Trends in safety of catheter-based electrophysiology procedures in the last 2 decades: A meta-analysis.

BACKGROUND: Rapid technologic development and expansion of procedural expertise have led to widespread proliferation of catheter-based electrophysiology procedures. It is unclear whether these advances come at cost to patient safety. OBJECTIVE: This meta-analysis aimed to assess complication rates after modern electrophysiology procedures during the lifetime of the procedures. METHODS: A comprehensive search was performed to identify relevant data published before May 30, 2023. Studies were included if they met the following inclusion criteria: prospective trials or registries, including comprehensive complications data; and patients undergoing atrial fibrillation ablation, ventricular tachyarrhythmia ablation, leadless cardiac pacemaker implantation, and percutaneous left atrial appendage occlusion. Pooled incidences of procedure-related complications were individually assessed by random effects models to account for heterogeneity. Temporal trends in complications were investigated by clustering trials by publication year (2000-2018 vs 2019-2023). RESULTS: A total of 174 studies (43,914 patients) met criteria for analysis: 126 studies of atrial fibrillation ablation (n = 24,057), 25 studies of ventricular tachyarrhythmia ablation (n = 1781), 21 studies of leadless cardiac pacemaker (n = 8896), and 18 studies of left atrial appendage occlusion (n = 9180). The pooled incidences of serious procedure-related complications (3.49% [2000-2018] vs 3.05% [2019-2023]; P < .001), procedure-related stroke (0.46% vs 0.28%; P = .002), pericardial effusion requiring intervention (1.02% vs 0.83%; P = .037), and procedure-related death (0.15% vs 0.06%; P = .003) significantly decreased over time. However, there was no significant difference in the incidence of vascular complications over time (1.86% vs 1.88%; P = .888). CONCLUSION: Despite an increase in cardiac electrophysiology procedures, procedural safety has improved over time.

A Case of Multifocal Ectopic Purkinje-related Premature Contractions While Pregnant.

Multifocal ectopic Purkinje-related premature contractions are a unique electrophysiological finding that can be characteristic of a rare sodium channelopathy. We describe the medical management of this rare channelopathy in a patient who was pregnant.

Early Ventricular Arrhythmias After Left Ventricular Assist Device Implantation.

BACKGROUND: Although sustained ventricular arrhythmias (VAs) are a common complication after durable left ventricular assist device (LVAD) implantation, the incidence, risk factors, and prognostic implications of postoperative early VAs (EVAs) in contemporary patients with LVAD are poorly understood. METHODS AND RESULTS: A single-center retrospective analysis was performed of patients who underwent LVAD implantation from October 1, 2006, to October 1, 2022. EVA was defined as an episode of sustained VA identified ≤30 days after LVAD implantation. A total of 789 patients underwent LVAD implantation (mean age 62.9 ± 0. years 5, HeartMate 3 41.4%, destination therapy 43.3%). EVAs occurred in 100 patients (12.7%). A history of end-stage renal disease (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.45-21.70), preoperative electrical storm (OR 2.82, 95% CI 1.11-7.16), and appropriate implantable cardiac defibrillator therapy before implantation (OR 2.8, 95% CI 1.26-6.19) are independently associated with EVAs. EVA was associated with decreased 30-day survival (hazard ratio 3.02, 95% CI 1.1-8.3, P = .032). There was no difference in transplant-free survival time between patients with and without EVAs (hazard ratio 0.82, 95% CI 0.5-1.4, P = .454). CONCLUSIONS: EVAs are common after durable LVAD implantation and are associated with an increased risk of 30-day mortality.

SGLT2 inhibitors reduce sudden cardiac death risk in heart failure: Meta-analysis of randomized clinical trials.

