Geometric description for the anatomy of the mitral valve: A review.

The mitral valve is a complex anatomical structure whose physiological functioning relies on the biomechanical properties and structural integrity of its components. Their compromise can lead to mitral valve dysfunction, associated with morbidity and mortality. Therefore, a review on the morphometry of the mitral valve is crucial, more specifically on the importance of valve dimensions and shape for its function. This review initially provides a brief background on the anatomy and physiology of the mitral valve, followed by an analysis of the morphological information available. A characterisation of mathematical descriptions of several parts of the valve is performed and the impact of different dimensions and shape changes in disease is then outlined. Finally, a section regarding future directions and recommendations for the use of morphometric information in clinical analysis of the mitral valve is presented.

Is follow-up echocardiogram mandatory after a STEMI?

Current guidelines do not advise follow-up echocardiograms after ST-segment elevation myocardial infarction (STEMI), unless the left ventricular ejection fraction is ≤40%. We present an interesting case of left ventricular pseudo-aneurysm-diagnosed 6 months after index STEMI presentation. Follow-up echocardiogram was performed in her case, due to jaw pain during routine haemodialysis. The patient was successfully treated with percutaneous closure device. This case raises the question of whether echo follow-up should be routinely advised after STEMI-even in those with minimal cardiac symptoms.

Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy.

BACKGROUND: Acute stress-induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable with that of myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy. METHODS: In a multicenter study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age-, sex-, and comorbidity-matched control subjects. During the index event and at the 5-month follow-up, patients with takotsubo cardiomyopathy underwent multiparametric cardiac magnetic resonance imaging, including ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement for detection of inflammatory macrophages in the myocardium. Blood monocyte subpopulations and serum cytokines were assessed as measures of systemic inflammation. Matched control subjects underwent investigation at a single time point. RESULTS: Subjects were predominantly middle-aged (64±14 years) women (90%). Compared with control subjects, patients with takotsubo cardiomyopathy had greater USPIO enhancement (expressed as the difference between pre-USPIO and post-USPIO T2*) in both ballooning (14.3±0.6 milliseconds versus 10.5±0.9 milliseconds; P<0.001) and nonballooning (12.9±0.6 milliseconds versus 10.5±0.9 milliseconds; P=0.02) left ventricular myocardial segments. Serum interleukin-6 (23.1±4.5 pg/mL versus 6.5±5.8 pg/mL; P<0.001) and chemokine (C-X-C motif) ligand 1 (1903±168 pg/mL versus 1272±177 pg/mL; P=0.01) concentrations and classic CD14++CD16- monocytes (90±0.5% versus 87±0.9%; P=0.01) were also increased whereas intermediate CD14++CD16+ (5.4±0.3% versus 6.9±0.6%; P=0.01) and nonclassic CD14+CD16++ (2.7±0.3% versus 4.2±0.5%; P=0.006) monocytes were reduced in patients with takotsubo cardiomyopathy. At 5 months, USPIO enhancement was no longer detectable in the left ventricular myocardium, although persistent elevations in serum interleukin-6 concentrations ( P=0.009) and reductions in intermediate CD14++CD16+ monocytes (5.6±0.4% versus 6.9±0.6%; P=0.01) remained. CONCLUSIONS: We demonstrate for the first time that takotsubo cardiomyopathy is characterized by a myocardial macrophage inflammatory infiltrate, changes in the distribution of monocyte subsets, and an increase in systemic proinflammatory cytokines. Many of these changes persisted for at least 5 months, suggesting a low-grade chronic inflammatory state. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02897739.

Comprehensive Echocardiographic and Cardiac Magnetic Resonance Evaluation Differentiates Among Heart Failure With Preserved Ejection Fraction Patients, Hypertensive Patients, and Healthy Control Subjects.

