Antithrombotic strategies in elderly patients with acute coronary syndrome.

Elderly patients represent a growing proportion of the acute coronary syndrome population in Western countries. However, their frequent atypical symptoms at presentation often lead to delays in management and to misdiagnosis. Furthermore, their prognosis is poorer than that of younger patients because of physiological changes in platelet function, haemostasis and fibrinolysis, but also a higher proportion of comorbidities and frailty, both of which increase the risk of recurrent thrombotic and bleeding events. This complex situation, with ischaemic and haemorrhagic risk factors often being intertwined, may lead to confusion about the required treatment strategy, sometimes resulting in inadequate management or even to therapeutic nihilism. It is therefore critical to provide a comprehensive overview of our understanding of the pathophysiological processes underlying acute coronary syndrome in elderly patients, and to summarise the results from the latest clinical trials to help decision making for these high-risk patients.

National French registry of spontaneous coronary artery dissections: prevalence of fibromuscular dysplasia and genetic analyses.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly reported but poorly understood condition. Few European data are available. AIMS: The aims of this study were to obtain European data on SCAD, determine the prevalence of fibromuscular dysplasia (FMD) and enable genetic analyses in this population. METHODS: Data from a national French registry of SCAD cases were analysed prospectively and retrospectively. Clinical and angiographic data and management strategy were collected. Major adverse cardiovascular events (MACE) were analysed after one year of follow-up. Subjects were screened for FMD and blood was collected for DNA extraction. RESULTS: From June 2016 to August 2018, 373 SCAD cases were confirmed by the core lab. Mean age was 51.5 years. Patients were mostly women (90.6%) and 54.7% of cases had less than two cardiovascular risk factors. At one year, 295 patients (79.1%) were treated conservatively, the MACE rate was 12.3%, and there were no cases of mortality. The recurrence rate of SCAD was 3.3%. FMD was found at ≥1 arterial site in 45.0% of cases. We also confirmed the genetic association between the PHACTR1 locus and SCAD (odds ratio=1.66, p=7.08×10-8). CONCLUSIONS: Here we describe the DISCO registry, the largest European SCAD cohort where FMD was found in 45% of cases and the genetic association with PHACTR1 was confirmed. This nationwide cohort is a valuable resource for future clinical and genetic investigation to understand SCAD aetiology.

Echocardiographic Assessment of Left Ventricular Remodeling in American Style Footballers.

Several athletic programs incorporate echocardiography during pre-participation screening of American Style Football (ASF) players with great variability in reported echocardiographic values. Pre-participation screening was performed in National Collegiate Athletic Association Division I ASF players from 2008 to 2016 at the Division of Sports Cardiology. The echocardiographic protocol focused on left ventricular (LV) mass, mass-to-volume ratio, sphericity, ejection fraction, and longitudinal Lagrangian strain. LV mass was calculated using the area-length method in end-diastole and end-systole. A total of two hundred and thirty players were included (18±1 years, 57% were Caucasian, body mass index 29±4 kg/m2) after four players (2%) were excluded for pathological findings. Although there was no difference in indexed LV mass by race (Caucasian 78±11 vs. African American 81±10 g/m2, p=0.089) or sphericity (Caucasian 1.81±0.13 vs. African American 1.78±0.14, p=0.130), the mass-to-volume ratio was higher in African Americans (0.91±0.09 vs. 0.83±0.08, p<0.001). No race-specific differences were noted in LV longitudinal Lagrangian strain. Player position appeared to have a limited role in defining LV remodeling. In conclusion, significant echocardiographic differences were observed in mass-to-volume ratio between African American and Caucasian players. These demographics should be considered as part of pre-participation screening.

Approaching Higher Dimension Imaging Data Using Cluster-Based Hierarchical Modeling in Patients with Heart Failure Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality, accounting for the majority of heart failure (HF) hospitalization. To identify the most complementary predictors of mortality among clinical, laboratory and echocardiographic data, we used cluster based hierarchical modeling. Using Stanford Translational Research Database, we identified patients hospitalized with HFpEF between 2005 and 2016 in whom echocardiogram and NT-proBNP were both available at the time of admission. Comprehensive echocardiographic assessment including left ventricular longitudinal strain (LVLS), right ventricular function and right ventricular systolic pressure (RVSP) was performed. The outcome was defined as all-cause mortality. Among patients identified, 186 patients with complete echocardiographic assessment were included in the analysis. The cohort included 58% female, with a mean age of 78.7 ± 13.5 years, LVLS of -13.3 ± 2.5%, an estimated RVSP of 38 ± 13 mmHg. Unsupervised cluster analyses identified six clusters including ventricular systolic-function cluster, diastolic-hemodynamic cluster, end-organ function cluster, vital-sign cluster, complete blood count and sodium clusters. Using a stepwise hierarchical selection from each cluster, we identified NT-proBNP (standard hazard ratio [95%CI] = 1.56 [1.17-2.08]) and RVSP (1.37 [1.09-1.78]) as independent correlates of outcome. When adding these parameters to the well validated Get with the Guideline Heart Failure risk score, the Chi-square was significantly improved (p = 0.01). In conclusion, NT-proBNP and RVSP were independently predictive in HFpEF among clinical, imaging, and biomarker parameters. Cluster-based hierarchical modeling may help identify the complementally predictive parameters in small cohorts with higher dimensional clinical data.

Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES: This study sought to test the association between the rs9349379 genotype and SCAD. METHODS: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Time based versus strain based myocardial performance indices in hypertrophic cardiomyopathy, the merging role of left atrial strain.

AIMS: The myocardial performance index (MPI) is a time-based index of global myocardial performance. In this study, we sought to compare the prognostic value of the MPI with other strain and remodelling indices in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We enrolled 126 patients with HCM and 50 age- and sex-matched controls. Along with traditional echocardiographic assessment, MPI, left ventricular global longitudinal strain (LVGLS), E/e' ratio, and total left atrial (LA) global strain (LAS) were also measured. Time-based MPI was calculated from flow or tissue-based pulse wave Doppler (PWD and TDI) as the (isovolumic-relaxation and contraction time)/systolic-time. We used hierarchical clustering and network analysis to better visualize the relationship between parameters. The primary endpoint was the composite of all-cause death, heart transplantation, left ventricular assist device implantation, and clinical worsening. Left ventricular outflow tract (LVOT) obstruction was present in 56% of patients. Compared with controls, patients with HCM had worse LVGLS (-14.0 ± 3.4% vs. -19.6 ± 1.5%), higher E/e' (12.9 ± 7.2 vs. 6.1 ± 1.5), LA volume index (LAVI) (36.4 ± 13.8 ml/m2 vs. 25.6 ± 6.7 ml/m2), and MPI (0.55 ± 0.17 vs. 0.40 ± 0.11 for PWD and 0.59 ± 0.22 vs. 0.46 ± 0.09 for TDI) (all P < 0.001). During a median follow-up of 55 months, 47 endpoints occurred. PWD or TDI-based MPI was not associated with outcome, while LAVI, LAS, LVGLS, and E/e' were (all P < 0.01). On multivariable analysis, LVOT obstruction (P < 0.001), LAS (P < 0.001), and E/e' (P = 0.02) were retained as independent associates. They were in different clusters suggesting complemental relationship between them. CONCLUSION: Time-based index is less predictive of outcome than strain or tissue Doppler indices. LAS may be a promising prognostic marker in HCM.

Long-term prognostic value of invasive and non-invasive measures early after heart transplantation.

BACKGROUND: Invasively assessed coronary microvascular resistance early after heart transplantation predicts worse long-term outcome; however, little is known about the relationship between microvascular resistance, left ventricular function and outcomes in this setting. METHODS: A total of 100 cardiac transplant recipients had fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) measured in the left anterior descending artery and echocardiographic assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at 1 year after heart transplantation. The primary endpoint was the composite of death and retransplantation occurring beyond the first post-operative year. RESULTS: The mean FFR, IMR, LVEF, and GLS values at 1 year were 0.87 ±â€¯0.06, 21.3 ±â€¯17.3, 60.4 ±â€¯5.4%, and 14.2 ±â€¯2.4%, respectively. FFR and IMR had no significant correlation with LVEF and GLS. During a mean follow-up of 6.7 ±â€¯4.2 years, the primary endpoint occurred in 24 patients (24.0%). By ROC curve analysis, IMR = 19.3 and GLS = 13.3% were the best cutoff values for predicting death or retransplantation. Cumulative event-free survival was significantly lower in patients with higher IMR (log-rank p = 0.02) and lower GLS (log-rank p < 0.001). Cumulative event-free survival can be further stratified by the combination of IMR and GLS (long-rank p < 0.001). By multivariable Cox proportional hazards model, higher IMR and lower GLS were independently associated with long-term death or retransplantation (elevated IMR, hazard ratio = 2.50, p = 0.04 and reduced GLS, hazard ratio = 3.79, p = 0.003, respectively). CONCLUSION: Invasively assessed IMR does not correlate with GLS at 1 year after heart transplantation. IMR and GLS determined at 1 year may be used as independent predictors of late death or retransplantation.

