Biomarkers in Peripartum Cardiomyopathy-What We Know and What Is Still to Be Found.

Peripartum cardiomyopathy (PPCM) is a form of heart failure, often severe, that occurs in previously healthy women at the end of their pregnancy or in the first few months after delivery. In PPCM, the recovery of heart function reaches 45-50%. However, the all-cause mortality in long-term observation remains high, reaching 20% irrespective of recovery status. The incidence of PPCM is increasing globally; therefore, effort is required to clarify the pathophysiological background of the disease, as well as to discover specific diagnostic and prognostic biomarkers. The etiology of the disease remains unclear, including oxidative stress; inflammation; hormonal disturbances; endothelial, microcirculatory, cardiomyocyte and extracellular matrix dysfunction; fibrosis; and genetic mutations. Currently, antiangiogenic 16-kDa prolactin (PRL), cleaved from standard 23-kDa PRL in the case of unbalanced oxidative stress, is recognized as the main trigger of the disease. In addition, 16-kDa PRL causes damage to cardiomyocytes, acting via microRNA-146a secreted from endothelial cells as a cause of the NF-κß pathway. Bromocriptine, which inhibits the secretion of PRL from the pituitary gland, is now the only specific treatment for PPCM. Many different phenotypes of the disease, as well as cases of non-responders to bromocriptine treatment, indicate other pathophysiological pathways that need further investigation. Biomarkers in PPCM are not well established. There is a deficiency in specific diagnostic biomarkers. Pro-brain-type natriuretic peptide (BNP) and N-terminal BNP are the best, however unspecific, diagnostic biomarkers of heart failure at the moment. Therefore, more efforts should be engaged in investigating more specific biomolecules of a diagnostic and prognostic manner such as 16-kDa PRL, galectin-3, myeloperoxidase, or soluble Fms-like tyrosine kinase-1/placental growth factor ratio. In this review, we present the current state of knowledge and future directions of exploring PPCM pathophysiology, including microRNA and heat shock proteins, which may improve diagnosis, treatment monitoring, and the development of specific treatment strategies, and consequently improve patients' prognosis and outcome.

Proteomic Profiling in Patients With Peripartum Cardiomyopathy: A Biomarker Study of the ESC EORP PPCM Registry.

BACKGROUND: Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed. OBJECTIVES: This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision. METHODS: Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy controls (HCs). Significant changes in protein intensities were determined with nonpaired Student's t-tests and were further classified by using the Boruta algorithm. The proteins' diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation. RESULTS: Patients with PPCM presented with a mean left ventricular ejection fraction of 33.5% ± 9.3% vs 57.0% ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs. CONCLUSIONS: Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.

Cardiovascular Magnetic Resonance in Peripartum Cardiomyopathy: Comparison with Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Peripartum (PPCM) and dilated (DCM) cardiomyopathies are distinct forms of cardiac disease that share certain aspects in clinical presentation. AIM: We hypothesized that different cardiac structural changes underlie PPCM and DCM, and we aimed to investigate them with cardiovascular magnetic resonance (CMR). METHODS: We included 21 PPCM patients (30.5 ± 5.9 years) and 30 female DCM patients (41.5 ± 16.8 years) matched for left ventricular ejection fraction. Biventricular and biatrial volumetric and functional parameters were assessed along with ventricular and atrial strain indices based on feature-tracking techniques. The presence of late gadolinium enhancement (LGE) was also assessed. RESULTS: In PPCM, the left ventricular (LV) stroke volume index was lower (p = 0.04), right atrial (RA) minimal and pre-systolic volumes were higher (p < 0.01 and p = 0.02, respectively), and the total RA ejection fraction was lower (p = 0.02) in comparison to DCM. Moreover, in PPCM, the LV global longitudinal strain (p = 0.03), global circumferential strain rate (p = 0.04), and global longitudinal strain rate (p < 0.01) were less impaired than in DCM. Both PPCM and DCM patients with LGE had more dilated ventricles and more impaired LV and left atrial function than in PPCM and DCM patients without LGE. CONCLUSIONS: Subtle differences appear on CMR between PPCM and DCM. Most importantly, the RA is larger and more impaired, and LV global longitudinal strain is less reduced in PPCM than in DCM. Furthermore, similarly to DCM, PPCM patients with LGE have more dilated and impaired ventricles than patients without LGE.

