Bio

Clinical Focus


  • Channelopathies (Long QT, Brugada, CPVT)
  • Atrial Fibrillation
  • Clinical Cardiac Electrophysiology
  • Arrhythmias, Cardiac

Academic Appointments


Administrative Appointments


  • Director, Stanford Inherited Cardiac Arrhythmia Clinic (2013 - Present)

Honors & Awards


  • Finalist, FGTB Young Investigator Award, American Heart Association (2013)
  • Harold Amos Faculty Development Award, Robert Wood Johnson Foundation (2012-2016)
  • Fellow to Faculty Award, American Heart Association (2011-2016)
  • Loan Repayment Program Award, NIH (20010-2014)
  • Dean's Fellow Research Award, Stanford University (2006-2008)
  • National Research Service Award, NIH (2006-2008)

Professional Education


  • Internship:Massachusetts General Hospital (7/2002) MA
  • Residency:Massachusetts General Hospital (6/2004) MA
  • Board Certification: Clinical Cardiac Electrophysiology, American Board of Internal Medicine (2011)
  • Fellowship:Stanford University School of Medicine (6/2007) CA
  • Fellowship:Stanford University Medical Center (12/2010) CA
  • Medical Education:Harvard University Health Services (06/2001) MA
  • Board Certification: Cardiovascular Disease, American Board of Internal Medicine (2007)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2004)
  • Fellowship, Stanford, Electrophysiology (2010)
  • Fellowship, Stanford, Cardiology (2007)
  • Residency, Maassachusetts General Hospital, Internal Medicine (2004)

Research & Scholarship

Clinical Trials


  • Attain Performa(TM) Quadripolar Lead Study Recruiting

    The purpose of the study is to evaluate the safety and efficacy of the Medtronic Attain Performa Quadripolar Leads (Model 4298, 4398, and 4598) during and post the implant procedure. This study will also assess the interactions of the Attain Performa leads with the entire Medtronic CRT-D system.

    View full details

Publications

Journal Articles


  • Patterns and prognosis of all components of the J-wave pattern in multiethnic athletes and ambulatory patients. American heart journal Muramoto, D., Yong, C. M., Singh, N., Aggarwal, S., Perez, M., Ashley, E., Hadley, D., Froelicher, V. 2014; 167 (2): 259-266

    Abstract

    Despite recent concern about the significance of the J-wave pattern (also often referred to as early repolarization) and the importance of screening in athletes, there are limited rigorous prognostic data characterizing the 3 components of the J-wave pattern (ST elevation, J waves, and QRS slurs). We aim to assess the prevalence, patterns, and prognosis of the J-wave pattern among both stable clinical and athlete populations.We retrospectively studied 4,041 electrocardiograms from a multiethnic clinical population from 1997 to 1999 at the Veterans Affairs Palo Alto Health Care System. We also examined preparticipation electrocardiograms of 1,114 Stanford University varsity athletes from 2007 to 2008. Strictly defined criteria for components of the J-wave pattern were examined. In clinical subjects, prognosis was assessed using the end point of cardiovascular death after 7 years of follow-up.Components of the J-wave pattern were most prevalent in males; African Americans; and, particularly, athletes, with the greatest variations demonstrated in the lateral leads. ST elevation was the most common. Inferior J waves and slurs, previously linked to cardiovascular risk, were observed in 9.6% of clinical subjects and 12.3% of athletes. J waves, slurs, or ST elevation was not associated with time to cardiovascular death in clinical subjects, and ST-segment slope abnormalities were not prevalent enough in conjunction with them to reach significance.J waves, slurs, or ST elevation was not associated with increased hazard of cardiovascular death in our large multiethnic, ambulatory population. Even subsets of J-wave patterns, recently proposed to pose a risk of arrhythmic death, occurred at such a high prevalence as to negate their utility in screening.

    View details for DOI 10.1016/j.ahj.2013.10.027

    View details for PubMedID 24439988

  • Prevalence and clinical correlates of right ventricular dysfunction in patients with hypertrophic cardiomyopathy. American journal of cardiology Finocchiaro, G., Knowles, J. W., Pavlovic, A., Perez, M., Magavern, E., Sinagra, G., Haddad, F., Ashley, E. A. 2014; 113 (2): 361-367

    Abstract

    Hypertrophic cardiomyopathy (HC) is a disease that mainly affects the left ventricle (LV), however recent studies have suggested that it can also be associated with right ventricular (RV) dysfunction. The objective of this study was to determine the prevalence of RV dysfunction in patients with HC and its relation with LV function and outcome. A total of 324 consecutive patients with HC who received care at Stanford Hospital from 1999 to 2012 were included in the study. A group of 99 prospectively recruited age- and gender-matched healthy volunteers were used as controls. RV function was quantified using the RV fractional area change, tricuspid annular plane systolic excursion (TAPSE), and RV myocardial performance index (RVMPI). Compared with the controls, the patients with HC had a higher RVMPI (0.51 ± 0.18 vs 0.25 ± 0.06, p <0.001) and lower TAPSE (20 ± 3 vs 24 ± 4, p <0.001). RV dysfunction based on an RVMPI >0.4 and TAPSE <16 mm was found in 71% and 11% of the HC and control groups, respectively. Worst LV function and greater pulmonary pressures were independent correlates of RV dysfunction. At an average follow-up of 3.7 ± 2.3 years, 17 patients had died and 4 had undergone heart transplantation. LV ejection fraction <50% and TAPSE <16 mm were independent correlates of outcome (hazard ratio 3.98, 95% confidence interval 1.22 to 13.04, p = 0.02; and hazard ratio 3.66, 95% confidence interval 1.38 to 9.69, p = 0.009, respectively). In conclusion, RV dysfunction based on the RVMPI is common in patients with HC and more frequently observed in patients with LV dysfunction and pulmonary hypertension. RV dysfunction based on the TAPSE was independently associated with an increased likelihood of death or transplantation.

    View details for DOI 10.1016/j.amjcard.2013.09.045

    View details for PubMedID 24230980

  • Use of Medicare Data to Identify Coronary Heart Disease Outcomes in the Women's Health Initiative. Circulation. Cardiovascular quality and outcomes Hlatky, M. A., Ray, R. M., Burwen, D. R., Margolis, K. L., Johnson, K. C., Kucharska-Newton, A., Manson, J. E., Robinson, J. G., Safford, M. M., Allison, M., Assimes, T. L., Bavry, A. A., Berger, J., Cooper-DeHoff, R. M., Heckbert, S. R., Li, W., Liu, S., Martin, L. W., Perez, M. V., Tindle, H. A., Winkelmayer, W. C., Stefanick, M. L. 2014; 7 (1): 157-162

    Abstract

    . Unique identifier: NCT00000611.

