Stress-Induced Cardiomyopathy Complicated by Dynamic Left Ventricular Outflow Obstruction, Cardiogenic Shock, and Ventricular Septal Rupture.

We describe the case of a 68-year-old woman presenting with stress cardiomyopathy (SCM), with concomitant cardiogenic shock, left ventricular outflow tract obstruction, and ventricular septal rupture. These complications have not simultaneously been reported in a single SCM case. The importance of early diagnosis of serial complications of SCM and using mechanical circulatory support as a treatment strategy are highlighted.

Clinical and echocardiographic correlates of elevated troponin in amyloid light-chain cardiac amyloidosis.

Increased troponin is associated with poor survival in patients with amyloid light-chain (AL) amyloidosis with cardiac involvement (CAL). The purpose of this investigation was to define the relation between increased troponin and clinical, morphologic, and functional features. The comparative utility of clinical, echocardiographic, and biochemical measurements in predicting survival in CAL was also investigated. One hundred seventeen patients with CAL were divided into 2 groups: normal troponin I (<0.06 ng/ml, n = 42) or increased troponin I (≥0.06 ng/ml, n = 75). Patients in the high troponin I group were older (63 vs 58 years, p = 0.04), with higher B-type natriuretic peptide levels (1,417 vs 936 pg/ml, p = 0.0004). The high troponin I group also had higher echocardiography-determined early/late mitral inflow velocity ratio (2.2 vs 1.4, p = 0.005) and myocardial performance index (0.59 vs 0.45, p = 0.04) and lower stroke index (28 vs 38 ml/beat/m(2), p <0.0001) and left atrial systolic force (5.9 vs 8.4 k-dynes, p = 0.037) than the normal troponin group. Median survival was significantly shorter in the high troponin group (11 vs 45 months, p <0.001). At time of CAL diagnosis, univariate predictors of all-cause mortality included increased troponin, older age, male gender, New York Heart Association class III to IV, >2 organs involved, higher B-type natriuretic peptide, lower creatinine clearance, greater ventricular septal thickness, and higher myocardial performance index. However, by multivariate Cox survival analysis, only increased troponin was a significant predictor for all-cause mortality (hazard ratio 3.1, p = 0.002). In conclusion, increased troponin is associated with worse left ventricular and left atrial functions by echocardiography in patients with CAL. Among baseline variables, it is the strongest predictor of all-cause mortality in multivariate analysis. Troponin is a powerful tool in clinical and prognostic assessments of patients with CAL.

Relation of components of the metabolic syndrome to left ventricular geometry in hispanic and non-hispanic black adults.

BACKGROUND: Left ventricular (LV) hypertrophy is an independent predictor of increased cardiovascular morbidity and mortality. It remains unclear whether components of the metabolic syndrome are associated with LV hypertrophy. METHODS AND RESULTS: Accordingly, we analyzed echocardiograms in 192 consecutive ambulatory patients referred for echocardiography from October to December 2004. Patients were excluded if they had atrial fibrillation, significant valvular heart disease or failed to cooperate for echocardiogram. Of these, 126 (66%) patients met Adult Treatment Panel (ATP) III diagnostic criteria for the metabolic syndrome. 29% had any 3 metabolic syndrome components, 18% had any 4 metabolic syndrome components and 17% had all 5 metabolic syndrome components. In analyses of variance adjusted for age and sex, LV mass and LV mass adjusted to its allometric relation to height(2.7) (LV mass/height(2.7)) were higher in patients with metabolic syndrome compared to those without metabolic syndrome (237 g [228-239 95%CI] vs. 224 g [206-239 95%CI] p=0.005 and 62 g/m(2.7) [59-65 95%CI] vs. 56 g/m(2.7) [52-60 95%CI] p=0.014, respectively). The prevalence of LV hypertrophy using prognostically-validated gender-specific partition values for LV mass/height(2.7) was significantly higher in metabolic syndrome patients than in those without metabolic syndrome (81 v. 58%, p<0.001). There was a step-wise increase in LV mass/height(2.7) in those with no metabolic syndrome components to those with increasing number of metabolic syndrome components (Figure, p<0.001). In this study of high-risk patients, the significant independent predictors of LV hypertrophy were only high blood pressure (OR=3.2, p=0.008) and increased waist circumference (OR=2.8, p=0.006) with no interaction between blood pressure and waist circumference. CONCLUSION: Metabolic syndrome is associated with higher LV mass and prevalence of LV hypertrophy. Increasing number of metabolic syndrome components is associated with step-wise increases in LV mass. Identification of LV hypertrophy in metabolic syndrome patients may provide an additional prognostic tool to further risk-stratify these patients.

Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome.

