Soraya El Ghannudi

Cardiovascular Mortality in Chronic Kidney Disease Patients Undergoing Percutaneous Coronary Intervention Is Mainly Related to Impaired P2Y12 Inhibition by Clopidogrel

OBJECTIVES We sought to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) differentially affects outcomes in patients with or without chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). BACKGROUND Although both CKD and impaired platelet responsiveness to clopidogrel are strong predictors of unfavorable outcome after PCI, the impact of their association is unknown. The platelet VASP-FCT assay is specific for the P2Y(12) ADP receptor pathway. In this test, platelet activation is expressed as the platelet reactivity index (PRI). METHODS Four-hundred forty unselected patients (CKD: 126, estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m(2)), no-CKD: 314 eGFR >60 ml/min/1.73 m(2)) undergoing urgent (n = 336) or planned (n = 104) PCI were prospectively enrolled. In each subgroup, patients were classified as low-responders (LR: PRI ≥ 61%) or responders (R: PRI <61%) to clopidogrel. RESULTS At a mean follow-up of 9 ± 2 months, all-cause mortality, cardiac death, and possible stent thrombosis were higher in CKD than in no-CKD patients. Within the CKD group, the LR status was associated with higher rates of all-cause mortality (25.5% vs. 2.8%, p < 0.001), cardiac death (23.5% vs. 2.8%, p < 0.001), all stent thrombosis (19.6% vs. 2.7%, p = 0.003), and MACE (33.3% vs. 12.3%, p = 0.007). Conversely, in no-CKD patients, the LR status did not affect outcomes. Multivariate analysis identified Killip class ≥ 3, drug-eluting stent implantation, and the interaction between LR and CKD (hazard ratio: 11.96, 95% confidence interval: 1.22 to 116.82; p = 0.033) as independent predictors of cardiac death. CONCLUSIONS In CKD patients, the presence of low platelet response to clopidogrel is associated with worse outcomes after PCI.

Myocardial Tagging with MR Imaging: Overview of Normal and Pathologic Findings

Magnetic resonance tagging is used to evaluate the dynamic deformation of lines or grids superimposed on the myocardium during the cardiac cycle. From these data, a specific postprocessing procedure provides two kinds of metrics: (a) three orthogonal components of myocardial motion (longitudinal, circumferential, and radial), and (b) rotation and torsion. Strain expresses the local myocardial deformation and is prone to important physiologic heterogeneities. Peak systolic strain is in the range of -15% to -20% for the longitudinal and circumferential components (fiber shortening) and 30%-40% for the radial component (wall thickening). The helical arrangement of myofibers that run in opposite directions at the epicardium and endocardium explains systolic twist (~15°). This torsion may be enhanced during the early stage of several diseases (eg, hypertrophic cardiomyopathy) or in heart failure with a normal left ventricular ejection fraction. Strain is generally impaired in ischemic heart disease and cardiomyopathy, but the most diagnostically significant finding is the early identification of contractile dysfunction on the basis of longitudinal and circumferential strain reduction in patients with apparently preserved systolic function. Thus, strain impairment appears to be a sensitive and promising marker of subclinical disease, with the potential for improving patient management.

Impact of P2Y12 Inhibition by Clopidogrel on Cardiovascular Mortality in Unselected Patients Treated by Percutaneous Coronary Angioplasty: A Prospective Registry

