Publications by authors named "Srinivas Denduluri"

7 Publications

  • Page 1 of 1

Cardiology Involvement in Patients with Breast Cancer Treated with Trastuzumab.

JACC CardioOncol 2020 Jun 16;2(2):179-189. Epub 2020 Jun 16.

Department of Medicine, Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Background: There is limited evidence regarding the impact of cardiology involvement in the care of cancer patients.

Objectives: We evaluated the impact of cardiology involvement on guideline-adherent cardiovascular monitoring and risk factor management in breast cancer patients treated with trastuzumab.

Methods: In a single-center retrospective cohort study, we evaluated electronic health records from 1,047 breast cancer patients receiving trastuzumab between January 2009 and July 2018. A visit to a cardiology provider beginning from the 3 months prior to cancer therapy initiation until the last contact date defined cardiology involvement. Guideline-adherent monitoring, defined by echocardiography assessment within the 4 months prior to trastuzumab initiation and follow-up echocardiography at least every 4 months during therapy, was compared in patients with and without cardiology involvement prior to treatment initiation. Multivariable associations between cardiology involvement and time-varying risk factors blood pressure (BP) and body mass index (BMI) were assessed using generalized estimating equations.

Results: Cardiology involvement occurred in 293 (28%) patients. A higher proportion of patients with cardiology involvement prior to trastuzumab initiation had guideline-adherent monitoring (76.4% versus 60.1%, p=0.007). Cardiology involvement was associated with an average 1.5mmHg (95% CI -2.9,-0.1, p=0.035) lower systolic BP; which was more pronounced in those with hypertension (-2.7mmHg (95% CI -4.6,-0.7, p=0.007)). Cardiology involvement was associated with a lower BMI in patients with baseline BMI≥25 kg/m (mean difference; -0.5 (95% CI -1.0,-0.1, p=0.027)).

Conclusions: Cardiology involvement in breast cancer patients treated with trastuzumab is associated with greater adherence to cardiovascular monitoring and modest improvements in risk factor control.
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June 2020

Diagnostic accuracy of SPECT and PET myocardial perfusion imaging in patients with left bundle branch block or ventricular-paced rhythm.

J Nucl Cardiol 2021 Jun 20;28(3):981-988. Epub 2020 Oct 20.

Division of Cardiology, Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Blvd, 11-154 South Pavilion, Philadelphia, PA, 19104, USA.

Background: The difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown.

Methods: We identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery.

Results: Of the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02).

Conclusions: PET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.
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June 2021

Symptomatic Heart Failure in Acute Leukemia Patients Treated With Anthracyclines.

JACC CardioOncol 2019 Dec 17;1(2):208-217. Epub 2019 Dec 17.

Division of Cardiovascular Diseases, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Objectives: The purpose of this study was to investigate the occurrence and develop a risk score for heart failure (HF) in acute leukemia.

Background: Knowledge is scarce regarding the incidence and risk factors of symptomatic HF in patients with acute leukemia.

Methods: Baseline clinical and echocardiographic parameters, including indices of cardiac function (left ventricular ejection fraction and myocardial strain [global longitudinal strain; GLS]), were obtained in 450 patients with acute leukemia treated with anthracyclines, before chemotherapy initiation. Potential risk factors for HF were evaluated using Fine and Gray's regression analysis, and from this, a 21-point risk score was generated.

Results: Forty patients (8.9%) developed HF. The HF risk score included a baseline GLS >-15% (indicative of greater impairment) (6 points), baseline left ventricular ejection fraction <50%, pre-existing cardiovascular disease, acute myeloid leukemia (4 points each), cumulative anthracycline dose ≥250 mg/m (2 points), and age >60 years (1 point). Patients were stratified into low (score 0 to 6), moderate (score 7 to 13), and high risk (score 14 to 21). The estimated 1-year cumulative incidence of HF for low-, moderate-, and high-risk groups was 1.0%, 13.6%, and 35.0%, respectively (p < 0.001). The HF risk score was also predictive of all-cause mortality (p < 0.001). After adjustment for age and leukemia type, however, only GLS was significantly associated with all-cause mortality (hazard ratio: 1.73; 95% confidence interval: 1.30 to 2.31; p < 0.001).

Conclusions: We developed a baseline risk score to determine risk of HF in patients with acute leukemia. Additional studies are needed to determine the external validity of these findings.
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December 2019

COVID-19 and cardiac arrhythmias.

Heart Rhythm 2020 Sep 22;17(9):1439-1444. Epub 2020 Jun 22.

Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.

Objectives: The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality.

Methods: We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.

Results: Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality.

Conclusion: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.
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September 2020

Clinic nonattendance is associated with increased emergency department visits in adults with congenital heart disease.