OBJECTIVES: The aim of this study was to investigate the utility of a comprehensive imaging protocol including echocardiography and cardiac magnetic resonance in the diagnosis and differentiation of hypertensive heart disease and heart failure with preserved ejection fraction (HFpEF). BACKGROUND: Hypertension is present in up to 90% of patients with HFpEF and is a major etiological component. Despite current recommendations and diagnostic criteria for HFpEF, no noninvasive imaging technique has as yet shown the ability to identify any structural differences between patients with hypertensive heart disease and HFpEF. METHODS: We conducted a prospective cross-sectional study of 112 well-characterized patients (62 with HFpEF, 22 with hypertension, and 28 healthy control subjects). All patients underwent cardiopulmonary exercise and biomarker testing and an imaging protocol including echocardiography with speckle-tracking analysis and cardiac magnetic resonance including T1 mapping pre- and post-contrast. RESULTS: Echocardiographic global longitudinal strain (GLS) and extracellular volume (ECV) measured by cardiac magnetic resonance were the only variables able to independently stratify among the 3 groups of patients. ECV was the best technique for differentiation between hypertensive heart disease and HFpEF (ECV area under the curve: 0.88; GLS area under the curve: 0.78; p < 0.001 for both). Using ECV, an optimal cutoff of 31.2% gave 100% sensitivity and 75% specificity. ECV was significantly higher and GLS was significantly reduced in subjects with reduced exercise capacity (lower peak oxygen consumption and higher minute ventilation-carbon dioxide production) (p < 0.001 for both ECV and GLS). CONCLUSIONS: Both GLS and ECV are able to independently discriminate between hypertensive heart disease and HFpEF and identify patients with prognostically significant functional limitation. ECV is the best diagnostic discriminatory marker of HFpEF and could be used as a surrogate endpoint for therapeutic studies.

Characterization of the Myocardial Inflammatory Response in Acute Stress-Induced (Takotsubo) Cardiomyopathy.

Takotsubo cardiomyopathy is an acute stress-induced heart failure syndrome for which the exact pathogenic mechanisms are unclear, and consequently, no specific treatment exists. In an experimental model of stress-induced takotsubo-like cardiomyopathy, the authors describe the temporal course of a chronic inflammatory response post-induction, with an initial early influx of neutrophils into myocardial tissue followed by macrophages that are typical of a proinflammatory M1 phenotype, and a nonsignificant increase in systemic inflammatory cytokines. Post-mortem myocardium from the more complex clinical takotsubo patients share features of the study's experimental model. These findings suggest modulators of inflammation could be a potential therapeutic option.

Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience.

