Parin J. Patel

The Anti-Oxidative Capacity of High-Density Lipoprotein Is Reduced in Acute Coronary Syndrome But Not in Stable Coronary Artery Disease

OBJECTIVES This study examined an anti-inflammatory property of high-density lipoprotein (HDL) in subjects with acute coronary syndrome (ACS) and stable coronary artery disease (CAD) compared with control subjects. BACKGROUND HDL has anti-inflammatory properties in vitro, but its relationship to coronary disease in humans is unclear. The high-density lipoprotein inflammatory index (HII) measures the ability of HDL to mitigate oxidation of low-density lipoprotein; this function may be impaired in ACS and/or CAD. METHODS We measured HII in 193 patients undergoing angiography for symptoms of CAD. Control subjects (n = 99) had no angiographic CAD, chronic CAD subjects (n = 51) had ≥ 70% vessel stenosis, and ACS subjects (n = 43) had ≥ 20% vessel stenosis and ischemia or infarction. We also examined HII in a cohort of healthy subjects randomly assigned to a statin or placebo. RESULTS Subjects who had ACS had higher HII (less antioxidative capacity) compared with controls (1.57 vs. 1.17, p = 0.005) or those with chronic CAD (1.57 vs. 1.11, p = 0.006). HII was not different in subjects with stable CAD compared with controls. Furthermore, those subjects with higher HII were more likely to have ACS than no CAD (quartile 4 vs. 1, odds ratio [OR]: 1.74, p = 0.008). In a multivariate logistic regression model, HII was associated with ACS after adjusting for traditional cardiac risk factors (OR: 3.8, p = 0.003). There was a small improvement in HII after statin therapy compared with placebo (-14%, p = 0.03). CONCLUSIONS HDL has less anti-inflammatory capacity as assessed by HII in the setting of ACS compared with controls or subjects with chronic CAD.

The addition of niacin to statin therapy improves high-density lipoprotein cholesterol levels but not metrics of functionality

To the Editor: The role of niacin in the era of widespread statin use has been called into question by 2 recent clinical trials, AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health) and HPS2-THRIVE (Treatment of HDL to Reduce the

Anti-oxidative and cholesterol efflux capacities of high-density lipoprotein are reduced in ischaemic cardiomyopathy.

Various pathological changes lead to the development of heart failure (HF). HDL is dysfunctional in both acute coronary syndrome, as measured by the HDL inflammatory index (HII) assay, and stable coronary disease, as measured by cholesterol efflux capacity. We therefore hypothesized that these functions of HDL are also impaired in subjects with ischaemic cardiomyopathy.

Optimal QT interval correction formula in sinus tachycardia for identifying cardiovascular and mortality risk: Findings from the Penn Atrial Fibrillation Free study.

BACKGROUND The QT interval measures cardiac repolarization, and prolongation is associated with adverse cardiovascular outcomes and death. The exponential Bazett correction formula overestimates the QT interval during tachycardia. OBJECTIVE We evaluated 4 formulas of QT interval correction in individuals with sinus tachycardia for the identification of coronary artery disease, heart failure, and mortality. METHODS The Penn Atrial Fibrillation Free study is a large cohort study of patients without atrial fibrillation. The present study examined 6723 Penn Atrial Fibrillation Free study patients without a history of heart failure and with baseline sinus rate ≥100 beats/min. Medical records were queried for index clinical parameters, incident cardiovascular events, and all-cause mortality. The QT interval was corrected by using Bazett (QT/RR(0.5)), Fridericia (QT/RR(0.33)), Framingham [QT + 0.154 * (1000 - RR)], and Hodges (QT + 105 * (1/RR - 1)) formulas. RESULTS In 6723 patients with a median follow-up of 4.5 years (interquartile range 1.9-6.4 years), the annualized cardiovascular event rate was 2.3% and the annualized mortality rate was 2.2%. QT prolongation was diagnosed in 39% of the cohort using the Bazett formula, 6.2% using the Fridericia formula, 3.7% using the Framingham formula, and 8.7% using the Hodges formula. Only the Hodges formula was an independent risk marker for death across the range of QT values (highest tertile: hazard ratio 1.26; 95% confidence interval 1.03-1.55). CONCLUSION Although all correction formulas demonstrated an association between QTc values and cardiovascular events, only the Hodges formula identified one-third of individuals with tachycardia that are at higher risk of all-cause mortality. Furthermore, the Bazett correction formula overestimates the number of patients with a prolonged QT interval and was not associated with mortality. Future work may validate these findings and result in changes to automated algorithms for QT interval assessment.

