Various Subsets Of Patients Research Articles

The Emerging Role of Sodium-glucose Cotransporter 2 Inhibitors in Heart Failure

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively novel drug class that most cardiologists are becoming familiar with. By contrasting glucose reabsorption in the proximal convoluted tubule of the nephron, SGLT2 inhibition results in glycosuria with improved glycemic control. Although originally introduced as anti-diabetic medications, the cardiovascular effects of SGLT2i have progressively emerged, leading them to become one of the four pillars for the treatment of heart failure with reduced ejection fraction (HFrEF) according to the 2021 guidelines from the European Society of Cardiology. Also, two recent randomized trials have demonstrated SGLT2i as the first compounds with proven prognostic impact in heart failure with preserved ejection fraction (HFpEF), setting a milestone in the treatment for this condition. While the exact pathogenic mechanisms mediating the substantial reduction in cardiovascular death and heart failure (HF) hospitalizations are still controversial, there is growing clinical evidence on the efficacy and safety of SGLT2i in various subsets of patients with HF. As known, heart failure is a complex and heterogeneous clinical syndrome with a magnitude of phenotypes and a variety of underlying hemodynamic and physiological aspects which cannot be fully incorporated into the traditional left ventricular ejection fraction based classification adopted in clinical trials. The aim of this review is to provide an overview of the cardiovascular benefits and indications of SGLT2i across different HF patterns and to highlight current gaps in knowledge that should be addressed by future research.

ARNI in cardiovascular disease: current evidence and future perspectives.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the mainstay of therapy for cardiovascular disease and heart failure (HF). The angiotensin receptor II blocker - neprilysin inhibitor (ARNI), sacubitril-valsartan has an established role in treatment of patients with HF with reduced ejection fraction (HFrEF) based on the results of PARADIGM-HF trial. This trial has provided a strong evidence base for treatment of HFrEF in various subsets of patients. Several studies are done using ARNI in various indications such as HFrEF, HFrEF, patients hospitalized with acute decompensated HF, HF with preserved EF, AMI with LVEF <40%, hypertension, chronic kidney disease, pulmonary hypertension, obstructive sleep apnea, so on and so forth. This review provides an update of current literature and future perspective on ARNI in various cardiovascular disorders.

Abstract WP167: Changing Face of Carotid Revascularization Procedures in the United States

Background: Carotid revascularization procedure, carotid endarterectomy (CEA) and carotid stent placement (CAS), are some of the most common procedures performed in United States and expected to change due to wider adoption of CAS. We performed this study to determine the changes in utilization of CEA and CAS in United States using nationally representative data. Methods: We used the National Inpatient Sample (NIS) from 2005 to 2014 to assess the changes in utilization of CEA and CAS over last 10 years in patients with symptomatic and asymptomatic carotid artery stenosis. NIS is the largest all payer dataset that includes diagnoses, admissions and discharge, demographics, and outcomes data of patients admitted to short stay non-Federal hospitals in the United States. We analyzed patterns of changes in utilization in various subsets of patients with carotid artery stenosis. Results: A total of 1,186,182 patients underwent carotid revascularization procedures during study period; 1,032,148 (87.1%) and 154,035 (12.9%) were CEA and CAS, respectively. The overall carotid revascularization procedures decreased over last 10 years (11.1% in 2005 to 8.4%in 2014, trend test p &lt;.0001). Carotid revascularization in symptomatic patients increased (7.64% in 2005 to 11.01% in 2014, trend test p &lt;.0001) while it decreased in asymptomatic patients (92.36% in 2006 to 88.99% in 2014, trend test p &lt;.0001). There was an overall decrease in CEA (11.6% in 2005 to 8.3% in 2014, trend test &lt;.0001) while in CAS remained unchanged (8.1% in 2005 to 8.9% in 2014, p=NS). There was an increase in carotid revascularization in teaching hospitals (40.9% in 2005 to 67.1% in 2014, trend test p &lt;.0001) while decrease in non-teaching hospitals (50.9% in 2006 to 27.1% in 2014, trend test p &lt;.0001). There was a decrease in carotid revascularization procedures in patients aged ≥80 years (19.8% in 2005 to 18.7% in 2014, trend test p &lt;.0001) and CEA (19.6% in 2006 to 18.8% in 2014, trend test P&lt;.0001) and CAS (21.2% in 2006 to 18.6% in 2014, trend test p=&lt;.0001). Conclusion: Although CAS is increasing in a disproportionate manner within patient subgroups in United States, overall carotid revascularization procedures have decreased for unclear reasons.

Thromboprophylaxis in Neuro Intensive Care Unit

AbstractThe propensity for venous thromboembolism in patients admitted to neurocritical care setups is high because of predilection toward venous stasis as well as pathological processes favoring embolus formation and dissemination. The application of routine thromboprophylaxis guidelines in the various subsets of neurologically injured patients is limited by the fear of bleeding inside neurologically significant closed locations. The aim of this review is to lay out thromboprophylaxis guidelines in various subsets of patients admitted to neurocritical care setups according to recent evidence base, which is still an evolving process.

