Dapagliflozin-induced abnormal uterine bleeding in a patient with dilated cardiomyopathy and chronic heart failure: a case report
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ABSTRACT:
SUBMITTER: Gong S
PROVIDER: S-EPMC11344891 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:End stage heart failure due to ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have similar characteristics, enlargement of the ventricles, relatively thin-walled ventricle, which leads to a limited contraction force and blood loading. Nevertheless, the response for present therapeutics is very variable and the prognosis is still very bad for ICM and DCM in general. Thus, the ability to differentiate the etiologies of heart failure based structural and physiological changes of the heart would be a step forward to enhance the specificity and the success of given therapy.
2007-10-31 | E-CVDE-1 | biostudies-arrayexpress
Project description:Two common disorders of the elderly are heart failure and Alzheimer disease (AD). Heart failure usually results from dilated cardiomyopathy (DCM). DCM of unknown cause in families has recently been shown to result from genetic disease, highlighting newly discovered disease mechanisms. AD is the most frequent neurodegenerative disease of older Americans. Familial AD is caused most commonly by presenilin 1 (PSEN1) or presenilin 2 (PSEN2) mutations, a discovery that has greatly advanced the field. The presenilins are also expressed in the heart and are critical to cardiac development. We hypothesized that mutations in presenilins may also be associated with DCM and that their discovery could provide new insight into the pathogenesis of DCM and heart failure. A total of 315 index patients with DCM were evaluated for sequence variation in PSEN1 and PSEN2. Families positive for mutations underwent additional clinical, genetic, and functional studies. A novel PSEN1 missense mutation (Asp333Gly) was identified in one family, and a single PSEN2 missense mutation (Ser130Leu) was found in two other families. Both mutations segregated with DCM and heart failure. The PSEN1 mutation was associated with complete penetrance and progressive disease that resulted in the necessity of cardiac transplantation or in death. The PSEN2 mutation showed partial penetrance, milder disease, and a more favorable prognosis. Calcium signaling was altered in cultured skin fibroblasts from PSEN1 and PSEN2 mutation carriers. These data indicate that PSEN1 and PSEN2 mutations are associated with DCM and heart failure and implicate novel mechanisms of myocardial disease.
| S-EPMC1698711 | biostudies-literature
Project description:Heart failure is a major health burden, affecting 40 million people globally. One of the main causes of systolic heart failure is dilated cardiomyopathy (DCM), the leading global indication for heart transplantation. Our understanding of the genetic basis of both DCM and systolic heart failure has improved in recent years with the application of next-generation sequencing and genome-wide association studies (GWAS). This has enabled rapid sequencing at scale, leading to the discovery of many novel rare variants in DCM and of common variants in both systolic heart failure and DCM. Identifying rare and common genetic variants contributing to systolic heart failure has been challenging given its diverse and multiple etiologies. DCM, however, although rarer, is a reasonably specific and well-defined condition, leading to the identification of many rare genetic variants. Truncating variants in titin represent the single largest genetic cause of DCM. Here, we review the progress and challenges in the detection of rare and common variants in DCM and systolic heart failure, and the particular challenges in accurate and informed variant interpretation, and in understanding the effects of these variants. We also discuss how our increasing genetic knowledge is changing clinical management. Harnessing genetic data and translating it to improve risk stratification and the development of novel therapeutics represents a major challenge and unmet critical need for patients with heart failure and their families.
| S-EPMC5322656 | biostudies-literature
Project description:Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLNR9C/+). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT, P = 8 × 10-4) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGFβ2 and TGFβ3. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT, P = 6 × 10-33). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box transcription factor 15 (Tbx15). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM.
| S-EPMC4882118 | biostudies-literature
Project description:AimsThe aims of this paper were to investigate the analytical performance of the nine prognostic scales commonly used in heart failure (HF), in patients with dilated cardiomyopathy (DCM), and to develop a unique prognostic model tailored to DCM patients.Methods and resultsThe hospital and outpatient records of 406 DCM patients were retrospectively analysed. The information on patient status was gathered after 48.2 ± 32.0 months. Tests were carried out to ascertain the prognostic accuracy in DCM using some of the most frequently applied HF prognostic scales (Barcelona Bio-Heart Failure, Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity, Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure, Meta-Analysis Global Group in Chronic Heart Failure, MUerte Subita en Insuficiencia Cardiaca, Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure, Seattle Heart Failure Model) and one dedicated to DCM, that of Miura et al. At follow-up, 70 DCM patients (17.2%) died. Most analysed scores substantially overestimated the mortality risk, especially in survivors. The prognostic accuracy of the scales were suboptimal, varying between 60% and 80%, with the best performance from Barcelona Bio-Heart Failure and Seattle Heart Failure Model for 1-5 year mortality [areas under the receiver operating curve 0.792-0.890 (95% confidence interval 0.725-0.918) and 0.764-0.808 (95% confidence interval 0.682-0.934), respectively].Based on our accumulated data, a self-developed DCM prognostic model was constructed. The model consists of age, gender, body mass index, symptoms duration, New York Heart Association class, diabetes mellitus, prior stroke, abnormal liver function, dyslipidaemia, left bundle branch block, left ventricle end-diastolic diameter, ejection fraction, N terminal pro brain natriuretic peptide, haemoglobin, estimated glomerular filtration rate, and pharmacological and resynchronisation therapy. This newly created prognostic model outperformed the analysed HF scales.ConclusionsAn analysis of various HF prognostic models found them to be suboptimal for DCM patients. A self-developed DCM prognostic model showed improved performance over the nine other models studied. However, further validation of the prognostic model in different DCM populations is required.
