Mayank Kansal

Relationship of contrast-enhanced magnetic resonance imaging-derived intramural scar distribution and speckle tracking echocardiography-derived left ventricular two-dimensional strains

AIMS Information is limited regarding the functional correlates of intramural scar burden in myopathic hearts. We aimed to explore the use of speckle tracking echocardiography selectively at three intramural locations, to investigate the variance in cardiac strains and their relationship to contrast-enhanced magnetic resonance imaging-derived scar distribution and global left ventricular systolic function. METHODS AND RESULTS Fifty-nine patients with evidence of myocardial fibrosis on contrast-enhanced magnetic resonance imaging and 18 healthy subjects underwent speckle tracking echocardiography for measuring subendocardial, midmyocardial, and subepicardial strains in longitudinal, circumferential, and radial directions. Patients were divided into three categories of scar distribution: Group A, endocardial and midmyocardial; Group B, midmyocardial and epicardial; and Group C, transmural. When these patients were compared with 18 healthy control subjects, longitudinal left ventricular deformation was attenuated equally for all three groups, whereas circumferential strain was relatively well preserved. On multivariate analysis, circumferential strain and scar burden were independent determinants of left ventricular ejection fraction (R(2) = 0.57; P = 0.003 for strain burden and P = 0.01 for scar burden). CONCLUSION Longitudinal strains are attenuated independent of myocardial scar location. This alteration in left ventricular deformation is associated with circumferential mechanics becoming a key determinant of global left ventricular pump function in myopathic hearts.

Hand‐Held Echocardiogram Does Not Aid in Triaging Chest Pain Patients from the Emergency Department

Background: Accurate triage of emergency department (ED) patients presenting with chest pain is a primary goal of the ED physician. In addition to standard clinical history and examination, a hand‐held echocardiogram (HHE) may aid the emergency physician in making correct decisions. We tested the hypothesis that an HHE performed and interpreted by a cardiology fellow could help risk‐stratify patients presenting to the ED with chest pain. Methods: ED physicians evaluated 36 patients presenting with cardiovascular symptoms. Patients were then dispositioned to either an intensive care bed, a monitored bed, an unmonitored bed, or home. Following disposition, an HHE was performed and interpreted by a cardiology fellow to evaluate for cardiac function and pathology. The outcomes evaluated (1) a change in the level of care and (2) additional testing ordered as a result of the HHE. Results: The HHE showed wall motion abnormalities in 31% (11 out of 36) of the studies, but the level of care did not change after HHE for any patients who presented with chest pain to the ED. No additional laboratory or imaging tests were ordered for any patients based on the results of the HHE. Eighty‐six percent (31 out of 36) of the studies were of adequate quality for interpretation, and 32 out of 36 (89%) interpretations correlated with an attending overread. Conclusion: Despite the high prevalence of abnormal wall motion in this population, hand‐held echocardiography performed in this ED setting did not aid in the risk stratification process of chest pain patients. (ECHOCARDIOGRAPHY, Volume 26, July 2009)

Outcomes of a Pharmacist-Managed Heart Failure Medication Titration Assistance Clinic

Background: National guidelines recommend angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and β-blockers (BBs) at target doses for morbidity and mortality benefits in heart failure with reduced ejection fraction (HFrEF); regardless, titration of these therapies in practice remains suboptimal. We implemented an outpatient pharmacist-managed HFrEF medication titration assistance clinic (MTAC) at one institution to improve titration for general cardiology (GC) patients. Objective: To evaluate MTAC impact by determining the proportion of patients on target or maximum tolerated ACE inhibitor/ARB and BB doses. Methods: A retrospective chart review of adult patients with documented ejection fraction ≤40% managed in the MTAC or GC from 2011 to 2013 was conducted. HFrEF medication regimens were collected at initial visit and months 1, 2, 3, 6, 9, and 12 to assess titration. Target doses were defined per guideline or dose at which ejection fraction recovered during the study. Maximum tolerated doses were defined as the highest dose patients tolerated without physiological limitations. Results: Of 148 patients, the MTAC managed 51 and GC managed 97. At baseline, 90% of MTAC versus 82% of GC patients were prescribed ACE inhibitors/ARBs and BBs. In the MTAC, 4% were at target or maximum tolerated doses compared with 32% of GC patients (P < 0.001). At 12 months, 95% of patients in the MTAC and 87% in GC were prescribed ACE inhibitors/ARBs and BBs. Of those prescribed ACE inhibitors/ARBs and BBs, 64% in the MTAC versus 40% in GC reached target or maximum tolerated doses (P = 0.01). Conclusions: The pharmacist-managed MTAC increased the proportion of patients on optimal HFrEF therapies and are a resource for GC patients.