Optimal medical therapy in patients with stable coronary artery disease in Poland: the ISCHEMIA trial experience.

Introduction: Optimal medical therapy (OMT) is the cornerstone of treatment for stable coronary disease with the ISCHEMIA trial showing similar outcomes using OMT with or without an initial invasive approach. Objectives: To describe OMT goal attainment in Polish ISCHEMIA participants compared with other countries. Patients and methods: Among 5179 trial participants, 333 were randomized in Poland. The median follow-up was 3.2 years. OMT targets were: not smoking, high-intensity statin therapy, low-density lipoprotein cholesterol (LDL-C) of less than 70 mg/dl, systolic blood pressure of less than 140 mm Hg, aspirin therapy, and ACEI / ARB, and ß-blocker therapy if indicated. Results: Compared with 36 other countries, at randomization, patients in Poland were older (67 [62­75] y vs 65 [58­71] y); P <⁠0.001), more often female (30% vs 22%; P = 0.002), with a longer history of angina (3 [1­9] y vs 1 [0­3] y; P <⁠0.001), and there were more cases of prior myocardial infarction (32% vs 18%; P <⁠0.01) and revascularization (PCI, 40% vs 19%; CABG, 11% vs 3%; P <⁠0.001 for both). The number of OMT goals attained increased from baseline to follow-up visits (5 [4­5] vs 6 [5­6]; P <⁠0.001) in Poland and other countries alike (P = 0.89 vs P = 0.14). In Poland, significant improvements were achieved regarding high-intensity statin therapy (27% vs 50%), LDL-C <⁠70 mg/dl (29% vs 65%), and systolic blood pressure of less than 140 mm Hg (63% vs 81%) (P <⁠0.001 for all), whereas not-smoking (89% vs 89%), aspirin (90% vs 88%), ACEI / ARB (93% vs 95%), and ß-blocker therapy (94% vs 90%) remained high. Conclusions: With regular surveillance and contemporary medical therapy, high OMT goal attainment was achievable among the participants of the ISCHEMIA trial in Poland relative to other countries. There is still room for improvement in LDL-C and blood pressure management.

Fibrinogen and a Triad of Thrombosis, Inflammation, and the Renin-Angiotensin System in Premature Coronary Artery Disease in Women: A New Insight into Sex-Related Differences in the Pathogenesis of the Disease.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in women worldwide. Its social impact in the case of premature CAD is particularly devastating. Many differences in the presentation of the disease in women as compared to men, including atypical symptoms, microvascular involvement, and differences in pathology of plaque formation or progression, make CAD diagnosis in women a challenge. The contribution of different risk factors, such as smoking, diabetes, hyperlipidemia, or obesity, may vary between women and men. Certain pathological pathways may have different sex-related magnitudes on CAD formation and progression. In spite of the already known differences, we lack sufficiently powered studies, both clinical and experimental, that assess the multipathogenic differences in CAD formation and progression related to sex in different age periods. A growing quantity of data that are presented in this article suggest that thrombosis with fibrinogen is of more concern in the case of premature CAD in women than are other coagulation factors, such as factors VII and VIII, tissue-type plasminogen activator, and plasminogen inhibitor-1. The rise in fibrinogen levels in inflammation is mainly affected by interleukin-6 (IL-6). The renin-angiotensin (RA) system affects the inflammatory process by increasing the IL-6 level. Unlike in men, in young women, the hypertensive arm of the RA system is naturally downregulated by estrogens. At the same time, estrogens promote the fibrinolytic path of the RA system. In young women, the promoted fibrinolytic process upregulates IL-6 release from leukocytes via fibrin degradation products. Moreover, fibrinogen, whose higher levels are observed in women, increases IL-6 synthesis and exacerbates inflammation, contributing to CAD. Therefore, the synergistic interplay between thrombosis, inflammation, and the RA system appears to have a more significant influence on the underlying CAD atherosclerotic plaque formation in young women than in men. This issue is further discussed in this review. Fibrinogen is the biomolecule that is central to these three pathways. In this review, fibrinogen is shown as the biomolecule that possesses a different impact on CAD formation, progression, and destabilization in women to that observed in men, being more pathogenic in women at the early stages of the disease than in men. Fibrinogen is a three-chain glycoprotein involved in thrombosis. Although the role of thrombosis is of great magnitude in acute coronary events, fibrinogen also induces atherosclerosis formation by accumulating in the arterial wall and enabling low-density lipoprotein cholesterol aggregation. Its level rises during inflammation and is associated with most cardiovascular risk factors, particularly smoking and diabetes. It was noted that fibrinogen levels were higher in women than in men as well as in the case of premature CAD in women. The causes of this phenomenon are not well understood. The higher fibrinogen levels were found to be associated with a greater extent of coronary atherosclerosis in women with CAD but not in men. Moreover, the lysability of a fibrin clot, which is dependent on fibrinogen properties, was reduced in women with subclinical CAD compared to men at the same stage of the disease, as well as in comparison to women without coronary artery atherosclerosis. These findings suggest that the magnitude of the pathological pathways contributing to premature CAD differs in women and men, and they are discussed in this review. While many gaps in both experimental and clinical studies on sex-related differences in premature CAD exist, further studies on pathological pathways are needed.

