Ramdas G. Pai

Calcific mitral stenosis, commonly seen in the elderly in developed countries, occurs primarily due to mitral annular calcification, and its prevalence is increasing secondary to an aging population. Mitral regurgitation, commonly seen across all age groups, occurs primarily due to anatomical or functional impairment of one or more components of the mitral apparatus or the left ventricle that are necessary for normal valve function, and its prevalence is increasing secondary to an increasing number of patients with heart failure. The current review discusses the diagnosis of and treatment options (medical, surgical, and transcatheter) for mitral valve disease, including the associated challenges, specifically in the elderly.

Adult patients with congenital heart disease have now surpassed the pediatric population due to advances in surgery and improved survival. One such complex congenital heart disease seen in adult patients is the Fontan circulation. These patients have complex physiology and are at risk for several complications, including thrombosis of the Fontan pathway, pulmonary vascular disease, heart failure, atrial arrhythmias, atrioventricular valve regurgitation, and protein-losing enteropathy. This review discusses the commonly encountered phenotypes of Fontan circulatory failure and their contemporary management.

The syndrome of heart failure (HF) with preserved ejection fraction (HFpEF) makes up about half of the HF population. The HF mechanisms in these patients are varied and not fully understood. In addition, the term “diastolic HF” was switched to HFpEF because of difficulties in measuring the left ventricular (LV) diastolic performance. In the late stages, HFpEF carries a prognosis that is as bad as or worse than that of HFrEF. Hence, it is important to recognize LV diastolic impairment at an earlier stage so that the causal mechanisms, if any, can be treated to retard its progression. Despite the availability of numerous disease-modifying agents for HFrEF, there are hardly any available treatments for HFpEF. With our aging population, there will be an epidemic of HFpEF and hence this entity needs attention and respect. In this paper, we review the fundamental mechanisms of HFpEF, the physiology of LV filling and how LV diastolic function can be comprehensively measured. We also speculate how this may help with the early recognition of diastolic HF and its treatment.

Mitral regurgitation (MR) is commonly seen in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). But the long-term implications of MR in AS are unknown. To investigate MR’s impact on survival of patients undergoing surgical AVR for severe AS. Of the 740 consecutive patients with severe AS evaluated between 1993 and 2003, 287 underwent AVR forming the study cohort. They were followed up to death or till the end of 2019. Chart reviews were performed for clinical, echocardiographic, and therapeutic data. MR was graded on a 1-4 scale. Mortality data was obtained from chart review and the Social Security Death Index. Survival was analyzed as a function of degree of MR. The mean age of the severe AS patients who had AVR (n = 287) was 72 ± 13 years, 46% women. Over up to 26 years of follow up, there were 201 (70%) deaths, giving deep insights into the determinants of survival of severe AS who had AVR. The 5, 10 and 20 years survival rates were 75%, 45% and 25% respectively. Presence of MR was associated with higher mortality in a graded fashion (P = 0.0003). MR was significantly associated with lower left ventricular (LV) ejection fraction and larger LV size. Impact of MR on mortality was partially mediated through lower LV ejection fraction and larger LV size. By Cox regression, MR, lower ejection fraction (EF) and larger LV end-systolic dimension were independent predictors of higher mortality (χ² = 33.2). Presence of greater than 2+ MR in patients with severe AS is independently associated with reduced survival in surgically managed patients, an effect incremental to reduced EF and larger LV size. We suggest that aortic valve intervention should be considered in severe AS patients when > 2+ MR occurs irrespective of EF or symptoms.

Objectives: We sought to evaluate the effect of gender on biology, therapeutic decisions, and survival in patients with severe aortic regurgitation (AR). Background: Gender affects adaptive response to the presence of valvular heart diseases and therapeutic decisions. The impact of these on survival in severe AR patients is not known. Methods: This observational study was compiled from our echocardiographic database which was screened (1993–2007) for patients with severe AR. Detailed chart reviews were performed. Mortality data were obtained from the Social Security Death Index and analyzed as a function of gender. Results: Of the 756 patients with severe AR, 308 (41%) were women. Over a follow-up of up to 22 years, there were 434 deaths. Women compared to men were older (64 ± 18 vs. 59 ± 17 years, p = 0.0002). Women also had smaller left ventricular (LV) end diastolic dimension (5.2 ± 1.1 vs. 6.0 ± 1.0 cm, p < 0.0001), higher EF (56% ± 17% vs. 52% ± 18%, p = 0.003), higher prevalence of diabetes mellitus (18% vs. 11%, p = 0.006), and higher prevalence of ≥2+ mitral regurgitation (52% vs. 40%, p = 0.0008) despite a smaller LV size. Women were also less likely to receive aortic valve replacement (AVR) (24% vs. 48%, p < 0.0001) compared to men and had a lower survival on univariate analysis (p = 0.001). However, after adjusting for group differences including AVR rates, gender was not an independent predictor of survival. However, the survival benefit associated with AVR was similar in both women and men. Conclusions: This study strongly suggests that female gender is associated with different biological responses to AR compared to men. There is also a lower AVR rate in women, but women derive similar survival benefit as men with AVR. Gender does not seem to affect survival in an independent fashion in patients with severe AR after adjusting for group differences and AVR rates.

