Sirous Darabian

Cardiorenal syndrome: pathophysiology and potential targets for clinical management

Combined dysfunction of the heart and the kidneys, which can be associated with haemodynamic impairment, is classically referred to as cardiorenal syndrome (CRS). Cardiac pump failure with resulting volume retention by the kidneys, once thought to be the major pathophysiologic mechanism of CRS, is now considered to be only a part of a much more complicated phenomenon. Multiple body systems may contribute to the development of this pathologic constellation in an interconnected network of events. These events include heart failure (systolic or diastolic), atherosclerosis and endothelial cell dysfunction, uraemia and kidney failure, neurohormonal dysregulation, anaemia and iron disorders, mineral metabolic derangements including fibroblast growth factor 23, phosphorus and vitamin D disorders, and inflammatory pathways that may lead to malnutrition–inflammation–cachexia complex and protein–energy wasting. Hence, a pathophysiologically and clinically relevant classification of CRS based on the above components would be prudent. With the existing medical knowledge, it is almost impossible to identify where the process has started in any given patient. Rather, the events involved are closely interrelated, so that once the process starts at a particular point, other pathways of the network are potentially activated. Current therapies for CRS as well as ongoing studies are mostly focused on haemodynamic adjustments. The timely targeting of different components of this complex network, which may eventually lead to haemodynamic and vascular compromise and cause refractoriness to conventional treatments, seems necessary. Future studies should focus on interventions targeting these components.

Coronary Calcium: New Insights, Recent Data, and Clinical Role

Calcium artery calcium (CAC) scoring has become an integral part in the era of preventive cardiology, it has been extensively studied and been validated as a powerful tool for cardiovascular risk assessment in conjunction with other traditional well established scoring systems such as Framingham risk score. In addition, CAC testing has found its way into emergency department algorithms assessing low to intermediate risk patients presenting with chest pain, this strategy was recently adopted by the UK NICE guidelines, confidently ruling out cardiac origin of chest pain. Several studies have demonstrated that risk assessment using CAC was motivational to patients leading to better adherence to their preventive practices as well as to medications. Accordingly, this test has several recommendations for use by national and international guidelines.

The Role of Carotid Intimal Thickness Testing and Risk Prediction in the Development of Coronary Atherosclerosis

Carotid ultrasonography is a safe and available noninvasive diagnostic tool that provides information about the carotid arteries’ characteristics and may be used for early detection of coronary artery disease as well as cardiovascular and stroke event risk stratifications. We performed a systematic search of articles discussing carotid ultrasonography in the English literature recorded in PubMed from 2010 to September 2012. Generally, the studies showed that internal carotid artery intima–media thickness is a more powerful variable than common carotid artery intima–media thickness. Moreover, the presence of carotid plaque and plaque volumes are more reliable and accurate estimators of coronary artery disease and risk of a stroke or cardiovascular event than intima–media thickness.

Use of noninvasive imaging in the evaluation of coarctation of aorta.

Abstract Coarctation of the aorta is a congenital heart disease, which is often associated with other cardiac and noncardiac anomalies. Early diagnoses, information about associated anomalies, and defining the severity of the disease are critical for appropriate treatment planning. In this regard, several noninvasive imaging modalities, such as echocardiography, cardiac computed tomography (CT), and cardiac magnetic resonance imaging, have been used. Echocardiography, as an available and safe method, should be used as a primary screening test. It is also useful for intraoperative and hemodynamic studies, but cardiac CT is recommended before any corrective procedure or surgery. Cardiac CT angiography showed an excellent spatial resolution and a good capability for finding associated anomalies. After correction of coarctation of the aorta, serial cardiac magnetic resonance imaging is most commonly performed to avoid repeated radiation exposure.

The Cardiovascular Trial of the Testosterone Trials: rationale, design, and baseline data of a clinical trial using computed tomographic imaging to assess the progression of coronary atherosclerosis.

BackgroundData from prior studies have yielded inconsistent results on the association of serum testosterone levels with the risk for cardiovascular disease. There are no clinical trial data on the effects of testosterone replacement therapy on plaque progression. ObjectiveWe designed a study to investigate the effect of testosterone therapy on coronary artery plaque progression using serial coronary computed tomographic angiography (CCTA). In this paper, we describe the study design, methods, and characteristics of the study population. MethodsThe Cardiovascular Trial of the Testosterone Trials (TTrials; NCT00799617) is a double-blind, placebo-controlled trial of 1 year of testosterone therapy in men 65 years or older with clinical manifestations of androgen deficiency and unequivocally low serum testosterone concentrations (<275 ng/dl). CCTA performed at baseline and after 12 months of therapy will determine the effects of testosterone on the progression of the total volume of noncalcified plaques. All scans are evaluated at a central reading center by an investigator blinded to treatment assignment. ResultsA total of 165 men were enrolled. The average age is 71.1 years, and the average BMI is 30.7. About 9% of men had a history of myocardial infarction, 6% angina, and 10% coronary artery revascularization. A majority reported hypertension and/or high cholesterol; 31.8% reported diabetes. Total noncalcified plaque at baseline showed a slight but nonsignificant trend toward lower plaque volume with higher serum testosterone concentrations (P=0.12). ConclusionThe Cardiovascular Trial will test the hypothesis that testosterone therapy inhibits coronary plaque progression, as assessed by serial CCTA.