Congenit Heart Dis 2019 Sep 9;14(5):726-734. Epub 2019 May 9.

Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: To determine the prevalence and predictors of nonattendance in an ACHD outpatient clinic, and to examine the relationship between nonattendance and emergency department (ED) visits, hospitalizations, and death.

Methods: Patients ≥ 18 years who had scheduled appointments at an ACHD outpatient clinic between August 1, 2014 and December 31, 2014 were included. The primary outcome of interest was nonattendance of the first scheduled appointment of the study period, defined as "no-show" or "same-day cancellation." Secondary outcomes of interest were ED visits, hospitalizations, and death until December 2017.

Results: Of 527 scheduled visits, 55 (10.4%) were nonattended. Demographic and socioeconomic characteristics such as race, income, and insurance type were associated with non-attendance (all P values < .05), whereas age, gender, and disease complexity were not. On multivariable analysis, predictors of nonattendance were black race (adjusted odds ratio [AOR] 4.95; P < .001), other race (AOR 3.54; P = .003), and history of no-show in the past (AOR 4.95; P < .001). Compared to patients who attended clinic, patients with a nonattended visit had a threefold increased odds of multiple ED visits and a significantly lower rate of ED-free survival over time. There were no significant differences in hospitalizations or death by attendance.

Conclusions: ACHD clinic nonattendance is associated with race and prior history of no-show, and may serve as a marker of higher ED utilization for patients with ACHD.
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September 2019

Effect of comedication of bupropion and other antidepressants on body mass index.

Ther Adv Psychopharmacol 2015 Jun;5(3):158-65

Director Medical Informatics Group, Allscripts, 101 Lindenwood Drive, Malvern, PA 19355, USA.

Background: Weight gain as an adverse effect of monotherapy of antidepressant has been well-studied. The effects of augmentation therapy involving multiple antidepressants, on weight changes needs to be adequately addressed.

Objective: To study the co-medication effects of bupropion in combination with six individual antidepressants on body mass index (BMI) using EMR based data analysis.

Methods: Allscripts data warehouse was used to identify patients on monotherapy of five selective serotonin reuptake inhibitor (SSRI) drugs, escitalopram, sertraline, citalopram, paroxetine, fluoxetine, one selective norepinephrine reuptake inhibitor (SNRI) duloxetine and the aminoketone, bupropion for at least 180 days. We also identified patients on co-medication of SSRI/SNRI drugs with bupropion. Six ANCOVA models were built to compare the short term effects on BMI, among monotherapy and co-medication groups. The patients' clinical conditions and demographics were included to account for confounding effects.

Results: Monotherapy of all the SSRI/SNRI drugs showed significant weight increase, consistent with that of previous studies. The co-medication of bupropion and escitalopram showed a significantly higher increase in BMI than monotherapy (P = 0.0102). The increase in BMI in the other five co-medication groups was not significantly different from their respective monotherapy groups.

Conclusion: Our study reports an adverse weight gain on co-medication of escitalopram and bupropion, which warrants further validation studies. Considering co-medication effects of antidepressants on weight is important to design robust depression treatment plans.
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June 2015

Co-medication of pravastatin and paroxetine-a categorical study.

J Clin Pharmacol 2013 Nov 13;53(11):1212-9. Epub 2013 Aug 13.

Allscripts, Malvern, PA, USA.

Electronic Medical Records (EMRs) are wealthy storehouses of patient information, to which data mining techniques can be prudently applied to reveal clinically significant patterns. Detecting patterns in drug-drug interactions, leading to adverse drug reactions is a powerful application of EMR data mining. Adverse effects of drug treatments can be investigated by mining clinical laboratory tests data which are reliable indicators of abnormal physiological functions. We report here the co-medication effects of pravastatin (HMG-CoA reductase inhibitor) and paroxetine (selective serotonin reuptake inhibitor (SSRI) anti-depressant) on significant clinical parameters, identified through a data mining analysis conducted on the Allscripts data warehouse. We found that the concomitant drug treatments of pravastatin and paroxetine increased the mean values of glucose serum from 113.2 to 132.1 mg/dL and international normalized ratio (INR) from 2.18 to 2.52, respectively. It also decreased the mean values of estimated glomerular filtration rate (eGFR) from 43 to 37 mL/min/1.73 m(3) and blood CO2 levels from 24.8 to 23.9 mEq/L respectively. Our findings indicate that co-medication of pravastatin and paroxetine might have significant impact on blood anti-coagulation, kidney function, and glucose homeostasis. Our methodology can be applied to any EMR data set to reveal co-medication effects of any drug pairs.
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November 2013