Vikas Veeranna

Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRD

Capillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysis-dependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Per-patient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all-cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2-1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log-transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.14; P<0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all-cause and cardiovascular mortality in patients with dd-ESRD.

18F-Florbetapir Binds Specifically to Myocardial Light Chain and Transthyretin Amyloid Deposits: Autoradiography Study.

Background—18F-florbetapir is a promising imaging biomarker for cardiac light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). Our aim, using human autopsy myocardial specimens, was to test the hypothesis that 18F-florbetapir binds specifically to myocardial AL and ATTR amyloid deposits. Methods and Results—We studied myocardial sections from 30 subjects with autopsy-documented AL (n=10), ATTR (n=10), and nonamyloid controls (n=10) using 18F-florbetapir and cold florbetapir compound and digital autoradiography. Total and nonspecific binding of 18F-florbetapir was determined using the maximum signal intensity values. Specific binding of 18F-florbetapir was calculated by subtracting nonspecific from total binding measurements (in decays per minute/mm2, DPM mm2) and was compared with cardiac structure and function on echocardiography and the histological extent of amyloid deposits. Diffuse or focally increased 18F-florbetapir uptake was noted in all AL and ATTR samples and in none of the control samples. Compared with control samples, mean 18F-florbetapir–specific uptake was significantly higher in the amyloid samples (0.94±0.43 versus 2.00±0.58 DPM/mm2; P<0.001), and in the AL compared with the ATTR samples (2.48±0.40 versus 1.52±0.22 DPM/mm2; P<0.001). The samples from subjects with atypical echocardiographic features of amyloidosis showed quantitatively more intense 18F-florbetapir–specific uptake compared with control samples (1.50±0.17 versus 0.94±0.43 DPM/mm2; P=0.004), despite smaller amyloid extent than in subjects with typical echocardiograms. Conclusions—18F-florbetapir specifically binds to myocardial AL and ATTR deposits in humans and offers the potential to screen for the 2 most common types of myocardial amyloid.

Coronary Computed Tomography Angiography in the Evaluation of Chest Pain of Suspected Cardiac Origin.

Case Presentation: A 54-year-old man with history of dyslipidemia is evaluated in the outpatient setting for several months of intermittent atypical chest pain. He is not on any medical therapy. His resting heart rate in the office is 70 beats per minute. His outpatient cardiologist is wondering if coronary computed tomography angiography may be useful for further evaluation. Because of the high prevalence of coronary artery disease (CAD) and the lack of specific diagnostic clinical signs and symptoms, current guidelines recommend a Bayesian approach, using pretest probability scores for evaluating patients with stable chest pain of suspected cardiac origin.1–3 For individuals with an intermediate pretest probability of obstructive CAD, a noninvasive test is usually recommended. Current test options have become increasingly complex and range from anatomic evaluation via coronary computed tomography angiography (CTA) to functional imaging tests to evaluate ischemia, including exercise treadmill testing with or without nuclear (positron emission tomography or single-photon emission computed tomography) or echocardiographic imaging. In patients who are unable to exercise, pharmacological testing with imaging can be performed. Test selection often varies according to local availability and expertise, and patient characteristics, as well. Although both coronary CTA and various functional testing strategies are considered appropriate for the initial evaluation of patients with intermediate pretest probability of obstructive CAD, selecting the most optimal testing strategy can be challenging. Table 1 lists various patient factors to consider when selecting optimal candidates for coronary CTA who are more likely to have diagnostic quality images, and a clinical benefit from the examination, as well. View this table: Table 1. Patient Factors to Consider When Selecting Optimal Candidates for Coronary CTA Multiple studies have established the high accuracy of coronary CTA to diagnose obstructive CAD in comparison with invasive coronary angiography (ICA).4 A recent meta-analysis demonstrated that coronary CTA has a …

Ranolazine in Symptomatic Diabetic Patients Without Obstructive Coronary Artery Disease: Impact on Microvascular and Diastolic Function