BACKGROUND: Takotsubo syndrome is an increasingly recognized cause of chest pain and occasionally of cardiogenic shock. Despite rapid improvement of the left ventricular (LV) ejection fraction, recent registry data raise concerns about long-term prognosis. The aim of this study was to test the hypothesis that restoration of normal ejection fraction after acute takotsubo syndrome is not equivalent to full functional recovery. METHODS: Fifty-two patients with takotsubo syndrome (according to the Mayo Clinic criteria plus cardiac magnetic resonance imaging to exclude myocardial infarction) and 44 healthy control subjects of the same age, gender, and cardiovascular comorbidity distribution were prospectively recruited. The focus of the investigation was on patients with takotsubo syndrome presenting with ST-segment elevation-type electrocardiographic findings or malignant arrhythmias and with LV apical ballooning variant, and a 4-month recovery endpoint was assessed. Patients underwent echocardiographic assessment of LV myocardial deformation (global longitudinal, radial, and circumferential strain; LV twist, torsion, and untwist; and time to peak twist and untwist) and assessment of LV myocardial structure by pre- and post-contrast-enhanced cardiac magnetic resonance by T1 mapping acutely and at 4-month follow-up. Control subjects underwent a single-time-point investigation. Data were analyzed using paired or unpaired tests, as appropriate for their distribution, and corrected for multiple comparisons. RESULTS: The patients' mean age was 66 years (range, 28-87 years), and 92% were women. All abnormal echocardiographic indices observed acutely in patients with takotsubo syndrome improved (but did not necessarily normalize) at follow-up. Significant mechanotemporal alterations characterizing both systole (global longitudinal strain and apical circumferential strain, P < .01 for both; LV twist, twist rate, and torsion, P < .0001 for all) and diastole (untwist rate and time to peak untwisting, P < .001 for both) persisted at 4-month follow-up compared with control subjects, despite normalization of LV ejection fraction and volumes. Although native T1 (which demonstrates edema) normalized at 4-months follow-up only in segments contracting normally during the acute phase (T1 = 1,180 ± 40.6 msec [normally contracting segments, P = .20 vs control value of 1,189 ± 16 msec] and T1 = 1,208 ± 60.3 msec [dysfunctional segments, P < .05 vs control]), the extracellular volume fraction (which demonstrates diffuse fibrosis) remained significantly abnormal in all LV segments (whether normally contracting [0.328 ± 0.043, P < .001] or ballooning during acute presentation [0.320 ± 0.044, P < .001], both vs control value of 0.273 ± 0.045). CONCLUSIONS: In patients with the most clinically severe spectrum of takotsubo cardiomyopathy, regional LV systolic and diastolic deformation abnormalities persist beyond the acute event, despite normalization of global LV ejection fraction and size. In addition, although myocardial edema partly subsides, a process of global microscopic fibrosis develops in its place, detected as early as 4 months.

Lack of effect of nitrogen dioxide exposure on heart rate variability in patients with stable coronary heart disease and impaired left ventricular systolic function.

OBJECTIVES: Epidemiological studies of air pollution on cardiovascular health show associations of cardiac mortality and admissions with exposure to nitrogen dioxide (NO(2)) at low concentrations. These associations could be causal or NO(2) could be acting as a surrogate measure for another air pollutant, most likely ultrafine particles. No studies of cardiac susceptibility to acute exposure to NO(2) have been undertaken. METHODS: Randomised controlled exposures to NO(2) (400 ppb for 1 h) and air in subjects with coronary heart disease and impaired left ventricular systolic function not taking ß adrenoceptor blocking drugs. RESULTS: There were no significant changes in heart rate, blood pressure, leucocyte coping capacity or any heart rate variability measure following NO(2) exposure compared with air. CONCLUSION: These findings suggest that NO(2) does not affect heart rate variability at these concentrations (which are high for urban background levels) and in the absence of other pollutants. While a synergistic effect has not been ruled out, these data lend support to the idea that the epidemiological data associating cardiac outcomes with NO(2) are more likely due to an associated pollutant rather than NO(2) itself.

The antidepressant effects of risperidone and olanzapine in bipolar disorder.