Pregnancy-related cardiac non-elective hospitalizations and pregnancy outcomes. A tertiary referral cardiac center experience.

BACKGROUND: Pregnant women with cardiovascular diseases (CVD) and their offspring are at higher risk of morbidity and mortality. AIMS: To provide data on pregnancy outcomes among women with different types of CVD requiring non-elective cardiac hospitalization in a tertiary referral cardiac center. METHODS: We identified all records of non-elective hospitalizations of pregnant women hospitalized between January 2009 through March 2018, at our institution - a tertiary referral cardiac center. The incidence and types of cardiac complications during pregnancy, as well as the pregnancy and offspring outcomes, were determined. RESULTS: One hundred and sixty-one out of 328 pregnancy-related hospitalizations in 140 pregnancies were non-elective. Cardiac complications occurred in 62 (44%) pregnancies, with the most frequent being episodes of arrhythmia (22.1% pregnancies), followed by heart failure exacerbations (6.4% pregnancies). Maternal mortality reached 2.1% and affected only women with primary cardiomyopathies (CMP). Offspring mortality was 2.8%. Newborns of mothers with cardiac complications had significantly lower Apgar scores and gestational age at delivery, compared to mothers without cardiac complications. CONCLUSIONS: In our series mortality and morbidity among pregnant women with CVD hospitalizations were high. An unfavorable maternal outcome mainly affected women with CMP. Offspring of mothers with cardiovascular complications are prone to have a lower gestational age and Apgar score.

Peripartum cardiomyopathy - a cardiovascular disease in pregnancy and puerperium. The actual state of knowledge, challenges, and perspectives.

Peripartum cardiomyopathy (PPCM) is an idiopathic, multifactor cause of heart failure occurring at the end of pregnancy or in the first months after delivery. Although the prevalence of the disease is increasing, the awareness of both physicians and patients is rather low. Symptoms of PPCM are unspecific, making a prompt diagnosis even more difficult. In severe functional insufficiency and dilatation of the left ventricle, the recovery rate is particularly low. Therefore, the later PPCM is diagnosed, the more severe heart failure, and the worse the patient's outcome. Despite the increasing frequency of PPCM, the exact pathophysiology and predictors of outcome are still not well determined. Therapeutic management in patients with PPCM remains a challenge, requiring a multidisciplinary approach. At the base of the disease lies dysfunction of microcirculation with 16-kDa prolactin as the main trigger of this state. Therefore, adding bromocriptine to standard heart failure pharmacotherapy may be particularly beneficial. In this review, we present the current state of knowledge and diagnostic and management recommendations and perspectives.