    View details for DOI 10.1161/CIRCOUTCOMES.113.000373

    View details for PubMedID 24399330

  • Does CHA2DS2-VASc Improve Stroke Risk Stratification in Postmenopausal Women with Atrial Fibrillation? American journal of medicine Abraham, J. M., Larson, J., Chung, M. K., Curtis, A. B., Lakshminarayan, K., Newman, J. D., Perez, M., Rexrode, K., Shara, N. M., Solomon, A. J., Stefanick, M. L., Torner, J. C., Wilkoff, B. L., Wassertheil-Smoller, S. 2013; 126 (12): 1143 e1-8

    Abstract

    Risk stratification of atrial fibrillation patients with a congestive heart failure (C), hypertension (H), age ≥ 75 (A), diabetes (D), stroke or transient ischemic attack (TIA) (S2) (CHADS2) score of <2 remains imprecise, particularly in women. Our objectives were to validate the CHADS2 and congestive heart failure (C), hypertension (H), age ≥ 75 (A2), diabetes (D), stroke, TIA or prior thromboembolic disease (S2)- vascular disease (V), age 65-74 (A), female gender (S) (CHA2DS2-VASc) stroke risk scores in a healthy cohort of American women with atrial fibrillation and to determine whether CHA2DS2-VASc further risk-stratifies individuals with a CHADS2 score of <2.We identified a cohort of 5981 women with atrial fibrillation not on warfarin at baseline (mean age 65.9 ± 7.2 years) enrolled in the Women's Health Initiative and followed for a median of 11.8 years. Univariate and multivariate proportional hazards analyses were used to examine these 2 risk scores, with main outcome measures being annualized event rates of ischemic stroke or transient ischemic attack stratified by risk score.Annualized stroke/transient ischemic attack rates ranged from 0.36% to 2.43% with increasing CHADS2 score (0-4+) (hazard ratio [HR] 1.57; 95% confidence interval [CI], 1.45-1.71 for each 1-point increase) and 0.20%-2.02% with increasing CHA2DS2-VASc score (1-6+) (HR 1.50; 95% CI, 1.41-1.60 for each 1-point increase). CHA2DS2-VASc had a higher c statistic than CHADS2: 0.67 (95% CI, 0.65-0.69) versus 0.65 (95% CI, 0.62-0.67), P <.01. For CHADS2 scores <2, stroke risk almost doubled with every additional CHA2DS2-VASc point.Although both CHADS2, and CHA2DS2-VASc are predictive of stroke risk in postmenopausal women with atrial fibrillation, CHA2DS2-VASc further risk-stratifies patients with a CHADS2 score <2.

    View details for DOI 10.1016/j.amjmed.2013.05.023

    View details for PubMedID 24139523

  • Variation in Use of Left Ventriculography in the Veterans Affairs Health Care System CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Heidenreich, P. A., Lin, S., Knowles, J. W., Perez, M., Maddox, T. M., Ho, M. P., Rumsfeld, J. S., Sahay, A., Massie, B. M., Tsai, T. T., Witteles, R. M. 2013; 6 (6): 687-693

    Abstract

    Contrast left ventriculography is a method of measuring left ventricular function usually performed at the discretion of the invasive cardiologist during cardiac catheterization. We sought to determine variation in the use of left ventriculography in the Veterans Affairs (VA) Health Care System.We identified adult patients who underwent cardiac catheterization including coronary angiography between 2000 and 2009 in the VA Health Care System. We determined patient and hospital predictors of the use of left ventriculography as well as the variation in use across VA facilities. Results were validated using data from the VA's Clinical Assessment, Reporting, and Tracking (CART) program. Of 457 170 cardiac catheterization procedures among 336 853 patients, left ventriculography was performed on 263 695 (58%) patients. Use of left ventriculography decreased over time (64% in 2000 to 50% in 2009) and varied markedly across facilities (<1->95% of cardiac catheterizations). Patient factors explained little of the large variation in use between facilities. When the cohort was restricted to those with an echocardiogram in the prior 30 days and no intervening event, left ventriculography was still performed in 50% of cases.There is large variation in the use of left ventriculography across VA facilities that is not explained by patient characteristics.

    View details for DOI 10.1161/CIRCOUTCOMES.113.000199

    View details for Web of Science ID 000330362400017

    View details for PubMedID 24192569

  • Prognostic implications of the J wave ECG patterns. Journal of electrocardiology Yong, C. M., Perez, M., Froelicher, V. 2013; 46 (5): 408-410

    View details for DOI 10.1016/j.jelectrocard.2013.06.010

    View details for PubMedID 23870660

  • J wave patterns and their prognostic value in African Americans. Journal of electrocardiology Perez, M. V., Froelicher, V. 2013; 46 (5): 442-445

    Abstract

    Examples of racial differences in physiologic measurements and disease rates abound. What is considered "normal" in one population can be interpreted as a marker of disease in another. Differences in early repolarization patterns, such as J-waves, QRS slurs and ST elevations (STE), on the electrocardiogram (ECG) in those of African compared to non-African descent are prime examples. Here we will review some of the initial observations made in the ECG in Africans, discuss the cohort studies that compare these patterns in African Americans and Caucasians, summarize some of our own observations, and speculate on the nature of these differences.

    View details for DOI 10.1016/j.jelectrocard.2013.06.015

    View details for PubMedID 23885885

  • African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative. American heart journal Perez, M. V., Hoffmann, T. J., Tang, H., Thornton, T., Stefanick, M. L., Larson, J. C., Kooperberg, C., Reiner, A. P., Caan, B., Iribarren, C., Risch, N. 2013; 166 (3): 566-572 e1

    Abstract

    Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk.The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses.Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort.African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans.

    View details for DOI 10.1016/j.ahj.2013.05.024

    View details for PubMedID 24016508

  • Risk factors for atrial fibrillation and their population burden in postmenopausal women: the Women's Health Initiative Observational Study. Heart Perez, M. V., Wang, P. J., Larson, J. C., Soliman, E. Z., Limacher, M., Rodriguez, B., Klein, L., Manson, J. E., Martin, L. W., Prineas, R., Connelly, S., Hlatky, M., Wassertheil-Smoller, S., Stefanick, M. L. 2013; 99 (16): 1173-1178

    Abstract

    OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors. DESIGN: Prospective observational study. SETTING: The Women's Health Initiative (WHI) Observational Study. PATIENTS: 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF. MAIN OUTCOME MEASURES: Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF. RESULTS: Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians. CONCLUSIONS: Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.

