The Role of Platelet-Derived Growth Factor Signaling in Healing Myocardial Infarcts

ObjectivesThis study sought to examine the role of platelet-derived growth factor (PDGF) signaling in healing myocardial infarcts.BackgroundPlatelet-derived growth factor isoforms exert potent fibrogenic effects through interactions with PDGF receptor (PDGFR)-α and PDGFR-β. In addition, PDGFR-β signaling mediates coating of developing vessels with mural cells, leading to the formation of a mature vasculature. We hypothesized that PDGFR activation may regulate fibrosis and vascular maturation in healing myocardial infarcts.MethodsMice undergoing reperfused infarction protocols were injected daily with a neutralizing anti–PDGFR-β antibody (APB5), an anti-PDGFR-α antibody (APA5), or control immunoglobulin G, and were killed after 7 days of reperfusion.ResultsThe PDGF-B, PDGFR-α, and PDGFR-β mRNA expression was induced in reperfused mouse infarcts. Perivascular cells expressing phosphorylated PDGFR-β were identified in the infarct after 7 days of reperfusion, indicating activation of the PDGF-BB/PDGFR-β pathway. The PDGFR-β blockade resulted in impaired maturation of the infarct vasculature, enhanced capillary density, and formation of dilated uncoated vessels. Defective vascular maturation in antibody-treated mice was associated with increased and prolonged extravasation of red blood cells and monocyte/macrophages, suggesting increased permeability. These defects resulted in decreased collagen content in the healing infarct. In contrast, PDGFR-α inhibition did not affect vascular maturation, but significantly decreased collagen deposition in the infarct.ConclusionsPlatelet-derived growth factor signaling critically regulates postinfarction repair. Both PDGFR-β– and PDGFR-α–mediated pathways promote collagen deposition in the infarct. Activation of PDGF-B/PDGFR-β is also involved in recruitment of mural cells by neovessels, regulating maturation of the infarct vasculature. Acquisition of a mural coat and maturation of the vasculature promotes resolution of inflammation and stabilization of the scar

Safety of Transcatheter Aortic Valve Replacement in Patients with Aortic Aneurysm: A Propensity-Matched Analysis

Introduction There is a paucity of data regarding the outcomes of transcatheter aortic valve replacement (TAVR) among patients with thoracic or abdominal aortic aneurysms (AA). Using the Nationwide Inpatient Sample (NIS) database, we explored the safety of TAVR among patients with a diagnosis of AA. Methods We queried the National Inpatient Sample database (2012–2017) for hospitalized patients undergoing TAVR, using ICD-9 and ICD-10 codes for endovascular TAVR. Reports show that \u3e 95% of endovascular TAVR in the US is via transfemoral access, so our population are mostly patients undergoing transfemoral TAVR. Using propensity score matching, we compared the trends and outcomes of TAVR procedures among patients with versus without AA. Results From a total sample of 29,517 individuals who had TAVR procedures between January 2012 and December 2017, 910 had a diagnosis of AA. In 774 matched-pair analysis, all-cause in-hospital mortality was similar in patients with and without AA OR 0.63 [(95% CI 0.28–1.43), p = 0.20]. The median length of stay was higher in patients with AA: 4 days (IQR 2.0–7.0) versus 3 days (IQR 2.0–6.0) p = 0.01. Risk of AKI [OR 1.01 (0.73–1.39), p = 0.87], heart block requiring pacemaker placement [OR 1.17 (0.81–1.69), p = 0.40], aortic dissection [OR 2.38 (0.41–13.75), p = 0.25], acute limb ischemia [OR 0.46 (0.18–1.16), p = 0.09], vascular complications [OR 0.80 (0.34–1.89), p = 0.53], post-op bleeding [OR 1.12 (0.81–1.57), p = 0.42], blood transfusion [OR 1.20 (0.84–1.70), p = 0.26], and stroke [OR 0.58 (0.24–1.39), p = 0.25] were similar in those with and without AA. Conclusions Data from a large nationwide database demonstrated that patients with AA undergoing TAVR are associated with similar in-hospital outcomes compared with patients without AA. Key Summary Points Patients with a diagnosis aortic aneurysm (thoracic or abdominal) undergoing transcatheter aortic valve replacement (TAVR) have same risk of periprocedural complications as those without a diagnosis of aortic aneurysms (AA). Patients with a diagnosis of aortic aneurysm had a longer length of hospital stay. Further studies are needed to determine how specific features of aortic aneurysm such as size, shape, thrombus burden, or calcifications affect the safety of TAVR

Healthcare and economic burden of heart failure with amyloidosis: An insight from National Readmission Database