Incremental Value of Deformation Imaging and Hemodynamics Following Heart Transplantation: Insights From Graft Function Profiling.

OBJECTIVES: This study investigated to define graft dysfunction and to determine its incremental association with long-term outcome after heart transplantation (HT). BACKGROUND: Although graft failure is an established cause of late mortality after HT, few studies have analyzed the prognostic value of graft dysfunction at 1- and 5-year follow-up of HT. METHODS: Patients who underwent HT and completed their first annual evaluation with right heart catheterization and echocardiography at Stanford University between January 1999 and December 2011 were included in the study. Hierarchical clustering was used to identify modules to capture independent features of graft dysfunction at 1 year. The primary endpoint for analysis consisted of the composite of cardiovascular mortality, re-transplantation, or heart failure hospitalization within 5 years of HT. The study further explored whether changes in graft dysfunction between 1 and 5 years were associated with 10-year all-cause mortality. RESULTS: A total of 215 HT recipients were included in the study. Using hierarchical clustering, 3 functional modules were identified; among them, left ventricular global longitudinal strain (LVGLS), stroke volume index, and right atrial pressure (RAP) or pulmonary capillary wedge pressure (PCWP) captured key features of graft function. Graft dysfunction based on pre defined LVGLS in absolute value <14%, stroke volume index <35 ml/m2, RAP >10 mm Hg, or PCWP >15 mm Hg were present in 41%, 36%, and 27%, respectively. The primary endpoint at 5 years occurred in 52 patients (24%), whereas 10-year all-cause mortality occurred in 30 (27%) of 110 patients alive at 5 years. On multivariate analysis, RAP (standardized hazard ratio: 1.63), LVGLS (standardized hazard ratio: 1.39), and a history of hemodynamically compromising rejection within 1 year (hazard ratio: 2.18) were independent predictors of 5-year outcome. RAP at 5 years, as well as change in RAP from 1 to 5 years, was predictive of 10-year all-cause mortality. CONCLUSIONS: RAP and LVGLS at the first annual evaluation provide complementary prognostic information in predicting 5-year outcome after HT.

Usefulness of intracardiac echocardiography for the diagnosis of infective endocarditis following percutaneous pulmonary valve replacement.

Infective endocarditis is a serious complication occurring after percutaneous pulmonary valve replacement with a Melody valve; it is of uncertain incidence, and presents a challenging diagnosis. Vegetations may be difficult to visualise with transthoracic and transoesophageal echocardiography. We report the role of intracardiac echocardiography in this condition by confirming the prosthesis involvement.

How and when to suspect spontaneous coronary artery dissection: novel insights from a single-centre series on prevalence and angiographic appearance.

AIMS: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed entity of acute coronary syndrome (ACS). Its prevalence remains unclear due to a challenging diagnosis, particularly in instances of intramural haematoma without intimal rupture. In the present study, we aimed to: 1) estimate the prevalence of SCAD among acute coronary syndrome (ACS) patients managed in a French coronary care centre, 2) demonstrate the value of specific angiographic signs for diagnosing SCAD, and 3) confirm the incremental value of intracoronary imaging in ambiguous cases. METHODS AND RESULTS: From 1999 to 2014, 55 cases of SCAD (all women, mean age 50.1 years) were diagnosed. Ignoring age, 51 (92.7%) had ≤2 cardiovascular risk factors. Thirty-six were diagnosed prospectively during the latter period (2012-2014). Among these, SCAD accounted for 35.7% of ACS (20/56) in women <60 years with ≤1 cardiovascular risk factor. Upon close investigation, five angiographic features commonly observed with SCAD were identified: 1) absence of atheroma on other coronary arteries, 2) radiolucent flap(s), 3) contrast dye staining of the arterial wall, 4) starting and/or ending of the angiographic ambiguity on a side branch, 5) long narrowing of lumen calibre: smooth and linear, or stenosis of varying severity mimicking a "stick insect" or "radish" aspect. Three of the above five signs were present in 51 (92.7%) cases. Optical computed tomography (OCT) was performed in 19 cases with no complication. All explored arteries had evidence of intramural haematoma and/or intimomedial membrane separation. An intimal rupture was observed in 10 (52.6%) patients. The diseased segment initiated or ended on a side branch in 14 (73.7%) patients. CONCLUSIONS: SCAD accounts for approximately one third of ACS in young women with ≤1 CRF. The combination of specific angiographic signs and OCT imaging facilitates the diagnosis of ambiguous cases without intimal rupture.