    View details for DOI 10.1136/heartjnl-2013-303798

    View details for PubMedID 23756655

  • Different patterns of bundle-branch blocks and the risk of incident heart failure in the Women's Health Initiative (WHI) study. Circulation. Heart failure Zhang, Z., Rautaharju, P. M., Soliman, E. Z., Manson, J. E., Martin, L. W., Perez, M., Vitolins, M., Prineas, R. J. 2013; 6 (4): 655-661

    Abstract

    We evaluated the risk of incident heart failure (HF) associated with bundle-branch blocks (BBBs) in postmenopausal women.Cox's regression was used to evaluate hazard ratios with 95% confidence intervals for HF among 65975 participants of the Women's Health Initiative (WHI) study during an average follow-up of 14 years. BBBs observed in 1676 women at baseline were categorized into left, right, and indetermined-type BBBs (LBBB, RBBB, and intraventricular conduction defect, respectively). Compared with women with no BBB, LBBB, and intraventricular conduction defect were strong predictors of incident HF in multivariable-adjusted risk models (hazard ratio, 3.79; confidence interval, 2.95-4.87 for LBBB and hazard ratio, 3.53; confidence interval, 2.14-5.81 for intraventricular conduction defect). RBBB was not a significant predictor of incident HF in multivariable-adjusted risk model, but the combination of RBBB and left anterior fascicular block was a strong predictor (hazard ratio, 2.96; confidence interval, 1.77-4.93). QRS duration was an independent predictor of incident HF only in LBBB, with more pronounced risk at QRS ≥ 140 ms than at <140 ms. QRS nondipolar voltage (RNDPV) was an independent predictor in both RBBB and LBBB and, in addition, in LBBB, QRS/STT angle and ST J-point depression in aVL were independent predictors.LBBB, intraventricular conduction defect, and RBBB combined with left anterior fascicular block are strong predictors of incident HF in multivariable-adjusted risk models, but RBBB is not a significant predictor. QRS duration ≥ 140 ms may warrant consideration in LBBB as an indication for further diagnostic evaluation for possible therapeutic and preventive action. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

    View details for DOI 10.1161/CIRCHEARTFAILURE.113.000217

    View details for PubMedID 23729198

  • Taming Rare Variation With Known Biology in Long QT Syndrome. Circulation. Cardiovascular genetics Perez, M. V., Ashley, E. A. 2013; 6 (3): 227-229

    View details for DOI 10.1161/CIRCGENETICS.113.000199

    View details for PubMedID 23778589

  • From bedside to bench JOURNAL OF ELECTROCARDIOLOGY Perez, M., Froelicher, V. 2013; 46 (2): 114-115
  • Exercise capacity and paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy. Heart (British Cardiac Society) Azarbal, F., Singh, M., Finocchiaro, G., Le, V. V., Schnittger, I., Wang, P., Myers, J., Ashley, E., Perez, M. 2013

    Abstract

    Atrial fibrillation (AF) is the most common arrhythmia among patients with hypertrophic cardiomyopathy (HCM). The relationship between paroxysmal AF and exercise capacity in this population is incompletely understood.Patients with HCM underwent symptom-limited cardiopulmonary testing with expired gas analysis at Stanford Hospital between October 2006 and October 2012. Baseline demographics, medical histories and resting echocardiograms were obtained for all subjects. Diagnosis of AF was established by review of medical records and baseline ECG. Those with paroxysmal AF were in sinus rhythm at the time of cardiopulmonary testing with expired gas analysis. Exercise intolerance was defined as peak VO2<20 mL/kg/min. We used multivariate logistic regression to evaluate the association between exercise intolerance and paroxysmal AF.Among the 265 patients recruited, 55 had AF (28 paroxysmal and 27 permanent). Compared with those without AF, subjects with paroxysmal AF were older, more likely to use antiarrhythmic and anticoagulant medications, and had larger left atria. Patients with paroxysmal AF achieved lower peak VO2 (21.9±9.2 mL/kg/min vs 26.9±10.8 mL/kg/min, p=0.02) and were more likely to have exercise intolerance (61% vs 28%, p<0.001) compared with those without AF. After adjustment for age, sex and body mass index (BMI) exercise intolerance remained significantly associated with paroxysmal AF (OR 4.65, 95% CI 1.83 to 11.83, p=0.001).Patients with HCM and paroxysmal AF demonstrate exercise intolerance despite being in sinus rhythm at the time of exercise testing.

    View details for DOI 10.1136/heartjnl-2013-304908

    View details for PubMedID 24326897

  • Effects of Postmenopausal Hormone Therapy on Incident Atrial Fibrillation The Women's Health Initiative Randomized Controlled Trials CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY Perez, M. V., Wang, P. J., Larson, J. C., Virnig, B. A., Cochrane, B., Curb, J. D., Klein, L., Manson, J. E., Martin, L. W., Robinson, J., Wassertheil-Smoller, S., Stefanick, M. L. 2012; 5 (6): 1108-1116

    Abstract

    Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.The Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.ClinicalTrials.gov; Identifier: NCT00000611.

    View details for DOI 10.1161/CIRCEP.112.972224

    View details for Web of Science ID 000313586900018

    View details for PubMedID 23169946

  • Semantic Confusion: The Case of Early Repolarization and the J Point AMERICAN JOURNAL OF MEDICINE Perez, M. V., Friday, K., Froelicher, V. 2012; 125 (9): 843-844

    View details for DOI 10.1016/j.amjmed.2011.08.024

    View details for Web of Science ID 000308693000010

    View details for PubMedID 22340816

  • Prognostic Implications of Q Waves and T-Wave Inversion Associated With Early Repolarization MAYO CLINIC PROCEEDINGS Uberoi, A., Sallam, K., Perez, M., Jain, N. A., Ashley, E., Froelicher, V. 2012; 87 (7): 614-619

    Abstract

    To evaluate the prevalence of early polarization (ER) in a stable population and to evaluate the prognostic significance of the association or absence of Q waves or T-wave inversion (TWI).In this retrospective study performed at the university-affiliated Palo Alto Veterans Affairs Health Care Center from March 1, 1987, through December 31, 1999, we evaluated outpatient electrocardiograms. Vital status and cause of death were determined in all patients, with a mean ± SD follow-up of 7.6±3.8 years.Of the 29,281 patients, 87% were men and 13% were African American. Inferior or lateral ER was present in 664 patients (2.3%): in inferior leads in 185 (0.6%), in lateral leads in 479 (1.6%) , and in both inferior and lateral leads in 163 (0.6%). Only when Q waves or TWI accompanied ER was there an increased risk of cardiovascular death (Cox proportional hazards regression model, 5.0; 95% confidence interval, 3.4-7.2; P<.001).Common patterns of ER without concomitant Q waves or TWI are not associated with increased risk of cardiovascular death; however, when either occurs with ER, there is a hazard ratio of 5.0. These findings confirm that ER is a benign entity; however, the presence of Q waves or TWI with ER is predictive of increased cardiovascular death.

    View details for DOI 10.1016/j.mayocp.2012.04.009

    View details for Web of Science ID 000306872800003

    View details for PubMedID 22766081

  • Use and overuse of left ventriculography AMERICAN HEART JOURNAL Witteles, R. M., Knowles, J. W., Perez, M., Morris, W. M., Spettell, C. M., Brennan, T. A., Heidenreich, P. A. 2012; 163 (4): 617-?

