Access and Outcomes Among Hypertrophic Cardiomyopathy Patients in a Large Integrated Health System.

Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. Current guidelines endorse management in expert centers, but patient socioeconomic status can affect access to specialty care. The effect of socioeconomic status and specialty care access on HCM outcomes has not been examined. Methods and Results We conducted a retrospective cohort study that examined outcomes among HCM patients receiving care in the Yale New Haven Health System between June 2011 and December 2017. Patients were assigned to lower or higher socioeconomic status groups (LSES/HSES) based on medical insurance provider and to receivers of specialty care (SC) at Yale's Inherited Cardiomyopathy clinic or general cardiology care (GC). The primary outcome was all-cause death, and the secondary outcome was all-cause hospitalization. We identified 953 HCM patients; 820 (86%) were HSES and 133 (14%) were LSES. Forty-three (4.5%) patients died from cardiac and noncardiac causes. LSES patients within the general cardiology care cohort had significantly higher all-cause mortality compared with HSES patients (adjusted hazard ratio, [95% CI]=10.06 [4.38-23.09]; P<0.001). This was not noted in the specialty care cohort (adjusted hazard ratio, [95% CI]=2.87 [0.56-14.73]; P=0.21). The moderator effect of specialty care on mortality difference between LSES versus HSES, however, did not reach statistical significance (hazard ratio, 0.29 [0.05-1.77]; P=0.18). Specialist care was associated with increased hospitalization (adjusted hazard ratio, [95% CI]=3.28 [1.11-9.73]; P=0.03 for LSES; 2.19 [1.40-3.40]; P=0.001 for HSES). Conclusions Socioeconomically vulnerable HCM patients had higher mortality when not referred to specialty care. Further study is needed to understand the underlying causes.

Improving Outcomes in INTERMACS Category 1 Patients with Pre-LVAD, Awake Venous-Arterial Extracorporeal Membrane Oxygenation Support.

Effective strategies to optimize Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS 1) patients are in much need. A novel awake venous-arterial extracorporeal membrane oxygenation (aVA ECMO) allows for clinical assessments while temporarily supporting biventricular function and stabilizing end-organ functions. The aim of the study was to assess outcomes of patients with aVA ECMO support before durable left ventricular assist device (LVAD) implantation. We evaluated 83 patients who received durable LVAD in 2012-2015, of whom 19 received aVA ECMO support before durable LVAD. Kaplan-Meier and Cox proportional hazards analyses were conducted to assess post-LVAD survival. No complications were observed during the mean aVA ECMO support of 2.7 days. Unadjusted survival of aVA ECMO-supported patients and non-aVA ECMO INTERMACS 1 patients at 1 year were 84.2% and 66.7%, respectively (p = 0.15). Survival of aVA ECMO patients was comparable with that of non-aVA ECMO INTERMACS 2 cohort (84.2% vs. 80.8%) at 1 year. Multivariate analysis demonstrated a significant reduction in the risk of death in aVA ECMO group compared with INTERMACS 1 non-aVA ECMO group (hazard ratio [HR]: 0.17; p = 0.035). Awake venous-arterial (VA) ECMO allows bridge to next therapy and improves outcomes in INTERMACS category 1 patients with an effect comparable with downgrading the disease severity on the INTERMACS scale.

Plasma Levels of MicroRNA-155 Are Upregulated with Long-Term Left Ventricular Assist Device Support.