The association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the plasma fibrinogen level in women and men with premature coronary artery atherosclerosis.

INTRODUCTION: The insertion/deletion (I/D) polymorphism of the angiotensin­converting enzyme (ACE) gene is associated with younger age at coronary artery disease (CAD) onset. Some data indicate the relationship between the DD genotype and the fibrinogen level. At the same time, the regulation of the renin-angiotensin system differs in women and men. OBJECTIVES: The objective of the study was to evaluate the sex­dependentassociation of the ACE I/D polymorphism with the plasma fibrinogen level in patients with premature CAD. PATIENTS AND METHODS: The study included 407 participants with premature CAD: 257 women not older than 55 years and 150 men not older than 45 years. Study participants had at least 1 stenosis ≥50% in a major epicardial coronary artery. The ACE I/D polymorphism (rs4343) was genotyped using polymerase chain reaction. Fibrinogen levels were measured with a modified Clauss method. We found a significant interaction indicating that sex modifies the influence of the I/D polymorphism of the ACE gene on fibrinogen levels (P = 0.02). The highest mean fibrinogen level, adjusted for age and smoking status, was observed in women with the DD genotype (575.7 mg/dl) and it was significantly higher than in men with the DD genotype (367.1 mg/dl; P <0.001) or in women with the ID genotype (491.7 mg/dl; P = 0.04). In men, there was no significant difference in mean adjusted fibrinogen levels across genotypes. CONCLUSIONS: The DD genotype of the ACE gene was associated with higher plasma fibrinogen levels in women with premature CAD yet not in men.

Giant Intrapericardial Myxoma Adjacent to the Left Main Coronary Artery.

A 62-years-old woman was admitted to the hospital because of chronic cough, expectoration of thick mucus, hoarseness and tightness in the precordial area. Computed Tomography (CT) examination revealed the presence of a giant intrapericardial tumor with the dimensions of 80 × 38 × 32 mm. It was located anteriorly and laterally to the left atrium, posteriorly to the pulmonary trunk and the ascending aorta. This hypodense change modeled the left atrium without evidence of invasion. CT coronary angiography and 3-dimensional reconstruction were applied to enable precise planning of cardiac surgery. CT evaluation confirmed that it is possible to remove the tumor without damage to the adjacent left main coronary artery. The patient underwent cardiac surgery with sternotomy and cardiopulmonary bypass. A cohesive, smooth, vascularized tumor pedunculated to the left atrial epicardium was visualized. The location and dimensions corresponded to those determined by CT scan examination. The entire tumor was successfully dissected together with adjacent adipose and fibrous tissue. Histological evaluation revealed the presence of myxoid cells, blood vessels, degenerative changes, and microcalcifications embedded in profuse hyalinized stroma. Those histological features enabled identification of the intrapericardial tumor as a myxoma. Follow-up CT examination did not demonstrate any signs of recurrence of the myxoma. According to our knowledge, a myxoma located inside the pericardial sac has never been described before.

Severe Course of Peripartum Cardiomyopathy and Subsequent Recovery in a Patient with a Novel TTN Gene-Truncating Mutation.

BACKGROUND Peripartum cardiomyopathy (PPCM) is a potentially life-threatening, pregnancy-associated cause of heart failure affecting previously healthy women. Recent research suggests a possible role of 16-kDa prolactin in promoting cardiomyocyte damage. However, the genetic predisposition is not well recognized. CASE REPORT We report the case of a 25-year-old woman with a severe course of PPCM with left ventricle ejection fraction of 25-30%, complicated by ventricular arrhythmia and postpartum thyroiditis. As no traditional risk factors of PPCM were identified, the patient was referred for genetic testing. Next-generation sequencing revealed a novel titin gene-truncating mutation NM_001267550: p.Leu23499fs/c.70497_40498insT in the proband as well as in her mother. In the patient, a very late recovery >12 months postpartum was observed, which required long-term medical treatment with bromocriptine. CONCLUSIONS PPCM may occur in women with the genetic predisposition, being modified by an interaction of biological factors, such as a high prolactin level, a ventricular arrhythmia, and an autoimmune disorder. Recovery from severe heart failure due to an inherited cardiomyopathy is possible with careful and appropriate medical management.