OBJECTIVE: To describe the antidepressant effectiveness of olanzapine and risperidone and compare their tolerability when employed adjunctively in bipolar I/II disorder. METHOD: In an observational study, twenty-one ambulatory subjects with DSM-IV defined bipolar I/II disorder, in any phase of the illness, openly received adjunctive risperidone or olanzapine. The primary efficacy parameters were the Hamilton Depression Rating Scale (HDRS-17) and the Maier and Philips Severity Subscale. Secondary efficacy parameters included the Young Mania Rating Scale (YMRS) along with the Clinical Global Impressions Scale (CGI). Response was defined as a significant change from baseline to endpoint in the total mean HDRS-17 score. The primary tolerability parameters were the Abnormal Involuntary Movement Scale (AIMS) along with changes in weight and body mass index (BMI-kg/m2). Patients were evaluated prospectively with repeated monthly assessments for up to 6 months. RESULTS: Eleven patients openly received risperidone; 10 received olanzapine adjunctive to either lithium or divalproex. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p=0.001), with the mean HDRS-17 total scores falling from 17(SD=3.2) to 5(SD=1.5) by 6 months in the risperidone-treated group and from 18 (SD=1.9) to 7 (SD=2.0) in the olanzapine-treated group. Differences between the risperidone-treated group and the olanzapine-treated group were not significant at 6 months (p=0.754). The mean doses of study medication were 2.88 (SD=1.6) mg/day for the risperidone-treated group and 12.69 (SD=2.3) mg/day for the olanzapine-treated group. Both risperidone and olanzapine were generally well tolerated. No patients developed tardive dyskinesia. Significant weight gain was experienced by patients in both groups [mean weight gain at endpoint was 5.9 kg in risperidone (p=0.023) and 11.3 kg in olanzapine (p=0.001)]. There was a significant difference in weight gain between the risperidone-treated group and the olanzapine-treated group (p=0.001). CONCLUSIONS: These pilot data, from the first prospective comparison study of risperidone and olanzapine in bipolar disorder, suggest that adjunctive administration of either agent may reduce depressive symptom severity. No subjects receiving risperidone or olanzapine developed tardive dyskinesia. Both compounds imparted substantial weight gain with significantly more weight gain accrual with olanzapine. As this was an observational study, the antidepressant effect and tolerability profile of these compounds requires validation via double-blind placebo controlled investigations.

Patient attitudes regarding causes of depression: implications for psychoeducation.

OBJECTIVE: Patient attitudes toward mental illness are an important determinant of treatment compliance and treatment outcome. A patient's age, sex, style of thinking, lifestyle, and beliefs all may influence perceptions. This study aimed to determine patient attitudes. METHOD: Patients with a depressive disorder (n = 102) who were referred for psychiatric consultation and treatment to a community general hospitial psychiatric outpatient clinic completed a 9-item self-report questionnaire to determine their perceptions of the biological, psychological, cognitive, and spiritual causes of their depressive disorder. RESULTS: Women were more likely to endorse their depressive disorder as related to a biological abnormality. With respect to age, older individuals were less likely to identify cognitive factors and loss of spirituality as causal factors in their depression. CONCLUSIONS: A relation exists between demographic variables, including sex and age, and beliefs about causes of depression and related disorders. These findings have implications for refining patient psychoeducation.

Antipsychotic-induced weight gain: bipolar disorder and leptin.

Novel antipsychotics impart substantial weight gain. Persons with bipolar disorder are frequently treated with these and other agents known to impart substantial weight gain. We sought to describe the influence of adjunctive risperidone and olanzapine on body weight, body mass index (BMI, kg/m2) and serum leptin levels over a prospective observation period of 6 months. Throughout the 6-month investigation, significant increases from baseline to end point in weight were noted with both agents; with significantly greater weight gain with olanzapine (t(10) = 2.761, P = 0.023; t(9) = 4.783, P = 0.001). Leptin levels were highly correlated with increases in weight and were significantly elevated from baseline at 4 months (r = 0.658, P < 0.05). Significant increases in weight and body mass index were apparent at 3 months (P < 0.05). The temporal association between weight increase and leptin changes does not support the notion that leptin is a primary promoter of antipsychotic-induced weight gain; however, a secondary perpetuating role cannot be ruled out.

Valproate, bipolar disorder and polycystic ovarian syndrome.

