Structural and functional cardiac changes in endomyocardial fibrosis treated with endomyocardial resection: Disease progression captured by multimodality imaging.

Eosinophilic myocarditis, a rare and under-recognized disease process, occurs due to cytotoxic inflammation of the endomyocardium that over time may lead to a restrictive cardiomyopathy. We report clinical, multimodality imaging, and pathologic findings in a 45-year-old woman over a 17-month period as she progressed from suspected acute eosinophilic myocarditis to phenotypic endomyocardial fibrosis resulting in recurrent ascites. Interval echocardiograms demonstrate definitive pathologic structural changes that reflect the hemodynamic consequences of the underlying cardiomyopathy. Despite a negative myocardial biopsy, characteristic findings on cardiovascular magnetic resonance imaging clarified the diagnosis which led to successful treatment with endomyocardial resection and valve replacements.

Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

BACKGROUND: The 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published. METHODS: We performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1 000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: The cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84-0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73-0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79-0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes. CONCLUSIONS: In a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.

Cardiac Myosin Inhibition for Treatment of LVOT Obstruction in a Patient With Severe AS.

Aortic stenosis and obstructive hypertrophic cardiomyopathy are common conditions. When both are present in the same patient, the management can be challenging. We report what we believe to be the first time a cardiac myosin inhibitor has been used before transcutaneous aortic valve replacement.

The Eye as the Window to the Heart: Optical Coherence Tomography Angiography Biomarkers as Indicators of Cardiovascular Disease.

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure.

Augmentation index and aortic stiffness in bicuspid aortic valve patients with non-dilated proximal aortas.

BACKGROUND: We compared aortic stiffness, aortic impedance and pressure from wave reflections in the setting of bicuspid aortic valve (BAV) to the tricuspid aortic valve (TAV) in the absence of proximal aortic dilation. We hypothesized BAV is associated with abnormal arterial stiffness. METHODS: Ten BAV subjects (47 ± 4 years, 6 male) and 13 TAV subjects (46 ± 4 years, 10 male) without significant aortic valve disease were prospectively recruited. Characteristic impedance (Zc) was derived from echocardiographic images and pulse wave Doppler of the left ventricular outflow tract. Applanation tonometry was performed to obtain pulse wave velocity (PWV) at several sites as measures of arterial stiffness and augmentation index (AIx) as a measure of wave reflection. RESULTS: There were no significant differences between BAV and TAV subjects with regard to heart rate or blood pressure. Zc was similar between BAV and TAV subjects (p=0.25) as was carotid-femoral pulse wave velocity (cf-PWV) and carotid-radial PWV (cr-PWV) between BAV and TAV subjects (p=0.99). Carotid AIx was significantly higher in BAV patients compared with TAV patients (14.3 ± 4.18% versus -3.02 ± 3.96%, p=0.007). CONCLUSIONS: Aortic stiffness and impedance is similar between subjects with BAV and TAV with normal aortic dimensions. The significantly higher carotid AIx in BAV, a proxy of increased pressure from wave reflections, may reflect abnormal vascular function distal to the aorta.

The syndrome of degenerative calcific aortic stenosis: prevalence of multiple pathophysiologic disorders in association with valvular stenosis and their implications.

BACKGROUND: We hypothesized that degenerative calcific aortic stenosis (DCAS) is a syndrome influenced by factors beyond aortic valve stenosis (AS). The aim of this study was to assess how frequently DCAS is complicated by increased vascular load, systolic and/or diastolic left ventricular (LV) dysfunction, and comorbid disorders. METHODS: In 215 consecutive patients > 60 years of age with severe and moderate AS, we analyzed systemic arterial compliance, global hemodynamic load, LV ejection fraction (EF), the presence of diastolic dysfunction, and other valvular or systemic disorders. RESULTS: A total of 164 patients had severe AS and 51 had moderate AS. In patients with severe AS, the prevalence of increased vascular load was 42%; LV systolic and diastolic dysfunction was present in 27% and 42%; other valve diseases in 23%; and comorbid disorders in 82%. In the moderate AS group, abnormal vascular load was found in 52%; LV systolic and diastolic dysfunction was prevalent in 26% and 31%; other valve diseases in 17%; and comorbid disorders in 78% patients. More than half the patients in both groups had symptoms. In both severe and moderate AS groups, the prevalence of increased vascular load and systolic dysfunction was higher in the symptomatic group. CONCLUSION: Considerable number of patients with DCAS have abnormal vascular load, abnormal LV function, and significant coexisting disorders. These could influence the total pathophysiologic burden on the heart and symptom expression. Thus, DCAS should not be considered just as valvular stenosis, but a syndrome of DCAS because of the diagnostic, prognostic, and therapeutic implications of various factors associated with it.