Nivolumab, a type of immunotherapy, has enhanced the 5-year survival of patients with renal cell cancer, melanoma, and lung cancer which is now mechanistically understood. However, relatively sparse information assesses its relationship with shaping the gut microbiome. We aimed to assess the degree to which nivolumab treatment contributes to alterations in the species composition of the colon in lung cancer patients undergoing nivolumab treatment. Our pilot study utilized stool samples of five lung cancer patients at Inland Hematology Oncology (IHO) before administration of nivolumab and three months after initiation of treatment. 16S and ITS rRNA sequence analysis were used to assess alterations in species abundance and richness of the colon. After sequencing, statistical analysis, specifically a paired t-test, was performed to assess if any significant differences in any microbial species were observed before and after immunotherapy treatment. Although different proportions of microorganisms existed at baseline prior to treatment for each patient, a significant reduction in the Megasphaera elsdenii population was observed (p=.0488; n=4), when comparing before and after treatment. Our findings differ from that of Huang et. al (2022), who has recently posited that a positive association exists between Megasphaera elsdenii and the survival of patients with pancreatic ductal adenocarcinomas. Our conclusions suggest that different cancers may elicit differential effects on Megasphaera elsdenii in the gut microbiome. Importance: Nivolumab is a relatively new form of cancer therapy called immunotherapy, which enables the body to use its own immune system to effectively fight cancer. Due to advances in microbial sequencing in 16S rRNA, this project explores differences in the abundance of microbial communities before and three months of treatment in patients who have advanced on chemotherapy. Our findings suggest that reduction of Megasphaera elsdenii , a metabolically active bacterium, is associated with positive outcomes, which differs from findings from other literature. Our project advocates for a more robust profiling of the microbiome during lung cancer treatment, and immunotherapy, in particular, to establish a more substantive profile of the changing gut in the midst of treatment.

Ischemic heart disease, a major risk factor for myocardial infarction (MI), occurs when the blood vessels supplying oxygen-rich blood to the heart become partially or fully occluded by lipid-rich plaques, resulting in myocardial cell death, remodeling, and scarring. In addition, MI occurs as result of lipid-rich plaque rupture, resulting in thrombosis and vessel occlusion. Cardiac fibroblasts (CFs) and CF-derived growth factors are crucial post-MI in myocardial remodeling. Information regarding the regenerative phenotypes of CFs is scarce; however, regenerative CFs are translationally relevant in myocardial regeneration following MI. The emerging technologies in regenerative cardiology offer cutting-edge translational opportunities, including synthetic cells. In this review, we critically reviewed the current knowledge and the ongoing research efforts on application of synthetic cells for improving cardiac regeneration post-MI. Impact statement: Synthetic cells offer tremendous regenerative potential in otherwise deleterious cardiac remodeling postmyocardial infarction. Understanding the role of fibroblasts in cardiac healing and the therapeutic applications of synthetic cells would open a multitude of novel cardiac regenerative approaches. The novel concept of synthetic fibroblasts that emulate native cardiac fibroblasts can provide an effective solution in cardiac healing.

Background-Previous studies on coronavirus disease 2019 (COVID-19) were limited to specific geographical locations and small sample sizes. Therefore, we used the National Inpatient Sample (NIS) 2020 database to determine the risk factors for severe outcomes and mortality in COVID-19. Methods-We included adult patients with COVID-19. Univariate and multivariate logistic regression was performed to determine the predictors of severe outcomes and mortality in COVID-19. Results-1,608,980 (95% CI 1,570,803–1,647,156) hospitalizations with COVID-19 were included. Severe complications occurred in 78.3% of COVID-19 acute respiratory distress syndrome (ARDS) and 25% of COVID-19 pneumonia patients. The mortality rate for COVID-19 ARDS was 54% and for COVID-19 pneumonia was 16.6%. On multivariate analysis, age > 65 years, male sex, government insurance or no insurance, residence in low-income areas, non-white races, stroke, chronic kidney disease, heart failure, malnutrition, primary immunodeficiency, long-term steroid/immunomodulatory use, complicated diabetes mellitus, and liver disease were associated with COVID-19 related complications and mortality. Cardiac arrest, septic shock, and intubation had the highest odds of mortality. Conclusions-Socioeconomic disparities and medical comorbidities were significant determinants of mortality in the US in the pre-vaccine era. Therefore, aggressive vaccination of high-risk patients and healthcare policies to address socioeconomic disparities are necessary to reduce death rates in future pandemics.