Suchi Grover

Left and right ventricular effects of anthracycline and trastuzumab chemotherapy: A prospective study using novel cardiac imaging and biochemical markers

This article appeared in a journal published by Elsevier. Under Elseviers copyright, mandated authors are not permitted to make work available in an institutional repository.

Nonvolumetric Echocardiographic Indices of Right Ventricular Systolic Function: Validation with Cardiovascular Magnetic Resonance and Relationship with Functional Capacity

Purpose: Right ventricular (RV) systolic function as measured by right ventricular ejection fraction (RVEF) has long been recognized as an important predictor of outcome in heart failure patients. The echocardiographic measurement of RV volumes and RVEF is challenging, however, owing to the unique geometry of the right ventricle. Several nonvolumetric echocardiographic indices of RV function have demonstrated prognostic value in heart failure. Comparison studies of these techniques with each other using RVEF as a benchmark are limited, however. Furthermore, the contribution of these various elements of RV function to patient functional status is uncertain. We therefore aimed to: (1) Determine which nonvolumetric echocardiographic index correlates best with RVEF as determined by cardiac magnetic resonance (CMR) imaging (the accepted gold standard measure of RV systolic function) and (2) Ascertain which echocardiographic index best predicts functional capacity. Methods: Eighty‐three subjects (66 with systolic heart failure and 17 healthy controls) underwent CMR, 2D echocardiography, and cardiopulmonary exercise testing for comparison of echocardiographic indices of RV function with CMR RVEF, 6‐minute walk distance and VO2 PEAK. Results: Speckle tracking strain RV strain exhibited the closest association with CMR RV ejection fraction. Indices of RV function demonstrated weak correlation with 6‐minute walk distance, but basal RV strain rate by tissue velocity imaging had good correlation with VO2 PEAK. Conclusion: Strain by speckle tracking echocardiography and strain rate by tissue velocity imaging may offer complementary information in the evaluation of RV contractility and its functional effects. (Echocardiography 2012;29:455‐463)

Early and late changes in markers of aortic stiffness with breast cancer therapy

Anthracyclines and trastuzumab are well recognised to cause cardiac toxicity. Further to their effects on left ventricular (LV) function, anthracyclines in particular are considered to cause negative arterial remodelling. Whether these changes reverse is unknown. In addition, whether trastuzumab causes specific effects on arterial remodelling is yet undetermined.

Early use of N-acetylcysteine with nitrate therapy in patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction reduces myocardial infarct size (the NACIAM trial [N-acetylcysteine in acute myocardial infarction])

Background: Contemporary ST-segment–elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging–assessed infarct size. Secondary end points included cardiac magnetic resonance–determined myocardial salvage and creatine kinase kinetics. Results: Of 112 randomized patients with ST-segment–elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance–assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P=0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37–79) compared with placebo (27%; interquartile range, 14–42; P<0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively (P=0.08). Conclusions: High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000.

Mapping and Ablation of the Pulmonary Veins and Cavo-Tricuspid Isthmus With a Magnetic Resonance Imaging-Compatible Externally Irrigated Ablation Catheter and Integrated Electrophysiology System

Background— Magnetic resonance imaging (MRI)–guided interventional electrophysiology (EP) has rapidly emerged as a promising alternative to x-ray–guided ablation. We aimed to evaluate an externally irrigated MRI-compatible ablation catheter and integrated EP pacing and recording system, testing the feasibility of pulmonary vein and cavo-tricuspid isthmus ablation. Methods and Results— Externally irrigated MRI-compatible ablation and diagnostic EP catheters and an integrated EP recording system (Imricor Medical Systems, Burnsville, MN) were tested in n=11 sheep in a 1.5-T MRI scanner. Power-controlled (40 W, 120-second duration) lesions were formed at the pulmonary vein and cavo-tricuspid isthmus. Real-time intracardiac electrograms were recorded during MRI. Steady-state free precession non–breath-hold images were repeatedly acquired to guide catheter navigation. Lesion visualization was performed using noncontrast (T2-weighted turbo spin echo pulse sequence) and gadolinium-diethylene triamine pentaacetic acid–enhanced T1-weighted imaging (inversion-recovery gradient echo pulse sequence). Catheters were able to be visualized and navigated under cardiovascular magnetic resonance guidance. In total, 8±2.5 lesions (radiofrequency time, 16±4.2 minutes) were formed at the pulmonary vein ostia, and 6.5±1.3 lesions (radiofrequency time, 13±2.2 minutes) were formed at the cavo-tricuspid isthmus, with the end point of bidirectional block. The mean procedure time was 150±55 minutes. Lesion visualization with both T2W imaging and contrast-enhanced imaging correlated with sites of injury at autopsy. Conclusions— These data demonstrate the feasibility of using multiple catheters, an integrated EP pacing and recording system, and externally irrigated ablation with cardiovascular magnetic resonance guidance to undertake clinically relevant biatrial mapping and ablation.