INTRODUCTION: Multiple randomized controlled trials have demonstrated sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease the composite endpoint of cardiovascular death or heart failure hospitalizations in all heart failure patients. It is uncertain whether SGLT2i impacts the risk of sudden cardiac death in patients with heart failure. METHODS: A comprehensive search was performed to identify relevant data published before August 28, 2022. Trials were included if: (1) all patients had clinical heart failure (2) SGLT2i and placebo were compared (3) all patients received conventional medical therapy and (4) reported outcomes of interest (sudden cardiac death [SCD], ventricular arrhythmias, atrial arrhythmias). RESULTS: SCD was reported in seven of the eleven trials meeting selection criteria: 10 796 patients received SGLT2i and 10 796 received placebo. SGLT2i therapy was associated with a significant reduction in the risk of SCD (risk ratios [RR]: 0.68; 95% confidence intervals [CI]: 0.48-0.95; p = .03; I2 = 0%). Absent dedicated rhythm monitoring, there were no significant differences in the incidence of sustained ventricular arrhythmias not associated with SCD (RR: 1.03; 95% CI: 0.83-1.29; p = .77; I2 = 0%) or atrial arrhythmias (RR: 0.91; 95% CI: 0.77-1.09; p = .31; I2 = 29%) between patients receiving an SGLT2i versus placebo. CONCLUSION: SGLT2i therapy is associated with a reduced risk of SCD in patients with heart failure receiving contemporary medical therapy. Prospective trials are needed to determine the long-term impact of SGLT2i therapy on atrial and ventricular arrhythmias.

A case report of acute heart failure and cardiogenic shock caused by catastrophic antiphospholipid syndrome and lupus myocarditis.

Background: Catastrophic antiphospholipid syndrome and lupus myocarditis are two rare life-threatening conditions. Case summary: We present a case of a 47-year-old woman admitted in profound cardiogenic shock due to catastrophic antiphospholipid syndrome and lupus myocarditis requiring advanced heart failure therapies, including early mechanical circulatory support. She improved with steroids, immunoglobulins, mycophenolate, and eculizumab. Discussion: This case highlights the importance of early identification of cardiogenic shock secondary to catastrophic antiphospholipid syndrome and lupus myocarditis, the arrhythmogenic complications of myocarditis, and the subsequent management of the disease progression with mechanical and medical support.

Intramural Needle Ablation for Refractory Premature Ventricular Contractions.

BACKGROUND: Frequent premature ventricular contractions (PVCs) are often amenable to catheter ablation. However, a deep intramural focus may lead to failure due to inability of standard ablation techniques to penetrate the focus. We sought to assess the efficacy and safety of infusion needle ablation (INA) for PVCs that are refractory to standard radiofrequency ablation. METHODS: Under 2 Food and Drug Administration approved protocols, INA was evaluated in patients with frequent PVCs that were refractory to standard ablation. Initial targets for ablation were selected by standard mapping techniques. INA was performed with a deflectable catheter equipped with an extendable/retractable needle at the tip that can be extended up to 12 mm into the myocardium and is capable of pacing and recording. After contrast injection for location assessment, radiofrequency ablation was performed with the needle tip using a temperature-controlled mode (maximum temperature 60 °C) with saline infusion from the needle. The primary end point was a decrease in PVC burden to <5000/24 hours at 6 months. The primary safety end point was incidence of procedure- or device-related serious adverse events. RESULTS: At 4 centers, 35 patients (age 55.3±16.9 years, 74.2% male) underwent INA. The baseline median PVC burden was 25.4% (interquartile range, 18.4%-33.9%) and mean left ventricular ejection fraction was 37.7±12.3%. Delivering 10.3±8.0 INA lesions/patient (91% had adjunctive standard radiofrequency ablation also) resulted in acute PVC elimination in 71.4%. After a mean follow-up of 156±109 days, the primary efficacy end point was met in 73.3%. The median PVC burden decreased to 0.8% (interquartile range, 0.1%-6.0%; P<0.001). The primary safety end point occurred in 14.3% consisting of 1 (2.9%) heart block, 1 (2.9%) femoral artery dissection, and 3 (8.6%) pericardial effusions (all treated percutaneously). CONCLUSIONS: INA is effective for the elimination of frequent PVCs that are refractory to conventional ablation and is associated with an acceptable safety profile. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01791543 and NCT03204981.