    Abstract

    Left ventriculography provided the first imaging of left ventricular function and was historically performed as part of coronary angiography despite a small but significant risk of complications. Because modern noninvasive imaging techniques are more accurate and carry smaller risks, the routine use of left ventriculography is of questionable utility. We sought to analyze the frequency that left ventriculography was performed during coronary angiography in patients with and without a recent alternative assessment of left ventricular function.We performed a retrospective analysis of insurance claims data from the Aetna health care benefits database including all adults who underwent coronary angiography in 2007. The primary outcome was the concomitant use of left ventriculography during coronary angiography.Of 96,235 patients who underwent coronary angiography, left ventriculography was performed in 78,705 (81.8%). Use of left ventriculography was high in all subgroups, with greatest use in younger patients, those with a diagnosis of coronary disease, and those in the Southern United States. In the population who had undergone a very recent ejection fraction assessment by another modality (within 30 days) and who had had no intervening diagnosis of new heart failure, myocardial infarction, hypotension, or shock (37,149 patients), left ventriculography was performed in 32,798 patients (88%)-a rate higher than in the overall cohort.Left ventriculography was performed in most coronary angiography cases and often when an alternative imaging modality had been recently completed. New clinical practice guidelines should be considered to decrease the overuse of this invasive test.

    View details for DOI 10.1016/j.ahj.2011.12.018

    View details for Web of Science ID 000303106800023

    View details for PubMedID 22520528

  • The prognostic value of early repolarization with ST-segment elevation in African Americans HEART RHYTHM Perez, M. V., Uberoi, A., Jain, N. A., Ashley, E., Turakhia, M. P., Froelicher, V. 2012; 9 (4): 558-565

    Abstract

    Increased prevalence of classic early repolarization, defined as ST-segment elevation (STE) in the absence of acute myocardial injury, in African Americans is well established. The prognostic value of this pattern in different ethnicities remains controversial.Measure association between early repolarization and cardiovascular mortality in African Americans.The resting electrocardiograms of 45,829 patients were evaluated at the Palo Alto Veterans Affairs Hospital. Subjects with inpatient status or electrocardiographic evidence of acute myocardial infarction were excluded, leaving 29,281 subjects. ST-segment elevation, defined as an elevation of >0.1 mV at the end of the QRS, was electronically flagged and visually adjudicated by 3 observers blinded to outcomes. An association between ethnicity and early repolarization was measured by using multivariate logistic regression. We analyzed associations between early repolarization and cardiovascular mortality by using the Cox proportional hazards regression analysis.Subjects were 13% women and 13.3% African Americans, with an average age of 55 years and followed for an average of 7.6 years, resulting in 1995 cardiovascular deaths. There were 479 subjects with lateral STE and 185 with inferior STE. After adjustment for age, sex, heart rate, and coronary artery disease, African American ethnicity was associated with lateral or inferior STE (odds ratio 3.1; P = .0001). While lateral or inferior STE in non-African Americans was independently associated with cardiovascular death (hazard ratio 1.6; P = .02), it was not associated with cardiovascular death in African Americans (hazard ratio 0.75; P = .50).Although early repolarization is more prevalent in African Americans, it is not predictive of cardiovascular death in this population and may represent a distinct electrophysiologic phenomenon.

    View details for DOI 10.1016/j.hrthm.2011.11.020

    View details for Web of Science ID 000302258100020

    View details for PubMedID 22094072

  • Catheter ablation of atrial fibrillation: state-of-the-art techniques and future perspectives JOURNAL OF CARDIOVASCULAR MEDICINE Santangeli, P., Di Biase, L., Burkhardt, D. J., Horton, R., Sanchez, J., Bai, R., Pump, A., Perez, M., Wang, P. J., Natale, A., Al-Ahmad, A. 2012; 13 (2): 108-124

    Abstract

    The impact of atrial fibrillation on the healthcare systems of Western countries is overwhelming, due to its independent association with death, systemic thromboembolism, impaired quality of life and hospitalizations. Catheter ablation is the only treatment thus far demonstrated capable of achieving cure in a substantial proportion of patients. Pulmonary vein antrum isolation (PVAI) is the cornerstone of current atrial fibrillation ablation techniques, with the greatest efficacy as a stand-alone procedure in patients with paroxysmal atrial fibrillation. Use of general anesthesia, open-irrigated ablation catheters and maintenance of periprocedural therapeutic warfarin has been demonstrated to increase the safety and effectiveness of PVAI. In patients with paroxysmal atrial fibrillation, the systematic addition of superior vena cava isolation increases the long-term freedom from atrial fibrillation recurrence. A more extensive ablation approach extending to the entire left atrial posterior wall and to complex fractionated electrograms (CFAEs) is warranted in nonparoxysmal atrial fibrillation patients, in whom nonpulmonary vein trigger sites are frequently identified. Up to one-third of these patients experiencing atrial fibrillation recurrence after ablation have evidence of triggers from the left atrial appendage. Isolation of this structure is the best treatment strategy to improve the long-term success rate. In recent years, in addition to the development of ablation techniques to increase the success rate, outcomes of atrial fibrillation treatment trials have been reconsidered. In particular, reduction of hospitalization, stroke and mortality, as well as economic factors, have all been considered relevant to evaluate the effectiveness of atrial fibrillation treatment. Large ongoing trials are specifically evaluating the impact of atrial fibrillation ablation on these outcomes. This article will summarize the state-of-the art techniques for atrial fibrillation ablation, and will discuss the contribution of ongoing studies to the future of atrial fibrillation ablation.

    View details for DOI 10.2459/JCM.0b013e32834f2371

    View details for Web of Science ID 000299652200004

    View details for PubMedID 22193837

  • Early Repolarization in an Ambulatory Clinical Population CIRCULATION Uberoi, A., Jain, N. A., Perez, M., Weinkopff, A., Ashley, E., Hadley, D., Turakhia, M. P., Froelicher, V. 2011; 124 (20): 2208-2214

    Abstract

    The significance of early repolarization, particularly regarding the morphology of the R-wave downslope, has come under question.We evaluated 29 281 resting ambulatory ECGs from the VA Palo Alto Health Care System. With PR interval as the isoelectric line and amplitude criteria ?0.1 mV, ST-segment elevation is defined at the end of the QRS, J wave as an upward deflection, and slur as a conduction delay on the QRS downstroke. Associations of ST-segment elevation patterns, J waves, and slurs with cardiovascular mortality were analyzed with Cox analysis. With a median follow-up of 7.6 years, there were 1995 cardiac deaths. Of 29 281 subjects, 87% were male (55±14 years) and 13% were female (56±17 years); 13% were black, 6% were Hispanic, and 81% were white or other. Six hundred sixty-four (2.3%) had inferior or lateral ST-segment elevation: 185 (0.6%) in inferior leads and 479 (1.6%) in lateral leads, 163 (0.6%) in both, and 0.4% had global elevation. A total of 4041 ECGs were analyzed with enhanced display, and 583 (14%) had J waves or slurring, which were more prevalent in those with than in those without ST-segment elevation (61% versus 13%; P<0.001). ST-segment elevation occurred more in those with than in those without J waves or slurs (12% versus 1.3%; P<0.001). Except when involving only inferior leads, all components of early repolarization were more common in young individuals, male subjects, blacks, and those with bradycardia. All patterns and components of early repolarization were associated with decreased cardiovascular mortality, but this was not significant after adjustment for age.We found no significant association between any components of early repolarization and cardiac mortality.