Mapping and Ablation of the Pulmonary Veins and Cavo-Tricuspid Isthmus with an MRI Compatible Externally-Irrigated Ablation Catheter and Integrated Electrophysiology System

Background— Magnetic resonance imaging (MRI)–guided interventional electrophysiology (EP) has rapidly emerged as a promising alternative to x-ray–guided ablation. We aimed to evaluate an externally irrigated MRI-compatible ablation catheter and integrated EP pacing and recording system, testing the feasibility of pulmonary vein and cavo-tricuspid isthmus ablation. Methods and Results— Externally irrigated MRI-compatible ablation and diagnostic EP catheters and an integrated EP recording system (Imricor Medical Systems, Burnsville, MN) were tested in n=11 sheep in a 1.5-T MRI scanner. Power-controlled (40 W, 120-second duration) lesions were formed at the pulmonary vein and cavo-tricuspid isthmus. Real-time intracardiac electrograms were recorded during MRI. Steady-state free precession non–breath-hold images were repeatedly acquired to guide catheter navigation. Lesion visualization was performed using noncontrast (T2-weighted turbo spin echo pulse sequence) and gadolinium-diethylene triamine pentaacetic acid–enhanced T1-weighted imaging (inversion-recovery gradient echo pulse sequence). Catheters were able to be visualized and navigated under cardiovascular magnetic resonance guidance. In total, 8±2.5 lesions (radiofrequency time, 16±4.2 minutes) were formed at the pulmonary vein ostia, and 6.5±1.3 lesions (radiofrequency time, 13±2.2 minutes) were formed at the cavo-tricuspid isthmus, with the end point of bidirectional block. The mean procedure time was 150±55 minutes. Lesion visualization with both T2W imaging and contrast-enhanced imaging correlated with sites of injury at autopsy. Conclusions— These data demonstrate the feasibility of using multiple catheters, an integrated EP pacing and recording system, and externally irrigated ablation with cardiovascular magnetic resonance guidance to undertake clinically relevant biatrial mapping and ablation.

Troponin-positive chest pain with unobstructed coronary arteries: incremental diagnostic value of cardiovascular magnetic resonance imaging

AIMS Troponin-positive chest pain patients with unobstructed coronaries represent a clinical dilemma. Cardiovascular magnetic resonance (CMR) imaging has an increasingly prominent role in the assessment of these patients; however, its utility in addition to expert clinical judgement is unclear. We sought to determine the incremental diagnostic value of CMR and the heterogeneity in diagnoses by experienced cardiologists when presented with blinded clinical and investigative data in this population. METHODS AND RESULTS A total of 125 consecutive patients presenting to a tertiary centre between 2010 and 2014 with cardiac chest pain, elevated troponin (>29 ng/L), and unobstructed coronaries were enrolled and underwent CMR. A panel of three experienced cardiologists unaware of the CMR diagnosis and blinded to each others assessment provided a diagnosis based on clinical and investigative findings. A consensus panel diagnosis was defined as two or more cardiologists sharing the same clinical diagnosis. Findings were classified into acute myocarditis, Takotsubo cardiomyopathy, acute myocardial infarction (AMI), or indeterminate. CMR provided a diagnosis in 87% of patients. Consensus panel diagnosis and CMR were concordant in 65/125 (52%) patients. There was an only moderate level of agreement between the three cardiologists (k = 0.47, P < 0.05) and a poor level of agreement between the consensus panel and CMR (k = 0.38, P < 0.05) with the most disagreement seen in patients with AMI diagnosed on CMR. CONCLUSION The clinical diagnosis of patients with non-obstructive coronaries and positive troponin remains a challenge. The concordance between CMR and clinical diagnosis is poor. CMR provides a diagnosis in majority of these patients.

Cardiovascular magnetic resonance of total and atrial pericardial adipose tissue: a validation study and development of a 3 dimensional pericardial adipose tissue model.