Electroanatomic Mapping of the Intercaval Bundle in Atrial Fibrillation

Maintenance of sinus rhythm by catheter-based ablation of atrial fibrillation (AF) has become a common strategy for symptom control. The cornerstone of AF ablation is pulmonary vein isolation (PVI) with both entrance and exit block. Wide area circumferential ablation (WACA) in the antrum has increasingly replaced pulmonary vein (PV) ostial ablation because of a higher success rate and reduced risk of PV stenosis.1 However, a percentage of patients require a second procedure for AF control.2,3 At repeat ablation, PV reconnection is a common finding, and occasionally, it is difficult to achieve true entrance and exit block, especially for the right pulmonary veins (RPVs). Editor’s Perspective see p 1268 When faced with difficulty in obtaining RPV isolation, we follow a stepwise approach (Figure 1) to successfully identify the area of persistent connection. If WACA fails to achieve RPV entrance and exit block, some alternatives include (1) ablation more ostially and into the carina region, which potentially risks PV stenosis; (2) wider encirclement, which requires a larger ablation region and more radiofrequency application, and may be unsuccessful as a result of anatomic factors (in many cases because of the presence of the phrenic nerve in the septal aspect of the RPVs); or (3) mapping the activation pattern of the persistent connection. Voltage mapping can demonstrate the extent of prior ablation lesions and can also document lesion maturity at the interface of healthy tissue and scar. Activation mapping during pacing from the reconnected PV can reveal the connection pathways, which could be either via the left atrium (gaps in the line of WACA ablation) or connection to adjacent structures (RPV to right atrium). During pacing, if the earliest signal is on the left atrial side of the WACA line, there is a gap in the line, which should be …

Usefulness of QRS Axis Change to Predict Mortality in Patients With Left Bundle Branch Block

QRS duration correlates with poor prognosis in patients with left bundle branch block (LBBB), but the importance of left-axis deviation (LAD) is not well established. To determine if LAD confers a mortality risk in patients with LBBB, a single-center, retrospective, population-based cohort study was conducted. Included were all patients at 1 hospital with LBBB on electrocardiography from 1995 to 2005 over a 17-year follow-up period (n = 2,794, median follow-up duration 20 months, interquartile range 6 to 64). Half of all patients with LBBB had LAD. The all-cause mortality rate in the entire cohort was 15%. LAD was not associated with mortality, either as a single outcome (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.88 to 1.3, p = 0.50) or in time-to-event analysis (p = 0.40). Significant risk factors for mortality included high creatinine (OR 1.2, 95% CI 1.1 to 1.3), low hemoglobin (OR 1.2, 95% CI 1.1 to 1.3), history of atrial fibrillation (OR 1.6, 95% CI 1.3 to 2.1), electrocardiographic evidence of previous infarct (OR 1.5, 95% CI 1.2 to 1.9), and history of ventricular tachycardia (OR 1.4, 95% CI 1.0 to 1.9). On bivariate analysis, LAD was associated with atrial fibrillation, ventricular tachycardia, age, and congestive heart failure. Patients with LBBB who converted from normal axis to LAD had significantly higher mortality in time-to-event analysis (p = 0.02). In conclusion, in patients with LBBB, LAD does not confer significant mortality risk. However, those with normal axis who developed LAD during the study period had significantly higher mortality. Perhaps when LBBB and LAD develop concurrently, there is no increased risk over baseline LBBB development, but it may herald a worse prognosis if LAD develops against the background of previous LBBB, from an unknown mechanism.

