Predicting functional mitral stenosis after restrictive annuloplasty for ischemic mitral regurgitation

Background: Although it has been realized that restrictive mitral valve annuloplasty (MVA) may re­sult in clinically significant functional mitral stenosis (MS), it still cannot be predicted. The purpose of this study was to identify risk factors for clinically significant functional MS following restrictive MVA surgery for chronic ischemic mitral regurgitation (CIMR). Methods: One hundred and fourteen patients who underwent restrictive MVA with coronary artery bypass grafting (CABG) for treatment of CIMR were retrospectively reviewed. Clinically significant functional MS was defined as resting transmitral peak pressure gradient (PPG) ≥ 13 mmHg. Results: During the follow-up period (range 6–12 months), 28 (24.56%) patients developed clinically significant functional MS. The PPG at follow-up was significantly higher than that measured in the early postoperative stage (3–5 days after surgery). Moreover, there was a linear correlation between the two measurements (r = 0.398, p < 0.001). Annuloplasty size ≤ 27 mm and early postoperative PPG ≥ 7.4 mmHg could predict clinically significant functional MS at 6–12 months postoperatively. Conclusions: Chronic ischemic mitral regurgitation patients treated with restrictive MVA and CABG have significant increases in PPG postoperatively. Annuloplasty size ≤ 27 mm and early postopera­tive PPG ≥ 7.4 mmHg can predict clinically significant functional MS at 6–12 months after surgery

Long-term outcomes of mitral valve annuloplasty versus subvalvular sparing replacement for severe ischemic mitral regurgitation

Background: Although practice guidelines recommend surgery for patients with severe chronic ischemic mitral regurgitation (CIMR), they do not specify whether to repair or replace the mitral valve. The purpose of this study was to evaluate the long-term outcomes in patients with severe CIMR undergoing mitral valve annuloplasty (MVA) versus subvalvular sparing mitral valve replacement (MVR).  Methods: 392 consecutive patients who underwent MVA or subvalvular sparing MVR for treatment of severe CIMR were retrospectively reviewed. Results: After adjustment for baseline differences with multivariable regression analysis at 53 months follow-up (interquartile range, 34–81 months), there was no significant difference between the two groups for risk of major adverse cardiac or cerebrovascular events (MACCE), cardiac death, or all-cause death. Propensity score matching extracted 77 pairs. During the follow-up, compared with the MVR group, both the left atrium and left ventricle end-diastolic diameter were markedly larger (p = 0.013 and p = 0.033, respectively), and the incidence of mitral regurgitation recurrence was significantly higher in the MVA group (p < 0.001). No significant difference was observed between the two propensity score-matched groups in composite in-hospital outcomes, overall survival, freedom from cardiac death or MACCE, except subvalvular sparing MVR was associated with a lower incidence of hospitalization for heart failure than MVA (p = 0.015). Conclusions: Subvalvular sparing MVR is a suitable management of patients with severe CIMR, it is more favorable to ventricular remodeling and is associated with a lower incidence of hospitalization for heart failure than MVA

Optimal Confidence Intervals for the Relative Risk and Odds Ratio

The relative risk and odds ratio are widely used in many fields, including biomedical research, to compare two treatments. Extensive research has been done to infer the two parameters through approximate or exact confidence intervals. However, these intervals may be liberal or conservative. A natural question is whether the intervals can be further improved in maintaining the correct confidence coefficient of an approximate interval or shortening an exact but conservative interval. In this article, when two independent binomials are observed we offer an effort to improve any of the existing intervals by applying the -function method. In particular, if the given interval is approximate, then the improved interval is exact; if the given interval is exact, then the improved interval is a subset of the given interval. This method is also applied multiple times to the improved intervals until the final resultant interval cannot be shortened any further. To demonstrate the effectiveness of the method, we use three real datasets to illustrate in detail how several good intervals in practice are improved. Two exact intervals are then recommended for estimating each of the two parameters in different scenarios

