Zaid Almarzooq

Characteristics of Hospitalizations for Heart Failure with Preserved Ejection Fraction

BACKGROUND Hospitalizations for heart failure with preserved ejection fraction (HFpEF) are increasing. There are limited data examining national trends in patients hospitalized with HFpEF. METHODS Using the Nationwide Inpatient Sample, we examined 5,046,879 hospitalizations with a diagnosis of acute heart failure in 2003-2012, stratifying hospitalizations by HFpEF and heart failure with reduced ejection fraction (HFrEF). Patient and hospital characteristics, in-hospital mortality, and length of stay were examined. RESULTS Compared with HFrEF, those with HFpEF were older, more commonly female, and more likely to have hypertension, atrial fibrillation, chronic lung disease, chronic renal failure, and anemia. Over time, HFpEF comprised increasing proportions of men and patients aged ≥75 years. In-hospital mortality rate for HFpEF decreased by 13%, largely due to improved survival in those aged ≥65 years. Multivariable regression analyses showed that pulmonary circulation disorders, liver disease, and chronic renal failure were independent predictors of in-hospital mortality, whereas treatable diseases including hypertension, coronary artery disease, and diabetes were inversely associated. CONCLUSIONS This study represents the largest cohort of patients hospitalized with HFpEF to date, yielding the following observations: number of hospitalizations for HFpEF was comparable with that of HFrEF; patients with HFpEF were most often women and elderly, with a high burden of comorbidities; outcomes appeared improved among a subset of patients; pulmonary hypertension, liver disease, and chronic renal failure were strongly associated with poor outcomes.

Sex‐ and Race‐Related Differences in Characteristics and Outcomes of Hospitalizations for Heart Failure With Preserved Ejection Fraction

Background Sex and race have emerged as important contributors to the phenotypic heterogeneity of heart failure with preserved ejection fraction (HFpEF). However, there remains a need to identify important sex‐ and race‐related differences in characteristics and outcomes using a nationally representative cohort. Methods and Results Data were obtained from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project—Nationwide Inpatient Sample files between 2008 and 2012. Hospitalizations with a diagnosis of HFpEF were included for analysis. Demographics, hospital characteristics, and age‐adjusted comorbidity prevalence rates were compared between men and women and whites and blacks. In‐hospital mortality was determined and compared for each subgroup. Multivariable regression analyses were used to identify and compare correlates of in‐hospital mortality for each subgroup. A sample of 1 889 608 hospitalizations was analyzed. Men with HFpEF were slightly younger than women with HFpEF and had a higher Elixhauser comorbidity score. Men experienced higher in‐hospital mortality compared with women, a finding that was attenuated after adjusting for comorbidity. Blacks with HFpEF were younger than whites with HFpEF, with lower rates of most comorbidities. Hypertension, diabetes, anemia, and chronic renal failure were more common among blacks. Blacks experienced lower in‐hospital mortality compared with whites, even after adjusting for age and comorbidity. Important correlates of mortality among all 4 subgroups included pulmonary circulation disorders, liver disease, and chronic renal failure. Atrial fibrillation was an important correlate of mortality only among women and blacks. Conclusions Differences in patient characteristics and outcomes reinforce the notion that sex and race contribute to the phenotypic heterogeneity of HFpEF.

Role of molecular imaging with positron emission tomographic in aortic aneurysms

Aortic aneurysms (AA) are often asymptomatic before the occurrence of acute, potentially fatal complications including dissection and/or rupture. Beyond aortic size, the ability to assess aortic wall characteristics and processes contributing to aneurysm development may allow improved selection of patients who may benefit from prophylactic surgical intervention. Current risk stratification for aneurysms relies upon routine noninvasive imaging of aortic size without assessing the underlying pathophysiologic processes, including features such as inflammation, which may be associated with aneurysm development and progression. The use of molecular imaging modalities with positron emission tomographic (PET) scan allows characterization of aortic wall inflammatory activity. Elevated uptake of Fuorine-2-deoxy-D-glucose (FDG), a radiotracer with elevated avidity in highly-metabolic cells, has been correlated with the development and progression of both abdominal and thoracic AA in a number of animal models and clinical studies. Other novel PET radiotracers targeting matrix metalloproteinases (MMPs), mitochondrial translocator proteins (TSPO) and endothelial cell adhesion molecules are being investigated for clinical utility in identifying progression of disease in AA. By further defining the activation of molecular pathways in assessing aortic regions at risk for dilatation, this imaging modality can be integrated into future clinical decision-making models.

Atrial fibrillation and heart failure with preserved ejection fraction: Insights on a unique clinical phenotype from a nationally-representative United States cohort

BACKGROUND Atrial fibrillation (AF) and heart failure often occur concomitantly, representing a clinical phenotype at high-risk for poor outcomes. Differences in the characteristics, management, and in-hospital outcomes of AF among those with heart failure with preserved ejection fraction (HFpEF) and those with heart failure with reduced ejection fraction (HFrEF) are not well characterized. METHODS AND RESULTS Using the National Inpatient Sample, we identified hospitalizations in 2008-2012 for HFpEF and for HFrEF, with and without AF based on ICD-9-CM codes. We examined patient characteristics, procedural rates, and in-hospital outcomes. AF was common among both HFpEF and HFrEF, and increased in prevalence over the study period. A very low proportion of the cohort underwent either direct-current cardioversion or catheter-ablation. Compared to those without AF, those with AF experienced higher in-hospital mortality regardless of heart failure subtype. In multivariable regression analysis, AF was associated with in-hospital mortality in HFpEF (OR 1.10, CI [1.08-1.11]), but not in HFrEF (OR 0.93 [0.92-0.94], p-for-interaction < 0.001). CONCLUSIONS Our study revealed that the prevalence and adverse impact of AF on those with HFpEF is substantial, providing a rationale to rigorously investigate strategies, such as rhythm-control, to improve outcomes for this particularly vulnerable subpopulation.