Identification of Patients in Need of Advanced Care for Depression Using Data Extracted From a Statewide Health Information Exchange: A Machine Learning Approach

BackgroundAs the most commonly occurring form of mental illness worldwide, depression poses significant health and economic burdens to both the individual and community. Different types of depression pose different levels of risk. Individuals who suffer from mild forms of depression may recover without any assistance or be effectively managed by primary care or family practitioners. However, other forms of depression are far more severe and require advanced care by certified mental health providers. However, identifying cases of depression that require advanced care may be challenging to primary care providers and health care team members whose skill sets run broad rather than deep.ObjectiveThis study aimed to leverage a comprehensive range of patient-level diagnostic, behavioral, and demographic data, as well as past visit history data from a statewide health information exchange to build decision models capable of predicting the need of advanced care for depression across patients presenting at Eskenazi Health, the public safety net health system for Marion County, Indianapolis, Indiana.MethodsPatient-level diagnostic, behavioral, demographic, and past visit history data extracted from structured datasets were merged with outcome variables extracted from unstructured free-text datasets and were used to train random forest decision models that predicted the need of advanced care for depression across (1) the overall patient population and (2) various subsets of patients at higher risk for depression-related adverse events; patients with a past diagnosis of depression; patients with a Charlson comorbidity index of ≥1; patients with a Charlson comorbidity index of ≥2; and all unique patients identified across the 3 above-mentioned high-risk groups.ResultsThe overall patient population consisted of 84,317 adult (aged ≥18 years) patients. A total of 6992 (8.29%) of these patients were in need of advanced care for depression. Decision models for high-risk patient groups yielded area under the curve (AUC) scores between 86.31% and 94.43%. The decision model for the overall patient population yielded a comparatively lower AUC score of 78.87%. The variance of optimal sensitivity and specificity for all decision models, as identified using Youden J Index, is as follows: sensitivity=68.79% to 83.91% and specificity=76.03% to 92.18%.ConclusionsThis study demonstrates the ability to automate screening for patients in need of advanced care for depression across (1) an overall patient population or (2) various high-risk patient groups using structured datasets covering acute and chronic conditions, patient demographics, behaviors, and past visit history. Furthermore, these results show considerable potential to enable preventative care and can be easily integrated into existing clinical workflows to improve access to wraparound health care services.

Predictors of survival in octogenarians after mitral valve surgery for degenerative disease: The Mitral Surgery in Octogenarians study

ObjectivesAn increasing number of octogenarians are referred to undergo mitral valve surgery for degenerative disease, and percutaneous approaches are being increasingly used in this subgroup of patients. We sought to determine the survival and its predictors after Mitral Valve Surgery in Octogenarians (MiSO) in a multicenter UK study of high-volume specialized centers. MethodsPooled data from 3 centers were collected retrospectively. To identify the predictors of short-term composite outcome of 30 days mortality, acute kidney injury, and cerebrovascular accident, a multivariable logistic regression model was developed. Multiple Cox regression analysis was performed for late mortality. Kaplan–Meier curves were generated for long-term survival in various subsets of patients. Receiver operating characteristic analysis was done to determine the predictive power of the logistic European System for Cardiac Operative Risk Evaluation. ResultsA total of 247 patients were included in the study. The median follow-up was 2.9 years (minimum 0, maximum 14 years). A total of 150 patients (60.7%) underwent mitral valve repair, and 97 patients (39.3%) underwent mitral valve replacement. Apart from redo cardiac surgery (mitral valve repair 6 [4%] vs mitral valve replacement 11 [11.3%], P = .04) and preoperative atrial fibrillation (mitral valve repair 79 [52.6%] vs mitral valve replacement 34 [35.1%], P < .01), there was no significant difference in terms of any other preoperative characteristics between the 2 groups. Patient operative risk, as estimated by logistic European System for Cardiac Operative Risk Evaluation, was lower in the mitral valve repair group (10.2 ± 11.8 vs 13.7 ± 15.2 in mitral valve replacement; P = .07). No difference was found between groups for duration of cardiopulmonary bypass and aortic crossclamp times. The 30-day mortality for the whole cohort was 13.8% (mitral valve repair 4.7% vs mitral valve replacement 18.6%; P < .01). No differences were found in terms of postoperative cerebrovascular accident (2% vs 3.1%; P = .9), acute kidney injury requiring dialysis (6.7% vs 13.4%; P = .12), and superficial or deep sternal wound infection (10% vs 16.5%, P = .17; 2% vs 3.1%, P = .67, respectively). The final multiple regression model for short-term composite outcome included previous cardiac surgery (odds ratio [OR], 4.47; 95% confidence interval [CI], 1.37-17.46; P = .02), intra-aortic balloon pump use (OR, 4.77; 95% CI, 1.67-15.79; P < .01), and mitral valve replacement (OR, 7.7; 95% CI, 4.04-14.9; P < .01). Overall survival for the entire cohort at 1, 5, and 10 years was 82.4%, 63.7%, and 45.5% (mitral valve repair vs mitral valve replacement: 89.9% vs 70.7% at 1 year, 69.6% vs 54% at 5 years, and 51.8% vs 35.5% at 10 years; P = .0005). Cox proportional hazard model results showed mitral valve replacement (hazard ratio, 1.88; 95% CI, 1.22-2.89; P < .01) and intra-aortic balloon pump use (hazard ratio, 2.54; 95% CI, 1.26-5.13; P < .01) to be independent predictor factors affecting long-term survival. Logistic European System for Cardiac Operative Risk Evaluation did not perform well in predicting early mortality (area under the curve, 0.57%). ConclusionsIn octogenarians, mitral valve repair for degenerative disease is associated with good survival and remains the gold standard, whereas mitral valve replacement is still associated with significant mortality. Logistic European System for Cardiac Operative Risk Evaluation was unable to predict early mortality in our cohort of patients. Larger international multicenter registries are required to optimize the decision-making process in such a high-risk subgroup.

