Benefit of Early Invasive Therapy in Acute Coronary Syndromes A Meta-Analysis of Contemporary Randomized Clinical Trials

ObjectivesThis study sought to systematically determine whether early invasive therapy improves survival and reduces adverse cardiovascular events in the management of non–ST-segment elevation acute coronary syndromes.BackgroundAlthough early invasive therapy reduces recurrent unstable angina, the magnitude of benefit on other important adverse outcomes is unknown.MethodsClinical trials that randomized non–ST-segment elevation acute coronary syndrome patients to early invasive therapy versus a more conservative approach were included for analysis.ResultsIn all there were 7 trials with 8,375 patients available for analysis. At a mean follow-up of 2 years, the incidence of all-cause mortality was 4.9% in the early invasive group, compared with 6.5% in the conservative group (risk ratio [RR] = 0.75, 95% confidence interval [CI] 0.63 to 0.90, p = 0.001), and at 1 month (RR = 0.82, 95% CI 0.50 to 1.34, p = 0.43). At 2 years of follow-up, the incidence of nonfatal myocardial infarction was 7.6% in the invasive group, versus 9.1% in the conservative group (RR = 0.83, 95% CI 0.72 to 0.96, p = 0.012), and at 1 month (RR = 0.93, 95% CI 0.73 to 1.19, p = 0.57). At a mean of 13 months of follow-up, there was a reduction in rehospitalization for unstable angina (RR = 0.69, 95% CI 0.65 to 0.74, p < 0.0001).ConclusionsManaging non–ST-segment elevation acute coronary syndromes by early invasive therapy improves long-term survival and reduces late myocardial infarction and rehospitalization for unstable angina

Shotgun Sequencing Analysis of Trypanosoma cruzi I Sylvio X10/1 and Comparison with T. cruzi VI CL Brener

Trypanosoma cruzi is the causative agent of Chagas disease, which affects more than 9 million people in Latin America. We have generated a draft genome sequence of the TcI strain Sylvio X10/1 and compared it to the TcVI reference strain CL Brener to identify lineage-specific features. We found virtually no differences in the core gene content of CL Brener and Sylvio X10/1 by presence/absence analysis, but 6 open reading frames from CL Brener were missing in Sylvio X10/1. Several multicopy gene families, including DGF, mucin, MASP and GP63 were found to contain substantially fewer genes in Sylvio X10/1, based on sequence read estimations. 1,861 small insertion-deletion events and 77,349 nucleotide differences, 23% of which were non-synonymous and associated with radical amino acid changes, further distinguish these two genomes. There were 336 genes indicated as under positive selection, 145 unique to T. cruzi in comparison to T. brucei and Leishmania. This study provides a framework for further comparative analyses of two major T. cruzi lineages and also highlights the need for sequencing more strains to understand fully the genomic composition of this parasite

Left ventricular remodeling in aortic stenosis

Aortic stenosis (AS) is a progressive condition associated with high mortality if not treated. The hemodynamic effects of AS have serious implications for the left ventricle. In this review, we describe the responses of the left ventricle to AS by highlighting the process of adaptive remodelling, which begins as a beneficial compensatory mechanism but ultimately transitions to a maladaptive process with potentially irreversible consequences. We discuss the impact of left ventricular (LV) remodelling on diastolic and systolic function and on the development of symptoms. In addition, we review the adverse consequences of maladaptive LV remodelling on clinical outcomes before and after aortic valve replacement. The relative irreversibility of maladaptive remodelling and the clear relationship between its progression and clinical outcomes suggest a need to incorporate measures of LV performance beyond simply systolic function when deciding on the timing of valve replacement.La sténose aortique (SA) est une affection évolutive associée à une mortalité élevée lorsqu’elle n’est pas traitée. Les effets hémodynamiques de la SA ont des conséquences sérieuses sur le ventricule gauche. Dans cette revue, nous décrivons les réponses du ventricule gauche à la SA par la mise en évidence du processus de remodelage adaptatif, qui agit au début en tant que mécanisme compensatoire bénéfique, mais finalement en tant que transition vers un processus maladaptatif ayant des conséquences potentiellement irréversibles. Nous traitons des conséquences du remodelage ventriculaire gauche (VG) sur la fonction diastolique et systolique et sur la manifestation des symptômes. De plus, nous passons en revue les conséquences indésirables du remodelage VG maladaptatif sur les résultats cliniques avant et après le remplacement valvulaire aortique. L’irréversibilité relative du remodelage maladaptatif et le lien évident entre sa progression et les résultats cliniques montrent la nécessité d’intégrer les mesures de la performance VG au-delà de la simple fonction systolique lors de la détermination du moment opportun du remplacement valvulaire

