Adhiraj Chakrabarty

Effects of myocardial fibrosis and ventricular dyssynchrony on response to therapy in new-presentation idiopathic dilated cardiomyopathy: insights from cardiovascular magnetic resonance and echocardiography

AIMS To determine whether the extent of myocardial fibrosis by late-gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR), and echocardiographic ventricular dyssynchrony are independently associated with response to medical therapy in patients with newly diagnosed idiopathic dilated cardiomyopathy (DCM). Myocardial fibrosis and ventricular dyssynchrony are frequent findings in DCM. Previous studies focused on patients with established cardiomyopathy; however, the degree of myocardial fibrosis and ventricular dyssynchrony at presentation and their role in perpetuating left ventricular (LV) dysfunction in DCM remains unclear. Those studies of individuals with long-standing DCM did not characterize patients early in the disease course, and may not have included those with significant improvement in LV function. Thus factors contributing to LV recovery are uncertain. METHODS AND RESULTS Consecutive patients with a new diagnosis of DCM [LV ejection fraction (EF) ≤45%] made within the preceding 2 weeks were recruited. Patients underwent LGE-CMR, echocardiography, 6-minute walk testing, cardiopulmonary exercise testing, and blood sampling for measurement of serum amino-terminal pro-brain natiuretic peptide (NT-pro-BNP) concentration at baseline. Baseline patient characteristics were compared with a cohort of healthy volunteers. Myocardial fibrosis by LGE-CMR was quantified, identified by experienced observers blinded to patient outcome. Left ventricular systolic function was reassessed after 5 months of optimal medical therapy. Sixty-eight patients with DCM and 19 healthy volunteers were studied. DCM patients were studied a median 12.5 days following diagnosis. Compared with healthy controls, DCM patients exhibited greater inter- and intra-ventricular dyssynchrony. Twenty-four per cent of DCM patients exhibited LGE at diagnosis. Among DCM patients with LGE, the mean fibrosis mass was 2.2 ± 1.3 g. On multivariate analysis, strain dyssynchrony index, and fibrosis mass were independently associated with change in the LVEF over time (P≤ 0.001). Late-gadolinium enhancement cardiovascular magnetic resonance conferred additive value for modelling change in the LVEF beyond clinical and echocardiographic dyssynchrony parameters. CONCLUSION The extent of myocardial fibrosis is independently associated with lack of response to medical therapy in new-presentation DCM, and LGE-CMR may thus be an important risk-stratifying investigation in these patients. Accurate risk stratification may permit more targeted pharmacological and device therapies for patients with newly diagnosed DCM.

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 effects of transcatheter aortic valve implantation and aortic valve replacement on myocardial function and aortic valve hemodynamics: Insights from cardiovascular magnetic resonance imaging

OBJECTIVES There remains a paucity of mechanistic data on the effect of transcatheter aortic valve implantation (TAVI) on early left and right ventricular function and quantitative aortic valve regurgitation. We sought to assess and compare the early effects on myocardial function and aortic valve hemodynamics of TAVI and aortic valve replacement (AVR) using serial cardiovascular magnetic resonance (CMR) imaging and echocardiography. METHODS A prospective comparison study of 47 patients with severe aortic stenosis undergoing either TAVI (n = 26) or high-risk AVR (n = 21). CMR (for left ventricle/right ventricle function, left ventricular mass, left atrial volume, and aortic regurgitation) was carried out before the procedure and early postprocedure (<14 days). RESULTS Groups were similar with respect to Society of Thoracic Surgeons score (TAVI, 7.7 vs AVR, 5.9; P = .11). Preoperative left ventricular (TAVI, 69% ± 13% vs AVR, 73% ± 10%; P = .10) and right ventricular (TAVI, 61% ± 11% vs AVR, 59% ± 8%; P = .5) ejection fractions were similar. Postoperative left ventricular ejection fraction was preserved in both groups. In contrast, decline in right ventricular ejection fraction was more significant in the TAVI group (61%-54% vs 59%-58%; P = .01). Postprocedure aortic regurgitant fraction was significantly greater in the TAVI group (16% vs 4%; P = .001), as was left atrial size (110 vs 84 mL; P = .02). Further analysis revealed a significant relationship between the increased aortic regurgitant fraction and greater left atrial size (P = .006), and a trend toward association between the decline in right ventricle dysfunction and increased postprocedure aortic regurgitation (P = .08). CONCLUSIONS There was no significant difference in early left ventricular systolic function between techniques. Whereas right ventricle systolic function was preserved in the AVR group, it was significantly impaired early after TAVI, possibly reflecting a clinically important pathophysiologic consequence of paravalvular aortic regurgitation.