Thromboelastography does not predict outcome in different etiologies of cirrhosis

Unlabelled Box BackgroundNew laboratory tests that measure global hemostasis indicate generally preserved hemostatic function in patients with cirrhosis. It is not known whether normal hemostatic function is maintained across various subsets of patients. ObjectivesIn the present study, we investigated clot generation and clot lysis kinetics in a large group of patients with different etiologies of disease. Patients/MethodsBlood samples of 270 patients with cirrhosis were studied using thromboelastography (TEG), which measures the dynamic and physical properties of clot formation and lysis in whole blood. TEG parameters of different subsets of the patient population were compared. Correlations with routine laboratory tests as well as clinical outcomes were explored. ResultsOverall, TEG parameters were normal and similar between underlying disease etiologies. A proportion of subjects showed hypocoagulable features, with the exception of patients with cholestatic cirrhosis in whom TEG readings showed hypercoagulable features. In all groups, K‐time, α‐Angle, and MA correlated well with platelet counts and fibrinogen plasma levels. After a mean follow‐up of 2 years and 11 months, 31 patients had experienced a bleeding event, 8 had developed thrombosis, and 173 patients (64%) had undergone liver transplantation and/or had died. TEG baseline parameters were similar between patients subdivided according to outcome. ConclusionsTEG parameters reflected generally preserved function of the hemostatic system in patients with cirrhosis, with hypo‐ and hypercoagulable features in subsets of patients with specific underlying disease etiologies. Abnormalities in TEG parameters did however not predict bleeding, thrombosis, or risk of liver transplantation and/or death.

Emerging Data Support Benefits of Yoga for Patients With Heart Disease.

Diaphragmatic breathing techniques that 1 patient learned during a yoga-based cardiac rehabilitation class helped him overcome the stress and anxiety he often felt in the waiting room of his cardiologist’s office. The patient, like many seen by Sara Chambers, RN, BSN, assistant nurse manager in Cardiac Rehabilitation at Palm Beach Gardens Medical Center, said yoga helped him learn valuable coping techniques he uses in daily life. “Cardiac patients in particular tend to have a lot of stress,” said Chambers, who is is among the >20 million, or 9.5%, of US individuals who practice yoga, according to the 2012 National Health Interview Survey. Now, an emerging body of evidence suggests that yoga, which combines breathing exercises, strengthening and stretching poses, and relaxation techniques, can be beneficial for individuals with heart conditions or other chronic diseases. It seems to have comparable safety to other forms of exercise. “There are multiple studies that [suggest] that regular yoga practice with breathing exercises can increase lung volume, decrease heart rate and blood pressure, help regulate the parasympathetic and sympathetic nervous systems, lower anxiety, and physical endurance,” said Chambers. Although many forms of exercise can be beneficial for patients with chronic diseases, the unique aspect of yoga “is the strong focus on breathing technique and …

JS ISH-ESH-2 UPDATE ON THE DETECTION AND FOLLOW-UP OF EARLY HYPERTENSIVE HEART DISEASE

JS ISH-ESH-2 UPDATE ON THE DETECTION AND FOLLOW-UP OF EARLY HYPERTENSIVE HEART DISEASE

Short and long-term outcomes of alcohol septal ablation with the trans-radial versus the trans-femoral approach: A single center-experience