BackgroundRecently pericardial adipose tissue (PAT) has been shown to be an independent predictor of atrial fibrillation (AF). Atrial PAT may influence underlying atrial musculature creating a substrate for AF. This study sought to validate the assessment of total and atrial PAT by standard cardiovascular magnetic resonance (CMR) measures and describe and validate a three dimensional atrial PAT model.Methods10 merino cross sheep underwent CMR using a 1.5 Tesla system (Siemens, Sonata, Erlangen, Germany). Atrial and ventricular short axis (SA) images were acquired, using ECG -gated steady state free precession sequences. In order to quantify total volume of adipose tissue, a three dimensional model was constructed from consecutive end-diastolic images using semi-automated software. Regions of adipose tissue were marked in each slice followed by linear interpolation of pixel intensities in spaces between consecutive image slices. Total volume of adipose tissue was calculated as a total volume of the three dimensional model and the mass estimated from volume measurements. The sheep were euthanized and pericardial adipose tissue was removed and weighed for comparison to the corresponding CMR measurements.ResultsAll CMR adipose tissue estimates significantly correlated with autopsy measurements (ICC > 0.80; p < 0.03). Intra- observer reliability in CMR measures was high, with 95% levels of agreement within 5.5% (ICC = 0.995) for total fat mass and its individual atrial (95% CI ± 8.3%, ICC = 0.993) and ventricular components (95% CI ± 6.6%, ICC = 0.989). Inter- observer 95% limits of agreement were within ± 10.7% (ICC = 0.979), 7.4% (ICC = 0.991) and 7.2% (ICC = 0.991) for atrial, ventricular and total pericardial adipose tissue, respectively.ConclusionThis study validates the use of a semi-automated three dimensional atrial PAT model utilizing standard (clinical) CMR sequences for accurate and reproducible assessment of atrial PAT. The measurement of local cardiac fat stores via this methodology could provide a sensitive tool to examine the regional effect of fat deposition on atrial substrate which potentially may influence AF ablation strategies in obese patients.

Evaluation of Myocardial Viability With Cardiac Magnetic Resonance Imaging

Assessment of myocardial viability is of clinical and scientific significance. Traditionally, the detection of myocardial viability (either stunning or hibernation) has been used in aiding diagnosis before revascularization, especially in high-risk patients. There is a considerable body of observational evidence showing substantial improvement after revascularization in patients with significant left ventricular dysfunction and myocardial viability. Recent randomized evidence has questioned the benefit of viability testing but must be interpreted with caution. Dobutamine stress echocardiography, nuclear imaging, and cardiovascular magnetic resonance are the mainstays of viability testing and provide information on contractile function, cellular metabolism, and myocardial fibrosis, respectively. Larger, multicenter trials with outcome data are needed to define the nature of viability testing and, particularly, cardiovascular magnetic resonance in moderate-to-severe ischemic cardiomyopathy.

Impaired Myocardial Oxygenation Response to Stress in Patients With Chronic Kidney Disease

Background Coronary artery disease and left ventricular hypertrophy are prevalent in the chronic kidney disease (CKD) and renal transplant (RT) population. Advances in cardiovascular magnetic resonance (CMR) with blood oxygen level–dependent (BOLD) technique provides capability to assess myocardial oxygenation as a measure of ischemia. We hypothesized that the myocardial oxygenation response to stress would be impaired in CKD and RT patients. Methods and Results Fifty-three subjects (23 subjects with CKD, 10 RT recipients, 10 hypertensive (HT) controls, and 10 normal controls without known coronary artery disease) underwent CMR scanning. All groups had cine and BOLD CMR at 3 T. The RT and HT groups also had late gadolinium CMR to assess infarction/replacement fibrosis. The CKD group underwent 2-dimensional echocardiography strain to assess fibrosis. Myocardial oxygenation was measured at rest and under stress with adenosine (140 μg/kg per minute) using BOLD signal intensity. A total of 2898 myocardial segments (1200 segments in CKD patients, 552 segments in RT, 480 segments in HT, and 666 segments in normal controls) were compared using linear mixed modeling. Diabetes mellitus (P=0.47) and hypertension (P=0.57) were similar between CKD, RT, and HT groups. The mean BOLD signal intensity change was significantly lower in the CKD and RT groups compared to HT controls and normal controls (−0.89±10.63% in CKD versus 5.66±7.87% in RT versus 15.54±9.58% in HT controls versus 16.19±11.11% in normal controls, P<0.0001). BOLD signal intensity change was associated with estimated glomerular filtration rate (β=0.16, 95% CI=0.10 to 0.22, P<0.0001). Left ventricular mass index and left ventricular septal wall diameter were similar between the CKD predialysis, RT, and HT groups. None of the CKD patients had impaired global longitudinal strain and none of the RT group had late gadolinium hyperenhancement. Conclusions Myocardial oxygenation response to stress is impaired in CKD patients and RT recipients without known coronary artery disease, and unlikely to be solely accounted for by the presence of diabetes mellitus, left ventricular hypertrophy, or myocardial scarring. The impaired myocardial oxygenation in CKD patients may be associated with declining renal function. Noncontrast BOLD CMR is a promising tool for detecting myocardial ischemia in the CKD population.