    View details for DOI 10.1161/CIRCULATIONAHA.111.047191

    View details for Web of Science ID 000297060700013

    View details for PubMedID 21986288

  • The Impact of ST Elevation on Athletic Screening CLINICAL JOURNAL OF SPORT MEDICINE Leo, T., Uberoi, A., Jain, N. A., Garza, D., Chowdhury, S., Freeman, J. V., Perez, M., Ashley, E., Froelicher, V. 2011; 21 (5): 433-440

    Abstract

    To demonstrate the prevalence and patterns of ST elevation (STE) in ambulatory individuals and athletes and compare the clinical outcomes.Retrospective cohort study. ST elevation was measured by computer algorithm and defined as ?0.1 mV at the end of the QRS complex. Elevation was confirmed, and J waves and slurring were coded visually.Veterans Affairs Palo Alto Health Care System and Stanford University varsity athlete screening evaluation.Overall, 45 829 electrocardiograms (ECGs) were obtained from the clinical patient cohort and 658 ECGs from athletes. We excluded inpatients and those with ECG abnormalities, leaving 20 901 outpatients and 641 athletes.Electrocardiogram evaluation and follow-up for vital status.All-cause and cardiovascular mortality and cardiac events.ST elevation in the anterior and lateral leads was more prevalent in men and in African Americans and inversely related to age and resting heart rate. Athletes had a higher prevalence of early repolarization even when matched for age and gender with nonathletes. ST elevation greater than 0.2 mV (2 mm) was very unusual. ST elevation was not associated with cardiac death in the clinical population or with cardiac events or abnormal test results in the athletes.Early repolarization is not associated with cardiac death and has patterns that help distinguish it from STE associated with cardiac conditions, such as myocardial ischemia or injury, pericarditis, and the Brugada syndrome.

    View details for DOI 10.1097/JSM.0B013E31822CF105

    View details for Web of Science ID 000294485000009

    View details for PubMedID 21892017

  • Interpretation of the Electrocardiogram of Young Athletes CIRCULATION Uberoi, A., Stein, R., Perez, M. V., Freeman, J., Wheeler, M., Dewey, F., Peidro, R., Hadley, D., Drezner, J., Sharma, S., Pelliccia, A., Corrado, D., Niebauer, J., Estes, M., Ashley, E., Froelicher, V. 2011; 124 (6): 746-757
  • Gene Coexpression Network Topology of Cardiac Development, Hypertrophy, and Failure CIRCULATION-CARDIOVASCULAR GENETICS Dewey, F. E., Perez, M. V., Wheeler, M. T., Watt, C., Spin, J., Langfelder, P., Horvath, S., Hannenhalli, S., Cappola, T. P., Ashley, E. A. 2011; 4 (1): 26-U129

    Abstract

    Network analysis techniques allow a more accurate reflection of underlying systems biology to be realized than traditional unidimensional molecular biology approaches. Using gene coexpression network analysis, we define the gene expression network topology of cardiac hypertrophy and failure and the extent of recapitulation of fetal gene expression programs in failing and hypertrophied adult myocardium.We assembled all myocardial transcript data in the Gene Expression Omnibus (n=1617). Because hierarchical analysis revealed species had primacy over disease clustering, we focused this analysis on the most complete (murine) dataset (n=478). Using gene coexpression network analysis, we derived functional modules, regulatory mediators, and higher-order topological relationships between genes and identified 50 gene coexpression modules in developing myocardium that were not present in normal adult tissue. We found that known gene expression markers of myocardial adaptation were members of upregulated modules but not hub genes. We identified ZIC2 as a novel transcription factor associated with coexpression modules common to developing and failing myocardium. Of 50 fetal gene coexpression modules, 3 (6%) were reproduced in hypertrophied myocardium and 7 (14%) were reproduced in failing myocardium. One fetal module was common to both failing and hypertrophied myocardium.Network modeling allows systems analysis of cardiovascular development and disease. Although we did not find evidence for a global coordinated program of fetal gene expression in adult myocardial adaptation, our analysis revealed specific gene expression modules active during both development and disease and specific candidates for their regulation.

    View details for DOI 10.1161/CIRCGENETICS.110.941757

    View details for Web of Science ID 000287353200014

    View details for PubMedID 21127201

  • Personalized Medicine and Cardiovascular Disease: From Genome to Bedside Current Cardiovascular Risk Reports S. Pan, F. E. Dewey, M. V. Perez, J. W. Knowles, R. Chen, A. J. Butte, E. A. Ashley 2011; 5: 542-551
  • Cost-Effectiveness of Genetic Testing in Family Members of Patients With Long-QT Syndrome CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Perez, M. V., Kumarasamy, N. A., Owens, D. K., Wang, P. J., Hlatky, M. A. 2011; 4 (1): 76-84

    Abstract

    Family members of patients with established long-QT syndrome (LQTS) often lack definitive clinical findings, yet may have inherited an LQTS mutation and be at risk of sudden death. Genetic testing can identify mutations in 75% of patients with LQTS, but genetic testing of family members remains controversial.We used a Markov model to assess the cost-effectiveness of 3 strategies for treating an asymptomatic 10-year-old, first-degree relative of a patient with clinically evident LQTS. In the genetic testing strategy, relatives undergo genetic testing only for the mutation identified in the index patient, and relatives who test positive for the mutation are treated with ?-blockers. This strategy was compared with (1) empirical treatment of relatives with ?-blockers and (2) watchful waiting, with treatment only after development of symptoms. The genetic testing strategy resulted in better survival and quality-adjusted life years at higher cost, with a cost-effectiveness ratio of $67 400 per quality-adjusted life year gained compared with watchful waiting. The cost-effectiveness of the genetic testing strategy improved to less than $50 000 per quality-adjusted life year gained when applied selectively either to (1) relatives with higher clinical suspicion of LQTS (pretest probability 65% to 81%), or to (2) families with a higher than average risk of sudden death, or to (3) larger families (2 or more first-degree relatives tested).Genetic testing of young first-degree relatives of patients with definite LQTS is moderately expensive, but can reach acceptable thresholds of cost-effectiveness when applied to selected patients.