BackgroundAlthough the trans-radial approach (TR) has been applied to various subsets of patients in percutaneous coronary intervention, the feasibility, efficacy, acute procedural and long-term outcomes of TR versus trans-femoral approach (TF) for alcohol septal ablation (ASA) have not yet been determined. ObjectivesThe aim of this study was to compare the short and long-term outcomes of ASA with the TR approach compared to the TF approach. MethodsWe retrospectively analyzed 240 patients who underwent an ASA procedure at our institution from November 1999 to November 2015. The TR approach was performed in 172 cases and the TF approach in the remaining 68 cases. ResultsThe use of TR approach progressively increased from 62% in 1999–2005 to 91% in 2011–2015 (p=0.0001). The TF and TR group had similar age, baseline NYHA class (NYHA 3 or 4) and mean left ventricular outflow tract peak gradient before ASA. Total contrast used (TR: 73.2±47.2ml; TF: 88.7±49.3ml, p=0.11), total radiation Air kerma area product (TR: 43.7±48.0Gycm−2; TF: 55.9±48.2Gycm−2; p=0.39) and peak left ventricular outflow tract gradient immediately after ASA (TR: 19.1±19.6mmHg; TF: 20.4±18.0mmHg, p=0.63) were similar in both groups.Procedural success was 91.9% and 91.2% in the TR and TF groups, respectively (p=0.53). At 30days, there was 2 intra-hospital death (1 in TF and 1 in TR), 1 major stroke in the TF group and 1 coronary artery dissection in the TR group. Vascular complications were less frequent in the TR group (0.58% vs. 7.3%; p=0.002). The mean length of follow-up was 4.56±4.34years (IQR 0.69–8.2; median 2.92years; maximum: 15.5years). By Kaplan–Meier estimate, the observed survival in the overall cohort was comparable to the expected survival for a sex and age-matched comparable general French population at 10years (86.9 vs. 83.6%, p=0.88). Survival was similar between the TR and TF group (92.1% vs. 89.7% at 6years, respectively; p=0.71). ConclusionsAlcohol septal ablation from the radial approach can be performed with similar acute and long-term success, but with lower vascular complications compared to the femoral approach.

Abstract LB-C07: Predictive biomarkers for detection and therapeutic response in genitourinary cancers using enumeration of circulating tumor cells

Abstract Introduction: Genitourinary (GU) cancers are common tumor types that have multiple therapeutic options, but the cure rate is low, and adaptation or acquired resistance to treatment are common. Biomarkers are lacking in these cancer types; thus, it is essential to develop a reliable, reproducible biomarker of detection, treatment guidance, and prognosis, such as enumeration of circulating tumor cells (CTCs). The challenge of CTCs has been the ability to capture mixed cell populations. We describe the results of a concept study using the Axon nCYTE DxTM System to enumerate EpCAM-positive and –negative CTCs from patients with prostate, bladder, and renal cell cancer at various stages of disease. Methods: One-time clinical blood samples (10 mL) were obtained from 50 patients with GU cancers; 6 mL (3 mL/slide) were used to enumerate CTCs (4 mL were stored for future study). Nucleated cells were fixed, permeabilized, and pelleted. Cell pellets were then rinsed and incubated in a proprietary cancer detection cocktail and run through the Axon nCYTE DxTM detection/enumeration instrument to detect and count CTCs (nucleus+/cytokeratin; non-specific binding-). All data was analyzed in a blinded manner. Results: The Axon nCYTE DxTM System was able to isolate CTCs from all patient samples analyzed to date. CTC (&amp;gt;4 μm) purity after the first enrichment step was in 100% (median, 2.1/mL; mean, 2.2/mL) of prostate samples, 100% (median, 2.1/mL; mean 2.1/mL) of bladder samples, and 100% (median, 1.6/mL; mean, 9.1/mL) of renal cell samples. We present data on the first 10 patient samples (table 1); another 18 are being analyzed and 22 being accrued. Conclusions: The Axon nCYTE Dx™ System consistently detected CTCs among various subsets of patients with GU cancers. We are in the process of completing accrual and analysis of remaining patient samples. A complete data set will be presented at the meeting. Our initial proof of principle will be prospectively validated longitudinally as a complement to our clinical research program in GU cancers to establish CTCs as a biomarker of detection, treatment response, and prognosis. Pt., cancer typeTreatmentPSA, ng/dLNo. CTCs/ml1, mRCCMTA1.32, mPCADT/chemo1.03.83, mPCADT/chemo28.62.74, CRPCSurveil0.52.65, mRCCMTA24.16, UT TCCChemo2.17, mRCCMTA1.68, mRCCMTA1.69, mCRPCABI4.2110, mCRPCABI8.21.6ABI, androgen biosynthesis inhibitor; ADT, androgen deprivation therapy; CRPC, castration-resistant prostate cancer; m, metastatic; MTA, molecular targeted agent; RCC, renal cell carcinoma; UT TCC, upper-tract urothelial cell carcinoma ABI, androgen biosynthesis inhibitor; ADT, androgen deprivation therapy; CRPC, castration-resistant prostate cancer; m, metastatic; MTA, molecular targeted agent; RCC, renal cell carcinoma; UT TCC, upper-tract urothelial cell carcinoma Citation Format: Robert J. Amato, Reynolds Brobey, Kent Murphy, Jeff Smith, Meeta Patnaik. Predictive biomarkers for detection and therapeutic response in genitourinary cancers using enumeration of circulating tumor cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-C07.