Left ventricular assist device (LVAD) therapy unloads the failing heart but exposes the human body to unique pathophysiologic demands such as continuous blood flow and complete univentricular support, which are associated with increased risk of adverse clinical outcomes. MicroRNAs (miRNAs) are 22-23 nucleotide RNAs involved in regulation of multiple biologic processes including the pathogenesis of heart failure (HF). Thus, measurement of miRNAs may have potential in both diagnostics as circulating biomarkers and in therapeutics for targeted interventions. We examined 23 distinct miRNAs that have previously been shown to play a role in HF pathogenesis and measured them in 40 individuals both before continuous-flow LVAD implantation and at a median of 96.5 days after implantation. Quantitative real-time polymerase chain reaction was performed for miRNA amplification, and 19 miRs were included in statistical analysis. Wilcoxon signed-rank tests were used to compare within-patient median relative quantification values pre- and post-LVAD placement. The median age of patients was 67 years, and 57.5% were at Interagency Registry for Mechanically Assisted Circulatory Support level 1-2. After LVAD support, only miR-155 was found to be statistically significant (p < 0.002), with an upregulation in plasma expression levels with LVAD support, which persisted regardless of the direction of change in serial HF biomarker levels. MicroRNA-155, which has been shown to play a central role in inflammation and neovascularization, was upregulated with long-term LVAD support. If validated by future studies, miR-155 may help further inform on underlying LVAD physiology and has a role as a therapeutic target in this patient population.

The relationship between tumor volume and the number of positive cores in men undergoing multisite extended biopsy: implication for expectant management.

PURPOSE: We assessed the relationship between the number of positive cores obtained at extended biopsy and tumor volume in radical prostatectomy specimens as a tool for predicting the biological significance of prostate cancer from biopsy data. MATERIALS AND METHODS: The study group included 207 men who were treated with radical prostatectomy without neoadjuvant therapy at our cancer center. All patients were diagnosed by systematic extended biopsy (10 or 11 cores) performed between 1997 and 2003. The variables analyzed were patient age, prostate specific antigen, clinical stage, biopsy Gleason score, maximum tumor length in a core, greatest percent of tumor in a core, total tumor length, total percent of tumor in all cores, positive core location, initial or repeat biopsy and prostate volume in subgroups based on the number of positive cores, that is group 1-1, group 2-2 and group 3-3 or more cores. Bivariate correlation analysis and multiple logistic regression analysis were used to determine the predictors of insignificant cancer. RESULTS: The number of positive cores was significantly related to total tumor volume (r = 0.433, p <0.001). Insignificant prostate cancer (volume less than 0.5 cc and Gleason score 6 or less) was found in 21.7% of patients (45 of 207). The incidence of insignificant cancer was 42.5% (31 of 73 patients) in group 1, 16.4% (10 of 61) in group 2 and 5.5% (4 of 73) in group 3. There was a significant difference in the incidence of insignificant cancer among the subgroups (group 1 vs 2 p <0.001, group 1 vs 3 p <0.0001 and group 2 vs 3 p <0.05). The best model for predicting insignificant cancer in group 1 was the combination of tumor length less than 2 mm, Gleason score 3 + 4 or less and prostate volume greater than 50 cc with 83.9% sensitivity (26 of 31 patients) and 61.9% specificity (26 of 42). CONCLUSIONS: The probability of insignificant cancer was directly related to the number of positive cores. Tumor length in a core, Gleason score and prostate volume significantly enhanced the prediction model for insignificant cancer in men with 1 positive core who underwent extended biopsy.

A streamlined three-dimensional volume estimation method accurately classifies prostate tumors by volume.

Prostate tumor volume has been suggested to be an important pathologic variable that predicts for clinical significance and outcome. However, the determination of tumor volume using standard methods such as computerized planimetry or image analysis is labor intensive. We studied whether length (L), width (W), and height (number of cross sections x sectional thickness, CST) of a tumor focus could be used to estimate prostate tumor volume. We studied 1091 tumor foci from 365 selected serially sectioned radical prostatectomy specimens. We randomly divided the specimens into evaluation (182 specimens) and validation (183 specimens) groups. After analyzing the evaluation group, we derived the formula 0.4 (slope of the regression line) x L x W x CST to estimate volume. We then tested whether our three-dimensional volume estimation formula could accurately classify tumor volume for specimens in the validation set as insignificant (0.5 cm3), and also into a five-category tumor volume scheme. Our three-dimensional estimate accurately classified tumors into insignificant and significant total volume categories in 94.0% of cases and into the five-category scheme in 85.8% cases. These accuracy rates were significantly better than rates for other methods. The three-dimensional estimate is an accurate and straightforward method for assessing prostate tumor volume.