    View details for DOI 10.1161/CIRCOUTCOMES.110.957365

    View details for Web of Science ID 000286311700014

    View details for PubMedID 21139095

  • Inappropriate pacing in a patient with managed ventricular pacing: What is the cause? HEART RHYTHM Perez, M. V., Al-Ahmad, A. A., Wang, P. J., Turakhia, M. P. 2010; 7 (9): 1336-1337

    Abstract

    A case of inappropriate atrial pacing in a patient with a pacemaker programmed with Managed Ventricular Pacing (MVP) mode, a proprietary algorithm in Medtronic devices, is presented. The patient was an 84-year-old woman who presented in sinus rhythm with complete atrioventricular block. A dual-chamber pacemaker was implanted and programmed to an MVP pacing mode. After the implant, the patient developed a relatively slow atrial tachyarrhythmia with 2:1 atrioventricular block and inappropriate atrial pacing, followed by a delay in tracking of the atrial tachyarrhythmia. The mechanisms for these behaviors are described.

    View details for DOI 10.1016/j.hrthm.2010.04.028

    View details for Web of Science ID 000281444100033

    View details for PubMedID 20435165

  • Addition of the Electrocardiogram to the Preparticipation Examination of College Athletes CLINICAL JOURNAL OF SPORT MEDICINE Le, V., Wheeler, M. T., Mandic, S., Dewey, F., Fonda, H., Perez, M., Sungar, G., Garza, D., Ashley, E. A., Matheson, G., Froelicher, V. 2010; 20 (2): 98-105

    Abstract

    Although the use of standardized cardiovascular (CV) system-focused history and physical examination is recommended for the preparticipation examination (PPE) of athletes, the addition of the electrocardiogram (ECG) has been controversial. Because the impact of ECG screening on college athletes has rarely been reported, we analyzed the findings of adding the ECG to the PPE of Stanford athletes.For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database.Although the use of standardized CV-focused history and physical examination are recommended for the PPE of athletes, the addition of the ECG has been controversial. Because the feasibility and outcomes of ECG screening on college athletes have rarely been reported, we present findings derived from the addition of the ECG to the PPE of Stanford athletes. For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database.Six hundred fifty-eight recordings were obtained (54% men, 10% African-American, mean age 20 years) representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete right bundle branch block (RBBB) (13%), right axis deviation (RAD) (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for left ventricular hypertrophy (LVH) were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7%, and only 5 men had abnormal Q-waves. Sixty-three athletes (10%) were judged to have distinctly abnormal ECG findings possibly associated with conditions including hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia/cardiomyopathy. These athletes were offered further testing but this was not mandated according to the research protocol.Six hundred fifty-three recordings were obtained (54% men, 7% African American, mean age 20 years), representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete RBBB (13%), RAD (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for LVH were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7% and only 5 men had abnormal Q-waves. Sixty-five athletes (10%) were judged to have distinctly abnormal ECG findings suggestive of arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, and/or biventricular hypertrophy. These athletes will be submitted to further testing.Mass ECG screening is achievable within the collegiate setting by using volunteers when the appropriate equipment is available. However, the rate of secondary testing suggests the need for an evaluation of cost-effectiveness for mass screening and the development of new athlete-specific ECG interpretation algorithms.

    View details for DOI 10.1097/JSM.0b013e3181d44705

    View details for Web of Science ID 000275481500005

    View details for PubMedID 20215891

  • Adding an Electrocardiogram to the Pre-participation Examination in Competitive Athletes: A Systematic Review CURRENT PROBLEMS IN CARDIOLOGY Perez, M., Fonda, H., Le, V., Mitiku, T., Ray, J., Freeman, J. V., Ashley, E., Froelicher, V. F. 2009; 34 (12): 586-662

    Abstract

    No matter how rare, the death of young athletes is a tragedy. Can it be prevented? The European experience suggests that adding the electrocardiogram (ECG) to the standard medical and family history and physical examination can decrease cardiac deaths by 90%. However, there has not been a randomized trial to demonstrate such a reduction. While there are obvious differences between the European and American experiences with athletes including very differing causes of athletic deaths, some would highlight the European emphasis on public welfare vs the protection of personal rights in the USA. Even the authors of this systematic review have differing interpretation of the data: some of us view screening as a hopeless battle against Bayes, while others feel that the ECG can save lives. What we all agree on is that the USA should implement the American Heart Association 12-point screening recommendations and that, before ECG screening is mandated, we need to gather more data and optimize ECG criteria for screening young athletes.

    View details for DOI 10.1016/j.cpcardiol.2009.08.002

    View details for Web of Science ID 000271915700002

    View details for PubMedID 19887232

  • Electrocardiographic predictors of atrial fibrillation AMERICAN HEART JOURNAL Perez, M. V., Dewey, F. E., Marcus, R., Ashley, E. A., Al-Ahmad, A. A., Wang, P. J., Froelicher, V. F. 2009; 158 (4): 622-628

    Abstract

    Atrial fibrillation (AF) is the most prevalent arrhythmia in the United States and accounts for more than 750,000 strokes per year. Noninvasive predictors of AF may help identify patients at risk of developing AF. Our objective was to identify the electrocardiographic characteristics associated with onset of AF.This was a retrospective cohort analysis of 42,751 patients with electrocardiograms (ECGs) ordered by physician's discretion and analyzed using a computerized system. The population was followed for detection of AF on subsequent ECGs. Cox proportional hazard regression analysis was performed to test the association between these ECG characteristics and development of AF.For a mean follow-up of 5.3 years, 1,050 (2.4%) patients were found to have AF on subsequent ECG recordings. Several ECG characteristics, such as P-wave dispersion (the difference between the widest and narrowest P waves), premature atrial contractions, and an abnormal P axis, were predictive of AF with hazard ratio of approximately 2 after correcting for age and sex. P-wave index, the SD of P-wave duration across all leads, was one of the strongest predictors of AF with a concordance index of 0.62 and a hazard ratio of 2.7 (95% CI 2.1-3.3) for a P-wave index >35. These were among the several independently predictive markers identified on multivariate analysis.Several ECG markers are independently predictive of future onset of AF. The P index, a measurement of disorganized atrial depolarization, is one of the strongest predictors of AF. The ECG contains valuable prognostic information that can identify patients at risk of AF.

    View details for DOI 10.1016/j.ahj.2009.08.002

    View details for Web of Science ID 000270706100020

    View details for PubMedID 19781423

  • Mechanisms of exercise intolerance in patients with hypertrophic cardiomyopathy AMERICAN HEART JOURNAL Le, V., Perez, M. V., Wheeler, M. T., Myers, J., Schnittger, I., Ashley, E. A. 2009; 158 (3): E27-E34

    Abstract

    To determine the relation between echocardiogram findings and exercise capacity in hypertrophic cardiomyopathy (HCM).Sixty-three patients (48 +/- 15 years) were referred for cardiopulmonary testing and exercise echocardiography. They were classified by morphology: proximal (n = 11), reverse curvature (n = 32), apical (n = 7), and concentric HCM (n = 13). There were more women in proximal and reverse curvature groups. Proximal HCM patients were older. Maximal left ventricular thickness was highest in reverse curvature group. At peak exercise, concentric HCM achieved the lowest percent predicted maximal Vo2. Excluding apical group, no significant differences in gradient were noted between groups. Overall, no statistically significant correlation was found between peak Vo2, wall thickness, and gradient. Significant correlations were noted between peak Vo2 and indexed left atrial (LA) volume (r = -0.52), lateral E' (r = 0.50), and lateral E/E' ratio (r = -0.46). A multivariate model including age, lateral E', indexed LA volume, and mitral A wave explained 46% of the variance in peak Vo2 (P = .01).Lateral E' and indexed LA volume are negatively correlated with functional capacity. Although patients with concentric morphology achieved the lowest peak Vo2, wall thickness and gradient did not predict exercise capacity.