A single-center experience with early adoption of physiologic pacing approaches.

BACKGROUND: Increasing interest in physiological pacing has been countered with challenges such as accurate lead deployment and increasing pacing thresholds with His-bundle pacing (HBP). More recently, left bundle branch area pacing (LBBAP) has emerged as an alternative approach to physiologic pacing. OBJECTIVE: To compare procedural outcomes and pacing parameters at follow-up during initial adoption of HBP and LBBAP at a single center. METHODS: Retrospective review, from September 2016 to January 2020, identified the first 50 patients each who underwent successful HBP or LBBAP. Pacing parameters were then assessed at first follow-up after implantation and after approximately 1 year, evaluating for acceptable pacing parameters defined as sensing R-wave amplitude >5 mV, threshold <2.5 V @ 0.5 ms, and impedance between 400 and 1200 Ω. RESULTS: The HBP group was younger with lower ejection fraction compared to LBBAP (73.2 ± 15.3 vs. 78.2 ± 9.2 years, p = .047; 51.0 ± 15.9% vs. 57.0 ± 13.1%, p = .044). Post-procedural QRS widths were similarly narrow (119.8 ± 21.2 vs. 116.7 ± 15.2 ms; p = .443) in both groups. Significantly fewer patients with HBP met the outcome for acceptable pacing parameters at initial follow-up (56.0% vs. 96.4%, p = .001) and most recent follow-up (60.7% vs. 94.9%, p ≤ .001; at 399 ± 259 vs. 228 ± 124 days, p ≤ .001). More HBP patients required lead revision due to early battery depletion or concern for pacing failure (0% vs. 13.3%, at a mean of 664 days). CONCLUSION: During initial adoption, HBP is associated with a significantly higher frequency of unacceptable pacing parameters, energy consumption, and lead revisions compared with LBBAP.

Echocardiography in the time of Covid-19: Ultrasound enhancing agents save time and augment diagnostic information.

BACKGROUND: There are currently no clear guidelines regarding the use of ultrasound enhancing agents (UEAs) with transthoracic echocardiography (TTE) for patients hospitalized with Covid-19. We investigated whether the performance of TTE with UEAs provides more diagnostic information and allows for shorter acquisition time compared to unenhanced TTE imaging in this patient population. METHODS: We analyzed the TTEs of 107 hospitalized Covid-19 patients between April and June 2020 who were administered UEAs (Definity®, Lantheus). The time to acquire images with and without UEAs was calculated. A level III echocardiographer determined if new, clinically significant findings were visualized with the addition of UEAs. RESULTS: There was a mean of 11.84±3.59 UEA cineloops/study vs 20.74±8.10 non-UEA cineloops/study (p < 0.0001). Mean time to acquire UEA cineloop images was 72.28±28.18 s/study compared to 188.07±86.04 s/study for non-UEA cineloop images (p < 0.0001). Forty-eight patients (45%) had at least one new finding on UEA imaging, with a total of 62 new findings seen. New information gained with UEAs was more likely to be found in patients with acute respiratory distress syndrome (21 vs 9, p < 0.001) and in those on mechanical ventilation (21 vs 15, p = 0.046). CONCLUSIONS: TTE with UEAs required less time and fewer cineloop images compared to non-UEA imaging in patients hospitalized with Covid-19. Additionally, Covid-19 patients with severe respiratory disease benefited most with regard to new diagnostic information. Health care personnel should consider early use of UEAs in select hospitalized Covid-19 patients in order to reduce exposure and optimize diagnostic yield.

Using Clinical and Echocardiographic Characteristics to Characterize the Risk of Ischemic Stroke in Patients with COVID-19.