Unraveling the Complexities of Treating Metastatic Colorectal Cancer With Angiogenesis Inhibitors

In the absence of sufficient clinical data to directly compare and determine the superiority of any angiogenesis inhibitor for different patient subpopulations in different disease settings, oncologists find it difficult to make complex decisions in selecting the optimal treatment regimen for their patients with metastatic colorectal cancer (mCRC). Intense research in recent years has yielded substantial advances in our understanding of the biology of tumors of the colon and rectum, resulting in the identification of essential biologic targets within the tumors and their microenvironment and incorporation of efficacious targeted agents into traditional treatment algorithms for mCRC. Targeted agents directed against the vascular endothelial growth factor (VEGF) pathway have gained prominence in the past decade; several angiogenesis inhibitors, such as the anti-VEGF monoclonal antibody bevacizumab, the soluble VEGF decoy receptor aflibercept, and the multikinase inhibitor regorafenib that targets tyrosine kinase receptors including the VEGF receptor (VEGFR), are approved as single agents or in combination with chemotherapy for patients with newly diagnosed and recurrent disease. 1-6 Ramucirumab, a monoclonal antibody targeting the VEGFR2, has also been shown to improve outcomes in mCRC patients in combination with chemotherapy. 7 These agents have different mechanisms of action for targeting the VEGF/VEGFR pathway and have demonstrated effectiveness in various subsets of patients with mCRC in phase III trials. In unresectable mCRC, the standard of care for initial treatment is chemotherapy (FOLFOX [folinic acid, 5-fluorouracil (5-FU), and oxaliplatin] or FOLFIRI [folinic acid, 5-FU, and irinotecan]) with bevacizumab. Despite the efficacy of the regimen, benefits are short-lived and disease in patients invariably progresses. 8 Based on the results of the treatment through multiple lines (TML) study (also referred to as ML18147), bevacizumab in combination with second-line chemotherapy is approved for treatment beyond disease progression in mCRC patients who receive a first-line chemotherapy or bevacizumab regimen. 3 In addition, multiple second-generation angiogenesis inhibitors have been investigated in the setting after disease progression to improve on the clinical outcomes with bevacizumab. Aflibercept is approved in combination with FOLFIRI for mCRC patients that are resistant to or have disease progression after an oxaliplatin-containing regimen. Benefit with aflibercept has been noted regardless of previous bevacizumab use. 4 Regorafenib has been investigated as a single agent and is approved in patients with mCRC who have previously received therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, with an anti-VEGF therapy, and, if Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type, with an anti-endothelial growth factor receptor therapy. Moreover, a phase III study that combined ramucirumab, a novel antiVEGFR2 monoclonal antibody, with FOLFIRI has reported to improvement of the outcome in patients with recurrence previously treated with chemotherapy with bevacizumab. 7 As yet, there are no prospective, direct comparisons between currently approved and emerging angiogenesis inhibitors in combination with standard chemotherapy in first- or second-line settings for mCRC. Health care professionals who manage patients with mCRC are faced with many challenges as they seek to develop optimal personalized treatment plans for their patients through multiple lines of therapy. Thus, clinicians who care for patients with mCRC need to able to evaluate the latest clinical trial data and critically interpret their results, including comparison of various selection and eligibility criteria for different angiogenesis inhibitors. In the era of targeted therapeutics for personalized care, expert recommendations are needed for the appropriate selection of efficacious new targeted regimens based on patient characteristics and eligibility, and optimal sequencing and combination of agents across multiple lines of therapy to maximize clinical benefit.

Prevalence of electrocardiographic and echocardiographic LVH in a general population in northern italy. The vobarno study

Background: A large number of studies have demonstrated that left ventricular hypertrophy (LVH) detected with standard electroand echocardiography is an independent predictor of future cardiovascular complications in various subsets of patients. Due its low cost and wide availability electrocardiography represents the first line test for the assessment of cardiac organ damage in hypertensive patients. However a significant limitation is represented by its low sensitivity in detecting LVH. Aim of this study was to evaluate the prevalence of LVH detected by electroor echocardiography and the relationship between these two measures in a general population sample(Vobarno study). Methods: A total of 385 subjects (mean age 57 10years,44%males,64% hypertensives,44% overweight and 16%obese)underwent clinical examination with blood pressure measurement,standard laboratory examinations,a 12 leads electrocardiogram standard and standard echocardiography.EKGLVH was defined as the presence of a Sokolow-Lyon voltage 38 mm and/ or a Cornell voltage QRS duration product>2440 mm*msec and/or R in aVL;Echo-LVH was defined as LVM>50 g/m2.7 in men and 47g/m2.7 in women. Results: LVH prevalence was 5.1% and 16.3% with EKG and Echo,respectively.LVH was detected by both methods only in 2.0% of patients.The prevalence of EKG-LVH was 1.7% with Sokolow-Lyon voltage,4.2% with Cornell product and 5.1% with both EKG criteria.In hypertensives the prevalence of LVH was significantly greater than normotensives(6.8% vs 2.2% with EKG-LVH and 22.7% vs 9.6% with Echo).The concordance of the two techniques in identifying patients with LVH was only partial,and in particular,among patients with EKG-LVH a significant proportion(39%) did not have echo-LVH.However,patients with EKG-LVH but without Echo-LVH had greater LV mass index(39.9 vs 34.4 gr/m2.7,p<0.01) and worse systolic and diastolic function (midwall fractional shortening:17.3 vs 19.5; E/Em 10.6 vs 8.1,all p<0.01)as compared with those without both EKG and Echo-LVH.A positive correlation was observed between LVMI and Sokolow-Lyon voltage(r1⁄40.13,p<0.015),Cornell product(r1⁄40.22,p<0.001),Cornell voltage(r1⁄40.45,p<0.001)and R in aVL(r1⁄40.38,p<0.001). Conclusions: Our data confirm the greater sensibility of echocardiography examination for detection of LVH.The presence of EKG-LVH is associated with greater LVMI and worse systolic and diastolic function,even in the absence of clear-cut echo-LVH.Our results confirm the importance of identifying cardiac organ damage with both methods for a better stratification of cardiovascular risk.

