noninvasive method for electrophysiologic mapping. This study of ten patients reveals that transplanted hearts have unique ventricular activation patterns in sinus rhythm, activating early in the epicardial aspect of the anterior or inferior septum, with intact right and left bundle branch conduction. They have late activation with slowing of conduction near the right ventricular (RV) basal free wall, causing a mild QRS prolongation and an rSr' pattern in lead V1 of the ECG. PVCs arise from both endocardial and epicardial locations in both ventricles.

Protected carotid artery stenting in patients at high risk for carotid endarterectomy.

OBJECTIVES: To compare the 30-day, six-month, and one-year outcomes of carotid artery stenting (CAS) and carotid endarterectomy (CEA) in male veterans, and to identify any predictors of adverse outcomes. CAS has been shown to be non-inferior to CEA in patients at high-risk for CEA. The outcome of CAS compared to low-risk CEA is less clear. METHODS: Retrospective analysis of 96 consecutive patients who underwent CAS (N = 31) or CEA (N = 65). The cumulative 30-day, six-month, and one-year incidence of ipsilateral transient ischemic attack (TIA) or stroke, restenosis or reocclusion, need for target vessel revascularization, non-fatal myocardial infarction (MI), and death were compared. RESULTS: All patients in the CAS group were at high risk for CEA. Among the CEA group, 50 (76.9%) were at high risk and the remaining 15 (23.1%) were considered to be at low risk. The cumulative incidence of adverse outcomes with CAS and CEA, respectively, at 30 days (3.2% vs 9.2%, P = ns), six months (3.2 vs 18.5%, P = 0.047), and one year (9.7% vs 18.5%, P = ns) favored CAS. This difference was primarily due to adverse events in the high-risk CEA patients. There was no significant difference in outcome between the CAS and low-risk CEA groups. The independent significant predictors for adverse outcomes within six months were the group (P = 0.047) and number of risk factors (P = 0.01). Interestingly, the use of angiotensin-converting enzyme inhibitors (ACE-I) predicted adverse outcomes within one year (P = 0.01). CONCLUSION: CAS may be superior to high-risk CEA with better six-month outcomes. The outcomes with CAS were not significantly different compared to low-risk CEA, suggesting that CAS may be non-inferior to low-risk CEA.

Platypnea-orthodeoxia syndrome: a diagnostic challenge.

Platypnea-orthodeoxia (P-O) syndrome is an underdiagnosed condition characterized by dyspnea and deoxygenation accompanying a change from a recumbent to an upright position. It is caused by increased right-to-left shunting of blood on assuming an upright position. The diagnosis of this shunt is often challenging. A case where a diagnosis was missed despite performing a tilt transesophageal echocardiogram with bubble study and a technetium labeled macroaggregated albumin scan is presented. However, a large patent foramen ovale (PFO) was found on autopsy. A brief overview of the diagnostic workup and management of this condition along with methods to increase the sensitivity of diagnostic tests is discussed.

Managing Multivessel Coronary Artery Disease in Patients With ST-Elevation Myocardial Infarction: A Comprehensive Review.

Multivessel coronary artery disease (CAD) is found in up to 60% of the patients presenting with an ST-elevation myocardial infarction (STEMI) and worsens the prognosis proportional to the extent of CAD severity. However, the 2013 American College of Cardiology/American Heart Association STEMI guidelines, based on mostly observational data, had recommended against a routine noninfarct-related artery percutaneous coronary intervention (PCI). After these guidelines were published, a handful of randomized trials became available, and they suggested that PCI of significant lesions in a noninfarct-related artery at the time of primary PCI might result in improved patient outcomes. The incidence of major adverse cardiac events was significantly reduced by 55% at 1 year and 65% at 2 years in patients undergoing angiographically guided PCI of nonculprit vessels at the time of primary PCI, in 2 different randomized trials. Fractional flow reserve-guided PCI of nonculprit vessels in this setting has also been shown to reduce cardiac events by 44% at 1 year. Meta-analyses of both nonrandomized and randomized trials have also suggested that complete revascularization at the time of STEMI significantly improves outcomes, including long-term all-cause mortality. In view of the emerging data, a focused update on primary PCI was published in 2015 and suggested that PCI of noninfarct-related arteries might be considered in selected patients. This article is a comprehensive review of the literature on the treatment of multivessel CAD in patients with STEMI, which provides the reader a critical analysis of the available information to determine the best therapeutic approach.

Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials.