Background Treatments for patients with myocardial ischemia in the absence of angiographic obstructive coronary artery disease are limited. In these patients, particularly those with diabetes mellitus, diffuse coronary atherosclerosis and microvascular dysfunction is a common phenotype and may be accompanied by diastolic dysfunction. Our primary aim was to determine whether ranolazine would quantitatively improve exercise‐stimulated myocardial blood flow and cardiac function in symptomatic diabetic patients without obstructive coronary artery disease. Methods and Results We conducted a double‐blinded crossover trial with 1:1 random allocation to the order of ranolazine and placebo. At baseline and after each 4‐week treatment arm, left ventricular myocardial blood flow and coronary flow reserve (CFR; primary end point) were measured at rest and after supine bicycle exercise using 13N‐ammonia myocardial perfusion positron emission tomography. Resting echocardiography was also performed. Multilevel mixed‐effects linear regression was used to determine treatment effects. Thirty‐five patients met criteria for inclusion. Ranolazine did not significantly alter rest or postexercise left ventricular myocardial blood flow or CFR. However, patients with lower baseline CFR were more likely to experience improvement in CFR with ranolazine (r=−0.401, P=0.02) than with placebo (r=−0.188, P=0.28). In addition, ranolazine was associated with an improvement in E/septal e′ (P=0.001) and E/lateral e′ (P=0.01). Conclusions In symptomatic diabetic patients without obstructive coronary artery disease, ranolazine did not change exercise‐stimulated myocardial blood flow or CFR but did modestly improve diastolic function. Patients with more severe baseline impairment in CFR may derive more benefit from ranolazine. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01754259.

Utility of multimodality imaging in diagnosis and follow-up of aortitis.

A 47-year-old male of European descent without any cardiac risk factors initially presented in 2005 with chest discomfort precipitated by emotional stress. Figure 1 illustrates work-up with multiple non-invasive cardiac imaging and invasive angiography studies prior to referral with suspected aortitis in 2013. At the time of his evaluation in 2013, he continued to have fleeting episodes of chest discomfort with emotional stress. Review of symptoms included recurrent aphthous ulcers and acne. Serologic work-up for relevant immunologic and infectious etiologies was negative, except for mildly elevated high sensitivity-C reactive protein (2.8 mg/L). Based on the findings of multimodality imaging in 2013, which included magnetic resonance angiogram (MRA) (limited due to motion), computed tomography angiogram (CTA) and Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) (Figure 2) and chronic symptoms with serologic work-up, a diagnosis of aortitis of undetermined etiology vs Behcet’s disease was considered. Follow-up imaging on corticosteroid therapy (initial high dose of prednisone 50 mg daily followed by taper to 20 mg) (Figure 3) and after termination of steroid therapy (Figure 4) demonstrated initial improvement followed by recrudescence.

Utility of multimodality imaging in suspected prosthetic valve endocarditis

An 85-year-old man with a history of three aortic valve replacements and pelvic surgery for bladder cancer presented with episodic fevers over a 2-week period. Urine and blood cultures grew pan-sensitive Escherichia coli. His evaluation confirmed three minor modified Duke criteria, indicating possible endocarditis. Transthoracic echocardiography did not reveal any abnormality of the bioprosthetic aortic valve. This patient was discharged on antibiotics but re-presented 3 days later with fevers. Transesophageal echocardiography demonstrated thickening of the aortic root without definite vegetations (Figure 1). Due to ongoing fevers, the suspicion for PVE was high, and an F-fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET)/computed tomography (CT) scan was performed. That scan revealed an intensely FDG-avid periaortic fluid collection consistent with an abscess (Figure 2) confirming PVE. The peri-aortic fluid collection was further characterized on a contrast-enhanced cardiac CT, which uncovered a pseudoaneurysm adjacent to the abscess and findings suggestive of a mycotic aneurysm (Figures 3 and 4). Due to co-morbidities, advanced age, and high surgical risk of a fourth aortic valve surgery, this patient elected to be treated conservatively. This case illustrates the complementary use of FDG-PET/CT and contrast-enhanced cardiac CT, in individuals with possible PVE, when echocardiography is inconclusive. It endorses the utility of the proposed algorithm described by Saby et al for evaluating patients with suspected PVE using FDG-PET/CT. Cardiac CT, a class IIa recommendation for suspected PVE in the 2014 ACC/AHA Valvular Heart Disease guidelines, uncovered a pseudoaneuysm. Periannular extensions complicate PVE in approximately 50% with PVE on echocardiography; FDG-PET/CT or cardiac CT