BACKGROUND: COVID-19 has been associated with an increased incidence of ischemic stroke. The use echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19 has not been explored. METHODS: We conducted a retrospective study of 368 patients hospitalized between 3/1/2020 and 5/31/2020 who had laboratory-confirmed infection with SARS-CoV-2 and underwent transthoracic echocardiography during hospitalization. Patients were categorized according to the presence of ischemic stroke on cerebrovascular imaging following echocardiography. Ischemic stroke was identified in 49 patients (13.3%). We characterized the risk of ischemic stroke using a novel composite risk score of clinical and echocardiographic variables: age <55, systolic blood pressure >140 mmHg, anticoagulation prior to admission, left atrial dilation and left ventricular thrombus. RESULTS: Patients with ischemic stroke had no difference in biomarkers of inflammation and hypercoagulability compared to those without ischemic stroke. Patients with ischemic stroke had significantly more left atrial dilation and left ventricular thrombus (48.3% vs 27.9%, p = 0.04; 4.2% vs 0.7%, p = 0.03). The unadjusted odds ratio of the composite novel COVID-19 Ischemic Stroke Risk Score for the likelihood of ischemic stroke was 4.1 (95% confidence interval 1.4-16.1). The AUC for the risk score was 0.70. CONCLUSIONS: The COVID-19 Ischemic Stroke Risk Score utilizes clinical and echocardiographic parameters to robustly estimate the risk of ischemic stroke in patients hospitalized with COVID-19 and supports the use of echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19.

Prognostic Value of Electrocardiographic QRS Diminution in Patients Hospitalized With COVID-19 or Influenza.

During the clinical care of hospitalized patients with COVID-19, diminished QRS amplitude on the surface electrocardiogram (ECG) was observed to precede clinical decompensation, culminating in death. This prompted investigation into the prognostic utility and specificity of low QRS complex amplitude (LoQRS) in COVID-19. We retrospectively analyzed consecutive adults admitted to a telemetry service with SARS-CoV-2 (n = 140) or influenza (n = 281) infection with a final disposition-death or discharge. LoQRS was defined as a composite of QRS amplitude <5 mm or <10 mm in the limb or precordial leads, respectively, or a ≥50% decrease in QRS amplitude on follow-up ECG during hospitalization. LoQRS was more prevalent in patients with COVID-19 than influenza (24.3% vs 11.7%, p = 0.001), and in patients who died than survived with either COVID-19 (48.1% vs 10.2%, p <0.001) or influenza (38.9% vs 9.9%, p <0.001). LoQRS was independently associated with mortality in patients with COVID-19 when adjusted for baseline clinical variables (odds ratio [OR] 11.5, 95% confidence interval [CI] 3.9 to 33.8, p <0.001), presenting and peak troponin, D-dimer, C-reactive protein, albumin, intubation, and vasopressor requirement (OR 13.8, 95% CI 1.3 to 145.5, p = 0.029). The median time to death in COVID-19 from the first ECG with LoQRS was 52 hours (interquartile range 18 to 130). Dynamic QRS amplitude diminution is a strong independent predictor of death over not only the course of COVID-19 infection, but also influenza infection. In conclusion, this finding may serve as a pragmatic prognostication tool reflecting evolving clinical changes during hospitalization, over a potentially actionable time interval for clinical reassessment.

Atrial Fibrillation in Patients Hospitalized With COVID-19: Incidence, Predictors, Outcomes, and Comparison to Influenza.

