Pathological and clinical study of calcification of the mitral valve ring

The pathology and clinical features of 258 cases of mitral ring calcification were reviewed. The overall incidence in patients over 50 years of age was 8.5%; it was more than twice as high in women (11.5%) as in men (4.5%) and rose sharply with age.Cardiac failure and systolic murmurs were each noted in over half the patients. Hypertension was slightly commoner than in age- and sex-matched groups without ring calcification, although the difference was not statistically significant.Small nodules of calcification were more frequent in men and heavy deposits in women. Distortion and atrial displacement of the posterior mitral cusp was present in 26% of the hearts with early ring calcification, in 56% of the hearts with moderate, and in almost all hearts with marked changes. Systolic murmurs had been heard in 73% of these cases. ;Caseation' of the calcified ring was seen in seven hearts and haemorrhagic valvulitis in three. Calcium had ulcerated through the cusp in 12 cases, with thrombotic and/or bacterial endocarditis in five. Aortic valve calcification was present in 36% of men and was quantitatively related to the severity of mitral ring calcification. In women the incidence was 30% and there was no corresponding quantitative relationship.Microscopy showed nonspecific chronic inflammatory changes adjacent to calcium in about half the cases in both sexes, with foreign body type giant cells in 6%. Similar inflammatory changes in the valve cusp were almost twice as common in women as in men.There was no evidence that previous endocarditis was responsible for mitral ring calcification, neither did parity influence its incidence. Severe coronary atherosclerosis was unrelated but severe aortic atherosclerosis was commoner in patients with calcified mitral rings. The difference, in women, was statistically significant.The higher incidence of severe degrees of ring calcification, complications, and valvular inflammation in women suggests a sex-determined difference in tissue response in the mitral area. Possible provoking factors apply to both sexes and both left side valves, and such a difference would account for the relative frequency and sex incidence of mitral ring calcification.     

Occupational stress and hypertension

Occupational stress, or job strain, resulting from a lack of balance between job demands and job control, is considered one of the frequent factors in the etiology of hypertension in modern society. Stress, with its multifactorial causes, is complex and difficult to analyze at the physiological and psychosocial levels. The possible relation between job strain and blood pressure levels has been extensively studied, but the literature is replete with conflicting results regarding the relationship between the two. Further analysis of this relationship, including the many facets of job strain, may lead to operative proposals at the individual and public health levels designed to reduce the effects on health and well-being. In this article, we review the literature on the subject, discussing the various methodologies, confounding variables, and suggested approaches for a healthier work environment.     

WOMENtorship: The #WomenInMedicine perspective

Abstract

Mentorship is essential for career development, personal development, and job satisfaction for physicians in academic medicine. Women in academic medicine face unique challenges including significant gender disparities in positions of leadership as well as difficulty finding mentors. As leaders in academic medicine, we have collated several structured recommendations for physicians of both genders seeking to be better mentors to female trainees and early career physicians. We discuss each of these recommendations in detail including the following: acknowledging your own strengths and limitations as a mentor, addressing issues of work-life integration, helping your mentee set long-term career goals, and acting as a sponsor as well as a mentor. We hope these suggestions are helpful for current and aspiring mentors and provide a platform to improve career development for female physicians and reduce gender inequities in academic medicine.     

Nonpharmacologic treatment of resistant hypertensives by device-guided slow breathing exercises

BACKGROUND: Recent studies have demonstrated the antihypertensive effect of slow breathing exercises, guided interactively by a device, in patients with uncontrolled blood pressure (BP) without changing medication. This study examined the response to the same treatment protocol in resistant hypertensives. METHODS: Seventeen resistant hypertensives exercised device-guided slow breathing for 8 weeks, 15 min daily, and self-monitored BP. Data stored in the devices were collected on a PC-based system. Clinical outcomes were office and home BP changes from baseline to end values. RESULTS: Significant reductions in both office BP (-12.9/-6.9 mm Hg, P <.001 and home BP (-6.4/-2.6 mm Hg, P <.01/P <.05) without side effects with 82% responders and good compliance. CONCLUSIONS: Resistant hypertensives can benefit from and are compliant with self-treatment by device-guided slow breathing.     

Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease

Abstract

Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy.

Methods

We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY.

Results

We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related – most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-γ on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (ΔψM), indicating mitochondrial dysfunction.

Conclusion

Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-γ-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.