Coronary flow reserve is predictive of the risk of cardiovascular death regardless of chronic kidney disease stage

Microvascular rarefaction is found in experimental uremia, but data from patients with chronic kidney disease (CKD) are limited. We therefore quantified absolute myocardial blood flow and coronary flow reserve (the ratio of peak to resting flow) from myocardial perfusion positron emission tomography scans at a single institution. Individuals were classified into standard CKD categories based on the estimated glomerular filtration rate. Associations of coronary flow reserve with CKD stage and cardiovascular mortality were analyzed in models adjusted for cardiovascular risk factors. The coronary flow reserve was significantly associated with CKD stage, declining in early CKD, but it did not differ significantly among individuals with stage 4, 5, and dialysis-dependent CKD. Flow reserve with preserved kidney function was 2.01, 2.06 in stage 1 CKD, 1.91 in stage 2, 1.68 in stage 3, 1.54 in stage 4, 1.66 in stage 5, and 1.55 in dialysis-dependent CKD. Coronary flow reserve was significantly associated with cardiovascular mortality in adjusted models (hazard ratio 0.76, 95% confidence interval: 0.63-0.92 per tertile of coronary flow reserve) without evidence of effect modification by CKD. Thus, coronary flow reserve is strongly associated with cardiovascular risk regardless of CKD severity and is low in early stage CKD without further decrement in stage 5 or dialysis-dependent CKD. This suggests that CKD physiology rather than the effects of dialysis is the primary driver of microvascular disease. Our findings highlight the potential contribution of microvascular dysfunction to cardiovascular risk in CKD and the need to define mechanisms linking low coronary flow reserve to mortality.

Utility of multimodality imaging in myopericarditis with aortitis.

Myopericarditis with concomitant proximal aortitis is rare and presents a challenging diagnostic and management dilemma. Inflammation of the pericardial reflections on the ascending aorta can mimic proximal aortitis in patients with pericarditis. Establishing the correct diagnosis has important therapeutic implications. Therefore, patients with acute myopericarditis are treated with a combination of colchicine and nonsteroidal anti-inflammatory drugs, whereas aortitis requires immunosuppressive therapy. This case demonstrates the critical role of multimodality imaging to definitively diagnose myopericarditis and rule out associated proximal aortitis.

Response by Hulten et al to Letter Regarding Article, “Coronary Computed Tomography Angiography in the Evaluation of Chest Pain of Suspected Cardiac Origin”

We appreciate the insightful comments from Dr Vrints regarding our Clinician Update on coronary computed tomography angiography (CTA)1 and our meta-analysis2 of CTA versus functional testing for the evaluation of stable chest pain. We agree that there is a paucity of data on how to select the best initial test for evaluating patients with suspected coronary heart disease. We also note that our invited review was focused on coronary CTA and was not a comprehensive overview of all the available testing options. When considering all available testing options, it is important to acknowledge that there is …

MYO-PERICARDITIS WITH AORTITIS: UTILITY OF MULTI-MODALITY IMAGING

Myo-pericarditis with concomitant aortitis is uncommon and poses a challenging diagnostic and management dilemma. A 27 year old male with no medical history presented for evaluation of pleuritic chest pain for 6 weeks. Physical exam was normal with a non-specific baseline electrocardiogram. Lab