The association of LVH with intraventricular dyssynchrony at diastolic phase during exercise in hypertevie patients

Background: A large number of studies have demonstrated that left ventricular hypertrophy (LVH) detected with standard electroand echocardiography is an independent predictor of future cardiovascular complications in various subsets of patients. Due its low cost and wide availability electrocardiography represents the first line test for the assessment of cardiac organ damage in hypertensive patients. However a significant limitation is represented by its low sensitivity in detecting LVH. Aim of this study was to evaluate the prevalence of LVH detected by electroor echocardiography and the relationship between these two measures in a general population sample(Vobarno study). Methods: A total of 385 subjects (mean age 57 10years,44%males,64% hypertensives,44% overweight and 16%obese)underwent clinical examination with blood pressure measurement,standard laboratory examinations,a 12 leads electrocardiogram standard and standard echocardiography.EKGLVH was defined as the presence of a Sokolow-Lyon voltage 38 mm and/ or a Cornell voltage QRS duration product>2440 mm*msec and/or R in aVL;Echo-LVH was defined as LVM>50 g/m2.7 in men and 47g/m2.7 in women. Results: LVH prevalence was 5.1% and 16.3% with EKG and Echo,respectively.LVH was detected by both methods only in 2.0% of patients.The prevalence of EKG-LVH was 1.7% with Sokolow-Lyon voltage,4.2% with Cornell product and 5.1% with both EKG criteria.In hypertensives the prevalence of LVH was significantly greater than normotensives(6.8% vs 2.2% with EKG-LVH and 22.7% vs 9.6% with Echo).The concordance of the two techniques in identifying patients with LVH was only partial,and in particular,among patients with EKG-LVH a significant proportion(39%) did not have echo-LVH.However,patients with EKG-LVH but without Echo-LVH had greater LV mass index(39.9 vs 34.4 gr/m2.7,p<0.01) and worse systolic and diastolic function (midwall fractional shortening:17.3 vs 19.5; E/Em 10.6 vs 8.1,all p<0.01)as compared with those without both EKG and Echo-LVH.A positive correlation was observed between LVMI and Sokolow-Lyon voltage(r1⁄40.13,p<0.015),Cornell product(r1⁄40.22,p<0.001),Cornell voltage(r1⁄40.45,p<0.001)and R in aVL(r1⁄40.38,p<0.001). Conclusions: Our data confirm the greater sensibility of echocardiography examination for detection of LVH.The presence of EKG-LVH is associated with greater LVMI and worse systolic and diastolic function,even in the absence of clear-cut echo-LVH.Our results confirm the importance of identifying cardiac organ damage with both methods for a better stratification of cardiovascular risk.

Response to the Comments on ‘Point of Care D-Dimer Testing in the Emergency Department–A Bioequivalence Study’ and Erratum to the Results

