Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction (HFpEF). MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp+/- mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident HFpEF. Aortic PWV was increased in older, but not young, female Mgp+/- mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation. CONCLUSIONS: This translational study demonstrates an association between ucMGP levels and arterial stiffness and future HFpEF in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in HFpEF.

Role of myocardial strain imaging in surveillance and management of cancer therapeutics-related cardiac dysfunction: A systematic review.

Transthoracic echocardiography is the primary cardiac imaging modality for the detection of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) through evaluation of serial changes in left ventricular ejection fraction (LVEF). However, LVEF assessment by standard methods including 3D Echo has important limitations including the fact that reduction in LVEF occurs late in the process of CTRCD. In contrast, by detecting early myocardial change, myocardial strain or deformation imaging has evolved to be a preferred parameter for detecting CTRCD. Peak systolic global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) has become an important prechemotherapy parameter that can independently predict subsequent adverse cardiac events as these abnormalities typically precede reduction in LVEF. While an absolute GLS measurement may be informative, a 10%-15% early reduction in GLS by STE appears to be the most useful prognosticator for cardiotoxicity while on therapy. In this paper, we present a current systematic literature review of application of myocardial strain imaging in cancer patients performed following PRISMA guidelines using electronic databases from MEDLINE, Embase, and SCOPUS Library from their inception until June 11th 2020. This review demonstrates the incremental value of myocardial deformation imaging over traditional LVEF in detection and its clinical implication in management of CTRCD.

A spectrum of sinus of Valsalva aneurysm-From the young to the old.

Sinus of Valsalva aneurysm (SVA) is a rare but potentially serious condition. Proper and timely diagnosis is crucial to the outcome of patients, particularly when rupture has occurred. Echocardiography is often the initial diagnostic imaging modality of choice as it is ubiquitous, relatively inexpensive, and without need for radiation or iodinated contrast administration. There are several congenital abnormalities that can appear similar to SVA on echocardiography, making the diagnosis challenging especially if providers are unfamiliar with these conditions. Here, we present a case series of three patients with SVA, representing a wide spectrum ranging from a young man presenting with acute rupture and decompensated heart failure to an elderly asymptomatic male with an incidental unruptured aneurysm. We will also present a brief literature overview and our approach to differentiating SVA from other congenital abnormalities on echocardiography.

The role of maximal inspiratory pressure on functional performance in adults with heart failure.

BACKGROUND: Exercise intolerance is common among adults with heart failure (HF) and is a strong prognostic indicator. We examined maximal inspiratory pressure (MIP) as an indicator of maximal and submaximal exercise capacity in older HF patients. METHODS: Fifty-one patients age ≥ 50 years with HF underwent MIP testing via the PrO2 device. Peak oxygen uptake (VO2), 6 min walk distance (6MWD), 30 s sit-to-stand test (STS), gait speed (GS), grip strength and lower extremity muscle strength [one-repetition maximum (1RM)] were measured. Correlation and exploratory multiple regression analyses investigated relationships between MIP, left ventricular ejection fraction (LVEF), age, body mass index (BMI) and physical function. MIP was then stratified by median (64 cm H2O), and endpoints were compared between median groups. RESULTS: The median age was 69 years [interquartile range (IQR): 66-73], and the median LVEF was 36.5% (IQR: 30%-45%). Regression identified MIP as an independent predictor for grip strength, 6MWD, 1RM weight and 30 s STS after adjustment for age, BMI and LVEF. MIP greater than the median (n = 25) independently predicted and reflected greater peak VO2 [14.2 (12.8-18.1) vs. 11.5 (9.7-13.0) mL/kg/min; P = 0.0007] as well as 6MWD, 1RM, 30 s STS and GS (all P < 0.05). CONCLUSION: The analysis demonstrates that MIP is a novel biometric for exercise tolerance in adults with HF. Assessments of MIP are safe and convenient, with the potential to enhance routine HF surveillance and provide novel biometrics to guide HF therapeutics.