OBJECTIVES The aim of this study was to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by Vasodilator-stimulated phosphoprotein flow cytometry test (VASP- FCT) predicts cardiovascular events in a high-risk population undergoing percutaneous coronary intervention (PCI). BACKGROUND Impaired platelet responsiveness to clopidogrel is thought to be a determinant of cardiovascular events after PCI. The platelet VASP-FCT is a new assay specific to the P2Y(12) adenosine diphosphate receptor-pathway. In this test, platelet activation is expressed as platelet reactivity index (PRI). METHODS Four-hundred sixty-one unselected patients undergoing urgent (n = 346) or planned (n = 115) PCI were prospectively enrolled. Patients were classified as low-response (LR) and response (R) to clopidogrel, depending on their PRI. Optimal PRI cutoff was determined by receiver-operator characteristic curve analysis to 61% (LR: PRI > or =61% and R: PRI <61%). Follow-up was obtained at a mean of 9 +/- 2 months in 453 patients (98.3%). RESULTS At follow-up, total cardiac mortality rates and possible and total stent thrombosis were higher in LR patients. Multivariate analysis identified creatinine clearance (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.93 to 0.98, p < 0.001), drug-eluting stent (HR: 5.73; 95% CI: 1.40 to 23.43, p = 0.015), C-reactive protein (HR: 1.01; 95% CI: 1.001 to 1.019, p = 0.024), and LR to clopidogrel (HR: 4.00; 95% CI: 1.08 to 14.80, p = 0.037) as independent predictors of cardiac death. The deleterious impact of LR to clopidogrel on cardiovascular death was significantly higher in patients implanted with drug-eluting stent. CONCLUSIONS In patients undergoing PCI, LR to clopidogrel assessed by VASP-FCT is an independent predictor of cardiovascular death at the PRI cutoff value of > or =61%. The LR clinical impact seems to be dependent on the type of stent implanted.

Association of Estimated GFR With Platelet Inhibition in Patients Treated With Clopidogrel

BACKGROUND The reasons that decreased glomerular filtration rate (GFR) might alter the clinical efficacy of clopidogrel are poorly understood. STUDY DESIGN In this study, we sought to evaluate whether decreased GFR alters platelet response to clopidogrel in patients receiving a maintenance dose of clopidogrel (75 mg/d for at least 8 days). SETTINGS & PARTICIPANTS 126 consecutive patients categorized by estimated GFR: stages 1-2 (>60 mL/min/1.73 m(2); n = 29), stage 3a (45-59 mL/min/1.73 m(2); n = 21); stage 3b (30-44 mL/min/1.73 m(2); n = 26), stage 4 (15-29 mL/min/1.73 m(2); n = 14), and stage 5 (<15 mL/min/1.73 m(2); n = 36) were prospectively enrolled. PREDICTOR Residual platelet reactivity, defined in the VASP (Vasodilator Stimulated Phosphoprotein) flow cytometry test as platelet reactivity index (PRI) ≥61% and in the VerifyNow turbidimetric-based assay as a value >235 PRU (adenosine diphosphate receptor reaction units) or percentage of platelet inhibition <15%. OUTCOMES We examined factors associated with low response to clopidogrel using logistic regression. RESULTS A significant relationship between estimated GFR, PRI, PRU, and percentage of inhibition was found. The prevalence of residual platelet reactivity was highest in patients with GFR stage 5. PRI ≥61% occurred in 52.8% of patients with stage 5 versus 30.8% of stage 3b and 24.1% of stages 1-2 (P = 0.1). PRU >235 was found in 63.6% of patients with stage 5 versus 36.8% of stage 3b and 17.2% of stages 1-2 (P = 0.005). Inhibition <15% affected 66.7% of patients with stage 5 versus 21.1% of stage 3b and 17.2% of stages 1-2 (P < 0.001). In the multivariable model, GFR stage 5 (adjusted prevalence ratio [PR], 3.10; 95% CI, 1.23-9.43; P = 0.02), and obesity (adjusted PR, 1.92; 95% CI, 1.34-2.23; P = 0.004) were the sole predictors of residual platelet reactivity. LIMITATIONS Interference of hemodialysis with the pharmacokinetics of clopidogrel could not be excluded. CONCLUSION GFR stage 5 is associated with substantial impairment of platelet inhibition independently of diabetes mellitus.

