Nima Ghasemzadeh

Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis.

OBJECTIVES The aim of this study was to compare transfemoral transcatheter aortic valve replacement (TF TAVR) performed in a catheterization laboratory (minimalist approach [MA]) with TF TAVR performed in a hybrid operating room (standard approach [SA]). BACKGROUND A MA-TF TAVR can be performed without general anesthesia, transesophageal echocardiography, or a surgical hybrid room. The outcomes and cost of MA-TF TAVR compared with those of the SA have not been described. METHODS Patients who underwent elective, percutaneous TF TAVR using the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) were studied. Baseline characteristics, outcomes, and hospital costs of MA-TF TAVR and SA-TF TAVR were compared. RESULTS A total of 142 patients were studied (MA-TF TAVR, n = 70 and SA-TF TAVR, n = 72). There were no differences in baseline comorbidities (Society of Thoracic Surgeons score, 10.6 ± 4.3 vs. 11.4 ± 5.8; p = 0.35). All procedures in the MA-TF TAVR group were successful; 1 patient was intubated. Three patients in the SA-TF TAVR group had procedure-related death. Procedure room time (150 ± 48 min vs. 218 ± 56 min, p < 0.001), total intensive care unit time (22 h vs. 28 h, p < 0.001), length of stay from procedure to discharge (3 days vs. 5 days, p < 0.001), and cost (

Circulating CD34+ Progenitor Cells and Risk of Mortality in a Population with Coronary Artery Disease

45,485 ± 14,397 vs.

Sex and Age Differences in the Association of Depression With Obstructive Coronary Artery Disease and Adverse Cardiovascular Events

55,377 ± 22,587, p < 0.001) were significantly less in the MA-TF TAVR group. Mortality at 30 days was not significantly different in the MA-TF TAVR group (0 vs. 6%, p = 0.12) and 30-day stroke/transient ischemic attack was similar (4.3% vs. 1.4%, p = 0.35). Moderate or severe paravalvular leak and device success were similar in the MA-TF TAVR and SA-TF TAVR groups (3% vs. 5.8%, p = 0.4 and 90% vs. 88%, p = 0.79, respectively) at 30 days. At a median follow-up of 435 days, there was no significant difference in survival (MA-TF TAVR, 83% vs. SA-TF TAVR, 82%; p = 0.639). CONCLUSIONS MA-TF TAVR can be performed with minimal morbidity and mortality and equivalent effectiveness compared with SA-TF TAVR. The shorter length of stay and lower resource use with MA-TF TAVR significantly lowers hospital costs.

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Rationale: Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. Objectives: To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk. Methods and Results: Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34+ and CD34+/CD133+ cell counts and risk of death in cohort 1 (&bgr;=−0.92, P=0.043 and &bgr;=−1.64, P=0.019, respectively) that was confirmed in cohort 2 (&bgr;=−1.25, P=0.020 and &bgr;=−1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67–7.50) and 2.46 (1.18–5.13), respectively. CD34+/CD133+ cell counts improved risk prediction metrics beyond standard risk factors. Conclusions: Reduced circulating progenitor cell counts, identified primarily as CD34+ mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.

Mediterranean Dietary Patterns and Cardiovascular Health

Background Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (CAD) and adverse outcomes compared with similarly aged men and older women. Methods and Results We examined 3237 patients undergoing coronary angiography for evaluation of CAD and followed them for 2.9 years (median). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)‐9, and CAD burden was dichotomized based on its presence or absence. After multivariable adjustment for CAD risk factors, depressive symptoms predicted CAD presence in women aged ≤55 years (odds ratio=1.07 95% confidence interval [CI] 1.02 to 1.13 per 1 point increase in PHQ‐9 score), but not in men aged ≤55 years or women aged >55 years. Depressive symptoms also predicted increased risk of death in women aged ≤55 years (adjusted hazard ratio=1.07, 95% CI 1.02 to 1.14, per 1 point increase in PHQ‐9 score), but not in men aged ≤55 years and women aged >55 years, with P=0.02 for the depression‐sex interaction and P=0.02 for depression‐sex‐age interaction. Conclusions Among patients with suspected or established CAD, depressive symptoms are associated with increased risk of death, particularly in young women. This group may be especially vulnerable to the adverse cardiovascular effects of depression.

Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease

Introduction Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Coxs proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C‐reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youdens index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C‐statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. Conclusion Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.

Plasma PCSK9 Levels Are Elevated with Acute Myocardial Infarction in Two Independent Retrospective Angiographic Studies

The Mediterranean dietary pattern has been linked with reduced cardiovascular disease incidence and mortality. Components of the Mediterranean diet associated with better cardiovascular health include low consumption of meat and meat products, moderate consumption of ethanol (mostly from wine), and high consumption of vegetables, fruits, nuts, legumes, fish, and olive oil. Increasing evidence indicates that the synergy among these components results in beneficial changes in intermediate pathways of cardiometabolic risk, such as lipids, insulin sensitivity, oxidative stress, inflammation, and vasoreactivity. As a result, consumption of a Mediterranean dietary pattern favorably affects numerous cardiovascular disease risk factors, such as dyslipidemia, hypertension, metabolic syndrome, and diabetes. Moreover, strong evidence links this dietary pattern with reduced cardiovascular disease incidence, reoccurrence, and mortality. This review evaluates the current evidence behind the cardioprotective effects of a Mediterranean dietary pattern.

Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death

Background— Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. Methods and Results— Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (>+1 SD and <−1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19–2.21; HR, 2.19; 95% CI, 1.50–3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39–2.64) and was independent of and additive to high-sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. Conclusions— A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress.

The role of cardiovascular magnetic resonance in stratifying paravalvular leak severity after transcatheter aortic valve replacement: an observational outcome study

Objective Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein (LDL) receptor. Mutations that block PCSK9 secretion reduce LDL-cholesterol and the incidence of myocardial infarction (MI). However, it remains unclear whether elevated plasma PCSK9 associates with coronary atherosclerosis (CAD) or more directly with rupture of the plaque causing MI. Methods and Results Plasma PCSK9 was measured by ELISA in 645 angiographically defined controls (<30% coronary stenosis) and 3,273 cases of CAD (>50% stenosis in a major coronary artery) from the Ottawa Heart Genomics Study. Because lipid lowering medications elevated plasma PCSK9, confounding association with disease, only individuals not taking a lipid lowering medication were considered (279 controls and 492 with CAD). Replication was sought in 357 controls and 465 with CAD from the Emory Cardiology Biobank study. PCSK9 levels were not associated with CAD in Ottawa, but were elevated with CAD in Emory. Plasma PCSK9 levels were elevated in 45 cases with acute MI (363.5±140.0 ng/ml) compared to 398 CAD cases without MI (302.0±91.3 ng/ml, p = 0.004) in Ottawa. This finding was replicated in the Emory study in 74 cases of acute MI (445.0±171.7 ng/ml) compared to 273 CAD cases without MI (369.9±139.1 ng/ml, p = 3.7×10−4). Since PCSK9 levels were similar in CAD patients with or without a prior (non-acute) MI, our finding suggests that plasma PCSK9 is elevated either immediately prior to or at the time of MI. Conclusion Plasma PCSK9 levels are increased with acute MI.

Coronary heart disease alters intercellular communication by modifying microparticle-mediated microRNA transport

BackgroundGenetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.MethodsPeripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death.ResultsIn both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio = 8.5, P < 0.0001) and improved the C-statistic (area under the curve 0.82 to 0.91, P = 0.03) after adjustment for traditional covariates.ConclusionsA specific blood gene expression profile is associated with a significant risk of death in Caucasian subjects with CAD. This comprises a subset of transcripts that are also altered in expression during acute myocardial infarction.