BACKGROUND: Persons with bipolar disorder are often overweight and cluster risk factors for cardiovascular disease. Some antibipolar agents adversely impact upon weight and the lipid milieu. Recent data suggest that valproic acid, a commonly prescribed mood stabilizer, may be associated with polycystic ovarian syndrome (PCOS). This adverse event has not been systematically studied in bipolar disorder. METHOD: Thirty-eight female subjects, aged 18-50 years, meeting DSM-IV criteria for bipolar I or II disorder, in any phase of illness were evaluated. Eighteen females received valproate (sodium valproate and valproic acid) and 20 females received lithium. Patients completed questions regarding their menstrual, reproductive and medical histories. During the follicular phase they were assessed for weight, body mass index (BMI kg/m2), and changes in the reproductive endocrine milieu that included morning estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex-hormone binding globulin (SHBG), androstenedione, dehydroepiandrosterone-sulfate (DHEAS), testosterone, free testosterone, prolactin and thyroid-stimulating hormone (TSH). The blood was also analyzed for fasting metabolic parameters which included total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin, glycosylated hemoglobin (HbA1C), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding-protein 1 (IGFBP-1), fasting blood glucose and morning leptin. RESULTS: Nine (50%) of the valproate-treated females had menstrual abnormalities versus three (15%) of the lithium-treated females (p < 0.05). Valproate-treated females had significantly higher levels of follicular phase androgen concentrations than lithium-treated females (p < 0.05). Nine (50%) of females who were overweight (BMI > or = 25 kg/m2) and with a history of menstrual irregularities also exhibited laboratory evidence of hyperandrogenism (p < 0.05). Persons receiving valproate exhibited significant increases in fasting biochemical parameters suggestive of an adverse metabolic syndrome (p < 0.05). Leptin levels were significantly elevated in the valproate-treated females (p < 0.05). CONCLUSIONS: In this pilot, open-label cross-sectional study, valproate-treated females exhibited higher rates of menstrual abnormalities and biochemical evidence of both hyperandrogenism and adverse metabolic parameters when compared with lithium-treated females. These preliminary data suggest that valproate may, in some predisposed females, adversely impact upon the reproductive endocrine milieu and result in aspects of the metabolic syndrome.

Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study.

OBJECTIVE: Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV criteria for bipolar I/II depression. METHODS: A total of 36 out-patients with Hamilton Depression Rating Scale (HDRS-17) scores > or = 16 were randomized to receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis using the last observation carried forward method. RESULTS: The percentage of patients meeting a priori response criteria (> or = 50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17) = 2.542, p = 0.04 and t(17) = 2.661, p = 0.03, respectively]. Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD = 102 mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the bupropion SR-treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p = 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36) = 1.754, p = 0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side-effects (six in the topiramate and four in the bupropion SR-treated group). There were no cases of affective switch in either arm. Weight loss was experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17) = 2.325, p = 0.061 and t(17) = 2.481, p = 0.043, respectively]. CONCLUSIONS: These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation.

Prevalence and risk factors for depression in a rural setting. Results from the North Wales arm of the ODIN project.

BACKGROUND: Depressive disorders are common, and result in high individual and societal costs. The majority of research assessing depression has occurred in urban areas. There is a paucity of research examining the prevalence of and risk factors for depression in rural general practice. AIM: The aim of this study was to examine the prevalence of and risk factors for depression in a rural area of North Wales in the context of a large multi-centre European study. METHOD: One thousand nine hundred and ninety-nine people randomly selected from a health authority database underwent a two-phase screening method to identify depression. The first phase involved patients completing a self-rating postal questionnaire (the Beck Depression Inventory or BDI). In the second phase, those scoring above cut-off underwent detailed diagnostic interview (Schedules of Clinical Assessment in Neuropsychiatry or SCAN). The SCAN diagnostic interview can generate either DSM-IV or ICD-10 diagnoses; the DSM-IV classification system was used here. RESULTS: One thousand two hundred and thirty-nine (63 %) people responded to the initial screening questionnaire. The prevalence rate for all DSM-IV depressive disorders was calculated to be 6.1 % (95 % CI 4.1, 9.0) whereas the prevalence rate for DSM-IV major depressive disorder was 5.1 % (CI 3.37, 7.66). Multivariate analysis indicated that several variables were related to BDI caseness, including gender, employment status, social support and negative life events. CONCLUSION: Levels of reported depression are relatively low in North Wales compared to those observed in a neighbouring urban area using comparable data collection methods. A number of factors traditionally associated with increased risk from depression were predictive of scoring above cut-off on the BDI in a rural North Wales sample.