Papers by Saad Sikanderkhel
ASA Newsletter, Feb 1, 2009
Journal of the American College of Cardiology, May 1, 2021
Journal of the American College of Cardiology, Mar 1, 2020
John Wiley & Sons, Ltd eBooks, Jul 5, 2019
Journal of the American College of Cardiology, Oct 1, 2017

Journal of the American College of Cardiology, Mar 1, 2018
Background: Transthyretin (TTR) cardiac amyloidosis (CA) is an increasingly recognized cause of h... more Background: Transthyretin (TTR) cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure. Diagnosis of TTR-CA relies on visual and semi-quantitative interpretation of planar 99m Tc-PYP imaging. However, new methods that directly quantify PYP uptake may improve risk stratification and/or evaluation of treatment response to novel anti-TTR agents. The goal of this study was to develop methods for 99m Tc-PYP SUV quantification in TTR-CA using the GE Alcyone CZT camera and evaluate their relationship to clinical TTR-CA severity. Methods: Fourteen patients were imaged first with planar 99m Tc-PYP imaging (12.7±3.2mCi) at one hour, immediately followed by SPECT/ CT with a GE Alcyone 570C CZT camera. Planar images were quantified using heart (H): contralateral (CL) ratio. Global and segmental SUVs were calculated after deriving camera-and reconstruction-specific scaling factors from a cardiac phantom, and these were compared to patient age at diagnosis, left ventricular mass from cardiac magnetic resonance (CMR) and planar H:CL ratio. Results: Patients had a mean age of 72+ 8 years at the time of diagnosis and mean follow up period was 485±185 days. Mean H:CL on planar imaging was 1.78±0.34. Mean global SUV was as 6.58±0.18 g/ml. There was a strong correlation between mean SUV and LV mass by CMR (r 2 = 0.72, P=0.007) and a weaker correlation with H:CL ratio (r 2 = 0.35, P=0.05). A weak negative correlation between mean SUV and age at TTR-CA diagnosis (r 2 =0.17, P=0.13) was also noted. Conclusion: We developed a new quantitative tool for evaluating TTR-CA by calculating 99m Tc-PYP SUVs from CZT SPECT/CT acquisitions, which correlate strongly with LV mass by CMR. As SUV quantification becomes more widely available on CZT and non-CZT SPECT cameras, this technique may provide a novel method to monitor disease progression and response to treatments in TTR-CA.
Journal of the American College of Cardiology, Mar 1, 2020
Circulation, Nov 14, 2017
Introduction: FFR has become the gold standard for assessing inducible myocardial ischemia in pat... more Introduction: FFR has become the gold standard for assessing inducible myocardial ischemia in patients being evaluated for revascularization of intermediate grade coronary lesions. Outcomes in FFR ...

Circulation Research, Jul 18, 2014
Introduction: Atrial fibrillation is common in heart failure (HF). Understanding of the mechanism... more Introduction: Atrial fibrillation is common in heart failure (HF). Understanding of the mechanisms of atrial fibrillation (AF) is limited by the paucity of large animal AF models, especially in the failing heart. We developed a large animal model of nonischemic heart failure (HF) in dogs by combined aortic insufficiency and aortic constriction and observed that a number of HF dogs developed paroxysmal AF on holter monitor. Here we characterize the spontaneously-occurring pAF in these HF dogs and perform electrophysiologic (EP) assessment of atrial refractoriness and AF inducibility along with echocardiographic imaging of left ventricle (LV) and left atrium (LA). Methods: HF was induced in dogs by aortic insufficiency and aortic constriction, and serial echocardiography (for LV fractional shortening (FS) and LA size) and Holter monitoring was performed. In control and HF dogs, EP study of atrial refractory period (AERP) and AF inducibility (duration and atrial cycle length (CL)) was performed. Results: By Holter monitoring, paroxysmal AF was noted in 5 dogs with episodes ranging from 15 to 94 beats long (mean of 49±27 beats, n=12). In EP studies, control dogs (N=3) exhibited AERP of 176±8 ms. Burst pacing resulted in AF of very brief duration (mean 32±24 sec) and a mean AF CL of 138±6 ms. LV FS averaged 37% and LA size averaged 4.3 cm2. HF dogs (N=5) exhibited RAERP of 150±8 (p=0.05 vs control). Two of these dogs had sustained AF with ventricular response up to 230 bpm on Holter monitor. In the other 3 HF dogs, burst pacing induced AF with a mean duration of 232±185 sec (at times with conversion to atrial flutter) and with a mean AF CL = 110±4 ms (p=0.002 vs control). Echo data showed LVFS averaged 30% and LA area of 14.9 cm2 (p=0.05 vs control). Conclusion: Thus we have developed a novel large animal model of HF that exhibits paroxysmal and sustained AF. This model will provide an opportunity for the study of underlying AF mechanisms, the progression of remodeling in HF hearts leading to AF, and the assessment of human-scale interventions to better treat and prevent this arrhythmia.
Journal of Cardiac Surgery, Jul 2, 2017
Diarrhea following organ transplantation is usually associated with infection and immunosuppressi... more Diarrhea following organ transplantation is usually associated with infection and immunosuppression therapy. We describe two patients with diarrhea following orthotopic heart transplantation due to tertiary adrenal insufficiency.
Journal of Nuclear Cardiology, Nov 16, 2017
An 83-year-old man underwent exercise stress test with single photon emission computed tomography... more An 83-year-old man underwent exercise stress test with single photon emission computed tomography (SPECT) myocardial perfusion imaging for new electrocardiogram (EKG) changes. The stress EKG did not show any significant changes. Myocardial perfusion imaging with SPECT demonstrated an inferior wall defect and extracardiac uptake of nuclear tracer. Simultaneous cardiac computed tomography performed for attenuation correction showed presence of intrapericardial hepatic tissue in an anterior diaphragmatic hernia. The herniated tissue was noted to influence the perfusion image and cause the defect. To date, this is a unique finding based on review of literature.
Journal of the American College of Cardiology, May 1, 2021
Journal of the American College of Cardiology, May 1, 2021
Journal of the American College of Cardiology, May 1, 2021