Racial differences in central hemodynamic burden in men with HIV: preliminary findings.

OBJECTIVES: African Americans infected with HIV are almost 3 times more likely to die from cardiovascular disease (CVD) than their White HIV-infected counterparts. The purpose of this study was to examine racial differences in novel measures of vascular function and CVD risk in African American and White men infected with HIV. DESIGN: Our study uses a cross-sectional approach. SETTING: Participants were recruited from the nutrition/infectious disease clinic at a large metropolitan hospital. PARTICIPANTS: African American men (n=21) and White men (n=21) with HIV on stable anti-retroviral therapy were included in this study. MAIN OUTCOME MEASURES: High resolution ultrasound was used to assess brachial artery flow mediated dilation (FMD). Applanation tonometry was used to measure carotid-femoral and carotid-radial pulse wave velocity (PWV), carotid augmentation index (Alx) and carotid-brachial pulse pressure (PP) amplification. Left ventricular (LV) pressure effort was derived from the contour of the central BP waveform. RESULTS: There were no racial differences in brachial FMD (African American: 4.9 +/- 1.1 vs White: 5.4 +/- 1.0%; P>.05) or carotid-femoral PWV (African American: 8.9 +/- .6 vs White: 8.7 +/- .4 m/s; P>.05). African American men with HIV had significantly higher carotid-radial PWV (11.3 +/- .4 vs 9.8 +/- .3 m/s; P<.05), higher carotid Alx (6 +/- 3 vs -1 +/- 2%; P<.05), higher LV pressure effort (2262 +/- 369 vs 1030 +/- 140 dyne sec/cm2; P<.05) and lower PP amplification (1.10 +/- .03 vs 1.24 +/- .03; P<.05) compared to White men with HIV. CONCLUSION: Elevated CVD risk in African American men with HIV may be partially mediated by increased central hemodynamic burden and not endothelial dysfunction or increased aortic stiffness.

Peripheral augmentation index as a biomarker of vascular aging: an invasive hemodynamics approach.

We compared two measures of vascular function obtained from digital volume waveforms with measures of target organ damage and novel invasive measures of vascular function as they relate to vascular aging. Aortic pulse pressure amplification, pulsatility, form factor and extent of coronary atherosclerosis (modified Gensini score) were obtained invasively in 59 patients undergoing left heart catheterization. Digital volume waveforms were captured via peripheral arterial tone (PAT) and used to derive augmentation index (AIx) and the pulse wave amplitude-reactive hyperemia index (PWA-RHI). AIx was associated with age (r = 0.50, p < 0.05) and aortic pulsatility (r = 0.45, p < 0.05) and inversely associated with estimated glomerular filtration rate (-0.29, p < 0.05) aortic pulse pressure amplification (r = -0.28, p < 0.05) and aortic form factor (r = -0.38, p < 0.05). AIx was slightly higher in patients with left ventricular hypertrophy (LVH) versus those without left ventricular hypertrophy (30 vs. 14%, p = 0.058). There was no association between AIx and Gensini score. PWA-RHI was not associated with age, estimated glomerular filtration rate or invasive vascular parameters and did not differ in patients with versus without LVH (p = ns). PWA-RHI was inversely associated with Gensini score (r = -0.32, p < 0.05). AIx derived from PAT is correlated with age-associated changes in vascular function and target organ damage but not coronary atherosclerotic burden. PWA-RHI is associated with coronary atherosclerotic burden but is not associated with target organ damage or other measures of vascular aging assessed in this study. Each parameter provides distinct insight into systemic vascular aging and target organ damage.

Peripheral augmentation index and vascular inflammation in autosomal dominant polycystic kidney disease.

BACKGROUND: Cardiovascular disease is the leading cause of premature mortality in autosomal dominant polycystic kidney disease (ADPKD). We examined peripheral augmentation index (AIx) as a measure of systemic vascular function and circulating markers of vascular inflammation in patients with ADPKD. METHODS: Fifty-two ADPKD patients with hypertension and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), 50 ADPKD patients with hypertension and eGFR ≥ 60 mL/min/1.73 m(2), 42 normotensive ADPKD patients with eGFR ≥ 60 mL/min/1.73 m(2) and 51 normotensive healthy controls were enrolled in this study. AIx was measured from peripheral artery tone recordings using finger plethysmography. Serum levels of soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule-1, P-selectin, E-selectin, soluble Fas (sFas) and Fas ligand (FasL) were measured as markers of vascular inflammation. RESULTS: AIx was higher in all three patient groups with ADPKD compared to healthy controls (P < 0.05). AIx was similar between the normotensive ADPKD patients with eGFR ≥ 60 mL/min/1.73 m(2) and hypertensive ADPKD patients with eGFR < 60 mL/min/1.73 m(2) (P > 0.05). ICAM, P-selectin, E-selectin and sFas were higher and FasL lower in all ADPKD groups compared to controls (P < 0.05). ICAM, P-selectin and E-selectin were similar between the normotensive ADPKD patients with eGFR ≥ 60 mL/min/1.73 m(2) and hypertensive ADPKD patients with eGFR < 60 mL/min/1.73 m(2) (P > 0.05). According to multiple regression analysis, predictors of AIx in ADPKD included age, height, heart rate and mean arterial pressure (P < 0.05). Vascular inflammatory markers were not predictors of AIx in ADPKD. CONCLUSIONS: Systemic vascular dysfunction, manifesting as an increase in AIx and vascular inflammation is evident in young normotensive ADPKD patients with preserved renal function. Vascular inflammation is not associated with elevated AIx in ADPKD.