Association of Left Atrial Function Index with Atrial Fibrillation and Cardiovascular Disease: The Framingham Offspring Study.

BACKGROUND: Left atrial (LA) size, a marker of atrial structural remodeling, is associated with increased risk for atrial fibrillation (AF) and cardiovascular disease (CVD). LA function may also relate to AF and CVD, irrespective of LA structure. We tested the hypothesis that LA function index (LAFI), an echocardiographic index of LA structure and function, may better characterize adverse LA remodeling and predict incident AF and CVD than existing measures. METHODS AND RESULTS: In 1786 Framingham Offspring Study eighth examination participants (mean age, 66±9 years; 53% women), we related LA diameter and LAFI (derived from the LA emptying fraction, left ventricular outflow tract velocity time integral, and indexed maximal LA volume) to incidence of AF and CVD on follow-up. Over a median follow-up of 8.3 years (range, 7.5-9.1 years), 145 participants developed AF and 139 developed CVD. Mean LAFI was 34.5±12.7. In adjusted Cox regression models, lower LAFI was associated with higher risk of incident AF (hazard ratio=3.83, 95% confidence interval=2.23-6.59, lowest [Q1] compared with highest [Q4] LAFI quartile) and over 2-fold higher risk of incident CVD (hazard ratio=2.20, 95% confidence interval=1.32-3.68, Q1 versus Q4). Addition of LAFI, indexed maximum LA volume, or LA diameter to prediction models for AF or CVD did not significantly improve model discrimination for either outcome. CONCLUSIONS: In our prospective investigation of a moderate-sized community-based sample, LAFI, a composite measure of LA size and function, was associated with incident AF and CVD. Addition of LAFI to the risk prediction models for AF or CVD, however, did not significantly improve their performance.

Clinical and Echocardiographic Correlates of Left Atrial Function Index: The Framingham Offspring Study.

BACKGROUND: Left atrial (LA) remodeling is a predictor of cardiovascular disease (CVD). We performed measurement of the LA function index (LAFI), a composite measure of LA structure and function, in a community-based cohort and here report the distribution and cross-sectional correlates of LAFI. METHODS: In 1,719 Framingham Offspring Study participants (54% women, mean age 66 ± 9 years), we derived LAFI from the LA emptying fraction, left ventricular (LV) outflow tract velocity time integral, and indexed maximal LA volume. We used multivariable linear regression to assess the clinical and echocardiographic correlates of LAFI adjusting for age, sex, anthropometric measurements, and CVD risk factors. RESULTS: The average LAFI was 35.2 ± 12.1. Overall, LAFI declined with advancing age (ß = -0.27, P < .001). LAFI was significantly higher (37.5 ± 11.6) in a subgroup of participants free of CVD and CVD risk factors compared with those with either of these conditions (34.5 ± 12.2). In multivariable models, LAFI was inversely related to antihypertensive use (ß = -1.26, P = .038), prevalent atrial fibrillation (ß = -4.46, P = .001), heart failure (ß = -5.86, P = .008), and coronary artery disease (ß = -2.01, P = .046). In models adjusting for echocardiographic variables, LAFI was directly related to LV ejection fraction (ß = 14.84, P < .001) and inversely related to LV volume (ß = -7.03, P < .001). CONCLUSIONS: LAFI was inversely associated with antihypertensive use and prevalent CVD and was related to established echocardiographic traits of LV remodeling. Our results offer normative ranges for LAFI in a white community-based sample and suggest that LAFI represents a marker of pathological atrial remodeling.

Prognosis of Adults With Borderline Left Ventricular Ejection Fraction.