Hypertension, Feb 1, 2010
Neointimal hyperplasia (NIH) can lead to restenosis after clinical vascular interventions. NIH re... more Neointimal hyperplasia (NIH) can lead to restenosis after clinical vascular interventions. NIH results from complex and poorly understood interactions between signaling cascades in the extracellular matrix and the disrupted endothelium, which lead to vessel occlusion. Quantitative trait loci (QTLs) were reported previously on rat chromosomes 3 and 6 through linkage analysis of postinjury NIH in midiliac arterial sections. In the current study, substitution mapping validated the RNO3 NIH QTL but not the RNO6 NIH QTL. The SHR.BN3 congenic strain had a 3-fold increase in the percentage of NIH compared with the parental spontaneously hypertensive rat strain. A double congenic study of RNO3ϩRNO6 NIH QTL segments suggested less than additive effects of these 2 genomic regions. To test the hypothesis that changes in vessel dynamics account for the differences in NIH formation, we performed vascular reactivity studies in the Brown Norway (BN), spontaneously hypertensive rat (SHR), SHR.BN3, and SHR.BN6 strains. De-endothelialized left common carotid artery rings of the SHR.BN3 showed an increased vascular responsiveness when treated with serotonin or prostaglandin F2 ␣ , with significant differences in EC 50 and maximum effect (PϽ0.01) values compared with the spontaneously hypertensive rat parental strain. Because both vascular reactivity and percentage of NIH formation in the SHR.BN3 strain are significantly higher than the SHR strain, we postulate that these traits may be associated and are controlled by genetic elements on RNO3. In summary, these results confirm that the RNO3 NIH QTL carries the gene(s) contributing to postinjury NIH formation. (Hypertension. 2010;55[part 2]:555-561.
Circulation, Nov 16, 2021

Hypertension, 2010
Neointimal hyperplasia (NIH) can lead to restenosis after clinical vascular interventions. NIH re... more Neointimal hyperplasia (NIH) can lead to restenosis after clinical vascular interventions. NIH results from complex and poorly understood interactions between signaling cascades in the extracellular matrix and the disrupted endothelium, which lead to vessel occlusion. Quantitative trait loci (QTLs) were reported previously on rat chromosomes 3 and 6 through linkage analysis of postinjury NIH in midiliac arterial sections. In the current study, substitution mapping validated the RNO3 NIH QTL but not the RNO6 NIH QTL. The SHR.BN3 congenic strain had a 3-fold increase in the percentage of NIH compared with the parental spontaneously hypertensive rat strain. A double congenic study of RNO3+RNO6 NIH QTL segments suggested less than additive effects of these 2 genomic regions. To test the hypothesis that changes in vessel dynamics account for the differences in NIH formation, we performed vascular reactivity studies in the Brown Norway (BN), spontaneously hypertensive rat (SHR), SHR.BN3, ...
Journal of the American College of Cardiology, 2021
Journal of the American College of Cardiology, 2021

Circulation Research, 2014
Introduction: Atrial fibrillation is common in heart failure (HF). Understanding of the mechanism... more Introduction: Atrial fibrillation is common in heart failure (HF). Understanding of the mechanisms of atrial fibrillation (AF) is limited by the paucity of large animal AF models, especially in the failing heart. We developed a large animal model of nonischemic heart failure (HF) in dogs by combined aortic insufficiency and aortic constriction and observed that a number of HF dogs developed paroxysmal AF on holter monitor. Here we characterize the spontaneously-occurring pAF in these HF dogs and perform electrophysiologic (EP) assessment of atrial refractoriness and AF inducibility along with echocardiographic imaging of left ventricle (LV) and left atrium (LA). Methods: HF was induced in dogs by aortic insufficiency and aortic constriction, and serial echocardiography (for LV fractional shortening (FS) and LA size) and Holter monitoring was performed. In control and HF dogs, EP study of atrial refractory period (AERP) and AF inducibility (duration and atrial cycle length (CL)) was ...
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Papers by Saad Sikanderkhel