Echocardiographic characterization of left ventricular apical hypoplasia accompanied by a patent ductus arteriosus.

Left ventricular (LV) apical hypoplasia is an unusual, recently identified cardiomyopathy, whose clinical course is uncertain. In this report, we describe a case of this cardiomyopathy occurring in an asymptomatic 50-year-old male with a remote history of a surgically corrected patent ductus arteriosus (PDA), primarily using transthoracic echocardiography (TTE) to illustrate the imaging characteristics. This patient had been referred to our institution for an abnormal electrocardiogram, and TTE subsequently (Figure 1) revealed a dilated left ventricle with moderately to severely reduced function; LV ejection fraction was 30% by two- and three-dimensional quantification. The left ventricle had a spherical appearance with a thin-walled, truncated, and akinetic distal LV. The right ventricle appeared elongated and was noted to wrap around the distal left ventricle, but right ventricular systolic function was normal. There were no significant valvular abnormalities, and no evidence of residual PDA flow. Subsequent cardiac magnetic resonance (CMR) imaging confirmed these findings (Figure 1). The TTE and CMR findings seen in this patient are consistent with LV apical hypoplasia. Until now, this cardiomyopathy has been described only as an isolated congenital anomaly primarily using CMR and cardiac computed tomography. To our knowledge, this is the first reported case of LV apical hypoplasia in conjunction with another congenital cardiac abnormality, and the findings demonstrate that the distinctive appearance of this cardiomyopathy can be easily identified with echocardiography. As more cases are recognized and patients are followed over time, the natural history and optimal treatment for this cardiomyopathy may be further elucidated.

Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events.

AIMS: There is growing need for the identification of novel non-invasive methodologies for the identification of individuals at risk for adverse cardiovascular (CV) events. We examined whether endothelial dysfunction, as detected by non-invasive peripheral arterial tonometry (EndoPAT), can predict late CV events. METHODS AND RESULTS: Reactive hyperaemia (RH) was induced following upper arm occlusion of systolic blood pressure in 270 outpatients (54 +/- 12 years, 48% female). The natural logarithmic scaled RH index (L_RHI) was calculated from the ratio between the digital pulse volume during RH and at baseline. The patients were followed for CV adverse events (AE: cardiac death, myocardial infarction, revascularization or cardiac hospitalization) during a 7-year follow-up (inter-quartile range = 4.4-8). Cox models were used to estimate the association of EndoPAT results with AE adjusted for age. During the follow-up, AE occurred in 86 patients (31%). Seven-year AE rate was 48% in patients with L_RHI < 0.4 vs. 28% in those with L_RHI >or= 0.4 (P = 0.03). Additional univariate predictors of AE were advancing age (P = 0.02) and prior coronary bypass surgery (P = 0.01). The traditional Framingham risk score was not higher in patients with AE. Multivariate analysis identified L_RHI < 0.4 as an independent predictor of AE (P = 0.03). CONCLUSION: A low RH signal detected by EndoPAT, consistent with endothelial dysfunction, was associated with higher AE rate during follow-up. L_RHI was an independent predictor of AE. Non-invasive assessment of peripheral vascular function may be useful for the identification of patients at risk for cardiac AEs.

Endothelium-dependent vasodilation is associated with exercise capacity in smokers and non-smokers.