CAC score as a possible criterion for administration of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers: the MultiEthnic Study of Atherosclerosis.

IntroductionSeveral trials have demonstrated that angiotensin converting enzyme inhibitors (ACEIs) decrease cardiovascular (CV) mortality rates in patients with heart failure; however, the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) and European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) trials failed to show significant similar preventive effects in normal ejection fraction patients. We evaluated the baseline coronary artery calcium (CAC) score as a predictor of the effects of ACEIs/angiotensin receptor blockers (ARBs) on outcomes among normal ejection fraction participants. MethodologyOf 6814 MultiEthnic Study for Atherosclerosis population participants (after exclusion of the patients temporarily using ACEIs and/or ARBs during follow-up), we evaluated 2906 participants who never used ACEIs/ARBs and 368 (8.7%) participants who constantly used them during all baseline and follow-up examinations. In the population studied, 53.9% were men, aged 60.8±10.0 years, who had no apparent clinical CV disease. We compared CV event rates and multivariable-adjusted hazard ratios after stratifying by ACEI/ARB use and stratifying CAC scores by category (0, 1–399, and ≥400). ResultsThe event rates varied from 1.8 to 41.2/1000 person years among the CAC groups. Among the participants with a 1–399 CAC score, ACEI/ARB users had significantly lower event rates than nonusers (4.9 vs. 8.2, respectively). Hazard ratio in the adjusted model was 3.1 (95% confidence interval 1.14–8.78, P<0.05). There was no significant event rate difference between ACEI/ARB users and nonusers among other CAC groups. ConclusionThe use of ACEIs/ARBs was associated with significantly fewer CV events in asymptomatic participants with low to intermediate CAC scores. Thus, better risk stratification in asymptomatic individuals (such as using CAC scores) may assist in proper selection of patients for further CV risk reduction strategies.

Significance of epicardial and intrathoracic adipose tissue volume among type 1 diabetes patients in the DCCT/EDIC: A pilot study

Introduction Type 1 diabetes (T1DM) patients are at increased risk of coronary artery disease (CAD). This pilot study sought to evaluate the relationship between epicardial adipose tissue (EAT) and intra-thoracic adipose tissue (IAT) volumes and cardio-metabolic risk factors in T1DM. Method EAT/IAT volumes in 100 patients, underwent non-contrast cardiac computed tomography in the Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were measured by a certified reader. Fat was defined as pixels’ density of -30 to -190 Hounsfield Unit. The associations were assessed using–Pearson partial correlation and linear regression models adjusted for gender and age with inverse probability sample weighting. Results The weighted mean age was 43 years (range 32–57) and 53% were male. Adjusted for gender, Pearson correlation analysis showed a significant correlation between age and EAT/IAT volumes (both p<0.001). After adjusting for gender and age, participants with greater BMI, higher waist to hip ratio (WTH), higher weighted HbA1c, elevated triglyceride level, and a history of albumin excretion rate of equal or greater than 300 mg/d (AER≥300) or end stage renal disease (ESRD) had significantly larger EAT/IAT volumes. Conclusion T1DM patients with greater BMI, WTH ratio, weighted HbA1c level, triglyceride level and AER≥300/ESRD had significantly larger EAT/IAT volumes. Larger sample size studies are recommended to evaluate independency.

Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease

Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic–hematologic, (6) inflammatory–oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 μg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.

Association of Vitamin D Level and Subclinical Coronary Artery Disease

Background: The role of vitamin D level in subclinical atherosclerosis remains controversial. We aimed to investigate the relationship between vitamin D level and coronary artery calcium score (CACS). Patients methods: We investigated 303 consecutive patients referred to an outpatient clinic for CACS. The 25-hydroxy vitamin D [25(OH) D] levels were checked within three months of CACS evaluation. Vitamin D levels of <30 and <20 ng/mL were used as thresholds of vitamin D insufficiency and deficiency, respectively. The correlation between CACS and vitamin D was assessed. Unadjusted and covariate-adjusted logistic regression analyses were used to predict positive CACS. Results: The mean age in this study is 61.8 ± 11.8 years (39.9% female). The majority of patients enrolled were Caucasian (87.4%). Median (interquartile range) serum 25(OH) D concentration was 30.0 (23.0, 39.0) ng/ml. Vitamin D was insufficient ( 0) was prevalent in 206 (68%) participants. In the unadjusted model, the 25 (OH) D levels were not associated with the prevalence of CACS among all cases or among patients with positive CACS. Logistic regression models, after controlling for risk factors, did not change the results. In addition, among the 206 participants with prevalent CACS, 25 (OH) D levels were not associated with CACS severity. Conclusions: Our single centre retrospective study in a population with low prevalence of vitamin D deficiency failed to find a significant relation between 25(OH) D level and CACS even when adjusted for risk factors.

LEFT MAIN TRACT AND RIGHT CORONARY ARTERY OSTIAL DISEASE

Association of the left main ostium (LMO) and right coronary artery ostium (RCAO) disease was considered as one of the worst coronary artery disease (CAD) scenarios. Locating at the transition zone between coronary vessels and aorta suggest possibility of a different pathophysiology and risk factors