Smoking intensity and duration is associated with cardiac structure and function: the ECHOcardiographic Study of Hispanics/Latinos

Objective Cardiovascular disease is the leading cause of death in smokers and this relationship is complicated by the multiplicity of cardiovascular effects of smoking. However, the relationship between intensity and duration of cigarette smoking and echocardiographic measures of right and left ventricular structure and function has been poorly studied. Methods We examined ECHO-SOL (Echocardiographic Study of Hispanics/Latinos) participants, a subset of the Hispanic Community Health Study/Study of Latinos. Participants were administered a detailed tobacco exposure questionnaire and a comprehensive echocardiography exam. Multivariable linear regression models (adjusted for age, sex, obesity, hypertension and diabetes statuses) were performed using sampling weights. Statistical significance was defined at p<0.01. Results There were 1818 ECHO-SOL participants (57.4% women, mean age 56.4 years). Among current smokers (n=304), increased duration of smoking, as measured by a younger age of smoking initiation, was significantly associated with higher mean left ventricular mass (LVM) and lower right ventricular (RV) function (lower right ventricular stroke volumes). More cigarettes smoked per day was significantly associated with higher mean LVM, worse diastolic function (higher E/e′ ratio), worse LV geometry (increased relative wall thickness) and worse RV function (decreasing right ventricular stroke volume). Among current smokers, higher mean lifetime pack-years (a combined measure of smoking intensity and duration) was associated with higher LVM, worse LV geometry, worse diastolic function, greater RV dilatation and worse RV function. Conclusions There is a dose–response relationship between intensity and duration of cigarette tobacco smoking with unfavourable changes of multiple measures of right-sided and left-sided cardiac structure and function.

Associations of prolonged QTc in sickle cell disease

Sudden death is a leading cause of mortality in sickle cell disease, implicating ventricular tachyarrhythmias. Prolonged QTc on an electrocardiogram (ECG), commonly seen with myocardial ischemia, is a known risk for polymorphic ventricular tachycardia (VT). We hypothesized that prolonged QTc is associated with mortality in sickle cell disease. ECG were analyzed from a cohort of 224 sickle patients (University of Illinois at Chicago, UIC) along with available laboratory, and echocardiographic findings, and from another cohort of 38 patients (University of Chicago, UC) for which cardiac MRI and free heme values were also measured. In the UIC cohort, QTc was potentially related to mortality with a hazard ratio (HR) of 1.22 per 10ms, (P = 0.015), and a HR = 3.19 (P = 0.045) for a QTc>480ms. In multivariate analyses, QTc remained significantly associated with survival after adjusting for inpatient ECG status (HR 1.26 per 10ms interval, P = 0.010) and genotype status [HR 1.21 per 10ms interval, P = 0.037). QTc trended toward association with mortality after adjusting for both LDH and hydroxyurea use (HR 1.21 per 10ms interval, P = 0.062) but was not significant after adjusting for TRV. In univariate analyses, QTc was related to markers of hemolysis including AST (P = 0.031), hemoglobin (P = 0.014), TR velocity (P = 0.036), higher in inpatients (P<0.001) and those with an SS compared to SC genotype (P<0.001) in the UIC cohort as well as to free heme in the UC cohort (P = 0.002). These findings support a relationship of prolonged QTc with hemolysis and potentially mortality in sickle cell disease.

Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients

The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P = 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.

