Publications

2015

Lange DC, Glidden D, Secemsky EA, Ordovas K, Deeks SG, Martin JN, Bolger AF, Hsue PY. Mitral Annular and Coronary Artery Calcification Are Associated with Mortality in HIV-Infected Individuals.. PloS one. 2015;10(7):e0130592. PMID: 26132465

BACKGROUND: HIV infection increases cardiovascular risk. Coronary artery calcification (CAC) and mitral annular calcification (MAC) identify patients at risk for cardiovascular disease (CVD). The purpose of this study was to examine the association between MAC, CAC and mortality in HIV-infected individuals.

METHODS AND RESULTS: We studied 152 asymptomatic HIV-infected individuals with transthoracic echocardiography (TTE) and computed tomography (CT). MAC was identified on TTE using standardized criteria. Presence of CAC, CAC score and CAC percentiles were determined using the modified Agatston criteria. Mortality data was obtained from the Social Security and National Death Indices (SSDI/NDI). The median age was 49 years; 87% were male. The median duration of HIV was 16 years; 84% took antiretroviral therapy; 64% had an undetectable viral load. CVD risk factors included hypertension (35%), smoking (62%) and dyslipidemia (35%). Twenty-five percent of individuals had MAC, and 42% had CAC. Over a median follow-up of 8 years, 11 subjects died. Subjects with CAC had significantly higher mortality compared to those with MAC only or no MAC. The Harrell's C-statistic of CAC was 0.66 and increased to 0.75 when MAC was added (p = 0.05). MAC, prior CVD, age and HIV viral load were independently associated with higher age- and gender-adjusted CAC percentiles in an adjusted model (p < 0.05 for all).

CONCLUSION: In HIV patients, the presence of MAC, traditional risk factors and HIV viral load were independently associated with CAC. Presence of CAC and MAC may be useful in identifying HIV-infected individuals at higher risk for death.

2014

Moyers BS, Secemsky EA, Vittinghoff E, Wong JK, Havlir D V, Hsue PY, Tseng ZH. Effect of left ventricular dysfunction and viral load on risk of sudden cardiac death in patients with human immunodeficiency virus.. The American journal of cardiology. 2014;113(7):1260–5. PMID: 24521717

Human immunodeficiency virus (HIV)-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EF<30% predicted SCD (hazard ratio [HR] 9.5, 95% confidence interval [CI] 1.7 to 53.3, p=0.01 and HR 38.5, 95% CI 7.6 to 195.0, p<0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, p<0.001) but not AIDS death, even after adjusting for EF. The association between EF<40% and SCD was greater in subjects with detectable versus undetectable HIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p=0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population.

Waldo SW, Secemsky EA, O’Brien C, Kennedy KF, Pomerantsev E, Sundt TM, McNulty EJ, Scirica BM, Yeh RW. Surgical ineligibility and mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention.. Circulation. 2014;130(25):2295–301. PMID: 25391519

BACKGROUND: Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention.

METHODS AND RESULTS: All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16-18.15; P<0.001) and long-term mortality (hazard ratio, 2.98; 95% confidence interval, 1.88-4.72, P<0.001) after percutaneous coronary intervention.

CONCLUSIONS: Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization.

Patel RB, Secemsky EA. Clinical features of heart failure and acute coronary syndromes.. Clinics in laboratory medicine. 2014;34(1):15–30, xi. PMID: 24507784

This article provides a brief overview of the clinical presentation, laboratory and radiologic features, and basic management principles in patients with congestive heart failure (CHF) and acute coronary syndromes (ACS). CHF is a clinical syndrome that typically results in symptoms of congestion and hypoperfusion. A thorough physical examination complemented by cardiac biomarkers and imaging are essential in making the diagnosis. Medical and device therapies for CHF target improvement in survival as well as control of symptoms. The management of ACS involves making a prompt diagnosis through the use of a focused history and physical examination, electrocardiogram assessment, and cardiac biomarker evaluation. Timely revascularization along with optimal medical management have helped to improve patient outcomes and mortality.

2013

2012

Tseng ZH, Secemsky EA, Dowdy D, Vittinghoff E, Moyers B, Wong JK, Havlir D V, Hsue PY. Sudden cardiac death in patients with human immunodeficiency virus infection.. Journal of the American College of Cardiology. 2012;59(21):1891–6. PMID: 22595409

OBJECTIVES: The aim of this study was to determine the incidence and clinical characteristics of sudden cardiac death (SCD) in patients with human immunodeficiency virus (HIV) infection.

BACKGROUND: As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described.

METHODS: The records of 2,860 consecutive patients in a public HIV clinic in San Francisco between April 2000 and August 2009 were examined. Identification of deaths, causes of death, and clinical characteristics were obtained by search of the National Death Index and/or clinic records. SCDs were determined using published retrospective criteria: 1) the International Classification of Diseases-10th Revision, code for all cardiac causes of death; and (2) circumstances of death meeting World Health Organization criteria.