Native T1 Mapping of the Heart – A Pictorial Review

T1 mapping is now a clinically feasible method, providing pixel-wise quantification of the cardiac structures T1 values. Beyond focal lesions, well depicted by late gadolinium enhancement sequences, it has become possible to discriminate diffuse myocardial alterations, previously not assessable by noninvasive means. The strength of this method includes the high reproducibility and immediate clinical applicability, even without the use of contrast media injection (native or pre-contrast T1). The two most important determinants of native T1 augmentation are (1) edema related to tissue water increase (recent infarction or inflammation) and (2) interstitial space increase related to fibrosis (infarction scar, cardiomyopathy) or to amyloidosis. Conversely, lipid (Anderson–Fabry) or iron overload diseases are responsible for T1 reduction. In this pictorial review, the main features provided by native T1 mapping are discussed and illustrated, with a special focus on the awaited clinical purpose of this unique, promising new method.

Longitudinal 2D strain can help diagnose coronary artery disease in patients with suspected non-ST-elevation acute coronary syndrome but apparent normal global and segmental systolic function

BACKGROUND The clinical work-up of patients presenting with chest pain is a diagnostic challenge. We investigated the diagnostic performance of global (GLS) and territorial (TLS) longitudinal strain to predict coronary artery disease (CAD) in patients presenting with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) but apparent normal global and regional systolic function. METHODS 150 consecutive suspected NSTE-ACS patients were initially screened for inclusion ; 58 patients with normal LVEF (≥55%) and WMSI (=1) were prospectively enrolled. Speckle-tracking echocardiography was performed on admission and all the patients underwent coronary angiography. CAD was defined as the presence of stenosis of >50%. RESULTS CAD was present in 33 patients (57%). LVEF was 60.7±4.6% in group 1 (CAD) and 61.1±5.0% in group 2 (no CAD). Global longitudinal strain (GLS) was altered in group 1 (-16.7±3.4%) as compared to group 2 (-22.4±2.9%, p<0.001). ROC curve analysis showed a high diagnostic value of GLS for the prediction of CAD (AUC=0.92 [0.84-1.00], p=0.0001). TLS was able to discriminate between coronary stenosis in the LAD, LCX or RCA. CONCLUSIONS Longitudinal 2D strain has a good diagnostic value and can efficiently localize the culprit lesion in patients presenting with NSTE-ACS but apparent normal global and regional systolic function.

Left Ventricular Involvement in Arrhythmogenic Right Ventricular Cardiomyopathy – A Cardiac Magnetic Resonance Imaging Study

Background Few studies evaluated left ventricular (LV) involvement in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The aim of this study is to determine the frequency, clinical presentation, and pattern of LV involvement in ARVD/C (LV-ARVD/C). Methods We retrospectively evaluated the cardiac magnetic resonance (CMR) in 202 patients referred between 2008 and 2012 to our institution, and we determined the presence or the absence of CMR criteria in the revised task force criteria 2010 for the diagnosis of ARVD/C. A total of 21 patients were diagnosed with ARVD/C according to the revised task force criteria 2010. All included patients had no previous history of myocarditis, acute coronary syndrome, or any other cardiac disease that could interfere with the interpretations of structural abnormalities. The LV involvement in ARVD/C was defined by the presence of one or more of the following criteria: LV end-diastolic volume (LVEDV; >95 mL/m2), LV ejection fraction (LVEF; <55%), LV late enhancement of gadolinium (LVLE) in a non-ischemic pattern, and LV wall motion abnormalities (WMAs). In the follow-up for the occurrence of cardiac death, ventricular tachycardia (VT) was obtained at a mean of 31 ± 20.6 months. Results A total of 21 patients had ARVD/C. The median age was 48 (33-63) years. In all, 11 patients (52.4%) had LV-ARVD/C. The demographic characteristics of patients with or without LV were similar. There was a higher frequency of left bundle-branch block (LBBB) VT morphology in ARVD/C (P = 0.04). In CMR, regional WMAs of right ventricle (RV) and RV ejection fraction (RVEF; <45%) were strongly correlated with LV-WMAs (r = 0.72, P = 0.02, r = 0.75, P = 0.02, respectively). RV late enhancement of gadolinium (RVLE) was associated with LV-WMs and LVLE (r = 0.7, P = 0.03; r = 0.8, P = 0.006). LVLE was associated with LV-WMAs, LVEF, and LVEDV (r = 0.9, P = 0.001; r = 0.8, P = 0.001; r = 0.8, P = 0.01). Conclusion LV involvement in ARVD/C is common and frequently associated with moderate to severe right ventricular (RV) abnormalities. The impact of LV involvement in ARVD/C on the prognosis needs further investigations.