OBJECTIVE: To compare the long term efficacy and adverse events of dual blockade of the renin-angiotensin system with monotherapy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, and the Cochrane central register of controlled trials, January 1990 to August 2012. STUDY SELECTION: Randomised controlled trials comparing dual blockers of the renin-angiotensin system with monotherapy, reporting data on either long term efficacy (≥ 1 year) or safety events (≥ 4 weeks), and with a sample size of at least 50. Analysis was stratified by trials with patients with heart failure versus patients without heart failure. RESULTS: 33 randomised controlled trials with 68,405 patients (mean age 61 years, 71% men) and mean duration of 52 weeks were included. Dual blockade of the renin-angiotensin system was not associated with any significant benefit for all cause mortality (relative risk 0.97, 95% confidence interval 0.89 to 1.06) and cardiovascular mortality (0.96, 0.88 to 1.05) compared with monotherapy. Compared with monotherapy, dual therapy was associated with an 18% reduction in admissions to hospital for heart failure (0.82, 0.74 to 0.92). However, compared with monotherapy, dual therapy was associated with a 55% increase in the risk of hyperkalaemia (P<0.001), a 66% increase in the risk of hypotension (P<0.001), a 41% increase in the risk of renal failure (P=0.01), and a 27% increase in the risk of withdrawal owing to adverse events (P<0.001). Efficacy and safety results were consistent in cohorts with and without heart failure when dual therapy was compared with monotherapy except for all cause mortality, which was higher in the cohort without heart failure (P=0.04 v P=0.15), and renal failure was significantly higher in the cohort with heart failure (P<0.001 v P=0.79). CONCLUSION: Although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events such as hyperkalaemia, hypotension, and renal failure compared with monotherapy. The risk to benefit ratio argues against the use of dual therapy.

The electrophysiological cardiac ventricular substrate in patients after myocardial infarction: noninvasive characterization with electrocardiographic imaging.

OBJECTIVES: The aim of this study was to noninvasively image the electrophysiological (EP) substrate of human ventricles after myocardial infarction and define its characteristics. BACKGROUND: Ventricular infarct border zone is characterized by abnormal cellular electrophysiology and altered structural architecture and is a key contributor to arrhythmogenesis. The ability to noninvasively image its electrical characteristics could contribute to understanding of mechanisms and to risk-stratification for ventricular arrhythmia. METHODS: Electrocardiographic imaging, a noninvasive functional EP imaging modality, was performed during sinus rhythm (SR) in 24 subjects with infarct-related myocardial scar. The abnormal EP substrate on the epicardial aspect of the scar was identified, and its location, size, and morphology were compared with the anatomic scar imaged by other noninvasive modalities. RESULTS: Electrocardiographic imaging constructs epicardial electrograms that have characteristics of reduced amplitude (low voltage) and fractionation. Electrocardiographic imaging colocalizes the epicardial electrical scar to the anatomic scar with a high degree of accuracy (sensitivity 89%, specificity 85%). In nearly all subjects, SR activation patterns were affected by the presence of myocardial scar. Late potentials could be identified and were almost always within ventricular scar. CONCLUSIONS: Electrocardiographic imaging accurately identifies areas of anatomic scar and complements standard anatomic imaging by providing scar-related EP characteristics of low voltages, altered SR activation, electrogram fragmentation, and presence of late potentials.

Transthoracic echocardiogram is a useful tool in the hemodynamic assessment of patients with chest trauma.

INTRODUCTION: The utility of transthoracic echocardiogram (TTE) in patients on the trauma service is not well defined. The aim of this study was to evaluate the frequency of abnormal echocardiographic findings that would aid in the assessment and management of cardiovascular hemodynamics in patients with chest trauma. METHODS: A retrospective analysis of all patients who had a TTE on the trauma service at a level 1 trauma center during a 12-month period was performed. RESULTS: There were 94 patients in the study. TTE was performed after cardiac surgery in 5 patients. One of the 5 patients with prior cardiac surgery was excluded from the study because of poor quality images, and each of the remaining 4 patients showed significant TTE abnormalities. Of the 89 patients without prior cardiac surgery, 38 (43%) had significant TTE findings although 32 (84%) of them had no known history of cardiac abnormalities. A decreased left ventricular ejection fraction (<50%) was found in 18% of all patients, and half of them were hemodynamically unstable. Significant valvular regurgitation or stenosis was found in 31 patients, pulmonary hypertension in 25 patients, left ventricular wall motion abnormalities in 12 patients and pericardial effusion in 11 patients. CONCLUSION: Significant echocardiographic abnormalities are detected by TTE in patients with chest trauma. Such findings can be used in the hemodynamic assessment and management of unstable patients during their hospitalization and in planning long-term follow-up and management of these patients after discharge from the hospital.

Noninvasive electroanatomic mapping of human ventricular arrhythmias with electrocardiographic imaging.

The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.