Cine-CMR partial voxel segmentation demonstrates increased aortic stiffness among patients with Marfan syndrome

BACKGROUND Standard cine-cardiac magnetic resonance (CMR) imaging is commonly used to evaluate cardiac structure, geometry and function. Prior studies have shown that automated segmentation via partial voxel interpolation (PVI) accurately quantifies phantom-based cardiac chamber volumes and necropsy left ventricular myocardial mass. Despite this, the applicability and usefulness of PVI in the determination of physiologic parameters of the aorta such as aortic stiffness has yet to be investigated. METHODS Routine CMR was conducted with a 1.5T (GE) scanner with pulse sequences similar to that of standard CMR (parameters: TR 3.4 msec, TE 1.14 msec, flip angle 60°, temporal resolution ~30-40 msec). Views were obtained in standard cardiac-oriented longitudinal or axial views (2, 3 and 4 chambers). Within non-dilated regions of the descending thoracic aorta, aortic area was quantified via a novel PVI automated process (LV-METRIC), which discerns relative amounts of blood pool in each voxel. Aortic stiffness, as calculated from brachial artery pulse pressure and aortic area at maximal and minimal dimensions, was evaluated in 60 total segments (one segment per patient). All segments were in the descending aorta and were not aneurysmal. RESULTS Sixty patients in total were studied, including 50 that had genetically-related aortic disorder [35 bicuspid aortic valve (BAV), 15 Marfan syndrome (MFS)]. Ten normal controls without aortic disease were included for comparison purposes. All patients (n=60) had evaluable CMR images for assessment of the descending aorta with use of automated segmentation. Patients with BAV and MFS were similar to controls in age, systolic blood pressure, brachial artery pulse pressure, smoking status or hypercholesterolemia (all P=NS). There were more women (P<0.001), lower body mass index (P=0.008), and greater height (P<0.001) in the MFS cohort compared to BAV and controls. Descending aortic area in either systole (maximal) or diastole (minimal) was similar among all three cohorts. However, change in aortic area (ΔArea) throughout the cardiac cycle was substantially lower in MFS than control subjects (P<0.001). In contrast, change in aortic area throughout the cardiac cycle was not significantly different between BAV vs. controls (P=0.62). Aortic stiffness was increased among MFS patients versus control subjects (P=0.014). When comparing MFS to BAV subjects, a comparable trend was observed (P=0.09). No statistical difference was evident in aortic stiffness in patients with BAV versus control subjects (P=0.29). CONCLUSIONS The application of PVI to standard CMR imaging can assess abnormal descending aorta functional indices in normal caliber segments in MFS subjects. Future prospective studies with larger subject populations are warranted to further determine the overall utility of automated aortic segmentation as a possible early biomarker of aortic dysfunction before overt dilatation.

Cholesterol-Lowering Drugs and Therapies in Cardiovascular Disease

Dyslipidemia is a major risk factor for cardiovascular disease (CVD). The relationship between low-density lipoprotein concentration and cardiovascular (CV) risk has been well established in numerous epidemiological studies. The benefit of cholesterollowering agents has been demonstrated in patients with known CVD. On the other hand, in patients without known CVD the decision to start therapy depends on their 10-year risk prediction of CV events. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors (“statins”), a mainstay of cholesterol-lowering therapy, have been shown to reduce both CV events and all-cause mortality. Other lipid-lowering measures (both pharmacological and nonpharmacological) have also been demonstrated in clinical trials to reduce CV outcomes. In this chapter, we review contemporary therapies used to treat dyslipidemia and discuss future directions including novel agents on the horizon.

CHARACTERIZATION AND IMPACT OF COMORBIDITY AMONG GENDER AND RACIAL SUBGROUPS HOSPITALIZED WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION

Heart failure with preserved ejection fraction (HFpEF) is challenging to treat in part due to its phenotypic heterogeneity. There are limited data on differences in characteristics and outcomes of gender and race subgroups. Using the Nationwide Inpatient Sample, we examined 2,102,780

Routine cine-CMR segmentation via a novel automated algorithm (LV-METRIC) for assessment of aortic physiology: a clinical validation study

Methods Cine-CMR (SSFP) was performed on 1.5 Tesla (GE) scanners; pulse sequence parameters were equivalent to those for routine CMR (typical TR 3.4 msec, TE 1.14 msec, flip angle 60, temporal resolution 30 msec). Images were acquired in conventional cardiac (2, 3, 4 chamber) long axis or axial imaging planes. Aortic area was uniformly measured in a non-aneurysmal location within the mid-descending thoracic aorta: Cine-CMR was quantified via a novel “partial voxel” segmentation algorithm (LV-METRIC) that accounts for relative proportion of blood within each individual imaging voxel. Maximum (systolic) and minimum (diastolic) aortic areas and brachial pulse pressure were used to calculate distensibility, a measure of arterial compliance, of the mid-descending thoracic aorta.