Smoking is an established cardiovascular risk factor that impairs endothelial function and reduces exercise capacity. Peripheral vascular endothelial function correlates with exercise capacity, but whether this association prevails in smokers is unknown. The purpose of this investigation was to examine the association between endothelial function and exercise capacity in chronic smokers and non-smoking controls. Brachial artery flow-mediated dilation (FMD, endothelium-dependent) following 5 minutes of upper arm occlusion was compared in 26 smokers (age 58 +/- 2 years; 15 female; BMI (body mass index) = 28 +/- 1) and 39 non-smokers (age 58 +/- 2 years; 24 female; BMI = 28 +/- 1) using ultrasound. Exercise treadmill time (ETT) was recorded from a standard Bruce protocol during symptom limited stress testing. There was found to be a significant positive association between FMD and ETT in smokers (r = 0.60, p < 0.05) and non-smokers (r = 0.28, p < 0.05). FMD was significantly lower in smokers versus non-smokers (8.9 +/- 0.9 vs 12.6 +/- 0.7%, p < 0.05). ETT was significantly lower in smokers (425 +/- 35 seconds) versus non-smokers (522 +/- 25 seconds, p < 0.05). After adjusting for FMD, there were no longer group differences in ETT. When patients were matched according to FMD, there were no differences in ETT between smokers and non-smokers. In conclusion, peripheral endothelial dysfunction is a correlate of low exercise capacity in smokers and non-smokers alike. Future research is needed to examine if improving endothelial function will lead to concomitant increases in exercise capacity in chronic smokers.

Pulse wave amplitude is associated with brachial artery diameter: implications for gender differences in microvascular function.

The ratio of pulse wave amplitude (PWA) during reactive hyperemia compared to baseline as measured by peripheral arterial tonometry (PAT) is a non-invasive measure of microvascular endothelial function referred to as the pulse wave amplitude reactive hyperemia index (PWA-RHI). Whether upstream conduit vessel structure may affect downstream resistance vessel PWA has not been clearly examined. We tested the hypothesis that digital PWA is influenced by brachial artery diameter (BAD) and that this association would influence comparison of PWA-RHI between genders. Measures of vascular structure and microvascular function were carried out in 115 patients varying in cardiovascular risk profiles (average age 57 years, male n = 79, CAD n = 43). PWA was assessed using plethysmography at baseline and following 5 minutes of brachial artery occlusion. BAD was assessed using high-resolution ultrasonography. Results : There was a negative association between BAD and PWA-RHI ( r = -0.34, p < 0.05). Women had greater PWA-RHI and smaller BAD compared with men (p < 0.05). When co-varying for BAD, there were no longer gender differences in PWA-RHI. Moreover, when a sub-group of men and women without CAD (n = 40), matched for BAD, were examined, there were no gender differences in PWA-RHI. In conclusion, PWA-RHI obtained from PAT is associated with BAD. Studies examining gender differences in microvascular endothelial function with PAT may need to correct for BAD as a potential confounder.

Myocardial hypoattenuation in cardiac sarcoidosis: CT correlation with CMR, PET and SPECT.

We report a marked abnormality in myocardial attenuation on non-gated contrast-enhanced CT in a patient with multiorgan sarcoidosis and correlate our findings with CMR, PET and SPECT. The noteworthy observation of myocardial hypoattenuation, in correspondence with the multimodality cardiovascular imaging findings, suggests that standard contrast-enhanced CT may provide information regarding tissue characterization. This report also demonstrates the independent clinical utility of CMR and PET in the evaluation and management of cardiac sarcoidosis.

Modestly overweight women have vascular endothelial dysfunction.

BACKGROUND: Vascular endothelial dysfunction occurs early in the atherosclerotic process and is predictive of cardiovascular prognosis. However, the association between specific cardiovascular risk factors and endothelial dysfunction in women has not been well characterized. This study examined the relationship between endothelial dysfunction and cardiovascular risk factors (body mass index [BMI] >or= 25 kg/m(2), current smoking, age, diabetes, hypertension, hypercholesterolemia, and family history of early coronary heart disease) in a population of women that included those already being treated for risk factors. METHODS: Endothelial function was assessed by brachial artery ultrasound flow-mediated vasodilation (FMD) in 185 consecutive women without a history of coronary heart disease. Women with hypertension, diabetes, or hyperlipidemia were allowed to continue on their usual therapy. RESULTS: There was an inverse linear association between age and FMD. Subjects who were active smokers had lower FMD compared with nonsmokers, and subjects with BMI >or= 25 kg/m(2) had lower FMD than subjects with BMI < 25 kg/m(2). FMD in overweight women (BMI >or= 25 and < 30 kg/m(2)) was similar to that of obese women (BMI >or= 30 kg/m(2)). Multivariate analysis demonstrated that body mass index, current smoking, and age were independent predictors of endothelial dysfunction in this population. CONCLUSION: Modestly elevated BMI, smoking, and age predict endothelial dysfunction in women, even in the presence of treatment for other atherosclerotic risk factors. These findings demonstrate the importance of modest elevation in BMI as a risk factor for impaired vascular health in women, and underscore the need for focusing further attention on lifestyle modification as a component of cardiovascular disease prevention.