Race and stroke in an atrial fibrillation inception cohort: Findings from the Penn Atrial Fibrillation Free study

BACKGROUND Stroke may be the initial manifestation of atrial fibrillation (AF). Limited studies, however, have evaluated racial differences in stroke before the diagnosis of AF. OBJECTIVE We assessed racial differences in strokes that occurred before and after AF diagnosis in the Penn Atrial Fibrillation Free study. METHODS The Penn Atrial Fibrillation Free study consists of 56,835 patients from the University of Pennsylvania Health System who were free of AF at the index visit. We developed an inception cohort of 3507 patients with incident AF and without any remote history of stroke. RESULTS Among the AF inception cohort, there were 538 patients with ischemic strokes and 54 with hemorrhagic strokes. Nearly half (n = 254; 47%) of the ischemic strokes occurred within a 6-month period before the diagnosis of AF. Of these, the majority of strokes occurred either on the day of (n = 158) or within a 7-day period before (n = 30) the diagnosis of incident AF. The remaining 284 (53%) ischemic strokes occurred a median of 3.6 years (interquartile range 1.9-5.4 years) after AF diagnosis. Compared with whites, blacks had an independently higher risk of having an ischemic stroke either before (adjusted odds ratio 1.37; 95% confidence interval 1.03-1.81) or after (adjusted hazard ratio 1.67; 95% confidence interval 1.30-2.14) AF diagnosis. CONCLUSION In the population with incident AF, nearly half of the ischemic strokes occurred before the diagnosis of AF. Compared with whites, blacks had a higher risk of developing an ischemic stroke that persisted whether the stroke occurred in the period either before or after AF diagnosis.

Effective management of acute coronary thrombosis in a young woman with lupus using aggressive medical therapy.

Systemic lupus erythematosus is a chronic inflammatory disorder that predisposes to acute coronary thrombosis. To demonstrate how the pathophysiology of lupus-mediated coronary events may be unique, we offer the case and management of a young woman with lupus who presented with acute myocardial infarction. She was initially managed with medical therapy including the standard regimen of aspirin, heparin, and clopidogrel. Despite a Thrombolysis in Myocardial Infarction risk score of only 2, she was also given eptifibatide infusion because of clinical concerns. Repeated cardiac catheterization showed marked regression of the thrombus, and coronary fractional flow reserve calculation demonstrated full recovery of coronary vasculature with this therapy. This case demonstrates effective management of life-threatening coronary thrombosis with medical therapy only in a young woman with lupus. We briefly review the pathophysiology of acute coronary thrombosis in lupus patients and distinguish this from the more common process of age-related atherosclerosis. Given the lack of evidence in this specific population, we discuss a pathophysiology-based clinical decision-making tool. Assessing clinical risk factors and using technologies such as intravascular ultrasound can help make the correct treatment decision.

OPTIMAL MEASUREMENT OF THE QT INTERVAL IN PATIENTS WITH TACHYCARDIA

QT prolongation is associated with death and adverse cardiovascular outcomes. Classic, exponentially-derived equations overestimate the QT interval during tachycardia and can result in misdiagnosis of prolonged QT. We evaluated two methods of correcting the QT interval (linear and exponential) and

QTCC, A NOVEL METHOD FOR CORRECTING QT INTERVAL FOR QRS DURATION, PREDICTS ALL-CAUSE MORTALITY

Longer QT is associated with adverse cardiovascular outcomes, but wide QRS due to bundle branch block (BBB) or intraventricular conduction delay (IVCD) can obscure QT measurement. Our hypothesis is that adjusting the QT for QRS duration using a novel correction method is clinically relevant. We