Childhood and adult exposure to secondhand tobacco smoke and cardiac structure and function: results from Echo-SOL

Objective To describe the relationship of household secondhand smoke (SHS) exposure and cardiac structure and function. Methods Participants (n=1069; 68 % female; age 45–74 years) without history of tobacco use, coronary artery disease or severe valvular disease were included. Past childhood (starting at age <13 years), adolescent/adult and current exposure to household SHS was assessed. Survey linear regression analyses were used to model the relationship of SHS exposure and echocardiographic measures of cardiac structure and function, adjusting for covariates (age, sex, study site, alcohol use, physical activity and education). Results SHS exposure in childhood only was associated with reduced E/A velocity ratio (β=−0.06 (SE 0.02), p=0.008). SHS exposure in adolescence/adult only was associated with increased left ventricular ejection fraction (LVEF) (1.2 (0.6), p=0.04), left atrial volume index (1.7 (0.8), p=0.04) and decreased isovolumic relaxation time (−0.003 (0.002), p=0.03). SHS exposure in childhood and adolescence/adult was associated with worse left ventricular global longitudinal strain (LVGLS) (two-chamber) (0.8 (0.4), p= 0.049). Compared with individuals who do not live with a tobacco smoker, individuals who currently live with at least one tobacco smoker had reduced LVEF (−1.4 (0.6), p=0.02), LVGLS (average) (0.9 (0.40), p=0.03), medial E′ velocity (−0.5 (0.2), p=0.01), E/A ratio (−0.09 (0.03), p=0.003) and right ventricular fractional area change (−0.02 (0.01), p=0.01) with increased isovolumic relaxation time (0.006 (0.003), p=0.04). Conclusions Past and current household exposure to SHS was associated with abnormalities in cardiac systolic and diastolic function. Reducing household SHS exposure may be an opportunity for cardiac dysfunction prevention to reduce the risk of future clinical heart failure.

Association of Cardiac Structure and Function With Neurocognition in Hispanics/Latinos: The Echocardiographic Study of Latinos

Objective To study the associations of comprehensive measures of cardiac structure and function with multidimensional neurocognitive measures. Patients and Methods The Echocardiographic Study of Latinos is a population-based cohort of Hispanic/Latino adults older than 45 years enrolled from October 1, 2011, through June 30, 2014. Neurocognitive measures included Word Fluency (WF), Brief-Spanish English Verbal Learning Test (B-SEVLT), and Digit Symbol Substitution Test. The B-SEVLT included B-SEVLT-recall and B-SEVLT-sum. Echocardiographic measures included cardiac structure, systolic and diastolic function, and myocardial strain. Multivariable regression models were fit using survey statistics and sampling probabilities. Results A total of 1794 participants (mean age, 56±0.5 years; 56% women) were included in the analysis. In the adjusted model, higher left ventricular mass index was associated with lower B-SEVLT-sum and Digit Symbol Substitution Test scores. Left ventricular systolic dysfunction was associated with lower WF scores. Abnormal left ventricular geometry was associated with lower B-SEVLT-sum scores. Higher relative wall thickness was associated with B-SEVLT-recall and B-SEVLT-sum scores. Mitral annular relaxation velocities were associated with lower B-SEVLT-recall, B-SEVLT-sum, and WF scores. Higher mitral inflow to annular early diastolic velocity ratio was associated with lower B-SEVLT-recall and B-SEVLT-sum scores. Diastolic dysfunction was associated with lower B-SEVLT-sum scores. Finally, lower global longitudinal strain was associated with lower WF scores. Conclusion Alterations in cardiac structure, systolic and diastolic function, and myocardial strain were associated with worse neurocognitive function. Further study is needed to determine the mechanisms (ie, impairment of cerebral flow and silent brain infarctions) mediating these heart-brain associations.

Coronary artery rotation in native and stented porcine coronary arteries

Coronary arteries are exposed to several complex biomechanical forces during the cardiac cycle. These biomechanical forces potentially contribute to both native coronary artery disease, development of atherosclerosis and eventual stent failure. The aim of the present study was to characterize and define coronary artery axial rotation and the effect of stent implantation on this biomechanical factor.

Left ventricular global longitudinal strain predicts mortality and heart failure admissions in African American patients: Left ventricular strain in African Americans with heart failure

Several studies have demonstrated the importance of left ventricular (LV) global longitudinal strain (GLS) as a reliable prognostic indicator in patients with heart failure (HF). These studies have included few African American (AA) patients, despite the growing prevalence and severity of HF in this patient population.