Successful catheter ablation decreases platelet activation and improves endothelial function in patients with atrial fibrillation

BACKGROUND Nonvalvular atrial fibrillation (AF) confers a five-fold increased risk of stroke. Whether catheter ablation (CA) subsequently decreases prothrombotic risk is unknown. OBJECTIVE The purpose of this study was to assess the long-term effects of CA for AF on prothrombotic risk. METHODS Fifty-seven patients undergoing CA for AF were prospectively studied. Platelet activation (CD62P [platelet P-selectin] and PAC-1 [glycoprotein IIb/IIIa] expression) and endothelial function (asymmetric dimethylarginine [ADMA] levels) were measured at baseline and 6-months postablation. RESULTS Thirty-seven (65%) patients remained in sinus rhythm (SR group) and 20 (35%) sustained AF recurrence (AF recurrence group) at 6-months. Patients with AF-recurrence were older, had a higher proportion of hypertension and long-standing persistent AF. There were no significant differences in CD62P (P = .3), PAC-1 (P = .1) and ADMA (P = .7) levels at baseline between the two groups. In the SR group, markers of platelet activation decreased significantly at 6-month follow-up compared to baseline; log CD62P % 0.79 ± 0.28 vs 1.03 ± 0.27 (P <.05) and log PAC-1 % 0.22 ± 0.58 vs 0.89 ± 0.31 (P <.01). This was not significant in the AF-recurrence group (P = .8, log CD62P; P = .1, log PAC-1). For endothelial function, ADMA levels decreased significantly at 6-months compared to baseline in the SR group (log ADMA μM/L 0.15 ± 0.02 vs 0.17 ± 0.04; P <.05), but did not alter significantly in the AF-recurrence group (P = .4, log ADMA). CONCLUSION Catheter ablation and successful maintenance of SR leads to a decrease in platelet activation and improvement in endothelial function in patients with AF. These findings suggest that AF is an important determinant of the prothrombotic state and that this may be reduced by successful catheter ablation.

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.

Early cardiac changes following anthracycline chemotherapy in breast cancer: a prospective multi-centre study using advanced cardiac imaging and biochemical markers

Summary This prospective study is designed to identify novel ima- ging (utilizing cardiovascular magnetic resonance and advance echocardiography) and biochemical markers to detect early, sub-clinical cardiotoxicity following chemotherapy. Background Cardiac toxicity is an important long term side effect of anthracyline chemotherapy. We hypothesized that novel cardiovascular magnetic resonance (CMR) and echocar- diographic markers of myocardial function, oedema, and necrosis can detect early, subclinical cardiac toxicity in patients receiving anthracycline therapy for breast cancer. recovery fast-spin echo sequence (short-TI inversion recovery) was used in 3 short-axis views of the left ven- tricle. For assessment of myocardial oedema, the ratio of mean signal intensity (SI) of the myocardium was com- pared to that of skeletal muscle. Results In the study patients, the mean CMR LV end-systolic volume index (LVESVI) increased from baseline of 17.8 ± 6.2 to 20.3 ± 5.9 mL/m2 (p 1.9 as specified by Lake Louis criteria) in one or more short axis slices post chemotherapy. There was no new late gadolinium hyperenhancement to suggest focal myocar- dial necrosis/fibrosis in any patient following therapy.

Utility of CMR Markers of Myocardial Injury in Predicting LV Functional Recovery: Results from PROTECTION AMI CMR Sub-study

BACKGROUND Adverse left ventricular (LV) remodelling following acute ST-segment elevation myocardial infarction (STEMI) has prognostic importance. We aimed to predict 90-day left ventricular (LV) function following acute STEMI using variables from clinical presentation, biomarkers, and cardiovascular magnetic resonance imaging (CMR). METHODS Consecutive patients undergoing primary percutaneous coronary intervention for anterior STEMI as part of the Selective Inhibition of Delta-protein Kinase C for the Reduction of Infarct Size in Acute Myocardial Infarction (PROTECTION-AMI) trial were enrolled into the CMR sub-study at selected sites. CMR was performed at baseline (days 3 to 5) and 90 days and used to evaluate infarct size, myocardial salvage index, infarct heterogeneity, microvascular obstruction and global LV function. Biochemical markers including creatinine kinase area under the curve (CK AUC), peak CK, peak CK-myocardial band (CK-MB) and AUC, and troponin I were collected at specific time-points. RESULTS Ninety-six patients were enrolled in the CMR sub study and 85 completed the 90-day follow-up, across 24 centres worldwide. LV ejection fraction (EF) was 56% (46-63%) at baseline and 60% (49-67%) at 90 days (p<0.001). Infarct size had moderate inverse correlation with 90-day EF (Spearmans rho=-0.7, p < 0.001) and had the strongest correlation when compared to myocardial salvage index (Spearmans rho=0.5, p=0.001), infarct heterogeneity (Spearmans rho=-0.4, p=0.02 or microvascular obstruction (Spearmans rho=-0.4, p<0.001). All biochemical markers had similar moderate relationship to LVEF at 90 days (Spearmans rho -0.6 to -0.8, p=0.001). In a multivariable model, only baseline LVEF, CMR infarct size and infarct heterogeneity independently predicted 90-day LVEF. CONCLUSION This study reports findings of a combined CMR protocol (including myocardial oedema imaging) in a multi-centre, multi-vendor setting. We found infarct size, infarct heterogeneity and myocardial salvage index correlated favourably with 90-day LVEF, however only the former two were independently predictive.

Early and late left ventricular effects of breast cancer chemotherapy: a prospective multi-centre study using advanced cardiac imaging

Background Myocardial dysfunction is a recognized toxicity of anthracycline (A) and herceptin (H) chemotherapy. Whilst there is much current focus on the incidence and magnitude of myocardial dysfunction following the A/H regimen, whether these changes are mediated by reversible or irreversible myocardial injury remains unknown. We sought to determine rates of persistent LV dysfunction at 12 months (as defined by left ventricular ejection fraction (LVEF) decrease by 10% or below lower limits of normal) following A/H and explore the mechanism of myocardial dysfunction using advance cardiac imaging.