    View details for DOI 10.1016/j.ahj.2009.06.006

    View details for Web of Science ID 000269641200027

    View details for PubMedID 19699847

  • Statin Use and Ventricular Arrhythmias During Clinical Treadmill Testing JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Dewey, F. E., Perez, M., Hadley, D., Freeman, J. V., Wang, P., Ashley, E. A., Myers, J., Froelicher, V. F. 2009; 20 (2): 193-199

    Abstract

    Premature ventricular complexes (PVCs) during exercise are associated with adverse prognosis, particularly in patients with intermediate treadmill test findings. Statin use reduces the incidence of resting ventricular arrhythmias in patients with coronary artery disease; however, the relationship between statin use and exercise-induced ventricular arrhythmias has not been investigated.We evaluated the association between statin use and PVCs in 1,847 heart-failure-free patients (mean age 58, 95% male) undergoing clinical exercise treadmill testing between 1997 and 2004 in the VA Palo Alto Health Care System. PVCs were quantified in beats per minute and frequent PVCs were defined as PVC rates greater than the median value (0.43 and 0.60 PVCs per minute for exercise and recovery, respectively). Propensity-adjusted logistic regression was used to evaluate the odds of developing PVCs during exercise and recovery periods associated with statin use. There were 431 subjects who developed frequent PVCs during exercise and 284 subjects had frequent recovery PVCs. After propensity score adjustment, subjects treated with statins (n = 145) had 42% lower odds of developing frequent PVCs during exercise (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37-0.93) and 44% lower odds of developing frequent PVCs during recovery (OR 0.56, 95% CI 0.30-0.94). These effects were not modified by age, prior coronary disease, hypercholesterolemia, exercise-induced angina, or exercise capacity.Statin use was associated with reduced odds of frequent PVCs during and after clinical exercise testing in a manner independent of associations with coronary disease or ischemia in our study population.

    View details for DOI 10.1111/j.1540-8167.2008.01284.x

    View details for Web of Science ID 000262889000012

    View details for PubMedID 18775041

  • Added Value of a Resting ECG Neural Network That Predicts Cardiovascular Mortality ANNALS OF NONINVASIVE ELECTROCARDIOLOGY Perez, M. V., Dewey, F. E., Tan, S. Y., Myers, J., Froelicher, V. F. 2009; 14 (1): 26-34

    Abstract

    The resting 12-lead electrocardiogram (ECG) remains the most commonly used test in evaluating patients with suspected cardiovascular disease. Prognostic values of individual findings on the ECG have been reported but may be of limited use.The characteristics of 45,855 ECGs ordered by physician's discretion were first recorded and analyzed using a computerized system. Ninety percent of these ECGs were used to train an artifical neural network (ANN) to predict cardiovascular mortality (CVM) based on 132 ECG and four demographic characteristics. The ANN generated a Resting ECG Neural Network (RENN) score that was then tested in the remaining ECGs. The RENN score was finally assessed in a cohort of 2189 patients who underwent exercise treadmill testing and were followed for CVM.The RENN score was able to better predict CVM compared to individual ECG markers or a traditional Cox regression model in the testing cohort. Over a mean of 8.6 years, there were 156 cardiovascular deaths in the treadmill cohort. Among the patients who were classified as intermediate risk by Duke Treadmill Scoring (DTS), the third tertile of the RENN score demonstrated an adjusted Cox hazard ratio of 5.4 (95% CI 2.0-15.2) compared to the first RENN tertile. The 10-year CVM was 2.8%, 8.6% and 22% in the first, second and third RENN tertiles, respectively.An ANN that uses the resting ECG and demographic variables to predict CVM was created. The RENN score can further risk stratify patients deemed at moderate risk on exercise treadmill testing.

    View details for DOI 10.1111/j.1542-474X.2008.00270.x

    View details for Web of Science ID 000262508800005

    View details for PubMedID 19149790

  • Isolated Disease of the Proximal Left Anterior Descending Artery Comparing the Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Surgery JACC-CARDIOVASCULAR INTERVENTIONS Kapoor, J. R., Gienger, A. L., Ardehali, R., Varghese, R., Perez, M. V., Sundaram, V., McDonald, K. M., Owens, D. K., Hlatky, M. A., Bravata, D. M. 2008; 1 (5): 483-491

    Abstract

    This study sought to systematically compare the effectiveness of percutaneous coronary intervention and coronary artery bypass surgery in patients with single-vessel disease of the proximal left anterior descending (LAD) coronary artery.It is uncertain whether percutaneous coronary interventions (PCI) or coronary artery bypass grafting (CABG) surgery provides better clinical outcomes among patients with single-vessel disease of the proximal LAD.We searched relevant databases (MEDLINE, EMBASE, and Cochrane from 1966 to 2006) to identify randomized controlled trials that compared outcomes for patients with single-vessel proximal LAD assigned to either PCI or CABG.We identified 9 randomized controlled trials that enrolled a total of 1,210 patients (633 received PCI and 577 received CABG). There were no differences in survival at 30 days, 1 year, or 5 years, nor were there differences in the rates of procedural strokes or myocardial infarctions, whereas the rate of repeat revascularization was significantly less after CABG than after PCI (at 1 year: 7.3% vs. 19.5%; at 5 years: 7.3% vs. 33.5%). Angina relief was significantly greater after CABG than after PCI (at 1 year: 95.5% vs. 84.6%; at 5 years: 84.2% vs. 75.6%). Patients undergoing CABG spent 3.2 more days in the hospital than those receiving PCI (95% confidence interval: 2.3 to 4.1 days, p < 0.0001), required more transfusions, and were more likely to have arrhythmias immediately post-procedure.In patients with single-vessel, proximal LAD disease, survival was similar in CABG-assigned and PCI-assigned patients; CABG was significantly more effective in relieving angina and led to fewer repeat revascularizations.