We have read with interest the comments made on our study titled 'Point of care (POC) D-dimer testing in the Emergency department-a bioequivalence study' [1]. Ekelund and Heilmann, referring to the results and conclusions of the study, have suggested that one of the discrepancies may be caused by a typographical error, and this inference probably stems from the use of the term 'range' in the published article. This should have been termed 'Bland-Altman limits of agreement' (0.24-2.13) for all the cases where both tests were ordered and not just for the 8 POC-negative VIDAS (VIDAS D-dimer assay; bioMerieux SA, RCS Lyon, France)-positive patients. The data have been reconfirmed by our database as not being a reporting error. Our study reflects a real-life scenario of replacing an existing laboratory test within the emergency department with another POC assay (AQT90 FLEX POC D-dimer analyzer; radiometer medical ApS, Akandevej, Denmark). This involves conducting a bioequivalence study between the two assays to rule out the risk of missed positive results-the outcome by which clinicians would be guided. Raising the cut-off values, including age-appropriate cut-offs has been suggested in the literature as a measure to improve the specificity of D-dimer assay and reduce the implications of radiological investigations for various subsets of patients [2-7]. Furthermore, a separate study on the sensitivity and specificity of D-dimer test in venous thromboembolism is in progress. As pointed out in the results of our study, the POC D-dimer assay demonstrated better specificity than the VIDAS assay; however, our study was neither designed nor powered to investigate this question as the primary outcome measure. If statistically proven in a larger cohort of patients, the improved specificity of POC D-dimer assay may reduce the risk of unnecessary radiation or other interventions for a subset of patients, which could be considered as a significant strength of the assay. As pointed out by Sukhu et al. [8], discordant values are increasingly obtained near the cut-off levels leading to mismatched results between the two assays, therefore, a larger study would be required before implementing a new methodology in a clinical setting. A study on bioequivalence between the two assays was not enough to make an informed decision to replace one test with the other, a conclusion also supported by Sukhu et al. [8] in their study. The criteria for bioequivalence studies and cut-offs for drugs are well established [9, 10], but the question can be raised whether the same standards can be applied for bioequivalence of diagnostic assays, especially in diseases of low prevalence [11]. Our study results show that the 8 patients who were tested positive by the VIDAS assay demonstrated negative POC D-dimer results, and these results together with the wide Bland-Altman limits of agreement (0.24-2.13) led to a conclusion that the two assays were not bioequivalent. This conclusion does not refer to the performance of the POC assay, but only to the comparison with the VIDAS method. It was reassuring to see that amongst the 40 patients evaluated using the 'gold standard' imaging test, all of the 12 POC D-dimer-negative patients also had negative imaging results as, for that matter, did the 6 patients with negative VIDAS results. Much larger studies on comparison of both methods to the 'gold standard' imaging test are required before significant differences in sensitivity or specificity between these tests can be claimed. A review of the manuscript, data files, clinical details of the participants' medical records, and discussions with the data collectors has revealed that contrary to the reported results, only 6 of the 8 patients who were positive by the VIDAS but negative by POC testing had imaging during their stay in the emergency department. For cases 3 and 8 in Table 2 of the original manuscript, the imaging procedure was deferred at their admission to the emergency room. Although in both cases the imaging results were negative, they were obtained after the patients discharge from the emergency department. These 2 cases were not included in the sensitivity and specificity calculations reported in Tables 4 and 5 of the manuscript because of a significant time delay (over 24 hr) between the D-dimer data collection and the imaging. The authors would like to apologize for not having disclosed it in the original manuscript.

To RAS or Not to RAS? The Evidence for and Cautions with Renin‐Angiotensin System Inhibition in Patients with Diabetic Kidney Disease

Substantial morbidity, mortality, and costs are associated with progressive diabetic kidney disease (DKD). A goal of Healthy People 2020 is to reduce kidney disease attributable to diabetes mellitus and increase the proportion of patients who receive agents that interrupt the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). The mechanisms that contribute to progressive loss of kidney function in patients with diabetes are disrupted by inhibition of the RAS. ACEIs, ARBs and direct renin inhibitors (DRIs) all reduce the effect of angiotensin II, yet each works through a different mechanism and displays properties that may or may not be replicated by the others. As single agents, RAS inhibitors and blockers have been shown to slow the rate of progression of DKD and to reduce new cases of end-stage renal disease in various subsets of patients with diabetes and proteinuria (e.g., albuminuria). However, even with contemporary use of ACEIs, ARBs, and, more recently, DRIs, the burden of kidney disease remains high. Thus investigators sought to explore the utility of combining agents (e.g., dual RAS therapy) in various regimens for cardiovascular and kidney end points. Recent data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) studies suggest that kidney-related outcomes (composite of dialysis initiation, doubling serum creatinine concentration, or death) were increased with ACEI plus ARB or DRI plus ARB combinations. Consequently, dual therapy should not be routinely prescribed in patients with diabetes until further data become available from other future studies. This review provides an introduction to DKD and a rationale for using RAS inhibition; discusses screening, detection, and monitoring of patients with DKD; and summarizes results from meta-analyses and critical reviews and from recent large randomized controlled studies published since the meta-analyses or reviews. Finally, we suggest a clinical approach for using RAS agents in patients with DKD.

Temporary epicardial left ventricular and biventricular pacing improves cardiac output after cardiopulmonary bypass

BackgroundTo evaluate, with different pacing modes, acute changes in left ventricular systolic function, obtained by continuous cardiac output thermodilution in various subsets of patients undergoing cardiopulmonary bypass surgery. Increments of mean arterial pressure and cardiac output were considered the end point.MethodsFifty cases electively submitted to cardiac surgery were analyzed. Isolated valve surgery 62%, coronary revascularization 30% and 8% mixed disease. Left ventricular ejection fraction was preserved in 50%,36% had moderate depression,(EF 36%-50%) whereas 14% had severe depression (EF < 35%). Left bundle branch block occurred in 18%. Preoperatively 84% were in sinus rhythm and 16% in atrial fibrillation. The different subgroups were analyzed for comparisons. Right atrial-right ventricular and right atrial-left ventricular pacing were employed in sinus rhytm. Biventricular pacing was also used in atrial fibrillation.ResultsRight atrium-right ventricular pacing, decreased significantly mean arterial pressure and cardiac output (2.3%) in the overall population and in the subgroups studied. Right atrium-left ventricle, increased mean arterial pressure and cardiac output in 79% of patients and yielded cardiac output increments of 7.5% (0.40 l/m) in the low ejection fraction subgroup and 7.3% (0.43 l/m) in the left bundle branch block subset. In atrial fibrillation patients, left ventricular and biventricular pacing produced a significant increase in cardiac output 8.5% (0.39 l/min) and 11.6% (0.53 l/min) respectively. The dP/dt max increased significantly with both modes (p = 0.021,p = 0.028).ConclusionRight atrial-right ventricular pacing generated adverse hemodynamic effects. Right atrium-left ventricular pacing produced significant CO improvement particularly in cases with depressed ventricular function and left bundle branch block. The greatest increments were observed with left ventricular or biventricular pacing in atrial fibrillation with depressed ejection fraction.

Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Atrial Fibrillation.

AF=Atrial fibrillation, CHS=Cardiovascular Health Study,CABG=Coronary artery bypass surgery, d=Day, DHA=Docosahexaenoic acid, EPA=Eicosapentaenoic acid, ERP= Effective refractory period, g=Gram, PAF= Paroxysmal atrial fibrillation, PeAF= Persistent atrial fibrillation PUFA= Polyunsaturated fatty acid.

Standard of practice: endovascular treatment of intracranial atherosclerosis

BackgroundSymptomatic intracranial atherosclerotic disease (ICAD) worldwide represents one of the most prevalent causes of stroke. When severe, studies show that it has a very high risk for recurrent stroke, highlighting...

Valproate effects on generalized spike-wave discharges and photoparoxysmal response

To the Editors: We commend Muhle et al. on their 30-year review of the use of valproate (VPA) in idiopathic generalized epilepsy (IGE). We note some comments and concerns, most importantly, the title and conclusion: “valproate does not reduce photoparoxysmal responses in IGEs” is not supported by their data, which indicates that treatment with VPA eliminated the photoparoxysmal response (PPR) in 7 (29%) of 24 patients. The authors did not cite landmark literature of VPA effectiveness in IGE patients in general and its effect on the PPR in particular. VPA reduces frequency and duration of (poly) spike-wave activity in IGE patients and reduces PPR in a dose-related way (Rowan et al., 1979; Stephan et al., 1981; Rimmer et al., 1987; Braathen et al., 1988). Muhle counted and quantified spike-wave discharges (SWDs), and their result with respect to spontaneous and hyperventilation (HV)-induced SWDs mirrors well-established literature. However, their method may have been less than optimal, as “up to four” 20-min EEGs appears to be a rather slender sample, and SWD quantification would be better assessed by a series of 24-h EEGs (Stephan et al., 1981). Concerning the effect of VPA on the PPR: Harding & Jeavons’ investigations demonstrated that VPA significantly reduces or fully suppresses the PPR in 78%, including abolition of the response in 54% (Harding & Jeavons, 1994). Comparable results have been obtained by other groups (Villarreal et al., 1978; Kasteleijn-Nolst Trenite, 1989). In addition, there are methodologic problems with the Muhle study: How were Muhle’s patients selected? Were they consecutive? How were the referrals obtained? We note the high percentage of patients with photosensitivity (50%) and possible confounding with an excess of female patients (79%). There is a study that shows that female patients might respond to VPA less well than male patients (Kasteleijn-Nolst Trenite & Reed, 2007), so perhaps a higher dose is needed in that group to abolish the PPR, but we are not informed whether treatment was titrated. Change in PPR range is an important measure of VPA effect. Muhle has not determined the PPR range, and because of their method, confusion with spontaneous discharges was also possible. VPA initially narrows the PPR range, and then if fully effective, it abolishes the PPR in a dose-dependent way (Stephan et al., 1981; Binnie et al., 1986; Kasteleijn-Nolst Trenite, 1989; Trenite, 2006). Reduction in the PPR range is reported as a more consistent marker of decreased tendency to seizures than normalization of the EEG (Binnie et al., 1986; Binnie, 2001), and it is a more reproducible physiologic measure, similar in concept to an exercise electrocardiography (ECG) test compared to a resting ECG. Muhle’s PPR terminology is inconsistent, and we have difficulty defining exactly how many patients had a PPR. Localized PPRs are usually not reported, as it is well established that type I and type II (localized) responses correlate poorly with epilepsy or photosensitive seizures, and are a poor marker of antiepileptic drug efficacy (Bickford et al., 1952; Binnie et al., 1986; Kasteleijn-Nolst Trenite, 1989; Waltz et al., 1992; Binnie, 2001; Trenite, 2006). There is inconsistency in numbers of patients: Several patients seem to disappear from the sample as the report proceeds and computation of the various subsets of patients is difficult. The Muhle article illustrates a number of important issues. It reports an EEG intermittent photic stimulation (IPS) test strategy, which although forward thinking in 1975 is not generally accepted. Recent iterations of EEG IPS protocols have led to the point of consensus and a standardized IPS protocol that results in quantifiable data with robust interobserver and trans-Atlantic reproducibility (Binnie, 2001; Kasteleijn-Nolst Trenite et al., 2007; Trenite et al., 2007). It leaves the reader puzzled when terminology is inconsistently used and data presented that does not match the conclusion. None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.