Relationship of Race/Ethnicity With Door‐to‐Balloon Time and Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for ST‐Elevation Myocardial Infarction: Findings From Get With the Guidelines–Coronary Artery Disease

BackgroundPrior studies have described racial/ethnic disparities in door-to-balloon (DTB) time for patients undergoing primary percutaneous coronary intervention (PCI). We sought to compare DTB time between different racial/ethnic groups undergoing primary PCI for ST-elevation myocardial infarction in Get With the Guidelines (GWTG).HypothesisThere may be differences in D2B time associated with race/ethnicity.MethodsWe identified 7445 white (n = 6365), African American (n = 568), and Hispanic (n = 512) patients undergoing primary PCI.ResultsThere were no differences in the median DTB time between white (74 minutes; intraquartile range [IQR], 54-99), African American (77 minutes; IQR, 57-100), and Hispanic (75 minutes; IQR, 56-100) (P = 0.13) patients. There were no crude differences in DTB time ≤90 minutes; however, after adjusting for confounders, African American race was associated with lower odds of DTB time ≤90 minutes (odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.70-0.99; P = 0.04). This association was seen in African American males (OR: 0.66; 95% CI: 0.55-0.80) but not African American females (OR: 1.27; 95% CI: 0.96-1.68). Overall, Hispanic ethnicity was not associated with a difference in DTB time ≤90 minutes (OR: 0.98; 95% CI: 0.77-1.25; P = 0.88); although Hispanic males did have a slightly longer median DTB time compared with whites. During the study, the proportion of patients with DTB times ≤90 minutes increased for all groups, and mortality was similar between groups (white 3.8%, African American 3.0%, Hispanic 4.1%, P = 0.62).ConclusionsIn GWTG-Coronary Artery Disease, small differences in DTB times persist among different races/ethnicities. However, the proportion achieving DTB times ≤90 minutes has increased substantially for all patients over time, and there was no association between race/ethnicity and in-hospital mortality

Transcatheter Edge-to-Edge Repair in Patients With Anatomically Complex Degenerative Mitral Regurgitation

BACKGROUND: Mitral valve transcatheter edge-to-edge repair is safe and effective in treating degenerative mitral regurgitation (DMR) patients at prohibitive surgical risk, but outcomes in complex mitral valve anatomy patients vary. OBJECTIVES: The PASCAL IID registry assessed safety, echocardiographic, and clinical outcomes with the PASCAL system in prohibitive risk patients with significant symptomatic DMR and complex mitral valve anatomy. METHODS: Patients in the prospective, multicenter, single-arm registry had 3+ or 4+ DMR, were at prohibitive surgical risk, presented with complex anatomic features based on the MitraClip instructions for use, and were deemed suitable for the PASCAL system by a central screening committee. Enrolled patients were treated with the PASCAL system. Safety, effectiveness, and functional and quality-of-life outcomes were assessed. Study oversight also included an echocardiographic core laboratory and clinical events committee. RESULTS: The study enrolled 98 patients (37.2% ≥2 independent significant jets, 15.0% severe bileaflet/multi scallop prolapse, 13.3% mitral valve orifice area \u3c4.0 cm2, and 10.6% large flail gap and/or large flail width). The implant success rate was 92.9%. The 30-day composite major adverse event rate was 11.2%. At 6 months, 92.4% patients achieved MR ≤2+ and 56.1% achieved MR ≤1+ (P \u3c 0.001 vs baseline). The Kaplan-Meier estimates for survival, freedom from major adverse events, and heart failure hospitalization at 6 months were 93.7%, 85.6%, and 92.6%, respectively. Patients experienced significant symptomatic improvement compared with baseline (P \u3c 0.001). CONCLUSIONS: The outcomes of the PASCAL IID registry establish the PASCAL system as a useful therapy for prohibitive surgical risk DMR patients with complex mitral valve anatomy. (PASCAL IID Registry within the Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID] NCT03706833)