Optimal Confidence Intervals for the Relative Risk and Odds Ratio

The relative risk and odds ratio are widely used in many fields, including biomedical research, to compare two treatments. Extensive research has been done to infer the two parameters through approximate or exact confidence intervals. However, these intervals may be liberal or conservative. A natural question is whether the intervals can be further improved in maintaining the correct confidence coefficient of an approximate interval or shortening an exact but conservative interval. In this article, when two independent binomials are observed we offer an effort to improve any of the existing intervals by applying the -function method. In particular, if the given interval is approximate, then the improved interval is exact; if the given interval is exact, then the improved interval is a subset of the given interval. This method is also applied multiple times to the improved intervals until the final resultant interval cannot be shortened any further. To demonstrate the effectiveness of the method, we use three real datasets to illustrate in detail how several good intervals in practice are improved. Two exact intervals are then recommended for estimating each of the two parameters in different scenarios

MYH7 mutation is associated with mitral valve leaflet elongation in patients with obstructive hypertrophic cardiomyopathy

Mitral valve (MV) leaflet elongation is recognized as a primary phenotypic expression of hypertrophic cardiomyopathy (HCM) that contributes to obstruction. This study investigates the correlation between MV length and genotype mutations in the two predominant genes, myosin-binding protein C (MYBPC3), and the β-myosin heavy chain (MYH7) in patients with obstructive HCM (OHCM). Among the 402 OHCM patients, there were likely pathogenic or pathogenic variations in MYH7 (n = 94) and MYBPC3 (n = 76), along with a mutation-negative group (n = 212). Compared to genotype-negative patients, genotype-positive individuals exhibited elongated MV length, thicker interventricular septum, and increased instances of late gadolinium enhancement. Notably, MYH7 mutations were associated with a more severe disease trajectory than MYBPC3 mutations. After adjusting for potential confounders, multivariate linear regression analysis revealed that MYH7 gene mutations and left ventricular volume were independently associated with MV leaflet elongation. The study indicates that mutations in MYH7 and hemodynamics factors are significant risk factors for elongated MV leaflet. Consequently, regular assessment of MV length, especially in patients with MYH7 mutation and enlarged LV volume, is crucial for timely preoperative strategic planning and improved prognosis

Development of Infectious Clones for Virulent and Avirulent Pichinde Viruses: a Model Virus To Study Arenavirus-Induced Hemorrhagic Fevers ▿ †

Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the pathogenic mechanism of which is poorly understood due to their virulent nature and the lack of molecular clones. A safe, convenient, and economical small animal model of arenavirus hemorrhagic fever is based on guinea pigs infected by the arenavirus Pichinde (PICV). PICV does not cause disease in humans, but an adapted strain of PICV (P18) causes a disease in guinea pigs that mimics arenavirus hemorrhagic fever in humans in many aspects, while a low-passaged strain (P2) remains avirulent in infected animals. In order to identify the virulence determinants within the PICV genome, we developed the molecular clones for both the avirulent P2 and virulent P18 viruses. Recombinant viruses were generated by transfecting plasmids that contain the antigenomic L and S RNA segments of PICV under the control of the T7 promoter into BSRT7-5 cells, which constitutively express T7 RNA polymerase. By analyzing viral growth kinetics in vitro and virulence in vivo, we show that the recombinant viruses accurately recapitulate the replication and virulence natures of their respective parental viruses. Both parental and recombinant virulent viruses led to high levels of viremia and titers in different organs of the infected animals, whereas the avirulent viruses were effectively controlled and cleared by the hosts. These novel infectious clones for the PICV provide essential tools to identify the virulence factors that are responsible for the severe VHF-like disease in infected animals

Direct interaction between alpha-actinin and hepatitis C virus NS5B

It has been suggested that cellular proteins are involved in hepatitis C virus (HCV) RNA replication. By using the yeast two-hybrid system, we isolated seven cDNA clones encoding proteins interacting with HCV RNA polymerase (NS5B) from a human liver cDNA library. For one of these, alpha-actinin, we confirmed the interaction by coimmunoprecipitation, immunofluorescent staining and confocal microscopic analysis. Experiments with deletion mutants showed that domains NS5B(84-95), NS5B(466-478), and alpha-actinin(621-733) are responsible for the interaction. Studies of the HCV subgenomic replicon system with small interference RNA indicate that alpha-actinin is essential for HCV RNA replication. Our results suggest alpha-actinin may be a component of the HCV replication complex.</p