OBJECTIVES: The goal of this study is to determine the incidence, predictors, and outcomes of atrial fibrillation (AF) or atrial flutter (AFL) in patients hospitalized with coronavirus disease-2019 (COVID-19). BACKGROUND: COVID-19 results in increased inflammatory markers previously associated with atrial arrhythmias. However, little is known about their incidence or specificity in COVID-19 or their association with outcomes. METHODS: This is a retrospective analysis of 3,970 patients admitted with polymerase chain reaction-positive COVID-19 between February 4 and April 22, 2020, with manual review performed of 1,110. The comparator arm included 1,420 patients with influenza hospitalized between January 1, 2017, and January 1, 2020. RESULTS: Among 3,970 inpatients with COVID-19, the incidence of AF/AFL was 10% (n = 375) and in patients without a history of atrial arrhythmias it was 4% (n = 146). Patients with new-onset AF/AFL were older with increased inflammatory markers including interleukin 6 (93 vs. 68 pg/ml; p < 0.01), and more myocardial injury (troponin-I: 0.2 vs. 0.06 ng/ml; p < 0.01). AF and AFL were associated with increased mortality (46% vs. 26%; p < 0.01). Manual review captured a somewhat higher incidence of AF/AFL (13%, n = 140). Compared to inpatients with COVID-19, patients with influenza (n = 1,420) had similar rates of AF/AFL (12%, n = 163) but lower mortality. The presence of AF/AFL correlated with similarly increased mortality in both COVID-19 (relative risk: 1.77) and influenza (relative risk: 1.78). CONCLUSIONS: AF/AFL occurs in a subset of patients hospitalized with either COVID-19 or influenza and is associated with inflammation and disease severity in both infections. The incidence and associated increase in mortality in both cohorts suggests that AF/AFL is not specific to COVID-19, but is rather a generalized response to the systemic inflammation of severe viral illnesses.

Characterization of Myocardial Injury in Patients With COVID-19.

BACKGROUND: Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data. OBJECTIVES: This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. METHODS: We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. RESULTS: A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities. CONCLUSIONS: Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

Trimming the need for invasive ventilation: pragmatic critical care during the COVID-19 pandemic.

COVID-19 has challenged all medical professionals to optimise non-invasive positive pressure ventilation (NIV) as a means of limiting intubation. We present a case of a middle-aged man with a voluminous beard for religious reasons who developed progressive hypoxic respiratory failure secondary to COVID-19 infection which became refractory to NIV. After gaining permission to trim the patient's facial hair by engaging with the patient, his family and religious leaders, his mask fit objectively improved, his hypoxaemia markedly improved and an unnecessary intubation was avoided. Trimming of facial hair should be considered in all patients on NIV who might have any limitations with mask fit and seal that would hamper ventilation, including patients who have facial hair for religious reasons.

Syncope and presyncope in patients with COVID-19.

INTRODUCTION: Recent studies have described several cardiovascular manifestations of COVID-19 including myocardial ischemia, myocarditis, thromboembolism, and malignant arrhythmias. However, to our knowledge, syncope in COVID-19 patients has not been systematically evaluated. We sought to characterize syncope and/or presyncope in COVID-19. METHODS: This is a retrospective analysis of consecutive patients hospitalized with laboratory-confirmed COVID-19 with either syncope or presyncope. This "study" group (n = 37) was compared with an age and gender-matched cohort of patients without syncope ("control") (n = 40). Syncope was attributed to various categories. We compared telemetry data, treatments received, and clinical outcomes between the two groups. RESULTS: Among 1000 COVID-19 patients admitted to the Mount Sinai Hospital, the incidence of syncope/presyncope was 3.7%. The median age of the entire cohort was 69 years (range 26-89+ years) and 55% were men. Major comorbidities included hypertension, diabetes, and coronary artery disease. Syncopal episodes were categorized as (a) unspecified in 59.4% patients, (b) neurocardiogenic in 15.6% patients, (c) hypotensive in 12.5% patients, and (d) cardiopulmonary in 3.1% patients with fall versus syncope and seizure versus syncope in 2 of 32 (6.3%) and 1 of 33 (3.1%) patients, respectively. Compared with the "control" group, there were no significant differences in both admission and peak blood levels of d-dimer, troponin-I, and CRP in the "study" group. Additionally, there were no differences in arrhythmias or death between both groups. CONCLUSIONS: Syncope/presyncope in patients hospitalized with COVID-19 is uncommon and is infrequently associated with a cardiac etiology or associated with adverse outcomes compared to those who do not present with these symptoms.

Human Disease Ontology 2018 update: classification, content and workflow expansion.

