Usefulness of Left Ventricular Strain by Cardiac Magnetic Resonance Feature-Tracking to Predict Cardiovascular Events in Patients With and Without Heart Failure.

There is controversy regarding the utility of left ventricular (LV) mechanics assessed by feature-tracking steady-state free-precession (FT-SSFP), a readily implementable technique in clinical practice. In particular, whether LV mechanics assessed by FT-SSFP predicts outcomes in subjects with heart failure (HF) with reduced ejection fraction (HFrEF), with preserved ejection fraction (HFpEF), or without HF is unknown. We aimed to assess whether LV mechanics measured with FT-SSFP cine magnetic resonance imaging (MRI) predicts adverse outcomes. We prospectively enrolled 612 adults without HF (n = 402), with HF with reduced ejection fraction (HFrEF; n = 113), or HFpEF (n = 97) and assessed LV strain using FT-SSFP cine MRI. Over a median follow-up of 39.5 months, 75 participants had an HF admission, and 85 died. In Cox proportional hazards models, lower global longitudinal (Standardized hazard ratio 1.56, 95% confidence interval [CI] 1.22 to 2.00, p = 0.0004), circumferential (Standardized HR 1.46, 95% CI 1.08 to 1.95, p = 0.0123), and radial strain (Standardized HR 0.59, 95% CI 0.43 to 0.83, p = 0.0019) were independently associated with the composite endpoint, after adjustment for HF status, LV ejection fraction (LVEF), age, sex, ethnicity, body mass index, systolic and diastolic blood pressure, hypertension, diabetes, coronary artery disease, and glomerular filtration rate. Furthermore, global longitudinal strain stratified the risk of adverse outcomes across tertiles better than LVEF. In analyses that included only participants with a preserved LVEF, systolic radial, circumferential and longitudinal strain were independently predictive of adverse outcomes. We conclude that LV longitudinal, circumferential and radial strain measured using FT-SSFP cine MRI (a readily implementable technique in clinical practice) predict the risk of adverse events, independently of LVEF.

Vitamin K Status, Warfarin Use, and Arterial Stiffness in Heart Failure.

Large artery stiffening contributes to the pathophysiology of heart failure (HF) and associated comorbidities. MGP (matrix Gla-protein) is a potent inhibitor of vascular calcification. MGP activation is vitamin K-dependent. We aimed (1) to compare dp-ucMGP (dephospho-uncarboxylated MGP) levels between subjects with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) and subjects without HF; (2) to assess the relationship between dp-ucMGP levels and arterial stiffness; and (3) to assess the relationship between warfarin use, dp-ucMGP levels, and arterial stiffness in HF. We enrolled 348 subjects with HFpEF (n=96), HFrEF (n=53), or no HF (n=199). Carotid-femoral pulse wave velocity, a measure of large artery stiffness, was measured with arterial tonometry. Dp-ucMGP was measured with ELISA. Dp-ucMGP levels were greater in both HFrEF (582 pmol/L; 95% CI, 444-721 pmol/L) and HFpEF (549 pmol/L; 95% CI, 455-643 pmol/L) compared with controls (426 pmol/L; 95% CI, 377-475 pmol/L; ANCOVA P=0.0067). Levels of dp-ucMGP were positively associated with carotid-femoral pulse wave velocity (standardized ß, 0.31; 95% CI, 0.19-0.42; P<0.0001), which was also true in analyses restricted to patients with HF (standardized ß, 0.34; 95% CI, 0.16-0.52; P=0.0002). Warfarin use was significantly associated with carotid-femoral pulse wave velocity (standardized ß, 0.13; 95% CI, 0.004-0.26; P=0.043), but this relationship was eliminated after adjustment for dp-ucMGP. In conclusion, levels of dp-ucMGP are increased in HFpEF and HFrEF and are independently associated with arterial stiffness. Future studies should investigate whether vitamin K supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffness in HFpEF and HFrEF.

Association of arginine vasopressin with low atrial natriuretic peptide levels, left ventricular remodelling, and outcomes in adults with and without heart failure.

AIMS: The arginine vasopressin (AVP) pathway has been extensively studied in heart failure (HF) with reduced ejection fraction (HFrEF), but less is known about AVP in HF with preserved EF (HFpEF). Furthermore, the association between AVP and atrial natriuretic peptide (ANP, a well-known inhibitor of AVP secretion) in HF is unknown. METHODS AND RESULTS: We studied subjects with HFpEF (n = 28) and HFrEF (n = 25) and without HF (n = 71). Left ventricular (LV) mass and left atrial (LA) volumes were measured with cardiac magnetic resonance imaging. Arginine vasopressin and ANP were measured with enzyme-linked immunosorbent assay. Arginine vasopressin levels were significantly greater in HFpEF [0.96 pg/mL; 95% confidence interval (CI) = 0.83-1.1 pg/mL] compared with subjects without HF (0.69 pg/mL; 95% CI = 0.6-0.77 pg/mL; P = 0.0002). Heart failure with preserved ejection fraction (but not HFrEF) was a significant predictor of higher AVP after adjustment for potential confounders. Arginine vasopressin levels were independently associated with a greater LA volume and also paradoxically, with lower ANP levels. Key independent correlates of higher AVP were the presence of HFpEF (standardized ß = 0.32; 95% CI = 0.09-0.56; P = 0.0073) and the ANP/LA volume ratio (standardized ß = -0.23; 95% CI = -0.42 to -0.04; P = 0.0196). Arginine vasopressin levels were independently associated with LV mass (ß = 0.26; 95% CI = 0.09-0.43; P = 0.003) and with an increased risk of death or HF admissions during follow-up (hazard ratio = 1.61; 95% CI = 1.13-2.29; P = 0.008). CONCLUSIONS: Arginine vasopressin is increased in HFpEF and is associated with LV hypertrophy and poor outcomes. Higher AVP is associated with the combination of LA enlargement and paradoxically low ANP levels. These findings may indicate that a relative deficiency of ANP (an inhibitor of AVP secretion) in the setting of chronically increased LA pressure may contribute to AVP excess.

Genetic modification of stem cells for improved therapy of the infarcted myocardium.

The conventional treatment modalities for ischemic heart disease only provide symptomatic relief to the patient without repairing and regenerating the damaged myocardium. Stem cell transplantation has emerged as a promising alternative therapeutic approach for cardiovascular diseases. Stem cells possess the potential of differentiation to adopt morphofunctional cardiac and vasculogenic phenotypes to repopulate the scar tissue and restore regional blood flow in the ischemic myocardium. These beneficial therapeutic effects make stem cell transplantation the method of choice for the treatment of ischemic heart disease. The efficacy of stem cell transplantation may be augmented by genetic manipulation of the cells prior to transplantation. Not only will insertion of therapeutic transgene(s) into the stem cells support the survival and differentiation of cells in the unfavorable microenvironment of the ischemic myocardium, but also the genetically manipulated stem cells will serve as a source of the transgene expression product in the heart for therapeutic benefits. We provide an overview of the extensively studied stem cell types for cardiac regeneration, the various methods in which these cells have been genetically manipulated and rationale of genetic modification of stem cells for use in regenerative cardiovascular therapeutics.