RESULTS: Of 230 deaths over a median of 3.7 years of follow-up, 30 (13%) met SCD criteria, 131 (57%) were due to acquired immune deficiency syndrome (AIDS), 25 (11%) were due to other (natural) diseases, and 44 (19%) were due to overdoses, suicides, or unknown causes. SCDs accounted for 86% of all cardiac deaths (30 of 35). The mean SCD rate was 2.6 per 1,000 person-years (95% confidence interval: 1.8 to 3.8), 4.5-fold higher than expected. SCDs occurred in older patients than did AIDS deaths (mean 49.0 vs. 44.9 years, p = 0.02). Compared with AIDS and natural deaths combined, SCDs had a higher prevalence of prior myocardial infarction (17% vs. 1%, p < 0.0005), cardiomyopathy (23% vs. 3%, p < 0.0005), heart failure (30% vs. 9%, p = 0.004), and arrhythmias (20% vs. 3%, p = 0.003).

CONCLUSIONS: SCDs account for most cardiac and many non-AIDS natural deaths in HIV-infected patients. Further investigation is needed to ascertain underlying mechanisms, which may include inflammation, antiretroviral therapy interruption, and concomitant medications.

2011

Secemsky EA, Verrier RL, Cooke G, Ghossein C, Subacius H, Manuchehry A, Herzog CA, Passman R. High prevalence of cardiac autonomic dysfunction and T-wave alternans in dialysis patients.. Heart rhythm. 2011;8(4):592–8. PMID: 21126602

BACKGROUND: Chronic hemodialysis (HD) patients have an elevated risk of sudden cardiac death (SCD), particularly in the 24 hours before the first HD of the week. Temporal changes in cardiac autonomic dysfunction, as characterized by abnormalities in heart rate variability (HRV) and heart rate turbulence (HRT), along with T-wave alternans (TWA), may contribute to this dispersion of risk.

OBJECTIVE: This study sought to determine the prevalence of abnormal HRV, HRT, and TWA in HD patients and to compare their temporal distribution among periods of variable SCD risk.

METHODS: HRV, HRT, and TWA were analyzed from 72-hour Holter monitors in HD patients, and results were compared among the 24-hour high-risk period before the first dialysis session of the week, the 24-hour intermediate-risk period beginning with the weeks' first dialysis, and the low-risk period the day after the first dialysis. Positive cut points were standard deviation of all normal R-R intervals ≤70 ms for HRV, onset ≥0% and/or slope ≤2.5 ms/R-R for HRT, and ≥53 μV for TWA.

RESULTS: Of 41 enrollees, 28 (46% male, age 55 ± 12, ejection fraction 57% ± 11%) had sufficient data for analysis. Abnormalities were prevalent with 82%, 75%, and 96% of patients reaching threshold for HRV, HRT, and TWA in at least one 24-hour period, respectively. There was no significant difference in the prevalence of abnormal measures among dialytic intervals nor in the intraindividual distribution of abnormal measures (P >.05 for all).

CONCLUSION: Abnormal HRV, HRT, and TWA are prevalent in HD patients and may indicate heightened SCD risk. No significant correlation was observed among these measures and recognized periods of variable risk.

Secemsky E, Lange D, Waters DD, Goldschlager NF, Hsue PY. Hemodynamic and arrhythmogenic effects of cocaine in hypertensive individuals.. Journal of clinical hypertension (Greenwich, Conn.). 2011;13(10):744–9. PMID: 21974762

Despite the increased risk of myocardial infarction, aortic dissection, and arrhythmias in patients with hypertension who use cocaine, the hemodynamic and arrhythmogenic effects of cocaine use have not been well characterized in this population. The authors hypothesized that patients with hypertension demonstrate extreme, transient changes in arterial pressures as well as new arrhythmic activity during cocaine use. Ambulatory blood pressures, heart rates, and electrocardiograms (AECGs) were recorded for 48 hours in 10 patients with a history of hypertension who smoke cocaine. Active cocaine use was identified through patient diaries and manual activation of the blood pressure cuff. Of the 10 patients studied (6 men, 7 African Americans, age 49±8 years), 8 were taking antihypertensive medications. The mean blood pressure prior to cocaine use was 126/77 mm Hg and average increase in systolic, diastolic, and mean arterial pressure after use was 74 mm Hg, 30 mm Hg, and 45 mm Hg, respectively (P<.0001 for all). There was no significant change in heart rate. AECGs demonstrated arrhythmic activity during cocaine use, including 6 patients with increased atrial and ventricular ectopy, 2 patients with episodes of nonsustained atrial tachycardia, and 1 patient with 3 episodes of nonsustained monomorphic ventricular tachycardia. Cocaine use resulted in extreme elevations in arterial pressures in patients with hypertension taking medication. Cocaine use was also associated with an increase in arrhythmic activity. These findings may underlie the heightened risk of myocardial infarction, aortic dissection, and potentially lethal arrhythmias in patients with hypertension who use cocaine.