The Human Disease Ontology (DO) (http://www.disease-ontology.org), database has undergone significant expansion in the past three years. The DO disease classification includes specific formal semantic rules to express meaningful disease models and has expanded from a single asserted classification to include multiple-inferred mechanistic disease classifications, thus providing novel perspectives on related diseases. Expansion of disease terms, alternative anatomy, cell type and genetic disease classifications and workflow automation highlight the updates for the DO since 2015. The enhanced breadth and depth of the DO's knowledgebase has expanded the DO's utility for exploring the multi-etiology of human disease, thus improving the capture and communication of health-related data across biomedical databases, bioinformatics tools, genomic and cancer resources and demonstrated by a 6.6× growth in DO's user community since 2015. The DO's continual integration of human disease knowledge, evidenced by the more than 200 SVN/GitHub releases/revisions, since previously reported in our DO 2015 NAR paper, includes the addition of 2650 new disease terms, a 30% increase of textual definitions, and an expanding suite of disease classification hierarchies constructed through defined logical axioms.

Management of Sleep Disordered Breathing in Patients with Heart Failure.

PURPOSE OF REVIEW: This paper reviews treatment options for sleep disordered breathing (SDB) in patients with heart failure. We sought to identify therapies for SDB with the best evidence for long-term use in patients with heart failure and to minimize uncertainties in clinical practice by examining frequently discussed questions: what is the role of continuous positive airway pressure (CPAP) in patients with heart failure? Is adaptive servo-ventilation (ASV) safe in patients with heart failure? To what extent is SDB a modifiable risk factor? RECENT FINDINGS: Consistent evidence has demonstrated that the development of SDB in patients with heart failure is a poor prognostic indicator and a risk factor for cardiovascular mortality. However, despite numerous available interventions for obstructive sleep apnea and central sleep apnea, it remains unclear what effect these therapies have on patients with heart failure. To date, all major randomized clinical trials have failed to demonstrate a survival benefit with SDB therapy and one major study investigating the use of adaptive servo-ventilation demonstrated harm. Significant questions persist regarding the management of SDB in patients with heart failure. Until appropriately powered trials identify a treatment modality that increases cardiovascular survival in patients with SDB and heart failure, a patient's heart failure management should remain the priority of medical care.

Novel polymorphisms associated with hyperalphalipoproteinemia and apparent cardioprotection.

BACKGROUND: Hyperalphalipoproteinemia (HALP) is inversely correlated with coronary heart disease (CHD) although genetic variants associated with high serum levels of high-density lipoprotein cholesterol (HDL-C) have not been shown to be cardioprotective. OBJECTIVE: The objective of the study was to uncover novel genetic variants associated with HALP and possibly with reduced risk of CHD. METHODS: Exome sequencing data, HDL-C, and triglyceride levels were analyzed in 1645 subjects. They included the University of Maryland outpatients with high HDL-C (n = 12), Cardiovascular Health Study (n = 210), Jackson Heart Study (n = 402), Multi-Ethnic Study of Atherosclerosis (n = 404), Framingham Heart Study (n = 463), and Old Order Amish (n = 154). RESULTS: Novel nonsynonymous single-nucleotide polymorphisms (nsSNPs) were identified in men and women with primary HALP (mean HDL-C, 145 ± 30 mg/dL). Using PolyPhen-2 and Combined Annotation Dependent Depletion to estimate the predictive effect of each nsSNP on the gene product, rare, deleterious polymorphisms in UGT1A3, PLLP, PLEKHH1, ANK2, DIS3L, ACACB, and LRP4 were identified in 16 subjects with HALP but not in any tested subject with low HDL-C (<40 mg/dL). In addition, a single novel polymorphism, rs376849274, was found in OSBPL1A. The majority of these candidate genes have been implicated in fat and lipid metabolism, and none of these subjects has a history of CHD despite 75% of subjects having risk factors for CHD. Overall, the probability of finding these nsSNPs in a non-high HDL-C population ranges from 1 × 10-17 to 1 × 10-25. CONCLUSION: Novel functional polymorphisms in 8 candidate genes are associated with HALP in the absence of CHD. Future study is required to examine the extent to which these genes may affect HDL function and serve as potential therapeutic targets for CHD risk reduction.