Takotsubo and Takotsubo-like syndrome: A common neurogenic myocardial stunning pathway?

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Late Detection of Left Ventricular Dysfunction Using Two-Dimensional and Three-Dimensional Speckle-Tracking Echocardiography in Patients with History of Nonsevere Acute Myocarditis

Background: Acute myocarditis (AM) often involves the left ventricular (LV) subepicardium that might be displayed by cardiac magnetic resonance even late after the acute phase. In the absence of global or regional LV dysfunction, conventional transthoracic echocardiography (TTE) does not accurately identify tissue sequelae of AM. We sought to evaluate the diagnostic value of two‐dimensional (2D) and three‐dimensional (3D) speckle‐tracking echocardiography to identify patients with a history of AM with preserved LV ejection fraction (LVEF). Methods: Fifty patients (group 1: age, 31.4 ± 10.5 years; 76% males) with a history of cardiac magnetic resonance–confirmed diagnosis of AM (according to the Lake Louise criteria) were retrospectively identified and then (21.7 ± 23.4 months later) evaluated by complete echocardiography including 2D and 3D speckle‐tracking analysis, as well as 50 age‐ and gender‐matched healthy controls (group 2: age, 31.2 ± 9.5 years: 76% males). Patients with a history of severe clinical presentation of AM (sudden death, ventricular arrhythmia, heart failure, alteration of LVEF) were excluded. Results: At diagnosis, peak troponin and C‐reactive protein were 11.97 (interquartile range, 4.52‐25.92) &mgr;g/L and 32.3 (interquartile range, 14.85‐70.45) mg/L, respectively. Mean delay between acute phase and follow‐up study TTE was 21.7 ± 23.4 months. LVEF was not statistically different between groups (62.1% vs 63.5%, P = .099). Two‐dimensional global longitudinal strain (GLS) was lower in magnitude in group 1 (−17.8% vs −22.1%, P < .0001) as were 2D layer‐specific subepicardial GLS (−15.4% vs −19.7%, P < .0001) and subendocardial GLS (−20.71% vs −25.08%, P < .0001). Three‐dimensional global longitudinal, circumferential, area, and radial strains were lower in magnitude in group 1 (−11.80% vs −14.98%, P < .0001; −12.57% vs −15.12%, P < .0001; −22.28% vs −25.87%, P < .0001; 31.47% vs 38.06%, P < .0001, respectively). Receiver operating characteristic curve analysis showed that subepicardial GLS displayed a better diagnostic performance to detect sequelae of AM as compared with GLS (area under the curve = 0.97 vs 0.93, P = .045). Conclusions: In patients with a history of AM, a subtle LV dysfunction can be detected by 2D and 3D speckle‐tracking echocardiography, even though LVEF is conserved, adding incremental information over conventional TTE. HighlightsIn patients with a history of AM, a subtle myocardial dysfunction can be detected even late after the episode.Both LV and right ventricular strain parameters are altered compared with healthy controls.Layer‐specific 2DSTE is useful to detect subepicardial alteration of LV longitudinal function.These tools represent a potential novel approach for noninvasive multimodality evaluation of AM patients.

Acute Myocarditis Diagnosed by Layer‐Specific 2D Longitudinal Speckle Tracking Analysis

A 34-year-old patient was referred to our cardiology department for acute chest pain. His medical history included Hodgkin’s lymphoma (in complete remission). Physical examination was unremarkable. ECG revealed diffuse concave-upward ST-segment elevation. Biology test results were as follows: troponin Ic, 3.61 ng/mL; C-reactive protein 53 mg/L. Angio-coronarography was normal. Echocardiography was performed on admission: Global and regional systolic LV functions were normal (LVEF > 55%, without wall motion abnor-