BACKGROUND: Obese women with polycystic ovary syndrome (PCOS) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) insulin mediator during oral glucose tolerance testing (OGTT), which appears to be restored by the administration of metformin. This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator. The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped. METHODS: We performed a cross-sectional case-control study at the clinical research center of an academic medical center. A two-step euglycemic-hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women, during which DCI-IPG bioactivity was monitored. RESULTS: At baseline, PCOS women were significantly more obese, hyperinsulinemic, and insulin resistant than the controls. During the clamp studies, DCI-IPG bioactivity increased significantly over the first 45 min of the low-insulin step of the clamp in normal nonobese women (P = 0.046) and then decreased to baseline levels; DCI-IPG increased again after initiation of the high-insulin step (P = 0.029). Despite higher insulin levels during the clamp in PCOS women, DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps. CONCLUSIONS: The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women, which may contribute to the insulin resistance in these women.

Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism.

UNLABELLED: BACKGROUND We have shown that American women with polycystic ovary syndrome (PCOS) have decreased glucose-stimulated release of a putative mediator of insulin action, D-chiro-inositol (DCI)-containing inositolphosphoglycan (DCI-IPG), and increased urinary clearance of DCI (uCl(DCI)), which was associated with hyperinsulinemia. METHODS: DCI levels and the release of insulin and DCI-IPG during an oral glucose tolerance test (AUCs) were assessed in 27 Greek PCOS and 10 normal Greek women. RESULTS: PCOS women were heavier than controls (BMI = 28.4 versus 23.7 kg/m(2), P = 0.05) with higher waist-to-hip ratios (WHR = 0.78 versus 0.71, P = 0.009) and increased free testosterone (P = 0.048) and AUC(insulin) (P = 0.04). In PCOS women, incremental AUC(DCI-IPG) was significantly decreased by 59% (2158 versus 5276%.min, P = 0.01), even after correction for BMI and WHR. Finally, increased uCl(DCI) (r = 0.35, P = 0.04) and decreased AUC(DCI-IPG) (r = 0.46, P = 0.004) were significantly associated with hyperinsulinemia in all women together, even after correction for BMI and WHR (Ps = 0.02 and 0.007), and regardless of PCOS status. CONCLUSIONS: Greek women, with or without PCOS, display increased uCl(DCI) and decreased AUC(DCI-IPG) in association with higher insulin levels but independent of adiposity. Increased clearance of inositols might reduce tissue availability of DCI and decrease the release of DCI-IPG mediator, which could contribute to insulin resistance and compensatory hyperinsulinemia in Greek women, as previously described in American women.

Effects of short-term and long-term metformin treatment on menstrual cyclicity in women with polycystic ovary syndrome.

The purpose of this retrospective study was to compare the frequency of menstrual cyclicity between two groups of patients with polycystic ovary syndrome: women who were followed while on metformin for 3-6 months and those who were followed for >6 months. The results showed that metformin is highly effective in normalizing menstrual cyclicity in women with polycystic ovary syndrome (the overall response rate was 69%, with 88% of responders achieving normal cyclicity), especially with a treatment duration of 6 months or longer (the response rate was 40% higher for women who were treated with metformin for >6 months vs. 3-6 months, 77% vs. 55%).

Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome.

Dyslipidemia is a feature of polycystic ovary syndrome (PCOS), but its pathogenesis remains controversial. We performed this study of mothers of women with PCOS to test the hypothesis that dyslipidemia is a heritable trait in families of women with PCOS and to investigate the impact of age on reproductive and metabolic phenotypes. Fasting blood was obtained in 215 non-Hispanic white mothers of women with PCOS and 62 control women. The prevalence of metabolic syndrome was compared with that in non-Hispanic white women of comparable age from the National Health and Nutrition Examination Survey III. Mothers had higher total (P < 0.001) and low-density lipoprotein (LDL) cholesterol levels (P = 0.007), whereas high-density lipoprotein and triglyceride levels did not differ compared with control women. The only predictors of LDL levels in mothers were their daughters' LDL levels (r2 = 0.11, P < 0.001) and their own unbound testosterone levels (r2 = 0.04, P = 0.03). The prevalence of metabolic syndrome was increased in obese (body mass index > or = 30 kg/m2) mothers compared with obese non-Hispanic white women from the National Health and Nutrition Examination Survey III (P = 0.04). Thirty-one percent of mothers reported a history of menstrual irregularity. These mothers had higher androgen levels, markers of insulin resistance, and LDL levels than mothers with regular menses. LDL levels are increased in mothers of women with PCOS, suggestive of a heritable trait. A history of menstrual irregularity identifies mothers with features of PCOS. Obese mothers have a very high prevalence of metabolic syndrome. These findings suggest that both the reproductive and metabolic abnormalities persist with age in PCOS.

Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome.

OBJECTIVE: Evidence suggests that some actions of insulin are effected by inositolphosphoglycan (IPG) mediators. We hypothesize that a deficiency in D-chiro-inositol (DCI) and/or a DCI-containing IPG (DCI-IPG) may contribute to insulin resistance in humans. RESEARCH DESIGN AND METHODS: To assess this possibility in polycystic ovary syndrome (PCOS), we determined insulin sensitivity (Si by frequently sampled intravenous glucose tolerance test), plasma and urinary DCI and myo-inositol (MYO) levels (by gas chromatography/mass spectrometry), and the release of insulin and DCI-IPG during the oral glucose tolerance test (area under the curve [AUC]) in 23 women with PCOS and 26 normal women. RESULTS: Women with PCOS were heavier than control subjects (P = 0.002 for BMI), but also had decreased Si (P < 0.001) and increased AUC(insulin) (P < 0.001) compared with normal women, even when corrected for BMI. The urinary clearance of DCI (uCl(DCI)) was increased almost sixfold in PCOS compared with normal women (P = 0.001), but not MYO clearance (P = 0.10). uCl(DCI) correlated inversely with Si when all women were analyzed together (n = 49, r = -0.50, P < 0.001) and was one of the three best independent parameters predicting Si. Finally, the ratio of AUC(DCI-IPG) to AUC(insulin) was decreased threefold in women with PCOS (P < 0.001). CONCLUSIONS: uCl(DCI) is inversely correlated with insulin sensitivity in women and is a strong independent predictor of insulin resistance in multivariate models. PCOS, which is characterized by insulin resistance, is associated with a selective increase in uCl(DCI) and impaired DCI-IPG release in response to insulin. These findings are consistent with a defect in tissue availability or utilization of DCI in PCOS that may contribute to the insulin resistance of the syndrome.

Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is characterized by insulin resistance with compensatory hyperinsulinemia. Insulin resistance also plays a role in the metabolic syndrome (MBS). We hypothesized that the MBS is prevalent in PCOS and that women with both conditions would present with more hyperandrogenism and menstrual cycle irregularity than women with PCOS only. We conducted a retrospective chart review of all women with PCOS seen over a 3-yr period at an endocrinology clinic. Of the 161 PCOS cases reviewed, 106 met the inclusion criteria. The women were divided into two groups: 1) women with PCOS and the MBS (n = 46); and 2) women with PCOS lacking the MBS (n = 60). Prevalence of the MBS was 43%, nearly 2-fold higher than that reported for age-matched women in the general population. Women with PCOS had persistently higher prevalence rates of the MBS than women in the general population, regardless of matched age and body mass index ranges. Acanthosis nigricans was more frequent in women with PCOS and the MBS. Women with PCOS and the MBS had significantly higher levels of serum free testosterone (P = 0.002) and lower levels of serum SHBG (P = 0.001) than women with PCOS without the MBS. No differences in total testosterone were observed between the groups. We conclude that the MBS and its components are common in women with PCOS, placing them at increased risk for cardiovascular disease. Women with PCOS and the MBS differ from their counterparts lacking the MBS in terms of increased hyperandrogenemia, lower serum SHBG, and higher prevalence of acanthosis nigricans, all features that may reflect more severe insulin resistance.

Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome.

Some actions of insulin are mediated by putative inositolphosphoglycan mediators, and a deficiency in D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Furthermore, similar effects of DCI and metformin, an insulin-sensitizing drug, have been demonstrated in PCOS women. To determine whether metformin improves insulin actions by increasing biologically active DCI-IPG in women with PCOS, we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women with PCOS before and after 4-8 wk of metformin or placebo. After treatment, the mean (+/-SE) area under the curve (AUC) during the oral glucose tolerance test of insulin (AUC(insulin)) decreased significantly more in the metformin group, compared with the placebo group [-3574 +/- 962 vs. +1367 +/- 1021 micro IU/min.ml (-26 +/- 7 vs. +10 +/- 7 nmol/min.liter), P = 0.003], but the AUC of DCI-IPG (AUC(DCI-IPG)) decreased similarly in both groups (-1452 +/- 968 vs. -2207 +/- 1021%/min, P = 0.60). However, the ratio of AUC(DCI-IPG)/AUC(insulin) increased by 160% after metformin and decreased by 29% after placebo (P = 0.002 between groups). Moreover, metformin seemed to improve the positive correlation between AUC(DCI-IPG) and AUC(insulin) but not placebo (r = 0.32, P = 0.68 at baseline; r = 0.52, P = 0.12 after metformin; and r = -0.39, P = 0.30 after placebo). We conclude that in obese women with PCOS, metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators, as evidenced by increased bioactive DCI-IPG released per unit of insulin.