Menopause improves the predictive value of common cardiovascular risk scores in women with premature coronary artery disease.

OBJECTIVE: Menopause, particularly its early stage (≤3 years from onset), may be an important risk factor for premature coronary artery disease. The objective of the study was to assess whether the addition of the presence of menopause in women with premature coronary artery disease could improve the predictive value of the Atherosclerotic Cardiovascular Disease risk estimator and the Systematic COronary Risk Evaluation model. METHODS: The case-control study included 307 women with coronary artery disease aged 55 or less, and 347 age-matched controls without coronary artery disease. Diagnostic accuracy parameters were evaluated for traditional risk models versus those enriched with menopausal status. Early and late postmenopausal periods were defined as ≤3 and >3 years from the onset of menopause, respectively. RESULTS: Only the addition of the presence of the early postmenopausal stage to the 10-year Atherosclerotic Cardiovascular Disease risk classes resulted in significantly increased c-statistics from 0.66 (95% confidence interval [CI] 0.62-0.7) to 0.705 (95%CI 0.66-0.75) (P = 0.0003) and an increase of accuracy from 61.3% to 63.8% (P = 0.0025).Adding the presence of early postmenopause to the Systematic COronary Risk Evaluation risk classes also resulted in significantly increased c-statistics from 0.59 (95% CI 0.55-0.63) to 0.641 (95%CI 0.6-0.68) (P = 0.0024) and an increase of accuracy from 64.1% versus 57.5% (P = 0.001). CONCLUSION: Adding the early menopausal period may significantly improve the predictive value of the 10-year Atherosclerotic Cardiovascular Disease risk score and the Systematic COronary Risk Evaluation model in women with premature coronary artery disease.

Patterns of Coronary Calcification and Their Impact on the Diagnostic Accuracy of Computed Tomography Coronary Angiography.

OBJECTIVE: Despite coronary calcifications being a major factor affecting the diagnostic accuracy of coronary computed tomography angiography (CTA), there is a lack of established criteria for categorizing calcifications. We aimed to evaluate patterns of coronary calcification based on quantitative radiodensity and size parameters to provide coronary calcium categories and assess their impact on the accuracy of coronary CTA. METHODS AND RESULTS: We analyzed length, maximum thickness, volume, mean density, and maximum density of coronary calcium and divided each of these parameters into tertiles. Subsequently, we summarized the tertiles for each individual calcification and divided them into 3 equal groups of: mild, moderate, and severe calcification. The accuracy of coronary CTA was defined as the difference between the measurements obtained on coronary CTA versus the reference of intravascular ultrasound (IVUS). We evaluated 252 coronary calcifications within 97 arteries of 60 patients. There was an expected increase in size and density values for mild versus moderate versus severe calcifications, but there was no difference in IVUS measured minimum lumen area among the 3 groups. Of note, coronary CTA significantly underestimated IVUS minimum lumen area measurement by 1.2 ± 1.6 mm (14.6 ± 23.1%, P < 0.001) for severe calcifications and by 0.5 ± 2.0 mm (3.7 ± 32.1%, P = 0.021) for moderate calcifications. Within mild calcifications, the difference was not significant. CONCLUSION: Based on their dimensional and radiodensity characteristics, our analysis revealed patterns of individual coronary artery calcifications that affected the accuracy of coronary CTA measurements; coronary CTA inaccuracy was associated with the presence of moderate or severe calcifications, but not mild calcifications.

Impact of coronary artery calcium characteristics on accuracy of CT angiography.