OBJECTIVES: This study sought to examine the association of a borderline left ventricular ejection fraction (LVEF) of 50% to 55% with cardiovascular morbidity and mortality in a community-based cohort. BACKGROUND: Guidelines stipulate a LVEF >55% as normal, but the optimal threshold, if any, remains uncertain. The prognosis of a "borderline" LVEF, 50% to 55%, is unknown. METHODS: This study evaluated Framingham Heart Study participants who underwent echocardiography between 1979 and 2008 (n = 10,270 person-observations, mean age 60 years, 57% women). Using pooled data with up to 12 years of follow-up and multivariable Cox regression, we evaluated the associations of borderline LVEF and continuous LVEF with the risk of developing a composite outcome (heart failure [HF] or death; primary outcome) and incident HF (secondary outcome). RESULTS: During follow-up (median 7.9 years), HF developed in 355 participants, and 1,070 died. Among participants with an LVEF of 50% to 55% (prevalence 3.5%), rates of the composite outcome and HF were 0.24 and 0.13 per 10 years of follow-up, respectively, versus 0.16 and 0.05 in participants having a normal LVEF. In multivariable-adjusted analyses, LVEF of 50% to 55% was associated with increased risk of the composite outcome (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.05 to 1.80) and HF (HR: 2.15; 95% CI: 1.41 to 3.28). There was a linear inverse relationship of continuous LVEF with the composite outcome (HR per 5 LVEF% decrement: 1.12; 95% CI: 1.07 to 1.16) and HF (HR per 5 LVEF% decrement: 1.23; 95% CI: 1.15 to 1.32). CONCLUSIONS: Persons with an LVEF of 50% to 55% in the community have greater risk for morbidity and mortality relative to persons with an LVEF >55%. Additional studies are warranted to elucidate the optimal management of these individuals.

Clinical profile and underdiagnosis of pulmonary hypertension in US veteran patients.

BACKGROUND: Pulmonary hypertension (PH) is a key contributor to cardiovascular morbidity and early mortality; however, reports are lacking on the epidemiology of PH in at-risk patient populations. METHODS AND RESULTS: The echocardiography registries from 2 major Veterans Affairs hospitals were accessed to identify patients with at least moderate PH, defined here as a pulmonary artery systolic pressure ≥60 mm Hg detected echocardiographically. From a total of 10 471 individual patient transthoracic echocardiograms, we identified moderate or severe PH in 340 patients (332 men; mean, 77 years; mean pulmonary artery systolic pressure, 69.4±10.5 mm Hg), of which PH was listed as a diagnosis in the medical record for only 59 (17.3%). At a mean of 832 days (0-4817 days) following echocardiography diagnosing PH, 150 (44.1%) patients were deceased. PH was present without substantial left heart remodeling: the mean left ventricular ejection fraction was 0.50±0.16, left ventricular end-diastolic dimension was 5.0±0.9 cm, and left atrial dimension was 4.4±0.7 cm. Cardiac catheterization (n=122, 36%) demonstrated a mean pulmonary artery pressure of 40.5±11.4 mm Hg, pulmonary capillary wedge pressure of 22.6±8.9 mm Hg, and pulmonary vascular resistance of 4.6±2.9 Wood units. Diagnostic strategies for PH were variable and often incomplete; for example, only 16% of appropriate patients were assessed with a nuclear ventilation/perfusion scan for thromboembolic causes of PH. CONCLUSIONS: in an at-risk patient population, PH is underdiagnosed and associated with substantial mortality. Enhanced awareness is necessary among practitioners regarding contemporary PH diagnostic strategies.

Cardiac sarcoidosis with primary involvement of the tricuspid valve.

Sarcoid granulomas usually involve the myocardium with rare focal extensions into the pericardium and endocardium with resultant conduction defects, ventricular arrhythmias, and ventricular systolic and diastolic dysfunction. Primary involvement of valvular leaflets resulting in valvular regurgitation or stenosis is not known. We present a case of a wastewater consultant who developed tricuspid regurgitation and symptomatic atrioventricular block secondary to infiltration of tricuspid leaflets and conduction system from sarcoid granulomas. The patient later developed severe dilated cardiomyopathy as a result of extensive cardiac sarcoidosis necessitating cardiac transplantation. Valvular regurgitation should be included as one of the presenting manifestations of cardiac sarcoidosis.