| S-EPMC7524139 | biostudies-literature
Project description:Cardiovascular disease is the leading cause of human morbidity and mortality. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy associated with heart failure. Here, we report that cardiac-specific knockout of Dicer, a gene encoding a RNase III endonuclease essential for microRNA (miRNA) processing, leads to rapidly progressive DCM, heart failure, and postnatal lethality. Dicer mutant mice show misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicate significantly reduced heart rates and decreased fractional shortening of Dicer mutant hearts. Consistent with the role of Dicer in animal hearts, Dicer expression was decreased in end-stage human DCM and failing hearts and, most importantly, a significant increase of Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions.
| S-EPMC2542870 | biostudies-other
Project description:Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.
| S-EPMC5603726 | biostudies-literature
Project description:Peripartum cardiomyopathy (PPCM) is a severe cardiac disease occurring in the last month of pregnancy or in the first 5 months after delivery and shows many similar clinical characteristics as dilated cardiomyopathy (DCM) such as ventricle dilation and systolic dysfunction. While PPCM was believed to be DCM triggered by pregnancy, more and more studies show important differences between these diseases. While it is likely they share part of their pathogenesis such as increased oxidative stress and an impaired microvasculature, discrepancies seen in disease progression and outcome indicate there must be differences in pathogenesis as well. In this review, we compared studies in DCM and PPCM to search for overlapping and deviating disease etiology, pathogenesis and outcome in order to understand why these cardiomyopathies share similar clinical features but have different underlying pathologies.
| S-EPMC4295435 | biostudies-other
Project description:BackgroundPropionic acidaemia (PA) is an autosomal recessive disorder resulting from deficiency of propionyl-CoA carboxylase, a mitochondrial enzyme that metabolizes propionyl-CoA. Generally, patients with PA develop symptoms in the neonatal period due to protein intake through breastfeeding; however, late-onset PA with atypical symptoms, including cardiomyopathy, has been recently reported.Case summaryWe present the case of a 25-year-old male with late-onset PA complicated by advanced heart failure (HF) due to isolated secondary dilated cardiomyopathy, who required left ventricular assist device (LVAD) implantation and finally underwent heart transplantation (HTx). Initially, the patient developed HF at the age of 16 and was diagnosed with mitochondrial cardiomyopathy. Due to refractory HF, he underwent an LVAD implantation and was scheduled for HTx. During the preoperative period for HTx, the patient suffered from sepsis due to the worsening of LVAD driveline exit-site infection complicated by overt metabolic acidosis, finally leading to the diagnosis of late-onset PA. After this diagnosis, adequate nutritional interventions were introduced, and the cardiac function was partially restored enough for him to be weaned-off LVAD; however, the patient became inotrope dependent and underwent HTx. The post-HTx course was uneventful with special nutritional management, and he has experienced no adverse metabolic events in the past 3 years.DiscussionLate-onset PA can cause isolated adult-onset cardiomyopathy, and LVAD or HTx should be considered when PA is complicated by advanced HF and is unresponsive to conventional medical therapies.
| S-EPMC9174551 | biostudies-literature
Project description:Uterine leiomyomas and endometrial pathology are both associated with abnormal uterine bleeding. We report a case in which a nulliparous woman with heavy uterine bleeding and leiomyomas had undergone two prior hysteroscopic myomectomies for benign leiomyomas. She was evaluated, but was ineligible for a clinical trial of a novel Magnetic Resonance guided High Intensity Focused Ultrasound (MRgx200B;HIFU) device. The 8 cm, prolapsed submucosal leiomyoma hindered endometrial sampling and was inaccessible to HIFU treatment. Preoperatively, neither endometrial sampling nor saline sonohysterography was technically feasible. She underwent hysterectomy, and on histological examination of specimen, stage 1A grade 1 endometrial carcinoma was found on the endometrial side of the prolapsing fibroid. Endometrial pathology is an important consideration in the evaluation of abnormal uterine bleeding, even in women with large prolapsing leiomyoma.
| S-EPMC4516716 | biostudies-literature