    View details for DOI 10.1016/j.jcin.2008.07.001

    View details for Web of Science ID 000207586300004

    View details for PubMedID 19463349

  • Genetics of Arrhythmia: Disease Pathways Beyond Ion Channels JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH Perez, M. V., Wheeler, M., Ho, M., Pavlovic, A., Wang, P., Ashley, E. A. 2008; 1 (2): 155-165

    Abstract

    Diseases of the electrical conduction system that lead to irregularities in cardiac rhythm can have morbid and often lethal clinical outcomes. Linkage analysis has been the principal tool used to discover the genetic mutations responsible for Mendelian arrhythmic disease. Although the majority of arrhythmias can be accounted for by mutations in genes encoding ion channels, linkage analysis has also uncovered the role of other gene families such as those encoding members of the desmosome. With a list of candidates in mind, mutational analysis has helped confirm the suspicion that proteins found in caveolae or gap junctions also play a role in arrhythmogenesis. Atrial fibrillation and sudden cardiac death are relatively common arrhythmias that may be caused by multiple factors including common genetic variants. Genome-wide association studies are already revealing the important and poorly understood role of intergenic regions in atrial fibrillation. Despite the great advancements that have been made in our understanding of the genetics of these diseases, we are still far from able to routinely use genomic data to make clinical management decisions. There remain several hurdles in the study of genetics of arrhythmia, including the costs of genotyping, the need to find large affected families for linkage analysis, or to recruit large numbers of patients for genome-wide studies. Novel techniques that incorporate epigenetic information, such as known gene-gene interactions, biologic pathways, and experimental gene expression, will need to be developed to better interpret the large amount of genetic data that can now be generated. The study of arrhythmia genetics will continue to elucidate the pathophysiology of disease, help identify novel therapies, and ultimately allow us to deliver the individualized medical therapy that has long been anticipated.

    View details for DOI 10.1007/s12265-008-9030-4

    View details for Web of Science ID 000207734800012

    View details for PubMedID 20559910

  • Systematic review: The comparative effectiveness of percutaneous coronary interventions and coronary artery bypass graft surgery ANNALS OF INTERNAL MEDICINE Bravata, D. M., Gienger, A. L., McDonald, K. M., Sundaram, V., Perez, M. V., Varghese, R., Kapoor, J. R., Ardehali, R., Owens, D. K., Hlatky, M. A. 2007; 147 (10): 703-U139

    Abstract

    The comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) for patients in whom both procedures are feasible remains poorly understood.To compare the effectiveness of PCI and CABG in patients for whom coronary revascularization is clinically indicated.MEDLINE, EMBASE, and Cochrane databases (1966-2006); conference proceedings; and bibliographies of retrieved articles.Randomized, controlled trials (RCTs) reported in any language that compared clinical outcomes of PCI with those of CABG, and selected observational studies.Information was extracted on study design, sample characteristics, interventions, and clinical outcomes.The authors identified 23 RCTs in which 5019 patients were randomly assigned to PCI and 4944 patients were randomly assigned to CABG. The difference in survival after PCI or CABG was less than 1% over 10 years of follow-up. Survival did not differ between PCI and CABG for patients with diabetes in the 6 trials that reported on this subgroup. Procedure-related strokes were more common after CABG than after PCI (1.2% vs. 0.6%; risk difference, 0.6%; P = 0.002). Angina relief was greater after CABG than after PCI, with risk differences ranging from 5% to 8% at 1 to 5 years (P < 0.001). The absolute rates of angina relief at 5 years were 79% after PCI and 84% after CABG. Repeated revascularization was more common after PCI than after CABG (risk difference, 24% at 1 year and 33% at 5 years; P < 0.001); the absolute rates at 5 years were 46.1% after balloon angioplasty, 40.1% after PCI with stents, and 9.8% after CABG. In the observational studies, the CABG-PCI hazard ratio for death favored PCI among patients with the least severe disease and CABG among those with the most severe disease.The RCTs were conducted in leading centers in selected patients. The authors could not assess whether comparative outcomes vary according to clinical factors, such as extent of coronary disease, ejection fraction, or previous procedures. Only 1 small trial used drug-eluting stents.Compared with PCI, CABG was more effective in relieving angina and led to fewer repeated revascularizations but had a higher risk for procedural stroke. Survival to 10 years was similar for both procedures.

    View details for Web of Science ID 000251259500005

    View details for PubMedID 17938385

  • Prognostic value of the computerized ECG in Hispanics CLINICAL CARDIOLOGY Perez, M. V., Yaw, T. S., Myers, J., Froelicher, V. F. 2007; 30 (4): 189-194

    Abstract

    The prevalence and prognostic values of electrocardiogram (ECG) abnormalities in Hispanics have not been compared to other ethnicities in a large population. Despite a worse cardiovascular risk profile, the prevalence of cardiovascular disease is lower in Hispanics compared to non-Hispanics.We hypothesized that ECG abnormalities were less common in Hispanics and were not as strongly associated with cardiovascular mortality.45,563 ECGs ordered for usual clinical indications in a Veteran's hospital were available for analysis. 1,392 patients who died within one week of the ECG were excluded. Demographic characteristics were recorded and the population was followed for an average of 7.5 years using the California Death Index. The presence of baseline ECG characteristics were recorded and analyzed using the GE/Marquette computerized ECG system. Age, sex and heart rate adjusted Cox hazard ratio analyses were performed.Being Hispanic was associated with lower cardiovascular death, with a hazard ratio (HR) of 0.76 (95% CI 0.65-0.89). Findings such as atrial fibrillation, presence of Q-waves, left ventricular hypertrophy (LVH), upright T-waves in aortic valve replacement (aVR) and cardiac Infarction Injury Scores > 6 were significantly less prevalent in Hispanics than in non-Hispanics. These findings were similarly associated with increased cardiovascular mortality in both groups, each with a HR of approximately 2.The lower prevalence of ECG characteristics associated with coronary heart disease, atrial fibrillation and left ventricular hypertrophy support prior observations that cardiovascular disease is less prevalent in the Hispanic population. These findings, however, are similarly associated with increased mortality compared to non-Hispanics.

    View details for DOI 10.1002/clc.20053

    View details for Web of Science ID 000245794400008

    View details for PubMedID 17443659

  • Giant coronary aneurysms in heart transplantation: an unusual presentation of cardiac allograft vasculopathy JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Perez, M., Fleischmann, D., Valantine, H., Hunt, S. A. 2006; 25 (11): 1367-1370

    Abstract

    Cardiac allograft vasculopathy is a leading cause of death during long-term follow-up of heart transplant recipients. We report 2 cases of cardiac allograft vasculopathy associated with giant coronary aneurysms. To our knowledge, these are the first reported cases of spontaneous giant coronary aneurysms in heart transplant recipients.

    View details for DOI 10.1016/j.healun.2006.07.006

    View details for Web of Science ID 000242222100015

    View details for PubMedID 17097503

  • p300/MDM2 complexes participate in MDM2-mediated p53 degradation MOLECULAR CELL Grossman, S. R., Perez, M., Kung, A. L., Joseph, M., Mansur, C., Xiao, Z. X., Kumar, S., Howley, P. M., Livingston, D. M. 1998; 2 (4): 405-415

    Abstract

    Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.

    View details for Web of Science ID 000076678900001

    View details for PubMedID 9809062

Stanford Medicine Resources: