Usefulness of PA32540 in Protecting the Gastric Layer While Providing Secondary Prevention for Coronary Artery Disease.

Aspirin has been the mainstay for secondary prevention of coronary artery disease to decrease early recurrence and severity of recurrent cardiovascular events. However, an increase in gastrointestinal bleeding due to aspirin is preventing many patients from adhering to this daily regimen. PA32540, a combination pill with aspirin and omeprazole, is a newly emerging intervention that has the potential to reinforce patient compliance with the aspirin regimen due to fewer gastrointestinal adverse effects. This systematic review assessed three recent phase 3 clinical trials investigating the safety and efficacy of PA32540. Clinical trials were chosen based on inclusion criteria such as phase 3, randomized, open-label or blinded studies, utilization of enteric-coated aspirin 325 mg dose, and measured GI adverse effects and major adverse cardiac events (MACE) as primary outcomes. Study A, a 6-month phase-3 study by Whellan et al., used two identically designed, randomized, double-blind trials to compare the GI adverse events and MACE after the use of PA32540 to 325mg of enteric coated Aspirin (EC-ASA) in subjects at risk for aspirin-associated gastric ulcers. Results showed fewer upper GI symptoms, decreased size of ulcers, and improved heartburn symptoms in subjects receiving PA32540 compared to EC-ASA. Study B, a 12-month phase-3 study by Hatoum et al., assessed secondary cardiovascular event prevention in a study population that was treated with PA32540 in comparison to a community setting (CS) group that was started on a standard antiplatelet treatment. Results indicated a 28% reduction of CV events in subjects treated with PA32540 compared to the CS group. Study C, a phase-3 open-label study by Goldstein et al., evaluating secondary prevention of cardiovascular/cerebrovascular events with the use of PA32450 for 12 months found that none of the 12-month completers were reported to have new-onset gastric ulcers. In conclusion, PA32540 could be an effective therapy for secondary prevention of coronary artery disease as studies are showing similar efficacy in preventing MACE with reduced GI side effects.

More than just muscle spasms: a rare presentation of aortic dissection.

Acute aortic dissection is associated with significant morbidity and mortality, often from complications including aortic regurgitation, cardiac tamponade and myocardial infarction. Typical clinical presentation includes a sudden onset of severe chest pain, although this is not always consistent. Clinical signs and symptoms are diverse with an estimated 38% of cases being missed on initial evaluation. Primary neurological symptoms at presentation are rare but have been reported often to coexist with chest pain. We present a case of acute aortic dissection in which the initial presenting symptoms were predominantly neurological. Stanford type A dissection is a surgical emergency with a high burden of cardiovascular death; thus, aggressive identification and management is paramount. Our case re-emphasises the importance of having a higher index of suspicion and a keen clinical eye for atypical presentations of acute aortic dissection.

Impedance-guided Radiofrequency Ablation: Using Impedance to Improve Ablation Outcomes.

Despite the achievement of acute conduction block during catheter ablation, the recovery of conduction at previously ablated sites remains a primary factor implicated in arrhythmia recurrence after initial ablation. Real-time markers of adequate ablation lesion creation are needed to ensure durable ablation success. However, the assessment of acute lesion formation is challenging, and requires interpretation of surrogate markers of lesion creation that are frequently unreliable. Careful monitoring of impedance changes during radiofrequency catheter ablation has emerged as a highly specific marker of local tissue destruction. Ablation strategies guided by close impedance monitoring during ablation applications have been demonstrated to achieve high levels of success for ablation of atrial fibrillation. Impedance decrease during ablation may therefore be used as an additional endpoint beyond acute conduction block, in order to improve the durability of ablation lesions. In this manuscript, available methods of real-time lesion assessment are reviewed, and the rationale and technique for impedance-guided ablation are described.

Selective His-bundle Pacing May Preserve Intrinsic Repolarization as Well as Depolarization.

A 79-year-old man with chronic atrial fibrillation underwent single-chamber His-bundle pacemaker implantation. The post-implant electrocardiogram (ECG) demonstrated selective His-bundle capture, with a narrow paced QRS and repolarization pattern similar to that of the baseline ECG. Furthermore, repolarization changes prototypic of ventricular pacing did not occur with selective His-bundle capture. While His-bundle pacing, with or without selective His-bundle capture, can preserve physiologic patterns of depolarization, only His-bundle selective pacing can preserve intrinsic ST- and T-wave patterns. Thus, the maintenance of physiologic repolarization may have various advantages, including accurate interpretation of ECG changes that are not generally interpretable in the setting of ventricular pacing.

Circumstances and outcomes of sudden unexpected death in patients with high-risk myocardial infarction: implications for prevention.

BACKGROUND: Sudden death (SD) is a frequent catastrophic complication in patients after myocardial infarction. Circumstances of SD may affect strategies for prevention. METHODS AND RESULTS: We reviewed source documentation for 1067 patients who had SD in the Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial. We determined the circumstances of these events and assessed long-term mortality in patients who were resuscitated. Location of the SD event was available in 978 of 1067 patients, with 226 events occurring within the first 40 days. Although SD was more likely to occur at home (645 of 978, 66%) than in hospital (204 of 978, 21%), the proportion of in-hospital events was higher early on (99 of 226, 44%). Home events were less likely to be witnessed regardless of time frame. Preceding activity was known for 42% of patients with home arrest; of these, 52% were determined to be asleep at time of event, and these deaths were more likely to be unwitnessed. A majority of patients for whom initial ECG rhythm was reported had ventricular tachycardia/ventricular fibrillation (189 of 283, 67%). Of the 155 patients successfully resuscitated, 24% subsequently received an implantable cardioverter-defibrillator. Nineteen percent of those who received an implantable cardioverter-defibrillator subsequently died compared with 49% of patients who did not receive an implantable cardioverter-defibrillator (hazard ratio, 0.36; 95% confidence interval, 0.14 to 0.93; P=0.04). CONCLUSIONS: A high proportion of SD events after high-risk myocardial infarction occurred at home, but in-hospital events were more common early on. Patients who were asleep were more likely to have unwitnessed arrests. Alternative strategies for the prevention of SD in patients who are not candidates for implantable cardioverter-defibrillator will need to take into account the circumstances of SD events.

ECG identification of scar-related ventricular tachycardia with a left bundle-branch block configuration.

BACKGROUND: A left bundle-branch block (LBBB)-like pattern with a dominant S-wave in V(1) is common in idiopathic ventricular arrhythmias (VA). Discrimination between idiopathic and scar-related LBBB pattern VA has important clinical implications. We hypothesized that the VA QRS morphology is influenced by the presence of ventricular scar, allowing ECG discrimination of VA arising from structurally normal versus scarred myocardium. METHODS AND RESULTS: Twelve-lead ECGs of 297 LBBB pattern monomorphic VA were recorded during catheter ablation procedures. QRS morphology characteristics associated with scar-related VA were identified in retrospective analysis of 118 LBBB pattern VA (95 scar-related, 23 idiopathic) to develop a stepwise algorithm that was prospectively tested in 179 LBBB pattern VA (120 scar-related, 59 idiopathic). The diagnosis of scar was based on sinus rhythm surface ECG, cardiovascular imaging, and electroanatomic catheter mapping. A precordial transition beyond V4, notching of the S-wave downstroke in lead V1 or V2, and a duration from the onset of QRS to the S-nadir in V1 >90 ms were independent predictors for scar-related VA. The proposed algorithm classified a VA as scar-related if any of these criteria was met. If none of the criteria was present, a VA was classified as idiopathic. In prospective validation, the algorithm was highly sensitive (96%) and specific (83%) for the identification of scar-related LBBB pattern VA. CONCLUSIONS: The QRS morphology of VA is different between scar-related and idiopathic VA. A simple ECG algorithm is sensitive for identifying scar-related LBBB VA, which could be helpful in guiding further evaluation of these patients.

When, how, and why should sinus rhythm be restored in patients with persistent atrial fibrillation?

The results of the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial indicate that the rate control strategy is preferred for the majority of patients with paroxysmal and persistent atrial fibrillation (AF). If the patient remains symptomatic despite adequate rate control or if rate control cannot be achieved, then rhythm control therapies are indicated. The most likely explanation for the disappointing results of the AFFIRM trial is the poor efficacy and excessive toxicity of rhythm control medications, because the presence of sinus rhythm was associated with a favorable prognosis in AFFIRM. As a result, there is currently great interest in nonpharmacologic therapies such as AF ablation and development of new drugs for AF with a more favorable efficacy and toxicity profile. AF ablation should be reserved for patients who fail an initial trial of a rhythm control medication until additional clinical trial information is available to justify the use of AF ablation as first-line therapy. When rhythm control therapy is indicated, the choice of antiarrhythmic medication should be dictated by the presence or absence of structural heart disease, congestive heart failure, renal dysfunction, or other comorbidities in order to maximize efficacy and minimize the chance of proarrhythmia or extracardiac toxicity.

Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: the VALIANT experience.

BACKGROUND: In survivors of myocardial infarction (MI), new left bundle branch block (LBBB) is associated with adverse outcomes, but its impact is not well described in post-MI patients with left ventricular (LV) systolic dysfunction and/or heart failure (HF). OBJECTIVES: The aim of this study was to determine if new LBBB is an independent predictor of long-term fatal and nonfatal outcomes in high-risk survivors of MI by reviewing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. METHODS: In VALIANT, 14,703 patients with LV systolic dysfunction and/or HF were randomized to valsartan, captopril, or both a mean of 5 days after MI. Baseline ECG data were available from 14,259 patients. We assessed the predictive value of new LBBB for death and major cardiovascular outcomes after 3 years, adjusting for multiple baseline covariates including LV ejection fraction. RESULTS: At follow-up, patients with new LBBB (608 [4.2%]) compared with patients without new LBBB had more comorbidities and increased adjusted risk of death (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.6), cardiovascular death (HR 1.4, 95% CI 1.2-1.7), HF (HR 1.3, 95% CI 1.1-1.6), MI (HR 1.5, 95% CI 1.2-1.9), and the composite of death, HF, or MI (HR 1.4, 95% CI 1.2-1.6). CONCLUSION: In post-MI survivors with LV systolic dysfunction and/or HF, new LBBB was an independent predictor of all major adverse cardiovascular outcomes during long-term follow-up. This readily available ECG marker should be considered a major risk factor for long-term cardiovascular complications in high-risk patients after MI.

Phrenic nerve injury after catheter ablation of atrial fibrillation.

UNLABELLED: Phrenic Nerve Injury (PNI) has been well studied by cardiac surgeons. More recently it has been recognized as a potential complication of catheter ablation with a prevalence of 0.11 to 0.48 % after atrial fibrillation (AF) ablation. This review will focus on PNI after AF ablation. Anatomical studies have shown a close relationship between the right phrenic nerve and it's proximity to the superior vena cava (SVC), and the antero-inferior part of the right superior pulmonary vein (RSPV). In addition, the proximity of the left phrenic nerve to the left atrial appendage has been well established. Independent of the type of ablation catheter (4 mm, 8 mm, irrigated tip, balloon) or energy source used (radiofrequency (RF), ultrasound, cryothermia, and laser); the risk of PNI exists during ablation at the critical areas listed above. Although up to thirty-one percent of patients with PNI after AF ablation remain asymptomatic, dyspnea remain the cardinal symptom and is present in all symptomatic patients. Despite the theoretical risk for significant adverse effect on functional status and quality of life, short-term outcomes from published studies appear favorable with 81% of patients with PNI having a complete recovery after 7 +/- 7 months. CONCLUSION: Existing studies have described PNI as an uncommon but avoidable complication in patients undergoing pulmonary vein isolation for AF. Prior to ablation at the SVC, antero-inferior RSPV ostium or the left atrial appendage, pacing should be performed before energy delivery. If phrenic nerve capture is documented, energy delivery should be avoided at this site. Electrophysiologist's vigilance as well as pacing prior to ablation at high risk sites in close proximity to the phrenic nerve are the currently available tools to avoid the complication of PNI.

Entrainment mapping for rapid distinction of left and right atrial tachycardias.

BACKGROUND: Distinguishing left from right atrial tachycardia is a critical step for guiding ablation. OBJECTIVES: The purpose of this study was to develop and validate a simple algorithm predicting the location of macroreentrant atrial tachycardia (AT) circuits from limited entrainment mapping in right atrium (RA) and coronary sinus (CS). METHODS: In 180 patients with organized reentrant AT, entrainment was performed at the high RA, proximal CS, and distal CS. The difference between the postpacing interval (PPI) and tachycardia cycle length (TCL) was calculated at each site. The location of the AT reentrant circuit was determined by mapping and ablation. An algorithm predicting AT regions was developed from 104 ATs in the first 90 patients (group I) and prospectively evaluated in a validation cohort of 106 ATs in the second 90 patients (group II). RESULTS: In group I, PPI-TCL difference <50 or >50 ms at the high RA distinguished RA from LA reentrant circuits. For RA tachycardias, PPI-TCL difference at the proximal CS distinguished common flutter from lateral RA circuits. For LA circuits, PPI-TCL difference at the proximal and distal CS distinguished perimitral reentry from reentry involving the right pulmonary veins and septum. In group II, an algorithm based on PPI-TCL difference >50 or <50 ms at the high RA, proximal CS, or distal CS had sensitivity of 94%, specificity of 88%, and predictive accuracy of 93% for predicting the successful ablation region. CONCLUSION: Limited entrainment from sites accessible from the RA can expeditiously suggest the AT location to guide more detailed mapping and potentially avoid unnecessary transseptal punctures in some patients.

Neointimal formation after endovascular arterial injury is markedly attenuated in db/db mice.

OBJECTIVE: A diabetic mouse model of accelerated neointimal formation would be a useful tool to understand the increased incidence of restenosis in patients with diabetes. METHODS AND RESULTS: Femoral artery endoluminal wire injury was performed in diabetic insulin 2 Akita (ins2Akita) and leptin receptor db/db (leprdb/db) mutant mice. Neointima size in ins2Akita mouse arteries was unchanged compared with nondiabetic wild-type littermates. Although Ki67 labeling demonstrated similar rates of replication in the neointima of leprdb/db mouse arteries, neointimal formation in leprdb/db mice was surprisingly reduced by approximately 90% compared with nondiabetic lepr+/+ mice. Four hours after arterial injury, medial smooth muscle cell death was diminished in leprdb/db arteries, suggesting that the initial response to arterial injury was altered in leprdb/db mice. CONCLUSIONS: These studies highlight a differential response to arterial injury in leprdb/db mice and suggest a potential role for leptin in the regulation of neointimal formation in response to arterial injury.