OBJECTIVES: This study sought to evaluate which specific calcium characteristics impact diagnostic accuracy of coronary computed tomography angiography (CTA). BACKGROUND: Coronary calcifications comprise one of the most significant factors interfering with diagnostic accuracy of coronary CTA. Despite this fact, there is paucity of data regarding this phenomenon. METHODS: A total of 525 coronary lesions (252 calcified and 273 reference [noncalcified] lesions) within 97 arteries of 60 patients (19 women, age 63 ± 10 years) underwent assessment with both 2 × 64-slice computed tomography and intravascular ultrasound (IVUS). Nineteen calcium characteristics were determined. The main outcome was coronary CTA inaccuracy defined as the deviation of minimum lumen area within the calcification measured with coronary CTA from that measured with IVUS, in both absolute (mm(2)) and relative (%) terms. RESULTS: Presence of calcification was found to be independently correlated to coronary CTA inaccuracy in both absolute and relative terms (p < 0.001 for both). The relative (%) inaccuracy of coronary CTA was independently correlated to total calcium length (p = 0.004), total calcium volume (p = 0.008), cross section calcium thickness (p = 0.023), cross section calcium area (p = 0.023), and cross section lumen area (p = 0.001). The absolute inaccuracy of CTA was correlated to calcium length (p = 0.010), calcium volume (p = 0.017), and cross section calcium area (p < 0.001). The presence of both total calcium arc ≥47° and mean lumen diameter of ≤2.8 mm provided the best predictive accuracy for detection of excessive lumen underestimation by CTA. The best accuracy for prediction of excessive lumen overestimation provided combination of 2 of 3 features: maximum calcium density <869 HU, OR whole calcium length <2.4 mm, OR total calcium volume <6.4 mm(3). CONCLUSIONS: Our results indicate which specific calcium characteristics impact accuracy of coronary CTA in lumen assessment within calcified lesions. This may provide practical assistance in predicting coronary lumen underestimation or overestimation by coronary CTA, therefore mitigating risk of diagnostic errors in clinical practice.

Lumen and calcium characteristics within calcified coronary lesions. Comparison of computed tomography coronary angiography versus intravascular ultrasound.

INTRODUCTION: Computed tomography coronary angiography (CTCA) is a diagnostic method used for exclusion of coronary artery disease. However, lower accuracy of CTCA in assessment of calcified lesions is a significant factor impeding applicability of CTCA for assessment of coronary atherosclerosis. AIM: To provide insight into lumen and calcium characteristics assessed with CTCA, we compared these parameters to the reference of intravascular ultrasound (IVUS). MATERIAL AND METHODS: Two hundred and fifty-two calcified lesions within 97 arteries of 60 patients (19 women, age 63 ±10 years) underwent assessment with both 2 × 64 slice CT (Somatom Definition, Siemens) and IVUS (s5, Volcano Corp.). Coronary lumen and calcium dimensions within calcified lesions were assessed with CTCA and compared to the reference measurements made with IVUS. RESULTS: On average CTCA underestimated mean lumen diameter (2.8 ±0.7 mm vs. 2.9 ±0.8 mm for IVUS), lumen area (6.4 ±3.4 mm(2) vs. 7.0 ±3.7 mm(2) for IVUS, p < 0.001) and total calcium arc (52 ±35° vs. 83 ±54°). However, analysis of tertiles of the examined parameters revealed that the mean lumen diameter, lumen area and calcium arc did not significantly differ between CTCA and IVUS within the smallest lumens (1(st) tertile of mean lumen diameter at 2.1 mm, and 1(st) tertile of lumen area at 3.7 mm(2)) and lowest calcium arc (mean of 40°). CONCLUSIONS: Although, on average, CTCA underestimates lumen diameter and area as well as calcium arc within calcified lesions, the differences are not significant within the smallest vessels and calcium arcs. The low diagnostic accuracy of CTCA within calcified lesions may be attributed to high variance and not to systematic error of measurements.

What is the optimal cut-off point for low coronary artery calcium score assessed by computed tomography? Multi-Detector Computed Tomography ANIN Registry.