Introduction:We analyzed trends, causes and predictors of 30-days readmission in cardiac amyloidosis and inspected the impact of these readmissions on mortality, morbidity, and utilization of healthcare resources. Methods:Heart Failure with cardiac amyloidosis patients were selected from National readmission Database (NRD) using ICD-10 CM codes. Patients younger than 18 years, elective readmissions, readmissions due to trauma, patients with missing data and December 2018 admissions were excluded. Primary outcome was all-cause 30-day readmissions rate, secondary outcomes were factors associated with 30-days readmissions and their effect on morbidity, mortality, and healthcare resource utilization. Results:Out of 4123 total heart failure with cardiac amyloidosis index admissions in 2018, 3374 patients were included in final analysis. 19.6% were readmitted within 30 days. Readmitted patients were younger, sicker, admitted to small or large hospital. Hypertensive heart and Chronic Kidney Disease (CKD Stage I-IV) with Congestive Heart Failure (CHF), hypertensive heart and CKD (Stage V) or End Stage Renal Disease (ESRD) with CHF, hypertensive heart disease with CHF, acute kidney failure, and sepsis were the most common causes of readmissions. Young age, admission to small and large size hospitals were independent predictors of 30-day readmissions. Readmissions had higher mortality, costed 6.6 extra in hospital days to patients and $16380 per admission to healthcare system. Conclusions:Cardiac amyloidosis readmissions were associated with increased morbidity and mortality of patients and extra burden on the healthcare system. There is a need to identify patients at risk for readmissions to improve patient outcomes and decrease healthcare cost

Genomic correlates of extreme pathologic response following neoadjuvant chemotherapy in locally advanced gastric cancer to reveal distinct vulnerabilities

441 Background: Clinical factors associated with pathologic response (PResp) following neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (LAGC) are well studied; however, genomic correlates of such response have not been previously investigated. Methods: Evaluable pre-NCT tumor samples from patients with LAGC who underwent resection and demonstrated extreme pathologic response (EPR; ≤10% PResp: n = 21, ≥80% PResp: n = 19) were sequenced using a targeted exome capture platform. Gene- and signaling pathway-level correlates of EPR and disease-specific survival (DSS) were examined. Results: Of 40 patients, a majority had ≥cT2/N+ disease and were treated with predominantly platinum (98%) or 5-FU (88%) based NCT regimens. Two patients with MSI-high tumors had ≤10% PResp and were excluded from analysis. The EPR cohorts did not differ significantly in demographic or clinical (i.e., tumor location, cT/N status, NCT regimen, extent of gastrectomy, number of lymph nodes examined, or margin status) characteristics. Although EPR cohorts did not differ with respect to tumor differentiation/grade, Lauren classification, proportions of TCGA consensus CIN or GS subtypes, tumors with ≤10% PResp were more likely to have vascular (P < 0.001) and perineural (P = 0.007) invasion. At median follow-up of 31m (IQR 21-57), ≥80% PResp was associated with improved DSS compared with ≤10% PResp (median NR vs. 32m, P = 0.04). On gene-level analysis, tumors with ≤10% PResp were significantly more likely to be ERBB2-altered (32% vs 5%, P = 0.04) compared with ≥80% PResp tumors. Conversely, ARID1A truncating mutations were enriched in tumors with ≥80% vs ≤10% PResp (32% vs 5%, P = 0.04). There was no difference in pathway-level alteration frequency between EPR cohorts. While frequency of oncogenic TP53 alterations was similar between EPR cohorts, TP53-altered tumors were associated with worse DSS vs TP53-wildtype tumors (median 80m vs 24m, P = 0.005) in patients demonstrating ≤10%, but not ≥80%, PResp. Conclusions: Genomic comparison of cohorts demonstrating EPR after NCT in LAGC reveal molecular vulnerabilities with distinct prognostic and therapeutic implications

Outcomes of transcatheter versus surgical aortic valve replacement among solid organ transplant recipients.

BACKGROUND: There is a paucity of data regarding the outcomes of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) among solid-organ transplant recipients. METHODS: Temporal trends in hospitalizations for aortic valve replacement among solid-organ transplant recipients were determined using the National Inpatient Sample database years 2012-2017. Propensity matching was conducted to compare admissions who underwent TAVR versus SAVR. The primary outcome was in-hospital mortality. RESULTS: The analysis included 1,730 hospitalizations for isolated AVR; 920 (53.2%) underwent TAVR and 810 (46.7%) underwent SAVR. TAVR was increasingly utilized for solid-organ transplant recipients (P CONCLUSION: This contemporary observational nationwide analysis showed that TAVR is increasingly performed among solid-organ transplant recipients. Compared with SAVR, TAVR was associated with lower in-hospital mortality, complications, and shorter length of stay

Atrial Speckle Tracking Echocardiography for Detecting Atrial Fibrillation in Cryptogenic Stroke: A Meta-Analysis

Cryptogenic stroke (CS) accounts for approximately 25% of ischemic stroke cases, with atrial fibrillation (AF) accounting for 30% of CS cases. We investigated the utility of left atrial (LA) speckle-tracking echocardiography in identifying patients at high risk of AF after CS and potentially guiding patients who will benefit from long-term rhythm monitoring devices. Cochrane Library, MEDLINE, and EMBASE were searched for relevant studies. We included studies that examined patients with new CS without a history of AF and further examined LA strain parameters (peak and/or reservoir strain). Continuous data were pooled as a mean difference (MD) comparing patients who developed AF vs no AF. We used the inverse variance method with the DerSimonian-Laird estimator for tau2 and Hartung-Knapp adjustment for random effect analysis. I was used to assess heterogeneity. Thirteen observational studies met our criteria and included 3031 patients with new CS. Of those, 420 patients developed AF on follow-up, and 2611 patients did not develop AF. The AF group vs. no AF had significantly reduced LA reservoir strain (LARS) [MD: -8.61; 95% CI: -10.76, -6.47, I2 = 85%, p \u3c 0.01] at presentation. LARS is significantly lower in patients who developed AF after CS. More studies are needed to validate this data