AIM: This prospective study was conducted to evaluate the incidence and predictors of coronary artery disease (CAD) in relation to the low coronary artery calcium (CAC) score among patients with intermediate probability of CAD. MATERIAL AND METHODS: A total of 1132 consecutive patients were included in the analysis (58.7 ±10.9 years, 46.7% males). Coronary computed tomography (CCT) angiography was performed in a multi-detector computed tomography scanner. Coronary artery calcium score was calculated by the Agatston method. Obstructive CAD was defined as the presence of coronary artery stenosis ≥ 50% on CCT angiography. RESULTS: Coronary artery disease was diagnosed in nearly one-fourth of patients (n = 272, 24%). In the receiver operating characteristics (ROC) curve analysis a CAC score of 10 was used as an optimal cut-off point for discriminating obstructive CAD (sensitivity: 0.79, specificity: 0.75, p < 0.0001) whereas for a CAC score of 100 the sensitivity and specificity were 0.48 and 0.92, respectively. On multivariate analysis after adjustment for age, gender, hypertension, hyperlipidemia, creatinine levels, only in patients with CAC score ≤ 10 age (OR = 1.05, 95% CI: 1.02-1.08, p = 0.0005, OR = 1.05, 95% CI: 1.03-1.08, p < 0.0001) and male gender (OR = 3.45, 95% CI: 1.92-6.22, p < 0.0001), likewise in group with CAC score ≤ 100 age (OR = 1.05, 95% CI: 1.03-1.08, p < 0.0001) and male gender (OR = 3.31, 95% CI: 1.88-5.81, p < 0.0001) were independent predictors of obstructive CAD. CONCLUSIONS: The cut-off point of 10 for CAC score determined patients with CAD with the best sensitivity and specificity. Therefore, a total CAC score < 10 should be classified as "low". In patients with a low CAC score obstructive high risk plaques prone to rupture are presented and are associated with increasing age and male gender.

Therapeutic challenges and management of heart failure during pregnancy (part 2).

A particularly dangerous condition in pregnant women is already dilated left ventricle with severe functional impairment. Taking as an example the case of woman with dilated cardiomyopathy (DCM) first diagnosed in 17th week of pregnancy, the paper discusses diagnostic, therapeutic challenges and management of heart failure during pregnancy. Repeat measurements of brain natiuretic peptide levels should be helpful in diagnosing heart failure. To distinguish DCM from peripartum cardiomyopathy the time of manifestation should be considered. The risk of serious events is associated with NYHA class and impairment of left ventricular ejection fraction. Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin-II receptor blockers are contraindicated in pregnancy because of fetal toxicity. The incidence of sight effects is associated with time of administration of ACE-I and duration of treatment. Possible sight effects of drugs in fetus should be monitored (mainly ultrasonographically). ICD can be implanted during pregnancy if indicated. To assess the time and mode of delivery, a multidisciplinary team of different specialists is required. Subsequent pregnancy is contraindicated in a patient with DCM and low ejection fraction of left ventricle.

Therapeutic challenges and management of heart failure during pregnancy (part I).

Therapeutic management in pregnant patients with heart failure still remains a challenge, even though in most pregnant women with cardiac diseases an outcome is good. A 32-year-old woman, 17 weeks pregnant, was admitted to hospital with heart failure (HF) NYHA class III/IV. Echocardiography revealed enlarged LV, LVEF 13%, significant mitral insufficiency and pulmonary hypertension. The patient wished to continue the pregnancy. In a life-threatening condition, metoprolol, enalapril, spironolactone (for 5 days), furosemide, and digitalis were administered. Enalapril was continued for 42 days. Then the patient was switched to a dihydralazine and isosorbide mononitrate regimen. The fetus was controlled ultrasonographically. In the 19th week of pregnancy, the patient's condition improved (NYHA class II, LVEF 23%). The patient experienced 2 more episodes of HF exacerbation. In the 26th week of pregnancy, in a primary prevention of sudden cardiac death and because of 2nd-degree AV block, an ICD was implanted. In the 32nd week of pregnancy a cesarean section was performed. A male infant was delivered. The patient made a good recovery and was discharged on the 7th postoperative day. The newborn was discharged after 4 weeks, in good general condition. At 1-year follow-up the patient presented NYHA class II.